Circulating microRNAs correlated with the level of coronary artery calcification in symptomatic patients

PubMed Central

Liu, Wei; Ling, Shukuan; Sun, Weijia; Liu, Tong; Li, Yuheng; Zhong, Guohui; Zhao, Dingsheng; Zhang, Pengfei; Song, Jinping; Jin, Xiaoyan; Xu, Zi; Song, Hailin; Li, Qi; Liu, Shujuan; Chai, Meng; Dai, Qinyi; He, Yi; Fan, Zhanming; Zhou, Yu Jie; Li, Yingxian

2015-01-01

The purpose of this study was to find the circulating microRNAs (miRNAs) co-related with the severity of coronary artery calcification (CAC), and testify whether the selected miRNAs could reflect the obstructive coronary artery disease in symptomatic patients. Patients with chest pain and moderated risk for coronary artery disease (CAD) were characterized with coronary artery calcium score (CACS) from cardiac computed tomography (CT). We analyzed plasma miRNA levels of clinical matched 11 CAC (CACS > 100) and 6 non-CAC (CACS = 0) subjects by microarray profile. Microarray analysis identified 34 differentially expressed miRNAs between CAC and non CAC groups. Eight miRNAs (miR-223, miR-3135b, miR-133a-3p, miR-2861, miR-134, miR-191-3p, miR-3679-5p, miR-1229 in CAC patients) were significantly increased in CAC plasma in an independent clinical matched cohort. Four miRNAs (miR-2861, 134, 1229 and 3135b) were correlated with the degree of CAC. Validation test in angiographic cohort showed that miR-134, miR-3135b and miR-2861 were significantly changed in patients with obstructive CAD . We identified three significantly upregulated circulating miRNAs (miR-134, miR-3135b and 2861) correlated with CAC while detected obstructive coronary disease in symptomatic patients. PMID:26537670

Absent right coronary artery: A case of single coronary artery or congenital ostial atresia?

PubMed

Gupta, Mohit D; Girish, M P; Vignesh, Vickram; Narang, Poonam; Trehan, Vijay; Tyagi, Sanjay

2015-12-01

Atresia of the right coronary artery ostium is a rare anatomic variant of the coronary circulation. It is often difficult to differentiate from single coronary artery. Its presence unassociated with any other anomaly has never been described in an adult individual. We report this unusual anomaly and discuss its anatomical and pathophysiological significance and possible ways to differentiate from single coronary artery. Copyright © 2015 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

Large right ventricular sinusoids in an infant with aorta-left ventricular tunnel and proximal right coronary artery atresia.

PubMed

Chen, Peter C; Spinner, Joseph A; Heinle, Jeffrey S

2018-07-01

We report a 1-month-old infant diagnosed with an aorta-left ventricular tunnel, ventricular septal defect, and right coronary atresia with right ventricular sinusoids. The patient's anatomy and physiology did not indicate right-ventricular-dependent coronary circulation, and therefore right ventricular decompression could be performed without compromising coronary perfusion during surgical correction. A detailed understanding of the coronary anatomy is critical in managing this defect when coronary anomalies are present.

Left dominant circulation increases mortality in acute coronary syndrome: A systematic review and meta-analysis of observational studies involving 255,718 patients.

PubMed

Khan, Abdur R; Khan Luni, Faraz; Bavishi, Chirag; Khan, Sobia; Eltahawy, Ehab A

2016-08-01

The effect of coronary dominance on mortality in patients with acute coronary syndrome (ACS) remains unclear. We performed a meta-analysis to evaluate the effect of coronary dominance in patients with ACS. Several data sources were searched for studies which compared studies that compared outcomes between right and left dominant coronary circulation in patients with ACS. The measured outcomes were in-hospital, 30-day or long-term mortality as reported in individual studies. The Generic inverse variance method was used in a random-effects model to pool mortality as an outcome. Odds ratio (OR) was calculated for mortality in the left dominant circulation relative to a right dominant one. Sub-group analysis was performed after stratification of mortality by duration. A total of 5 studies with 8 comparisons and 255,718 participants revealed an increased risk mortality (OR = 1.27 (95% CI: 1.13 - 1.42; P < 0.0001; I(2)  = 34%). Sub-group analysis revealed that the increased risk was evident at all time periods after the ACS; in-hospital (OR = 1.37; 95% CI: 1.07 - 1.76; P = 0.01; I(2)  = 50%), at 30 days (OR = 1.69; 95% CI: 1.14 - 2.52; P = 0.009; I(2)  = 18%) and long-term (OR = 1.15; 95% CI: 1.03 - 1.28; P = 0.01; I(2)  = 0%). In this meta-analysis we found that there is an increased risk of mortality with LD coronary circulation in patients with ACS. The knowledge of coronary dominance may not only be helpful as an incremental prognostic factor beyond pre-procedural risk scores in all patients with ACS, but may also aid in clinical decision making in a subset of these patients. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Minimized extracorporeal circulation in coronary artery bypass surgery is equivalent to standard extracorporeal circulation in patients with reduced left ventricular function.

PubMed

Puehler, T; Haneya, A; Philipp, A; Camboni, D; Hirt, S; Zink, W; Lehle, K; Rupprecht, L; Kobuch, R; Diez, C; Schmid, C

2010-06-01

Minimized extracorporeal circulation (MECC) is a promising alternative to standard extracorporeal circulation (ECC) and its use is increasing in routine coronary bypass surgery. We analyzed the clinical outcome of patients with reduced left ventricular function who underwent coronary artery bypass surgery with MECC or with standard ECC. From January 2003 to September 2008, 238 patients with a left ventricular function < 30 % underwent bypass surgery with ECC or MECC. The primary end point of our retrospective observational study was 30-day mortality. Secondary endpoints were the transfusion requirements, as well as intensive care and the in-hospital course. Demographic data, comorbidities and left ventricular function were similar in the study groups. MECC patients had a tendency towards a lower 30-day mortality rate, a better postoperative renal function and reduced ventilation times. Extracorporeal circulation time and postoperative high-dose inotropic support were significantly lower in the MECC group, while the stays in the intensive care unit and in hospital were comparable between the two groups. In our study, age in the ECC group, and previous infarction and New York Heart Association grade IV in the MECC group were preoperative risk factors associated with a higher mortality. Coronary bypass surgery using MECC is feasible and safe for patients with severely impaired left ventricular function. It is a promising alternative to ECC with a low mortality rate and a more favorable postoperative course.

B‐type natriuretic peptide release in the coronary effluent after acute transient ischaemia in humans

PubMed Central

Pascual‐Figal, Domingo A; Antolinos, María J; Bayes‐Genis, Antoni; Casas, Teresa; Nicolas, Francisco; Valdés, Mariano

2007-01-01

Background The association between B‐type natriuretic peptide (BNP) and coronary artery disease is not fully understood. Objective To assess whether ischaemia per se is a stimulus for BNP secretion. Setting University tertiary hospital, Spain (Virgen de la Arrixaca). Design Prospective interventional study. Patients 11 patients (55 (9) years, left ventricular ejection fraction (LVEF) 45% (7%) with a non‐complicated anterior myocardial infarction (MI) and isolated stenosis of the left anterior descending (LAD) coronary artery, successfully treated by primary angioplasty. Interventions 11.0 (0.9) days after MI, the LAD was occluded (20 min) for intracoronary infusion of progenitor cells. Blood samples were obtained from the femoral artery (peripheral circulation (PC)) and the coronary sinus (coronary circulation (CC)) immediately before and after coronary occlusion. Main outcome measures BNP (pg/ml) was measured and ischaemia biomarkers were monitored. Results During coronary occlusion, all patients experienced transitory chest pain and ST‐segment dynamic changes. After coronary occlusion, lactic acid levels rose in CC (1.42 (0.63) –1.78 (0.68) ng/ml, p = 0.003). Myoglobin and cardiac troponin T did not differ in CC or PC at 24 h. No differences were found in LVEF (+0.18% (2.4)%, p = 0.86) and motion score index (–0.02 (0.06), p = 0.37). Before occlusion, BNP levels did not differ significantly in CC versus PC (253 (56) vs 179 (34), p = 0.093). After occlusion, BNP showed a significant increase in CC (vs 332 (61), p = 0.004), but no change occurred in PC (vs 177 (23), p = 0.93), and circulating BNP levels were higher in CC versus PC (p = 0.008). Conclusions In response to acute ischaemia, BNP levels immediately increase in coronary sinus but not at the peripheral level. BNP release in the coronary effluent may exert local beneficial effects. PMID:17395669

Usefulness of Circulating Decoy Receptor 3 in Predicting Coronary Artery Disease Severity and Future Major Adverse Cardiovascular Events in Patients With Multivessel Coronary Artery Disease.

PubMed

Chang, Ting-Yung; Hsu, Chien-Yi; Huang, Po-Hsun; Chiang, Chia-Hung; Leu, Hsin-Bang; Huang, Chin-Chou; Chen, Jaw-Wen; Lin, Shing-Jong

2015-10-01

Decoy receptor 3 (DcR3), a member of the tumor necrosis factor receptor superfamily, is an antiapoptotic soluble receptor considered to play an important role in immune modulation and has pro-inflammatory functions. This study was designed to test whether circulating DcR3 levels are associated with coronary artery disease (CAD) severity and predict future major adverse cardiovascular events (MACEs) in patients with CAD. Circulating DcR3 levels and the Syntax score (SXscore) were determined in patients with multivessel CAD. The primary end point was the MACE within 12 months. In total, 152 consecutive patients with angiographically confirmed multivessel CAD who had received percutaneous coronary intervention were enrolled and were divided into 3 groups according to CAD lesion severity. Group 1 was defined as low SXscore (≤13), group 2 as intermediate SXscore (>13 and ≤22), and group 3 as high SXscore (>22). DcR3 levels were significantly higher in the high SXscore group than the other 2 groups (13,602 ± 7,256 vs 8,025 ± 7,789 vs 4,637 ± 4,403 pg/ml, p <0.001). By multivariate analysis, circulating DcR3 levels were identified as an independent predictor for high SXscore (adjusted odds ratio 1.15, 95% confidence interval 1.09 to 1.21; p <0.001). The Kaplan-Meier analysis showed that increased circulating DcR3 levels are associated with enhanced 1-year MACE in patients with multivessel CAD (log-rank p <0.001). In conclusion, increased circulating DcR3 levels are associated with CAD severity and predict future MACE in patients with multivessel CAD. Copyright © 2015 Elsevier Inc. All rights reserved.

Late Diagnosed Left Coronary to the Pulmonary Artery Large Fistulae: An Interesting and Incidental Cath Lab Finding

PubMed Central

de Melo, Pedro H. M. Craveiro; Abreu-Silva, Érlon O.; Coura, Fernando Barbiero; Rios, Gleyson Moraes; Potério, Daniel Izzet

2016-01-01

Coronary artery anomalies are congenital changes in their origin, course, and/or structure. Most of them are discovered as incidental findings during coronary angiographic studies or at autopsies. A coronary artery fistulae involve a communication between a coronary artery and a chamber of the heart or any segment of the systemic or pulmonary circulation. We present herein the case of a 67-year-old man with a recent history of exertional angina and dyspnea to usual daily activities whose coronary angiogram revealed an interesting and incidental coronary-pulmonary artery large fistulae. PMID:28053791

Late Diagnosed Left Coronary to the Pulmonary Artery Large Fistulae: An Interesting and Incidental Cath Lab Finding.

PubMed

Oliveira, Marcos Danillo P; de Melo, Pedro H M Craveiro; Abreu-Silva, Érlon O; Coura, Fernando Barbiero; Rios, Gleyson Moraes; Potério, Daniel Izzet

2016-01-01

Coronary artery anomalies are congenital changes in their origin, course, and/or structure. Most of them are discovered as incidental findings during coronary angiographic studies or at autopsies. A coronary artery fistulae involve a communication between a coronary artery and a chamber of the heart or any segment of the systemic or pulmonary circulation. We present herein the case of a 67-year-old man with a recent history of exertional angina and dyspnea to usual daily activities whose coronary angiogram revealed an interesting and incidental coronary-pulmonary artery large fistulae.

Coronary Heart Disease Alters Intercellular Communication by Modifying Microparticle-Mediated MicroRNA Transport

PubMed Central

Finn, Nnenna A.; Eapen, Danny; Manocha, Pankaj; Kassem, Hatem Al; Lassegue, Bernard; Ghasemzadeh, Nima; Quyyumi, Arshed; Searles, Charles D.

2013-01-01

Coronary heart disease (CHD) is characterized by abnormal intercellular communication and circulating microRNAs (miRNAs) are likely involved in this process. Here, we show that CHD was associated with changes in the transport of circulating miRNA, particularly decreased miRNA enrichment in microparticles (MPs). Additionally, MPs from CHD patients were less efficient at transferring miRNA to cultured HUVECs, which correlated with their diminished capacity to bind developmental endothelial locus-1 (Del-1). In summary, CHD was associated with distinct changes in circulating miRNA transport and these changes may contribute to the abnormal intercellular communication that underlies CHD initiation and progression. PMID:24042051

Early Coronary Reperfusion Facilitates Return of Spontaneous Circulation and Improves Cardiovascular Outcomes After Ischemic Cardiac Arrest and Extracorporeal Resuscitation in Pigs.

PubMed

Hutin, Alice; Lamhaut, Lionel; Lidouren, Fanny; Kohlhauer, Matthias; Mongardon, Nicolas; Carli, Pierre; Berdeaux, Alain; Ghaleh, Bijan; Tissier, Renaud

2016-12-22

Extracorporeal cardiopulmonary resuscitation (ECPR) is widely proposed for the treatment of refractory cardiac arrest. It should be associated with coronary angiography if coronary artery disease is suspected. However, the prioritization of care remains unclear in this situation. Our goal was to determine whether coronary reperfusion should be instituted as soon as possible in such situations in a pig model. Anesthetized pigs were instrumented and submitted to coronary artery occlusion and ventricular fibrillation. After 5 minutes of untreated cardiac arrest, conventional cardiopulmonary resuscitation (CPR) was started. Fifteen minutes later, ECPR was initiated for a total duration of 240 minutes. Animals randomly underwent either early or late coronary reperfusion at 20 or 120 minutes of ECPR, respectively. This timing was adapted to the kinetic of infarct extension in pigs. Return of spontaneous circulation was determined as organized electrocardiogram rhythm with systolic arterial pressure above 80 mm Hg. During conventional CPR, hemodynamic parameters were not different between groups. Carotid blood flow then increased by 70% after the onset of ECPR in both groups. No animal (0 of 7) elicited return of spontaneous circulation after late reperfusion versus 4 of 7 after early reperfusion (P=0.025). The hemodynamic parameters, such as carotid blood flow, were also improved in early versus late reperfusion groups (113±20 vs 43±17 mL/min after 240 minutes of ECPR, respectively; P=0.030), along with infarct size decrease (71±4% vs 84±2% of the risk zone, respectively; P=0.013). Early reperfusion improved hemodynamic status and facilitated return of spontaneous circulation in a porcine model of ischemic cardiac arrest treated by ECPR. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Coronary Artery Revascularization in Patients with Diabetes Mellitus

MedlinePlus

... Bridging Disciplines Circulation at Major Meetings Special Themed Issues Global Impact of the 2017 ACC/AHA Hypertension Guidelines Circulation Supplements Cardiovascular Case Series ECG Challenge Hospitals of History Brigham and ...

Single left coronary artery with separate origins of proximal and distal right coronary arteries from left anterior descending and circumflex arteries--a previously undescribed coronary circulation.

PubMed

Kaul, Pankaj; Javangula, Kalyana

2007-04-20

A single left coronary artery with right coronary artery arising from either left main stem (LMS) or left anterior descending artery (LAD) or circumflex artery (Cx) is an extremely rare coronary anomaly. This is the first report of separate origins of proximal and distal RCA from LAD and circumflex arteries respectively in a patient with a single left coronary artery. This 57 year old patient presented with unstable angina and severe stenotic disease of LAD and Cx arteries and underwent urgent successful quadruple coronary artery bypass grafting. The anomalies of right coronary artery in terms of their origin, number and distribution are reviewed.

Coronary heart disease alters intercellular communication by modifying microparticle-mediated microRNA transport.

PubMed

Finn, Nnenna A; Eapen, Danny; Manocha, Pankaj; Al Kassem, Hatem; Lassegue, Bernard; Ghasemzadeh, Nima; Quyyumi, Arshed; Searles, Charles D

2013-11-01

Coronary heart disease (CHD) is characterized by abnormal intercellular communication and circulating microRNAs (miRNAs) are likely involved in this process. Here, we show that CHD was associated with changes in the transport of circulating miRNA, particularly decreased miRNA enrichment in microparticles (MPs). Additionally, MPs from CHD patients were less efficient at transferring miRNA to cultured HUVECs, which correlated with their diminished capacity to bind developmental endothelial locus-1 (Del-1). In summary, CHD was associated with distinct changes in circulating miRNA transport and these changes may contribute to the abnormal intercellular communication that underlies CHD initiation and progression. Published by Elsevier B.V.

Relation of coronary collateral circulation with epicardial fat volume in patients with stable coronary artery disease

PubMed Central

Enhos, Asım; Sahin, Irfan; Can, Mehmet Mustafa; Biter, Ibrahim; Dinckal, Mustafa Hakan; Serebruany, Victor

2013-01-01

Objective To investigated the relationship between epicardial fat volume (EFV) and coronary collateral circulation (CCC) in patients with stable coronary artery disease (CAD). Methods The study population consisted of 152 consecutive patients with CAD who underwent coronary angiography and were found to have at least 95% significiant lesion in at least one major coronary artery. EFV was assessed utilizing 64-multislice computed tomography. The patients were classifield into impaired CCC group (Group 1, Rentrop grades 0−1, n = 58), or adequate CCC (Group 2, Rentrop grades 2−3, n = 94). Results The EFV values were significantly higher in paitients with adequate CCC than in those with impaired CCC. In multivariate logistic regression analysis, EFV (OR = 1.059; 95% CI: 1.035−1.085; P = 0.001); and presence of angina were independent predictors of adequate CCC. In receiver-operating characteristic curve analysis, the EFV value > 106.5 mL yielded an area under the curve value of 0.84, with the test sensitivity of 49.3%, and with 98.3% specifity. Conclusions High EFV, and the presence of angina independently predict adequate CCC in patients with stable coronary artery disease. This association offers new diagnostic opportinities to assess collateral flow by conventional ultrasound techniques. PMID:24454327

Why is coronary collateral growth impaired in type II diabetes and the metabolic syndrome?

PubMed Central

Rocic, Petra

2012-01-01

Type II diabetes and the metabolic syndrome are strong predictors of severity of occlusive coronary disease and poorer outcomes of coronary revascularization therapies. Coronary collateral growth can provide an alternative or accessory pathway of revascularization. However, collateral growth is impaired in type II diabetes and the metabolic syndrome. Although many factors necessary for collateral growth are known and many interventions have shown promising results in animal studies, not a single attempt to induce coronary collateral growth in human clinical trials has led to satisfactory results. Accordingly, the first part of this review outlines the known deleterious effects of diabetes and the metabolic syndrome on factors necessary for collateral growth, including pro-angiogenic growth factors, endothelial function, the redox state of the coronary circulation, intracellular signaling, leukocytes and bone marrow-derived progenitors cells. The second section highlights the gaps in our current knowledge of how these factors interact with the radically altered environment of the coronary circulation in diabetes and the metabolic syndrome. The interplay between these pathologies and inadequately explored areas related to the temporal regulation of collateral remodeling and the roles of the extracellular matrix, vascular cell phenotype and pro-inflammatory cytokines are emphasized with implications to development of efficient therapies. PMID:22342811

Right Ventricular Perfusion: Physiology and Clinical Implications.

PubMed

Crystal, George J; Pagel, Paul S

2018-01-01

Regulation of blood flow to the right ventricle differs significantly from that to the left ventricle. The right ventricle develops a lower systolic pressure than the left ventricle, resulting in reduced extravascular compressive forces and myocardial oxygen demand. Right ventricular perfusion has eight major characteristics that distinguish it from left ventricular perfusion: (1) appreciable perfusion throughout the entire cardiac cycle; (2) reduced myocardial oxygen uptake, blood flow, and oxygen extraction; (3) an oxygen extraction reserve that can be recruited to at least partially offset a reduction in coronary blood flow; (4) less effective pressure-flow autoregulation; (5) the ability to downregulate its metabolic demand during coronary hypoperfusion and thereby maintain contractile function and energy stores; (6) a transmurally uniform reduction in myocardial perfusion in the presence of a hemodynamically significant epicardial coronary stenosis; (7) extensive collateral connections from the left coronary circulation; and (8) possible retrograde perfusion from the right ventricular cavity through the Thebesian veins. These differences promote the maintenance of right ventricular oxygen supply-demand balance and provide relative resistance to ischemia-induced contractile dysfunction and infarction, but they may be compromised during acute or chronic increases in right ventricle afterload resulting from pulmonary arterial hypertension. Contractile function of the thin-walled right ventricle is exquisitely sensitive to afterload. Acute increases in pulmonary arterial pressure reduce right ventricular stroke volume and, if sufficiently large and prolonged, result in right ventricular failure. Right ventricular ischemia plays a prominent role in these effects. The risk of right ventricular ischemia is also heightened during chronic elevations in right ventricular afterload because microvascular growth fails to match myocyte hypertrophy and because microvascular dysfunction is present. The right coronary circulation is more sensitive than the left to α-adrenergic-mediated constriction, which may contribute to its greater propensity for coronary vasospasm. This characteristic of the right coronary circulation may increase its vulnerability to coronary vasoconstriction and impaired right ventricular perfusion during administration of α-adrenergic receptor agonists.

The Five-Year Clinical and Angiographic Follow-Up Outcomes of Intracoronary Transfusion of Circulation-Derived CD34+ Cells for Patients With End-Stage Diffuse Coronary Artery Disease Unsuitable for Coronary Intervention-Phase I Clinical Trial.

PubMed

Sung, Pei-Hsun; Lee, Fan-Yen; Tong, Meng-Shen; Chiang, John Y; Pei, Sung-Nan; Ma, Ming-Chun; Li, Yi-Chen; Chen, Yung-Lung; Wu, Chiung-Jen; Sheu, Jiunn-Jye; Lee, Mel S; Yip, Hon-Kan

2018-05-01

This study investigated the clinical and angiographic long-term outcomes of intracoronary transfusion of circulation-derived CD34+ cells for patients with end-stage diffuse coronary artery disease unsuitable for coronary intervention. A single-center prospective randomized double-blinded phase I clinical trial. Thirty-eight patients undergoing CD34+ cell therapy were allocated into groups 1 (1.0 × 10 cells/each vessel; n = 18) and 2 (3.0 × 10 cells/each vessel; n = 20). Those with end-stage diffuse coronary artery disease were unsuitable for percutaneous and surgical coronary revascularization. Intracoronary delivery of circulation-derived CD34+ cells. We prospectively evaluated long-term clinical and echocardiographic/angiographic outcomes between survivors and nonsurvivors. By the end of 5-year follow-up, the survival rate and major adverse cardio/cerebrovascular event were 78.9% (30/38) and 36.8% (14/38), respectively. During follow-up period, 31.6% patients (12/38) received coronary stenting for reason of sufficient target vessel size grown-up after the treatment. Endothelial function was significantly reduced in the nonsurvivors than the survivors (p = 0.039). Wimasis image analysis of angiographic findings showed that the angiogenesis was significantly and progressively increased from baseline to 1 and 5 years (all p < 0.001). The 3D echocardiography showed left ventricular ejection fraction increased from baseline to 1 year and then remained stable up to 5 years, whereas left ventricular chamber diameter exhibited an opposite pattern to left ventricular ejection fraction among the survivors. The clinical scores for angina and heart failure were significantly progressively reduced from baseline to 1 and 5 years (all p < 0.001). CD34+ cell therapy for end-stage diffuse coronary artery disease patients might contribute to persistently long-term effects on improvement of left ventricular function, angina/heart failure, and amelioration of left ventricular remodeling.

MicroRNA-939 governs vascular integrity and angiogenesis through targeting γ-catenin in endothelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hou, Shiqiang; Fang, Ming; Zhu, Qian

Coronary collateral circulation (CCC) functions as a natural bypass in the event of coronary obstruction, which markedly improves prognosis in patients with coronary artery disease (CAD). MicroRNAs (miRNAs) have been implicated in multiple physiological and pathological processes, including angiogenesis involved in CCC growth. The roles that miRNA-939 (miR-939) plays in angiogenesis remain largely unknown. We conducted this study to explore the expression of miR-939 in CAD patients and its role in angiogenesis. For the first time, our results indicated that the expression of circulating miR-939 was down-regulated in patients with sufficient CCC compared with patients with poor CCC. Overexpression ofmore » miR-939 in primary human umbilical vein endothelial cells (HUVECs) significantly inhibited the proliferation, adhesion and tube formation, but promoted the migration of cells. In contrast, miR-939 knockdown exerted reverse effects. We further identified that γ-catenin was a novel target of miR-939 by translational repression, which could rescue the effects of miR-939 in HUVECs. In summary, this study revealed that the expression of circulating miR-939 was down-regulated in CAD patients with sufficient CCC. MiR-939 abolished vascular integrity and repressed angiogenesis through directly targeting γ-catenin. It provided a potential biomarker and a therapeutic target for CAD. - Highlights: • Circulating miR-939 is decreased in sufficient coronary collateral circulation. • MiR-939 abolishes vascular integrity in endothelial cells. • MiR-939 represses angiogenesis. • γ-catenin is a novel target of miR-939.« less

What You Need to Know If You Have Coronary Artery Disease

MedlinePlus

... Bridging Disciplines Circulation at Major Meetings Special Themed Issues Global Impact of the 2017 ACC/AHA Hypertension Guidelines Circulation Supplements Cardiovascular Case Series ECG Challenge Hospitals of History Brigham and ...

Influence of depression and anxiety on circulating endothelial progenitor cells in patients with acute coronary syndromes.

PubMed

Felice, Francesca; Di Stefano, Rossella; Pini, Stefano; Mazzotta, Gianfranco; Bovenzi, Francesco M; Bertoli, Daniele; Abelli, Marianna; Borelli, Lucia; Cardini, Alessandra; Lari, Lisa; Gesi, Camilla; Michi, Paola; Morrone, Doralisa; Gnudi, Luigi; Balbarini, Alberto

2015-05-01

Circulating endothelial progenitor cells (EPCs) are related to endothelial function and progression of coronary artery disease. There is evidence of decreased numbers of circulating EPCs in patients with a current episode of major depression. We investigated the relationships between the level of circulating EPCs and depression and anxiety in patients with acute coronary syndrome (ACS). Patients with ACS admitted to three Cardiology Intensive Care Units were evaluated by the SCID-I to determine the presence of lifetime and/or current mood and anxiety disorders according to DSM-IV criteria. The EPCs were defined as CD133(+) CD34(+) KDR(+) and evaluated by flow cytometry. All patients underwent standardized cardiological and psychopathological evaluations. Parametric and nonparametric statistical tests were performed where appropriate. Out of 111 ACS patients, 57 were found to have a DSM-IV lifetime or current mood or anxiety disorder at the time of the inclusion in the study. The ACS group with mood or anxiety disorders showed a significant decrease in circulating EPC number compared with ACS patients without affective disorders. In addition, EPC levels correlated negatively with severity of depression and anxiety at index ACS episode. The current study indicates that EPCs circulate in decreased numbers in ACS patients with depression or anxiety and, therefore, contribute to explore new perspectives in the pathophysiology of the association between cardiovascular disorders and affective disorders. Copyright © 2015 John Wiley & Sons, Ltd.

Circulating B-vitamins and smoking habits are associated with serum polyunsaturated Fatty acids in patients with suspected coronary heart disease: a cross-sectional study.

PubMed

Skeie, Eli; Strand, Elin; Pedersen, Eva R; Bjørndal, Bodil; Bohov, Pavol; Berge, Rolf K; Svingen, Gard F T; Seifert, Reinhard; Ueland, Per M; Midttun, Øivind; Ulvik, Arve; Hustad, Steinar; Drevon, Christian A; Gregory, Jesse F; Nygård, Ottar

2015-01-01

The long-chain polyunsaturated fatty acids are considered to be of major health importance, and recent studies indicate that their endogenous metabolism is influenced by B-vitamin status and smoking habits. We investigated the associations of circulating B-vitamins and smoking habits with serum polyunsaturated fatty acids among 1,366 patients who underwent coronary angiography due to suspected coronary heart disease at Haukeland University Hospital, Norway. Of these, 52% provided information on dietary habits by a food frequency questionnaire. Associations were assessed using partial correlation (Spearman's rho). In the total population, the concentrations of most circulating B-vitamins were positively associated with serum n-3 polyunsaturated fatty acids, but negatively with serum n-6 polyunsaturated fatty acids. However, the associations between B-vitamins and polyunsaturated fatty acids tended to be weaker in smokers. This could not be solely explained by differences in dietary intake. Furthermore, plasma cotinine, a marker of recent nicotine exposure, showed a negative relationship with serum n-3 polyunsaturated fatty acids, but a positive relationship with serum n-6 polyunsaturated fatty acids. In conclusion, circulating B-vitamins are, in contrast to plasma cotinine, generally positively associated with serum n-3 polyunsaturated fatty acids and negatively with serum n-6 polyunsaturated fatty acids in patients with suspected coronary heart disease. Further studies should investigate whether B-vitamin status and smoking habits may modify the clinical effects of polyunsaturated fatty acid intake.

Role of smooth muscle cells on endothelial cell cytosolic free calcium in porcine coronary arteries.

PubMed

Budel, S; Schuster, A; Stergiopoulos, N; Meister, J J; Bény, J L

2001-09-01

We tested the hypothesis that the cytosolic free calcium concentration in endothelial cells is under the influence of the smooth muscle cells in the coronary circulation. In the left descending branch of porcine coronary arteries, cytosolic free calcium concentration ([Ca(2+)](i)) was estimated by determining the fluorescence ratio of two calcium probes, fluo 4 and fura red, in smooth muscle and endothelial cells using confocal microscopy. Acetylcholine and potassium, which act directly on smooth muscle cells to increase [Ca(2+)](i), were found to indirectly elevate [Ca(2+)](i) in endothelial cells; in primary cultures of endothelial cells, neither stimulus affected [Ca(2+)](i), yet substance P increased the fluorescence ratio twofold. In response to acetylcholine and potassium, isometric tension developed by arterial strips with intact endothelium was attenuated by up to 22% (P < 0.05) compared with strips without endothelium. These findings suggest that stimuli that increase smooth muscle [Ca(2+)](i) can indirectly influence endothelial cell function in porcine coronary arteries. Such a pathway for negative feedback can moderate vasoconstriction and diminish the potential for vasospasm in the coronary circulation.

Coronary effects of diadenosine tetraphosphate resemble those of adenosine in anesthetized pigs: involvement of ATP-sensitive potassium channels.

PubMed

Nakae, I; Takahashi, M; Takaoka, A; Liu, Q; Matsumoto, T; Amano, M; Sekine, A; Nakajima, H; Kinoshita, M

1996-07-01

Diadenosine tetraphosphate (Ap4A) is an adenine nucleotide with vasodilatory properties. We examined the effects of Ap4A on coronary circulation in comparison with those of adenosine, its metabolite, in anesthetized pigs. Left atrial (LA) infusion of Ap4A at increasing doses of 100, 200, and 300 micrograms/kg/min increased coronary blood flow (CBF) and decreased systemic blood pressure (BP) and coronary vascular resistance (CVR). Ap4A had no effect on large epicardial coronary artery diameter (CoD). Likewise, LA infusion of adenosine at doses of 150 and 300 micrograms/kg/min increased CBF and decreased BP and coronary vascular resistance (CVR) but did not affect CoD. Therefore, the vasodilatory effects of Ap4A and adenosine were predominant in small coronary resistance vessels and negligible in large coronary arteries. Pretreatment with glibenclamide (2 mg/kg, intravenously, i.v.), a specific blocker of ATP-sensitive potassium channels (KATP), attenuated alterations of CBF, BP, and CVR induced by Ap4A and by adenosine. In contrast, treatment with cromakalim (0.5 microgram/kg/min i.v.), an activator of KATP, enhanced the coronary effects of Ap4A and adenosine. Therefore, the opening of KATP in the pig coronary circulation is involved in the in vivo vasodilatory effects of Ap4A and adenosine. Treatment with 8-phenyltheophylline (8-PT, 4 mg/kg i.v.), an adenosine receptor antagonist, suppressed CBF increases induced by Ap4A (20 micrograms/kg/min, intracoronarily, i.c.) and adenosine (5 micrograms/kg/min i.c.) by 68 and 90%, respectively. These findings suggest that the in vivo coronary effects of Ap4A are largely caused by the opening of KATP through rapid degradation to adenosine to activate adenosine receptors.

Circulating sortilin level as a potential biomarker for coronary atherosclerosis and diabetes mellitus.

PubMed

Oh, Tae Jung; Ahn, Chang Ho; Kim, Bo-Rahm; Kim, Kyoung Min; Moon, Jae Hoon; Lim, Soo; Park, Kyong Soo; Lim, Cheong; Jang, HakChul; Choi, Sung Hee

2017-07-20

A previous genome-wide association study showed that a genetic variant of sortilin was associated with the risk of coronary artery disease (CAD). However, the role of circulating sortilin is still unknown. We investigated the potential role of plasma sortilin as a biomarker for CAD and diabetes mellitus. We enrolled statin-naïve subjects with CAD (n = 31) who underwent coronary artery bypass surgery and control subjects (n = 116) who were free from CAD as evaluated by coronary CT angiography. The presence of diabetes mellitus was evaluated and plasma sortilin levels were measured with a commercial ELISA kit. Plasma sortilin levels were higher in subjects with CAD and subjects with diabetes mellitus than in those without CAD or diabetes mellitus. Subjects in the highest sortilin tertile group were older and had higher glucose and HbA1c levels, but lipid profiles in the three tertile groups were comparable. Multivariable logistic regression analysis revealed that sortilin levels were independently associated with CAD. In addition, the receiver operating characteristic curve analysis showed that plasma sortilin levels could identify the presence of CAD or diabetes mellitus. Elevated circulating sortilin levels are associated with CAD and diabetes mellitus and can be used as a biomarker of both diseases in statin-naïve subjects.

Effect of pacing-induced myocardial ischemia on platelet activation and fibrin formation in the coronary circulation.

PubMed

Nichols, A B; Gold, K D; Marcella, J J; Cannon, P J; Owen, J

1987-07-01

The effect of pacing-induced myocardial ischemia on platelet activation and fibrin formation was investigated in seven patients with severe proximal lesions of the left anterior descending coronary artery to determine if acute ischemia activates the coagulation system. Fibrin formation was assessed from plasma levels of fibrinopeptide A. Platelet activation was assessed by levels of platelet factor 4, beta-thromboglobulin and thromboxane B2. Plasma levels were measured before, during and after acute myocardial ischemia induced by rapid atrial pacing. Blood samples were collected from the ascending aorta and from the great cardiac vein through heparin-bonded catheters. The occurrence of anterior myocardial ischemia was established by electrocardiography and by myocardial lactate extraction. No significant transmyocardial gradients in the levels of fibrinopeptide A, platelet factor 4, beta-thromboglobulin or thromboxane B2 were found at rest, during ischemia or in the recovery period, and levels in the great cardiac vein did not change in response to ischemia. These data indicate that pacing-induced myocardial ischemia does not result in release of fibrinopeptide A, platelet factor 4, beta-thromboglobulin or thromboxane B2 into the coronary circulation, and imply that acute ischemia does not induce platelet activation or fibrin formation in the coronary circulation.

Non-extracorporeal circulation for coronary artery bypass graft surgery is more beneficial than extracorporeal circulation.

PubMed

Yang, F-Y; Bao, Y-Z; Liu, F-S; Zhu, Y-C; Zheng, J; Zhang, J-H; Zheng, X-F; Wei, G-C

2015-04-01

The objective of this study was to compare coronary artery bypass graft (CABG) surgery with non-extracorporeal vs. extracorporeal circulation. The study outcomes included operative time, number of graft vessels, pulmonary infection rates, and systemic inflammatory markers. 96 patients received selective CABG, either with non-extracorporeal (study group; n = 48) or extracorporeal circulation (control group; n = 48). Operative time, pulmonary infection rates, and blood levels of inflammatory markers TNF-α, IL-6, and IL-8 before and 4, 24, and 48 hours after the surgery were quantified. Graft vessels were quantified using computed tomography. Operative time was significantly shorter in study group (4.58 ± 0.91 vs. 5.36 ± 1.12 hours in control group; p < 0.05). The number of graft vessels and pulmonary infection rates were comparable between both techniques. However, systemic inflammatory markers were significantly (p < 0.05) lower in study group at 4 and, partly, 24 hours after the surgery. Extracorporeal circulation prolongs operation and can aggravate systemic inflammatory response. Therefore, CABG with non-extracorporeal circulation offers more beneficial outcomes.

Stable coronary syndromes: pathophysiology, diagnostic advances and therapeutic need

PubMed Central

Corcoran, David

2018-01-01

The diagnostic management of patients with angina pectoris typically centres on the detection of obstructive epicardial CAD, which aligns with evidence-based treatment options that include medical therapy and myocardial revascularisation. This clinical paradigm fails to account for the considerable proportion (approximately one-third) of patients with angina in whom obstructive CAD is excluded. This common scenario presents a diagnostic conundrum whereby angina occurs but there is no obstructive CAD (ischaemia and no obstructive coronary artery disease—INOCA). We review new insights into the pathophysiology of angina whereby myocardial ischaemia results from a deficient supply of oxygenated blood to the myocardium, due to various combinations of focal or diffuse epicardial disease (macrovascular), microvascular dysfunction or both. Macrovascular disease may be due to the presence of obstructive CAD secondary to atherosclerosis, or may be dynamic due to a functional disorder (eg, coronary artery spasm, myocardial bridging). Pathophysiology of coronary microvascular disease may involve anatomical abnormalities resulting in increased coronary resistance, or functional abnormalities resulting in abnormal vasomotor tone. We consider novel clinical diagnostic techniques enabling new insights into the causes of angina and appraise the need for improved therapeutic options for patients with INOCA. We conclude that the taxonomy of stable CAD could improve to better reflect the heterogeneous pathophysiology of the coronary circulation. We propose the term ‘stable coronary syndromes’ (SCS), which aligns with the well-established terminology for ‘acute coronary syndromes’. SCS subtends a clinically relevant classification that more fully encompasses the different diseases of the epicardial and microvascular coronary circulation. PMID:29030424

Ventricular distension and diastolic coronary blood flow in the anaesthetized dog.

PubMed

Gattullo, D; Linden, R J; Losano, G; Pagliaro, P; Westerhof, N

1993-01-01

There appears to be no agreement as to whether or not an increase in diastolic left ventricular pressure and/or volume can cause a decrease in diastolic coronary blood flow. We investigated the problem in the anaesthetized dog using a flaccid freely distensible latex balloon inserted into the left ventricle with the animal on extracorporeal circulation and the coronary perfusion pressure constant at about 45 mm Hg. Maximal vasodilatation and suppression of autoregulation in coronary vasculature was obtained by the intracoronary infusion of dipyridamole (10-40 mg/h). Ventricular volume was changed in steps of 10 ml from 10 to 70 ml and back to 10 ml, whilst recording coronary blood flow and left ventricular pressure in the left circumflex coronary artery. Over a range of ventricular volumes from 20 to 50 ml and a concomitant rise in diastolic ventricular pressure to about 20 mm Hg there was no change in the diastolic coronary flow. Only when the ventricular volume was more than two times the control value (i.e. exceeded 50 ml) and left ventricular pressure was more than 20 mm Hg, was there a decrease in coronary flow. During the return of the volume to the control level there was a fall in diastolic flow and ventricular contractility with respect to the values obtained when the volume was increased; these two effects were transient lasting less than 10 min. It was not considered that any of the three models of the coronary circulation, waterfall, intramyocardial pump or varying elastance model could explain our results.(ABSTRACT TRUNCATED AT 250 WORDS)

GPER modulates tone and coronary vascular reactivity in male and female rats.

PubMed

Debortoli, Angelina Rafaela; Rouver, Wender do Nascimento; Delgado, Nathalie Tristão Banhos; Mengal, Vinicius; Claudio, Erick Roberto Gonçalves; Pernomian, Laena; Bendhack, Lusiane Maria; Moysés, Margareth Ribeiro; Santos, Roger Lyrio Dos

2017-08-01

Compared with age-matched men, premenopausal women are largely protected from coronary artery disease, a difference that is lost after menopause. The effects of oestrogens are mediated by the activation of nuclear receptors (ERα and ERβ) and by the G protein-coupled oestrogen receptor (GPER). This study aims to evaluate the potential role of GPER in coronary circulation in female and male rats. The baseline coronary perfusion pressure (CPP) and the concentration-response curve with a GPER agonist (G-1) were evaluated in isolated hearts before and after the blockade of GPER. GPER, superoxide dismutase (SOD-2), catalase and gp91phox protein expression were assessed by Western blotting. Superoxide production was evaluated ' in situ ' via dihydroethidium fluorescence (DHE). GPER blockade significantly increased the CPP in both groups, demonstrating the modulation of coronary tone by GPER. G-1 causes relaxation of the coronary bed in a concentration-dependent manner and was significantly higher in female rats. No differences were detected in GPER, SOD-2 and catalase protein expression. However, gp91phox expression and DHE fluorescence were higher in male rats, indicating elevated superoxide production. Therefore, GPER plays an important role in modulating coronary tone and reactivity in female and male rats. The observed differences in vascular reactivity may be related to the higher superoxide production in male rats. These findings help to elucidate the role of GPER-modulating coronary circulation, providing new information to develop a potential therapeutic target for the treatment of coronary heart disease. © 2017 Society for Endocrinology.

Circulating endothelial progenitor cells are inversely correlated with in-stent restenosis in patients with non-ST-segment elevation acute coronary syndromes treated with EPC-capture stents (JACK-EPC trial).

PubMed

Wojakowski, W; Pyrlik, A; Król, M; Buszman, P; Ochała, A; Milewski, K; Smolka, G; Kawecki, D; Rudnik, A; Pawłowski, T; Jadczyk, T; Wyderka, R; Cybulski, W; Dworowy, S; Tendera, M

2013-06-01

Aim of the study was to evaluate the association between circulating endothelial progenitor cells (EPCs) and angiographic outcomes after implantation of GenousTM stent in patients with non-ST-segment elevation acute coronary syndromes (ACS) (NSTE-ACS) undergoing urgent percutaneous coronary intervention (PCI). Sixty patients treated with EPC-capture stent (N.=30) or bare metal stents (BMS) (N.=30) receiving 80 mg atorvastatin and dual antiplatelet therapy (DAT) for 12 months. Restenosis was assessed after 6 months by quantitative coronary angiography (QCA) and major acute coronary events (MACE) evaluated after 6 and 12 months. de novo lesion >70% in native vessel, diameter 2.5-4 mm, lesion length <30 mm. diabetes, previous revascularization, significant left main stenosis, chronic total occlusions (CTO) and multivessel disease. Majority of patients in EPC-capture stent and BMS groups presented with NSTEMI (73.3% and 70%, respectively). Mean stent length was 20.1±8 and 19.9±10 mm, diameter 3±0.97 and 3.1±0.88 mm in respective groups. The binary restenosis was significantly lower in GenousTM (13 vs. 26.6%, P=0.04). Risk of MACE after 6 and 12 months were comparable in both groups. There was no stent thrombosis. Numbers of circulating EPCs were significantly approximately 2-fold higher during the ACS than after 6 months. Mobilization of EPCs during acute ischemia was significantly lower in patients who developed restenosis after 6 months (3 vs. 4.5 cells/μL, P=0.002) and it was negatively correlated with late-loss after 6 months (R=-0.42; P<0.03). Use of GenousTM stents in NSTE-ACS is associated with lower restenosis rate than BMS at 6 months. There was no ST through 1 year. The number of circulating EPCs is inversely correlated with in-stent late loss (LL).

Contrast-Induced Nephropathy Is Less Common in Patients with Good Coronary Collateral Circulation.

PubMed

Avci, Eyup; Yildirim, Tarik; Kadi, Hasan

2017-10-01

Contrast-induced nephropathy (CIN) is a typically reversible type of acute renal failure that develops after exposure to contrast agents; underlying endothelial dysfunction is thought to be an important risk factor for CIN. Although the mechanism of coronary collateral circulation (CCC) is not fully understood, a pivotal role of the endothelium has been reported in many studies. The aim of this study was to investigate whether there is a relationship between CCC and CIN. Patients with at least one occluded major coronary artery and blood creatinine analyses performed before and on the second day after angiography were included in the study. CIN was defined as a 25% or greater elevation of creatinine on the second day after exposure to the contrast agent. Collateral grading was performed according to the Rentrop classification. Patients were grouped according to whether they developed CIN or not, i.e., CIN(-) and CIN(+) group. A total of 214 patients who met the inclusion criteria were included in the study. CIN was diagnosed in 43 patients (20.1%) in the study population. Good CCC was identified in 112 patients (65.5%) in the CIN(-) group, whereas it was identified in 13 patients (30.2%) in the CIN(+) group. In the CIN(-) group, good CCC was significantly more frequent ( p < 0.001). Furthermore, collateral circulation was an independent predictor of CIN. Good collateral circulation was associated with a lower frequency of CIN, and poor collateral circulation was an independent predictor of CIN.

[Myocardial bridge as the only cause of acute coronary syndrome among the young patients].

PubMed

Miakinkova, Liudmila O; Teslenko, Yurii V; Tsyhanenko, Irina V

2018-01-01

Introduction: Myocardial bridge is an inborn anomaly of coronary artery development, when a part of it is submerged in a myocard, which is pressing the coronary artery to a systola and restrains coronary blood circulation. Generally this feature of coronary blood circulation does not cause any clinical symptoms because the 85% of coronary blood stream of the left ventricle is provided by diastolic filling. Hemodynamic changes in atherosclerosis, tahicardie, hypertrophie of myocard are leading to the manifestation of clinical symptoms of ischemia. The aim: The purpose of the investigation was to discover the features of clinical development of acute coronary syndrome caused by myocardial bridge of young patients without the features of atherosclerotical harm of coronary arteries. Materials and methods: Eight causes of acute coronary syndrome among patients of 28±8,5 years with myocardial bridge which was revealed during coronary angiography, were investigated. Standardized examination and conservative treatment of patients was held, except for three who have got interventional therapy. Results: According to our investigation, myocardial bridge of all investigated patients was located in the middle of the third front interventricular branch of the left coronary artery. Causes of acute coronary syndrome manifestation were tahicardia, spasms of coronary artery, inducted by iatrogenic factors hypertrophie of myocard, hypertrophic cardiomyopatie. Connection between the manifestation of clinical symptoms and length of tunneled segment which did not depend on the level of systolic compres was discovered. The results of conservative and interventional treatment were analyzed. Conclusions: Myocardial bridge can be the cause of myocardial ischemia among patients without signs of coronary atherosclerosis with additional hemodynamic risk facts such as tahicardia, spasms of coronary artery, hypertrophie of myocard. Clinical symptomatology of the acute coronary syndrome is more often observed among patients who's myocsrdial bridge is located in the middle of the third front interventricular branch of the left coronary artery. This is caused by perpendicular location of muscle fibers to coronary artery that increases systolic compression. Diastolic function and blood filling of coronary artery can be improved due to the medication beta-blockers therapy of patients with symptomatic myocardial bridge. A higher risk of appearance of restenosis of the stent is possible due to interventional treatment of young patients with myocardial bridge without atherosclerosis of coronary arteries.

[Oxygen-transporting function of the blood circulation system in sevoflurane anesthesia during myocardial revascularization under extracorporeal circulation].

PubMed

Skopets, A A; Lomivorotov, V V; Karakhalis, N B; Makarov, A A; Duman'ian, E S; Lomivorotova, L V

2009-01-01

The purpose of the study was to evaluate the efficiency of oxygen-transporting function of the circulatory system under sevoflurane anesthesia during myocardial revascularization operations under extracorporeal circulation. Twenty-five patients with coronary heart disease were examined. Mean blood pressure, heart rate, cardiac index, total peripheral vascular resistance index, pulmonary pressure, pulmonary wedge pressure, and central venous pressure were measured. Arterial and mixed venous blood oxygen levels, oxygen delivery and consumption index, arteriovenous oxygen difference, and glucose and lactate concentrations were calculated. The study has demonstrated that sevoflurane is an effective and safe anesthetic for myocardial revascularization operations in patients with coronary heart disease. The use of sevoflurane contributes to steady-state oxygen-transporting function of the circulatory system at all surgical stages.

Dor procedure for pulmonary atresia with intact ventricular septum in an infant.

PubMed

Kang, Yoonjin; Kwak, Jae Gun; Kim, Eung Rae; Kim, Woong-Han

2018-02-01

Pulmonary atresia with intact ventricular septum and right ventricle-dependent coronary circulation confers a high risk for myocardial infarction and complications of ischaemia, including left ventricle aneurysms. We describe an infant with pulmonary atresia with intact ventricular septum and right ventricle-dependent coronary circulation and a left ventricle apical aneurysm who successfully underwent the Dor procedure and a subsequent Fontan operation. Surgery for postinfarction left ventricle aneurysm can be considered in infants. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

A taurine-supplemented vegan diet may blunt the contribution of neutrophil activation to acute coronary events.

PubMed

McCarty, Mark F

2004-01-01

Neutrophils are activated in the coronary circulation during acute coronary events (unstable angina and myocardial infarction), often prior to the onset of ischemic damage. Moreover, neutrophils infiltrate coronary plaque in these circumstances, and may contribute to the rupture or erosion of this plaque, triggering thrombosis. Activated neutrophils secrete proteolytic enzymes in latent forms which are activated by the hypochlorous acid (HOCl) generated by myeloperoxidase. These phenomena may help to explain why an elevated white cell count has been found to be an independent coronary risk factor. Low-fat vegan diets can decrease circulating leukocytes--neutrophils and monocytes--possibly owing to down-regulation of systemic IGF-I activity. Thus, a relative neutropenia may contribute to the coronary protection afforded by such diets. However, vegetarian diets are devoid of taurine - the physiological antagonist of HOCl--and tissue levels of this nutrient are relatively low in vegetarians. Taurine has anti-atherosclerotic activity in animal models, possibly reflecting a role for macrophage-derived myeloperoxidase in the atherogenic process. Taurine also has platelet-stabilizing and anti-hypertensive effects that presumably could reduce coronary risk. Thus, it is proposed that a taurine-supplemented low-fat vegan diet represents a rational strategy for diminishing the contribution of activated neutrophils to acute coronary events; moreover, such a regimen would work in a number of other complementary ways to promote cardiovascular health. Moderate alcohol consumption, the well-tolerated drug pentoxifylline, and 5-lipoxygenase inhibitors--zileuton, boswellic acids, fish oil--may also have potential in this regard. Copyright 2004 Elsevier Ltd.

Influence of collaterals on the left ventricular end-diastolic pressure and serum NT-proBNP levels in patients with coronary chronic total occlusion.

PubMed

Samadov, Fuad; Yesildag, Osman; Sari, Ibrahim; Atas, Halil; Akhundova, Aysel; Basaran, Yelda

2017-06-01

Although numerous studies have shown the protective effects of the well-developed coronary collaterals on left ventricular functions, the relationship between collateral grade and left ventricular end diastolic pressure has not been studied in chronic total occlusion patients. Also, there are conflicting data on the effect of collaterals on NT-proBNP levels. The aim of our study was to evaluate the relationship between coronary collateral circulation and left ventricular end diastolic pressure and NT-proBNP levels in chronic total occlusion patients. Study group was retrospectively selected from the patients who had undergone coronary angiography at our hospital between June 2011 and March 2013. Clinical, biochemical, angiographic and hemodynamic data of 199 consecutive patients having at least one totally occluded major epicardial coronary artery were evaluated. Coronary collateral circulation was graded according to Rentrop classification. While Rentrop grade 3 was defined as well-developed, all the remaining collateral grades were regarded as poor collaterals. Overall 87 patients were found to have good collaterals and 112 patients had poor collaterals. There was no significant difference between the patients with well- or poorly developed coronary collaterals with regard to left ventricular end diastolic pressure (16.84 ± 5.40 mmHg vs 16.10 ± 6.09, respectively, p  = 0,632) and log NT-proBNP (2.46 ± 0.58 vs 2.59 ± 0.76, respectively, p  = 0,335). In patients with coronary chronic total occlusion even well-developed coronary collaterals are not capable of protecting the rise of left ventricular end diastolic pressure and NT-proBNP levels which are reliable markers of the left ventricular dysfunction.

Association of circulating levels of nicotinamide phosphoribosyltransferase (NAMPT/Visfatin) and of a frequent polymorphism in the promoter of the NAMPT gene with coronary artery disease in diabetic and non-diabetic subjects

PubMed Central

2013-01-01

Background Nicotinamide phosphoribosyltransferase (NAMPT) is the limiting enzyme in one of pathways of synthesis of Nicotinamide Adenine Dinucleotide, a redox coenzyme. NAMPT is considered as an insulin-mimetic factor and a potential regulatory factor in inflammatory and immune processes. Associations of circulating NAMPT levels with cardiovascular disease (CVD) and insulin resistance have been reported. We investigated association of circulating NAMPT levels and the rs9770242 NAMPT gene polymorphism with coronary artery disease (CAD). Methods We studied 594 Brazilian subjects undergoing a coronary angiography (49% of whom had type 2 diabetes). CAD, defined as stenosis greater than 50% in one major coronary vessel or branch, was observed in 68% of subjects. Genetic studies were also performed in 858 North-American Non-Hispanic White subjects with type 2 diabetes (49% with CAD). Results We observed an interaction between glycemic and CAD status on the comparison of NAMPT levels by CAD status. NAMPT levels were higher in type 2 diabetic patients with CAD as compared to those without CAD: 5.27 ± 2.93 ng/ml vs. 4.43 ± 2.94 ng/ml, p = 0.006 (mean ± SD). NAMPT levels were not significantly different in non-diabetic subjects with or without CAD. The T-allele of rs9770242 was associated with CAD in the Brazilian cohort (OR 1.46, 95% CI 1.06 - 2.01, p = 0.02) while no association was observed in the North-American cohort. Conclusions Our data suggest that circulating NAMPT levels are associated with CAD in type 2 diabetic patients. NAMPT rs9770242 polymorphism may be associated with CAD in some populations. PMID:23968400

The relationship of plasma decoy receptor 3 and coronary collateral circulation in patients with coronary artery disease.

PubMed

Yan, Youyou; Song, Dandan; Liu, Lulu; Meng, Xiuping; Qi, Chao; Wang, Junnan

2017-11-15

Previously, decoy receptor 3 (DcR3) was found to be a potential angiogenetic factor, while the relationship of DcR3 with coronary collateral circulation formation has not been investigated. In this study, we aimed to investigate whether plasma decoy receptor 3 levels was associated with CCC formation and evaluate its predictive power for CCC status in patients with coronary artery disease. Among patients who underwent coronary angiography with coronary artery disease and had a stenosis of ≥90% were included in our study. Collateral degree was graded according to Rentrope Cohen classification. Patients with grade 2 or 3 collateral degree were enrolled in good CCC group and patients with grade 0 or 1 collateral degree were enrolled in poor CCC group. Plasma DcR3 level was significantly higher in good CCC group (328.00±230.82 vs 194.84±130.63ng/l, p<0.01) and positively correlated with Rentrope grade (p<0.01). In addition, plasma DcR3 was also positively correlated with VEGF-A. Both ROC (receiver operating characteristic curve) and multinomial logistical regression analysis showed that plasma DcR3 displayed potent predictive power for CCC status. Higher plasma DcR3 level was related to better CCC formation and displayed potent predictive power for CCC status. Copyright © 2017. Published by Elsevier Inc.

Minimized extracorporeal circulation is improving outcome of coronary artery bypass surgery in the elderly.

PubMed

Freundt, Miriam; Ried, Michael; Philipp, Alois; Diez, Claudius; Kolat, Philipp; Hirt, Stephan W; Schmid, Christof; Haneya, Assad

2016-03-01

Advanced age is a known risk factor for morbidity and mortality after coronary artery bypass grafting (CABG). Minimized extracorporeal circulation (MECC) has been shown to reduce the negative effects associated with conventional extracorporeal circulation (CECC). This trial assesses the impact of MECC on the outcome of elderly patients undergoing CABG. Eight hundred and seventy-five patients (mean age 78.35 years) underwent isolated CABG using CECC (n=345) or MECC (n=530). The MECC group had a significantly shorter extracorporeal circulation time (ECCT), cross-clamp time and reperfusion time and lower transfusion needs. Postoperatively, these patients required significantly less inotropic support, fewer blood transfusions, less postoperative hemodialysis and developed less delirium compared to CECC patients. In the MECC group, intensive care unit (ICU) stay was significantly shorter and 30-day mortality was significantly reduced [2.6% versus 7.8%; p<0.001]. In conclusion, MECC improves outcome in elderly patients undergoing CABG surgery. © The Author(s) 2015.

Association between circulating vitamin K1 and coronary calcium progression in community-dwelling adults: the Multi-Ethnic Study of Atherosclerosis

USDA-ARS?s Scientific Manuscript database

While animal studies found vitamin K treatment reduced vascular calcification, human data are limited. Using a case-cohort design, we determined the association between vitamin K status and coronary artery calcium (CAC) progression in the Multi-ethnic Study of Atherosclerosis. Serum phylloquinone (v...

The correlation between lymphocyte/monocyte ratio and coronary collateral circulation in stable coronary artery disease patients.

PubMed

Kurtul, Alparslan; Duran, Mustafa

2017-01-01

Coronary collateral circulation (CCC) has an important impact on cardiovascular prognosis and well-developed CCC is associated with better clinical outcomes. We investigated whether lymphocyte/monocyte ratio (LMR) has an association with CCC in patients with stable coronary artery disease (SCAD). The study population consisted of 245 patients with SCAD. Patients were classified into a poor CCC group (Rentrop grades 0/1, n = 87), or good CCC group (Rentrop grades 2/3, n = 158). LMR values were significantly higher in patients with good CCC than in those with poor CCC (4.41 ± 1.58 vs 2.76 ± 1.10; p < 0.001). In receiver operating characteristic analysis, optimal cutoff of LMR for predicting well-developed CCC was 3.38. In multivariate analysis, LMR >3.38 (OR 4.637; p = 0.004), high sensitivity C-reactive protein (OR 0.810, p < 0.001), dyslipidemia (OR 2.485; p = 0.039), and presence of chronic total occlusion (OR 16.836; p < 0.001) were independent predictors of well-developed CCC. Increased LMR predicts well-developed CCC in SCAD patients.

Therapeutic Approaches in the Stimulation of the Coronary Collateral Circulation

PubMed Central

Degen, Achim; Millenaar, Dominic; Schirmer, Stephan H.

2014-01-01

Arteriogenesis as a way to restore blood flow after arterial occlusion has been under investigation for the treatment of coronary artery disease (CAD) for decades. Therapeutic approaches so far have included delivery of cytokines and growth factors as well as mechanical stimulation such as external counterpulsation. As knowledge on the mechanisms of arteriogenesis expanded, new therapeutic approaches have emerged. This review summarizes recent attempts to stimulate the growth of the coronary vasculature and discusses their potential in clinical application. This article also delivers an overview of current studies and trials on coronary arteriogenesis. PMID:23721076

Reciprocal ST-Segment Changes in Myocardial Infarction: Ischemia at Distance Versus Mirror Reflection of ST-Elevation.

PubMed

Vaidya, Gaurang Nandkishor; Antoine, Steve; Imam, Syed Haider; Kozman, Hani; Smulyan, Harold; Villarreal, Daniel

2018-02-01

Reciprocal ST-depression in the electrocardiograms (ECGs) of patients with ST-elevation myocardial infarction (STEMI) results from either true ischemia at a distance via collateral circulation diverting blood to the infarcted region or an electrical phenomenon that results from a mirror reflection of ST-elevation. We aimed to identify the role of reciprocal ECG changes in predicting collateral circulation to the infarcted area determined angiographically. In a retrospective study, ECG and angiography of 53 STEMI patients admitted to SUNY Upstate Medical University in 2014 were reviewed independently by experts blinded to the results of ECG and coronary angiography. Reciprocal changes (RC) in ECG were present in 41 patients (77%) and on angiography, 14 patients (26%) exhibited collateral vessels to the ischemic areas. No correlation was found between the presence of RC and collateral circulation (P = 0.384), or between the depth of reciprocal ST-depression and the degree of the collateral circulation (P = 0.195). However, 84% of patients without collaterals exhibited resolution of RC after successful percutaneous coronary intervention (PCI) (P = 0.036), suggesting that the ST depressions that resolved after reperfusion were directly caused by the culprit vessel. Patients without RC presented late after symptom onset (9.25 versus 3.83 hours, P = 0.004), also suggesting time related resolution. RC had no relation to or predictive value for collaterals on angiography. Among late presenting patients, RC were less frequent. Thus, reciprocal ST-depression may represent subendocardial ischemia from the primary coronary event or simply an electrical phenomenon, rather than ischemia at distance from impaired collateral circulation. Published by Elsevier Inc.

Prospective randomized comparison of coronary bypass grafting with minimal extracorporeal circulation system (MECC) versus off-pump coronary surgery.

PubMed

Mazzei, Valerio; Nasso, Giuseppe; Salamone, Giovanni; Castorino, Filippo; Tommasini, Antonello; Anselmi, Amedeo

2007-10-16

We aimed to evaluate the clinical results and biocompatibility of the minimal extracorporeal circulation system (MECC) compared with off-pump coronary revascularization (OPCABG). In a prospective randomized study, 150 patients underwent coronary surgery with the use of MECC and 150 underwent OPCABG. End points were (1) circulating markers of inflammation and organ injury, (2) operative results, and (3) outcome at 1-year follow-up. Operative mortality and morbidity were comparable between the groups. Release of inflammatory markers was similar between groups at all time points (peak interleukin-6 167.2+/-13.5 versus 181+/-6.5 pg/mL, P=0.14, OPCABG versus MECC group, respectively). Peak creatine kinase was 419.3+/-103.5 versus 326+/-84.2 mg/dL (P=0.28), and peak S-100 protein was 0.13+/-0.08 versus 0.29+/-0.1 pg/mL (P=0.058, OPCABG versus MECC group, respectively). Length of hospital stay and use of blood products were similar between groups. Two cases of angina recurrence at 1 year in the MECC group were observed versus 5 cases observed in the OPCABG group (P=0.44). A residual perfusion defect at myocardial nuclear scan was less frequent among patients in the MECC group (3 versus 9 cases, P=0.14; odds ratio 0.32, 95% confidence interval 0.07 to 1.32). Six (OPCABG group) versus 3 (MECC group) coronary grafts were occluded or severely stenotic at 1 year (P=0.33, odds ratio 0.47, 95% confidence interval 0.09 to 2.14). Clinical results of coronary revascularization with MECC are optimal when this procedure is performed by experienced teams. Postoperative morbidity is comparable to that with OPCABG. MECC is associated with little pump-related systemic and organ injury. It may achieve the benefits of OPCABG (less morbidity in high-risk patients) while facilitating complete revascularization in the case of complex lesions unsuitable for OPCABG.

The number and function of circulating CD34+CD133+ progenitor cells decreased in stable coronary artery disease but not in acute myocardial infarction

PubMed Central

Kondo, Takahisa; Shintani, Satoshi; Maeda, Kengo; Hayashi, Mutsuharu; Inden, Yasuya; Numaguchi, Yasushi; Sugiura, Kaichiro; Morita, Yasuhiro; Kitamura, Tomoya; Kamiya, Haruo; Sone, Takahito; Ohno, Miyoshi; Murohara, Toyoaki

2010-01-01

Objective Circulating CD34+CD133+ cells are one of the main sources of circulating endothelial progenitor cells (EPCs). Age is inversely related to the number and function of CD34+CD133+ progenitor cells in stable coronary artery disease (CAD), but the relationship remains unclear in acute myocardial infarction (AMI). The authors aimed to clarify how ageing affects the number and function of mobilised CD34+CD133+ progenitor cells in AMI. Design and results Circulating CD34+CD133+ progenitor cells were measured by flow cytometry. Measurements were made at admission for CAD, or on day 7 after the onset of AMI. In stable CAD (n=131), circulating CD34+CD133+ cells decreased with age (r=−0.344, p<0.0001). In AMI, circulating CD34+CD133+ cells did not correlate with age (n=50), and multivariate analysis revealed that the decreased number of circulating CD34+CD133+ cells was associated with male sex and higher peak creatinine kinase. The ability to give rise to functional EPCs, which show good migratory and tube-forming capabilities, deteriorated among stable CAD subjects (n=10) compared with AMI subjects (N=6). Conclusions In stable CAD, the number and function of circulating CD34+CD133+ progenitor cells decreased with age, whereas those mobilised and circulating in AMI did not. PMID:27325937

Influence of oxidative stress on the development of collateral circulation in total coronary occlusions.

PubMed

Demirbag, Recep; Gur, Mustafa; Yilmaz, Remzi; Kunt, Alper Sami; Erel, Ozcan; Andac, M Halit

2007-03-02

The purpose of this study was to investigate whether the levels of total antioxidant capacity (TAC), total peroxide and oxidative stress index (OSI) are associated with the development of collaterals in total coronary occlusions. Our study group contained 176 consecutive men patients with single-vessel TCO, 94 of whom had poorly developed coronary collateral, while 82 had well-developed coronary collateral. TAC and total peroxide concentration were measured of plasma. The ratio of TAC to total peroxide was accepted as an indicator of oxidative stress. The values of total peroxide and OSI in the Group I were significantly lower than that in Group II (p<0.001, for both). TAC levels were significantly higher in patients with poorly developed collaterals than in well-developed collateral group (p<0.001). OSI values were also significantly different among the Rentrop class-0, -1, -2 and -3 (ANOVA p<0.001). We found significant correlations between collaterals score and TAC, total peroxide and OSI levels (p<0.001 for all). In multiple linear regression analysis, total peroxide and OSI were independent predictors of collaterals score (p=0.006 and p<0.001 respectively). This study clearly demonstrates that the level of OSI is independently and positively associated with the presence of collateral circulation in total coronary occlusion patients.

The relationship between ischaemia-modified albumin and good coronary collateral circulation.

PubMed

Gök, Murat; Kundi, Harun; Kızıltunç, Emrullah; Topcuoglu, Canan; Ornek, Ender

2018-01-01

It is important to determine the grade of the coronary collateral circulation (CCC) in patients with stable coronary artery disease. In this study, we aimed to investigate the relationship between the ischaemia-modified albumin (IMA) level and good CCC. A total of 95 patients with coronary angiography and at least one epicardial coronary artery obstruction were included in the study. The Rentrop classification was used with CCC grading, where 0 and 1 were defined as poor collateral, and 2 and 3 were defined as good collateral. The IMA level of the patients was measured using an enzyme-linked immunosorbent assay (ELISA). The receiver-operating characteristic curve was used to show the sensitivity and specificity of IMA levels and the optimal cut-off value for predicting good CCC. The multiple logistic regression analysis revealed that the IMA level in the good CCC group was higher (p < 0.045). Conversely, the high-sensitivity C-reactive protein level was lower in the good CCC group (p < 0.023). We found an IMA cut-off value (4.7 ng/mL) that indicated good CCC level, and this shows good CCC with 70.2% sensitivity and 60.3% specificity. The IMA level could serve as a simple and useful predictor of well-developed CCC.

Angiotensin-converting enzyme DD polymorphism is associated with poor coronary collateral circulation in patients with coronary artery disease.

PubMed

Ceyhan, Koksal; Kadi, Hasan; Celik, Atac; Burucu, Turgay; Koc, Fatih; Sogut, Erkan; Sahin, Semsettin; Onalan, Orhan

2012-01-01

Although association between angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism and cardiovascular diseases was reported by many studies, the relation between ACE I/D polymorphism and coronary collateral circulation (CCC) has not been studied yet. The aim of the present study was to investigate a possible relationship between ACE I/D polymorphism and CCC. Patients who were subjected to coronary angiography in the 2006 to 2009 period and had at least a completely occluded major artery were included in this study. To classify collateral circulation, we used the Rentrop classification. Patients were classified as having poor CCC (Rentrop grades 0 to 1) or good CCC (Rentrop grades 2 to 3). Gene polymorphism was detected through the detailed melting curve analysis of polymerase chain reaction products after amplification using real-time polymerase chain reaction method and LightCycler 1.5 apparatus. We prospectively studied 113 patients who had at least 1 totally occluded major epicardial coronary artery. Forty-seven patients had poor CCC and 67 patients had good CCC. There were no differences among groups in age, sex, risk factors, lipid profile, uses of cardiovascular drugs, and number of diseased vessels. Plasma ACE levels were significantly higher in poor CCC group (P < 0.001). The frequency of DD polymorphism was higher in the poor CCC group (P < 0.001). In allele frequency, we found that the frequency of the D allele was higher in poor CCC group than in the good CCC group (95% confidence interval [CI], 2.16-7.38; P < 0.001). Multiple regression analysis with CCC development as the dependent variable revealed that the presence of total occlusion of the left circumflex artery (95% CI, 1.29-6.6; P = 0.001), ACE DD genotype (95% CI, 2.55-12.79; P = 0.001), presence of diabetes (95% CI, 1.03-3.16; P = 0.005), and pulse pressure (95% CI, 1.04-1.56; P = 0.045) were independent determinants of poor coronary collateral development. This study showed that ACE DD polymorphism is associated with poor CCC. Poor collateral circulation in patients carrying the D allele may be associated with endothelial dysfunction and elevated blood ACE levels in these patients.

Wave energy patterns of counterpulsation: a novel approach with wave intensity analysis.

PubMed

Lu, Pong-Jeu; Yang, Chi-Fu Jeffrey; Wu, Meng-Yu; Hung, Chun-Hao; Chan, Ming-Yao; Hsu, Tzu-Cheng

2011-11-01

In counterpulsation, diastolic augmentation increases coronary blood flow and systolic unloading reduces left ventricular afterload. We present a new approach with wave intensity analysis to revisit and explain counterpulsation principles. In an acute porcine model, a standard intra-aortic balloon pump was placed in descending aorta in 4 pigs. We measured pressure and velocity with probes in left anterior descending artery and aorta during and without intra-aortic balloon pump assistance. Wave intensities of aortic and left coronary waves were derived from pressure and flow measurements with synchronization correction. We identified predominating waves in counterpulsation. In the aorta, during diastolic augmentation, intra-aortic balloon inflation generated a backward compression wave, with a "pushing" effect toward the aortic root that translated to a forward compression wave into coronary circulation. During systolic unloading, intra-aortic balloon pump deflation generated a backward expansion wave that "sucked" blood from left coronary bed into the aorta. While this backward expansion wave translated to reduced left ventricular afterload, the "sucking" effect resulted in left coronary blood steal, as demonstrated by a forward expansion wave in left anterior descending coronary flow. The waves were sensitive to inflation and deflation timing, with just 25 ms delay from standard deflation timing leading to weaker forward expansion wave and less coronary regurgitation. Intra-aortic balloon pumps generate backward-traveling waves that predominantly drive aortic and coronary blood flow during counterpulsation. Wave intensity analysis of arterial circulations may provide a mechanism to explain diastolic augmentation and systolic unloading of intra-aortic balloon pump counterpulsation. Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Systemic and myocardial inflammatory response in coronary artery bypass graft surgery with miniaturized extracorporeal circulation: differences with a standard circuit and off-pump technique in a randomized clinical trial.

PubMed

Formica, Francesco; Mariani, Silvia; Broccolo, Francesco; Caruso, Rosa; Corti, Fabrizio; D'Alessandro, Stefano; Amigoni, Pietro; Sangalli, Fabio; Paolini, Giovanni

2013-01-01

Inflammatory response and hemodilution are the main drawbacks of extracorporeal circulation. We hypothesize that the use of miniaturized extracorporeal circulation (MECC) might lower the systemic and myocardial inflammatory patterns compared with a standard system (SECC) and off-pump coronary artery bypass grafting (OPCABG). Sixty-one patients undergoing isolated coronary artery bypass graft were prospectively randomized to MECC (n = 19), SECC (n = 20), or OPCABG (n = 22). Blood samples were collected from radial artery and coronary sinus to analyze blood lactate, hemodilution, and markers for inflammation and endothelial activation such as tumor necrosis factor (TNF)-α, interleukin-6, monocyte chemotactic protein-1, and E-selectin. No differences were observed in early clinical outcome. Interleukin -6 levels increased in every group during and after cardiac surgery, whereas TNF-α values grew in the SECC group (p = 0.05). E-selectin systemic values decreased during and after operation (p = 0.001) in every group. Monocyte chemotactic protein-1 systemic and cardiac levels raised only in SECC group (p = 0.014). In conclusion, MECC is comparable to SECC and OPCABG in the clinical outcome of low-risk patients, and it might be extensively used with no additional intraoperative risk. The analysis of the inflammatory patterns of endothelial activation shows MECC as effective as OPCABG, suggesting further studies to clarify MECC recommendation in high-risk patients.

Transcoronary gradients of HDL-associated MicroRNAs in unstable coronary artery disease.

PubMed

Choteau, Sébastien A; Cuesta Torres, Luisa F; Barraclough, Jennifer Y; Elder, Alexander M M; Martínez, Gonzalo J; Chen Fan, William Y; Shrestha, Sudichhya; Ong, Kwok L; Barter, Philip J; Celermajer, David S; Rye, Kerry-Anne; Patel, Sanjay; Tabet, Fatiha

2018-02-15

MicroRNAs (miRNAs) are transported on high-density lipoproteins (HDLs) and HDL-associated miRNAs are involved in intercellular communication. We explored HDL-associated miRNAs concentration gradients across the coronary circulation in stable and unstable coronary artery disease patients and whether changes in the transcoronary gradient were associated with changes in HDL composition and size. Acute coronary syndrome (ACS, n=17) patients, those with stable coronary artery disease (stable CAD, n=19) and control subjects without CAD (n=6) were studied. HDLs were isolated from plasma obtained from the coronary sinus (CS), aortic root (arterial blood) and right atrium (venous blood). HDL-associated miRNAs (miR-16, miR-20a, miR-92a, miR-126, miR-222 and miR-223) were quantified by TaqMan miRNA assays. HDL particle sizes were determined by non-denaturing polyacrylamide gradient gel electrophoresis. HDL composition was measured immunoturbidometrically or enzymatically. A concentration gradient across the coronary circulation was observed for all the HDL-associated miRNAs. In ACS patients, there was a significant inverse transcoronary gradient for HDL-associated miR-16, miR-92a and miR-223 (p<0.05) compared to patients with stable CAD. Changes in HDL-miRNA transcoronary gradients were not associated with changes in HDL composition or size. HDLs are depleted of miR-16, miR-92a and miR-223 during the transcoronary passage in patients with ACS compared to patients with stable CAD. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

PCSK9 and lipoprotein (a) levels are two predictors of coronary artery calcification in asymptomatic patients with familial hypercholesterolemia.

PubMed

Alonso, Rodrigo; Mata, Pedro; Muñiz, Ovidio; Fuentes-Jimenez, Francisco; Díaz, Jose Luis; Zambón, Daniel; Tomás, Marta; Martin, Cesar; Moyon, Thomas; Croyal, Mikaël; Thedrez, Aurélie; Lambert, Gilles

2016-11-01

We aimed to assess whether elevated PCSK9 and lipoprotein (a) [Lp(a)] levels associate with coronary artery calcification (CAC), a good marker of atherosclerosis burden, in asymptomatic familial hypercholesterolemia. We selected 161 molecularly defined FH patients treated with stable doses of statins for more than a year. CAC was measured using the Agatston method and quantified as categorical variable. Fasting plasma samples were collected and analyzed for lipids and lipoproteins. PCSK9 was measured by ELISA, Lp(a) and apolipoprotein (a) concentrations by inmunoturbidimetry and LC-MS/MS, respectively. Circulating PCSK9 levels were significantly reduced in patients without CAC (n = 63), compared to those with CAC (n = 99). Patients with the highest CAC scores (above 100) had the highest levels of circulating PCSK9 and Lp(a). In multivariable regression analyses, the main predictors for a positive CAC score was age and sex followed by circulating PCSK9 and Lp(a) levels. In statin treated asymptomatic FH patients, elevated PCSK9 and Lp(a) levels are independently associated with the presence and severity of CAC, a good predictor of coronary artery disease. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Intravascular ultrasound for intracranial angioplasty and stent placement: technical case report.

PubMed

Wehman, J Christopher; Holmes, David R; Hanel, Ricardo A; Levy, Elad I; Hopkins, L Nelson

2006-10-01

Intravascular ultrasound (IVUS) imaging has been used extensively in coronary artery interventions and has provided invaluable information for the understanding and treatment of coronary arterial disease. We present here the first description, to our knowledge, of IVUS-guided intracranial arterial interventions in the clinical setting. Two patients underwent intracranial angioplasty and stent placement with the assistance of IVUS for the evaluation of their lesions. One patient underwent stenting to treat an occlusive dissection of the left internal carotid artery that occurred during arteriovenous malformation embolization. Another patient underwent angioplasty and stenting for high-grade restenosis of a basilar artery atherosclerotic lesion. Both patients underwent successful revascularization procedures. The patient with the dissection had a small intraventricular and parenchymal hemorrhage documented by computed tomography 4 hours after treatment, but did not develop hydrocephalus or further hemorrhage. Both patients did well clinically and had no permanent neurological deficits. IVUS provided important information in terms of lesion evaluation, stent selection, and stent placement in each case. IVUS of the intracranial circulation may assist the performance of intracranial angioplasty and stenting. It provides useful information that can affect clinical decisions. It may prove to be a valuable tool in clinical use and enhance our understanding of vascular disease of the intracranial circulation, as it has in the coronary circulation.

Heterogeneity in Kv7 channel function in the cerebral and coronary circulation.

PubMed

Lee, Sewon; Yang, Yan; Tanner, Miles A; Li, Min; Hill, Michael A

2015-02-01

Kv7 channels are considered important regulators of vascular smooth muscle contractility. The present study aimed to examine the hypotheses that (i) Kv7 channels are present in mouse cerebral and coronary arteries and regulate vascular reactivity and (ii) regional differences exist in the activity of these channels. PCR confirmed that basilar, Circle of Willis and LAD arteries express predominantly Kv7.1 and 7.4. Western blot analysis, however, showed greater Kv7.4 protein levels in the cerebral vessels. Relaxation to the Kv7 channel activator, retigabine (1-50 μM) was significantly greater in the basilar artery compared to the LAD artery. Similarly, the Kv7 channel inhibitor, linopirdine (10 μM) caused a stronger contraction of the basilar artery. Furthermore, pre-incubation with linopirdine reduced forskolin (cAMP activator)-induced vasorelaxation in basilar while not altering forskolin-induced vasorelaxation of the LAD, suggesting that Kv7 channels play a more prominent role in the cerebral than in the coronary circulation. Consistent with the vessel data, whole cell Kv7 currents in cerebral VSMCs were potentiated by retigabine and inhibited by linopirdine, while these responses were blunted in coronary VSMCs. This study provides evidence that mouse Kv7 channels may contribute differently to regulating the functional properties of cerebral and coronary arteries. Such heterogeneity has important implications for developing novel therapeutics for cardiovascular dysfunction. © 2014 John Wiley & Sons Ltd.

Heterogeneity in Kv7 channel function in the Cerebral and Coronary Circulation

PubMed Central

Tanner, Miles A.; Li, Min; Hill, Michael A.

2014-01-01

Kv7 channels are considered important regulators of vascular smooth muscle contractility. The present study examined the hypotheses that 1. Kv7 channels are present in mouse cerebral and coronary arteries and regulate vascular reactivity, and 2. regional differences exist in the activity of these channels. PCR confirmed that basilar, Circle of Willis and left anterior descending (LAD) arteries express predominantly Kv7.1 and 7.4. Western blot analysis, however, showed greater Kv7.4 protein levels in the cerebral vessels. Relaxation to the Kv7 channel activator, retigabine (1-50μM) was significantly greater in basilar compared to LAD. Similarly, the Kv7 channel inhibitor, linopirdine (10μM) caused stronger contraction of the basilar artery. Furthermore, pre-incubation with linopirdine reduced forskolin (cAMP activator)-induced vasorelaxation in basilar while not altering forskolin-induced vasorelaxation of the LAD, suggesting that Kv7 channels play a more prominent role in the cerebral than coronary circulation. Consistent with the vessel data, whole cell Kv7 currents in cerebral VSMCs were potentiated by retigabine and inhibited by linopirdine, while these responses were blunted in coronary VSMCs. This study provides evidence that mouse Kv7 channels may contribute differently to regulating the functional properties of cerebral and coronary arteries. Such heterogeneity has important implications for developing novel therapeutics for cardiovascular dysfunction. PMID:25476662

Effects of amlodipine and adenosine on coronary haemodynamics: in vivo study and numerical simulation.

PubMed

De Lazzari, Claudio; L'Abbate, Antonio; Micalizzi, Mauro; Trivella, Maria Giovanna; Neglia, Danilo

2014-11-01

Amlodipine (AMLO) is a calcium channel blocker with vasodilating properties, in which the specific effects on the coronary circulation are not fully known. Coronary flow velocity-pressure (F/P) curves were obtained at rest and during administration of AMLO (10 mg to 20 mg iv) or adenosine (ADO, 1 mg ic) in 10 normal subjects (six women, age 48 ± 14 years). F/P curves were reproduced in a numerical simulator of systemic and coronary circulations (CARDIOSIM(©)) by adjustment of coronary resistance ( > or < 100 μm diameter vessels) and extravascular resistance applied to smaller vessels at endocardial (ENDO), middle and epicardial (EPI) myocardial layers. Best matching of in silico to in vivo curves was achieved by trial and error approach. ADO induced 170% and 250% increase in coronary flow velocity CFV and F/P diastolic slope as compared to 80% and 25-30% increase induced by AMLO, respectively. In the cardiovascular model, AMLO effects were predicted by progressive reduction of>100 μm vessels resistance from EPI to ENDO. ADO effects were mimicked by reducing resistance of both>100 μm and < 100 μm vessels, progressively from EPI to ENDO in the latter. Additional reduction in extravascular resistance avoided to impose a transmural gradient of vasodilating effect for both drugs. Numerical simulation predicts vasodilating effects of AMLO mainly on larger arteries and of ADO on both>and < 100 μm vessels. In vivo F/P loops could be completely reproduced in silico by adding extravascular resistance reduction for both drugs. Numerical simulator is useful tool for exploring the coronary effects of cardioactive drugs.

Association between circulating microRNA-208a and severity of coronary heart disease.

PubMed

Zhang, Yao; Li, Hai-Hong; Yang, Rui; Yang, Bai-Jing; Gao, Zhao-Yu

2017-09-01

Circulating microRNA (miR)-208a is specifically expressed in the heart muscle, which is involved in the regulation of myosin during cardiac development. Previous studies reported that cardiac-specific miR-208a level is significantly higher in plasma of coronary heart disease (CHD) patients. However, whether it correlates with severity of CHD, has never been elucidated before. The aim of this study was to explore the association between miR-208a and the presence and severity of CHD. Samples were collected from 290 CHD patients and 110 subjects with angiographic exclusion of CHD. Circulating miRNA-208a expression was detected using quantitative real-time PCR. The Gensini score was used to evaluate the severity of coronary stenotic lesions. Expression of miRNA-208a was identified on the basis of the quartiles of the Gensini score, and association between the miRNA-208a levels and CHD was analyzed. Diagnostic potential of miR-208a of CHD was performed by ROC analysis. CHD patients had higher miRNA-208a expression (1.61, 0.45-3.86 vs. 0.66, 0.11-1.42, p < .001), and the biomarker level significantly increased following an increasing the Gensini score (p < .001). Gensini score was significantly associated with miRNA-208a expression (r = 0.8525, p < .001). The optimal cut-off value of the relative level of miR-208a was with a specificity of 93.6% and a sensitivity of 75.5%. The AUC of miR-208a was 0.919 (95% CI, 0.893-0.945; p < .001). These preliminary results suggest that the expression of miR-208a may be associated with atherogenesis. The level of circulating miR-208a in predicting the severity of coronary atherosclerosis may have a relatively certain value.

Scaling laws of coronary circulation in health and disease.

PubMed

Huo, Yunlong; Kassab, Ghassan S

2016-08-16

The heterogeneity and complexity of coronary vasculature (structure) and myocardial flow (function) have fractal-like characteristics and can be described by scaling laws with remarkable simplicity. In contrast with allometric (interspecific) scaling law, intraspecific scaling laws describe the design rules of vascular trees within a species. This paper provides an overview of intraspecific scaling laws of vascular trees and the physiological and clinical implications thereof. The significance and shortcomings of these scaling laws are discussed in relation to diffuse coronary artery disease, Glagov's positive remodeling in early stages of coronary atherosclerosis, treatment guidelines of complex bifurcation lesions, and for estimation of outlet resistance values for computation of blood flow in epicardial coronary arteries. Finally, we summarize the highlights of scaling relations and suggest some future directions. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effect of postprandial hyperglycaemia on coronary flow reserve in patients with impaired glucose tolerance and type 2 diabetes mellitus.

PubMed

Ikeda, Hiroyuki; Uzui, Hiroyasu; Morishita, Tetsuji; Fukuoka, Yoshitomo; Sato, Takehiko; Ishida, Kentaro; Kaseno, Kenichi; Arakawa, Kenichiro; Amaya, Naoki; Tama, Naoto; Shiomi, Yuichiro; Lee, Jong-Dae; Tada, Hiroshi

2015-11-01

This study investigated whether postprandial hyperglycaemia has an adverse effect on coronary microvascular function and left ventricular diastolic function. In all, 28 patients with type 2 diabetes mellitus with no significant stenosis in left anterior descending artery were enrolled. In all subjects, plasma 1,5-anhydroglucitol was measured, and coronary flow reserve in the left anterior descending artery was evaluated using a Doppler wire. Membrane type-1 matrix metalloproteinase expression on circulating peripheral blood mononuclear cells was measured by flow cytometry. Correlation analyses were performed for coronary flow reserve and 1,5-anhydroglucitol, other coronary risk factors, membrane type-1 matrix metalloproteinase and E/e'. Strong correlations were found only between 1,5-anhydroglucitol and coronary flow reserve and membrane type-1 matrix metalloproteinase. On multiple regression analysis, 1,5-anhydroglucitol remained an independent predictor of coronary flow reserve (β = 0.38, p = 0.048). Postprandial hyperglycaemia appears to have an adverse effect on coronary microvascular function, suggesting that improvement of postprandial hyperglycaemia may contribute to the improvement of coronary microvascular dysfunction. © The Author(s) 2015.

Coronary artery bypass grafting in octogenarians: only when percutaneous coronary intervention is not feasible?

PubMed

Nicolini, Francesco

2015-11-01

The aim of this study was to review recent literature reporting the results of coronary revascularization by percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) in patients older than 80 years. The review of recent studies on octogenarians demonstrates a surgical CABG advantage in the case of patients with increasing baseline coronary risk, such as severe multivessel disease, chronic total occlusions, and left ventricular dysfunction. PCI seems to be more appropriate for less severe degree and distribution of coronary lesions, and for subgroups of patients with higher surgical risk, such as acute coronary syndromes, reoperations, malignancy, dementia, poor mobility, frailty, and serious comorbidities contraindicating extracorporeal circulation. It is not the case that CABG is indicated only when there are contraindications to PCI. CABG confers more benefit than PCI in patients with increasing baseline cardiac risk, in the absence of serious systemic diseases that can reasonably reduce their life expectancy.CABG and PCI, with proper selection, should be considered complementary rather than competitive procedures in the therapy of octogenarians affected by coronary artery disease.

A different kind of Christmas tree: anomalous origin of the right coronary artery from the pulmonary artery (ARCAPA).

PubMed

Afolabi-Brown, Olayinka; Witzke, Christian; Moldovan, Raul; Pressman, Gregg

2014-02-01

Anomalous right coronary artery from the pulmonary artery (ARCAPA) is a rare congenital coronary anomaly that has an incidence of 0.002%. We report a case of a previously healthy female who presented to our hospital with pneumonia and was incidentally discovered to have ARCAPA. This was initially diagnosed on echocardiography by the unusual echocardiographic finding of multiple color flow Doppler signals around the right ventricular free wall and apex which were subsequently confirmed by angiography to be due to extensive collateral circulation between the left and right coronary arteries. This represents an unusual echocardiographic manifestation of this very rare condition. © 2013, Wiley Periodicals, Inc.

Circulating dendritic cell precursors in chronic kidney disease: a cross-sectional study.

PubMed

Paul, Katharina; Kretzschmar, Daniel; Yilmaz, Atilla; Bärthlein, Barbara; Titze, Stephanie; Wolf, Gunter; Busch, Martin

2013-12-10

Dendritic cells (DC) are professional antigen-presenting cells in the immune system. They patrol the blood as circulating dendritic cell precursors (DCP). Decreased blood DCP count has been shown to be related to atherosclerotic plaque burden. Since chronic kidney disease (CKD) is associated with chronic inflammation and increased cardiovascular risk, the aim of our study was to investigate a potential effect of CKD on circulating DCP numbers especially in patients with a history of cardiovascular disease. The number of circulating myeloid (mDCP), plasmacytoid (pDCP), and total DCP (tDCP) was analysed by flow cytometry in 245 patients with CKD stage 3 (with and without known cardiovascular events) and 85 coronary healthy controls. In addition, data were compared with a historical group of 130 patients with known coronary artery disease (CAD). Compared to controls, patients with CKD 3 revealed a significant decrease in circulating mDCP (-29%), pDCP (-43%), and tDCP (-38%) (P < 0.001, respectively). Compared with CAD-patients, the decrease in circulating DCP in CKD was comparable or even more pronounced indicating a potential role for DCP in cardiovascular risk potentiation due to CKD. Based on previous findings in CAD, the marked decrease of DCP in CKD implicates a potential role for DCP as a mediator of cardiovascular disease. Whether DCP in CKD may act as new cardiovascular biomarkers needs to be established in future prospective trials.

Myocardial blood flow: Roentgen videodensitometry techniques

NASA Technical Reports Server (NTRS)

Smith, H. C.; Robb, R. A.; Wood, E. H.

1975-01-01

The current status of roentgen videodensitometric techniques that provide an objective assessment of blood flow at selected sites within the coronary circulation were described. Roentgen videodensitometry employs conventional radiopaque indicators, radiological equipment and coronary angiographic techniques. Roentgen videodensitometry techniques developed in the laboratory during the past nine years, and for the past three years were applied to analysis of angiograms in the clinical cardiac catheterization laboratory.

Wave intensity analysis and its application to the coronary circulation

PubMed Central

Davies, JE; Escaned, JE; Hughes, A; Parker, K

Wave intensity analysis (WIA) is a technique developed from the field of gas dynamics that is now being applied to assess cardiovascular physiology. It allows quantification of the forces acting to alter flow and pressure within a fluid system, and as such it is highly insightful in ascribing cause to dynamic blood pressure or velocity changes. When co-incident waves arrive at the same spatial location they exert either counteracting or summative effects on flow and pressure. WIA however allows waves of different origins to be measured uninfluenced by other simultaneously arriving waves. It therefore has found particular applicability within the coronary circulation where both proximal (aortic) and distal (myocardial) ends of the coronary artery can markedly influence blood flow. Using these concepts, a repeating pattern of 6 waves has been consistently identified within the coronary arteries, 3 originating proximally and 3 distally. Each has been associated with a particular part of the cardiac cycle. The most clinically relevant wave to date is the backward decompression wave, which causes the marked increase in coronary flow velocity observed at the start of the diastole. It has been proposed that this wave is generated by the elastic re-expansion of the intra-myocardial blood vessels that are compressed during systolic contraction. Particularly by quantifying this wave, WIA has been used to provide mechanistic and prognostic insight into a number of conditions including aortic stenosis, left ventricular hypertrophy, coronary artery disease and heart failure. It has proven itself to be highly sensitive and as such a number of novel research directions are encouraged where further insights would be beneficial. PMID:28971104

Plasma Omentin-1 Level as a Predictor of Good Coronary Collateral Circulation.

PubMed

Zhou, Ji-Peng; Tong, Xiao-Yu; Zhu, Ling-Ping; Luo, Jing-Min; Luo, Ying; Bai, Yong-Ping; Li, Chuan-Chang; Zhang, Guo-Gang

2017-09-01

Coronary collateral circulation (CCC) is crucial during an acute ischemic attack. Evidences showed that omentin-1 exhibited remarkable antiatherogenic effects and ischemia-induced revascularization. The aim of this study was to investigate the relationship between plasma omentin-1 levels and CCC in patients with ≥90% angiography-proven coronary occlusion. 142 patients with ≥90% luminal diameter stenosis in at least one major epicardial coronary artery were recruited. Among them, 79 patients with Rentrop 0-1 grade were classified into the poor CCC group and 63 patients with Rentrop 2-3 grade were included into the good CCC group. The association between plasma omentin-1 levels and CCC status was assessed. Plasma omentin-1 level was significantly higher in patients with good CCC than those with poor CCC (566.57±26.90 vs. 492.38±19.70 ng/mL, p=0.024). Besides, omentin-1 was positively correlated with total cholesterol (TC), high-density lipoprotein, and gensini score but inversely with hyperlipidemia and body mass index (all p values＜0.05). Multivariate regression analysis indicated that omentin-1 [odds ratio (OR)=1.002, 95% confidence interval (CI): 1.000-1.004, p=0.041)], TC, the number of the diseased vessels, a higher frequency of left circumflex artery and right coronary artery, chronic total occlusion, and gensini score remained as the independent predictors of good CCC. Higher plasma omentin-1 level was associated with better CCC development. Our findings suggest that omentin-1 may be an alternative marker for adequate CCC in patients with ≥90% coronary occlusion.

Dynamic interaction between myocardial contraction and coronary flow.

PubMed

Beyar, R; Sideman, S

1997-01-01

Phasic coronary flow is determined by the dynamic interaction between central hemodynamics and myocardial and ventricular mechanics. Various models, including the waterfall, intramyocardial pump and myocardial structural models, have been proposed for the coronary circulation. Concepts such as intramyocardial pressure, local elastance and others have been proposed to help explain the coronary compression by the myocardium. Yet some questions remain unresolved, and a new model has recently been proposed, linking a muscle collagen fibrous model to a physiologically based coronary model, and accounting for transport of fluids across the capillaries and lymphatic flow between the interstitial space and the venous system. One of the unique features of this model is that the intramyocardial pressure (IMP) in the interstitial space is calculated from the balance of forces and fluid transport in the system, and is therefore dependent on the coronary pressure conditions, the myocardial function and the transport properties of the system. The model predicts a wide range of experimentally observed phenomena associated with coronary compression.

Coronary artery surgery: indications and recent experience.

PubMed Central

Robinson, P. S.; Coltart, D. J.; Jenkins, B. S.; Webb-Peploe, M. M.; Braimbridge, M. V.; Williams, B. T.

1978-01-01

The comprehensive experience of coronary artery surgery in a Cardiothoracic Unit over a 31-month period is reviewed. Hospital mortality for elective bypass grafting was 3.9% overall and 2.5% in those with good pre-operative left ventricular function. Major influences on hospital mortality were pre-operative left ventricular function, extent of coronary artery disease and extent of the surgical procedure undertaken in terms of number of aortocoronary grafts inserted, coronary endarterectomy and particularly concomitant valve surgery or aneurysm resection. Follow-up experience shows 74% of grafted patients to be symptom-free and 85% symptomatically improved one year after surgery with 70% symptom-free and 80% improved at two years. Early post-operative deaths appear related to early graft closure and recurrence of symptoms postoperatively to late graft closure or progression of coronary disease in the native circulation. The study provides a guide to the relative risks of coronary artery surgery for symptomatic coronary artery disease and expected symptomatic results in the early follow-up period. PMID:310999

Coronary artery bypass grafting with minimal versus conventional extracorporeal circulation; an economic analysis.

PubMed

Anastasiadis, K; Fragoulakis, V; Antonitsis, P; Maniadakis, N

2013-10-15

This study aims to develop a methodological framework for the comparative economic evaluation between Minimal Extracorporeal Circulation (MECC) versus conventional Extracorporeal Circulation (CECC) in patients undergoing coronary artery bypass grafting (CABG) in different healthcare systems. Moreover, we evaluate the cost-effectiveness ratio of alternative comparators in the healthcare setting of Greece, Germany, the Netherlands and Switzerland. The effectiveness data utilized were derived from a recent meta-analysis which incorporated 24 randomized clinical trials. Total therapy cost per patient reflects all resources expensed in delivery of therapy and the management of any adverse events, including drugs, diagnostics tests, materials, devices, blood units, the utilization of operating theaters, intensive care units, and wards. Perioperative mortality was used as the primary health outcome to estimate life years gained in treatment arms. Bias-corrected uncertainty intervals were calculated using the percentile method of non-parametric Monte-Carlo simulation. The MECC circuit was more expensive than CECC, with a difference ranging from €180 to €600 depending on the country. However, in terms of total therapy cost per patient the comparison favored MECC in all countries. Specifically it was associated with a reduction of €635 in Greece, €297 in Germany, €1590 in the Netherlands and €375 in Switzerland. In terms of effectiveness, the total life-years gained were slightly higher in favor of MECC. Surgery with MECC may be dominant (lower cost and higher effectiveness) compared to CECC in coronary revascularization procedures and therefore it represents an attractive new option relative to conventional extracorporeal circulation for CABG. © 2013.

Highly increased Troponin I levels following high-intensity endurance cycling may detect subclinical coronary artery disease in presumably healthy leisure sport cyclists: The North Sea Race Endurance Exercise Study (NEEDED) 2013.

PubMed

Skadberg, Øyvind; Kleiven, Øyunn; Bjørkavoll-Bergseth, Magnus; Melberg, Tor; Bergseth, Rolf; Selvåg, Jone; Auestad, Bjørn; Greve, Ole J; Dickstein, Kenneth; Aarsland, Torbjørn; Ørn, Stein

2017-05-01

Background Circulating cardiac troponin levels increase following prolonged intense physical exercise. The aim of this study was to identify participants with highly elevated cardiac troponins after prolonged, high intensity exercise, and to evaluate these for subclinical coronary artery disease. Methods and results Ninety-seven recreational cyclists without known cardiovascular disease or diabetes, participating in a 91 km mountain bike race were included, 74 (76%) were males, age: 43 ± 10 years, race duration: 4.2 (3.6-4.7) h. Blood samples, rest electrocardiogram and physical examination were obtained 24 h prior to, and at 0, 3 and 24 h following the race. Median cardiac troponin I level at baseline: 3.4 (2.1-4.9) ng/l (upper limit of normal: 30.0 ng/l). There was a highly significant ( p < 0.0001) increase in circulating cardiac troponin I in all participants: immediately following the race; 50.5 (28.5-71.9) ng/l, peaking at 3 h 69.3 (42.3-97.7) ng/l and declining at 24 h: 14.2 (8.5-27.9) ng/l. No cyclist had symptoms or rest electrocardiogram changes compatible with coronary artery disease during or following the race. Coronary artery disease was detected by coronary angiography in the three cyclists with the three of the four highest cardiac troponin values (>370 ng/l) at 3 and 24 h following the race. Computed tomographic coronary angiography was performed in an additional 10 riders with the subsequently highest cardiac troponin I values, without identifying underlying coronary artery disease. Conclusions This study suggests that there is a pathologic cardiac troponin I response following exercise in individuals with subclinical coronary artery disease. This response may be associated with an excessive cardiac troponin I increase at 3 and 24 h following prolonged high-intensity exercise.

An integrated coronary circulation teaching model.

PubMed

van Oostrom, Johannes H; Kentgens, S; Beneken, J E W; Gravenstein, J S

2006-08-01

We present in this paper a model of the coronary circulation. This model is integrated with a model of the systemic circulation, and contains models for oxygen supply and demand. Three compartments are created: one for the right ventricle, one for the epicardial segment of the left ventricle and one for the endo-cardial segment of the left ventricle. The model was implemented in the Java programming language and contains a visual representation of the left and right ventricles which beat in real time. Color shading is used to represent the partial pressure of oxygen in the segments. A multitude of model parameters can be changed to simulate different scenarios. The output of the model was characterized under different conditions and the results verified by clinicians. Educational models of human physiology can be very useful for a more in depth understanding of complete physiologic systems. The models must however have enough complexity, interaction with other systems, and realism to show the concepts being taught.

Acute stress cardiomyopathy and deaths associated with electronic weapons.

PubMed

Cevik, Cihan; Otahbachi, Mohammad; Miller, Elizabeth; Bagdure, Satish; Nugent, Kenneth M

2009-03-06

Deaths associated with the use of electronic weapons almost always occur in young men involved in either civil disturbances or criminal activity. These situations are associated with high levels of circulating catecholamines and frequently associated with drug intoxication. The mechanism for these deaths is unclear. Clinical studies indicate that these high voltage electrical pulses do not cause cardiac arrhythmia. Acute stress cardiomyopathy provides an alternative explanation for deaths associated with electronic weapons and may provide a better explanation for the usual time course associated with taser deaths. Patients with acute stress cardiomyopathy usually have had an emotional or physical stress, have high circulating levels of catecholamines, present with an acute coronary syndrome but have normal coronary vessels without significant thrombus formation. They have unusual left ventricular dysfunction with so-called apical ballooning. This presentation has been attributed to the direct effects of catecholamines on myocardial cell function. Alternative explanations include vasospasm in the coronary microcirculation and/or acute thrombosis followed by rapid thrombolysis. Similar events could occur during the high stress situations associated with the use of electronic weapons. These events also likely explain restraint-related deaths which occur in independent of any use of electronic weapons. Forensic pathologists have the opportunity to provide important details about the pathogenesis of these deaths through histological studies and careful evaluation of coronary vessels.

Changes of electrocardiogram and hemodynamics in response to dipyridamole: In vivo comparative analyses using anesthetized beagle dogs and microminipigs.

PubMed

Ando, Kentaro; Takahara, Akira; Nakamura, Yuji; Wada, Takeshi; Chiba, Koki; Goto, Ai; Lubna, Nur Jaharat; Hagiwara-Nagasawa, Mihoko; Izumi-Nakaseko, Hiroko; Hoshiai, Kiyotaka; Akie, Yasuki; Naito, Atsuhiko T; Sugiyama, Atsushi

2018-02-01

Microminipigs are expected as a novel animal model for cardiovascular pharmacological experiments. Since inherent vulnerability of coronary circulation of microminipigs has not been characterized, we performed dipyridamole-stress test to both microminipigs and beagle dogs, and compared the results. Dipyridamole in doses of 0.056 and 0.56 mg/kg were intravenously infused over 10 min (n = 4 for each animal). Dipyridamole decreased the systolic/diastolic blood pressures and double product in dogs as well as in microminipigs; but it did not significantly alter the heart rate or the global balance between the myocardial oxygen demand and supply in either animal. While organic coronary arterial stenosis was not detected in either animal, dogs have well-developed epicardial intracoronary networks unlike microminipigs. Like in humans, dipyridamole did not affect the ST segment of microminipigs, whereas it substantially depressed that in dogs. The results indicate the onset of subendocardial ischemia by dipyridamole in dogs may be partly associated with their well-developed native coronary collateral channels. Microminipigs would be more useful to evaluate the drugs which may affect the coronary circulation in the pre-clinical study than dogs. Copyright © 2018 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Circulating factors induce coronary endothelial cell activation following exposure to inhaled diesel exhaust and nitrogen dioxide in humans: Evidence from a novel translational in vitro model**

EPA Science Inventory

The vascular toxicity of inhaled agents may be caused by soluble factors that are released into the systemic circulation. To confirm this in a straightforward manner, we obtained plasma from healthy human volunteers before and after exposure to diesel exhaust (DE) and nitrogen di...

Off-pump compared to minimal extracorporeal circulation surgery in coronary artery bypass grafting.

PubMed

Reuthebuch, Oliver; Koechlin, Luca; Gahl, Brigitta; Matt, Peter; Schurr, Ulrich; Grapow, Martin; Eckstein, Friedrich

2014-01-01

Coronary artery bypass grafting (CABG) using extracorporeal circulation (ECC) is still the gold standard. However, alternative techniques have been developed to avoid ECC and its potential adverse effects. These encompass minimal extracorporeal circulation (MECC) or off-pump coronary artery bypass grafting (OPCAB). However, the prevailing potential benefits when comparing MECC and OPCABG are not yet clearly established. In this retrospective study we investigated the potential benefits of MECC and OPCABG in 697 patients undergoing CABG. Of these, 555 patients had been operated with MECC and 142 off-pump. The primary endpoint was Troponin T level as an indicator for myocardial damage. Study groups were not significantly different in general. However, patients undergoing OPCABG were significantly older (65.01 years ± 9.5 vs. 69.39 years ± 9.5; p value <0.001) with a higher Logistic EuroSCORE I (4.92% ± 6.5 vs. 5.88% ± 6.8; p value = 0.017). Operating off pump significantly reduced the need for intra-operative blood products (0.7% vs. 8.6%; p-value <0.001) and the length of stay in the intensive care unit (ICU) (2.04 days ± 2.63 vs. 2.76 days ± 2.79; p value <0.001). Regarding other blood values a significant difference could not be found in the adjusted calculations. The combined secondary endpoint, major cardiac or cerebrovascular events (MACCE), was equal in both groups as well. Coronary artery bypass grafting using MECC or OPCABG are two comparable techniques with advantages for OPCABG regarding the reduced need for intra-operative blood products and shorter length of stay in the ICU. However serological values and combined endpoint MACCE did not differ significantly in both groups.

Coronary Collateral Growth—Back to the Future

PubMed Central

Chilian, William M.; Penn, Marc S.; Pung, Yuh Fen; Dong, Feng; Mayorga, Maritza; Ohanyan, Vahagn; Logan, Suzanna; Yin, Liya

2012-01-01

The coronary collateral circulation is critically important as an adaptation of the heart to prevent the damage from ischemic insults. In their native state, collaterals in the heart would be classified as part of the microcirculation, existing as arterial-arterial anastomotic connections in the range of 30 to 100 μM in diameter. However, these vessels also show a propensity to remodel into components of the macrocirculation and can become arteries larger than a 1000 μM in diameter. This process of outward remodelling is critically important in the adaptation of the heart to ischemia because the resistance to blood flow is inversely related to the fourth power of the diameter of the vessel. Thus, an expansion of a vessel from 100 to 1000 μM would reduce resistance (in this part of the circuit) to a negligible amount and enable delivery of flow to the region at risk. Our goal in this review is to highlight the voids in understanding this adaptation to ischemia—the growth of the coronary collateral circulation. In doing so we discuss the controversies and unknown aspects of the causal factors that stimulate growth of the collateral circulation, the role of genetics, and the role of endogenous stem and progenitor cells in the context of the normal, physiological situation and under more pathological conditions of ischemic heart disease or with some of the underlying risk factors, e.g., diabetes. The major conclusion of this review is that there are many gaps in our knowledge of coronary collateral growth and this knowledge is critical before the potential of stimulating collateralization in the hearts of patients can be realized. PMID:22210280

Medical imaging with synchrotron radiation

NASA Astrophysics Data System (ADS)

Rubenstein, Edward

1984-05-01

The present methods of detecting coronary artery disease before it causes serious heart damage or sudden death are unsatisfactory, because of the insensitivity of the screening tests and excessive risks and costs of the invasive coronary arteriographic technique. A number of other diagnostic approaches have been tried, but none has succeeded to date in providing the needed detailed information about the status of the coronary circulation. The intensity, monochromaticity and tunability of synchrotron radiation are well-suited for iodine K edge dichromographic angiography. In vivo images of the left anterior descending coronary artery of the dog have been recorded using synchrotron X-ray beams in this manner. Beams wide enough to record the image of the entire human heart in a single scanned swath are now under design.

External Compression of Epicardial Coronary Arteries with Partial Calcific Pericarditis

PubMed Central

Khan, Zubair Ahmed; Sardar, Muhammad Rizwan; Topalian, Simon K.

2017-01-01

Calcific pericarditis (CP) is a rare disease which results from long-standing pericardial inflammation. Pericardial calcification may completely or partially encase the ventricles, resulting in impaired diastolic filling. We present a case of a 53-year-old male who was incidentally found to have annular CP resulting in external compression of a large territory diagonal branch (D1) reaching the apex with likely chronically occluded left anterior descending artery with collateral circulation from the right coronary artery with hemodynamic compromise on coronary angiography. This was emergently treated with a drug-eluting stent with improved D1 flow and entailed the importance of percutaneous coronary intervention as a viable option in cases of CP resulting in acute hemodynamic compromise. PMID:28584590

External Compression of Epicardial Coronary Arteries with Partial Calcific Pericarditis.

PubMed

Khan, Zubair Ahmed; Sardar, Muhammad Rizwan; Topalian, Simon K

2017-01-01

Calcific pericarditis (CP) is a rare disease which results from long-standing pericardial inflammation. Pericardial calcification may completely or partially encase the ventricles, resulting in impaired diastolic filling. We present a case of a 53-year-old male who was incidentally found to have annular CP resulting in external compression of a large territory diagonal branch (D1) reaching the apex with likely chronically occluded left anterior descending artery with collateral circulation from the right coronary artery with hemodynamic compromise on coronary angiography. This was emergently treated with a drug-eluting stent with improved D1 flow and entailed the importance of percutaneous coronary intervention as a viable option in cases of CP resulting in acute hemodynamic compromise.

Connecting the coronaries: How the coronary plexus develops and is functionalized

PubMed Central

Dyer, Laura; Pi, Xinchun; Patterson, Cam

2015-01-01

The establishment of the coronary circulation is one of the final critical steps during heart development. Despite decades of research, our understanding of how the coronary vasculature develops and connects to the aorta remains limited. This review serves two specific purposes: it addresses recent advances in understanding the origin of the coronary endothelium, and it then focuses on the last crucial step of coronary vasculature development, the connection of the coronary plexus to the aorta. The chick and quail animal models have yielded most of the information for how these connections form, starting with a fine network of vessels that penetrate the aorta and coalesce to form two distinct ostia. Studies in mouse and rat confirm that at least some of these steps are conserved in mammals, but gaps still exist in our understanding of mammalian coronary ostia formation. The signaling cues necessary to guide the coronary plexus to the aorta are also incompletely understood. Hypoxia-inducible transcription factor-1 and its downstream targets are among the few identified genes that promote the formation of the coronary stems. Together, this review summarizes our current knowledge of coronary vascular formation and highlights the significant gaps that remain. In addition, it highlights some of the coronary artery anomalies known to affect human health, demonstrating that even seemingly subtle defects arising from incorrect coronary plexus formation can result in significant health crises. PMID:25173872

Cocaine-induced microvascular vasoconstriction but differential systemic haemodynamic responses in Yucatan versus Yorkshire varieties of swine.

PubMed Central

Miao, L.; Núñez, B. D.; Susulic, V.; Wheeler, S.; Carrozza, J. P.; Ross, J. N.; Morgan, J. P.

1996-01-01

1. Systemic and coronary haemodynamics were measured in 6 Yorkshire swine and 6 Yucatan miniature swine under isoflurane anaesthesia to investigate the influence of cocaine following its intravenous administration at 1, 3 and 7 mg kg-1. 2. Cocaine in Yorkshire swine decreased mean arterial pressure and rate pressure product (systolic pressure x heart rate), suggesting a cardiac depressant effect, whereas cocaine in Yucatan miniature swine increased these parameters, consistent with a hyperadrenergic state. 3. Cocaine in both Yorkshire swine and Yucatan miniature swine decreased coronary blood flow and coronary flow reserve, and increased coronary vascular resistance. 4. A modest generalized epicardial coronary artery constriction was observed by angiography, without evidence of focal spasm. 5. Our results confirm a marked vasoconstrictor effect of cocaine on the coronary arterial circulation, predominantly distal to the epicardial coronary arteries, but also indicate important differences in the systemic cardiovascular responses to the drug between two closely related strains of animals within the same species. Due to the similarities between the swine and human coronary arterial vasculature, we suggest that vasoconstriction in the coronary microcirculation may produce cardiac toxicity in man. PMID:8821549

Ventricular Fibrillation Waveform Changes during Controlled Coronary Perfusion Using Extracorporeal Circulation in a Swine Model.

PubMed

Gazmuri, Raúl J; Kaufman, Christopher L; Baetiong, Alvin; Radhakrishnan, Jeejabai

2016-01-01

Several characteristics of the ventricular fibrillation (VF) waveform have been found predictive of successful defibrillation and hypothesized to reflect the myocardial energy state. In an open-chest swine model of VF, we modeled "average CPR" using extracorporeal circulation (ECC) and assessed the time course of coronary blood flow, myocardial metabolism, and myocardial structure in relation to the amplitude spectral area (AMSA) of the VF waveform without artifacts related to chest compression. VF was induced and left untreated for 8 minutes in 16 swine. ECC was then started adjusting its flow to maintain a coronary perfusion pressure of 10 mmHg for 10 minutes. AMSA was calculated in the frequency domain and analyzed continuously with a 2.1 s timeframe and a Tukey window that moved ahead every 0.5 s. AMSA progressively declined during untreated VF. With ECC, AMSA increased from 7.0 ± 1.9 mV·Hz (at minute 8) to 12.8 ± 3.3 mV·Hz (at minute 14) (p < 0.05) without subsequent increase and showing a modest correlation with coronary blood flow of borderline statistical significance (r = 0.489, p = 0.0547). Myocardial energy measurements showed marked reduction in phosphocreatine and moderate reduction in ATP with increases in ADP, AMP, and adenosine along with myocardial lactate, all indicative of ischemia. Yet, ischemia did not resolve during ECC despite a coronary blood flow of ~ 30% of baseline. AMSA increased upon return of coronary blood flow during ECC. However, the maximal level was reached after ~ 6 minutes without further change. The significance of the findings for determining the optimal timing for delivering an electrical shock during resuscitation from VF remains to be further explored.

Plasma Omentin-1 Level as a Predictor of Good Coronary Collateral Circulation

PubMed Central

Zhou, Ji-Peng; Tong, Xiao-Yu; Zhu, Ling-Ping; Luo, Jing-Min; Luo, Ying; Bai, Yong-Ping

2017-01-01

Aims: Coronary collateral circulation (CCC) is crucial during an acute ischemic attack. Evidences showed that omentin-1 exhibited remarkable antiatherogenic effects and ischemia-induced revascularization. The aim of this study was to investigate the relationship between plasma omentin-1 levels and CCC in patients with ≥ 90% angiography-proven coronary occlusion. Methods: 142 patients with ≥ 90% luminal diameter stenosis in at least one major epicardial coronary artery were recruited. Among them, 79 patients with Rentrop 0–1 grade were classified into the poor CCC group and 63 patients with Rentrop 2–3 grade were included into the good CCC group. The association between plasma omentin-1 levels and CCC status was assessed. Results: Plasma omentin-1 level was significantly higher in patients with good CCC than those with poor CCC (566.57 ± 26.90 vs. 492.38 ± 19.70 ng/mL, p = 0.024). Besides, omentin-1 was positively correlated with total cholesterol (TC), high-density lipoprotein, and gensini score but inversely with hyperlipidemia and body mass index (all p values < 0.05). Multivariate regression analysis indicated that omentin-1 [odds ratio (OR) = 1.002, 95% confidence interval (CI): 1.000 – 1.004, p = 0.041)], TC, the number of the diseased vessels, a higher frequency of left circumflex artery and right coronary artery, chronic total occlusion, and gensini score remained as the independent predictors of good CCC. Conclusion: Higher plasma omentin-1 level was associated with better CCC development. Our findings suggest that omentin-1 may be an alternative marker for adequate CCC in patients with ≥ 90% coronary occlusion. PMID:28123148

Relationship of mean platelet volume to lymphocyte ratio and coronary collateral circulation in patients with stable angina pectoris.

PubMed

Ornek, Ender; Kurtul, Alparslan

2017-09-01

In patients with coronary artery disease, coronary collateral circulation (CCC) develops as an adaptation to ischemia and contributes toward reduction of cardiovascular events. Recently, the mean platelet volume-to-lymphocyte ratio (MPVLR) has emerged as a novel and readily available marker of inflammation and thrombosis. This study aimed to investigate the relationship between MPVLR and development of CCC. A total of 332 patients with stable angina pectoris undergoing coronary arteriography were enrolled and divided on the basis of the development of CCC into two groups: group with adequate CCC (n=243) and group with impaired CCC (n=89). Routine complete blood count parameters and high-sensitivity C-reactive protein (hsCRP) were measured before coronary arteriography. Both MPVLR and hsCRP levels were higher in the impaired CCC group (P<0.001 and P=0.007, respectively). Multivariate logistic regression analysis indicated that MPVLR was associated independently with impaired CCC [odds ratio (OR): 1.706, 95% confidence interval (CI): 1.328-2.192, P<0.001]. In addition to MPVLR, hsCRP (OR: 1.144, P=0.030) and fasting blood glucose (OR: 1.007, P=0.049) were also associated independently with impaired CCC. In receiver operating characteristics curve analysis, an optimal cut-off point for MPVLR (4.47) was found to predict the presence of good CCC with a sensitivity of 75.3% and a specificity of 71.2% (P<0001). Our findings suggest that measurement of MPVLR may predict the development of CCC in patients with stable coronary artery disease. An increased MPVLR is associated independently with impaired CCC in these patients.

Oxidative stress and inflammatory response increase during coronary artery bypass grafting with extracorporeal circulation.

PubMed

Melek, Flora Eli; Baroncini, Liz Andréa Villela; Repka, João Carlos Domingus; Nascimento, Celso Soares; Précoma, Dalton Bertolim

2012-01-01

Thiobarbituric acid-reactive substance is a marker of oxidative stress and has cytotoxic and genotoxic actions. C- reactive protein is used to evaluate the acute phase of inflammatory response. To assess the thiobarbituric acid-reactive substance and C-reactive protein levels during extracorporeal circulation in patients submitted to cardiopulmonary bypass. Twenty-five consecutive surgical patients (16 men and nine women; mean age 61.2 ± 9.7 years) with severe coronary artery disease diagnosed by angiography scheduled for myocardial revascularization surgery with extracorporeal circulation were selected. Blood samples were collected immediately before initializing extracorporeal circulation, T0; in 10 minutes, T10; and in 30 minutes, T30. The thiobarbituric acid-reactive substance levels increased after extracorporeal circulation (P=0.001), with average values in T0=1.5 ± 0.07; in T10=5.54 ± 0.35; and in T30=3.36 ± 0.29 mmoles/mg of serum protein. The C-reactive protein levels in T0 were negative in all samples; in T10 average was 0.96 ± 0.7 mg/dl; and in T30 average was 0.99 ± 0.76 mg/dl. There were no significant differences between the dosages in T10 and T30 (P=0.83). C-reactive protein and thiobarbituric acid-reactive substance plasma levels progressively increased during extracorporeal circulation, with maximum values of thiobarbituric acid-reactive substance at 10 min and of C-reactive protein at 30 min. It suggests that there are an inflammatory response and oxidative stress during extracorporeal circulation.

Mechanics of blood supply to the heart: wave reflection effects in a right coronary artery.

PubMed Central

Zamir, M

1998-01-01

Mechanics of blood flow in the coronary circulation have in the past been based largely on models in which the detailed architecture of the coronary network is not included because of lack of data: properties of individual vessels do not appear individually in the model but are represented collectively by the elements of a single electric circuit. Recent data from the human heart make it possible, for the first time, to examine the dynamics of flow in the coronary network based on detailed, measured vascular architecture. In particular, admittance values along the full course of the right coronary artery are computed based on actual lengths and diameters of the many thousands of branches which make up the distribution system of this vessel. The results indicate that effects of wave reflections on this flow are far more significant than those generally suspected to occur in coronary blood flow and that they are actually the reverse of the well known wave reflection effects in the aorta. PMID:9523440

[Angioplasty in native coronary circulation in patients treated with myocardial revascularization].

PubMed

Pimentel Filho, W A; Ascer, E; Büchler, J R; Assis, S F; Hirschfeld, R; Neves, M; Araújo, E C; Pinheiro, L F; Souza, J A; De Carvalho, V B

1992-05-01

To evaluate the clinical results after angioplasty in the native coronary vessels in patients who had undergone previous coronary artery surgery. From June 1987 to July 1990, 69 patients with previous coronary artery surgery underwent coronary angioplasty in the native arteries. Age ranged from 31 to 82 (mean = 57.5) years, fifty eight were males. Angina was present in all patients. The patients were classified in three groups according to the following criteria: group I--incomplete revascularization following bypass surgery (28 patients); group II--progression of the disease in ungrafted vessels (24 patients) and group III--progression of the disease in grafted vessels (17 patients). Primary success was achieved in 94% (65/69). Ninety-five percent in group I, 92% in group II and 94% in group III. Complications occurred in 4%; emergency surgery or deaths were not observed in this study. Forty patients (61%) repeated coronary arteriography an average follow-up of 4 months and restenosis was detected in 10 (25%); 8 of them were redilated. Survival rates was 95% and 75% of them were free of coronary events after an average follow-up of 13 months. Coronary angioplasty in these patients is a safe and effective interventional procedure in the treatment of coronary artery disease in native coronary vessels.

Immunoglobulins against Tyrosine Nitrated Epitopes in Coronary Artery Disease

PubMed Central

Thomson, Leonor; Tenopoulou, Margarita; Lightfoot, Richard; Tsika, Epida; Parastatidis, Ioannis; Martinez, Marissa; Greco, Todd M.; Doulias, Paschalis-Thomas; Wu, Yuping; Tang, W. H. Wilson; Hazen, Stanley L.; Ischiropoulos, Harry

2012-01-01

Background Several lines of evidence support a pathophysiological role of immunity in atherosclerosis. Tyrosine nitrated proteins, a footprint of oxygen and nitrogen derived oxidants generated by cells of the immune system, are enriched in atheromatous lesions and in circulation of coronary artery disease (CAD) subjects. However, the consequences of possible immune reactions triggered by the presence of nitrated proteins in subjects with clinically documented atherosclerosis have not been explored. Methods and Results Specific immunoglobulins that recognize 3-nitrotyrosine epitopes were identified in human lesions, as well as in circulation of CAD subjects. The levels of circulating immunoglobulins against 3-nitrotyrosine epitopes were quantified in CAD patients (n=374) and subjects without CAD (non CAD controls, n=313). A ten-fold increase in the mean level of circulating immunoglobulins against protein-bound 3-nitrotyrosine was documented in the CAD subjects (3.75 ± 1.8 μg antibody Eq/mL plasma vs. 0.36 ± 0.8 μg antibody Eq/mL plasma), and was strongly associated with angiographic evidence of significant CAD. Conclusions The results of this cross sectional study suggest that post-translational modification of proteins via nitration within atherosclerotic plaque-laden arteries and in circulation serve as neoepitopes for elaboration of immunoglobulins, thereby providing an association between oxidant production and the activation of the immune system in CAD. PMID:23081989

Circulating factors induce coronary endothelial ceIl activation foIlowing exposure to inhaled diesel exhaust and nitrogen dioxide in humans :Evidence from a novel translational in vitro model

EPA Science Inventory

The vascular toxicity of inhaled agents may be caused by soluble factors that are released into the systemic circulation. To confirm this in a straightforward manner, we obtained plasma from healthy human volunteers before and after exposure to diesel exhaust (DE) and nitrogen di...

Myocardial-specific R-spondin3 drives proliferation of the coronary stems primarily through the Leucine Rich Repeat G Protein coupled receptor LGR4.

PubMed

Da Silva, Fabio; Massa, Filippo; Motamedi, Fariba Jian; Vidal, Valerie; Rocha, Ana Sofia; Gregoire, Elodie P; Cai, Chen-Leng; Wagner, Kay Dietrich; Schedl, Andreas

2018-05-31

Coronary artery anomalies are common congenital disorders with serious consequences in adult life. Coronary circulation begins when the coronary stems form connections between the aorta and the developing vascular plexus. We recently identified the WNT signaling modulator R-spondin 3 (Rspo3), as a crucial regulator of coronary stem proliferation. Using expression analysis and tissue-specific deletion we now demonstrate that Rspo3 is primarily produced by cardiomyocytes. Moreover, we have employed CRISPR/Cas9 technology to generate novel Lgr4-null alleles that showed a significant decrease in coronary stem proliferation and thus phenocopied the coronary artery defects seen in Rspo3 mutants. Interestingly, Lgr4 mutants displayed slightly hypomorphic right ventricles, an observation also made after myocardial specific deletion of Rspo3. These results shed new light on the role of Rspo3 in heart development and demonstrate that LGR4 is the principal R-spondin 3 receptor in the heart. Copyright © 2018 Elsevier Inc. All rights reserved.

Stable cavitation using acoustic phase-change dodecafluoropentane nanoparticles for coronary micro-circulation thrombolysis.

PubMed

Hu, Bo; Jiang, Nan; Zhou, Qing; Cao, Sheng; Gao, Shunji; Zhang, Binghong; Chen, Jinling; Guo, Ruiqiang

2018-06-11

The thrombolysis in micro-circulation after acute myocardial infarction has been an unsolved issue, as elimination effect of acute thrombolysis and primary intervention were unsatisfied. Stable cavitation using acoustic phase-change nanoparticles may have potential for thrombolysis. Therefore, we sought to investigate a novel treatment method with dodecafluoropentane (DDFP) nanoparticles for rapid and effective thrombolysis in an in-vitro artificial vascular system, as a mimicking preparation of coronary circulation. To simulate thrombus embolism in coronary circulation, an in-vitro artificial vascular system was established with cavitation effect using DDFP nanoparticles. For PBS blank control (group A), SonoVue microbubbles (group B) and DDFP nanoparticles (group C), the durations for cavitation effect were recorded and the thrombolysis efficiency with low intensity focused ultrasound irradiation in the in-vitro vascular system were analyzed with weight loss and pathological changes of thrombus before and after thrombolysis. The optimal conditions for acoustic cavitation effect were power of 6 W for 20 min by ultrasound irradiation at 37 °C. The weight loss and weight loss rates of thrombus in group C (189.4 ± 30.2 mg and 34.2 ± 5.7%) were higher than those in group A (30.2 ± 16.0 mg and 5.2 ± 2.1%) and group B (84.0 ± 20.4 mg and 14.6 ± 1.5%) (P < 0.01, all). The duration for cavitation effect in group C (32.8 ± 3.9 min) was also longer than those in group A (0.0 ± 0.0 min) and group B (5.3 ± 0.3 min) (P < 0.01, all). By stable and sustaining cavitation in targeted area, DDFP nanoparticles with ultrasound irradiation have significantly increased the thrombolysis efficiency, which has provided a powerful experimental foundation for potential coronary thrombolysis. Copyright © 2017 Elsevier B.V. All rights reserved.

Association of Methylation Signals With Incident Coronary Heart Disease in an Epigenome-Wide Assessment of Circulating Tumor Necrosis Factor α.

PubMed

Aslibekyan, Stella; Agha, Golareh; Colicino, Elena; Do, Anh N; Lahti, Jari; Ligthart, Symen; Marioni, Riccardo E; Marzi, Carola; Mendelson, Michael M; Tanaka, Toshiko; Wielscher, Matthias; Absher, Devin M; Ferrucci, Luigi; Franco, Oscar H; Gieger, Christian; Grallert, Harald; Hernandez, Dena; Huan, Tianxiao; Iurato, Stella; Joehanes, Roby; Just, Allan C; Kunze, Sonja; Lin, Honghuang; Liu, Chunyu; Meigs, James B; van Meurs, Joyce B J; Moore, Ann Zenobia; Peters, Annette; Prokisch, Holger; Räikkönen, Katri; Rathmann, Wolfgang; Roden, Michael; Schramm, Katharina; Schwartz, Joel D; Starr, John M; Uitterlinden, André G; Vokonas, Pantel; Waldenberger, Melanie; Yao, Chen; Zhi, Degui; Baccarelli, Andrea A; Bandinelli, Stefania; Deary, Ian J; Dehghan, Abbas; Eriksson, Johan; Herder, Christian; Jarvelin, Marjo-Riitta; Levy, Daniel; Arnett, Donna K

2018-04-04

Tumor necrosis factor α (TNF-α) is a proinflammatory cytokine with manifold consequences for mammalian pathophysiology, including cardiovascular disease. A deeper understanding of TNF-α biology may enhance treatment precision. To conduct an epigenome-wide analysis of blood-derived DNA methylation and TNF-α levels and to assess the clinical relevance of findings. This meta-analysis assessed epigenome-wide associations in circulating TNF-α concentrations from 5 cohort studies and 1 interventional trial, with replication in 3 additional cohort studies. Follow-up analyses investigated associations of identified methylation loci with gene expression and incident coronary heart disease; this meta-analysis included 11 461 participants who experienced 1895 coronary events. Circulating TNF-α concentration. DNA methylation at approximately 450 000 loci, neighboring DNA sequence variation, gene expression, and incident coronary heart disease. The discovery cohort included 4794 participants, and the replication study included 816 participants (overall mean [SD] age, 60.7 [8.5] years). In the discovery stage, circulating TNF-α levels were associated with methylation of 7 cytosine-phosphate-guanine (CpG) sites, 3 of which were located in or near DTX3L-PARP9 at cg00959259 (β [SE] = -0.01 [0.003]; P = 7.36 × 10-8), cg08122652 (β [SE] = -0.008 [0.002]; P = 2.24 × 10-7), and cg22930808(β [SE] = -0.01 [0.002]; P = 6.92 × 10-8); NLRC5 at cg16411857 (β [SE] = -0.01 [0.002]; P = 2.14 × 10-13) and cg07839457 (β [SE] = -0.02 [0.003]; P = 6.31 × 10-10); or ABO, at cg13683939 (β [SE] = 0.04 [0.008]; P = 1.42 × 10-7) and cg24267699 (β [SE] = -0.009 [0.002]; P = 1.67 × 10-7), after accounting for multiple testing. Of these, negative associations between TNF-α concentration and methylation of 2 loci in NLRC5 and 1 in DTX3L-14 PARP9 were replicated. Replicated TNF-α-linked CpG sites were associated with 9% to 19% decreased risk of incident coronary heart disease per 10% higher methylation per CpG site (cg16411857: hazard ratio [HR], 0.86; 95% CI, 0.78-1.95; P = .003; cg07839457: HR, 0.89; 95% CI, 0.80-0.94; P = 3.1 × 10-5; cg00959259: HR, 0.91; 95% CI, 0.84-0.97; P = .002; cg08122652: HR, 0.81; 95% CI, 0.74-0.89; P = 2.0 × 10-5). We identified and replicated novel epigenetic correlates of circulating TNF-α concentration in blood samples and linked these loci to coronary heart disease risk, opening opportunities for validation and therapeutic applications.

Arterial Switch Operation With and Without Coronary Relocation for Intramural Coronary Arteries.

PubMed

Koshiyama, Hiroshi; Nagashima, Mitsugi; Matsumura, Goki; Hiramatsu, Takeshi; Nakanishi, Toshio; Yamazaki, Kenji

2016-10-01

The arterial switch operation (ASO) for the transposition of the great arteries (TGA) with intramural coronary arteries has been performed using several techniques to avoid coronary events. We mainly performed ASO without coronary relocation by creating an aortopulmonary fenestration (Imai technique). Coronary circulation was rerouted by covering the aortopulmonary window and coronary orifices with a nonfacing sinus flap. Long-term results have not been reported. We describe our early and late results. Among 551 patients who underwent an ASO between 1985 and 2014, intramural coronary arteries were detected in 15 of them. Coronary arteries were managed using 2 techniques: the double-button method in 5 patients (with unroofing and trapdoor incision in 1 patient) and the Imai technique in 10 patients. There were 3 hospital deaths and 3 deaths after discharge, 5 of which showed coronary complications. Actual survival and freedom from coronary complications at 15 years were 70% and 67%, respectively, with the Imai technique and 40% and 20%, respectively, with the double-button method. Late coronary intervention was performed for a long intramural coronary artery stenosis in 1 patient who underwent the Imai technique. In the others, late aortography showed good patency of the aortopulmonary window and growth of the coronary pouch after the Imai technique. The Imai technique can be an option for coronary management in the presence of high-risk coronary anatomy, particularly distal intramural coronary artery stenosis and inseparable coronary arteries with an almost single orifice. Adequate neopulmonary artery augmentation must be performed to prevent right ventricular outflow stenosis. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Biomarkers of coronary endothelial health: correlation with invasive measures of collateral function, flow and resistance in chronically occluded coronary arteries and the effect of recanalization.

PubMed

Ladwiniec, Andrew; Ettelaie, Camille; Cunnington, Michael S; Rossington, Jennifer; Thackray, Simon; Alamgir, Farquad; Hoye, Angela

2016-06-01

In the presence of a chronically occluded coronary artery, the collateral circulation matures by a process of arteriogenesis; however, there is considerable variation between individuals in the functional capacity of that collateral network. This could be explained by differences in endothelial health and function. We aimed to examine the relationship between the functional extent of collateralization and levels of biomarkers that have been shown to relate to endothelial health. We measured four potential biomarkers of endothelial health in 34 patients with mature collateral networks who underwent a successful percutaneous coronary intervention (PCI) for a chronic total coronary occlusion (CTO) before PCI and 6-8 weeks after PCI, and examined the relationship of biomarker levels with physiological measures of collateralization. We did not find a significant change in the systemic levels of sICAM-1, sE-selectin, microparticles or tissue factor 6-8 weeks after PCI. We did find an association between estimated retrograde collateral flow before CTO recanalization and lower levels of sICAM-1 (r=0.39, P=0.026), sE-selectin (r=0.48, P=0.005) and microparticles (r=0.38, P=0.03). Recanalization of a CTO and resultant regression of a mature collateral circulation do not alter systemic levels of sICAM-1, sE-selectin, microparticles or tissue factor. The identified relationship of retrograde collateral flow with sICAM-1, sE-selectin and microparticles is likely to represent an association with an ability to develop collaterals rather than their presence and extent.

Elevated plasma angiotensin converting enzyme 2 activity is an independent predictor of major adverse cardiac events in patients with obstructive coronary artery disease.

PubMed

Ramchand, Jay; Patel, Sheila K; Srivastava, Piyush M; Farouque, Omar; Burrell, Louise M

2018-01-01

Angiotensin converting enzyme 2 (ACE2) is an endogenous regulator of the renin angiotensin system. Increased circulating ACE2 predicts adverse outcomes in patients with heart failure (HF), but it is unknown if elevated plasma ACE2 activity predicts major adverse cardiovascular events (MACE) in patients with obstructive coronary artery disease (CAD). We prospectively recruited patients with obstructive CAD (defined as ≥50% stenosis of the left main coronary artery and/or ≥70% stenosis in ≥ 1 other major epicardial vessel on invasive coronary angiography) and measured plasma ACE2 activity. Patients were followed up to determine if circulating ACE2 activity levels predicted the primary endpoint of MACE (cardiovascular mortality, HF or myocardial infarction). We recruited 79 patients with obstructive coronary artery disease. The median (IQR) plasma ACE2 activity was 29.3 pmol/ml/min [21.2-41.2]. Over a median follow up of 10.5 years [9.6-10.8years], MACE occurred in 46% of patients (36 events). On Kaplan-Meier analysis, above-median plasma ACE2 activity was associated with MACE (log-rank test, p = 0.035) and HF hospitalisation (p = 0.01). After Cox multivariable adjustment, log ACE2 activity remained an independent predictor of MACE (hazard ratio (HR) 2.4, 95% confidence interval (CI) 1.24-4.72, p = 0.009) and HF hospitalisation (HR: 4.03, 95% CI: 1.42-11.5, p = 0.009). Plasma ACE2 activity independently increased the hazard of adverse long-term cardiovascular outcomes in patients with obstructive CAD.

Improvement in intra-aortic balloon pumping and evaluation of its efficacy by electrode methods of control.

PubMed

Ioseliani, G D; Chilaia, S M

1983-02-01

A basically new design for the reversing balloon pump has been proposed for increasing the efficacy of intra-aortic balloon pumping (IABP). The device not only causes a significant increase in discharge, but also permits control of the central and peripheral circulation within the desired limits owing to back-and-forth movements (like a piston) of the balloon pump. Standard one- and two-chamber balloon pumps were compared. In addition to traditional hemodynamic and biochemical indexes, the efficacy of IABP was assessed based on electrode monitor control of PO2 and pH in the myocardium, peripheral tissues, and circulating blood. Based on 54 experiments on dogs, it was found that IABP with reversing balloon pumps in synchronous pulsation resulted in survival of 69% of the cases; PO2 and pH levels in the myocardium, tissues, and blood in the coronary sinus were close to normal, and coronary blood flow and peripheral circulation were increased. With standard one-chamber balloon pumps, the survival rate did not exceed 33.4%; PO2 and pH in the peripheral tissues reached critical levels.

[The influence of cardiosurgical intervention type and conditions of artificial blood circulation of perioperative dynamics of cardiac biomarkers].

PubMed

Dement'eva, I I; Morozov, Iu A; Charnaia, M A

2013-01-01

125 patients after cardiac surgery operated on with the use of artificial blood circulation (ABC) were followed-up. Blood levels of cardiac protein, binding aliphatic acids and troponin 1 and 3 days after the operation were registered. The study showed that aorta clamping more then 90 minutes and hypothermic perfusion regimen influence cardiomyocites negatively. The state of "surgical trauma" and reperfusional myocardium damage was approximately the same during aortic surgery, myocardium revascularization with the use of aortic clamping and cardioplegia, and correction of the acquired heart disease, according to the dynamics of the studied proteins in blood. The minimal blood level of cardiac protein, binding aliphatic acids after coronary by-pass surgery on the working heart witnesses about negative influence of crystalloid hypothermic cardioplegia on coronary microcirculation.

Impairment of Circulating CD4⁺CD25⁺GARP⁺ regulatory T cells in patients with acute coronary syndrome.

PubMed

Meng, Kai; Zhang, Wei; Zhong, Yucheng; Mao, Xiaobo; Lin, Yingzhong; Huang, Ying; Lang, Mingjian; Peng, Yudong; Zhu, Zhengfeng; Liu, Yuzhou; Zhao, Xiaoqi; Yu, Kunwu; Wu, Bangwei; Ji, Qingwei; Zeng, Qiutang

2014-01-01

Atherosclerosis (AS) is an inflammatory and immune disease. Regulatory T cells (Tregs) suppress the activation of T cells and have been shown to play a protective role during the pathogenesis of AS. However, specific markers for Tregs are lacking. Recently, glycoprotein A repetitions predominant (GARP) was discovered as a specific marker of activated Tregs, and we therefore utilized GARP as a specific surface marker for Tregs in the current study. To assess whether GARP(+) Tregs are downregulated in patients with acute coronary syndrome (ACS), we examined CD4(+)CD25(+)GARP(+) T cell frequencies as well as their associated cytokines and suppressive function. Additionally, we compared GARP expression to that of FOXP3, which may be more sensitive as a marker of activated Tregs in patients with ACS. Patients with ACS demonstrated a significant decrease in circulating CD4(+)CD25(+)GARP(+) Tregs. Moreover, the suppressive function of Tregs and levels of related cytokines were also impaired in ACS patients compared to those with stable angina (SA) or normal coronary artery (NCA). Additionally, after TCR stimulation, peripheral blood mononuclear cells (PBMCs) from patients with ACS exhibited a decrease in CD4(+)CD25(+)GARP(+) Tregs. These fnding indicate that circulating CD4(+)CD25(+)GARP(+) Tregs are impaired in patients withACS. Thus, targeting GARP may promote the protective function of Tregs in ACS. © 2014 S. Karger AG, Basel.

Uncarboxylated matrix Gla protein (ucMGP) is associated with coronary artery calcification in haemodialysis patients.

PubMed

Cranenburg, Ellen C M; Brandenburg, Vincent M; Vermeer, Cees; Stenger, Melanie; Mühlenbruch, Georg; Mahnken, Andreas H; Gladziwa, Ulrich; Ketteler, Markus; Schurgers, Leon J

2009-02-01

Matrix gamma-carboxyglutamate (Gla) protein (MGP) is a potent local inhibitor of cardiovascular calcification and accumulates at areas of calcification in its uncarboxylated form (ucMGP). We previously found significantly lower circulating ucMGP levels in patients with a high vascular calcification burden. Here we report on the potential of circulating ucMGP to serve as a biomarker for vascular calcification in haemodialysis (HD) patients. Circulating ucMGP levels were measured with an ELISA-based assay in 40 HD patients who underwent multi-slice computed tomography (MSCT) scanning to quantify the extent of coronary artery calcification (CAC). The mean ucMGP level in HD patients (193 +/- 65 nM) was significantly lower as compared to apparently healthy subjects of the same age (441 +/- 97 nM; p < 0.001) and patients with rheumatoid arthritis (RA) without CAC (560 +/- 140 nM; p < 0.001). Additionally, ucMGP levels correlated inversely with CAC scores (r = -0.41; p = 0.009), and this correlation persisted after adjustment for age, dialysis vintage and high-sensitivity C-reactive protein (hs-CRP). Since circulating ucMGP levels are significantly and inversely correlated with the extent of CAC in HD patients, ucMGP may become a tool for identifying HD patients with a high probability of cardiovascular calcification.

A rare cause of exercise induced ventricular tachycardia.

PubMed

Aggarwal, Aakash; Arora, Sumant; Singh, Pahul; Nat, Amitpal

2015-01-01

Coronary fistulas are anomalous shunts from a coronary artery to a cardiac chamber or great vessel, bypassing the myocardial circulation. A 42-year-old Asian man with no significant history of cardiac disease presented with exertional chest discomfort in the form of chest tightness over the precordial area. The patient had no cardiac risk factors, but given the duration and persistence of symptoms, we did a stress echocardiogram. The exercise led to a 'coronary artery steal phenomenon' caused by the coronary fistula, which diverted the blood from the left anterior descending artery to the pulmonary artery thereby producing the ischemic symptoms and ventricular tachycardia. Transcatheter coil embolization was unsuccessful, but the fistula was eventually closed surgically. A repeat stress echocardiogram before discharge was completely normal. We emphasize the need to individualize treatment, taking into consideration all factors in a particular patient.

Hyperhomocysteinemia in bilateral anterior ischemic optic neuropathy after conventional coronary artery bypass graft: a case report.

PubMed

Niro, A; Sborgia, G; Sborgia, A; Alessio, G

2018-01-17

The incidence of anterior ischemic optic neuropathy after coronary artery bypass graft procedures ranges from 1.3 to 0.25%. The mechanisms of anterior ischemic optic neuropathy after cardiovascular procedures remain undefined but many systemic and related-to-surgery risk factors could underlie anterior ischemic optic neuropathy. In this case, we report a rare presentation of a bilateral anterior ischemic optic neuropathy after coronary artery bypass graft and speculate on the preoperative hyperhomocysteinemia as an independent risk factor for anterior ischemic optic neuropathy. A 56-year-old white man, a tobacco smoker with type 2 diabetes and coronary artery disease, underwent a conventional coronary artery bypass graft with extracorporeal circulation. In spite of ongoing anti-aggregation, antithrombotic, and vasodilator therapy, 10 days after the surgery he complained of severe bilateral visual loss. Funduscopy and fluorescein angiography revealed a bilateral anterior ischemic optic neuropathy. Analysis of preoperative laboratory tests revealed hyperhomocysteinemia. Hyperhomocysteinemia could increase the risk of ocular vascular damage and bilateral ocular involvement in patients who have undergone conventional coronary artery bypass graft.

[Surgical angioplasty of the left main coronary artery].

PubMed

Vranes, Mile; Velinović, Milos; Kocica, Mladen; Mikić, Aleksandar; Velimirović, Dusan; Djukić, Petar

2010-01-01

The conventional treatment for isolated stenosis of the left main coronary artery is bypass surgery (myocardial revascularization). However, the process of atherosclerosis is not arrested by myocardial revascularization and it will lead to the occlusion of the left main coronary artery. Revascularization will establish retrograde perfusion for 50-70% of the myocardium of the left ventricle. Direct surgical angioplasty of the left main coronary artery enables normal physiological perfusion of the whole myocardium and better myocardial function. The aim of our study is to point out a new surgical approach of treating left main coronary artery stenosis. Between October 2002 and October 2003, direct surgical angioplasty of the main left coronary artery was performed on three patients with isolated stenosis of the left main coronary artery using the anterior approach and the pericardium as a patch. The procedure was performed under total endotracheal anaesthesia and standard cardiopulmonary circulation, moderate hypothermia, anterograde St. Tomas cardioplegia and local cooling. Patients were followed clinically, echocardiographically and by load-tests. All three patients were without complications. In postoperative follow-up (54-68 months) neither angina pectoris nor electrocardiographically registered ischaemic changes were found. Load-tests performed every six months on all three patients were negative. Surgical angioplasty of isolated stenosis of the left main coronary artery is a preferred method for treating this type of coronary disease. Contraindications for this type of treatment are stenosis of the left main coronary artery with bifurcation and advanced calcification of the left main coronary artery.

Minimized extracorporeal circulation system in coronary artery bypass surgery: a 10-year single-center experience with 2243 patients.

PubMed

Puehler, Thomas; Haneya, Assad; Philipp, Alois; Zausig, York A; Kobuch, Reinhard; Diez, Claudius; Birnbaum, Dietrich E; Schmid, Christof

2011-04-01

Coronary artery bypass grafting (CABG) is the gold standard for the surgical therapy of multivessel coronary artery disease. To reduce the side effects, associated with standard extracorporeal circulation (ECC), a concept of minimal extracorporeal circulation (MECC) was devised in our center. We report on our 10-year experience with the MECC for coronary revascularization. From January 1998 to August 2009, 2243 patients underwent CABG with MECC in our center. In a retrospective observational study, we analyzed indication, preoperative patient co-morbidity, postoperative clinical course, and perioperative outcome of all patients operated on with MECC. Furthermore, the risk factors for mortality in the MECC group were assessed. Patients showed a mean logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE) of 4.5±0.1%. The mean age of the patients was 66.8±9.1 years. The overall 30-day mortality after CABG with MECC was 2.3%, ranging from 1.1% for elective to 13.0% for emergent patients and was significantly better than standard ECC. Only 15.3% (n=344) of patients with MECC required intra-operative blood transfusion. Postoperative catecholamine support, red blood cell transfusion, need for hemodialysis, release of creatinine kinase, incidence of stroke, and postoperative delirium were low after MECC revascularization. Ejection fraction below 30% (odds ratio (OR): 5.1), emergent operation (OR: 9.4), and high-dose catecholamine therapy (OR: 2.6) were associated predictors for mortality. MECC until now is an established concept and has become an alternative for ECC in routine CABG in our center. The use of the MECC system is associated with low mortality and conversion rate. Excellent survival rates and low transfusion requirements in the perioperative course were achieved. Copyright © 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Dynamic three-dimensional model of the coronary circulation

NASA Astrophysics Data System (ADS)

Lehmann, Glen; Gobbi, David G.; Dick, Alexander J.; Starreveld, Yves P.; Quantz, M.; Holdsworth, David W.; Drangova, Maria

2001-05-01

A realistic numerical three-dimensional (3D) model of the dynamics of human coronary arteries has been developed. High- resolution 3D images of the coronary arteries of an excised human heart were obtained using a C-arm based computed tomography (CT) system. Cine bi-plane coronary angiograms were then acquired from a patient with similar coronary anatomy. These angiograms were used to determine the vessel motion, which was applied to the static 3D coronary tree. Corresponding arterial bifurcations were identified in the 3D CT image and in the 2D angiograms. The 3D positions of the angiographic landmarks, which were known throughout the cardiac cycle, were used to warp the 3D image via a non-linear thin-plate spline algorithm. The result was a set or 30 dynamic volumetric images sampling a complete cardiac cycle. To the best of our knowledge, the model presented here is the first dynamic 3D model that provides a true representation of both the geometry and motion of a human coronary artery tree. In the future, similar models can be generated to represent different coronary anatomy and motion. Such models are expected to become an invaluable tool during the development of dynamic imaging techniques such as MRI, multi-slice CT and 3D angiography.

The effects of conventional extracorporeal circulation versus miniaturized extracorporeal circulation on microcirculation during cardiopulmonary bypass-assisted coronary artery bypass graft surgery.

PubMed

Yuruk, Koray; Bezemer, Rick; Euser, Mariska; Milstein, Dan M J; de Geus, Hilde H R; Scholten, Evert W; de Mol, Bas A J M; Ince, Can

2012-09-01

OBJECTIVES To reduce the complications associated with cardiopulmonary bypass (CPB) during cardiac surgery, many modifications have been made to conventional extracorporeal circulation systems. This trend has led to the development of miniaturized extracorporeal circulation systems. Cardiac surgery using conventional extracorporeal circulation systems has been associated with significantly reduced microcirculatory perfusion, but it remains unknown whether this could be prevented by an mECC system. Here, we aimed to test the hypothesis that microcirculatory perfusion decreases with the use of a conventional extracorporeal circulation system and would be preserved with the use of an miniaturized extracorporeal circulation system. METHODS Microcirculatory density and perfusion were assessed using sublingual side stream dark-field imaging in patients undergoing on-pump coronary artery bypass graft (CABG) surgery before, during and after the use of either a conventional extracorporeal circulation system (n = 10) or a miniaturized extracorporeal circulation system (n = 10). In addition, plasma neutrophil gelatinase-associated lipocalin and creatinine levels and creatinine clearance were assessed up to 5 days post-surgery to monitor renal function. RESULTS At the end of the CPB, one patient in the miniaturized extracorporeal circulation-treated group and five patients in the conventional extracorporeal circulation-treated group received one bag of packed red blood cells (300 ml). During the CPB, the haematocrit and haemoglobin levels were slightly higher in the miniaturized extracorporeal circulation-treated patients compared with the conventional extracorporeal circulation-treated patients (27.7 ± 3.3 vs 24.7 ± 2.0%; P = 0.03; and 6.42 ± 0.75 vs 5.41 ± 0.64 mmol/l; P < 0.01). The density of perfused vessels with a diameter <25 µm (i.e. perfused vessel density) decreased slightly in the conventional extracorporeal circulation-treated group from 16.4 ± 3.8 to 12.8 ± 3.3 mm/mm(2) (P < 0.01) and remained stable in the miniaturized extracorporeal circulation-treated group (16.3 ± 2.7 and 15.2 ± 2.9 mm/mm(2) before and during the pump, respectively). Plasma neutrophil gelatinase-associated lipocalin levels were increased following the use of extracorporeal circulation in both groups, and no differences were observed between the groups. Plasma creatinine levels and creatinine clearance were not affected by CABG surgery or CPB. CONCLUSIONS The results from this relatively small study suggest that the use of the miniaturized extracorporeal circulation system is associated with a statistically significant (but clinically insignificant) reduction in haemodilution and microcirculatory hypoperfusion compared with the use of the conventional extracorporeal circulation system.

Minimally Invasive Extracorporeal Circulation Circuit Is Not Inferior to Off-Pump Coronary Artery Bypass Grafting: Meta-Analysis Using the Bayesian Method.

PubMed

Winkler, Bernhard; Heinisch, Paul P; Gahl, Brigitta; Aghlmandi, Soheila; Jenni, Hans Jörg; Carrel, Thierry P

2017-01-01

The pathophysiologic side effects of cardiopulmonary bypass have already been identified. Minimally invasive extracorporeal circulation technologies (MiECT) and off-pump coronary artery bypass graft surgery (OPCABG) aim to reduce these problems. This meta-analysis provides a comparison of MiECT and OPCABG in randomized and observational studies. A fully probabilistic, Bayesian approach of primary and secondary endpoints was conducted. MiECT does not give inferior results when compared with OPCABG. However, there is a trend to borderline significantly higher blood loss in this group in randomized controlled trials. The question whether MiECT is equivalent to OPCABG can be answered with the affirmative, but long-term follow-up data are needed to detect any advantage over time. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Myocardial and Peripheral Ischemia Causes an Increase in Circulating Pregnancy-Associated Plasma Protein-A in Non-atherosclerotic, Non-heparinized Pigs.

PubMed

Steffensen, Lasse Bach; Poulsen, Christian Bo; Shim, Jeong; Bek, Marie; Jacobsen, Kevin; Conover, Cheryl A; Bentzon, Jacob Fog; Oxvig, Claus

2015-12-01

The usefulness of circulating pregnancy-associated plasma protein-A (PAPP-A) as a biomarker for acute coronary syndrome (ACS) is widely debated. We used the pig as a model to assess PAPP-A dynamics in the setting of myocardial ischemia. Induction of myocardial ischemia by ligation of the left anterior descending (LAD) coronary artery caused a systemic rise in PAPP-A. However, the ischemic myocardium was excluded as the source of PAPP-A. Interestingly, induction of ischemia in peripheral tissues by ligation of the left femoral artery caused a systemic rise in PAPP-A originating from the left hind limb. This is the first study to demonstrate PAPP-A elevations in the absence of atherosclerosis or heparin during myocardial ischemia. Our findings thus add to the current discussion of the usefulness of PAPP-A as a biomarker for ACS.

Perioperative Outcomes, Transfusion Requirements, and Inflammatory Response After Coronary Artery Bypass Grafting With Off-Pump, Mini-Extracorporeal, and On-Pump Circulation Techniques.

PubMed

Brinkman, William T; Squiers, John J; Filardo, Giovanni; Arsalan, Mani; Smith, Robert L; Moore, David; Mack, Michael J; DiMaio, J Michael

2015-12-01

Mini-extracorporeal circulation (MECC) units were developed to reduce postoperative morbidity, transfusion requirements, and inflammation associated with conventional on-pump coronary artery bypass (ONCAB) surgery without the technical demands of the off-pump (OPCAB) technique. We compared perioperative outcomes and inflammatory mediation among OPCAB, MECC, and ONCAB techniques. We prospectively enrolled 102 patients undergoing elective isolated coronary bypass grafting. Perfusion methods were OPCAB (n = 34), MECC (n = 34), and ONCAB (n = 34). Serial blood samples were collected to measure serum inflammatory markers. There were no operative deaths or strokes. Total red blood cell (RBC) products used in OPCAB, MECC, and ONCAB patients were 0.676, 1.000, and 1.235 units, respectively. Adjusted (by splined Society of Thoracic Surgeons operative risk score) analysis showed no statistically significant differences in mean RBC product use among the different operative systems (OPCAB vs MECC, P = 0.580; OPCAB vs ONCAB, P = 0.311; MECC vs ONCAB, P = 0.633). Adjusted (by Society of Thoracic Surgeons risk score and baseline level) mean plasma level differences (24 hours postoperative - baseline) of C-reactive protein for OPCAB (117.89; 95% confidence interval [95% CI], 106.23-129.54) and for MECC (124.88; 95% CI, 113.45-136.32) were significantly higher than for ONCAB (98.82; 95% CI, 86.40-111.24). No significant adjusted differences (P = 0.304) in interleukin-6 level changes were observed. Off-pump coronary artery bypass and MECC did not significantly reduce mean total RBC transfusion requirements. Off-pump coronary artery bypass and MECC were associated with greater C-reactive protein elevation than ONCAB, suggestive of an increased inflammatory response to each of these techniques.

The effect of modified Blalock-Taussig shunt size and coarctation severity on coronary perfusion after the Norwood operation.

PubMed

Corsini, Chiara; Biglino, Giovanni; Schievano, Silvia; Hsia, Tain-Yen; Migliavacca, Francesco; Pennati, Giancarlo; Taylor, Andrew M

2014-08-01

The size of the modified Blalock-Taussig shunt and the additional presence of aortic coarctation can affect the hemodynamics of the Norwood physiology. Multiscale modeling was used to gather insight into the effects of these variables, in particular on coronary perfusion. A model was reconstructed from cardiac magnetic resonance imaging data of a representative patient, and then simplified with computer-aided design software. Changes were systematically imposed to the semi-idealized three-dimensional model, resulting in a family of nine models (3-, 3.5-, and 4-mm shunt diameter; 0%, 60%, and 90% coarctation severity). Each model was coupled to a lumped parameter network representing the remainder of the circulation to run multiscale simulations. Simulations were repeated including the effect of preserved cerebral perfusion. The concomitant presence of a large shunt and tight coarctation was detrimental in terms of coronary perfusion (13.4% maximal reduction, 1.07 versus 0.927 mL/s) and oxygen delivery (29% maximum reduction, 422 versus 300 mL·min(-1)·m(-2)). A variation in the ratio of pulmonary to systemic blood flow from 0.9 to 1.6 also indicated a "stealing" phenomenon to the detriment of the coronary circulation. A difference could be further appreciated in the computational ventricular pressure-volume loops, with augmented systolic pressures and decreased stroke volumes for tighter coarctation. Accounting for constant cerebral perfusion did not produce substantially different results. Multiscale simulations performed in a parametric fashion revealed a reduction in coronary perfusion in the presence of a large modified Blalock-Taussig shunt and severe coarctation in Norwood patients. Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Less invasive coronary artery revascularization with a minimized extracorporeal circulation system: preliminary results of a comparative study with off-pump-procedures

PubMed Central

2013-01-01

Background Coronary-artery-bypass-grafting (CABG) with conventional extracorporeal circulation (CECC) is associated with adverse effects such as systemic inflammatory response leading to a decrease in systemic vascular resistance and hemodynamic instability. Modern "less invasive" procedures have been established recently which potentially avoid negative side effects of CECC. The aim of this study was to compare perioperative outcome following coronary revascularization using either a minimized extracorporeal circuit (Mini-HLM) or off-pump technique (OPCAB). Methods In this prospective ethics-approved trial, 120 patients referred for CABG were randomly assigned either to off-pump coronary artery bypass (OPCAB) or to a Mini-HLM procedure. Patient demographics, preoperative characteristics and extensive postoperative outcome were analyzed for both groups. Hemodynamic data were measured at seven time points perioperatively. Results Operation-time was longer in the Mini-HLM group (178,3 ± 32,9 min) compared to OPCAB (133,2 ± 32,7 min, p < 0,001) with higher graft numbers in Mini-HLM group (3,11 ± 0,7 vs. 1,78 ± 0,7, p < 0.001). There were no significant differences in perioperative hemodynamic criteria, catecholaminergic support, hospital (p = 0,534) and intensive care unit stay (p = 0,880), ventilation time (p = 0,113), blood loss (p = 0,570), transfusion requirements, postoperative atrial fibrillation rate (p = 0,706) and neurocognitive disturbance (p = 0,297). No deaths and no myocardial infarctions were observed. Conclusions Coronary revascularisation with Mini-HLM represents a suitable and "less invasive" procedure which achieves all benefits of OPCAB but may allow for less demanding revascularisation than OPCAB in special patients with complex coronary anatomy and can therefore be used both on a routine basis and in all "conversion" cases of OPCAB. PMID:23577663

Coronary arterial BK channel dysfunction exacerbates ischemia/reperfusion-induced myocardial injury in diabetic mice.

PubMed

Lu, Tong; Jiang, Bin; Wang, Xiao-Li; Lee, Hon-Chi

2016-09-01

The large conductance Ca(2+)-activated K(+) (BK) channels, abundantly expressed in coronary artery smooth muscle cells (SMCs), play a pivotal role in regulating coronary circulation. A large body of evidence indicates that coronary arterial BK channel function is diminished in both type 1 and type 2 diabetes. However, the consequence of coronary BK channel dysfunction in diabetes is not clear. We hypothesized that impaired coronary BK channel function exacerbates myocardial ischemia/reperfusion (I/R) injury in streptozotocin-induced diabetic mice. Combining patch-clamp techniques and cellular biological approaches, we found that diabetes facilitated the colocalization of angiotensin II (Ang II) type 1 receptors and BK channel α-subunits (BK-α), but not BK channel β1-subunits (BK-β1), in the caveolae of coronary SMCs. This caveolar compartmentation in vascular SMCs not only enhanced Ang II-mediated inhibition of BK-α but also produced a physical disassociation between BK-α and BK-β1, leading to increased infarct size in diabetic hearts. Most importantly, genetic ablation of caveolae integrity or pharmacological activation of coronary BK channels protected the cardiac function of diabetic mice from experimental I/R injury in both in vivo and ex vivo preparations. Our results demonstrate a vascular ionic mechanism underlying the poor outcome of myocardial injury in diabetes. Hence, activation of coronary BK channels may serve as a therapeutic target for cardiovascular complications of diabetes.

Complimentary use of epicardial echo imaging and Doppler in quantification of coronary artery stenoses

NASA Astrophysics Data System (ADS)

Richards, Kent L.; Cannon, Scott R.

1990-08-01

As more advanced therapeutic procedures are performed on coronary arteries during open chest surgery more advanced diagnostic procedures will be required to define the location and severity of coronary artery disease. This manuscript describes our preliminary experiences in identifying human coronary artery stenoses using epicardial two-dimensional color flow Doppler. Once the lesions were identified we used standard echo Doppler and imaging techniques to define their severity. The accuracy of stenotic cross sectional area calculated using the continuity equation and pressure gradient calculated using the Bernoulli equation were defined using a pulsatile flow model of the coronary circulation. Suggestions about further hardware development required to allow easy clinical application of this technique are described. 1 - CLINICAL NEED FOR INTRA-OPERATIVE EVAUJATION OFCORONARY ARTERIES The severity of coronary artery disease in adults who require coronary bypass surgery has changed significantly in the last ten years. More effective medications used to control angina pectoris and the wide use of percutaneous y artery angioplasty have delayed the timing of surgery until atherosclerotic involvement is more extensive. In addition patients who have had initial coronary bypass operations are now reaching ages at which atherosclerotic involvement of their bypass grafts and native vessels has progressed and reoperation is required. To meet the challenge of coronary arteries with multiple lesions or diffuse disease intraoperative angioplasty devices are being developed. Whether bypass surgery for advanced lesions or reoperation of

Cell-Free circulating DNA: a new biomarker for the acute coronary syndrome.

PubMed

Cui, Ming; Fan, Mengkang; Jing, Rongrong; Wang, Huimin; Qin, Jingfeng; Sheng, Hongzhuan; Wang, Yueguo; Wu, Xinhua; Zhang, Lurong; Zhu, Jianhua; Ju, Shaoqing

2013-01-01

In recent studies, concentrations of cell-free circulating DNA (cf-DNA) have been correlated with clinical characteristics and prognosis in several diseases. The relationship between cf-DNA concentrations and the acute coronary syndrome (ACS) remains unknown. Moreover, no data are available for the detection cf-DNA in ACS by a branched DNA (bDNA)-based Alu assay. The aim of the present study was to investigate cf-DNA concentrations in ACS and their relationship with clinical features. Plasma cf-DNA concentrations of 137 ACS patients at diagnosis, of 60 healthy individuals and of 13 patients with stable angina (SA) were determined using a bDNA-based Alu assay. ACS patients (median 2,285.0, interquartile range 916.4-4,857.3 ng/ml), especially in ST-segment elevation myocardial infarction patients (median 5,745.4, interquartile range 4,013.5-8,643.9 ng/ml), showed a significant increase in plasma cf-DNA concentrations compared with controls (healthy controls: median 118.3, interquartile range 81.1-221.1 ng/ml; SA patients: median 202.3, interquartile range 112.7-256.1 ng/ml) using a bDNA-based Alu assay. Moreover, we found positive correlations between cf-DNA and Gensini scoring and GRACE (Global Registry of Acute Coronary Events) scoring in ACS. cf-DNA may be a valuable marker for diagnosing and predicting the severity of coronary artery lesions and risk stratification in ACS. Copyright © 2013 S. Karger AG, Basel.

RAGE gene polymorphisms are associated with circulating levels of endogenous secretory RAGE but not with coronary artery disease in Chinese patients with type 2 diabetes mellitus.

PubMed

Peng, Wen Hui; Lu, Lin; Wang, Ling Jie; Yan, Xiao Xiang; Chen, Qiu Jing; Zhang, Qi; Zhang, Rui Yan; Shen, Wei Feng

2009-07-01

Engagement of the receptor for advanced glycation end products (RAGE) with advanced glycation end products and subsequent signaling play an important role in the development of diabetic complications. This pathophysiological effect was mitigated partially by endogenous secretory RAGE (esRAGE). The present study aimed to explore the possible association of RAGE polymorphism with serum esRAGE level and coronary artery disease (CAD) in Chinese patients with type 2 diabetes mellitus (T2DM). A total of 740 consecutive patients with T2DM undergoing coronary angiography were enrolled. The severity of coronary atherosclerosis was defined as the number of diseased vessels; 69 bp insertion/deletion was determined by polymerase chain reactions, and -429 T/C, -374A/T and G82S variants were assessed by polymerase chain reaction-restriction fragment length polymorphism. Patients with genotypes carrying C allele of -429 T/C and G allele of G82S had significantly higher esRAGE levels. 82S allele was also associated with increased tumor necrosis factor-alpha and interleukin-6 levels in diabetic patients with CAD (all p <0.05), but none of the polymorphisms or haplotypes was related to the presence and severity of CAD. G82S and -429 T/C polymorphisms of RAGE were associated with the circulating levels of esRAGE but not with CAD in Chinese patients with T2DM.

Acute myocardial infarction with changing axis deviation.

PubMed

Patanè, Salvatore; Marte, Filippo

2011-07-01

Changing axis deviation has been rarely reported also during atrial fibrillation or atrial flutter. Changing axis deviation has been rarely reported also during acute myocardial infarction associated with atrial fibrillation. Isolated left posterior hemiblock is a very rare finding but the evidence of transient right axis deviation with a left posterior hemiblock pattern has been reported during acute anterior myocardial infarction as related with significant right coronary artery obstruction and collateral circulation between the left coronary system and the posterior descending artery. Left anterior hemiblock development during acute inferior myocardial infarction can be an indicator of left anterior descending coronary artery lesions, multivessel coronary artery disease, and impaired left ventricular systolic function. We present a case of changing axis deviation in a 62-year-old Italian man with acute myocardial infarction. Also this case focuses attention on changing axis deviation during acute myocardial infarction. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

Rare presentation of intralobar pulmonary sequestration associated with repeated episodes of ventricular tachycardia

PubMed Central

Rao, D Sheshagiri; Barik, Ramachandra

2016-01-01

Arterial supply of an intralobar pulmonary sequestration (IPS) from the coronary circulation is extremely rare. A significant coronary steal does not occur because of dual or triple sources of blood supply to sequestrated lung tissue. We present a 60-year-old woman who presented to us with repeated episodes of monomorphic ventricular tachycardia (VT) in last 3 mo. Radio frequency ablation was ineffective. On evaluation, she had right lower lobe IPS with dual arterial blood supply, i.e., right pulmonary artery and the systemic arterial supply from the right coronary artery (RCA). Stress myocardial perfusion scan revealed significant inducible ischemia in the RCA territory. Coronary angiogram revealed critical stenosis of proximal RCA just after the origin of the systemic artery supplying IPS. The critical stenosis in the RCA was stented. At 12 mo follow-up, she had no further episodes of VT or angina. PMID:27468336

Rare presentation of intralobar pulmonary sequestration associated with repeated episodes of ventricular tachycardia.

PubMed

Rao, D Sheshagiri; Barik, Ramachandra

2016-07-26

Arterial supply of an intralobar pulmonary sequestration (IPS) from the coronary circulation is extremely rare. A significant coronary steal does not occur because of dual or triple sources of blood supply to sequestrated lung tissue. We present a 60-year-old woman who presented to us with repeated episodes of monomorphic ventricular tachycardia (VT) in last 3 mo. Radio frequency ablation was ineffective. On evaluation, she had right lower lobe IPS with dual arterial blood supply, i.e., right pulmonary artery and the systemic arterial supply from the right coronary artery (RCA). Stress myocardial perfusion scan revealed significant inducible ischemia in the RCA territory. Coronary angiogram revealed critical stenosis of proximal RCA just after the origin of the systemic artery supplying IPS. The critical stenosis in the RCA was stented. At 12 mo follow-up, she had no further episodes of VT or angina.

Management of cardiac arrest caused by coronary artery spasm: epinephrine/adrenaline versus nitrates.

PubMed

Kiss, Gabor; Corre, Olivier; Gueret, Gildas; Nguyen Ba, Vinh; Gilard, Martine; Boschat, Jaques; Arvieux, Charles Chistian

2009-01-01

Cardiopulmonary resuscitation guidelines imply the use of epinephrine/adrenaline during cardiopulmonary arrest. However, in cardiac arrest situations resulting from coronary artery spasm (CAS), the use of epinephrine/adrenaline could be deleterious. A 49-year-old patient underwent an emergency coronarography with an attempt to stent the coronary arteries. Radiologic imaging revealed a positive methylergonovine maleate (Methergine, Novartis Pharmaceuticals, East Hanover, NJ) test, with subocclusive CAS in several coronary vessels leading to electromechanical dissociation. Cardiopulmonary resuscitation was performed, and intracoronary boluses of isosorbide dinitrate were given to treat CAS. Epinephrine/adrenaline was not administered during resuscitation. Spontaneous circulation was obtained after cardioversion for ventricular fibrillation, and the patient progressively regained consciousness. Resuscitation guidelines do not specify the use of trinitrate derivatives in cardiac arrest situations caused by CAS. The pros and cons of the use of nitrates and epinephrine/adrenaline during cardiac arrest caused by CAS are analyzed in this case report.

Novel monorail infusion catheter for volumetric coronary blood flow measurement in humans: in vitro validation.

PubMed

van 't Veer, Marcel; Adjedj, Julien; Wijnbergen, Inge; Tóth, Gabor G; Rutten, Marcel C M; Barbato, Emanuele; van Nunen, Lokien X; Pijls, Nico H J; De Bruyne, Bernard

2016-08-20

The aim of this study is to validate a novel monorail infusion catheter for thermodilution-based quantitative coronary flow measurements. Based on the principles of thermodilution, volumetric coronary flow can be determined from the flow rate of a continuous saline infusion, the temperature of saline when it enters the coronary artery, and the temperature of the blood mixed with the saline in the distal part of the coronary artery. In an in vitro set-up of the systemic and coronary circulation at body temperature, coronary flow values were varied from 50-300 ml/min in steps of 50 ml/min. At each coronary flow value, thermodilution-based measurements were performed at infusion rates of 15, 20, and 30 ml/min. Temperatures and pressures were simultaneously measured with a pressure/temperature sensor-tipped guidewire. Agreement of the calculated flow and the measured flow as well as repeatability were assessed. A total of five catheters were tested, with a total of 180 measurements. A strong correlation (ρ=0.976, p<0.0001) and a difference of -6.5±15.5 ml/min were found between measured and calculated flow. The difference between two repeated measures was 0.2%±8.0%. This novel infusion catheter used in combination with a pressure/temperature sensor-tipped guidewire allows accurate and repeatable absolute coronary flow measurements. This opens a window to a better understanding of the coronary microcirculation.

Evaluation of hemodynamic and regional tissue perfusion effects of minimized extracorporeal circulation (MECC).

PubMed

Bauer, Adrian; Diez, Claudius; Schubel, Jens; El-Shouki, Nagi; Metz, Dietrich; Eberle, T; Hausmann, Harald

2010-03-01

Minimized extracorporeal circulation (MECC, Maquet, Cardiopulmonary AG, Hirrlingen, Germany) is an established procedure to perform coronary revascularization. Studies showed positive effects of MECC compared to conventional cardiopulmonary bypass (CCPB) procedures in terms of transfusion requirements, less inflammation reactions, and neurological impairments. Recent retrospective studies showed higher mean arterial pressure (MAP) and a lower frequency of vasoactive drug use. We addressed this issue in this study. The hypothesis was to find a higher MAP during coronary bypass grafting surgery in patients treated with MECC systems. We performed a prospective, controlled, randomized trial with 40 patients either assigned to MECC (n = 18) or CCPB (n = 22) undergoing coronary bypass grafting. Primary endpoints were the perioperative course of mean arterial pressure, and the consumption of norepinephrine. Secondary endpoints were the regional cerebral and renal oxygen saturation (rSO2) as an indicator of area perfusion and the course of hematocrit. Clinical and demographic characteristics did not significantly differ between both groups. Thirty-day mortality was 0%. At four of five time points during extracorporeal circulation (ECC) MAP values were significantly higher in the MECC group compared to CCPB patients (after starting the ECC 60 +/- 11 mmHg vs. 49 +/- 10 mmHg, p = .002). MECC patients received significantly less norepinephrine (MECC 22.5 +/- 35 microg vs. CCPB 60.5 +/- 75 microg, p = .045). The rSO2 measured at right and left forehead and the renal area was similar for both groups during ECC and significantly higher at CCPB group 1 and 4 hours after termination of CPB. Minimized extracorporeal circulation provides a higher mean arterial pressure during ECC and we found a lower consumption of vasoactive drugs in the MECC group. There was a decrease in regional tissue saturation at 1 and 4 hours post bypass in the MECC group possibly due to increased systemic inflammation and extravascular fluid shift in the CCPB group.

Evaluation of Hemodynamic and Regional Tissue Perfusion Effects of Minimized Extracorporeal Circulation (MECC®)

PubMed Central

Bauer, Adrian; Diez, Claudius; Schubel, Jens; El-Shouki, Nagi; Metz, Dietrich; Eberle, T.; Hausmann, Harald

2010-01-01

Abstract: Minimized extracorporeal circulation (MECC®, Maquet, Cardiopulmonary AG, Hirrlingen, Germany) is an established procedure to perform coronary revascularization. Studies showed positive effects of MECC compared to conventional cardiopulmonary bypass (CCPB) procedures in terms of transfusion requirements, less inflammation reactions, and neurological impairments. Recent retrospective studies showed higher mean arterial pressure (MAP) and a lower frequency of vasoactive drug use. We addressed this issue in this study. The hypothesis was to find a higher MAP during coronary bypass grafting surgery in patients treated with MECC systems. We performed a prospective, controlled, randomized trial with 40 patients either assigned to MECC (n = 18) or CCPB (n = 22) undergoing coronary bypass grafting. Primary endpoints were the perioperative course of mean arterial pressure, and the consumption of norepinephrine. Secondary endpoints were the regional cerebral and renal oxygen saturation (rSO2) as an indicator of area perfusion and the course of hematocrit. Clinical and demographic characteristics did not significantly differ between both groups. Thirty-day mortality was 0%. At four of five time points during extracorporeal circulation (ECC) MAP values were significantly higher in the MECC group compared to CCPB patients (after starting the ECC 60 ± 11 mmHg vs. 49 ± 10 mmHg, p = .002). MECC patients received significantly less norepinephrine (MECC 22.5 ± 35 μg vs. CCPB 60.5 ± 75 μg, p = .045). The rSO2 measured at right and left forehead and the renal area was similar for both groups during ECC and significantly higher at CCPB group 1 and 4 hours after termination of CPB. Minimized extracorporeal circulation provides a higher mean arterial pressure during ECC and we found a lower consumption of vasoactive drugs in the MECC group. There was a decrease in regional tissue saturation at 1 and 4 hours post bypass in the MECC group possibly due to increased systemic inflammation and extravascular fluid shift in the CCPB group. PMID:20437789

Circulating concentrations of insulin markers and coronary heart disease: a quantitative review of 19 Western prospective studies.

PubMed

Sarwar, Nadeem; Sattar, Naveed; Gudnason, Vilmundur; Danesh, John

2007-10-01

It is uncertain whether there are associations between circulating levels of insulin markers and coronary heart disease (CHD) risk. We report an updated meta-analysis of studies of circulating levels of three insulin markers (fasting insulin, non-fasting insulin, and pro-insulin) and CHD risk. Prospective studies based in Western populations that reported on associations between levels of fasting insulin, non-fasting insulin, and pro-insulin and incident CHD [defined as non-fatal myocardial infarction (MI) or coronary death] were identified by computer-based searches and by manual searches of the relevant literature. Nineteen relevant population-based studies were identified, of which 14 reported on fasting insulin levels involving 2649 CHD cases, eight reported on non-fasting insulin levels involving 1980 CHD cases and three reported on pro-insulin levels involving 413 CHD cases. In a comparison of individuals who had circulating levels of each of these markers in the top third with those in the bottom third of the population, the odds ratio for CHD was 1.12 [95% confidence interval (CI): 0.98-1.28] for raised fasting insulin, 1.35 (1.14-1.60) for raised non-fasting insulin, and 2.23 (1.65-3.00) for raised pro-insulin. There was no good evidence of heterogeneity in these estimates attributable to the several study characteristics recorded, including sex, assay methods used, or degree of adjustment of risk estimates, but the available data in many of these subgroups, particularly by sex, are sparse. Associations between CHD risk and fasting or non-fasting insulin levels are likely to be more modest than previously suspected. Preliminary data suggest that pro-insulin levels may be more strongly associated with CHD risk than are insulin levels, and this possibility should be evaluated in larger and more rigorous studies.

KV7 channels contribute to paracrine, but not metabolic or ischemic, regulation of coronary vascular reactivity in swine

PubMed Central

Goodwill, Adam G.; Fu, Lijuan; Noblet, Jillian N.; Casalini, Eli D.; Berwick, Zachary C.; Kassab, Ghassan S.; Tune, Johnathan D.

2016-01-01

Hydrogen peroxide (H2O2) and voltage-dependent K+ (KV) channels play key roles in regulating coronary blood flow in response to metabolic, ischemic, and paracrine stimuli. The KV channels responsible have not been identified, but KV7 channels are possible candidates. Existing data regarding KV7 channel function in the coronary circulation (limited to ex vivo assessments) are mixed. Thus we examined the hypothesis that KV7 channels are present in cells of the coronary vascular wall and regulate vasodilation in swine. We performed a variety of molecular, biochemical, and functional (in vivo and ex vivo) studies. Coronary arteries expressed KCNQ genes (quantitative PCR) and KV7.4 protein (Western blot). Immunostaining demonstrated KV7.4 expression in conduit and resistance vessels, perhaps most prominently in the endothelial and adventitial layers. Flupirtine, a KV7 opener, relaxed coronary artery rings, and this was attenuated by linopirdine, a KV7 blocker. Endothelial denudation inhibited the flupirtine-induced and linopirdine-sensitive relaxation of coronary artery rings. Moreover, linopirdine diminished bradykinin-induced endothelial-dependent relaxation of coronary artery rings. There was no effect of intracoronary flupirtine or linopirdine on coronary blood flow at the resting heart rate in vivo. Linopirdine had no effect on coronary vasodilation in vivo elicited by ischemia, H2O2, or tachycardia. However, bradykinin increased coronary blood flow in vivo, and this was attenuated by linopirdine. These data indicate that KV7 channels are expressed in some coronary cell type(s) and influence endothelial function. Other physiological functions of coronary vascular KV7 channels remain unclear, but they do appear to contribute to endothelium-dependent responses to paracrine stimuli. PMID:26825518

KV7 channels contribute to paracrine, but not metabolic or ischemic, regulation of coronary vascular reactivity in swine.

PubMed

Goodwill, Adam G; Fu, Lijuan; Noblet, Jillian N; Casalini, Eli D; Sassoon, Daniel; Berwick, Zachary C; Kassab, Ghassan S; Tune, Johnathan D; Dick, Gregory M

2016-03-15

Hydrogen peroxide (H2O2) and voltage-dependent K(+) (KV) channels play key roles in regulating coronary blood flow in response to metabolic, ischemic, and paracrine stimuli. The KV channels responsible have not been identified, but KV7 channels are possible candidates. Existing data regarding KV7 channel function in the coronary circulation (limited to ex vivo assessments) are mixed. Thus we examined the hypothesis that KV7 channels are present in cells of the coronary vascular wall and regulate vasodilation in swine. We performed a variety of molecular, biochemical, and functional (in vivo and ex vivo) studies. Coronary arteries expressed KCNQ genes (quantitative PCR) and KV7.4 protein (Western blot). Immunostaining demonstrated KV7.4 expression in conduit and resistance vessels, perhaps most prominently in the endothelial and adventitial layers. Flupirtine, a KV7 opener, relaxed coronary artery rings, and this was attenuated by linopirdine, a KV7 blocker. Endothelial denudation inhibited the flupirtine-induced and linopirdine-sensitive relaxation of coronary artery rings. Moreover, linopirdine diminished bradykinin-induced endothelial-dependent relaxation of coronary artery rings. There was no effect of intracoronary flupirtine or linopirdine on coronary blood flow at the resting heart rate in vivo. Linopirdine had no effect on coronary vasodilation in vivo elicited by ischemia, H2O2, or tachycardia. However, bradykinin increased coronary blood flow in vivo, and this was attenuated by linopirdine. These data indicate that KV7 channels are expressed in some coronary cell type(s) and influence endothelial function. Other physiological functions of coronary vascular KV7 channels remain unclear, but they do appear to contribute to endothelium-dependent responses to paracrine stimuli. Copyright © 2016 the American Physiological Society.

Dynamic release and clearance of circulating microparticles during cardiac stress.

PubMed

Augustine, Daniel; Ayers, Lisa V; Lima, Eduardo; Newton, Laura; Lewandowski, Adam J; Davis, Esther F; Ferry, Berne; Leeson, Paul

2014-01-03

Microparticles are cell-derived membrane vesicles, relevant to a range of biological responses and known to be elevated in cardiovascular disease. To investigate microparticle release during cardiac stress and how this response differs in those with vascular disease. We measured a comprehensive panel of circulating cell-derived microparticles by a standardized flow cytometric protocol in 119 patients referred for stress echocardiography. Procoagulant, platelet, erythrocyte, and endothelial but not leukocyte, granulocyte, or monocyte-derived microparticles were elevated immediately after a standardized dobutamine stress echocardiogram and decreased after 1 hour. Twenty-five patients developed stress-induced wall motion abnormalities suggestive of myocardial ischemia. They had similar baseline microparticle levels to those who did not develop ischemia, but, interestingly, their microparticle levels did not change during stress. Furthermore, no stress-induced increase was observed in those without inducible ischemia but with a history of vascular disease. Fourteen patients subsequently underwent coronary angiography. A microparticle rise during stress echocardiography had occurred only in those with normal coronary arteries. Procoagulant, platelet, erythrocyte, and endothelial microparticles are released during cardiac stress and then clear from the circulation during the next hour. This stress-induced rise seems to be a normal physiological response that is diminished in those with vascular disease.

Influence of anatomical dominance and hypertension on coronary conduit arterial and microcirculatory flow patterns: a multiscale modeling study.

PubMed

Mynard, Jonathan P; Smolich, Joseph J

2016-07-01

Coronary hemodynamics are known to be affected by intravascular and extravascular factors that vary regionally and transmurally between the perfusion territories of left and right coronary arteries. However, despite clinical evidence that left coronary arterial dominance portends greater cardiovascular risk, relatively little is known about the effects of left or right dominance on regional conduit arterial and microcirculatory blood flow patterns, particularly in the presence of systemic or pulmonary hypertension. We addressed this issue using a multiscale numerical model of the human coronary circulation situated in a closed-loop cardiovascular model. The coronary model represented left or right dominant anatomies and accounted for transmural and regional differences in vascular properties and extravascular compression. Regional coronary flow dynamics of the two anatomical variants were compared under normotensive conditions, raised systemic or pulmonary pressures with maintained flow demand, and after accounting for adaptations known to occur in acute and chronic hypertensive states. Key findings were that 1) right coronary arterial flow patterns were strongly influenced by dominance and systemic/pulmonary hypertension; 2) dominance had minor effects on left coronary arterial and all microvascular flow patterns (aside from mean circumflex flow); 3) although systemic hypertension favorably increased perfusion pressure, this benefit varied regionally and transmurally and was offset by increased left ventricular and septal flow demands; and 4) pulmonary hypertension had a substantial negative effect on right ventricular and septal flows, which was exacerbated by greater metabolic demands. These findings highlight the importance of interactions between coronary arterial dominance and hypertension in modulating coronary hemodynamics. Copyright © 2016 the American Physiological Society.

Changing axis deviation during acute myocardial infarction.

PubMed

Patanè, Salvatore; Marte, Filippo

2010-07-09

Changing axis deviation has been reported during acute myocardial infarction also associated with atrial fibrillation. Isolated left posterior hemiblock is a very rare finding but the evidence of transient right axis deviation with a left posterior hemiblock pattern has been reported during acute anterior myocardial infarction as related with significant right coronary artery obstruction and collateral circulation between the left coronary system and the posterior descending artery. We present a case of changing axis deviation in a 70-year-old Italian man with acute myocardial infarction. Copyright (c) 2008 Elsevier Ireland Ltd. All rights reserved.

Unique antibody responses to malondialdehyde-acetaldehyde (MAA)-protein adducts predict coronary artery disease.

PubMed

Anderson, Daniel R; Duryee, Michael J; Shurmur, Scott W; Um, John Y; Bussey, Walter D; Hunter, Carlos D; Garvin, Robert P; Sayles, Harlan R; Mikuls, Ted R; Klassen, Lynell W; Thiele, Geoffrey M

2014-01-01

Malondialdehyde-acetaldehyde adducts (MAA) have been implicated in atherosclerosis. The purpose of this study was to investigate the role of MAA in atherosclerotic disease. Serum samples from controls (n = 82) and patients with; non-obstructive coronary artery disease (CAD), (n = 40), acute myocardial infarction (AMI) (n = 42), or coronary artery bypass graft (CABG) surgery due to obstructive multi-vessel CAD (n = 72), were collected and tested for antibody isotypes to MAA-modifed human serum albumin (MAA-HSA). CAD patients had elevated relative levels of IgG and IgA anti-MAA, compared to control patients (p<0.001). AMI patients had a significantly increased relative levels of circulating IgG anti-MAA-HSA antibodies as compared to stable angina (p<0.03) or CABG patients (p<0.003). CABG patients had significantly increased relative levels of circulating IgA anti-MAA-HSA antibodies as compared to non-obstructive CAD (p<0.001) and AMI patients (p<0.001). Additionally, MAA-modified proteins were detected in the tissue of human AMI lesions. In conclusion, the IgM, IgG and IgA anti-MAA-HSA antibody isotypes are differentially and significantly associated with non-obstructive CAD, AMI, or obstructive multi-vessel CAD and may serve as biomarkers of atherosclerotic disease.

Unique Antibody Responses to Malondialdehyde-Acetaldehyde (MAA)-Protein Adducts Predict Coronary Artery Disease

PubMed Central

Anderson, Daniel R.; Duryee, Michael J.; Shurmur, Scott W.; Um, John Y.; Bussey, Walter D.; Hunter, Carlos D.; Garvin, Robert P.; Sayles, Harlan R.; Mikuls, Ted R.; Klassen, Lynell W.; Thiele, Geoffrey M.

2014-01-01

Malondialdehyde-acetaldehyde adducts (MAA) have been implicated in atherosclerosis. The purpose of this study was to investigate the role of MAA in atherosclerotic disease. Serum samples from controls (n = 82) and patients with; non-obstructive coronary artery disease (CAD), (n = 40), acute myocardial infarction (AMI) (n = 42), or coronary artery bypass graft (CABG) surgery due to obstructive multi-vessel CAD (n = 72), were collected and tested for antibody isotypes to MAA-modifed human serum albumin (MAA-HSA). CAD patients had elevated relative levels of IgG and IgA anti-MAA, compared to control patients (p<0.001). AMI patients had a significantly increased relative levels of circulating IgG anti-MAA-HSA antibodies as compared to stable angina (p<0.03) or CABG patients (p<0.003). CABG patients had significantly increased relative levels of circulating IgA anti-MAA-HSA antibodies as compared to non-obstructive CAD (p<0.001) and AMI patients (p<0.001). Additionally, MAA-modified proteins were detected in the tissue of human AMI lesions. In conclusion, the IgM, IgG and IgA anti-MAA-HSA antibody isotypes are differentially and significantly associated with non-obstructive CAD, AMI, or obstructive multi-vessel CAD and may serve as biomarkers of atherosclerotic disease. PMID:25210746

Comments on the 2015 ESC Guidelines for the Management of Acute Coronary Syndromes in Patients Presenting Without Persistent ST-segment Elevation.

PubMed

Barrabes, J

2015-12-01

Patients who have undergone angioplasty with stenting can be reintegrated into normal life at an early stage, thanks to the absence of sequelae associated with the procedure itself. Consequently, these patients can be involved earlier in the second stage of cardiac rehabilitation. Although rehabilitation for coronary patients follows the general guidelines used for all patients, which were developed with the secondary prevention of coronary artery atherosclerosis in mind, the specific form of rehabilitation adopted for each individual with ischemic heart disease will depend on the patient's circumstances, including the revascularization technique used. Regular physical exercise (i.e. physical training), in itself, has substantial cardiovascular benefits for both primary and secondary cardiovascular prevention. In patients who have had a myocardial infarction, training decreases mortality, increases functional capacity and improves ventricular function and remodeling. It is also thought to boost the collateral circulation. In addition, training improves endothelial function and stimulates the circulation of stem cells. It has been shown that physical training after percutaneous revascularization decreases the number of cardiac events. Moreover, in patients with stable angina, it results in fewer events than percutaneous revascularization. Copyright © 2015 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Potential advantages of treatment of transplanted saphenous vein aorto-coronary artery bypass grafts with beta irradiation to prevent graft occlusion.

PubMed

Smith, R G

1997-01-01

Intimal proliferation or Neointimal hyperplasia (NIH) is a vascular lesion that often arises in arteries after balloon angioplasty or other vessel wall injuries. FIH is a vascular lesion that develops in autologous saphenous vein grafts (SVG) after transplantation into the aorto-coronary circulation or the peripheral vascular circulation. FIH shares elements of smooth muscle migration, proliferation and fibrous tissue deposition in common with nibrointimal proliferation (NIH). Either NIH of a coronary artery or FIH of a SVG obstruct the vascular lumen and result in myocardial dysfunction. Local radiotherapy has been used for several decades to reduce the post-operative recurrence of the fibrovascular proliferations of pterygia and keloids. Similarly, in animal and human experiments, endovascular radiotherapy has been shown to reduce arterial smooth muscle proliferation. Consideration of the similarities of vascular smooth muscle cell proliferation in NIH and FIH leads one to suggest that endovascular beta irradiation can reduce FIH as well as it reduces NIH. The goal of such treatment is to achieve a clinically significant decrease in the morbidity and mortality resulting from SVG occlusions. The potential for large reduction of the consequences of SVG occlusion, the very large number of patients at risk, and the simplicity of the proposed intervention encourages prompt scientific evaluation of this technique.

Kinetics of plasma heat shock protein HSP-70 release in coronary artery surgery: on-pump versus off-pump.

PubMed

Pizon, M T; Gburek, T; Pizon, M; Sztefko, K

2006-12-01

Heat shock protein HSP-70 is known as protective chaperone molecule synthetized in response following ischemia and stress agents. It is detected in the myocardium and endothelium as well as in the circulation. Damaged as well as viable but exposed to stress cells contribute to the release of HSP-70 into the circulation. The aim of the study was to investigate if cardiopulmonary bypss (CPB) leads to more circulating HSP-70, on the basis of comparison dynamics of plasma concentration HSP-70 in 8 men undergoing procedures with the use of CPB (coronary artery bypass grafting, CABG group) and 8 men undergoing off-pump surgery (OPCAB group). Blood samples were taken preoperatively, twice intraoperatively, immediately after surgical procedure (1 h) and 24-hours thereafter. The concentration of plasma HSP-70 was measured by means of immunoassay. The derived results were compared statistically with the frequency of incidence postoperative atrial fibrillation (AF). In CABG group was observed continuous gradual increase of plasma HSP-70 concentration during the operation with the peak 1 h after surgery (P<0.01), in striking contrast to OPCAB group, in which was detected small, but non statistically significant increase of HSP-70 1 h after operation. Significantly more of circulating HSP-70 it was detected in CABG group during the operation and 1 h after surgery (CABG vs OPCAB, respectively P<0.015 and P<0.028). In both groups among patients witch AF it was found higher postoperative values of circulating HSP-70 compared with the non-AF group (P=0.0415). The use of CPB leads to significant more release of HSP-70 into the circulation. According to our findings high plasma concentration of HSP-70 may be the measure of operative cellular stress, ischemia or injury and may be related with greater onset of postoperative AF. High circulating HSP-70 levels is connected with higher incidence of postoperative AF after open heart surgery.

Coronary involvement in Churg-Strauss syndrome.

PubMed

Dendramis, Gregory; Paleologo, Claudia; Piraino, Davide; Arrotti, Salvatore; Assennato, Pasquale

2015-01-01

Systemic autoimmune diseases are themselves a relevant and independent risk factor for atherosclerosis and coronary ectasia. We describe a case of a 58-year-old Caucasian man who was admitted to our department for unstable angina. History of asthma, paranasal sinus abnormality, and peripheral eosinophilia given a high suspicion of Churg-Strauss syndrome (CSS). Diagnosis was performed with 5 of the 6 American College of Rheumatology criteria. The knowledge that CSS is often associated with significant coronary artery involvement and the persistence of chest pain led us to performing immediately a coronary angiography. Coronary angiography showed diffuse ectasic lesions, chronic occlusion of left anterior descending artery with homocoronary collateral circulation from left circumflex artery and subocclusive stenosis in the proximal tract of posterior descending artery. The early recognition of CSS, an aggressive invasive diagnostic approach, and an early appropriate therapy are important to prevent the progressive and permanent cardiac damage in these patients. In the setting of a multidisciplinary approach, careful cardiac assessment is an essential step in CSS, even in mildly symptomatic patients. Copyright © 2015 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

The effects of conventional extracorporeal circulation versus miniaturized extracorporeal circulation on microcirculation during cardiopulmonary bypass-assisted coronary artery bypass graft surgery

PubMed Central

Yuruk, Koray; Bezemer, Rick; Euser, Mariska; Milstein, Dan M.J.; de Geus, Hilde H.R.; Scholten, Evert W.; de Mol, Bas A.J.M.; Ince, Can

2012-01-01

OBJECTIVES To reduce the complications associated with cardiopulmonary bypass (CPB) during cardiac surgery, many modifications have been made to conventional extracorporeal circulation systems. This trend has led to the development of miniaturized extracorporeal circulation systems. Cardiac surgery using conventional extracorporeal circulation systems has been associated with significantly reduced microcirculatory perfusion, but it remains unknown whether this could be prevented by an mECC system. Here, we aimed to test the hypothesis that microcirculatory perfusion decreases with the use of a conventional extracorporeal circulation system and would be preserved with the use of an miniaturized extracorporeal circulation system. METHODS Microcirculatory density and perfusion were assessed using sublingual side stream dark-field imaging in patients undergoing on-pump coronary artery bypass graft (CABG) surgery before, during and after the use of either a conventional extracorporeal circulation system (n = 10) or a miniaturized extracorporeal circulation system (n = 10). In addition, plasma neutrophil gelatinase-associated lipocalin and creatinine levels and creatinine clearance were assessed up to 5 days post-surgery to monitor renal function. RESULTS At the end of the CPB, one patient in the miniaturized extracorporeal circulation-treated group and five patients in the conventional extracorporeal circulation-treated group received one bag of packed red blood cells (300 ml). During the CPB, the haematocrit and haemoglobin levels were slightly higher in the miniaturized extracorporeal circulation-treated patients compared with the conventional extracorporeal circulation-treated patients (27.7 ± 3.3 vs 24.7 ± 2.0%; P = 0.03; and 6.42 ± 0.75 vs 5.41 ± 0.64 mmol/l; P < 0.01). The density of perfused vessels with a diameter <25 µm (i.e. perfused vessel density) decreased slightly in the conventional extracorporeal circulation-treated group from 16.4 ± 3.8 to 12.8 ± 3.3 mm/mm2 (P < 0.01) and remained stable in the miniaturized extracorporeal circulation-treated group (16.3 ± 2.7 and 15.2 ± 2.9 mm/mm2 before and during the pump, respectively). Plasma neutrophil gelatinase-associated lipocalin levels were increased following the use of extracorporeal circulation in both groups, and no differences were observed between the groups. Plasma creatinine levels and creatinine clearance were not affected by CABG surgery or CPB. CONCLUSIONS The results from this relatively small study suggest that the use of the miniaturized extracorporeal circulation system is associated with a statistically significant (but clinically insignificant) reduction in haemodilution and microcirculatory hypoperfusion compared with the use of the conventional extracorporeal circulation system. PMID:22700685

The human coronary vasodilatory response to acute mental stress is mediated by neuronal nitric oxide synthase.

PubMed

Khan, Sitara G; Melikian, Narbeh; Shabeeh, Husain; Cabaco, Ana R; Martin, Katherine; Khan, Faisal; O'Gallagher, Kevin; Chowienczyk, Philip J; Shah, Ajay M

2017-09-01

Mental stress-induced ischemia approximately doubles the risk of cardiac events in patients with coronary artery disease, yet the mechanisms underlying changes in coronary blood flow in response to mental stress are poorly characterized. Neuronal nitric oxide synthase (nNOS) regulates basal coronary blood flow in healthy humans and mediates mental stress-induced vasodilation in the forearm. However, its possible role in mental stress-induced increases in coronary blood flow is unknown. We studied 11 patients (6 men and 5 women, mean age: 58 ± 14 yr) undergoing elective diagnostic cardiac catheterization and assessed the vasodilator response to mental stress elicited by the Stroop color-word test. Intracoronary substance P (20 pmol/min) and isosorbide dinitrate (1 mg) were used to assess endothelium-dependent and -independent vasodilation, respectively. Coronary blood flow was estimated using intracoronary Doppler recordings and quantitative coronary angiography to measure coronary artery diameter. Mental stress increased coronary flow by 34 ± 7.0% over the preceding baseline during saline infusion ( P < 0.01), and this was reduced to 26 ± 7.0% in the presence of the selective nNOS inhibitor S -methyl-l-thiocitrulline (0.625 µmol/min, P < 0.001). Mental stress increased coronary artery diameter by 6.9 ± 3.7% ( P = 0.02) and 0.5 ± 2.8% ( P = 0.51) in the presence of S -methyl-l-thiocitrulline. The response to substance P did not predict the response to mental stress ( r 2 = -0.22, P = 0.83). nNOS mediates the human coronary vasodilator response to mental stress, predominantly through actions at the level of coronary resistance vessels. NEW & NOTEWORTHY Acute mental stress induces vasodilation of the coronary microvasculature. Here, we show that this response involves neuronal nitric oxide synthase in the human coronary circulation.Listen to this article's corresponding podcast at http://ajpheart.podbean.com/e/nnos-and-coronary-flow-during-mental-stress/. Copyright © 2017 the American Physiological Society.

The human coronary vasodilatory response to acute mental stress is mediated by neuronal nitric oxide synthase

PubMed Central

Khan, Sitara G.; Melikian, Narbeh; Shabeeh, Husain; Cabaco, Ana R.; Martin, Katherine; Khan, Faisal; O’Gallagher, Kevin; Chowienczyk, Philip J.

2017-01-01

Mental stress-induced ischemia approximately doubles the risk of cardiac events in patients with coronary artery disease, yet the mechanisms underlying changes in coronary blood flow in response to mental stress are poorly characterized. Neuronal nitric oxide synthase (nNOS) regulates basal coronary blood flow in healthy humans and mediates mental stress-induced vasodilation in the forearm. However, its possible role in mental stress-induced increases in coronary blood flow is unknown. We studied 11 patients (6 men and 5 women, mean age: 58 ± 14 yr) undergoing elective diagnostic cardiac catheterization and assessed the vasodilator response to mental stress elicited by the Stroop color-word test. Intracoronary substance P (20 pmol/min) and isosorbide dinitrate (1 mg) were used to assess endothelium-dependent and -independent vasodilation, respectively. Coronary blood flow was estimated using intracoronary Doppler recordings and quantitative coronary angiography to measure coronary artery diameter. Mental stress increased coronary flow by 34 ± 7.0% over the preceding baseline during saline infusion (P < 0.01), and this was reduced to 26 ± 7.0% in the presence of the selective nNOS inhibitor S-methyl-l-thiocitrulline (0.625 µmol/min, P < 0.001). Mental stress increased coronary artery diameter by 6.9 ± 3.7% (P = 0.02) and 0.5 ± 2.8% (P = 0.51) in the presence of S-methyl-l-thiocitrulline. The response to substance P did not predict the response to mental stress (r2 = −0.22, P = 0.83). nNOS mediates the human coronary vasodilator response to mental stress, predominantly through actions at the level of coronary resistance vessels. NEW & NOTEWORTHY Acute mental stress induces vasodilation of the coronary microvasculature. Here, we show that this response involves neuronal nitric oxide synthase in the human coronary circulation. Listen to this article’s corresponding podcast at http://ajpheart.podbean.com/e/nnos-and-coronary-flow-during-mental-stress/. PMID:28646032

Differential effects of ascorbate on endothelium-derived hyperpolarizing factor (EDHF)-mediated vasodilatation in the bovine ciliary vascular bed and coronary artery.

PubMed

McNeish, Alister J; Nelli, Silvia; Wilson, William S; Dowell, Fiona J; Martin, William

2003-03-01

1. The ability of ascorbate to inhibit endothelium-derived hyperpolarizing factor (EDHF)-mediated vasodilatation was compared in the bovine perfused ciliary vascular bed and isolated rings of coronary artery. 2. Acetylcholine-induced, EDHF-mediated vasodilatation of the ciliary circulation was blocked following inclusion of ascorbate (50 micro M, 120 min) in the perfusion fluid. The blockade was highly selective since ascorbate had no effect on the vasodilator actions of the K(ATP) channel opener, levcromakalim, nor on the tonic vasodepressor action of basally released nitric oxide. 3. The possibility that concentration of ascorbate by the ciliary body was a prerequisite for blockade to occur was ruled out, since EDHF was still blocked when the anterior and posterior chambers were continuously flushed with Krebs solution or when both the aqueous and vitreous humour were drained. 4. Ascorbate at 50 micro M failed to affect bradykinin- or acetylcholine-induced, EDHF-mediated vasodilatation in rings of bovine coronary artery. Raising the concentration to 3 mM did produce blockade of EDHF, but this was nonselective, since vasodilator responses to endothelium-derived nitric oxide were also inhibited. 5. Thus, ascorbate (50 micro M) is not a universal blocker of EDHF. Whether its ability to block in the bovine ciliary circulation, but not in the coronary artery, is due to differences in the nature of EDHF at the two sites, differences in vessel size (resistance arterioles versus conduit artery), the presence or absence of flow, or to some other factor remains to be determined.

Reduced 30-day mortality in men after elective coronary artery bypass surgery with minimized extracorporeal circulation-a propensity score analysis

PubMed Central

2012-01-01

Background Impact of minimized extracorporeal circulation (MECC) for coronary surgery on mortality remains controversial and gender significantly influence outcome. Methods We analyzed 3,139 male patients undergoing elective coronary surgery between 01/2004 and 05/2009. Using propensity score matching after binary logistic regression, 1,005 patients (from 1,119 patients) undergoing surgery with MECC could be matched with 1,005 patients (from 2,020 patients) undergoing surgery with conventional extracorporeal circulation (CECC). Primary outcome was 30-day mortality. Results Unadjusted 30-day mortality was 2.7% in patients with CECC and 0.8% in those with MECC (mean difference -1.9%; p < 0.001). The adjusted mean difference (average treatment effect of the treated) after matching was -1.5% (95% confidence interval (CI) -2.6 to -0.4; p = 0.006). Postoperative hospital stay was shorter in patients operated with minimized systems (adjusted mean difference -0.8 days; 95% CI -1.46 to -0.09; p = 0.03) and incidence of postoperative neurocognitive dysfunction was also lower (adjusted mean difference -1.3%; 95% CI -2.2 to -0.4; p = 0.001). Chest tube drainage (adjusted mean difference +22 mL; 95% CI -47 to 91; p = 0.5) and risk for acute kidney injury, kidney injury and failure according to RIFLE criteria (adjusted mean difference -1.0%; 95% CI -2.5 to 0.6; p = 0.24) proved to be insignificant between both groups. Apart from reduced 30-day mortality, however, average treatment effects for intensive care unit stay, postoperative hospital stay, chest tube drainage and kidney injury did not significantly differ. Conclusion Using propensity score analysis, we observed an association between MECC and reduced 30-day mortality in men, but our results call for further analysis. PMID:22424497

Presence of irregularity in region between -1115 and -784 nt in P1 promoter of insulin-like growth factor-1 gene may indicate beneficial effect on coronary arteries in a group of patients with stable angina: preliminary data.

PubMed

Burchardt, Pawel; Nowak, Witold; Gozdzicka-Jozefiak, Anna; Link, Rafal; Grotowski, Tomasz; Wisniecka, Anna; Siminiak, Tomasz

2009-07-01

Insulin-like growth factor-1 (IGF-1) plays an important role in arterial homeostasis. Its properties seem to depend on circulating IGF-1 level changes. The various IGF-1 levels are caused by varied expression of IGF-1 gene, due to the polymorphic structure of IGF-1 gene or its regulatory sequences. We examined the P1 promoter, being responsible for most IGF-1 transcripts, in patients with stable angina, to evaluate its sequence changes and to assess its influence on protein synthesis as well as on the degree of arteriosclerosis. For that purpose we evaluated the DNA isolated from blood cells. The DNA was amplified by using polymerase chain reaction (PCR), then analyzed using the SSCP (single-strand conformation polymorphism) technique. Products of every stage were verified by electrophoresis on agarose gel. In addition, every patient had coronary angiography performed and IGF-1, IGFBP3, and lipid levels measured. The SSCP in the region between -1115 and -784 nt was less commonly observed among subjects with positive MI (myocardial infarction) familial history (P = 0.0008) and with MI history (P = 0.012) than in patients without these conditions. Subjects with this irregularity tended towards higher circulating IGF-1 levels. In addition high Gensini scores - over 95th percentile, 105 points in our study - were more frequent in SSCP patients (P = 0.03). We presume that presence of SSCP in the P1 region between -1115 and -784 nt may positively affect coronary arteries by increasing circulating IGF-1 levels, but its clinical importance requires molecular verification and further studies.

Effects of Acute Exposure to an Environmental Electrophile on Human Platelet Bioenergetics

EPA Science Inventory

Exposure to air pollution is a global public health problem associated with cardiovascular morbidity and mortality. Exposure to particulate matter (PM) has been reported to activate circulating platelets in vulnerable populations (patients with type 2 diabetes or coronary heart d...

Short-term effects of an intensive lifestyle modification program on lipid peroxidation and antioxidant systems in patients with coronary artery disease.

PubMed

Jatuporn, Srisakul; Sangwatanaroj, Somkiat; Saengsiri, Aem-Orn; Rattanapruks, Sopida; Srimahachota, Suphot; Uthayachalerm, Wasan; Kuanoon, Wanpen; Panpakdee, Orasa; Tangkijvanich, Pisit; Tosukhowong, Piyaratana

2003-01-01

The purpose of this study was to compare the short-term effects of an intensive lifestyle modification (ILM) program on lipid peroxidation and antioxidant systems in patients with coronary artery disease (CAD). Twenty-two patients in the control group continued to receive their conventional treatment with lipid-lowering drugs, whereas 22 patients in the experimental group were assigned to intensive lifestyle modification (ILM) without taking any lipid-lowering agent. The ILM program comprised dietary advice on low-fat diets, high antioxidants and high fiber intakes, yoga exercise, stress management and smoking cessation. After 4 months of intervention, patients in the experimental group revealed a statistically significant increase in plasma total antioxidants, plasma vitamin E and erythrocyte glutathione (GSH) compared to patients in the control group. There was no significant change in plasma malondialdehyde (MDA), a circulating product of lipid peroxidation, in either group. We concluded that the ILM program increased circulating antioxidants and reduced oxidative stress in patients with CAD.

Acute effect of oral flavonoid-rich dark chocolate intake on coronary circulation, as compared with non-flavonoid white chocolate, by transthoracic Doppler echocardiography in healthy adults.

PubMed

Shiina, Yumi; Funabashi, Nobusada; Lee, Kwangho; Murayama, Taichi; Nakamura, Koki; Wakatsuki, Yu; Daimon, Masao; Komuro, Issei

2009-01-24

To assess the effects of the oral intake of flavonoid-rich dark chocolate on coronary circulation, we measured coronary flow velocity reserve (CFVR) by noninvasive transthoracic Doppler echocardiography (TTDE) in healthy adult subjects. The study was a randomized, single-blind design conducted for 2 weeks in 39 healthy men (mean age 29.7+/-3.9 years, range 23-40 years). Subjects were randomly assigned a daily intake of either flavonoid-rich dark chocolate (Meiji Black Chocolate 45 g, Meiji Seika kaisya Ltd, including cacao polyphenol 550 mg/day, 200 kcal) or non-flavonoid white chocolate (Meiji White Chocolate 35 g, Meiji Seika kaisya Ltd, including cacao polyphenol 0 mg/day, 140 kcal) as a control. CFVR was recorded by TTDE, and assessed before and after 2 weeks of intake. At the same time, we also assessed serum asymmetric dimethylarginine, 8-isoprostanes, and malondialdehyde-modified low-density lipoprotein (MDA-LDL) as markers of oxidative stress. Flavonoid-rich dark chocolate consumption significantly improved CFVR (3.38+/-0.49 before intake, 4.28+/-0.85 after intake; p<0.01), whereas non-flavonoid white chocolate consumption did not (3.28+/-0.49 before intake, 3.16+/-0.49 after intake; p=0.44). All predictor variables were used as dependent variables in a multiple regression model of the incremental change in CFVR after 2 weeks of chocolate intake. Intake of dark (but not white) chocolate, MDA-LDL, triglyceride (TG) and heart rate (HR) significantly influenced the change of CFVR after 2 weeks of intake (p<0.01) according to the multiple regression formula: Y=1.01X(1)-0.005X(2)-0.003X(3)-0.017X4 (Y=change in CFVR after 2 weeks of chocolate intake, X1=intake of dark (but not white) chocolate, X2=MDA-LDL, X3=TG, X4=HR). Flavonoid-rich dark chocolate intake significantly improved coronary circulation in healthy adults, independent of changes in oxidative stress parameters, blood pressure and lipid profile, whereas non-flavonoid white chocolate had no such effects.

A computational framework to characterize and compare the geometry of coronary networks.

PubMed

Bulant, C A; Blanco, P J; Lima, T P; Assunção, A N; Liberato, G; Parga, J R; Ávila, L F R; Pereira, A C; Feijóo, R A; Lemos, P A

2017-03-01

This work presents a computational framework to perform a systematic and comprehensive assessment of the morphometry of coronary arteries from in vivo medical images. The methodology embraces image segmentation, arterial vessel representation, characterization and comparison, data storage, and finally analysis. Validation is performed using a sample of 48 patients. Data mining of morphometric information of several coronary arteries is presented. Results agree to medical reports in terms of basic geometric and anatomical variables. Concerning geometric descriptors, inter-artery and intra-artery correlations are studied. Data reported here can be useful for the construction and setup of blood flow models of the coronary circulation. Finally, as an application example, similarity criterion to assess vasculature likelihood based on geometric features is presented and used to test geometric similarity among sibling patients. Results indicate that likelihood, measured through geometric descriptors, is stronger between siblings compared with non-relative patients. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Circulating magnesium levels and incidence of coronary heart diseases, hypertension, and type 2 diabetes mellitus: a meta-analysis of prospective cohort studies.

PubMed

Wu, Jiang; Xun, Pengcheng; Tang, Qingya; Cai, Wei; He, Ka

2017-09-19

Data on the associations between circulating magnesium (Mg) levels and incidence of coronary heart diseases (CHD), hypertension, and type 2 diabetes mellitus (T2DM) are inconsistent and inconclusive. The aim of this study was to examine circulating Mg levels in relation to incidence of CHD, hypertension, and T2DM. Prospective cohort studies published before May 2017 were searched through PubMed, EmBase, SCOPUS, and Google Scholar. A total of 11 studies that reported multivariable-adjusted associations of interest were identified. Information on the characteristics of study and participants, exposure, main outcomes, risk estimates, and cofounders was extracted and analyzed. Of the 11 included studies, 5 reported results on CHD (38,808 individuals [4437 cases] with an average 10.5-year follow-up), 3 on hypertension (14,876 participants [3149 cases] with a 6.7-year follow-up), and 4 on T2DM (31,284 participants [2680 cases] with an 8.8-year follow-up). Comparing the highest to the lowest category of circulating Mg concentration, the pooled relative risks [RRs] (95% confidence intervals [CIs]) were 0.86 (0.74, 0.996), 0.91 (0.80, 1.02), and 0.64 (0.50, 0.81) for incidence of CHD, hypertension, and T2DM, respectively. Every 0.1 mmol/L increment in circulating Mg levels was associated with 4% (RR, 0.96; 95% CI: 0.94, 0.99) reduction in hypertension incidence. No significant linear association was found between circulating Mg levels and incidence of CHD (RR, 0.89; 95% CI: 0.77, 1.03) and T2DM (RR, 0.90; 95% CI: 0.81, 1.002). The observed associations of interest were sensitive to exclusion of individual studies. Findings in this meta-analysis suggest that circulating Mg levels are inversely associated with incidence of CHD, hypertension, and T2DM. Additional studies are needed to provide more solid evidence and identify the optimal range of circulating Mg concentration with respect to primary prevention of CHD, hypertension, and T2DM.

Cohort profile of BIOMArCS: the BIOMarker study to identify the Acute risk of a Coronary Syndrome—a prospective multicentre biomarker study conducted in the Netherlands

PubMed Central

Oemrawsingh, Rohit M; Akkerhuis, K Martijn; Umans, Victor A; Kietselaer, Bas; Schotborgh, Carl; Ronner, Eelko; Lenderink, Timo; Liem, Anho; Haitsma, David; van der Harst, Pim; Asselbergs, Folkert W; Maas, Arthur; Oude Ophuis, Anton J; Ilmer, Ben; Dijkgraaf, Rene; de Winter, Robbert-Jan; The, S Hong Kie; Wardeh, Alexander J; Hermans, Walter; Cramer, Etienne; van Schaik, Ron H; Hoefer, Imo E; Doevendans, Pieter A; Simoons, Maarten L; Boersma, Eric

2016-01-01

Purpose Progression of stable coronary artery disease (CAD) towards acute coronary syndrome (ACS) is a dynamic and heterogeneous process with many intertwined constituents, in which a plaque destabilising sequence could lead to ACS within short time frames. Current CAD risk assessment models, however, are not designed to identify increased vulnerability for the occurrence of coronary events within a precise, short time frame at the individual patient level. The BIOMarker study to identify the Acute risk of a Coronary Syndrome (BIOMArCS) was designed to evaluate whether repeated measurements of multiple biomarkers can predict such ‘vulnerable periods’. Participants BIOMArCS is a multicentre, prospective, observational study of 844 patients presenting with ACS, either with or without ST-elevation and at least one additional cardiovascular risk factor. Methods and analysis We hypothesised that patterns of circulating biomarkers that reflect the various pathophysiological components of CAD, such as distorted lipid metabolism, vascular inflammation, endothelial dysfunction, increased thrombogenicity and ischaemia, diverge in the days to weeks before a coronary event. Divergent biomarker patterns, identified by serial biomarker measurements during 1-year follow-up might then indicate ‘vulnerable periods’ during which patients with CAD are at high short-term risk of developing an ACS. Venepuncture was performed every fortnight during the first half-year and monthly thereafter. As prespecified, patient enrolment was terminated after the primary end point of cardiovascular death or hospital admission for non-fatal ACS had occurred in 50 patients. A case–cohort design will explore differences in temporal patterns of circulating biomarkers prior to the repeat ACS. Future plans and dissemination Follow-up and event adjudication have been completed. Prespecified biomarker analyses are currently being performed and dissemination through peer-reviewed publications and conference presentations is expected from the third quarter of 2016. Should identification of a ‘vulnerable period’ prove to be feasible, then future research could focus on event reduction through pharmacological or mechanical intervention during such periods of high risk for ACS. Trial registration number NTR1698 and NTR1106. PMID:28011810

Inactivating Variants in ANGPTL4 and Risk of Coronary Artery Disease

PubMed Central

Dewey, Frederick E.; Gusarova, Viktoria; O’Dushlaine, Colm; Gottesman, Omri; Trejos, Jesus; Hunt, Charleen; Van Hout, Cristopher V.; Habegger, Lukas; Buckler, David; Lai, Ka-Man V.; Leader, Joseph B.; Murray, Michael F.; Ritchie, Marylyn D.; Kirchner, H. Lester; Ledbetter, David H.; Penn, John; Lopez, Alexander; Borecki, Ingrid B.; Overton, John D.; Reid, Jeffrey G.; Carey, David J.; Murphy, Andrew J.; Yancopoulos, George D.; Baras, Aris; Gromada, Jesper; Shuldiner, Alan R.

2016-01-01

BACKGROUND Higher-than-normal levels of circulating triglycerides are a risk factor for ischemic cardiovascular disease. Activation of lipoprotein lipase, an enzyme that is inhibited by angiopoietin-like 4 (ANGPTL4), has been shown to reduce levels of circulating triglycerides. METHODS We sequenced the exons of ANGPTL4 in samples obtain from 42,930 participants of predominantly European ancestry in the DiscovEHR human genetics study. We performed tests of association between lipid levels and the missense E40K variant (which has been associated with reduced plasma triglyceride levels) and other inactivating mutations. We then tested for associations between coronary artery disease and the E40K variant and other inactivating mutations in 10,552 participants with coronary artery disease and 29,223 controls. We also tested the effect of a human monoclonal antibody against ANGPTL4 on lipid levels in mice and monkeys. RESULTS We identified 1661 heterozygotes and 17 homozygotes for the E40K variant and 75 participants who had 13 other monoallelic inactivating mutations in ANGPTL4. The levels of triglycerides were 13% lower and the levels of high-density lipoprotein (HDL) cholesterol were 7% higher among carriers of the E40K variant than among noncarriers. Carriers of the E40K variant were also significantly less likely than noncarriers to have coronary artery disease (odds ratio, 0.81; 95% confidence interval, 0.70 to 0.92; P = 0.002). K40 homozygotes had markedly lower levels of triglycerides and higher levels of HDL cholesterol than did heterozygotes. Carriers of other inactivating mutations also had lower triglyceride levels and higher HDL cholesterol levels and were less likely to have coronary artery disease than were noncarriers. Monoclonal antibody inhibition of Angptl4 in mice and monkeys reduced triglyceride levels. CONCLUSIONS Carriers of E40K and other inactivating mutations in ANGPTL4 had lower levels of triglycerides and a lower risk of coronary artery disease than did noncarriers. The inhibition of Angptl4 in mice and monkeys also resulted in corresponding reductions in these values. (Funded by Regeneron Pharmaceuticals.) PMID:26933753

Impact of minimized extracorporeal circulation on outcome in patients with preoperative anemia undergoing coronary artery bypass surgery.

PubMed

Haneya, Assad; Philipp, Alois; Von Suesskind-Schwendi, Marietta; Diez, Claudius; Hirt, Stephan W; Kolat, Philipp; Attmann, Tim; Schoettler, Jan; Zausig, York; Ried, Michael; Schmid, Christof

2013-01-01

Preoperative anemia and low hematocrit during cardiopulmonary bypass have been associated with worse outcome in patients undergoing cardiac surgery. The minimized extracorporeal circulation (MECC) allows a reduction of the negative effects associated with conventional extracorporeal circulation (CECC). In this study, the impact of the MECC on outcome of anemic patients after coronary artery bypass grafting (CABG) was assessed. Between January 2004 and December 2011, 1,945 consecutive patients with preoperative anemia underwent isolated CABG using CECC (44.8%) or MECC (55.2%). The cutoff point for anemia was 13 g/dl for men and 12 g/dl for women. The postoperative creatine kinase and lactate levels were significantly lower in the MECC group (p < 0.001). There was no difference in postoperative blood loss between the groups. However, the intraoperative and postoperative transfusion requirements were significantly lower in the MECC group (p < 0.05). Furthermore, MECC patients had lower incidences of postoperative acute renal failure, and low cardiac output syndrome, shorter intensive care unit lengths of stay and reduced 30-day mortality (p < 0.05). In conclusion, a reduced postoperative mortality, lower transfusion requirements, and less renal and myocardial damage encourage the use of MECC for CABG, especially in the specific high-risk subgroup of patients with anemia.

[Isolated mitral valve insufficiency in comparison with mitral-tricuspid insufficiency: various mechanisms of compensating for the defect and functional status of the myocardium].

PubMed

Petrovskiĭ, P F; Torbina, A M; Klemborskiĭ, A A

1988-09-01

A combined analysis of ventricular contractility and intracardiac hemodynamic compensatory mechanisms was carried out, on the basis of angiocardiographic findings, in 37 patients with rheumatic mitral incompetence. Atrial fibrillation aggravates essentially the defect's hemodynamics, while added tricuspid incompetence is accompanied by a certain off-loading in the lesser circulation network. A grossly perversed phasic structure of intramyocardial stress was noted, apparently being a compensatory mechanism. Reduced specific coronary flow and diastolic perfusion gradient in intact coronary arteries are shown to be causes of clinical angina.

Differential sensitivities of pulmonary and coronary arteries to hemoglobin-based oxygen carriers and nitrovasodilators: study in a bovine ex vivo model of vascular strips.

PubMed

Fonseca, Vera; Avizinis, Jessica; Moon-Massat, Paula; Freilich, Daniel; Kim, Hae Won; Hai, Chi-Ming

2010-01-01

Vasoconstriction is a major adverse effect of first and second generation hemoglobin-based oxygen carriers (HBOCs) that hinders their development as blood substitute. However, intravenous infusion of HBOC-201 (second generation) to patients induces significant pulmonary hypertension without significant coronary vasoconstriction. We compared contractile responses of isolated bovine pulmonary and coronary arterial strips to HBOC-201 and HBOC-205LL.LT.MW600 (third generation), polymerized bovine hemoglobins of different molecular weight, and their attenuation by nitroglycerin, sodium nitroprusside (SNP), and sodium nitrite. Pulmonary arteries developed negligible basal tone, but exhibited HBOC-dependent amplification of phenylephrine-induced contractions. In contrast, coronary arteries developed significant basal tone, and exhibited HBOC-dependent constant force increment to serotonin-induced contractions. Therefore, relative to basal tone, HBOC-induced contractions were greater in pulmonary than coronary arteries. Furthermore, HBOC-205LL.LT.MW600 appeared to be less vasoactive than HBOC-201. Unexpectedly, pulmonary and coronary arteries exhibited differential sensitivities to nitrovasodilators in parallel with their differential sensitivities to HBOC. However, SNP and sodium nitrite induced significant methemoglobin formation from HBOC, whereas nitroglycerin did not. These results suggest that phenotypic differences between pulmonary and coronary vascular smooth muscle cells could explain the differential hypertensive effects of HBOC on pulmonary and coronary circulation in patients. Among the three nitrovasodilators investigated, nitroglycerin appears to be the most promising candidate for attenuating HBOC-induced pulmonary hypertension in older HBOCs.

Treg/Th17 balance in stable CAD patients with different stages of coronary atherosclerosis.

PubMed

Potekhina, Alexandra V; Pylaeva, Ekaterina; Provatorov, Sergey; Ruleva, Natalya; Masenko, Valery; Noeva, Elena; Krasnikova, Tatiana; Arefieva, Tatiana

2015-01-01

Objective. Immune processes play a significant role in atherosclerosis plaque progression. Regulatory T cells and T helpers 17 were shown to possess anti- and pro-atherogenic activity, respectively. We aimed to investigate the balance of circulating Treg and Th17 in stable angina patients with different stages of coronary atherosclerosis. Methods. Treg, Th17 and Th1 cell frequencies were studied in 117 patients via direct immunofluorescence staining and flow cytometry. Group 1 had intact coronary arteries. Group 2 and Group 3 had undergone previous coronary stenting; in Group 2 no coronary atherosclerosis progression was found, in Group 3 patients had disease progression in non-invaded coronary arteries. Group 4 had severe coronary atherosclerosis. Results. The frequencies of CD4+CD25highCD127low, CD4+foxp3+, and CD4+IL10 + T cells were decreased, and CD4+IL17 + T cells frequencies were increased in group 4 vs. 1. Treg/Th17 ratios were declined in groups 3 and 4 vs. groups 1 and 2. IL-10 level was lower while hsCRP and sCD25 levels were higher in group 4 vs. 1. Conclusion. We assume that the imbalance in pro- and anti-inflammatory/atherogenic lymphocyte subpopulations is associated with atherosclerosis progression. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

The relationship of plasma miR-503 and coronary collateral circulation in patients with coronary artery disease.

PubMed

Fei, Yu; Hou, Jianhua; Xuan, Wei; Zhang, Chenghua; Meng, Xiuping

2018-06-02

Although angiogenesis plays an important role in coronary collateral circulation (CCC) formation and there are many determinants of coronary angiogenesis, they cannot fully explain the mechanism of CCC formation or as potent biomarker for CCC status. Therefore, there is of great clinical significance to identify the novel molecules associated with CCC. Previously, miR-503 exerts anti-angiogenesis effect via inhibition of VEGF-A and its expression is associated with many angiogenesis-related factors. Thus, we aimed to investigate the relationship of plasma miR-503 with CCC formation as well as its predictive power for CCC status in patients with coronary artery disease. Among patients who underwent coronary angiography with coronary artery disease and a stenosis of ≥90% were included in our study. Collateral degree was graded according to Rentrop Cohen classification. The patients were divided to good CCC group (grade 2 or 3) and poor CCC group (grade 0 or 1) according to Rentrop grade. We investigated the plasma levels of miR-503 and VEGF-A by ELISA or q RT-PCR, respectively. In addition, we assayed the correlations of plasma miR-503 with VEGF-A or Rentrop grade using the spearman correlation test and its predictive power by receiver operating characteristic (ROC) and binary logistical regression analysis. Our data showed that plasma VEGF-A was significantly higher in good CCC group than that in poor group. Plasma miR-503 was lower in CAD patients with good CCC or poor CCC compared with control subjects and lowest in good CCC group. In addition, miR-503 negatively correlated with VEGF-A and Rentrop grade, respectively. Moreover, miR-503 displayed more potent predictive power for CCC status than VEGF-A, but its sensitivity and specificity for CCC status were only 72.4 or 60.9%, respectively. Lower plasma miR-503 level was related to better CCC formation, accompanied by up-regulation of VEGF-A. In addition, miR-503 displayed potent predictive power for CCC status, but its sensitivity and specificity were not high enough, indicating that miR-503 might be as an additional prognosis biomarker for CCC. Copyright © 2017. Published by Elsevier Inc.

Alterations in cholesterol absorption and synthesis characterize Framingham offspring study participants with coronary heart disease

USDA-ARS?s Scientific Manuscript database

Data is limited on measures influencing cholesterol homeostasis in subjects at high risk of developing cardiovascular disease (CVD) relative to established risk factors. To address this, we quantified circulating indicators of cholesterol homeostasis (plasma phytosterols and cholesterol precursor co...

Investigations Regarding Anesthesia during Hypovolemic Conditions.

DTIC Science & Technology

1983-09-25

Wilson N, Ngsee J, Turnbull KW, Leighton K: Haemodynamics and plasma vasopressin responses with high-dose fentanyl anaesthesia dur- ing aorto-coronary...on the binding of CO2 to human haemoglobin and , . . 5. Christiansen J, Douglas CG, and Haldane on CO2 transport in the circulating blood. JS: The

Association of apelin and apelin receptor with the risk of coronary artery disease: a meta-analysis of observational studies

PubMed Central

Chen, Tianbao; Wu, Bing; Lin, Rong

2017-01-01

It is well established that apelin-APLNR (apelin receptor) pathway plays a central role in cardiovascular system. In this meta-analysis, we summarized published results on circulating apelin concentration in association with coronary artery disease (CAD), apelin and APLNR genetic polymorphism(s) in predisposition to CAD risk and circulating apelin changes after surgical treatment for CAD. The results from 15 articles were pooled. Two authors independently took charge of literature search, article selection and information collection. Overall, circulating apelin concentration was significantly lower in CAD patients (N=1021) than in controls (N=654) (weighted mean difference [WMD]: -1.285 ng/mL, 95% confidence interval [CI]: -1.790 to -0.780, P<0001), with significant heterogeneity (I2=99.3%) but without publication bias. For the association of APLNR gene rs9943582 polymorphism with CAD (patients/controls: 5975/4717), the mutant T allele was associated with a 5.2% increased risk relative to the wild C allele (odds ratio: 1.052, 95% CI: 0.990 to 1.117, P=0.100), without heterogeneity (I2=0.0%) or publication bias. Circulating apelin was increased significantly after surgical treatment for CAD (N=202) (WMD: 2.011 ng/mL, 95% CI: 0.541 to 3.481, P=0.007), with significant heterogeneity (I2=98.0%). Stratified analyses showed that circulating apelin was significantly reduced in studies with age- and sex-matched patients and controls (WMD: -1.881 ng/mL, 95% CI: -2.457 to -1.304, P<0.001) and with total sample size ≥125 (WMD: -1.657 ng/mL, 95% CI: -2.378 to -0.936, P<0.001), relative to studies without matching reports and with total sample size <125. In brief, our results suggested that circulating apelin was a prominent athero-protective marker against the development of CAD. PMID:28915675

Association of Circulating C1q/TNF-Related Protein 1 Levels with Coronary Artery Disease in Men

PubMed Central

Yuasa, Daisuke; Ohashi, Koji; Shibata, Rei; Takeshita, Kyosuke; Kikuchi, Ryosuke; Takahashi, Ryotaro; Kataoka, Yoshiyuki; Miyabe, Megumi; Joki, Yusuke; Kambara, Takahiro; Uemura, Yusuke; Matsuo, Kazuhiro; Hayakawa, Satoko; Hiramatsu-Ito, Mizuho; Ito, Masanori; Ikeda, Nobuo; Murohara, Toyoaki; Ouchi, Noriyuki

2014-01-01

Objective Obesity is a major risk factor for cardiovascular disease. Recent evidence demonstrates that dysregulation of fat-derived hormones, also known as adipokines, is linked with the pathogenesis of obesity-related disorders including coronary artery disease (CAD). Here, we investigated whether circulating level of an adipokine C1q/TNF-related protein (CTRP) 1 is associated with the prevalence of CAD. Methods and Results Consecutive 76 male CAD patients were enrolled from inpatients that underwent coronary angiography. Sixty four healthy male subjects served as controls. Plasma CTRP1 concentration was determined by enzyme-linked immunosorbent assay. CTRP1 levels were correlated positively with systolic blood pressure (BP) and triglyceride levels, and negatively with HDL cholesterol levels in all subjects. Plasma levels of CTRP1 were significantly higher in CAD patients than in control subjects (CAD: 443.3±18.6 ng/ml, control: 307.8±21.5 ng/ml, p<0.001). Multiple logistic regression analysis with body mass index, systolic BP, glucose, total cholesterol, HDL cholesterol, triglyceride, adiponectin and CTRP1 revealed that CTRP1 levels, together with systolic BP and HDL cholesterol, correlated with CAD. Conclusions Our data indicate the close association of high CTRP1 levels with CAD prevalence, suggesting that CTRP1 represents a novel biomarker for CAD. PMID:24945145

Circulating Myeloid‐Related Protein–8/14 is Related to Thromboxane‐Dependent Platelet Activation in Patients With Acute Coronary Syndrome, With and Without Ongoing Low‐Dose Aspirin Treatment

PubMed Central

Santilli, Francesca; Paloscia, Leonardo; Liani, Rossella; Di Nicola, Marta; Di Marco, Massimo; Lattanzio, Stefano; La Barba, Sara; Pascale, Silvia; Mascellanti, Marco; Davì, Giovanni

2014-01-01

Background Platelet activation is involved in acute coronary syndromes (ACS). Incomplete suppression by low‐dose aspirin treatment of thromboxane (TX) metabolite excretion (urinary 11‐dehydro‐TXB2) is predictive of vascular events in high‐risk patients. Myeloid‐related protein (MRP)‐8/14 is a heterodimer secreted on activation of platelets, monocytes, and neutrophils, regulating inflammation and predicting cardiovascular events. Among platelet transcripts, MRP‐14 has emerged as a powerful predictor of ACS. Methods and Results We enrolled 68 stable ischemic heart disease (IHD) and 63 ACS patients, undergoing coronary angiography, to evaluate whether MRP‐8/14 release in the circulation is related to TX‐dependent platelet activation in ACS and IHD patients and to residual TX biosynthesis in low‐dose aspirin–treated ACS patients. In ACS patients, plasma MRP‐8/14 and urinary 11‐dehydro‐TXB2 levels were linearly correlated (r=0.651, P<0.001) but significantly higher than those in IHD patients (P=0.012, P=0.044) only among subjects not receiving aspirin. In aspirin‐treated ACS patients, MRP‐8/14 and 11‐dehydro‐TXB2 were lower versus those not receiving aspirin (P<0.001) and still significantly correlated (r=0.528, P<0.001). Higher 11‐dehydro‐TXB2 significantly predicted higher MRP‐8/14 in both all ACS patients and ACS receiving aspirin (P<0.001, adj R2=0.463 and adj R2=0.497) after multivariable adjustment. Conversely, plasma MRP‐8/14 (P<0.001) and higher urinary 8‐iso‐prostaglandin F2α (P=0.050) levels were significant predictors of residual, on‐aspirin, TX biosynthesis in ACS (adjusted R2=0.384). Conclusions Circulating MRP‐8/14 is associated with TX‐dependent platelet activation in ACS, even during low‐dose aspirin treatment, suggesting a contribution of residual TX to MRP‐8/14 shedding, which may further amplify platelet activation. Circulating MRP‐8/14 may be a target to test different antiplatelet strategies in ACS. PMID:25037196

Enhanced recovery after elective coronary revascularization surgery with minimal versus conventional extracorporeal circulation: a prospective randomized study.

PubMed

Anastasiadis, Kyriakos; Asteriou, Christos; Antonitsis, Polychronis; Argiriadou, Helena; Grosomanidis, Vassilios; Kyparissa, Magdalena; Deliopoulos, Apostolos; Konstantinou, Dimitrios; Tossios, Paschalis

2013-10-01

A minimal extracorporeal circulation (MECC) circuit integrates the advances in cardiopulmonary bypass (CPB) technology into a single circuit and is associated with improved short-term outcome. The aim of this study was to prospectively evaluate MECC compared with conventional CPB in facilitating fast-track recovery after elective coronary revascularization procedures. Prospective randomized study. All patients scheduled for elective coronary artery surgery were evaluated, excluding those considered particularly high risk for fast-track failure. The fast-track protocol included careful preoperative patient selection, a fast-track anesthetic technique based on minimal administration of fentanyl, surgery at normothermia, early postoperative extubation in the cardiac recovery unit, and admission to the cardiothoracic ward within the first 24 hours postoperatively. One hundred twenty patients were assigned randomly into 2 groups (60 in each group). Group A included patients who were operated on using the MECC circuit, whereas patients in Group B underwent surgery on conventional CPB. Incidence of fast-track recovery was significantly higher in patients undergoing MECC (25% v 6.7%, p = 0.006). MECC also was recognized as a strong independent predictor of early recovery, with an odds ratio of 3.8 (p = 0.011). Duration of mechanical ventilation and cardiac recovery unit stay were significantly lower in patients undergoing MECC together with the need for blood transfusion, duration of inotropic support, need for an intra-aortic balloon pump, and development of postoperative atrial fibrillation and renal failure. MECC promotes successful early recovery after elective coronary revascularization procedures, even in a nondedicated cardiac intensive care unit setting. Copyright © 2013 Elsevier Inc. All rights reserved.

The Value of Big Endothelin-1 in the Assessment of the Severity of Coronary Artery Calcification.

PubMed

Wang, Fang; Li, Tiewei; Cong, Xiangfeng; Hou, Zhihui; Lu, Bin; Zhou, Zhou; Chen, Xi

2018-01-01

Progression of coronary artery calcification (CAC) was significantly associated with all-cause mortality, and high coronary artery calcium score (CACS) portends a particularly high risk of cardiovascular events. But how often one should rescan is still an unanswered question. Preliminary screening by testing circulating biomarker may be an alternative before repeat computed tomography (CT) scan. The aim of this study was to investigate the value of big endothelin-1 (bigET-1), the precursor of endothelin-1 (ET-1), in predicting the severity of CAC. A total of 428 consecutively patients who performed coronary computed tomography angiography (CCTA) due to chest pain in Fuwai Hospital were included in the study. The clinical characteristics, CACS, and laboratory data were collected, and plasma bigET-1 was detected by enzyme-linked immunosorbent assay (ELISA). The bigET-1 was positively correlated with the CACS ( r = .232, P < .001), and the prevalence of CACS >400 increased significantly in the highest bigET-1 tertile than the lowest tertile. Multivariate analysis showed that bigET-1was the independent predictor of the presence of CACS >400 (odds ratio [OR] = 1.721, 95% confidence interval [CI], 1.002-2.956, P = .049). The receiver operating characteristic (ROC) curve analysis showed that the optimal cutoff value of bigET-1 for predicting CACS >400 was 0.38 pmol/L, with a sensitivity of 59% and specificity of 68% (area under curve [AUC] = 0.65, 95% CI, 0.58-0.72, P < .001). The present study demonstrated that the circulating bigET-1 was valuable in the assessment of the severity of CAC.

Association of various blood pressure variables and vascular phenotypes with coronary, stroke and renal deaths: Potential implications for prevention.

PubMed

Harbaoui, Brahim; Courand, Pierre-Yves; Milon, Hughes; Fauvel, Jean-Pierre; Khettab, Fouad; Mechtouff, Laura; Cassar, Emmanuel; Girerd, Nicolas; Lantelme, Pierre

2015-11-01

The relationship between blood pressure (BP) and cardiovascular diseases has been extensively documented. However, the benefit of anti-hypertensive drugs differs according to the type of cardiovascular event. Aortic stiffness is tightly intertwined with BP and aorta cross-talk with small arteries. We endeavored to elucidate which BP component and type of vessel remodeling was predictive of the following outcomes: fatal myocardial infarction (MI), fatal stroke, renal -, coronary- or cerebrovascular-related deaths. Large vessel remodeling was estimated by an aortography-based aortic atherosclerosis score (ATS) while small vessel disease was documented by the presence of a hypertensive retinopathy. We included 1031 subjects referred for hypertension workup and assessed outcomes 30 years later. After adjustment for major risk factors, ATS and pulse pressure (PP) were predictive of coronary events while mean BP (MBP) and retinopathy were not. On the contrary, MBP was predictive of cerebrovascular and renal related deaths while ATS and PP were not. Retinopathy was only predictive of cerebrovascular related deaths. Lastly, the aortic atherosclerosis phenotype and increased PP identified patients prone to develop fatal MI whereas the retinopathy phenotype and increased MBP identified patients at higher risk of fatal stroke. These results illustrate the particular feature of the resistive coronary circulation comparatively to the brain and kidneys' low-resistance circulation. Our results advocate for a rational preventive strategy based on the identification of distinct clinical phenotypes. Accordingly, decreasing MBP levels could help preventing stroke in retinopathy phenotypes whereas targeting PP is possibly more efficient in preventing MI in atherosclerotic phenotypes. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Fruits and vegetables get a golden halo once again: Is there more to the story?

USDA-ARS?s Scientific Manuscript database

For decades, the data have been relatively consistent; individuals who report eating more fruits and vegetables have lower rates of cardiovascular disease, stroke, cancer, diabetes, heart failure, and all-cause mortality. In this issue of Circulation, from the Coronary Artery Risk Development in You...

Survival after heart and coronary-artery penetration by an air-rifle projectile.

PubMed

Doetsch, N; Wolfhard, U; Mathers, M J; Zerkowski, H R

1989-10-01

Gunshot injuries of the heart are extremely rare thoracic traumas in Europe during peacetime. Concomitant lesions of the coronary arteries occur in less than 5%. This case reports on a 26-year-old man who was shot with an air rifle at short range. On admission the patient showed signs of pericardial tamponade. Emergency thoracotomy was performed and a frontal cardiac lesion was found in the distal third of the anterior descending branch of the left coronary artery. The bullet crossed the cavum of the left ventricle and remained in the posterior wall in the subepicardial layer adjacent to the posterior descending coronary branch. Under the conditions of extracorporeal circulation we removed the bullet, repaired both ventricle walls using patches in sandwich technique, and bypassed the coronary lesion by single aortocoronary venous graft. No signs of myocardial infarction could be detected by ECG. The follow-up after 3 years shows no cardiac problems and normal stress tolerance. This case report proves that even air rifle shots, which in general are considered to be harmless, may result in life-threatening injuries. For the severity of the injury are decisive the kinetic energy at the muzzle as well as configuration and type of the bullet.

Impaired circulating CD4+ LAP+ regulatory T cells in patients with acute coronary syndrome and its mechanistic study.

PubMed

Zhu, Zheng-Feng; Meng, Kai; Zhong, Yu-Cheng; Qi, Liang; Mao, Xiao-Bo; Yu, Kun-Wu; Zhang, Wei; Zhu, Peng-Fei; Ren, Ze-Peng; Wu, Bang-Wei; Ji, Qin-Wei; Wang, Xiang; Zeng, Qiu-Tang

2014-01-01

CD4(+) latency-associated peptide (LAP)(+) regulatory T cells (Tregs) are a newly discovered T cell subset in humans and the role of these cells in patients with acute coronary syndrome (ACS) has not been explored. We designed to investigate whether circulating frequency and function of CD4(+)LAP(+) Tregs are defective in ACS. One hundred eleven ACS patients (acute myocardial infarction and unstable angina) and 117 control patients were enrolled in the study. The control patients consisted of chronic stable angina (CSA) and chest pain syndrome (CPS). The frequencies of circulating CD4(+)LAP(+) Tregs and the expression of the transmembrane protein glycoprotein-A repetitions predominant (GARP) on CD4(+) T cells were determined by flow cytometry. The function of CD4(+)LAP(+) Tregs was detected using thymidine uptake. Serum interleukin-10 (IL-10) and transforming growth factor-β protein (TGF-β) levels were detected using ELISA and expression of GARP mRNA in peripheral blood mononuclear cells (PBMCs) was measured by real time-polymerase chain reaction. We found ACS patients had a significantly lower frequency of circulating CD4(+)LAP(+) Tregs, and the function of these cells was reduced compared to controls. The expression of GARP in CD4(+) T cells and the serum levels of TGF-β in ACS patients were lower than those of control patients. The serum levels of IL-10 were similar between the two cohorts. A novel regulatory T cell subset, defined as CD4(+)LAP(+) T cells is defective in ACS patients.

Mechanisms underlying capsaicin effects in canine coronary artery: implications for coronary spasm

PubMed Central

Hiett, S. Christopher; Owen, Meredith K.; Li, Wennan; Chen, Xingjuan; Riley, Ashley; Noblet, Jillian; Flores, Sarah; Sturek, Michael; Tune, Johnathan D.; Obukhov, Alexander G.

2014-01-01

Aims The TRPV1, transient receptor potential vanilloid type 1, agonist capsaicin is considered to be beneficial for cardiovascular health because it dilates coronary arteries through an endothelial-dependent mechanism and may slow atheroma progression. However, recent reports indicate that high doses of capsaicin may constrict coronary arterioles and even provoke myocardial infarction. Thus far, the mechanisms by which TRPV1 activation modulates coronary vascular tone remain poorly understood. This investigation examined whether there is a synergistic interplay between locally acting vasoconstrictive pro-inflammatory hormones (autacoids) and capsaicin effects in the coronary circulation. Methods and results Experiments were performed in canine conduit coronary artery rings and isolated smooth muscle cells (CASMCs). Isometric tension measurements revealed that 1–10 μM capsaicin alone did not affect resting tension of coronary artery rings. In contrast, in endothelium-intact rings pre-contracted with a Gq/11-coupled FP/TP (prostaglandin F/thromboxane) receptor agonist, prostaglandin F2α (PGF2α; 10 μM), capsaicin first induced transient dilation that was followed by sustained contraction. In endothelium-denuded rings pre-contracted with PGF2α or thromboxane analogue U46619 (1 μM, a TP receptor agonist), capsaicin induced only sustained contraction. Blockers of the TP receptor or TRPV1 significantly inhibited capsaicin effects, but these were still observed in the presence of 50 μM nifedipine and 70 mM KCl. Capsaicin also potentiated 20 mM KCl-induced contractions. Fluorescence imaging experiments in CASMCs revealed that the Gq/11-phospholipase C (PLC)-protein kinase C (PKC) and Ca2+-PLC-PKC pathways are likely involved in sensitizing CASMC TRPV1 channels. Conclusion Capsaicin alone does not cause contractions in conduit canine coronary artery; however, pre-treatment with pro-inflammatory prostaglandin–thromboxane agonists may unmask capsaicin's vasoconstrictive potential. PMID:24935430

Coronary Serum Obtained After Myocardial Infarction Induces Angiogenesis and Microvascular Obstruction Repair. Role of Hypoxia-inducible Factor-1A.

PubMed

Ríos-Navarro, César; Hueso, Luisa; Miñana, Gema; Núñez, Julio; Ruiz-Saurí, Amparo; Sanz, María Jesús; Cànoves, Joaquin; Chorro, Francisco J; Piqueras, Laura; Bodí, Vicente

2018-06-01

Microvascular obstruction (MVO) exerts deleterious effects following acute myocardial infarction (AMI). We investigated coronary angiogenesis induced by coronary serum and the role of hypoxia-inducible factor-1A (HIF-1A) in MVO repair. Myocardial infarction was induced in swine by transitory 90-minute coronary occlusion. The pigs were divided into a control group and 4 AMI groups: no reperfusion, 1minute, 1 week and 1 month after reperfusion. Microvascular obstruction and microvessel density were quantified. The proangiogenic effect of coronary serum drawn from coronary sinus on endothelial cells was evaluated using an in vitro tubulogenesis assay. Circulating and myocardial HIF-1A levels and the effect of in vitro blockade of HIF-1A was assessed. Compared with control myocardium, microvessel density decreased at 90-minute ischemia, and MVO first occurred at 1minute after reperfusion. Both peaked at 1 week and almost completely resolved at 1 month. Coronary serum exerted a neoangiogenic effect on coronary endothelial cells in vitro, peaking at ischemia and 1minute postreperfusion (32 ± 4 and 41 ± 9 tubes vs control: 3 ± 3 tubes; P < .01). Hypoxia-inducible factor-1A increased in serum during ischemia (5-minute ischemia: 273 ± 52 pg/mL vs control: 148 ± 48 pg/mL; P < .01) being present on microvessels of all AMI groups (no reperfusion: 67% ± 5% vs control: 15% ± 17%; P < .01). In vitro blockade of HIF-1A reduced the angiogenic response induced by serum. Coronary serum represents a potent neoangiogenic stimulus even before reperfusion; HIF-1A might be crucial. Coronary neoangiogenesis induced by coronary serum can contribute to understanding the pathophysiology of AMI. Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Regression of left ventricular hypertrophy provides an additive physiological benefit following treatment of aortic stenosis: insights from serial coronary wave-intensity analysis.

PubMed

Broyd, Christopher J; Rigo, Fausto; Nijjer, Sukhjinder; Sen, Sayan; Petraco, Ricardo; Al-Lamee, Rasha; Foin, Nicolas; Chukwuemeka, Andrew; Anderson, Jon; Parker, Jessica; Malik, Iqbal S; Mikhail, Ghada W; Francis, Darrel P; Parker, Kim; Hughes, Alun D; Mayet, Jamil; Davies, Justin E

2018-06-23

Severe aortic stenosis frequently involves the development of left ventricular hypertrophy (LVH) creating a dichotomous hemodynamic state within the coronary circulation. Whilst the increased force of ventricular contraction enhances its resultant relaxation and thus increases the distal diastolic coronary 'suction' force, the presence of LVH has a potentially opposing effect on ventricular-coronary interplay. The aim of this study was to use non-invasive coronary wave-intensity analysis (WIA) to separate and measure the sequential effects of outflow-tract obstruction relief and then left ventricular hypertrophy (LVH) regression following intervention for aortic stenosis. 15 patients with unobstructed coronary arteries undergoing aortic valve intervention (11 SAVR, 4 TAVI) were successfully assessed before and after intervention, and at 6- and 12-months post-procedure. Coronary WIA was constructed from simultaneously acquired coronary flow from transthoracic echo and pressure from an oscillometric brachial-cuff system. Immediately following intervention, a decline in the BDW was noted (9.7±5.7 vs 5.1±3.6 x10 3 Wm -2 s -1 , p<0.01). Over 12 months, LV mass-index fell from 114±19 to 82±17 kg/m 2 . Accompanying this, the BDW fraction increased to 32.8±7.2% (p=0.01 vs post-procedure) and to 34.7±6.7% at 12 months (p<0.001 vs post-procedure). In aortic stenosis, both the outflow-tract gradient and the presence of LVH impact significantly on coronary haemodynamics that cannot be appreciated by examining resting coronary flow rates alone. An immediate change in coronary wave-intensity occurs following intervention with further effects appreciable with hypertrophy regression. The improvement in prognosis with treatment is likely to be attributable to both features. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

In vitro evaluation of the effect of aortic compliance on pediatric intra-aortic balloon pumping.

PubMed

Minich, L L; Tani, L Y; Hawkins, J A; Bartkowiak, R R; Royall, M L; Pantalos, G M

2001-04-01

OBJECTIVES: To evaluate the effect of aortic compliance on pediatric intra-aortic balloon pumping (IABP). DESIGN: In vitro study using a mechanical model of the pediatric left heart circulation. SETTING: Cardiovascular fluid dynamics research laboratory. SUBJECT: Pulsatile flow system simulating the pediatric left heart circulation and two different aortas with compliances comparable to those of the pediatric aorta (0.12 and 0.07 mL/mm Hg). INTERVENTIONS: Measurements were made at a baseline peak aortic flow of 4 L/min, at simulated shock (1.7 L/min), and with 1:1 IABP (rates, 130 and 150 bpm; balloon volumes, 2.5 and 5.0 mL). MEASUREMENTS AND MAIN RESULTS: Peak flow rates were measured in the ascending aorta, coronary arterial system, and brachiocephalic arterial systems. Aortic pressure was measured in the ascending aorta. For both aortas (0.12 and 0.07 mL/mm Hg), IABP resulted in diastolic augmentation (38 +/- 8 and 43 +/- 16 mm Hg) and afterload reduction (4 +/- 2 and 6 +/- 3 mm Hg). For both aortas, compared to shock, IABP resulted in significant increases in coronary arterial and brachiocephalic arterial flow and aortic pressure for both aortas. Aortic flow significantly increased only in the less-compliant aorta. CONCLUSIONS: In a laboratory model of pediatric left heart circulation, IABP results in diastolic augmentation, afterload reduction, and improved hemodynamics, even in aortas of greater compliance.

APOC3 -482C>T polymorphism, circulating apolipoprotein C-III and smoking: interrelation and roles in predicting type-2 diabetes and coronary disease.

PubMed

Onat, Altan; Erginel-Unaltuna, Nihan; Coban, Neslihan; Ciçek, Gökhan; Yüksel, Hüsniye

2011-04-01

We determined the relationship of smoking status on APOC3 -482C>T polymorphism and apolipoprotein C-III (apoC-III) concentrations and the latter two parameters' influence on risk of diabetes and coronary heart disease (CHD). Prediction of incident cases was assessed at 5.5years' follow-up in unselected 519 individuals of a general population genotyped for -482C>T polymorphism. Female sex and current smoking were significantly associated with low circulating apoC-III in subjects without (p≤0.033) than with abdominal obesity (p=0.053) or than insulin resistant -482TT homozygotes (p=0.034) who had 20-30% higher serum apoC-III. Multi-adjusted serum apoC-III was log-linearly associated with fasting triglycerides. ApoC-III levels determined the development of diabetes [RR 1.56 (95%CI 1.21; 2.01)] and CHD [RR 1.38 (1.10; 1.72) for an increment of 14%], after adjustment for confounders. APOC3 -482TT genotype is associated with high apoC-III concentrations only in the presence of abdominal obesity or insulin resistance, but not in current smokers who remain lean or insulin-sensitive. Rather than APOC3 -482C>T polymorphism, circulating apoC-III determines cardiometabolic risk. Copyright © 2011 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Trans fatty acids and cholesterol levels: an evidence map of the available science

USDA-ARS?s Scientific Manuscript database

High intakes of industrial trans fatty acids (iTFA) increase circulating low density lipoprotein cholesterol (LDL-C) levels, which has implicated iTFA in coronary heart disease (CHD) risk. Published data on iTFA and LDL-C, however, represent higher intake levels than the U.S. population currently co...

Mini-extracorporeal circulation minimizes coagulation abnormalities and ameliorates pulmonary outcome in coronary artery bypass grafting surgery.

PubMed

Zeitani, J; Buccisano, F; Nardella, S; Flaminio, M; Prati, P; Chiariello, G; Venditti, A; Chiariello, L

2013-07-01

Hemostasis is impaired during CABG and coagulation abnormalities often result in clinically relevant organ dysfunctions, eventually increasing morbidity and mortality rates. Fifteen consecutive patients with coronary artery disease submitted to conventional extracorporeal circulation (cECC) have been compared with 15 matched patients, using mini-ECC (MECC). Postoperative lung function was evaluated according to gas exchange, intubation time and lung injury score. In the MECC group, thrombin-antithrombin complex levels (TaTc), prothrombin fragments (PF1+2) formation and thromboelastography (TEG) clotting times were lower compared to the cECC group (p=0.002 and p<0.001, respectively) whereas postoperative blood loss was higher in the cECC group (p=0.030) and more patients required blood transfusion (p=0.020). In the MECC group, postoperative gas exchange values were better, intubation time shorter and lung injury score lower (p<0.001 for all comparisons). Our study suggests that MECC induces less coagulation disorders, leading to lower postoperative blood loss and better postoperative lung function. This approach may be advantageous in high-risk patients.

Pharmacological actions and therapeutic applications of Salvia miltiorrhiza depside salt and its active components.

PubMed

Wu, Wen-yu; Wang, Yi-ping

2012-09-01

Salvia miltiorrhiza, a traditional medical herb known as danshen, has been widely used in China to improve blood circulation, relieve blood stasis, and treat coronary heart disease. S miltiorrhiza depside salt is a novel drug recently developed at the Shanghai Institute of Materia Medica; it contains magnesium lithospermate B (MLB) and its analogs, rosmarinic acid (RA) and lithospermic acid (LA), as active components. The drug has been used in the clinic to improve blood circulation and treat coronary heart disease. The pharmacological effects of the depside salt from S miltiorrhiza and its components have been extensively investigated. Experimental studies have demonstrated that magnesium lithospermate B possesses a variety of biological activities, especially protective effects in the cardiovascular system such as attenuation of atherosclerosis and protection against myocardial ischemia-reperfusion injury. Rosmarinic acid and lithospermic acid also show beneficial effects on the cardiovascular system. This paper reviews the recent findings regarding the mechanisms underlying the pharmacological actions of the active components of S miltiorrhiza depside salt, based on published works and our own observations.

Non-obstructive prosthetic aortic valve thrombosis presenting with acute myocardial infarction and stroke in a patient with inadequate low-molecular-weight heparin treatment. The unlucky patient and the (pseudo)prudent physician.

PubMed

Paci, Anna Maria; Lattanzi, Fabio; Cabani, Enrico; Conti, Umberto; De Tommasi, Salvatore Mario

2007-04-01

Non-obstructive prosthetic valve thrombosis is a rare and underestimated complication in patients with left-sided mechanical heart valves. Systemic embolisation, mainly involving the cerebral circulation, often represents the first clinical manifestation. We report a case of multiple, successive embolizations in the coronary and cerebral circulation, presenting with an acute myocardial infarction and stroke in a patient with latent, non-obstructive thrombosis of a mechanical bileaflet aortic valve. Because of scheduled urological surgery, chronic vitamin K antagonist treatment had previously been discontinued and replaced with low-molecular-weight heparin, at inadequate dosage. Following coronary arteriography, brain computed tomography scan and transoesophageal echocardiography, thrombolysis was performed successfully. This case emphasises the utility of performing transoesophageal echocardiography routinely in the presence of ischaemic signs in patients with mechanical heart valves. In patients requiring discontinuation of oral anticoagulant therapy, accurate management and continuous monitoring of alternative medications are needed in order to avoid severe thromboembolic complications.

Hyperhomocysteinemia impairs regional blood flow: involvements of endothelial and neuronal nitric oxide.

PubMed

Toda, Noboru; Okamura, Tomio

2016-09-01

Increasing evidence support the idea that hyperhomocysteinemia (HHcy) is responsible for pathogenesis underlying cerebral, coronary, renal, and other vascular circulatory disorders and for hypertension. Impaired synthesis of nitric oxide (NO) in the endothelium or increased production of asymmetric dimethylarginine and activated oxygen species are involved in the impairment of vasodilator effects of NO. Impaired circulation in the brain derived from reduced synthesis and actions of NO would be an important triggering factor to dementia and Alzheimer's disease. Reduced actions of NO and brain hypoperfusion trigger increased production of amyloid-β that inhibits endothelial function, thus establishing a vicious cycle for impairing brain circulation. HHcy is involved in the genesis of anginal attack and coronary myocardial infarction. HHcy is also involved in renal circulatory diseases. The homocysteine (Hcy)-induced circulatory failure is promoted by methionine and is prevented by increased folic acid and vitamin B6/B12. Eliminating poor life styles, such as smoking and being sedentary; keeping favorable dietary habits; and early treatment maintaining constitutive NOS functions healthy, reducing oxidative stresses would be beneficial in protecting HHcy-induced circulatory failures.

[Stem cell mobilization after coronary artery bypass grafting].

PubMed

Gaspardone, Achille; De Fabritiis, Paolo; Scaffa, Raffaele; Nardi, Paolo; Palombi, Francesca; Versaci, Francesco; Chiariello, Luigi

2004-01-01

Recently, the role of stem cells as a potential therapeutic tool for ischemic heart disease has been evaluated by a number of experimental and clinical studies. Although preliminary clinical data appear to be promising, the precise pathophysiological role of stem cell mobilization during acute myocardial ischemia remains uncertain. The present study was aimed at assessing factors affecting stem cell mobilization after coronary artery bypass grafting used as a clinical model of controlled myocardial ischemia. Eighteen patients (16 men, 2 women, mean age 66 +/- 8 years) with three-vessel coronary artery disease undergoing coronary artery bypass grafting were included in the study; 24 age- and sex-matched healthy subjects served as controls. On admission, 10 patients had stable angina and 8 had unstable angina. Clinical history and instrumental evidence of previous myocardial infarction were present in 11 patients. Venous peripheral blood was sampled at baseline and 6, 24, 48 and 72 hours after coronary surgery. Duration of cardiac arrest and extracorporeal circulation were recorded as well as the release of total creatine kinase (CK), CK-MB, troponin I and C-reactive protein. CD34+ stem cells were analyzed by flow cytometry according to published methods. In patients with ischemic heart disease the peripheral concentration of CD34+ cells was higher than that of control subjects (0.202 +/- 0.30 vs 0.068 +/- 0.059%, p = 0.03). However, patients with stable and unstable angina had similar concentration of CD34+ cells (0.171 +/- 0.33 vs 0.241 +/- 0.275%, p = 0.63) as well as patients with and without previous myocardial infarction (0.134 +/- 0.19 vs 0.245 +/- 0.352%, p = 0.4). Coronary artery bypass grafting caused a non-significant increase in concentration of CD34+ cells at 24 hours which was similar in patients with stable and unstable angina. Finally, no significant correlation was found between peripheral concentration of CD34+ cells and aortic clamping and extracorporeal circulation duration, peak release of total CK, CK-MB, troponin I and C-reactive protein. Peripheral concentration of CD34+ stem cells is higher in patients with ischemic heart disease than in healthy controls but it is similar in patients with stable and unstable coronary syndromes. Peripheral mobilization of CD34+ cells is not correlated with the duration and severity of ischemic insult induced by surgical cardiac arrest. These preliminary findings suggest that CD34+ cell mobilization may be modulated more by tonically active than phasic factors.

Cyclosporine before Coronary Artery Bypass Grafting Does Not Prevent Postoperative Decreases in Renal Function: A Randomized Clinical Trial.

PubMed

Ederoth, Per; Dardashti, Alain; Grins, Edgars; Brondén, Björn; Metzsch, Carsten; Erdling, André; Nozohoor, Shahab; Mokhtari, Arash; Hansson, Magnus J; Elmér, Eskil; Algotsson, Lars; Jovinge, Stefan; Bjursten, Henrik

2018-04-01

Acute kidney injury is a common complication after cardiac surgery, leading to increased morbidity and mortality. One suggested cause for acute kidney injury is extracorporeal circulation-induced ischemia-reperfusion injury. In animal studies, cyclosporine has been shown to reduce ischemia-reperfusion injury in the kidneys. We hypothesized that administering cyclosporine before extracorporeal circulation could protect the kidneys in patients undergoing cardiac surgery. The Cyclosporine to Protect Renal Function in Cardiac Surgery (CiPRICS) study was an investigator-initiated, double-blind, randomized, placebo-controlled, single-center study. The primary objective was to assess if cyclosporine could reduce acute kidney injury in patients undergoing coronary artery bypass grafting surgery with extracorporeal circulation. In the study, 154 patients with an estimated glomerular filtration rate of 15 to 90 ml · min · 1.73 m were enrolled. Study patients were randomized to receive 2.5 mg/kg cyclosporine or placebo intravenously before surgery. The primary endpoint was relative plasma cystatin C changes from the preoperative day to postoperative day 3. Secondary endpoints included biomarkers of kidney, heart, and brain injury. All enrolled patients were analyzed. The cyclosporine group (136.4 ± 35.6%) showed a more pronounced increase from baseline plasma cystatin C to day 3 compared to placebo (115.9 ± 30.8%), difference, 20.6% (95% CI, 10.2 to 31.2%, P < 0.001). The same pattern was observed for the other renal markers. The cyclosporine group had more patients in Risk Injury Failure Loss End-stage (RIFLE) groups R (risk), I (injury), or F (failure; 31% vs. 8%, P < 0.001). There were no differences in safety parameter distribution between groups. Administration of cyclosporine did not protect coronary artery bypass grafting patients from acute kidney injury. Instead, cyclosporine caused a decrease in renal function compared to placebo that resolved after 1 month.

Circulating CD34+ progenitor cells and risk of mortality in a population with coronary artery disease.

PubMed

Patel, Riyaz S; Li, Qunna; Ghasemzadeh, Nima; Eapen, Danny J; Moss, Lauren D; Janjua, A Umair; Manocha, Pankaj; Kassem, Hatem Al; Veledar, Emir; Samady, Habib; Taylor, W Robert; Zafari, A Maziar; Sperling, Laurence; Vaccarino, Viola; Waller, Edmund K; Quyyumi, Arshed A

2015-01-16

Low circulating progenitor cell numbers and activity may reflect impaired intrinsic regenerative/reparative potential, but it remains uncertain whether this translates into a worse prognosis. To investigate whether low numbers of progenitor cells associate with a greater risk of mortality in a population at high cardiovascular risk. Patients undergoing coronary angiography were recruited into 2 cohorts (1, n=502 and 2, n=403) over separate time periods. Progenitor cells were enumerated by flow cytometry as CD45(med+) blood mononuclear cells expressing CD34, with additional quantification of subsets coexpressing CD133, vascular endothelial growth factor receptor 2, and chemokine (C-X-C motif) receptor 4. Coefficient of variation for CD34 cells was 2.9% and 4.8%, 21.6% and 6.5% for the respective subsets. Each cohort was followed for a mean of 2.7 and 1.2 years, respectively, for the primary end point of all-cause death. There was an inverse association between CD34(+) and CD34(+)/CD133(+) cell counts and risk of death in cohort 1 (β=-0.92, P=0.043 and β=-1.64, P=0.019, respectively) that was confirmed in cohort 2 (β=-1.25, P=0.020 and β=-1.81, P=0.015, respectively). Covariate-adjusted hazard ratios in the pooled cohort (n=905) were 3.54 (1.67-7.50) and 2.46 (1.18-5.13), respectively. CD34(+)/CD133(+) cell counts improved risk prediction metrics beyond standard risk factors. Reduced circulating progenitor cell counts, identified primarily as CD34(+) mononuclear cells or its subset expressing CD133, are associated with risk of death in individuals with coronary artery disease, suggesting that impaired endogenous regenerative capacity is associated with increased mortality. These findings have implications for biological understanding, risk prediction, and cell selection for cell-based therapies. © 2014 American Heart Association, Inc.

Cohort profile of BIOMArCS: the BIOMarker study to identify the Acute risk of a Coronary Syndrome-a prospective multicentre biomarker study conducted in the Netherlands.

PubMed

Oemrawsingh, Rohit M; Akkerhuis, K Martijn; Umans, Victor A; Kietselaer, Bas; Schotborgh, Carl; Ronner, Eelko; Lenderink, Timo; Liem, Anho; Haitsma, David; van der Harst, Pim; Asselbergs, Folkert W; Maas, Arthur; Oude Ophuis, Anton J; Ilmer, Ben; Dijkgraaf, Rene; de Winter, Robbert-Jan; The, S Hong Kie; Wardeh, Alexander J; Hermans, Walter; Cramer, Etienne; van Schaik, Ron H; Hoefer, Imo E; Doevendans, Pieter A; Simoons, Maarten L; Boersma, Eric

2016-12-23

Progression of stable coronary artery disease (CAD) towards acute coronary syndrome (ACS) is a dynamic and heterogeneous process with many intertwined constituents, in which a plaque destabilising sequence could lead to ACS within short time frames. Current CAD risk assessment models, however, are not designed to identify increased vulnerability for the occurrence of coronary events within a precise, short time frame at the individual patient level. The BIOMarker study to identify the Acute risk of a Coronary Syndrome (BIOMArCS) was designed to evaluate whether repeated measurements of multiple biomarkers can predict such 'vulnerable periods'. BIOMArCS is a multicentre, prospective, observational study of 844 patients presenting with ACS, either with or without ST-elevation and at least one additional cardiovascular risk factor. We hypothesised that patterns of circulating biomarkers that reflect the various pathophysiological components of CAD, such as distorted lipid metabolism, vascular inflammation, endothelial dysfunction, increased thrombogenicity and ischaemia, diverge in the days to weeks before a coronary event. Divergent biomarker patterns, identified by serial biomarker measurements during 1-year follow-up might then indicate 'vulnerable periods' during which patients with CAD are at high short-term risk of developing an ACS. Venepuncture was performed every fortnight during the first half-year and monthly thereafter. As prespecified, patient enrolment was terminated after the primary end point of cardiovascular death or hospital admission for non-fatal ACS had occurred in 50 patients. A case-cohort design will explore differences in temporal patterns of circulating biomarkers prior to the repeat ACS. Follow-up and event adjudication have been completed. Prespecified biomarker analyses are currently being performed and dissemination through peer-reviewed publications and conference presentations is expected from the third quarter of 2016. Should identification of a 'vulnerable period' prove to be feasible, then future research could focus on event reduction through pharmacological or mechanical intervention during such periods of high risk for ACS. NTR1698 and NTR1106. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Is everything clear about Tako-tsubo syndrome?

PubMed

Petrov, Ivo S; Tokmakova, Mariya P; Marchov, Daniel N; Kichukov, Kostadin N

2011-01-01

Tako-tsubo syndrome is a novel cardio-vascular disease affecting predominantly postmenopausal women exposed to unexpected strong emotional or physical stress, in the absence of significant coronary heart disease. It is characterized by acute onset of severe chest pain and/or acute left ventricular failure, ECG-changes, typical left ventricular angiographic findings, good prognosis and positive resolution of the morphological and clinical manifestations. First described in 1990 in Japan by Sato, Tako-tsubo cardiomyopathy is characterized by transient contractile abnormalities of the left ventricle, causing typical left ventricular apical ballooning at end-systole with concomitant compensatory basal hyperkinesia. There are also atypical forms, presenting with left ventricular systolic dysfunction which affects the mid-portions of the left ventricle. The etiology of the disease still remains unclear. Many theories have been put forward about the potential underlying pathophysiological mechanisms that may trigger this syndrome among which are the theory of catecholamine excess, the theory of multivessel coronary vasospasm, the ischemic theory, and the theory of microvascular dysfunction and dynamic left ventricular gradient induced by elevated circulating catecholamine levels. Adequate management of Tako-tsubo syndrome demands immediate preparation for coronary angiography. Once the diagnosis is made, treatment is primarily symptomatic and includes monitoring for complications. Patients with Tako-tsubo syndrome most frequently develop acute LV failure, pulmonary edema, rhythm and conductive disturbances and apical thrombosis. Treatment is symptomatic and includes administration of diuretics, vasodilators and mechanical support of circulation with intra-aortic balloon counterpulsation.

Triglyceride level affecting shared susceptibility genes in metabolic syndrome and coronary artery disease.

PubMed

Kisfali, P; Polgár, N; Sáfrány, E; Sümegi, K; Melegh, B I; Bene, J; Wéber, A; Hetyésy, K; Melegh, B

2010-01-01

Metabolic syndrome is characterized primarily by abdominal obesity, high triglyceride- and low HDL cholesterol levels, elevated blood pressure, and increased fasting glucose levels, which are often associated with coronary heart diseases. Several factors, such as physical inactivity, age, and several endocrine and genetic factors can increase the risk of the development of the disease. Gathered evidence shows, that metabolic syndrome is not only a risk factor for cardiovascular disease, but often both of them have the same shared susceptibility genes, as several genetic variants have shown a predisposition to both diseases. Due to the spread of robust genome wide association studies, the number of candidate genes in metabolic syndrome and coronary heart disease susceptibility increases very rapidly. From the growing spectrum of the genes influencing lipid metabolism (like the LPL; PPARA; APOE; APOAI/CIII/AIV genecluster and APOAS5), the current review focuses on shared susceptibility variants involved in triglyceride metabolism and consequently the effects on the circulating triglyceride levels. As the elevated levels of triglycerides can be associated with disease phenotypes, some of these SNPs can have susceptibility features in both metabolic syndrome and in coronary heart disease, thereby some of them can even represent a kind of susceptibility link between metabolic syndrome and coronary artery disease.

Lowering Interleukin-12 Activity Improves Myocardial and Vascular Function Compared With Tumor Necrosis Factor-a Antagonism or Cyclosporine in Psoriasis.

PubMed

Ikonomidis, Ignatios; Papadavid, Evangelia; Makavos, George; Andreadou, Ioanna; Varoudi, Maria; Gravanis, Kostas; Theodoropoulos, Kostas; Pavlidis, George; Triantafyllidi, Helen; Moutsatsou, Paraskevi; Panagiotou, Christina; Parissis, John; Iliodromitis, Efstathios; Lekakis, John; Rigopoulos, Dimitrios

2017-09-01

Interleukin (IL)-12 activity is involved in the pathogenesis of psoriasis and acute coronary syndromes. We investigated the effects of IL-12 inhibition on vascular and left ventricular (LV) function in psoriasis. One hundred fifty psoriasis patients were randomized to receive an anti-IL-12/23 (ustekinumab, n=50), anti-tumor necrosis factor-a (TNF-α; etanercept, n=50), or cyclosporine treatment (n=50). At baseline and 4 months post-treatment, we measured (1) LV global longitudinal strain, twisting, and percent difference between peak twisting and untwisting at mitral valve opening (%untwMVO) using speckle-tracking echocardiography, (2) coronary flow reserve, (3) pulse wave velocity and augmentation index, (4) circulating NT-proBNP (N-terminal pro-B-type natriuretic peptide), TNF-α, IL-6, IL-12, IL-17, malondialdehyde, and fetuin-a. Compared with baseline, all patients had improved global longitudinal strain (median values: -17.7% versus -19.5%), LV twisting (12.4° versus 14°), %untwMVO (27.8% versus 35%), and coronary flow reserve (2.8 versus 3.1) and reduced circulating NT-proBNP, IL-17, TNF-α, and IL-6 post-treatment ( P <0.05). Compared with anti-TNF-α and cyclosporine, anti-IL-12/23 treatment resulted in a greater improvement of global longitudinal strain (25% versus 17% versus 6%,), LV twist (27% versus 17% versus 1%), %untwMVO (31% versus 27% versus 17%), and coronary flow reserve (14% versus 11% versus 4%), as well as a greater reduction of IL-12 (-25% versus -4% versus -2%), malondialdehyde (-27% versus +5% versus +26%), and NT-proBNP(-26% versus -13.6% versus 9.1%) and increase of fetuin-a ( P <0.01). Pulse wave velocity and augmentation index were improved only after anti-IL-12/23 treatment and correlated with changes in global longitudinal strain, LV twisting-untwisting ( P <0.05). In psoriasis, IL-12/23 inhibition results in a greater improvement of coronary, arterial, and myocardial function than TNF-α inhibition or cyclosporine treatment. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02144857. © 2017 American Heart Association, Inc.

Coronary Artery-Bypass-Graft Surgery Increases the Plasma Concentration of Exosomes Carrying a Cargo of Cardiac MicroRNAs: An Example of Exosome Trafficking Out of the Human Heart with Potential for Cardiac Biomarker Discovery.

PubMed

Emanueli, Costanza; Shearn, Andrew I U; Laftah, Abas; Fiorentino, Francesca; Reeves, Barnaby C; Beltrami, Cristina; Mumford, Andrew; Clayton, Aled; Gurney, Mark; Shantikumar, Saran; Angelini, Gianni D

2016-01-01

Exosome nanoparticles carry a composite cargo, including microRNAs (miRs). Cultured cardiovascular cells release miR-containing exosomes. The exosomal trafficking of miRNAs from the heart is largely unexplored. Working on clinical samples from coronary-artery by-pass graft (CABG) surgery, we investigated if: 1) exosomes containing cardiac miRs and hence putatively released by cardiac cells increase in the circulation after surgery; 2) circulating exosomes and exosomal cardiac miRs correlate with cardiac troponin (cTn), the current "gold standard" surrogate biomarker of myocardial damage. The concentration of exosome-sized nanoparticles was determined in serial plasma samples. Cardiac-expressed (miR-1, miR-24, miR-133a/b, miR-208a/b, miR-210), non-cardiovascular (miR-122) and quality control miRs were measured in whole plasma and in plasma exosomes. Linear regression analyses were employed to establish the extent to which the circulating individual miRs, exosomes and exosomal cardiac miR correlated with cTn-I. Cardiac-expressed miRs and the nanoparticle number increased in the plasma on completion of surgery for up to 48 hours. The exosomal concentration of cardiac miRs also increased after CABG. Cardiac miRs in the whole plasma did not correlate significantly with cTn-I. By contrast cTn-I was positively correlated with the plasma exosome level and the exosomal cardiac miRs. The plasma concentrations of exosomes and their cargo of cardiac miRs increased in patients undergoing CABG and were positively correlated with hs-cTnI. These data provide evidence that CABG induces the trafficking of exosomes from the heart to the peripheral circulation. Future studies are necessary to investigate the potential of circulating exosomes as clinical biomarkers in cardiac patients.

Coronary Artery-Bypass-Graft Surgery Increases the Plasma Concentration of Exosomes Carrying a Cargo of Cardiac MicroRNAs: An Example of Exosome Trafficking Out of the Human Heart with Potential for Cardiac Biomarker Discovery

PubMed Central

Emanueli, Costanza; Fiorentino, Francesca; Reeves, Barnaby C.; Beltrami, Cristina; Mumford, Andrew; Clayton, Aled; Gurney, Mark; Shantikumar, Saran; Angelini, Gianni D.

2016-01-01

Introduction Exosome nanoparticles carry a composite cargo, including microRNAs (miRs). Cultured cardiovascular cells release miR-containing exosomes. The exosomal trafficking of miRNAs from the heart is largely unexplored. Working on clinical samples from coronary-artery by-pass graft (CABG) surgery, we investigated if: 1) exosomes containing cardiac miRs and hence putatively released by cardiac cells increase in the circulation after surgery; 2) circulating exosomes and exosomal cardiac miRs correlate with cardiac troponin (cTn), the current “gold standard” surrogate biomarker of myocardial damage. Methods and Results The concentration of exosome-sized nanoparticles was determined in serial plasma samples. Cardiac-expressed (miR-1, miR-24, miR-133a/b, miR-208a/b, miR-210), non-cardiovascular (miR-122) and quality control miRs were measured in whole plasma and in plasma exosomes. Linear regression analyses were employed to establish the extent to which the circulating individual miRs, exosomes and exosomal cardiac miR correlated with cTn-I. Cardiac-expressed miRs and the nanoparticle number increased in the plasma on completion of surgery for up to 48 hours. The exosomal concentration of cardiac miRs also increased after CABG. Cardiac miRs in the whole plasma did not correlate significantly with cTn-I. By contrast cTn-I was positively correlated with the plasma exosome level and the exosomal cardiac miRs. Conclusions The plasma concentrations of exosomes and their cargo of cardiac miRs increased in patients undergoing CABG and were positively correlated with hs-cTnI. These data provide evidence that CABG induces the trafficking of exosomes from the heart to the peripheral circulation. Future studies are necessary to investigate the potential of circulating exosomes as clinical biomarkers in cardiac patients. PMID:27128471

The importance of intraoperative selenium blood levels on organ dysfunction in patients undergoing off-pump cardiac surgery: a randomised controlled trial.

PubMed

Stevanovic, Ana; Coburn, Mark; Menon, Ares; Rossaint, Rolf; Heyland, Daren; Schälte, Gereon; Werker, Thilo; Wonisch, Willibald; Kiehntopf, Michael; Goetzenich, Andreas; Rex, Steffen; Stoppe, Christian

2014-01-01

Cardiac surgery is accompanied by an increase of oxidative stress, a significantly reduced antioxidant (AOX) capacity, postoperative inflammation, all of which may promote the development of organ dysfunction and an increase in mortality. Selenium is an essential co-factor of various antioxidant enzymes. We hypothesized a less pronounced decrease of circulating selenium levels in patients undergoing off-pump coronary artery bypass (OPCAB) surgery due to less intraoperative oxidative stress. In this prospective randomised, interventional trial, 40 patients scheduled for elective coronary artery bypass grafting were randomly assigned to undergo either on-pump or OPCAB-surgery, if both techniques were feasible for the single patient. Clinical data, myocardial damage assessed by myocard specific creatine kinase isoenzyme (CK-MB), circulating whole blood levels of selenium, oxidative stress assessed by asymmetric dimethylarginine (ADMA) levels, antioxidant capacity determined by glutathionperoxidase (GPx) levels and perioperative inflammation represented by interleukin-6 (IL-6) levels were measured at predefined perioperative time points. At end of surgery, both groups showed a comparable decrease of circulating selenium concentrations. Likewise, levels of oxidative stress and IL-6 were comparable in both groups. Selenium levels correlated with antioxidant capacity (GPx: r = 0.720; p<0.001) and showed a negative correlation to myocardial damage (CK-MB: r =  -0.571, p<0.001). Low postoperative selenium levels had a high predictive value for the occurrence of any postoperative complication. OPCAB surgery is not associated with less oxidative stress and a better preservation of the circulating selenium pool than on-pump surgery. Low postoperative selenium levels are predictive for the development of complications. ClinicalTrials.gov NCT01409057.

Vascular Reactivity Profile of Novel KCa3.1-Selective Positive-Gating Modulators in the Coronary Vascular Bed

PubMed Central

Oliván-Viguera, Aida; Valero, Marta Sofía; Pinilla, Estéfano; Amor, Sara; García-Villalón, Ángel Luis; Coleman, Nichole; Laría, Celia; Calvín-Tienza, Víctor; García-Otín, Ángel-Luis; Fernández-Fernández, José M.; Murillo, Ma Divina; Gálvez, José A.; Díaz-de-Villegas, María D.; Badorrey, Ramón; Simonsen, Ulf; Rivera, Luis; Wulff, Heike; Köhler, Ralf

2017-01-01

Opening of intermediate-conductance calcium-activated potassium channels (KCa3.1) produces membrane hyperpolarization in the vascular endothelium. Here, we studied the ability of two new KCa3.1-selective positive-gating modulators, SKA-111 and SKA-121, to (1) evoke porcine endothelial cell KCa3.1 membrane hyperpolarization, (2) induce endothelium-dependent and, particularly, endothelium-derived hyperpolarization (EDH)-type relaxation in porcine coronary arteries (PCA) and (3) influence coronary artery tone in isolated rat hearts. In whole-cell patch-clamp experiments on endothelial cells of PCA (PCAEC), KCa currents evoked by bradykinin (BK) were potentiated ≈7-fold by either SKA-111 or SKA-121 (both at 1 μM) and were blocked by a KCa3.1 blocker, TRAM-34. In membrane potential measurements, SKA-111 and SKA-121 augmented bradykinin-induced hyperpolarization. Isometric tension measurements in large- and small-calibre PCA showed that SKA-111 and SKA-121 potentiated endothelium-dependent relaxation with intact NO synthesis and EDH-type relaxation to BK by ≈2-fold. Potentiation of the BK response was prevented by KCa3.1 inhibition. In Langendorff-perfused rat hearts, SKA-111 potentiated coronary vasodilation elicited by BK. In conclusion, our data show that positive-gating modulation of KCa3.1 channels improves BK-induced membrane hyperpolarization and endothelium-dependent relaxation in small and large PCA as well as in the coronary circulation of rats. Positive-gating modulators of KCa3.1 could be therapeutically useful to improve coronary blood flow and counteract impaired coronary endothelial dysfunction in cardiovascular disease. PMID:26821335

Effect of atrial systole on canine and porcine coronary blood flow.

PubMed

Bellamy, R F

1981-09-01

A feature of phasic coronary flow patterns recorded in conscious chronically instrumented dogs is the atrial cove--a transient depression of arterial flow that occurs during atrial systole. The association between the hemodynamic effects of atrial systole and the atrial cove was studied in anesthetized dogs and pigs with complete heart block. Many atrial coves are available for study in these preparations because atrial activity continues unabated during the diastolic ventricular arrest that follows cessation of electrical pacing. The effect of atrial systole is to translate the pressure-flow relation found during diastole to a higher intercept pressure without change in slope. The increase in the intercept pressure equals the increase in intramyocardial pressure measured with microtransducers embedded in the left ventricular wall. The decrement in flow during the atrial cove is a direct function of the change in intramyocardial pressure and an inverse function of coronary vascular resistance. Each atrial systole is associated with a forward flow transient in the coronary veins, the peak of which occurs at the same instant as does the nadir of atrial flow. These data suggest that the coronary vessels are acting as collapsible tubes and that the waterfall model of the coronary circulation is applicable. The following sequence is proposed to account for the atrial cove. Atrial systole ejects a bolus of blood into the left ventricle increasing both ventricular cavity and intramyocardial pressures. The increase in intramyocardial pressure raises the back pressure opposing coronary flow, reducing the arterial perfusion pressure gradient and causing flow to fall.

Circulating vitamin K is inversely associated with incident cardiovascular disease risk among those treated for hypertension in the Health, Aging, and Body Composition Study (Health ABC)

USDA-ARS?s Scientific Manuscript database

Background: A role for vitamin K in coronary artery calcification (CAC), a subclinical manifestation of cardiovascular disease (CVD), has been proposed because vitamin K-dependent proteins, including the calcification inhibitor matrix Gla protein (MGP), are present in vascular tissue. Observational ...

Genetic variants on apolipoprotein gene cluster influence triglycerides with a risk of coronary artery disease among Indians.

PubMed

AshokKumar, Manickaraj; Subhashini, Navaneethan Gnana Veera; SaiBabu, Ramineni; Ramesh, Arabandi; Cherian, Kotturathu Mammen; Emmanuel, Cyril

2010-01-01

Apolipoprotein C3 and apolipoprotien A5 are proteins coded from the APOA1/C3/A4/A5 gene cluster. Sst I polymorphism on apolipoprotein C3 and -1131C polymorphism of apolipoprotien A5 are key variants involved in triglyceride metabolism and cause a significant cardio-metabolic risk. Here, we have evaluated these two variants for their roles in coronary artery disease in patients of the Indian population. The apolipoprotein gene cluster variants were analysed in 416 angiographically determined coronary artery disease patients and matched 416 controls using polymerase chain reaction-restriction fragment length polymorphism. The characteristics of the study subjects were analyzed statistically for their association with the polymorphisms. The alleles were combined as haplotypes and their combined risks were evaluated. The minor allele genotypes of both apolipoprotein C3 (S2) and apolipoprotien A5 (C) had a significant risk for coronary artery disease. The S2 allele genotyped patients had a significantly increased triglyceride level (P < 0.001) and increased triglycerides were observed among both patient and control CC genotype carriers. We identified the haplotype S2/C with a significant increased risk (P < 0.001) to coronary artery disease with increased levels of circulating triglycerides compared to other haplotypes in patients. We conclude that the variants on apolipoprotein C3 and apolipoprotien A5 modulate serum triglyceride levels and increase the risk of coronary artery disease.

Carbon dioxide coronary angiography: A mechanical feasibility study with a cardiovascular simulator

NASA Astrophysics Data System (ADS)

Corazza, Ivan; Taglieri, Nevio; Pirazzini, Edoardo; Rossi, Pier Luca; Lombi, Alessandro; Scalise, Filippo; Caridi, James G.; Zannoli, Romano

2018-01-01

The aim of this study was to carry out a bench evaluation of the biomechanical feasibility of carbon dioxide (CO2) coronary arteriography. Many patients among the aging population of individuals requiring cardiac intervention have underlying renal insufficiency making them susceptible to contrast-induced nephropathy. To include those patients, it is imperative to find an alternative and safe technique to perform coronary imaging on cardiac ischemic patients. As CO2 angiography has no renal toxicity, it may be a possible solution offering good imaging with negligible collateral effects. Theoretically, by carefully controlling the gas injection process, new automatic injectors may avoid gas reflux into the aorta and possible cerebral damage. A feasibility study is mandatory. A mechanical mock of the coronary circulation was developed and employed. CO2 was injected into the coronary ostium with 2 catheters (2F and 6F) and optical images of bubbles flowing inside the vessels at different injection pressures were recorded. The gas behavior was then carefully studied for quantitative and qualitative analysis. Video recordings showed that CO2 injection at a precise pressure in the interval between the arterial dicrotic notch and the minimum diastolic value does not result in gas reflow into the aorta. Gas reflow was easier to control with the smaller catheter, but the gas bubbles were smaller with different vascular filling. Our simulation demonstrates that carefully selected injection parameters allow CO2 coronary imaging without any risk of gas reflux into the aorta.

Breath-hold imaging of the coronary arteries using Quiescent-Interval Slice-Selective (QISS) magnetic resonance angiography: pilot study at 1.5 Tesla and 3 Tesla.

PubMed

Edelman, Robert R; Giri, S; Pursnani, A; Botelho, M P F; Li, W; Koktzoglou, I

2015-11-23

Coronary magnetic resonance angiography (MRA) is usually obtained with a free-breathing navigator-gated 3D acquisition. Our aim was to develop an alternative breath-hold approach that would allow the coronary arteries to be evaluated in a much shorter time and without risk of degradation by respiratory motion artifacts. For this purpose, we implemented a breath-hold, non-contrast-enhanced, quiescent-interval slice-selective (QISS) 2D technique. Sequence performance was compared at 1.5 and 3 Tesla using both radial and Cartesian k-space trajectories. The left coronary circulation was imaged in six healthy subjects and two patients with coronary artery disease. Breath-hold QISS was compared with T2-prepared 2D balanced steady-state free-precession (bSSFP) and free-breathing, navigator-gated 3D bSSFP. Approximately 10 2.1-mm thick slices were acquired in a single ~20-s breath-hold using two-shot QISS. QISS contrast-to-noise ratio (CNR) was 1.5-fold higher at 3 Tesla than at 1.5 Tesla. Cartesian QISS provided the best coronary-to-myocardium CNR, whereas radial QISS provided the sharpest coronary images. QISS image quality exceeded that of free-breathing 3D coronary MRA with few artifacts at either field strength. Compared with T2-prepared 2D bSSFP, multi-slice capability was not restricted by the specific absorption rate at 3 Tesla and pericardial fluid signal was better suppressed. In addition to depicting the coronary arteries, QISS could image intra-cardiac structures, pericardium, and the aortic root in arbitrary slice orientations. Breath-hold QISS is a simple, versatile, and time-efficient method for coronary MRA that provides excellent image quality at both 1.5 and 3 Tesla. Image quality exceeded that of free-breathing, navigator-gated 3D MRA in a much shorter scan time. QISS also allowed rapid multi-slice bright-blood, diastolic phase imaging of the heart, which may have complementary value to multi-phase cine imaging. We conclude that, with further clinical validation, QISS might provide an efficient alternative to commonly used free-breathing coronary MRA techniques.

Allogeneic Blood Product Usage in Coronary Artery Bypass Grafting (CABG) with minimalized Extracorporeal Circulation System (MECC) Versus Standard On-Pump Coronary Artery Bypass Grafting.

PubMed

Lisy, M; Schmid, E; Kozok, J; Rosenberger, P; Stock, U A; Kalender, G

2016-01-01

Intraoperative allogeneic blood product transfusion (ABPT) in cardiac surgery is associated with worse overall outcome, including mortality. The objective of this study was to evaluate the ABPTs in minimalized extracorporeal cardiopulmonary (MECC(TM)) compared with standard open system on-pump coronary revascularization. Data of 156 patients undergoing myocardial revascularization between September 2008 and September 2010 were reviewed. 83 patients were operated by the MECC technique and 73 were treated by standard extracorporeal circulation (sECC). ABPT and overall early postoperative complications were analyzed. Operative mortality and morbidity were similar in both groups. ABPT in the MECC group was significantly lower than in the sECC group both intraoperatively (7.2 vs. 60.3% of patients p<0.001) and during the first five postoperative days (19.3 vs. 57.5%; p<0.001). "Skin to skin"- (214 ± 45 vs. 232 ± 45 min; p=0.012), cardiopulmonary bypass (CPB) - (82 ± 25 vs. 95 ± 26 min; p=0.014), and X-clamp- times (50 ± 16 vs. 56 ± 17 min; p=0.024) were significantly lower in the MECC group than in the sECC group. Length of ICU (intensive care unit) - and hospital stay were also significantly lower in the MECC group vs. the sECC group (26.7 ± 20.2 vs. 54.5 ± 68.9 h; p<0.001, and 12.0 ± 4.1 vs. 14.5 ± 4.6 days; p<0.001). Application of MECC as on-pump coronary artery bypass graft (CABG) results in significantly lower ABPT as well as shorter ICU and in-hospital stay. In order to achieve these benefits of MECC autologous retrograde priming, Bispectral index (BIS) monitoring, intraoperative cell salvage, meticulous hemostasis and strict peri- and postoperative volume management are crucial.

Pathophysiology, prognostic significance and clinical utility of B-type natriuretic peptide in acute coronary syndromes.

PubMed

Wiviott, Stephen D; de Lemos, James A; Morrow, David A

2004-08-16

The natriuretic hormones are a family of vasoactive peptides that can be measured circulating in the blood. Because they serve as markers of hemodynamic stress, the major focus of the use of natriuretic peptide levels [predominantly B-type natriuretic peptide (BNP) and N-terminal (NT)-pro-BNP] has been as an aid to the clinical diagnosis and management of congestive heart failure (CHF). Recently, however, the measurement of natriuretic peptides in the acute coronary syndromes (ACS) has been shown to provide information complementary to traditional biomarkers (of necrosis) such as cardiac troponins and creatine kinase (CK). Studies in several types of acute coronary syndromes [ST-segment elevation myocardial infarction (STEMI), non-ST elevation MI (NSTEMI) and unstable angina (UA)] have shown that elevated levels of natriuretic peptides are independently associated with adverse outcomes, particularly mortality. Additional information is obtained from the use natriuretic peptides in combination with other markers of risk including biomarkers of necrosis and inflammation. This review will summarize the scientific rationale and clinical evidence supporting measurement of natriuretic peptides for risk stratification in acute coronary syndromes. Future research is needed to identify therapies of particular benefit for patients with ACS and natriuretic peptide elevation.

Truncus arteriosus with aortic arch interruption: cardiovascular magnetic resonance findings in the unrepaired adult

PubMed Central

2010-01-01

Truncus arteriosus (TA) is a rare congenital condition defined as a single arterial vessel arising from the heart that gives origin to the systemic, pulmonary and coronary circulations. We discuss the unique case of a 28 year-old female patient with unrepaired TA and interruption of the aortic arch who underwent cardiovascular magnetic resonance (CMR). PMID:20307275

There Is More to the Dissection of a Pig's Heart

ERIC Educational Resources Information Center

Lee, Yeung Chung

2004-01-01

The dissection of the mammalian heart in secondary biology classes need not be restricted to revealing the internal structure of the heart and its function. It could also be used to demonstrate other important aspects of blood circulation, including the blood supply to the heart itself as well as the causes and effects of coronary heart disease.…

[Successful use of an AED following anterior myocardial infarction].

PubMed

Harding, Ulf; Reifferscheid, Florian; von Olshausen, Klaus

2007-05-01

A participant of the annual Hamburg marathon collapses on the finish line. Medics at the scene find a conscious patient and prepare transport to the finish area medical center. During transport the patient becomes unconscious and pulseless. The medics immediately perform basic life support and cardiopulmonary resuscitation (CPR). An automated external defibrillator (AED) is attached and after analysis of the patient}s heart rhythm the patient is defibrillated twice. The ambulance service reach the scene with a delay. The emergency physician}s ECG shows ventricular fibrillation (VF) and two more defibrillations are delivered. Return of spontaneous circulation can be achieved. After stabilisation the patient is taken to hospital by ambulance. The ECG shows an anterior myocardial infarction and right bundle-branch block. The coronary angioplasty (PTCA) shows single-vessel disease with complete stenosis of the proximal part of the anterior interventricular branch. Revasucarisation is successful and a coronary stent is applied. The patient survives neurologically intact. This case report demonstrates the importance of readily available AED and specially trained medics. By immediately using the AED this patient was defibrillated before the ambulance service and emergency physician arrived at the scene. Spontaneous circulation was restored.

Vascular Reactivity Profile of Novel KCa 3.1-Selective Positive-Gating Modulators in the Coronary Vascular Bed.

PubMed

Oliván-Viguera, Aida; Valero, Marta Sofía; Pinilla, Estéfano; Amor, Sara; García-Villalón, Ángel Luis; Coleman, Nichole; Laría, Celia; Calvín-Tienza, Víctor; García-Otín, Ángel-Luis; Fernández-Fernández, José M; Murillo, M Divina; Gálvez, José A; Díaz-de-Villegas, María D; Badorrey, Ramón; Simonsen, Ulf; Rivera, Luis; Wulff, Heike; Köhler, Ralf

2016-08-01

Opening of intermediate-conductance calcium-activated potassium channels (KC a 3.1) produces membrane hyperpolarization in the vascular endothelium. Here, we studied the ability of two new KC a 3.1-selective positive-gating modulators, SKA-111 and SKA-121, to (1) evoke porcine endothelial cell KC a 3.1 membrane hyperpolarization, (2) induce endothelium-dependent and, particularly, endothelium-derived hyperpolarization (EDH)-type relaxation in porcine coronary arteries (PCA) and (3) influence coronary artery tone in isolated rat hearts. In whole-cell patch-clamp experiments on endothelial cells of PCA (PCAEC), KC a currents evoked by bradykinin (BK) were potentiated ≈7-fold by either SKA-111 or SKA-121 (both at 1 μM) and were blocked by a KC a 3.1 blocker, TRAM-34. In membrane potential measurements, SKA-111 and SKA-121 augmented bradykinin-induced hyperpolarization. Isometric tension measurements in large- and small-calibre PCA showed that SKA-111 and SKA-121 potentiated endothelium-dependent relaxation with intact NO synthesis and EDH-type relaxation to BK by ≈2-fold. Potentiation of the BK response was prevented by KC a 3.1 inhibition. In Langendorff-perfused rat hearts, SKA-111 potentiated coronary vasodilation elicited by BK. In conclusion, our data show that positive-gating modulation of KC a 3.1 channels improves BK-induced membrane hyperpolarization and endothelium-dependent relaxation in small and large PCA as well as in the coronary circulation of rats. Positive-gating modulators of KC a 3.1 could be therapeutically useful to improve coronary blood flow and counteract impaired coronary endothelial dysfunction in cardiovascular disease. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Intracoronary and Retrograde Coronary Venous Myocardial Delivery of Adipose-Derived Stem Cells in Swine Infarction Lead to Transient Myocardial Trapping with Predominant Pulmonary Redistribution

PubMed Central

Hong, Soon Jun; Hou, Dongming; Brinton, Todd J.; Johnstone, Brian; Feng, Dongni; Rogers, Pamela; Fearon, William F.; Yock, Paul; March, Keith L.

2012-01-01

Objectives To examine the comparative fate of adipose-derived stem cells (ASCs) as well as their impact on coronary microcirculation following either retrograde coronary venous or arterial delivery. Background Local delivery of ASCs to the heart has been proposed as a practical approach to limiting the extent of myocardial infarction. Mouse models of mesenchymal stem cell effects on the heart have also demonstrated significant benefits from systemic (intravenous) delivery, prompting a question about the advantage of local delivery. There has been no study addressing the extent of myocardial vs. systemic disposition of ASCs in large animal models following local delivery to the myocardium. Methods In an initial experiment, dose-dependent effects of ASC delivery on coronary circulation in normal swine were evaluated to establish a tolerable ASC dosing range for intracoronary delivery. In a set of subsequent experiments, an anterior acute myocardial infarction (AMI) was created by balloon occlusion of the proximal left anterior descending (LAD) artery, followed by either intracoronary (IC) or retrograde coronary venous (RCV) infusion of 107 111Indium-labeled autologous ASCs 6 days following AMI. Indices of microcirculatory resistance (IMR) and coronary flow reserve (CFR) were measured before sacrifices to collect tissues for analysis at 1 or 24 hours after cell delivery. Results IC delivery of porcine ASCs to normal myocardium was well-tolerated up to a cumulative dose of 14×106 cells (approximately 0.5×106 cells/kg). There was evidence suggesting microcirculatory trapping of ASC: at unit doses of 50×106 ASCs, IMR and CFR were found to be persistently altered in the target LAD distribution at 7 days following delivery, while at 10×106 ASCs, only CFR was altered. In the context of recent MI, a significantly higher percentage of ASCs was retained at 1 hour with IC delivery compared to RCV delivery (57.2 ± 12.7% vs. 17.9 ± 1.6%, p=0.037) but this initial difference was not apparent at 24 hours (22.6 ± 5.5% vs. 18.7 ± 8.6%; p= 0.722). In both approaches, most ASC redistributed to the pulmonary circulation by 24 hours post-delivery. There were no significant differences in CFR or IMR following ASC delivery to infarcted tissue by either route. Conclusions Selective intravascular delivery of ASC by coronary arterial and venous routes leads to similarly limited myocardial cell retention with predominant redistribution of cells to the lungs. Intracoronary arterial delivery of ASC leads to only transiently greater myocardial retention, which is accompanied by obstruction of normal regions of coronary microcirculation at higher doses. The predominant intrapulmonary localization of cells following local delivery via both methods prompts the notion that systemic delivery of ASC might provide similarly beneficial outcomes while avoiding risks of inadvertent microcirculatory compromise. PMID:22972685

The interleukin-6 receptor as a target for prevention of coronary heart disease: a mendelian randomisation analysis

PubMed Central

2012-01-01

Summary Background A high circulating concentration of interleukin 6 is associated with increased risk of coronary heart disease. Blockade of the interleukin-6 receptor (IL6R) with a monoclonal antibody (tocilizumab) licensed for treatment of rheumatoid arthritis reduces systemic and articular inflammation. However, whether IL6R blockade also reduces risk of coronary heart disease is unknown. Methods Applying the mendelian randomisation principle, we used single nucleotide polymorphisms (SNPs) in the gene IL6R to evaluate the likely efficacy and safety of IL6R inhibition for primary prevention of coronary heart disease. We compared genetic findings with the effects of tocilizumab reported in randomised trials in patients with rheumatoid arthritis. Findings In 40 studies including up to 133 449 individuals, an IL6R SNP (rs7529229) marking a non-synonymous IL6R variant (rs8192284; p.Asp358Ala) was associated with increased circulating log interleukin-6 concentration (increase per allele 9·45%, 95% CI 8·34–10·57) as well as reduced C-reactive protein (decrease per allele 8·35%, 95% CI 7·31–9·38) and fibrinogen concentrations (decrease per allele 0·85%, 95% CI 0·60–1·10). This pattern of effects was consistent with IL6R blockade from infusions of tocilizumab (4–8 mg/kg every 4 weeks) in patients with rheumatoid arthritis studied in randomised trials. In 25 458 coronary heart disease cases and 100 740 controls, the IL6R rs7529229 SNP was associated with a decreased odds of coronary heart disease events (per allele odds ratio 0·95, 95% CI 0·93–0·97, p=1·53×10−5). Interpretation On the basis of genetic evidence in human beings, IL6R signalling seems to have a causal role in development of coronary heart disease. IL6R blockade could provide a novel therapeutic approach to prevention of coronary heart disease that warrants testing in suitably powered randomised trials. Genetic studies in populations could be used more widely to help to validate and prioritise novel drug targets or to repurpose existing agents and targets for new therapeutic uses. Funding UK Medical Research Council; British Heart Foundation; Rosetrees Trust; US National Heart, Lung, and Blood Institute; Du Pont Pharma; Chest, Heart and Stroke Scotland; Wellcome Trust; Coronary Thrombosis Trust; Northwick Park Institute for Medical Research; UCLH/UCL Comprehensive Medical Research Centre; US National Institute on Aging; Academy of Finland; Netherlands Organisation for Health Research and Development; SANCO; Dutch Ministry of Public Health, Welfare and Sports; World Cancer Research Fund; Agentschap NL; European Commission; Swedish Heart-Lung Foundation; Swedish Research Council; Strategic Cardiovascular Programme of the Karolinska Institutet; Stockholm County Council; US National Institute of Neurological Disorders and Stroke; MedStar Health Research Institute; GlaxoSmithKline; Dutch Kidney Foundation; US National Institutes of Health; Netherlands Interuniversity Cardiology Institute of the Netherlands; Diabetes UK; European Union Seventh Framework Programme; National Institute for Healthy Ageing; Cancer Research UK; MacArthur Foundation. PMID:22421340

Endothelial Microparticles From Acute Coronary Syndrome Patients Induce Premature Coronary Artery Endothelial Cell Aging and Thrombogenicity: Role of the Ang II/AT1 Receptor/NADPH Oxidase-Mediated Activation of MAPKs and PI3-Kinase Pathways.

PubMed

Abbas, Malak; Jesel, Laurence; Auger, Cyril; Amoura, Lamia; Messas, Nathan; Manin, Guillaume; Rumig, Cordula; León-González, Antonio J; Ribeiro, Thais P; Silva, Grazielle C; Abou-Merhi, Raghida; Hamade, Eva; Hecker, Markus; Georg, Yannick; Chakfe, Nabil; Ohlmann, Patrick; Schini-Kerth, Valérie B; Toti, Florence; Morel, Olivier

2017-01-17

Microparticles (MPs) have emerged as a surrogate marker of endothelial dysfunction and cardiovascular risk. This study examined the potential of MPs from senescent endothelial cells (ECs) or from patients with acute coronary syndrome (ACS) to promote premature EC aging and thrombogenicity. Primary porcine coronary ECs were isolated from the left circumflex coronary artery. MPs were prepared from ECs and venous blood from patients with ACS (n=30) and from healthy volunteers (n=4) by sequential centrifugation. The level of endothelial senescence was assessed as senescence-associated β-galactosidase activity using flow cytometry, oxidative stress using the redox-sensitive probe dihydroethidium, tissue factor activity using an enzymatic Tenase assay, the level of target protein expression by Western blot analysis, platelet aggregation using an aggregometer, and shear stress using a cone-and-plate viscometer. Senescence, as assessed by senescence-associated β-galactosidase activity, was induced by the passaging of porcine coronary artery ECs from passage P1 to P4, and was associated with a progressive shedding of procoagulant MPs. Exposure of P1 ECs to MPs shed from senescent P3 cells or circulating MPs from ACS patients induced increased senescence-associated β-galactosidase activity, oxidative stress, early phosphorylation of mitogen-activated protein kinases and Akt, and upregulation of p53, p21, and p16. Ex vivo, the prosenescent effect of circulating MPs from ACS patients was evidenced only under conditions of low shear stress. Depletion of endothelial-derived MPs from ACS patients reduced the induction of senescence. Prosenescent MPs promoted EC thrombogenicity through tissue factor upregulation, shedding of procoagulant MPs, endothelial nitric oxide synthase downregulation, and reduced nitric oxide-mediated inhibition of platelet aggregation. These MPs exhibited angiotensin-converting enzyme activity and upregulated AT1 receptors and angiotensin-converting enzyme in P1 ECs. Losartan, an AT1 receptor antagonist, and inhibitors of either mitogen-activated protein kinases or phosphoinositide 3-kinase prevented the MP-induced endothelial senescence. These findings indicate that endothelial-derived MPs from ACS patients induce premature endothelial senescence under atheroprone low shear stress and thrombogenicity through angiotensin II-induced redox-sensitive activation of mitogen-activated protein kinases and phosphoinositide 3-kinase/Akt. They further suggest that targeting endothelial-derived MP shedding and their bioactivity may be a promising therapeutic strategy to limit the development of an endothelial dysfunction post-ACS. © 2016 American Heart Association, Inc.

Does Undersizing of Transcatheter Aortic Valve Bioprostheses during Valve-in-Valve Implantation Avoid Coronary Obstruction? An In Vitro Study.

PubMed

Stock, Sina; Scharfschwerdt, Michael; Meyer-Saraei, Roza; Richardt, Doreen; Charitos, Efstratios I; Sievers, Hans-Hinrich; Hanke, Thorsten

2017-04-01

Background  The transcatheter aortic valve-in-valve implantation (TAViVI) is an evolving treatment strategy for degenerated surgical aortic valve bioprostheses (SAVBs) in patients with high operative risk. Although hemodynamics is excellent, there is some concern regarding coronary obstruction, especially in SAVB with externally mounted leaflet tissue, such as the Trifecta (St. Jude Medical Inc., St. Paul, Minnesota, United States). We investigated coronary flow and hydrodynamics before and after TAViVI in a SAVB with externally mounted leaflet tissue (St. Jude Medical, Trifecta) with an undersized transcatheter aortic valve bioprosthesis (Edwards Sapien XT; Edwards Lifesciences LLC, Irvine, California, United States) in an in vitro study. Materials and Methods  An aortic root model was constructed incorporating geometric dimensions known as risk factors for coronary obstruction. Investigating the validity of this model, we primarily performed recommended TAViVI with the Sapien XT (size 26 mm) in a Trifecta (size 25 mm) in a mock circulation. Thereafter, hydrodynamic performance and coronary flow (left/right coronary diastolic flow [lCF/rCF]) after TAViVI with an undersized Sapien XT (size 23 mm) in a Trifecta (size 25 mm) were investigated at two different coronary ostia heights (COHs, 8 and 10 mm). Results  Validation of the model led to significant coronary obstruction ( p  < 0.001). Undersized TAViVI showed no significant reduction with respect to coronary flow (lCF: COH 8 mm, 0.90-0.87 mL/stroke; COH 10 mm, 0.89-0.82 mL/stroke and rCF: COH 8 mm, 0.64-0.60 mL/stroke; COH 10 mm, 0.62-0.58 mL/stroke). Mean transvalvular gradients (4-5 mm Hg, p  < 0.001) increased significantly after TAViVI. Conclusions  In our in vitro model, undersized TAViVI with the balloon-expandable Sapien XT into a modern generation SAVB (Trifecta) successfully avoided coronary flow obstruction. Georg Thieme Verlag KG Stuttgart · New York.

Resistin impairs endothelium-dependent dilation to bradykinin, but not acetylcholine, in the coronary circulation.

PubMed

Dick, Gregory M; Katz, Paige S; Farias, Martin; Morris, Michael; James, Jeremy; Knudson, Jarrod D; Tune, Johnathan D

2006-12-01

Elevated plasma levels of fat-derived signaling molecules are associated with obesity, vascular endothelial dysfunction, and coronary heart disease; however, little is known about their direct coronary vascular effects. Accordingly, we examined mechanisms by which one adipokine, resistin, affects coronary vascular tone and endothelial function. Studies were conducted in anesthetized dogs and isolated coronary artery rings. Resistin did not change coronary blood flow, mean arterial pressure, or heart rate. Resistin had no effect on acetylcholine-induced relaxation of artery rings; however, resistin did impair bradykinin-induced relaxation. Selective impairment was also observed in vivo, as resistin attenuated vasodilation to bradykinin but not to acetylcholine. Resistin had no effect on dihydroethidium fluorescence, an indicator of superoxide (O(2)(-)) production, and the inhibitory effect of resistin on bradykinin-induced relaxation persisted in the presence of Tempol, a superoxide dismutase mimetic. To determine whether resistin impaired production of and/or responses to nitric oxide (NO) or prostaglandins (e.g., prostacyclin; PGI(2)), we performed experiments with N(omega)-nitro-L-arginine methyl ester (L-NAME) and indomethacin. The effect of resistin to attenuate bradykinin-induced vasodilation persisted in the presence of L-NAME or indomethacin, suggesting resistin may act at a cell signaling point upstream of NO or PGI(2) production. Resistin-induced endothelial dysfunction is not generalized, and it is not consistent with effects mediated by O(2)(-) or interference with NO or PGI(2) signaling. The site of the resistin-induced impairment is unknown but may be at the bradykinin receptor or a closely associated signal transduction machinery proximal to NO synthase or cyclooxygenase.

[Blood coagulation and fibrinolysis in ischemic heart disease].

PubMed

Sakamoto, T; Ogawa, H; Miyao, Y; Yasue, H

1994-01-01

Intracoronary thrombus formation has been thought to play an important role in the genesis of acute myocardial infarction an unstable angina. To examine whether the coagulation and fibrinolytic systems are altered in such ischemic heart diseases, the plasma levels of fibrinopeptide A (FPA) and plasminogen activator (PAI) were measured. The plasma level of FPA was increased in patients with variant angina as compared with those with stable exertional angina and there was a significant circadian variation in the plasma level of FPA in parallel with that of the frequency of the attacks with the peak level occurring from midnight to early morning in patients with variant angina. The plasma FPA level increased in patients with coronary spastic angina after the ischemic attack induced by hyperventilation. Furthermore, FPA was released into the coronary circulation after the anginal attack induced by intracoronary injection of acetylcholine. These findings suggest that the coronary artery spasm may induce thrombin generation and trigger thrombus formation in the coronary artery. On the other hand, the plasma level of PAI activity was higher in patients with unstable angina and coronary spastic angina than in those with stable exertional angina. Moreover, the PAI activity in patients with unstable angina decreased to the level in patients with stable exertional angina after the stabilization of their symptoms by drugs. Our findings suggest that the increased plasma PAI activity may reduce fibrinolytic activity and attenuate removal of the thrombus and may ultimately lead to acute myocardial infarction in some patients with unstable angina and coronary spastic angina.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of angiographic collateral circulation on myocardial perfusion in patients with chronic total occlusion of a single coronary artery and no prior myocardial infarction.

PubMed

Aboul-Enein, Fatma; Kar, Saibal; Hayes, Sean W; Sciammarella, Maria; Abidov, Aiden; Makkar, Raj; Friedman, John D; Eigler, Neal; Berman, Daniel S

2004-06-01

The functional role of various angiographic grades for coronary collaterals remains controversial. The aim of this study was to assess the influence of the Rentrop angiographic grading of coronary collaterals on myocardial perfusion in patients with single-vessel chronic total occlusion (CTO) and no prior myocardial infarction (MI). The study included 56 patients with single-vessel CTO and no prior MI who underwent rest-stress myocardial perfusion SPECT and coronary angiography within 6 mo. All patients had angiographic evidence of coronary collaterals. Patients were divided according to the Rentrop classification: Group I had grade 1 or 2 (n = 25) and group II had grade 3 collaterals (n = 31). Group I had a higher frequency of resting regional wall motion abnormalities on left ventriculography (52.6% vs. 19.2% [P = 0.019]). The mean perfusion scores of the overall population showed severe and extensive stress perfusion defects (summed stress score of 14.1 +/- 7.1 and summed difference score of 12.9 +/- 6.9) but minimal resting perfusion defects (summed rest score of 1.0 +/- 2.7). No perfusion scores differed between the 2 groups. The perfusion findings suggested that chronic stunning rather than hibernation is the principal cause of regional wall motion abnormalities in these patients. In the setting of single-vessel CTO and no prior MI, coronary collaterals appear to protect against resting perfusion defects. Excellent angiographic collaterals may prevent resting regional wall motion abnormalities but do not appear to protect against stress-induced perfusion defects.

Diastolic coronary artery pressure-flow velocity relationships in conscious man.

PubMed

Dole, W P; Richards, K L; Hartley, C J; Alexander, G M; Campbell, A B; Bishop, V S

1984-09-01

We characterised the diastolic pressure-flow velocity relationship in the normal left coronary artery of conscious man before and after vasodilatation with angiographic contrast medium. Phasic coronary artery pressure and flow velocity were measured in ten patients during individual diastoles (0.5 to 1.0 s) using a 20 MHz catheter-tipped, pulsed Doppler transducer. All pressure-flow velocity curves were linear over the diastolic pressure range of 110 +/- 15 (SD) mmHg to 71 +/- 7 mmHg (r = 0.97 +/- 0.01). In the basal state, values for slope and extrapolated zero flow pressure intercept averaged 0.35 +/- 0.12 cm X s-1 X mmHg-1 and 51.7 +/- 8.6 mmHg, respectively. Vasodilatation resulted in a 2.5 +/- 0.5 fold increase in mean flow velocity. The diastolic pressure-flow velocity relationship obtained during peak vasodilatation compared to that during basal conditions was characterised by a steeper slope (0.80 +/- 0.48 cm X s-1 X mmHg-1, p less than 0.001) and lower extrapolated zero flow pressure intercept (37.9 +/- 9.8 mmHg, p less than 0.05). Mean right atrial pressure for the group averaged 4.4 +/- 1.7 mmHg, while left ventricular end-diastolic pressure averaged 8.7 +/- 2.8 mmHg. These observations in man are similar to data reported in the canine coronary circulation which are consistent with a vascular waterfall model of diastolic flow regulation. In this model, coronary blood flow may be regulated by changes in diastolic zero flow pressure as well as in coronary resistance.

Estimation of coronary wave intensity analysis using noninvasive techniques and its application to exercise physiology

PubMed Central

Nijjer, Sukhjinder; Sen, Sayan; Petraco, Ricardo; Jones, Siana; Al-Lamee, Rasha; Foin, Nicolas; Al-Bustami, Mahmud; Sethi, Amarjit; Kaprielian, Raffi; Ramrakha, Punit; Khan, Masood; Malik, Iqbal S.; Francis, Darrel P.; Parker, Kim; Hughes, Alun D.; Mikhail, Ghada W.; Mayet, Jamil; Davies, Justin E.

2015-01-01

Wave intensity analysis (WIA) has found particular applicability in the coronary circulation where it can quantify traveling waves that accelerate and decelerate blood flow. The most important wave for the regulation of flow is the backward-traveling decompression wave (BDW). Coronary WIA has hitherto always been calculated from invasive measures of pressure and flow. However, recently it has become feasible to obtain estimates of these waveforms noninvasively. In this study we set out to assess the agreement between invasive and noninvasive coronary WIA at rest and measure the effect of exercise. Twenty-two patients (mean age 60) with unobstructed coronaries underwent invasive WIA in the left anterior descending artery (LAD). Immediately afterwards, noninvasive LAD flow and pressure were recorded and WIA calculated from pulsed-wave Doppler coronary flow velocity and central blood pressure waveforms measured using a cuff-based technique. Nine of these patients underwent noninvasive coronary WIA assessment during exercise. A pattern of six waves were observed in both modalities. The BDW was similar between invasive and noninvasive measures [peak: 14.9 ± 7.8 vs. −13.8 ± 7.1 × 104 W·m−2·s−2, concordance correlation coefficient (CCC): 0.73, P < 0.01; cumulative: −64.4 ± 32.8 vs. −59.4 ± 34.2 × 102 W·m−2·s−1, CCC: 0.66, P < 0.01], but smaller waves were underestimated noninvasively. Increased left ventricular mass correlated with a decreased noninvasive BDW fraction (r = −0.48, P = 0.02). Exercise increased the BDW: at maximum exercise peak BDW was −47.0 ± 29.5 × 104 W·m−2·s−2 (P < 0.01 vs. rest) and cumulative BDW −19.2 ± 12.6 × 103 W·m−2·s−1 (P < 0.01 vs. rest). The BDW can be measured noninvasively with acceptable reliably potentially simplifying assessments and increasing the applicability of coronary WIA. PMID:26683900

Estimation of coronary wave intensity analysis using noninvasive techniques and its application to exercise physiology.

PubMed

Broyd, Christopher J; Nijjer, Sukhjinder; Sen, Sayan; Petraco, Ricardo; Jones, Siana; Al-Lamee, Rasha; Foin, Nicolas; Al-Bustami, Mahmud; Sethi, Amarjit; Kaprielian, Raffi; Ramrakha, Punit; Khan, Masood; Malik, Iqbal S; Francis, Darrel P; Parker, Kim; Hughes, Alun D; Mikhail, Ghada W; Mayet, Jamil; Davies, Justin E

2016-03-01

Wave intensity analysis (WIA) has found particular applicability in the coronary circulation where it can quantify traveling waves that accelerate and decelerate blood flow. The most important wave for the regulation of flow is the backward-traveling decompression wave (BDW). Coronary WIA has hitherto always been calculated from invasive measures of pressure and flow. However, recently it has become feasible to obtain estimates of these waveforms noninvasively. In this study we set out to assess the agreement between invasive and noninvasive coronary WIA at rest and measure the effect of exercise. Twenty-two patients (mean age 60) with unobstructed coronaries underwent invasive WIA in the left anterior descending artery (LAD). Immediately afterwards, noninvasive LAD flow and pressure were recorded and WIA calculated from pulsed-wave Doppler coronary flow velocity and central blood pressure waveforms measured using a cuff-based technique. Nine of these patients underwent noninvasive coronary WIA assessment during exercise. A pattern of six waves were observed in both modalities. The BDW was similar between invasive and noninvasive measures [peak: 14.9 ± 7.8 vs. -13.8 ± 7.1 × 10(4) W·m(-2)·s(-2), concordance correlation coefficient (CCC): 0.73, P < 0.01; cumulative: -64.4 ± 32.8 vs. -59.4 ± 34.2 × 10(2) W·m(-2)·s(-1), CCC: 0.66, P < 0.01], but smaller waves were underestimated noninvasively. Increased left ventricular mass correlated with a decreased noninvasive BDW fraction (r = -0.48, P = 0.02). Exercise increased the BDW: at maximum exercise peak BDW was -47.0 ± 29.5 × 10(4) W·m(-2)·s(-2) (P < 0.01 vs. rest) and cumulative BDW -19.2 ± 12.6 × 10(3) W·m(-2)·s(-1) (P < 0.01 vs. rest). The BDW can be measured noninvasively with acceptable reliably potentially simplifying assessments and increasing the applicability of coronary WIA. Copyright © 2016 the American Physiological Society.

In vitro comparison of support capabilities of intra-aortic balloon pump and Impella 2.5 left percutaneous.

PubMed

Schampaert, Stéphanie; van't Veer, Marcel; van de Vosse, Frans N; Pijls, Nico H J; de Mol, Bas A; Rutten, Marcel C M

2011-09-01

The Impella 2.5 left percutaneous (LP), a relatively new transvalvular assist device, challenges the position of the intra-aortic balloon pump (IABP), which has a long record in supporting patients after myocardial infarction and cardiac surgery. However, while more costly and more demanding in management, the advantages of the Impella 2.5 LP are yet to be established. The aim of this study was to evaluate the benefits of the 40 cc IABP and the Impella 2.5 LP operating at 47,000 rpm in vitro, and compare their circulatory support capabilities in terms of cardiac output, coronary flow, cardiac stroke work, and arterial blood pressure. Clinical scenarios of cardiogenic preshock and cardiogenic shock (CS), with blood pressure depression, lowered cardiac output, and constant heart rate of 80 bpm, were modeled in a model-controlled mock circulation, featuring a systemic, pulmonary, and coronary vascular bed. The ventricles, represented by servomotor-operated piston pumps, included the Frank-Starling mechanism. The systemic circulation was modeled with a flexible tube having close-to-human aortic dimensions and compliance properties. Proximally, it featured a branch mimicking the brachiocephalic arteries and a physiological correct coronary flow model. The rest of the systemic and pulmonary impedance was modeled by four-element Windkessel models. In this system, the enhancement of coronary flow and blood pressure was tested with both support systems under healthy and pathological conditions. Hemodynamic differences between the IABP and the Impella 2.5 LP were small. In our laboratory model, both systems approximately yielded a 10% cardiac output increase and a 10% coronary flow increase. However, since the Impella 2.5 LP provided significantly better left ventricular unloading, the circulatory support capabilities were slightly in favor of the Impella 2.5 LP. On the other hand, pulsatility was enhanced with the IABP and lowered with the Impella 2.5 LP. The support capabilities of both the IABP and the Impella 2.5 LP strongly depended on the simulated hemodynamic conditions. Maximum hemodynamic benefits were achieved when mechanical circulatory support was applied on a simulated scenario of deep CS. © 2011, Copyright Eindhoven University of Technology (TU/e). Artificial Organs © 2011, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Myocardial Drug Distribution Generated from Local Epicardial Application: Potential Impact of Cardiac Capillary Perfusion in a Swine Model Using Epinephrine

PubMed Central

Maslov, Mikhail Y.; Edelman, Elazer R.; Pezone, Matthew J.; Wei, Abraham E.; Wakim, Matthew G.; Murray, Michael R.; Tsukada, Hisashi; Gerogiannis, Iraklis S.; Groothuis, Adam; Lovich, Mark A.

2014-01-01

Prior studies in small mammals have shown that local epicardial application of inotropic compounds drives myocardial contractility without systemic side effects. Myocardial capillary blood flow, however, may be more significant in larger species than in small animals. We hypothesized that bulk perfusion in capillary beds of the large mammalian heart enhances drug distribution after local release, but also clears more drug from the tissue target than in small animals. Epicardial (EC) drug releasing systems were used to apply epinephrine to the anterior surface of the left heart of swine in either point-sourced or distributed configurations. Following local application or intravenous (IV) infusion at the same dose rates, hemodynamic responses, epinephrine levels in the coronary sinus and systemic circulation, and drug deposition across the ventricular wall, around the circumference and down the axis, were measured. EC delivery via point-source release generated transmural epinephrine gradients directly beneath the site of application extending into the middle third of the myocardial thickness. Gradients in drug deposition were also observed down the length of the heart and around the circumference toward the lateral wall, but not the interventricular septum. These gradients extended further than might be predicted from simple diffusion. The circumferential distribution following local epinephrine delivery from a distributed source to the entire anterior wall drove drug toward the inferior wall, further than with point-source release, but again, not to the septum. This augmented drug distribution away from the release source, down the axis of the left ventricle, and selectively towards the left heart follows the direction of capillary perfusion away from the anterior descending and circumflex arteries, suggesting a role for the coronary circulation in determining local drug deposition and clearance. The dominant role of the coronary vasculature is further suggested by the elevated drug levels in the coronary sinus effluent. Indeed, plasma levels, hemodynamic responses, and myocardial deposition remote from the point of release were similar following local EC or IV delivery. Therefore, the coronary vasculature shapes the pharmacokinetics of local myocardial delivery of small catecholamine drugs in large animal models. Optimal design of epicardial drug delivery systems must consider the underlying bulk capillary perfusion currents within the tissue to deliver drug to tissue targets and may favor therapeutic molecules with better potential retention in myocardial tissue. PMID:25234821

Early accelerated senescence of circulating endothelial progenitor cells in premature coronary artery disease patients in a developing country - a case control study.

PubMed

Vemparala, Kranthi; Roy, Ambuj; Bahl, Vinay Kumar; Prabhakaran, Dorairaj; Nath, Neera; Sinha, Subrata; Nandi, Pradipta; Pandey, Ravindra Mohan; Reddy, Kolli Srinath; Manhapra, Ajay; Lakshmy, Ramakrishnan

2013-11-19

The decreased number and senescence of circulating endothelial progenitor cells (EPCs) are considered markers of vascular senescence associated with aging, atherosclerosis, and coronary artery disease (CAD) in elderly. In this study, we explore the role of vascular senescence in premature CAD (PCAD) in a developing country by comparing the numerical status and senescence of circulating EPCs in PCAD patients to controls. EPCs were measured by flow cytometry in 57 patients with angiographically documented CAD, and 57 controls without evidence of CAD, recruited from random patients ≤ 50 years of age at All India Institute of Medical Sciences. EPC senescence as determined by telomere length (EPC-TL) and telomerase activity (EPC-TA) was studied by real time polymerase chain reaction (q PCR) and PCR- ELISA respectively. The number of EPCs (0.18% Vs. 0.039% of total WBCs, p < 0.0001), and EPC-TL (3.83 Vs. 5.10 kb/genome, p = 0.009) were markedly lower in PCAD patients compared to controls. These differences persisted after adjustment for age, sex, BMI, smoking and medications. EPC-TA was reduced in PCAD patients, but was statistically significant only after adjustment for confounding factors (1.81 Vs. 2.20 IU/cell, unadjusted p = 0.057, adjusted p = 0.044). We observed an association between increased vascular cell senescence with PCAD in a sample of young patients from India. This suggests that early accelerated vascular cell senescence may play an important mechanistic role in CAD epidemic in developing countries like India where PCAD burden is markedly higher compared to developed countries.

A servo-controlled canine model of stable severe ischemic left ventricular failure.

PubMed

Wagner, Richard L; Hood, William B; Howland, Peter A

2009-12-01

Reversible left ventricular failure was produced in conscious dogs by compromise of the coronary circulation. In animals with prior left anterior descending coronary artery occlusion, mean left atrial pressure (LAP) was incorporated into an automatic feedback control system used to inflate a balloon cuff on the circumflex (Cfx) coronary artery. The system could produce stable increases in LAP to 15-20 mm Hg. The dominating system transfer function was the ratio of LAP to balloon volume (BV), which was characterized by a fixed delay (5 s), with LAP/BV = (8e(-jomegatau ))/(0.02 + jomega). The system was stabilized by a phase lead network to reduce oscillations of LAP. A total of seven experiments were conducted in three dogs, and testing of inotropic agents was possible in three experiments under stable conditions with the pump off after an hour or more of operation. Problems encountered were 0.003-0.008 Hz oscillations in LAP in three experiments, which could usually be controlled by reducing the system gain. Late stage ventricular fibrillation occurred in all three animals, but defibrillation was easily accomplished after deflating the Cfx balloon. This system produces reversible left ventricular failure solely due to ischemia, thus closely simulating clinical heart failure due to coronary insufficiency.

The anatomy and development of normal and abnormal coronary arteries.

PubMed

Spicer, Diane E; Henderson, Deborah J; Chaudhry, Bill; Mohun, Timothy J; Anderson, Robert H

2015-12-01

At present, there is significant interest in the morphology of the coronary arteries, not least due to the increasingly well-recognised association between anomalous origin of the arteries and sudden cardiac death. Much has also been learnt over the last decade regarding the embryology of the arteries. In this review, therefore, we provide a brief introduction into the recent findings regarding their development. In particular, we emphasise that new evidence, derived using the developing murine heart, points to the arterial stems growing out from the adjacent sinuses of the aortic root, rather than the arteries growing in, as is currently assumed. As we show, the concept of outgrowth provides an excellent explanation for several of the abnormal arrangements encountered in the clinical setting. Before summarising these abnormal features, we draw attention to the need to describe the heart in an attitudinally appropriate manner, following the basic rule of human anatomy, rather than describing the cardiac components with the heart in the "Valentine" orientation. We then show how the major abnormalities involving the coronary arteries in humans can be summarised in terms of abnormal origin from the pulmonary circulation, abnormal aortic origin, or fistulous communications between the coronary arteries and the cardiac cavities. In the case of abnormal aortic origin, we highlight those malformations known to be associated with sudden cardiac death.

Lasting monitoring of immune state in patients with coronary atherosclerosis

NASA Astrophysics Data System (ADS)

Malinova, Lidia I.; Denisova, Tatyana P.; Tuchin, Valery V.

2007-02-01

Immune state monitoring is an expensive, invasive and sometimes difficult necessity in patients with different disorders. Immune reaction dynamics study in patients with coronary atherosclerosis provides one of the leading components to complication development, clinical course prognosis and treatment and rehabilitation tactics. We've chosen intravenous glucose injection as metabolic irritant in the following four groups of patients: men with proved coronary atherosclerosis (CA), non insulin dependent diabetes mellitus (NIDDM), men hereditary burden by CA and NIDDM and practically healthy persons with longlivers in generation. Immune state parameters such as quantity of leukocytes and lymphocytes, circulating immune complexes levels, serum immunoglobulin levels, HLA antigen markers were studied at 0, 30 and 60 minutes during glucose loading. To obtain continues time function of studied parameters received data were approximated by polynomials of high degree with after going first derivatives. Time functions analyze elucidate principally different dynamics studied parameters in all chosen groups of patients, which couldn't be obtained from discontinuous data compare. Leukocyte and lymphocyte levels dynamics correlated HLA antigen markers in all studied groups. Analytical estimation of immune state in patients with coronary atherosclerosis shows the functional "margin of safety" of immune system state under glucose disturbance. Proposed method of analytical estimation also can be used in immune system monitoring in other groups of patients.

Rapid transcapillary exchange and unidirectional neuronal uptake of noradrenaline in the perfused rabbit heart.

PubMed Central

Mann, G E; Yudilevich, D L

1984-01-01

Capillary permeability and cellular uptake of noradrenaline by the isolated artificially perfused rabbit heart was measured using rapid (less than 30 s) single-circulation tracer-dilution techniques. In a single coronary circulation capillary extractions of L-[14C]noradrenaline and D-[3H]mannitol (extracellular reference) relative to an intravascular marker, 125I-labelled albumin, were similar and above 60%. The 'apparent' volume of distribution for tracer noradrenaline was 2.5-fold larger than that measured for D-mannitol (0.32 ml g-1) suggesting cellular uptake of the amine. Unidirectional noradrenaline uptake was estimated by directly comparing coronary sinus dilution profiles of L-[3H]noradrenaline and D-[14C]mannitol. Michaelis-Menten saturation kinetics based on a single-entry system were determined (Km = 2.8 +/- 1.5 microM, Vmax = 2.1 +/- 0.5 nmol min-1 g-1, n = 4) by perfusing hearts with varying concentrations of L-noradrenaline (1-10 microM). Various known inhibitors of noradrenaline uptake were investigated to determine whether uptake was mediated by neuronal (uptake1) and/or extraneuronal (uptake2) mechanisms. Desipramine (5 microM), imipramine (5 microM) and metaraminol (2 microM) resulted in a 66-94% inhibition of noradrenaline influx. In comparison, the steroids, 17 beta-oestradiol (1 microM) and corticosterone (10 microM), and the noradrenaline metabolite normetanephrine (5 microM) caused virtually no inhibitory effects. The beta-adrenergic antagonist propranolol (5 microM) was also relatively ineffective. These results together with the kinetic constants estimated suggest that the rapid noradrenaline uptake reflects transport into adrenergic neurones lying in the coronary interstitium. The high resolution of this paired-tracer dilution technique has permitted a 'non-invasive' study of neuronal uptake mechanisms and its application may be of clinical value. PMID:6425496

Cardiac Ischemia Reperfusion Injury Following Instillation of 20 nm Citrate-capped Nanosilver

DOE Office of Scientific and Technical Information (OSTI.GOV)

Becak DP, Holland NA; Shannahan, Jonathan H.

Background: Silver nanoparticles (AgNP) have garnered much interest due to their antimicrobial properties, becoming one of the most utilized nano scale materials. However, any potential evocable cardiovascular injury associated with exposure has not been previously reported. We have previously demonstrated expansion of myocardial infarction after intratracheal (IT) instillation of other nanomaterials. We hypothesized that pulmonary exposure to Ag core AgNP induces persistent increase in circulating cytokines, expansion of cardiac ischemia-reperfusion (I/R) injury and associated with altered coronary vessel reactivity. Methods: Male Sprague-Dawley rats were exposed to 200 µg of 20 nm citrate capped Ag core AgNP, or a citrate vehiclemore » intratracheally (IT). One and 7 days following IT instillation lungs were evaluated for inflammation and silver presence, serum was analyzed for concentrations of selected cytokines, and cardiac I/R injury and coronary artery reactivity was assessed. Results: AgNP instillation resulted in modest pulmonary injury with detection of silver in lung tissue and infiltrating cells, elevation of serum cytokines: G-CSF, MIP-1α, IL-1β, IL-2, IL-6, IL-13, IL-10, IL-18, IL-17, TNFα, and RANTES, expansion of I/R injury and depression of the coronary vessel reactivity at 1 day post IT compared to vehicle treated rats. Seven days post IT instillation was associated with persistent detection of silver in lungs, elevation in cytokines: IL-2, IL-13, and TNFα and expansion of I/R injury. Conclusions: Based on these data, IT instillation of AgNP increases circulating levels of several cytokines, which may contribute to persistent expansion of I/R injury possibly through an impaired vascular responsiveness.« less

Adiponectin has a pivotal role in the cardioprotective effect of CP-3(iv), a selective CD36 azapeptide ligand, after transient coronary artery occlusion in mice.

PubMed

Huynh, David N; Bessi, Valérie L; Ménard, Liliane; Piquereau, Jérôme; Proulx, Caroline; Febbraio, Maria; Lubell, William D; Carpentier, André C; Burelle, Yan; Ong, Huy; Marleau, Sylvie

2018-02-01

CD36 is a multiligand receptor involved in lipid metabolism. We investigated the mechanisms underlying the cardioprotective effect of CP-3(iv), an azapeptide belonging to a new class of selective CD36 ligands. The role of CP-3(iv) in mediating cardioprotection was investigated because CD36 signaling leads to activation of peroxisome proliferator-activated receptor-γ, a transcriptional regulator of adiponectin. CP-3(iv) pretreatment reduced infarct size by 54% and preserved hemodynamics in C57BL/6 mice subjected to 30 min coronary ligation and reperfusion but had no effect in CD36-deficient mice. The effects of CP-3(iv) were associated with an increase in circulating adiponectin levels, epididymal fat adiponectin gene expression, and adiponectin transcriptional regulators ( Pparg, Cebpb, Sirt1) after 6 h of reperfusion. Reduced myocardial oxidative stress and apoptosis were observed along with an increase in expression of myocardial adiponectin target proteins, including cyclooxygenase-2, phospho-AMPK, and phospho-Akt. Moreover, CP-3(iv) increased myocardial performance in isolated hearts, whereas blockade of adiponectin with an anti-adiponectin antibody abrogated it. CP-3(iv) exerts cardioprotection against myocardial ischemia and reperfusion (MI/R) injury and dysfunction, at least in part, by increasing circulating and myocardial adiponectin levels. Hence, both paracrine and endocrine effects of adiponectin may contribute to reduced reactive oxygen species generation and apoptosis after MI/R, in a CD36-dependent manner.-Huynh, D. N., Bessi, V. L., Ménard, L., Piquereau, J., Proulx, C., Febbraio, M., Lubell, W. D., Carpentier, A. C., Burelle, Y., Ong, H., Marleau, S. Adiponectin has a pivotal role in the cardioprotective effect of CP-3(iv), a selective CD36 azapeptide ligand, after transient coronary artery occlusion in mice.

Endothelial microparticle-mediated transfer of MicroRNA-126 promotes vascular endothelial cell repair via SPRED1 and is abrogated in glucose-damaged endothelial microparticles.

PubMed

Jansen, Felix; Yang, Xiaoyan; Hoelscher, Marion; Cattelan, Arianna; Schmitz, Theresa; Proebsting, Sebastian; Wenzel, Daniela; Vosen, Sarah; Franklin, Bernardo S; Fleischmann, Bernd K; Nickenig, Georg; Werner, Nikos

2013-10-29

Repair of the endothelium after vascular injury is crucial for preserving endothelial integrity and preventing the development of vascular disease. The underlying mechanisms of endothelial cell repair are largely unknown. We sought to investigate whether endothelial microparticles (EMPs), released from apoptotic endothelial cells (ECs), influence EC repair. Systemic treatment of mice with EMPs after electric denudation of the endothelium accelerated reendothelialization in vivo. In vitro experiments revealed that EMP uptake in ECs promotes EC migration and proliferation, both critical steps in endothelial repair. To dissect the underlying mechanisms, Taqman microRNA array was performed, and microRNA (miR)-126 was identified as the predominantly expressed miR in EMPs. The following experiments demonstrated that miR-126 was transported into recipient human coronary artery endothelial cells by EMPs and functionally regulated the target protein sprouty-related, EVH1 domain-containing protein 1 (SPRED1). Knockdown of miR-126 in EMPs abrogated EMP-mediated effects on human coronary artery endothelial cell migration and proliferation in vitro and reendothelialization in vivo. Interestingly, after simulating diabetic conditions, EMPs derived from glucose-treated ECs contained significantly lower amounts of miR-126 and showed reduced endothelial repair capacity in vitro and in vivo. Finally, expression analysis of miR-126 in circulating microparticles from 176 patients with stable coronary artery disease with and without diabetes mellitus revealed a significantly reduced miR-126 expression in circulating microparticles from diabetic patients. Endothelial microparticles promote vascular endothelial repair by delivering functional miR-126 into recipient cells. In pathological hyperglycemic conditions, EMP-mediated miR-126-induced EC repair is altered.

Circulating autoantibodies against neuroblastoma suppressor of tumorigenicity 1 (NBL1): A potential biomarker for coronary artery disease in patients with obstructive sleep apnea

PubMed Central

Matsumura, Takuma; Kinoshita, Taku; Sakurai, Yoriko; Yahaba, Misuzu; Tsushima, Kenji; Sakao, Seiichiro; Nagashima, Kengo; Ozaki, Toshinori; Kobayashi, Yoshio; Hiwasa, Takaki; Tatsumi, Koichiro

2018-01-01

Objective Although severe obstructive sleep apnea (OSA) is an important risk factor for atherosclerosis-related diseases including coronary artery disease (CAD), there is no reliable biomarker of CAD risks in patients with OSA. This study aimed to test our hypothesis that circulating autoantibodies against neuroblastoma suppressor of tumorigenicity 1 (NBL1-Abs) are associated with the prevalence of CAD in patients with OSA. Methods Eighty-two adults diagnosed with OSA by polysomnography, 96 patients with a diagnosis of acute coronary syndrome (ACS) and 64 healthy volunteers (HVs) were consecutively enrolled. Serum samples were collected from patients with OSA at diagnostic polysomnography and from patients with ACS at disease onset. Serum NBL1-Ab level was measured by amplified luminescence proximity homogeneous assay and its association with clinical variables related to atherosclerosis was evaluated. Results NBL1-Ab level was significantly elevated in patients with both OSA and ACS compared with HVs. Subgroup analyses showed that NBL1-Ab level was markedly higher in patients with severe OSA and OSA patients with a history of CAD. Weak associations were observed between NBL1-Ab level and apnea-hypopnea index, age, mean SpO2 and arousal index, whereas significantly higher NBL1-Ab levels were observed in OSA patients with a history of CAD than in those without a history of CAD. Sensitivity analysis using a logistic regression model also demonstrated that increased NBL1-Ab levels were associated with the previous history of CAD in patients with OSA. Conclusions Elevated NBL1-Ab levels may be associated with the prevalence of CAD in patients with OSA, which needs to be confirmed further. PMID:29596467

Cancer in heart disease patients: what are the limitations in the treatment strategy?

PubMed

Mistiaen, Wilhelm P

2013-07-01

Cardiovascular disease and cancer are leading causes of morbidity and mortality, and can both be present in one patient. In patients with simultaneous disease, the most threatening disease should be treated first. This is usually heart disease, but this can pose specific problems. If percutaneous coronary intervention is preferred, bleeding and thrombotic tendencies have to be taken into account in the subsequent treatment of the malignancy. With coronary artery bypass grafting, the advantages and disadvantages of one- or two-stage procedures, and the use of extracorporeal circulation have to be balanced. Development of heart disease after treatment of malignancy could be due to radiotherapy and chemotherapy. The effects of these cancer treatments have to be taken into account for the treatment options of the heart disease and the postoperative prognosis.

Circulating CD4+CXCR5+ T cells contribute to proinflammatory responses in multiple ways in coronary artery disease.

PubMed

Ding, Ru; Gao, Wenwu; He, Zhiqing; Wu, Feng; Chu, Yang; Wu, Jie; Ma, Lan; Liang, Chun

2017-11-01

Coronary artery disease (CAD) is a common subtype of cardiovascular disease. The major contributing event is atherosclerosis, which is a progressive inflammatory condition resulting in the thickening of the arterial wall and the formation of atheromatous plaques. Recent evidence suggests that circulating CD4 + CXCR5 + T cells can contribute to inflammatory reactions. In this study, the frequency, phenotype, and function of circulating CD4 + CXCR5 + T cells in CAD patients were examined. Data showed that circulating CD4 + CXCR5 + T cells in CAD patients were enriched with a PD-1 + CCR7 - subset, which was previously identified as the most potent in B cell help. The CD4 + CXCR5 + T cells in CAD patients also secreted significantly higher levels of IFN-γ, IL-17A, and IL-21 than those from healthy controls. Depleting the PD-1 + population significantly reduced the cytokine secretion. Interestingly, the CD4 + CXCR5 + PD-1 - T cells significantly upregulated PD-1 following anti-CD3/CD28 or SEB stimulation. CD4 + CXCR5 + T cells from CAD patients also demonstrated more potent capacity to stimulate B cell inflammation than those from healthy individuals. The phosphorylation of STAT1 and STAT3 were significantly higher in B cells incubated with CD4 + CXCR5 + T cells from CAD than controls. The IL-6 and IFN-γ expression were also significantly higher in B cells incubated with CD4 + CXCR5 + T cells from CAD. Together, this study demonstrated that CAD patients presented a highly activated CD4 + CXCR5 + T cell subset that could contribute to proinflammatory responses in multiple ways. The possibility of using CD4 + CXCR5 + T cells as a therapeutic target should therefore be examined in CAD patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparing microvascular alterations during minimal extracorporeal circulation and conventional cardiopulmonary bypass in coronary artery bypass graft surgery: a prospective, randomized study.

PubMed

Donndorf, Peter; Kühn, Franziska; Vollmar, Brigitte; Rösner, Jan; Liebold, Andreas; Gierer, Philipp; Steinhoff, Gustav; Kaminski, Alexander

2012-09-01

Minimal extracorporeal circulation (MECC) has been introduced in coronary artery bypass graft (CABG) surgery, offering clinical benefits owing to reduced hemodilution and no blood-air interface. Yet, the effects of MECC on the intraoperative microvascular perfusion in comparison with conventional extracorporeal circulation (CECC) have not been studied so far. The current study aimed to analyze alterations in microvascular perfusion at 4 predefined time points (T1-T4) during on-pump CABG using orthogonal polarization spectral imaging. Forty patients were randomized for being operated on with either MECC or CECC. Changes in functional capillary density (FCD), blood flow velocity, and vessel diameter were analyzed by a blinded investigator. After start of extracorporeal circulation (ECC) and aortic crossclamping (T2), both groups showed a significant drop of FCD, with a significantly higher FCD in the MECC group (206.8 ± 33.6 cm/cm² in CECC group versus 217.8 ± 35.3 cm/cm² in MECC group; P = .034). In the late phase of the ECC (T3), FCD in the MECC group was already recovered, whereas FCD in the CECC group was still significantly depressed (223.1 ± 35.6 cm/cm² in MECC group; P = .100 vs T1; 211.1 ± 36.9 cm/cm² in CECC group; P = .017 vs T1). After termination of ECC (T4), FCD recovered in both groups to baseline. Blood flow velocity tended to be higher in the MECC group, with a significant intergroup difference after aortic crossclamping (T2). Orthogonal polarization spectral imaging data reveal an impairment of microvascular perfusion during on-pump CABG. Changes in FCD indicate a faster recovery of the microvascular perfusion in MECC during the reperfusion period. Beneficial recovery of microvascular organ perfusion could partly explain the perioperative advantages reported for MECC. Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

The effect of angiotensin-2 receptor blocker valsartan on circulating level of endothelial progenitor cells in diabetic patients with asymptomatic coronary artery disease.

PubMed

Berezin, Alexander E; Kremzer, Alexander A; Martovitskaya, Yulia V; Samura, Tatyana A

2015-01-01

Decreased circulating endothelial progenitor cells (EPCs) are considered as strong and robust biomarkers for the prediction of cardiovascular outcomes in diabetic populations. The perspectives for modulating EPCs levels in T2DM with known coronary artery disease (CAD) with different drugs, affected mechanisms of improving mobilization of EPCs from tissue, are not still understood. To evaluate an effect of angiotensin-2 receptor blocker valsartan on circulating level of EPCs in diabetic patients with asymptomatic CAD. The study population was structured retrospectively after determining the CAD by contrast-enhanced spiral computed tomography angiography in 126 asymptomatic subjects. All subjects were distributed into two cohorts depending on daily doses of valsartan given. Low (80-160 mg daily orally) and high doses (240-320 mg daily orally) of valsartan were used and they were adjusted depending on achieving BP level less than 140/80 mmHg. The change from baseline in CD34(+) subset cells (frequencies and absolute values) was not significantly different between treatment cohorts. We found a significant increase of circulating level of CD14(+)CD309(+) cells in two patient cohorts. But more prominent change of CD14(+)CD309(+) cells was verified in subjects who were given valsartan in high daily doses when compared with persons who were included into cohort with low daily doses of the drug (1.96% versus 2.59%, respectively; P<0.05). Therefore, both frequencies and absolute values in CD14(+)CD309(+)Tie(2+) were increased significantly in patients who were treated with high doses of valsartan only. We found positive influence of angiotensin-2 receptor blocker valsartan in escalation doses on bone marrow-derived EPCs phenotyped as CD14(+)CD309(+) and CD14(+)CD309(+)Tie(2+) in T2DM patients with known asymptomatic CAD. Copyright © 2014 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Quantitative evaluation of collateral circulation in patients with previous myocardial infarction: relation to myocardial ischemia, angiographic appearance and functional improvement of myocardium.

PubMed

Vukcevic, Vladan; Beleslin, Branko; Ostojic, Miodrag; Stojkovic, Sinisa; Stankovic, Goran; Nedeljkovic, Milan; Orlic, Dejan; Djordjevic-Dikic, Ana; Stepanovic, Jelena; Giga, Vojislav; Arandjelovic, Aleksandra; Dikic, Miodrag; Kostic, Jelena; Nedeljkovic, Ivana; Nedeljkovic-Beleslin, Biljana; Saponjski, Jovica

2009-04-01

Evaluation of coronary pressures during angioplasty may functionally quantify collateral circulation. The aim of the study was to evaluate the relation between the amount of collateral circulation and development of myocardial ischemia during balloon occlusion, anatomic degree of collaterals, and functional improvement of myocardium. Study population consisted of 31 pts (mean age 53 +/- 7 years; 25 male) with previous myocardial infarction and significant one-vessel stenosis undergoing angioplasty. Collateral circulation was calculated as the ratio between distal coronary pressure during balloon occlusion (P(w)) and aortic pressure (P(a)). Angiographic appearance of collaterals was evaluated by Rentrop classification. Patients were evaluated by echo for functional improvement of myocardium in the follow-up period. Mean P(w)/P(a) was 0.24 +/- 0.10 (range of 0.07-0.51). Rentrop grade 0 of collaterals was present in 16 patients (52%), grade 1 in11 patients (35%), and grade 2 in 4 patients (13%). A mild correlation between angio and hemodynamic evaluation of collaterals was observed (r = 0.38, P = 0.035). In patients without ECG changes during angioplasty (21 pts, 68%), P(w)/P(a) was significantly higher in comparison to patients with ECG changes (0.28 +/- 0.09 vs. 0.15 +/- 0.06, P < 0.001; area under the curve 0.93). In patients with myocardial functional improvement during follow-up (21 pts, 68%), P(w)/P(a) was significantly higher than in the patients without echo improvement (0.26 +/- 0.10 vs. 0.18 +/- 0.08, P = 0.035). The amount of recruitable collaterals is not negligible even in the patients with no angio visible collaterals. Low values of P(w)/P(a) are associated with ECG changes during balloon occlusion. Higher P(w)/P(a) was associated with better functional improvement of myocardium.

Dynamic micro- and macrovascular remodeling in coronary circulation of obese Ossabaw pigs with metabolic syndrome

PubMed Central

Katz, Paige S.; Kelly, Amy P.; Galantowicz, Maarten L.; Cismowski, Mary J.; West, T. Aaron; Neeb, Zachary P.; Berwick, Zachary C.; Goodwill, Adam G.; Alloosh, Mouhamad; Tune, Johnathan D.; Sturek, Michael; Lucchesi, Pamela A.

2012-01-01

Previous studies from our laboratory showed that coronary arterioles from type 2 diabetic mice undergo inward hypertrophic remodeling and reduced stiffness. The aim of the current study was to determine if coronary resistance microvessels (CRMs) in Ossabaw swine with metabolic syndrome (MetS) undergo remodeling distinct from coronary conduit arteries. Male Ossabaw swine were fed normal (n = 7, Lean) or hypercaloric high-fat (n = 7, MetS) diets for 6 mo, and then CRMs were isolated and mounted on a pressure myograph. CRMs isolated from MetS swine exhibited decreased luminal diameters (126 ± 5 and 105 ± 9 μm in Lean and MetS, respectively, P < 0.05) with thicker walls (18 ± 3 and 31 ± 3 μm in Lean and MetS, respectively, P < 0.05), which doubled the wall-to-lumen ratio (14 ± 2 and 30 ± 2 in Lean and MetS, respectively, P < 0.01). Incremental modulus of elasticity (IME) and beta stiffness index (BSI) were reduced in CRMs isolated from MetS pigs (IME: 3.6 × 106 ± 0.7 × 106 and 1.1 × 106 ± 0.2 × 106 dyn/cm2 in Lean and MetS, respectively, P < 0.001; BSI: 10.3 ± 0.4 and 7.3 ± 1.8 in Lean and MetS, respectively, P < 0.001). BSI in the left anterior descending coronary artery was augmented in pigs with MetS. Structural changes were associated with capillary rarefaction, decreased hyperemic-to-basal coronary flow velocity ratio, and augmented myogenic tone. MetS CRMs showed a reduced collagen-to-elastin ratio, while immunostaining for the receptor for advanced glycation end products was selectively increased in the left anterior descending coronary artery. These data suggest that MetS causes hypertrophic inward remodeling of CRMs and capillary rarefaction, which contribute to decreased coronary flow and myocardial ischemia. Moreover, our data demonstrate novel differential remodeling between coronary micro- and macrovessels in a clinically relevant model of MetS. PMID:22837170

System analysis of the dynamic response of the coronary circulation to a sudden change in heart rate.

PubMed

Dankelman, J; Stassen, H G; Spaan, J A

1990-03-01

In this study the response of driving pressure/flow ration on an abrupt change in heart rate was analysed. The difference between the response obtained with constant pressure and constant flow perfusion was also studied. The responses show a fast initial reversed phase followed by a slow phase caused by regulation. To test whether the initial phase could be the result of mechanical changes in the coronary circulation, a model for regulation was extended by the addition of four different mechanical models originating from the literature. These extended models were able to explain the fast initial phase. However, the mechanical model consisting of an intramyocardial compliance (C = 0.08 ml mm Hg-1 100 g-1) with a variable venous resistance, and the model consisting of a waterfall and a small compliance (C = 0.007 ml mm Hg-1 100g-1) both explained these responses best. The analysis showed that there is no direct relationship between rate of change of vascular tone and rate of change of pressure/flow ratio. However, on the basis of the two extended models, it can be predicted that the half-time for the response of regulation to be complete is about 9s with constant pressure perfusion and 15 s with constant flow perfusion.

Transcoronary sinus delivery of autologous bone marrow and angiogenesis in pig models with myocardial injury

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vicario, J.; Piva, J.; Pierini, A.

2002-06-01

Purpose: The aim of the investigation is to study myocardial injury on pig model with two objectives: (1) feasibility of stimulating angiogenesis with fresh autologous bone marrow; (2) administration of the same fresh autologous bone marrow via coronary sinus with transitory occlusion. Methods: A controlled study was done in animal model with three phases, in a study group of 12 pigs (bone marrow administration) as well as in control group of 4 pigs (saline administration). Phase 1--production of coronary stenosis and myocardial injury; Phase 2--two weeks later, administration of bone marrow through coronary sinus with 10 min occlusion in themore » study group and saline solution in the control group. Phase 3--two weeks later, histological staining with hematoxylin-eosin and inmunohistochemical staining with monoclonal antibody for smooth muscle {alpha}-actin were conducted on both study and control groups. Results: The percentage of angionenesis observed in the study group was 91% and 0% in control group. Counting of positive actin in affected and control areas showed statistically significant differences in relation to both groups: study group (1.37 vs. 0.79) and control group (0.47 vs. 0.51). The percentage of mononuclear immature cells observed in the myocardium in the study group was 25% and in the control group was 0%. There was no increment in the coronary collateral circulation when comparing coronary angiography. Conclusions: Autologous bone marrow in animal model with experimental myocardial injury enhances angiogenesis, as well as vessels with smooth muscles. The transitory occlusion of the coronary sinus might be an effective way to administer cells as those from the bone marrow.« less

Analysis of Plasma Albumin, Vitamin D, and Apolipoproteins A and B as Predictive Coronary Risk Biomarkers in the REGICOR Study.

PubMed

Vázquez-Oliva, Gabriel; Zamora, Alberto; Ramos, Rafel; Subirana, Isaac; Grau, María; Dégano, Irene R; Muñoz, Daniel; Fitó, Montserrat; Elosua, Roberto; Marrugat, Jaume

2018-05-12

New biomarkers could improve the predictive capacity of classic risk functions. The aims of this study were to determine the association between circulating levels of apolipoprotein A1 (apoA1), apolipoprotein B (apoB), albumin, and 25-OH-vitamin D and coronary events and to analyze whether these biomarkers improve the predictive capacity of the Framingham-REGICOR risk function. A case-cohort study was designed. From an initial cohort of 5404 individuals aged 35 to 74 years with a 5-year follow-up, all the participants who had a coronary event (n = 117) and a random group of the cohort (subcohort; n = 667) were selected. Finally, 105 cases and 651 individuals representative of the cohort with an available biological sample were included. The events of interest were angina, fatal and nonfatal myocardial infarction and coronary deaths. Case participants were older, had a higher proportion of men and cardiovascular risk factors, and showed higher levels of apoB and lower levels of apoA1, apoA1/apoB ratio, 25-OH-vitamin D and albumin than the subcohort. In multivariate analyses, plasma albumin concentration was the only biomarker independently associated with coronary events (HR, 0.73; P = .002). The inclusion of albumin in the risk function properly reclassified a significant proportion of individuals, especially in the intermediate risk group (net reclassification improvement, 32.3; P = .048). Plasma albumin levels are inversely associated with coronary risk and improve the predictive capacity of classic risk functions. Copyright © 2018 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Effects of coil closure of patent ductus arteriosus on left anterior descending coronary artery blood flow using transthoracic Doppler echocardiography.

PubMed

Harada, Kenji; Toyono, Manotomo; Tamura, Masamichi

2004-06-01

Transthoracic Doppler echocardiography provides noninvasive measurements of coronary blood flow in the left anterior descending coronary artery (LAD). This method has the potential to show the effects of acute changes in loading conditions on blood flow. Coil closure of patent ductus arteriosus (PDA) is a model of acute changes in blood pressure and left ventricular (LV) preload that influences coronary blood flow. We applied this technique to assess the coronary blood flow changes for patients with PDA before and immediately after PDA coil closure. We examined 9 patients (1.8 +/- 1.1 years) with simple PDA and 8 age-matched healthy children. LV dimensions and LV mass were measured. Maximum peak flow velocity and flow volume in the LAD were measured. Pulmonary to systemic flow ratios (Qp/Qs) were obtained by cardiac catheterization. After PDA coil closure, LV end-diastolic dimension decreased, and systolic and diastolic blood pressures increased significantly. The maximum peak flow velocity, LAD flow volume, and the ratio of LAD flow volume to LV mass increased significantly. The changes in maximum peak flow velocity and the ratio of LAD flow volume to LV mass (F/M) correlated positively with the changes in diastolic pressure and Qp/Qs. In 5 patients who had Qp/Qs > 1.5, the mean F/M was significantly lower compared with control subjects, but they increased to normal values after coil closure of PDA. PDA coil closure increases diastolic pressure and decreases Qp/Qs, resulting in improvement of myocardial perfusion. These findings provide new insights into the relationship between cardiac function and coronary circulation in pediatric patients with heart diseases associated with PDA.

Prognostic value of coronary collaterals in patients with acute coronary syndromes.

PubMed

Kurtul, Alparslan; Ozturk, Selcuk

2017-08-01

The presence of good coronary collateral circulation (CCC) can protect and preserve myocardium from ischemia, increase myocardial contractility, and reduce adverse clinical events. However, its impact on mortality is still a topic of debate, particularly in acute coronary syndrome (ACS). The aim of this study was to investigate the association of CCC with cardiac risk factors and in-hospital mortality in patients hospitalized with a diagnosis of ACS. The study population included 2286 patients with ACS who underwent coronary angiography and were found to have at least 90% significant lesion in at least one major coronary artery. The CCC was graded according to the Rentrop classification. The patients were classified into a poor CCC group (Rentrop grades 0-1, n=1859) or a good CCC group (Rentrop grades 2-3, n=427). Patients with good CCC had more high-risk patient characteristics such as older age, higher rate of Killip class of at least 2 at admission, lower left ventricular ejection fraction, and impaired renal functions compared with the patients with poor CCC. In multivariate analysis, the presence of good CCC [odds ratio (OR): 2.000; 95% confidence interval: 1.116-3.585; P=0.020], left ventricular ejection fraction less than 40% (OR: 2.381; P=0.003), Killip class of at least 2 at admission (OR: 3.609; P<0.001), age of at least 65 years (OR: 2.975; P=0.003), and hemoglobin (OR: 0.797; P=0.003) were independent predictors of in-hospital mortality. In contrast to previous studies, our study did not confirm a beneficial role of good CCC in patients with ACS; the presence of good CCC was even independently associated with increased in-hospital mortality in the multivariate analysis.

Cardiomyocyte-specific desmin rescue of desmin null cardiomyopathy excludes vascular involvement.

PubMed

Weisleder, Noah; Soumaka, Elisavet; Abbasi, Shahrzad; Taegtmeyer, Heinrich; Capetanaki, Yassemi

2004-01-01

Mice deficient in desmin, the muscle-specific member of the intermediate filament gene family, display defects in all muscle types and particularly in the myocardium. Desmin null hearts develop cardiomyocyte hypertrophy and dilated cardiomyopathy (DCM) characterized by extensive myocyte cell death, calcific fibrosis and multiple ultrastructural defects. Several lines of evidence suggest impaired vascular function in desmin null animals. To determine whether altered capillary function or an intrinsic cardiomyocyte defect is responsible for desmin null DCM, transgenic mice were generated to rescue desmin expression specifically to cardiomyocytes. Desmin rescue mice display a wild-type cardiac phenotype with no fibrosis or calcification in the myocardium and normalization of coronary flow. Cardiomyocyte ultrastructure is also restored to normal. Markers of hypertrophy upregulated in desmin null hearts return to wild-type levels in desmin rescue mice. Working hearts were perfused to assess coronary flow and cardiac power. Restoration of a wild-type cardiac phenotype in a desmin null background by expression of desmin specifically within cardiomyocyte indicates that defects in the desmin null heart are due to an intrinsic cardiomyocytes defect rather than compromised coronary circulation.

Intracoronary and retrograde coronary venous myocardial delivery of adipose-derived stem cells in swine infarction lead to transient myocardial trapping with predominant pulmonary redistribution.

PubMed

Hong, Soon Jun; Hou, Dongming; Brinton, Todd J; Johnstone, Brian; Feng, Dongni; Rogers, Pamela; Fearon, William F; Yock, Paul; March, Keith L

2014-01-01

To examine the comparative fate of adipose-derived stem cells (ASCs) as well as their impact on coronary microcirculation following either retrograde coronary venous (RCV) or arterial delivery. Local delivery of ASCs to the heart has been proposed as a practical approach to limiting the extent of myocardial infarction. Mouse models of mesenchymal stem cell effects on the heart have also demonstrated significant benefits from systemic (intravenous) delivery, prompting a question about the advantage of local delivery. There has been no study addressing the extent of myocardial vs. systemic disposition of ASCs in large animal models following local delivery to the myocardium. In an initial experiment, dose-dependent effects of ASC delivery on coronary circulation in normal swine were evaluated to establish a tolerable ASC dosing range for intracoronary (IC) delivery. In a set of subsequent experiments, an anterior acute myocardial infarction (AMI) was created by balloon occlusion of the proximal left anterior descending (LAD) artery, followed by either IC or RCV infusion of 10(7) (111)Indium-labeled autologous ASCs 6 days following AMI. Indices of microcirculatory resistance (IMR) and coronary flow reserve (CFR) were measured before sacrifices to collect tissues for analysis at 1 or 24 hr after cell delivery. IC delivery of porcine ASCs to normal myocardium was well tolerated up to a cumulative dose of 14 × 10(6) cells (approximately 0.5 × 10(6) cells/kg). There was evidence suggesting microcirculatory trapping of ASC: at unit doses of 50 × 10(6) ASCs, IMR and CFR were found to be persistently altered in the target LAD distribution at 7 days following delivery, whereas at 10 × 10(6) ASCs, only CFR was altered. In the context of recent MI, a significantly higher percentage of ASCs was retained at 1 hr with IC delivery compared with RCV delivery (57.2 ± 12.7% vs. 17.9 ± 1.6%, P = 0.037) but this initial difference was not apparent at 24 hr (22.6 ± 5.5% vs. 18.7 ± 8.6%; P = 0.722). In both approaches, most ASC redistributed to the pulmonary circulation by 24 hr postdelivery. There were no significant differences in CFR or IMR following ASC delivery to infarcted tissue by either route. Selective intravascular delivery of ASC by coronary arterial and venous routes leads to similarly limited myocardial cell retention with predominant redistribution of cells to the lungs. IC arterial delivery of ASC leads to only transiently greater myocardial retention, which is accompanied by obstruction of normal regions of coronary microcirculation at higher doses. The predominant intrapulmonary localization of cells following local delivery via both methods prompts the notion that systemic delivery of ASC might provide similarly beneficial outcomes while avoiding risks of inadvertent microcirculatory compromise. Copyright © 2012 Wiley Periodicals, Inc.

Hemodynamic directed cardiopulmonary resuscitation improves short-term survival from ventricular fibrillation cardiac arrest.

PubMed

Friess, Stuart H; Sutton, Robert M; Bhalala, Utpal; Maltese, Matthew R; Naim, Maryam Y; Bratinov, George; Weiland, Theodore R; Garuccio, Mia; Nadkarni, Vinay M; Becker, Lance B; Berg, Robert A

2013-12-01

During cardiopulmonary resuscitation, adequate coronary perfusion pressure is essential for establishing return of spontaneous circulation. Current American Heart Association guidelines recommend standardized interval administration of epinephrine for patients in cardiac arrest. The objective of this study was to compare short-term survival using a hemodynamic directed resuscitation strategy versus chest compression depth-directed cardiopulmonary resuscitation in a porcine model of cardiac arrest. Randomized interventional study. Preclinical animal laboratory. Twenty-four 3-month-old female swine. After 7 minutes of ventricular fibrillation, pigs were randomized to receive one of three resuscitation strategies: 1) Hemodynamic directed care (coronary perfusion pressure-20): chest compressions with depth titrated to a target systolic blood pressure of 100 mm Hg and titration of vasopressors to maintain coronary perfusion pressure greater than 20 mm Hg; 2) Depth 33 mm: target chest compression depth of 33 mm with standard American Heart Association epinephrine dosing; or 3) Depth 51 mm: target chest compression depth of 51 mm with standard American Heart Association epinephrine dosing. All animals received manual cardiopulmonary resuscitation guided by audiovisual feedback for 10 minutes before first shock. Forty-five-minute survival was higher in the coronary perfusion pressure-20 group (8 of 8) compared to depth 33 mm (1 of 8) or depth 51 mm (3 of 8) groups; p equals to 0.002. Coronary perfusion pressures were higher in the coronary perfusion pressure-20 group compared to depth 33 mm (p = 0.004) and depth 51 mm (p = 0.006) and in survivors compared to nonsurvivors (p < 0.01). Total epinephrine dosing and defibrillation attempts were not different. Hemodynamic directed resuscitation targeting coronary perfusion pressures greater than 20 mm Hg during 10 minutes of cardiopulmonary resuscitation for ventricular fibrillation cardiac arrest improves short-term survival, when compared to resuscitation with depth of compressions guided to 33 mm or 51 mm and standard American Heart Association vasopressor dosing.

Clinical study of the hypothesis of endogenous collateral wind on acute coronary syndrome: a review.

PubMed

Wang, Xian; Zhang, Cong; Yang, Ran; Zhu, Haiyan; Zhao, Huaibing; Li, Xiaoming

2014-01-01

Acute Coronary Syndrome (ACS), is a serious threat to people's health, and life, and in recent years, the incidence has increased yearly. This study was to propose the hypothesis of "endogenous collateral wind" based on the patho-mechanism of thrombogenesis complicated by ruptured plaque on ACS, and the theory of traditional Chinese medicine. Through successful coronary angiography (CAG), and intravascular ultrasound (IVUS), patients with coronary artery disease were made the differential diagnosis such as blood stasis, blood stasis due to phlegm obstruction, and endogenous collateral wind. The levels of plasma inflammatory marker were measured to study on the characteristics of "endogenous collateral wind". Luo heng dripping pills with promoting blood circulation to expel wind-evil, and remove wetness were made based on the hypothesis of "endogenous collateral wind" on ACS. Patients with unstable angina were randomly divided into 3, groups based on therapeutic methods: conventional therapy group, Luo Heng dripping pills group and Tongxinluo caps. Differences among groups were compared. There were great changes in number and degree of coronary arteriostenosis confirmed by CAG, the types of ACC/AHA lesion and Levin lesion confirmed by CAG, remodeling index, positive or negative remodeling percentage measured by IVUS, the plasma levels of plasma inflammatory marker measured by ELLSA in the patients with endogenous collateral wind, compared with patients with blood stasis and blood stasis due to phlegm obstruction. The total effective rate of improved angina in Luo Heng dripping pills group was significantly higher than those in other two groups. The levels of plasma inflammatory marker were significantly lower in Luo Heng dripping pills group. There were some pathological basis which were found about the hypothesis of "endogenous collateral wind" on acute coronary syndrome. It provided evidences for patients with coronary artery disease treated by medicines with expelling evil-wind, and removing wetness.

The adenosine A2A receptor — Myocardial protectant and coronary target in endotoxemia

PubMed Central

Reichelt, Melissa E.; Ashton, Kevin J.; Tan, Xing Lin; Mustafa, S. Jamal; Ledent, Catherine; Delbridge, Lea M.D.; Hofmann, Polly A.; Headrick, John P.; Morrison, R. Ray

2013-01-01

Background Cardiac injury and dysfunction are contributors to disease progression and mortality in sepsis. This study evaluated the cardiovascular role of intrinsic A2A adenosine receptor (A2AAR) activity during lipopolysaccharide (LPS)-induced inflammation. Methods We assessed the impact of 24 h of LPS challenge (20 mg/kg, IP) on cardiac injury, coronary function and inflammatory mediator levels in Wild-Type (WT) mice and mice lacking functional A2AARs (A2AAR KO). Results Cardiac injury was evident in LPS-treated WTs, with ∼7-fold elevation in serum cardiac troponin I (cTnI), and significant ventricular and coronary dysfunction. Absence of A2AARs increased LPS-provoked cTnI release at 24 h by 3-fold without additional demise of contraction function. Importantly, A2AAR deletion per se emulated detrimental effects of LPS on coronary function, and LPS was without effect in coronary vessels lacking A2AARs. Effects of A2AAR KO were independent of major shifts in circulating C-reactive protein (CRP) and haptoglobin. Cytokine responses were largely insensitive to A2AAR deletion; substantial LPS-induced elevations (up to 100-fold) in IFN-γ and IL-10 were unaltered in A2AAR KO mice, as were levels of IL-4 and TNF-α. However, late elevations in IL-2 and IL-5 were differentially modulated by A2AAR KO (IL-2 reduced, IL-5 increased). Data demonstrate that in the context of LPS-triggered cardiac and coronary injury, A2AAR activity protects myocardial viability without modifying contractile dysfunction, and selectively modulates cytokine (IL-2, IL-5) release. A2AARs also appear to be targeted by LPS in the coronary vasculature. Conclusions These experimental data suggest that preservation of A2AAR functionality might provide therapeutic benefit in human sepsis. PMID:22192288

Endothelial Progenitor Cells (EPC) Count by Multicolor Flow Cytometry in Healthy Individuals and Diabetes Mellitus (DM) Patients.

PubMed

Falay, Mesude; Aktas, Server

2016-11-01

The present study aimed to determine circulating Endothelial Progenitor Cell (EPC) counts by multicolor flow cytometry in healthy individuals and diabetic subjects by means of forming an analysis procedure using a combination of monoclonal antibodies (moAbs), which would correctly detect the circulating EPC count. The circulating EPC count was detected in 40 healthy individuals (20 Female, 20 Male; age range: 26 - 50 years) and 30 Diabetes Mellitus (DM) patients (15 Female, 15 Male; age range: 42 - 55) by multicolor flow cytometry (FCM) in a single-tube panel consisting of 5 CD45/CD31/CD34/CD309/ SYTO® and 16 monoclonal antibodies. Circulating EPC count was 11.33 (7.89 - 15.25) cells/µL in the healthy control group and 4.80 (0.70 - 10.85) cells/µL in the DM group. EPC counts were significantly lower in DM cases that developed coronary artery disease (53.3%) as compared to those that did not (p < 0.001). In the present study, we describe a method that identifies circulating EPC counts by multicolor flow cytometry in a single tube and determines the circulating EPC count in healthy individuals. This is the first study conducted on EPC count in Turkish population. We think that the EPC count found in the present study will be a guide for future studies.

Computational analysis of hybrid Norwood circulation with distal aortic arch obstruction and reverse Blalock-Taussig shunt.

PubMed

Ceballos, Andres; Argueta-Morales, I Ricardo; Divo, Eduardo; Osorio, Ruben; Caldarone, Christopher A; Kassab, Alain J; Decampli, William M

2012-11-01

The hemodynamics characteristics of the hybrid Norwood (HN) procedure differ from those of the conventional Norwood and are not fully understood. We present a multiscale model of HN circulation to understand local hemodynamics and effects of aortic arch stenosis and a reverse Blalock-Taussig shunt (RBTS) on coronary and carotid perfusion. Four 3-dimensional models of four HN anatomic variants were developed, with and without 90% distal preductal arch stenosis and with and without a 4-mm RBTS. A lumped parameter model of the circulation was coupled to a local 3-dimensional computational fluid dynamics model. Outputs from the lumped parameter model provided waveform boundary conditions for the computational fluid dynamics model. A 90% distal arch stenosis reduced pressure and net flow-rate through the coronary and carotid arteries by 30%. Addition of the RBTS completely restored pressure and flow rate to baseline in these vessels. Zones of flow stagnation, flow reversal, and recirculation in the presence of stenosis were rendered more orderly by addition of the RBTS. In the absence of stenosis, presence of the shunt resulted in extensive zones of disturbed flow within the RBTS and arch. We found that a 4-mm × 21-mm RBTS completely compensated for the effects of a 90% discrete stenosis of the distal aortic arch in the HN. Placed preventatively, the RBTS and arch displayed zones with thrombogenic potential showing recirculation and stagnation that persist for a substantial fraction of the cardiac cycle, indicating that anticoagulation should be considered with a prophylactic RBTS. Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Genome-wide association study for circulating levels of PAI-1 provides novel insights into its regulation

PubMed Central

Huang, Jie; Sabater-Lleal, Maria; Asselbergs, Folkert W.; Tregouet, David; Shin, So-Youn; Ding, Jingzhong; Baumert, Jens; Oudot-Mellakh, Tiphaine; Folkersen, Lasse; Johnson, Andrew D.; Smith, Nicholas L.; Williams, Scott M.; Ikram, Mohammad A.; Kleber, Marcus E.; Becker, Diane M.; Truong, Vinh; Mychaleckyj, Josyf C.; Tang, Weihong; Yang, Qiong; Sennblad, Bengt; Moore, Jason H.; Williams, Frances M. K.; Dehghan, Abbas; Silbernagel, Günther; Schrijvers, Elisabeth M. C.; Smith, Shelly; Karakas, Mahir; Tofler, Geoffrey H.; Silveira, Angela; Navis, Gerjan J.; Lohman, Kurt; Chen, Ming-Huei; Peters, Annette; Goel, Anuj; Hopewell, Jemma C.; Chambers, John C.; Saleheen, Danish; Lundmark, Per; Psaty, Bruce M.; Strawbridge, Rona J.; Boehm, Bernhard O.; Carter, Angela M.; Meisinger, Christa; Peden, John F.; Bis, Joshua C.; McKnight, Barbara; Öhrvik, John; Taylor, Kent; Franzosi, Maria Grazia; Seedorf, Udo; Collins, Rory; Franco-Cereceda, Anders; Syvänen, Ann-Christine; Goodall, Alison H.; Yanek, Lisa R.; Cushman, Mary; Müller-Nurasyid, Martina; Folsom, Aaron R.; Basu, Saonli; Matijevic, Nena; van Gilst, Wiek H.; Kooner, Jaspal S.; Hofman, Albert; Danesh, John; Clarke, Robert; Meigs, James B.; Kathiresan, Sekar; Reilly, Muredach P.; Klopp, Norman; Harris, Tamara B.; Winkelmann, Bernhard R.; Grant, Peter J.; Hillege, Hans L.; Watkins, Hugh; Spector, Timothy D.; Becker, Lewis C.; Tracy, Russell P.; März, Winfried; Uitterlinden, Andre G.; Eriksson, Per; Cambien, Francois; Morange, Pierre-Emmanuel; Koenig, Wolfgang; Soranzo, Nicole; van der Harst, Pim; Liu, Yongmei

2012-01-01

We conducted a genome-wide association study to identify novel associations between genetic variants and circulating plasminogen activator inhibitor-1 (PAI-1) concentration, and examined functional implications of variants and genes that were discovered. A discovery meta-analysis was performed in 19 599 subjects, followed by replication analysis of genome-wide significant (P < 5 × 10−8) single nucleotide polymorphisms (SNPs) in 10 796 independent samples. We further examined associations with type 2 diabetes and coronary artery disease, assessed the functional significance of the SNPs for gene expression in human tissues, and conducted RNA-silencing experiments for one novel association. We confirmed the association of the 4G/5G proxy SNP rs2227631 in the promoter region of SERPINE1 (7q22.1) and discovered genome-wide significant associations at 3 additional loci: chromosome 7q22.1 close to SERPINE1 (rs6976053, discovery P = 3.4 × 10−10); chromosome 11p15.2 within ARNTL (rs6486122, discovery P = 3.0 × 10−8); and chromosome 3p25.2 within PPARG (rs11128603, discovery P = 2.9 × 10−8). Replication was achieved for the 7q22.1 and 11p15.2 loci. There was nominal association with type 2 diabetes and coronary artery disease at ARNTL (P < .05). Functional studies identified MUC3 as a candidate gene for the second association signal on 7q22.1. In summary, SNPs in SERPINE1 and ARNTL and an SNP associated with the expression of MUC3 were robustly associated with circulating levels of PAI-1. PMID:22990020

Regional Myocardial Blood Flow*

PubMed Central

Sullivan, Jay M.; Taylor, Warren J.; Elliott, William C.; Gorlin, Richard

1967-01-01

A method is described which measures the local effectiveness of the myocardial circulation, expressed as a clearance constant. Uniform clearance constants have been demonstrated in the normal canine and human myocardium. A distinct difference in clearance constants has been demonstrated between the normal canine myocardium and areas of naturally occurring disease. Heterogeneous clearance constants have been found in a majority of human subjects with coronary artery disease—the lowest rates being noted in areas of fibrous aneurysm. PMID:6036537

Quality of Cardiopulmonary Resuscitation When Directing the Area of maximal Compression by Transesophageal Echocardiography During Cardiac Arrest in Swine (Sus scrofa)

DTIC Science & Technology

2013-12-30

E7(/(3+21(180%(5 ,QFOXGHDUHDFRGH 18-02-2014 Final Mar 2012 - Jan 2014 Quality of cardiopulmonary resuscitation when directing the area of...1. Protocol Number: FWH20110158A 2. Type of Research: Animal Research 3. Title: Quality of cardiopulmonary resuscitation when directing...Compressions over the Left Ventricle During Cardiopulmonary Resuscitation Increases Coronary Perfusion Pressure and Return of Spontaneous Circulation

Influences of Nutrition and Physical Forces on Bone Structure/Function Properties

DTIC Science & Technology

2005-10-01

weeks old. The mice were humanely euthanized at 20 wks of age, the left femur and eighth caudal vertebrae were dissected free of soft tissue and...regime, mice were humanely euthanized and the right tibiae were removed and dissected free of soft tissue and frozen in LRS. The right tibiae...Feld MS (1998) Histopathology of human coronary artherosclerosis by quantifying its chemical composition with Raman spectr- oscopy. Circulation 97:878

Analysis of the influence of respiratory disorders observed in preoperative spirometry on the dynamics of early inflammatory response in patients undergoing isolated coronary artery bypass grafting

PubMed Central

Szylińska, Aleksandra; Listewnik, Mariusz J; Rotter, Iwona; Rył, Aleksandra; Biskupski, Andrzej; Brykczyński, Mirosław

2017-01-01

Background Preoperative spirometry provides measurable information about the occurrence of respiratory disorders. The aim of this study was to assess the association between preoperative spirometry abnormalities and the intensification of early inflammatory responses in patients following coronary artery bypass graft in extracorporeal circulation. Material and methods The study involved 810 patients (625 men and 185 women) aged 65.4±7.9 years who were awaiting isolated coronary artery bypass surgery. On the basis of spirometry performed on the day of admittance to the hospital, the patients were divided into three groups. Patients without respiratory problems constituted 78.8% of the entire group. Restricted breathing was revealed by spirometry in 14.9% and obstructive breathing in 6.3% of patients. Results Inter-group analysis showed statistically significant differences in C-reactive protein (CRP) between patients with restrictive spirometry abnormalities and patients without any pulmonary dysfunction. CRP concentrations differed before surgery (P=0.006) and on the second (P<0.001), fourth (P=0.005) and sixth days after surgery (P=0.029). There was a negative correlation between CRP levels and FEV1. Conclusion In our study, the most common pulmonary disorders in the coronary artery bypass graft patients were restrictive. Patients with abnormal spirometry results from restrictive respiratory disorders have an elevated level of generalized inflammatory response both before and after the isolated coronary artery bypass surgery. Therefore, this group of patients should be given special postoperative monitoring and, in particular, intensive respiratory rehabilitation immediately after reconstitution. PMID:28769557

Short intra-aortic balloon pump in a swine model of myocardial ischaemia: a proof-of-concept study.

PubMed

Gelsomino, Sandro; Lozekoot, Pieter W J; Lorusso, Roberto; de Jong, Monique M J; Parise, Orlando; Matteucci, Francesco; Lucà, Fabiana; La Meir, Mark; Gensini, Gian Franco; Maessen, Jos G

2016-03-01

This proof-of-concept study examined the haemodynamic performance as well as the coronary and visceral organ perfusion using a new short balloon for intra-aortic counterpulsation (IABP) in a swine model of myocardial ischaemia. Eighteen healthy pigs underwent 120-min ligation of the left anterior descending coronary artery followed by 6 h of reperfusion, and they were randomly assigned into 3 groups undergoing IABP implantation with a 35-ml short balloon (n = 6), a 40-ml short balloon (n = 6) or no IABP implantation (controls, n = 6). Haemodynamics, and visceral and coronary flows were measured at baseline (t0), at 2 h of ischaemia (t1) and every hour thereafter until 6 h of reperfusion (from tR1 to tR6), respectively. Mesenteric and renal flows increased significantly at tR1 only in the IABP groups (all, P < 0.001) and were significantly higher than controls throughout the reperfusion periods (P < 0.001). Coronary systolic and diastolic blood flows increased only at tR1 in the IABP groups (all, P < 0.001) but were higher than controls at tR1-tR6. The IABP was associated with enhanced haemodynamics compared with controls. No difference was detected using different balloon volumes (all, P > 0.05). The new short balloon significantly increased visceral flow, enhanced haemodynamics and improved coronary circulation during reperfusion following myocardial ischaemia in our experimental model. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Pathology of Human Coronary and Carotid Artery Atherosclerosis and Vascular Calcification in Diabetes Mellitus.

PubMed

Yahagi, Kazuyuki; Kolodgie, Frank D; Lutter, Christoph; Mori, Hiroyoshi; Romero, Maria E; Finn, Aloke V; Virmani, Renu

2017-02-01

The continuing increase in the prevalence of diabetes mellitus in the general population is predicted to result in a higher incidence of cardiovascular disease. Although the mechanisms of diabetes mellitus-associated progression of atherosclerosis are not fully understood, at clinical and pathological levels, there is an appreciation of increased disease burden and higher levels of arterial calcification in these subjects. Plaques within the coronary arteries of patients with diabetes mellitus generally exhibit larger necrotic cores and significantly greater inflammation consisting mainly of macrophages and T lymphocytes relative to patients without diabetes mellitus. Moreover, there is a higher incidence of healed plaque ruptures and positive remodeling in hearts from subjects with type 1 diabetes mellitus and type 2 diabetes mellitus, suggesting a more active atherogenic process. Lesion calcification in the coronary, carotid, and other arterial beds is also more extensive. Although the role of coronary artery calcification in identifying cardiovascular disease and predicting its outcome is undeniable, our understanding of how key hormonal and physiological alterations associated with diabetes mellitus such as insulin resistance and hyperglycemia influence the process of vascular calcification continues to grow. Important drivers of atherosclerotic calcification in diabetes mellitus include oxidative stress, endothelial dysfunction, alterations in mineral metabolism, increased inflammatory cytokine production, and release of osteoprogenitor cells from the marrow into the circulation. Our review will focus on the pathophysiology of type 1 diabetes mellitus- and type 2 diabetes mellitus-associated vascular disease with particular focus on coronary and carotid atherosclerotic calcification. © 2016 American Heart Association, Inc.

The roles of salusins in atherosclerosis and related cardiovascular diseases.

PubMed

Watanabe, Takuya; Sato, Kengo; Itoh, Fumiko; Iso, Yoshitaka; Nagashima, Masaharu; Hirano, Tsutomu; Shichiri, Masayoshi

2011-01-01

Human salusin-α and -β are related peptides of 28 and 20 amino acids, respectively, produced from the same precursor, prosalusin. Salusin-β exerts more potent mitogenic effects on human vascular smooth muscle cells (VSMCs) and fibroblasts than salusin-α. Human macrophage foam cell formation is significantly stimulated by salusin-β, but suppressed by salusin-α. Chronic salusin-β infusion into apolipoprotein E-knockout mice enhances atherosclerotic lesions, paralleling increases in foam cell formation and upregulation of scavenger receptors and of acyl-CoA:cholesterol acyltransferase-1 (ACAT1) in macrophages. In contrast, chronic salusin-α infusion reduces atherosclerotic lesions accompanied by significant suppression of foam cell formation owing to ACAT1 downregulation. Salusin-β is expressed in proliferative neointimal lesions of porcine coronary arteries after stenting. Salusin-α and -β immunoreactivity has been detected in human coronary atherosclerotic plaques, with dominance of salusin-β in macrophage foam cells, VSMCs, and fibroblasts. Serum salusin-α levels are markedly decreased in patients with angiographically proven coronary artery disease compared with patients with mild hypertension and healthy volunteers. Furthermore, among patients with acute coronary syndrome, serum salusin-α levels are decreased in accordance with the severity of coronary atherosclerotic lesions. These findings suggest that salusin-β may contribute to the pathogenesis of atherosclerosis. Decreased levels of salusin-α in circulating blood and vascular tissue are closely linked with human atherosclerosis. Therefore, salusin-α could be a candidate biomarker for atherosclerosis and may be therapeutically useful for prevention of atherosclerotic cardiovascular diseases. Copyright © 2011 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

Combined ECG, Echocardiographic, and Biomarker Criteria for Diagnosing Acute Myocardial Infarction in Out-of-Hospital Cardiac Arrest Patients.

PubMed

Lee, Sang-Eun; Uhm, Jae-Sun; Kim, Jong-Youn; Pak, Hui-Nam; Lee, Moon-Hyoung; Joung, Boyoung

2015-07-01

Acute coronary lesions commonly trigger out-of-hospital cardiac arrest (OHCA). However, the prevalence of coronary artery disease (CAD) in Asian patients with OHCA and whether electrocardiogram (ECG) and other findings might predict acute myocardial infarction (AMI) have not been fully elucidated. Of 284 consecutive resuscitated OHCA patients seen between January 2006 and July 2013, we enrolled 135 patients who had undergone coronary evaluation. ECGs, echocardiography, and biomarkers were compared between patients with or without CAD. We included 135 consecutive patients aged 54 years (interquartile range 45-65) with sustained return of spontaneous circulation after OHCA between 2006 and 2012. Sixty six (45%) patients had CAD. The initial rhythm was shockable and non-shockable in 110 (81%) and 25 (19%) patients, respectively. ST-segment elevation predicted CAD with 42% sensitivity, 87% specificity, and 65% accuracy. ST elevation and/or regional wall motion abnormality (RWMA) showed 68% sensitivity, 52% specificity, and 70% accuracy in the prediction of CAD. Finally, a combination of ST elevation and/or RWMA and/or troponin T elevation predicted CAD with 94% sensitivity, 17% specificity, and 55% accuracy. In patients with OHCA without obvious non-cardiac causes, selection for coronary angiogram based on the combined criterion could detect 94% of CADs. However, compared with ECG only criteria, the combined criterion failed to improve diagnostic accuracy with a lower specificity.

miRNA-197 and miRNA-223 Predict Cardiovascular Death in a Cohort of Patients with Symptomatic Coronary Artery Disease.

PubMed

Schulte, Christian; Molz, Simon; Appelbaum, Sebastian; Karakas, Mahir; Ojeda, Francisco; Lau, Denise M; Hartmann, Tim; Lackner, Karl J; Westermann, Dirk; Schnabel, Renate B; Blankenberg, Stefan; Zeller, Tanja

2015-01-01

Circulating microRNAs (miRNAs) have been described as potential diagnostic biomarkers in cardiovascular disease and in particular, coronary artery disease (CAD). Few studies were undertaken to perform analyses with regard to risk stratification of future cardiovascular events. miR-126, miR-197 and miR-223 are involved in endovascular inflammation and platelet activation and have been described as biomarkers in the diagnosis of CAD. They were identified in a prospective study in relation to future myocardial infarction. The aim of our study was to further evaluate the prognostic value of these miRNAs in a large prospective cohort of patients with documented CAD. Levels of miR-126, miR-197 and miR-223 were evaluated in serum samples of 873 CAD patients with respect to the endpoint cardiovascular death. miRNA quantification was performed using real time polymerase chain reaction (RT-qPCR). The median follow-up period was 4 years (IQR 2.78-5.04). The median age of all patients was 64 years (IQR 57-69) with 80.2% males. 38.9% of the patients presented with acute coronary syndrome (ACS), 61.1% were diagnosed with stable angina pectoris (SAP). Elevated levels of miRNA-197 and miRNA-223 reliably predicted future cardiovascular death in the overall group (miRNA-197: hazard ratio (HR) 1.77 per one standard deviation (SD) increase (95% confidence interval (CI) 1.20; 2.60), p = 0.004, C-index 0.78; miRNA-223: HR 2.23 per one SD increase (1.20; 4.14), p = 0.011, C-index 0.80). In ACS patients the prognostic power of both miRNAs was even higher (miRNA-197: HR 2.24 per one SD increase (1.25; 4.01), p = 0.006, C-index 0.89); miRA-223: HR 4.94 per one SD increase (1.42; 17.20), p = 0.012, C-index 0.89). Serum-derived circulating miRNA-197 and miRNA-223 were identified as predictors for cardiovascular death in a large patient cohort with CAD. These results reinforce the assumption that circulating miRNAs are promising biomarkers with prognostic value with respect to future cardiovascular events.

Plasma urate concentration and risk of coronary heart disease: a Mendelian randomisation analysis.

PubMed

White, Jon; Sofat, Reecha; Hemani, Gibran; Shah, Tina; Engmann, Jorgen; Dale, Caroline; Shah, Sonia; Kruger, Felix A; Giambartolomei, Claudia; Swerdlow, Daniel I; Palmer, Tom; McLachlan, Stela; Langenberg, Claudia; Zabaneh, Delilah; Lovering, Ruth; Cavadino, Alana; Jefferis, Barbara; Finan, Chris; Wong, Andrew; Amuzu, Antoinette; Ong, Ken; Gaunt, Tom R; Warren, Helen; Davies, Teri-Louise; Drenos, Fotios; Cooper, Jackie; Ebrahim, Shah; Lawlor, Debbie A; Talmud, Philippa J; Humphries, Steve E; Power, Christine; Hypponen, Elina; Richards, Marcus; Hardy, Rebecca; Kuh, Diana; Wareham, Nicholas; Ben-Shlomo, Yoav; Day, Ian N; Whincup, Peter; Morris, Richard; Strachan, Mark W J; Price, Jacqueline; Kumari, Meena; Kivimaki, Mika; Plagnol, Vincent; Whittaker, John C; Smith, George Davey; Dudbridge, Frank; Casas, Juan P; Holmes, Michael V; Hingorani, Aroon D

2016-04-01

Increased circulating plasma urate concentration is associated with an increased risk of coronary heart disease, but the extent of any causative effect of urate on risk of coronary heart disease is still unclear. In this study, we aimed to clarify any causal role of urate on coronary heart disease risk using Mendelian randomisation analysis. We first did a fixed-effects meta-analysis of the observational association of plasma urate and risk of coronary heart disease. We then used a conventional Mendelian randomisation approach to investigate the causal relevance using a genetic instrument based on 31 urate-associated single nucleotide polymorphisms (SNPs). To account for potential pleiotropic associations of certain SNPs with risk factors other than urate, we additionally did both a multivariable Mendelian randomisation analysis, in which the genetic associations of SNPs with systolic and diastolic blood pressure, HDL cholesterol, and triglycerides were included as covariates, and an Egger Mendelian randomisation (MR-Egger) analysis to estimate a causal effect accounting for unmeasured pleiotropy. In the meta-analysis of 17 prospective observational studies (166 486 individuals; 9784 coronary heart disease events) a 1 SD higher urate concentration was associated with an odds ratio (OR) for coronary heart disease of 1·07 (95% CI 1·04-1·10). The corresponding OR estimates from the conventional, multivariable adjusted, and Egger Mendelian randomisation analysis (58 studies; 198 598 individuals; 65 877 events) were 1·18 (95% CI 1·08-1·29), 1·10 (1·00-1·22), and 1·05 (0·92-1·20), respectively, per 1 SD increment in plasma urate. Conventional and multivariate Mendelian randomisation analysis implicates a causal role for urate in the development of coronary heart disease, but these estimates might be inflated by hidden pleiotropy. Egger Mendelian randomisation analysis, which accounts for pleiotropy but has less statistical power, suggests there might be no causal effect. These results might help investigators to determine the priority of trials of urate lowering for the prevention of coronary heart disease compared with other potential interventions. UK National Institute for Health Research, British Heart Foundation, and UK Medical Research Council. Copyright © 2016 White et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.

Plasma urate concentration and risk of coronary heart disease: a Mendelian randomisation analysis

PubMed Central

White, Jon; Sofat, Reecha; Hemani, Gibran; Shah, Tina; Engmann, Jorgen; Dale, Caroline; Shah, Sonia; Kruger, Felix A; Giambartolomei, Claudia; Swerdlow, Daniel I; Palmer, Tom; McLachlan, Stela; Langenberg, Claudia; Zabaneh, Delilah; Lovering, Ruth; Cavadino, Alana; Jefferis, Barbara; Finan, Chris; Wong, Andrew; Amuzu, Antoinette; Ong, Ken; Gaunt, Tom R; Warren, Helen; Davies, Teri-Louise; Drenos, Fotios; Cooper, Jackie; Ebrahim, Shah; Lawlor, Debbie A; Talmud, Philippa J; Humphries, Steve E; Power, Christine; Hypponen, Elina; Richards, Marcus; Hardy, Rebecca; Kuh, Diana; Wareham, Nicholas; Ben-Shlomo, Yoav; Day, Ian N; Whincup, Peter; Morris, Richard; Strachan, Mark W J; Price, Jacqueline; Kumari, Meena; Kivimaki, Mika; Plagnol, Vincent; Whittaker, John C; Smith, George Davey; Dudbridge, Frank; Casas, Juan P; Holmes, Michael V; Hingorani, Aroon D

2016-01-01

Summary Background Increased circulating plasma urate concentration is associated with an increased risk of coronary heart disease, but the extent of any causative effect of urate on risk of coronary heart disease is still unclear. In this study, we aimed to clarify any causal role of urate on coronary heart disease risk using Mendelian randomisation analysis. Methods We first did a fixed-effects meta-analysis of the observational association of plasma urate and risk of coronary heart disease. We then used a conventional Mendelian randomisation approach to investigate the causal relevance using a genetic instrument based on 31 urate-associated single nucleotide polymorphisms (SNPs). To account for potential pleiotropic associations of certain SNPs with risk factors other than urate, we additionally did both a multivariable Mendelian randomisation analysis, in which the genetic associations of SNPs with systolic and diastolic blood pressure, HDL cholesterol, and triglycerides were included as covariates, and an Egger Mendelian randomisation (MR-Egger) analysis to estimate a causal effect accounting for unmeasured pleiotropy. Findings In the meta-analysis of 17 prospective observational studies (166 486 individuals; 9784 coronary heart disease events) a 1 SD higher urate concentration was associated with an odds ratio (OR) for coronary heart disease of 1·07 (95% CI 1·04–1·10). The corresponding OR estimates from the conventional, multivariable adjusted, and Egger Mendelian randomisation analysis (58 studies; 198 598 individuals; 65 877 events) were 1·18 (95% CI 1·08–1·29), 1·10 (1·00–1·22), and 1·05 (0·92–1·20), respectively, per 1 SD increment in plasma urate. Interpretation Conventional and multivariate Mendelian randomisation analysis implicates a causal role for urate in the development of coronary heart disease, but these estimates might be inflated by hidden pleiotropy. Egger Mendelian randomisation analysis, which accounts for pleiotropy but has less statistical power, suggests there might be no causal effect. These results might help investigators to determine the priority of trials of urate lowering for the prevention of coronary heart disease compared with other potential interventions. Funding UK National Institute for Health Research, British Heart Foundation, and UK Medical Research Council. PMID:26781229

Asymmetric Dimethylarginine versus Proton Pump Inhibitors Usage in Patients with Stable Coronary Artery Disease: A Cross-Sectional Study.

PubMed

Kruszelnicka, Olga; Świerszcz, Jolanta; Bednarek, Jacek; Chyrchel, Bernadeta; Surdacki, Andrzej; Nessler, Jadwiga

2016-04-15

A recent experimental study suggested that proton pump inhibitors (PPI), widely used to prevent gastroduodenal complications of dual antiplatelet therapy, may increase the accumulation of the endogenous nitric oxide synthesis antagonist asymmetric dimethylarginine (ADMA), an adverse outcome predictor. Our aim was to assess the effect of PPI usage on circulating ADMA in coronary artery disease (CAD). Plasma ADMA levels were compared according to PPI use for ≥1 month prior to admission in 128 previously described non-diabetic men with stable CAD who were free of heart failure or other coexistent diseases. Patients on PPI tended to be older and with insignificantly lower estimated glomerular filtration rate (GFR). PPI use was not associated with any effect on plasma ADMA (0.51 ± 0.11 (SD) vs. 0.50 ± 0.10 µmol/L for those with PPI (n = 53) and without PPI (n = 75), respectively; p = 0.7). Additionally, plasma ADMA did not differ between PPI users and non-users stratified by a history of current smoking, CAD severity or extent. The adjustment for patients' age and GFR did not substantially change the results. Thus, PPI usage does not appear to affect circulating ADMA in non-diabetic men with stable CAD. Whether novel mechanisms of adverse PPI effects on the vasculature can be translated into clinical conditions, requires further studies.

Intraoperative IR imaging in the cardiac operating room

NASA Astrophysics Data System (ADS)

Szabo, Tamas; Fazekas, Levente; Horkay, Ferenc; Geller, Laslu; Gyongy, Tibor; Juhasz-Nagy, Alexander

1999-07-01

The high blood flow rate and the considerable metabolic activity render the myocardium a possible candidate for IR imaging. The study was aimed to test cardiothermography in evaluating arterial bypass graft patency and in assessing myocardial protection during open-heart surgery. Ten patients underwent arterial bypass grafting. Thermograms were obtained immediately before and after opening the grafts. As the bypasses were opened in hypothermia the warmer blood coming from the extracorporeal circulation readily delineated graft and coronary anatomy. By the end of the 5 min observation period, the revascularized area exhibited a temperature increase of 5.9 +/- 0.7 degrees C. The affectivity of antegrade cardioplegia was monitored in 38 patients undergoing either valve implantations or aorto- coronary bypass surgery. Thermographic imags were taken after sternotomy, before aortic cross-clamping and after administrating the 4 degrees C cardioplegic solution. Most of the patients displayed adequate myocardial cooling, moreover the bypass-group exhibited a more profound temperature-decrease. In conclusion, cardiothermography can visualize arterial grafts, recipient coronaries and collaterals seconds after opening by bypass, thus it properly evaluated arterial bypass graft patency. The obtained images could easily be analyzed for qualitative flow- and quantitative temperature changes. Myocardial protection could also be safely assessed with thermography.

Hemodynamic Measurements for the Selection of Patients With Renal Artery Stenosis: A Systematic Review.

PubMed

van Brussel, Peter M; van de Hoef, Tim P; de Winter, Robbert J; Vogt, Liffert; van den Born, Bert-Jan

2017-05-22

Interventions targeting renal artery stenoses have been shown to lower blood pressure and preserve renal function. In recent studies, the efficacy of catheter-based percutaneous transluminal renal angioplasty with stent placement has been called into question. In the identification of functional coronary lesions, hyperemic measurements have earned a place in daily practice for clinical decision making, allowing discrimination between solitary coronary lesions and diffuse microvascular disease. Next to differences in clinical characteristics, the selection of renal arteries suitable for intervention is currently on the basis of anatomic grading of the stenosis by angiography rather than functional assessment under hyperemia. It is conceivable that, like the coronary circulation, functional measurements may better predict therapeutic efficacy of percutaneous transluminal renal angioplasty with stent placement. In this systematic review, the authors evaluate the available clinical evidence on the optimal hyperemic agents to induce intrarenal hyperemia, their association with anatomic grading, and their predictive value for treatment effects. In addition, the potential value of combined pressure and flow measurements to discriminate macrovascular from microvascular disease is discussed. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Is the metabolic syndrome a useful clinical concept in dogs? A review of the evidence.

PubMed

Verkest, Kurt R

2014-01-01

The metabolic syndrome is a set of risk factors for the development of type 2 diabetes, atherosclerosis, coronary heart disease and stroke in human beings. The term has recently been applied to dogs that exhibit components of the human metabolic syndrome, specifically visceral obesity, hypercholesterolaemia, hypertriglyceridaemia, hypertension and fasting hyperglycaemia. Obese dogs, like obese humans, are known to develop resistance to the glucose-lowering effects of insulin, and develop increased circulating concentrations of triglycerides, cholesterol and blood pressure. Unlike humans, however, obese dogs do not develop fasting hyperglycaemia or atherogenic hyperlipidaemia. Importantly, there is no evidence that dogs develop type 2 diabetes. Atherosclerosis, coronary heart disease and stroke are rare and not known to be associated with obesity in dogs. On the basis of current knowledge, the use of the term 'metabolic syndrome' in dogs does not appear to have merit. Copyright © 2013 Elsevier Ltd. All rights reserved.

Regional myocardial shape and dimensions of the working isolated canine left ventricle

NASA Technical Reports Server (NTRS)

Ritman, E.; Tsuiki, K.; Donald, D.; Wood, E. H.

1975-01-01

Angiographic experiments were performed on isolated canine left ventricle preparations using donor dog to supply blood to the coronary circulation via a rotary pump to control coronary flow. The angiographic record was transferred from video tape to video disk for detailed uninterrupted sequential analysis at a frequency of 60 fields/sec. It is shown that the use of a biplane X-ray technique and a metabolically supported isolated canine left ventricle preparation provides an angiographically ideal means of measuring the mechanical dynamics of the myocardium while the intact left ventricular myocardial structure and electrical activation pattern retain most of the in situ ventricular characteristics. In particular, biplane X-ray angiography of the left ventricle can provide estimates of total ventricular function such as ejection fraction, stroke volume, and myocardial mass correct to within 15% under the angiographically ideal conditions of the preparation.

Closed-loop controller for chest compressions based on coronary perfusion pressure: a computer simulation study.

PubMed

Wang, Chunfei; Zhang, Guang; Wu, Taihu; Zhan, Ningbo; Wang, Yaling

2016-03-01

High-quality cardiopulmonary resuscitation contributes to cardiac arrest survival. The traditional chest compression (CC) standard, which neglects individual differences, uses unified standards for compression depth and compression rate in practice. In this study, an effective and personalized CC method for automatic mechanical compression devices is provided. We rebuild Charles F. Babbs' human circulation model with a coronary perfusion pressure (CPP) simulation module and propose a closed-loop controller based on a fuzzy control algorithm for CCs, which adjusts the CC depth according to the CPP. Compared with a traditional proportion-integration-differentiation (PID) controller, the performance of the fuzzy controller is evaluated in computer simulation studies. The simulation results demonstrate that the fuzzy closed-loop controller results in shorter regulation time, fewer oscillations and smaller overshoot than traditional PID controllers and outperforms the traditional PID controller for CPP regulation and maintenance.

Elevated Adiponectin Antibody Levels in Sera of Patients with Atherosclerosis-Related Coronary Artery Disease, Cerebral Infarction and Diabetes Mellitus

PubMed Central

Hiwasa, Takaki; Zhang, Xiao-Meng; Kimura, Risa; Ohno, Mikiko; Chen, Po-Min; Nishi, Eiichiro; Ono, Koh; Kimura, Takeshi; Kamitsukasa, Ikuo; Wada, Takeshi; Aotsuka, Akiyo; Mine, Seiichiro; Takizawa, Hirotaka; Kashiwado, Koichi; Takemoto, Minoru; Kobayashi, Kazuki; Kawamura, Harukiyo; Ishibashi, Ryoichi; Yokote, Koutaro; Nakamura, Rika; Tomiyoshi, Go; Shinmen, Natsuko; Kuroda, Hideyuki

2016-01-01

Adiponectin secreted from the adipocytes plays pleiotropic, anti-atherosclerotic roles, such as enhancement of insulin secretion and an increase in energy expenditure. The measurement of levels of circulating adiponectin is useful to evaluate the progression of atherosclerosis-related diseases, such as coronary artery disease (CAD), cerebral infarction (CI) and diabetes mellitus (DM). We examined the serum antibody levels against recombinant adiponectin protein via the amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) method. The results revealed that the antibody levels were significantly higher in patients with CAD, CI and type 2 DM, than in healthy donors. Receiver operating curve analysis showed that the sensitivity was in a range of 41–48% for CAD, CI and DM. Thus, the serum anti-adiponectin antibody levels could be a common marker for atherosclerosis-related diseases. PMID:28936256

Complex of vitamins and antioxidants protects low-density lipoproteins in blood plasma from free radical oxidation and activates antioxidants enzymes in erythrocytes from patients with coronary heart disease.

PubMed

Konovalova, G G; Lankin, V Z; Tikhaze, A K; Nezhdanova, I B; Lisina, M O; Kukharchuk, V V

2003-08-01

We studied the effect of a complex containing antioxidant vitamins C and E, provitamin A, and antioxidant element selenium on the contents of primary (lipid peroxides) and secondary products (malonic dialdehyde) of free radical lipid oxidation in low-density lipoproteins isolated from the plasma of patients with coronary heart disease and hypercholesterolemia by means of preparative ultracentrifugation. Activity of key antioxidant enzymes in the blood was measured during treatment with the antioxidant preparation. Combination treatment with antioxidant vitamins and antioxidant element selenium sharply decreased the contents of primary and secondary free radical oxidation products in circulating low-density lipoproteins and increased activity of antioxidant enzymes in erythrocytes. Activities of superoxide dismutase and selenium-containing glutathione peroxidase increased 1 and 2 months after the start of therapy, respectively.

A retrospective comparative study of minimally invasive extracorporeal circulation versus conventional extracorporeal circulation in emergency coronary artery bypass surgery patients: a single surgeon analysis.

PubMed

Rufa, Magdalena; Schubel, Jens; Ulrich, Christian; Schaarschmidt, Jan; Tiliscan, Catalin; Bauer, Adrian; Hausmann, Harald

2015-07-01

At the moment, the main application of minimally invasive extracorporeal circulation (MiECC) is reserved for elective cardiac operations such as coronary artery bypass grafting (CABG) and/or aortic valve replacement. The purpose of this study was to compare the outcome of emergency CABG operations using either MiECC or conventional extracorporeal circulation (CECC) in patients requiring emergency CABG with regard to the perioperative course and the occurrence of major adverse cardiac and cerebral events (MACCE). We analysed the emergency CABG operations performed by a single surgeon, between January 2007 and July 2013, in order to exclude the differences in surgical technique. During this period, 187 emergency CABG patients (113 MiECC vs 74 CECC) were investigated retrospectively with respect to the following parameters: in-hospital mortality, MACCE, postoperative hospital stay and perioperative transfusion rate. The mean logistic European System for Cardiac Operative Risk Evaluation was higher in the CECC group (MiECC 12.1 ± 16 vs CECC 15.0 ± 20.8, P = 0.15) and the number of bypass grafts per patient was similar in both groups (MiECC 2.94 vs CECC 2.93). There was no significant difference in the postoperative hospital stay or in major postoperative complications. The in-hospital mortality was higher in the CECC group 6.8% versus MiECC 4.4% (P = 0.48). The perioperative transfusion rate was lower with MiECC compared with CECC (MiECC 2.6 ± 3.2 vs CECC 3.8 ± 4.2, P = 0.025 units of blood per patient). In our opinion, the use of MiECC in urgent CABG procedures is safe, feasible and shows no disadvantages compared with the use of CECC. Emergency operations using the MiECC system showed a significantly lower blood transfusion rate and better results concerning the unadjusted in-hospital mortality. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

[Clinical research of minimal extracorporeal circulation in perioperative blood conservation of coronary artery bypass graft].

PubMed

Liu, Yan; Cui, Hu-jun; Tao, Liang; Chen, Xu-fa

2011-04-01

To analyze the clinical effect of minimal extracorporeal circulation (MECC) in blood conservation perioperatively coronary artery bypass graft (CABG). The data of 120 cases received simple CABG since August 2006 to October 2009 was analyzed retrospectively. All the patients were divided to three groups according to the mode of circulation support in-operation: MECC, conventional extracorporeal circulation (cECC) or off-pump, 40 cases in each group. Jostra MECC system with normal temperature was used in MECC group, and common membrane oxygenator with moderate hypo-temperature was used in cECC group. Collect the data of coagulation and the blood cytological examination perioperatively, the draining volume during the first 24 h after operation, and consumption of blood products perioperatively. Standard and logistic EuroSCORE were higher in MECC group than the others (P < 0.01). The operative time and the number of distal anastomosis of off-pump group were less than MECC and cECC groups (P < 0.05), while no difference between MECC group and cECC group. Intrinsic coagulation (activated partial thromboplastin time) were much more prolonged early postoperatively in cECC group, and higher than in MECC group and off-pump group at 2 h, 6 h and 12 h postoperatively (P < 0.05), but no difference in extrinsic coagulation (prothrombin time) among three group. Adjusted by hematocrit of the same sample, free hemoglobin level rose up during the ECC procedure and reached the maximum at the end of ECC in cECC group and MECC group, but the levels were more higher in cECC group than in MECC group (P < 0.05). The draining volume during the first 24 h after operation of cECC group was larger than MECC group and off-pump group (P < 0.05). Although the decreased platelet count perioperatively and more consumed of the blood products in cECC group, but no difference among the three groups. MECC could reduce the ruin to blood cell and interfere to coagulation function during the conventional ECC procedure, decrease the postoperative draining volume and requirement of blood products.

Myocardial Blood Flow in Man: Effects of Coronary Collateral Circulation and Coronary Artery Bypass Surgery

PubMed Central

Smith, Sidney C.; Gorlin, Richard; Herman, Michael V.; Taylor, Warren J.; Collins, John J.

1972-01-01

The effects of coronary artery bypass graft (CAB) and coronary collaterals (CC) on myocardial blood flow (MBF) were studied in 24 patients undergoing 29 CAB's. MBF after CAB was compared to preexisting MBF by intraoperatively injecting 133xenon via distal CAB with proximal CAB first occluded then open. Pressure gradients across bypassed obstructions were measured. The results were correlated with preoperative coronary arteriograms to determine the effects of CC on MBF and postobstructive perfusion pressures. Mean MBF was increased by CAB from 32±6 (se) ml/min per 100 g (CAB occluded) to 118±13 ml/min per 100 g (CAB open). The 133Xe clearance curves with CAB open were resolved into slow (19±2 ml/min per 100 g) and rapid (133±12 ml/min per 100 g) phases, suggesting that MBF remained heterogeneous after CAB. Vessels with less than 80% stenosis by angiography had pressure gradients less than 20 mm Hg across obstructions, high postobstructive perfusion pressures (75±7 mm Hg), and normal MBF (87±6 ml/min per 100 g) even with CAB occluded. Vessels with greater than 80% stenosis or total occlusion by angiography had significant pressure gradients with marked reduction of postobstructive MBF. No significant difference in postobstructive MBF was found when vessels with CC (21±4 ml/min per 100 g) were compared to those without CC (17±4 ml/min per 100 g) (P > 0.4). These studies demonstrate that (a) mean MBF increased 268% after CAB, (b) heterogeneous MBF persisted after CAB, (c) CC were not associated with significant increases in MBF, and (d) vessels with less than 80% stenosis had less than 20 mm Hg gradient with minimal effect on resting MBF. Images PMID:5056655

Comparing short versus standard-length balloon for intra-aortic counterpulsation: results from a porcine model of myocardial ischaemia-reperfusion.

PubMed

Gelsomino, Sandro; Lozekoot, Pieter W J; Lorusso, Roberto; de Jong, Monique M J; Parise, Orlando; Matteucci, Francesco; Lucà, Fabiana; La Meir, Mark; Gensini, Gian Franco; Maessen, Jos G

2016-05-01

We compare a short and a standard-size balloon with same filling volumes to verify the differences in terms of visceral flow, coronary circulation and haemodynamic performance during aortic counterpulsation in an animal model of myocardial ischaemia-reperfusion injury. Eighteen healthy pigs underwent 120-min ligation of the left anterior descending coronary artery followed by 6 h of reperfusion, and they were randomly assigned to have intra-aortic balloon counterpulsation (IABP) with a 40-ml short-balloon (n = 6) or a 40-ml standard-length balloon (n = 6), or to undergo no IABP implantation (controls, n = 6). Haemodynamics and visceral and coronary flows were measured at baseline (t0), at 2 h of ischaemia (t1) and every hour thereafter until 6 h of reperfusion (from tR1 to tR6), respectively. Mesenteric flows increased significantly at tR1 only in the short-balloon group (P < 0.001) and it was constantly higher than in the standard-balloon group regardless of mean arterial pressure, systemic vascular resistance and cardiac output (CO; all, P < 0.001). Renal blood flows were significantly increased during IABP treatment with values constantly and significantly higher in short balloons at any following experimental step (all, P < 0.05). IABP improved CO and coronary blood flow, and reduced afterload, myocardial resistances and myocardial oxygen consumption without differences between the short and the standard-length balloon (all, P > 0.05). The short balloon prevents visceral ischaemia and, compared with the standard-size balloon, it does not lose IABP beneficial cardiac and coronary-related effects. Further studies are warranted to confirm our findings. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Design and Rationale for the Endothelin-1 Receptor Antagonism in the Prevention of Microvascular Injury in Patients with non-ST Elevation Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention (ENDORA-PCI) Trial.

PubMed

Liou, Kevin; Jepson, Nigel; Buckley, Nicolas; Chen, Vivien; Thomas, Shane; Russell, Elizabeth Anne; Ooi, Sze-Yuan

2016-04-01

Peri-procedural myocardial infarction (PMI) occurs in a small but significant portion of patients undergoing percutaneous intervention (PCI). The underlying mechanisms are complex and may include neurohormonal activation and release of vasoactive substances resulting in disruption of the coronary microcirculation. Endothelin in particular has been found in abundance in atherosclerotic plaques and in systemic circulation following PCI, and may be a potential culprit for PMI through its action on microvascular vasoconstriction, and platelet and neutrophil activation. In this study we aim to characterize the behavior of the coronary microcirculation during a PCI with the index of microvascular resistance (IMR) and the effect of peri-procedural endothelin antagonism. The ENDORA-PCI trial is a randomized, double-blind, placebo-controlled, single-center clinical trial designed to evaluate the efficacy of endothelin antagonism in attenuating the peri-procedural rise in IMR as a surrogate marker for PMI. The patients of interest are those with non-ST elevation acute coronary syndrome (NSTEACS) undergoing PCI, and we aim to recruit 52 patients overall to give the study a power of 80 % at an α level of 5 %. Patients will be randomized in a 1:1 fashion to either Ambrisentan, an endothelin antagonist, or placebo, prior to their PCI. IMR will be measured before and after PCI. The primary endpoint is the difference in peri-procedural changes in patients' IMR between the two groups. The ENDORA-PCI study will investigate whether endothelin antagonism with Ambrisentan attenuates the peri-procedural rise in IMR in patients with NSTEACS undergoing PCI, and thus potentially the risk of PMI.

Migration of mononuclear cells expressing β-actin through the adventitia into media and intima in coronary arteriogenesis and venogenesis in ischemic myocardium.

PubMed

Uchida, Yasuto; Uchida, Yasumi; Maezawa, Yoshiro; Maezawa, Yuko; Tabata, Tsuyoshi

2012-01-01

It was previously thought that arteriogenesis and venogenesis are induced not only by proliferation of vessel-resident smooth muscle cells (SMCs) and endothelial cells (ECs) but also by migration of their precursors. However, it is not well understood through what route(s) the precursors migrate into the existing vessels.We examined through what route or routes circulating mononuclear cells expressing β-actin (β-MNCs), which we identified in canine coronary vessels, migrate into coronary vessel walls and cause arteriogenesis and venogenesis at 1, 2, 4 and 8 weeks after induction of myocardial infarction.The following changes were observed: (1) The β-MNCs migrated via coronary microvessels to the interstitial space at one week; (2) β-MNCs traversed the adventitia into the media and settled in parallel with pre-existing smooth muscle cells (SMCs) in arterioles and arteries and lost β-actin and acquired α-smooth muscle actin (α-SMA) to become mature SMCs at 2-4 weeks; (3) at the same time, other β-MNCs migrated across the adventitia and media into the intima and settled in parallel with pre-existing endothelial cells (ECs) and lost β-actin, while acquiring CD(31), to become mature ECs, resulting in arteriogenesis; (4) Similarly, β-MNCs migrated into venular and venous walls and became SMCs or ECs, resulting in venogenesis.β-MNCs in the interstitial space expressed CD(34) but not other major vascular cell markers.β-MNCs, possibly a vascular progenitor, migrate not from the lumen but across the adventitia into the media or intima of coronary vessels and transit to SMCs or ECs, and participate in arteriogenesis and venogenesis in ischemic myocardium.

Oestradiol supplement minimises coronary occlusion-induced myocardial infarction and ventricular dysfunction in oophorectomised female rats.

PubMed

Zheng, Xiao-Pu; Ma, Ai-Qun; Dong, An-Ping; Wang, Shun; Jiang, Wen-Hui; Wang, Ting-Zhong; Fan, Fen-Ling; Ling, Shanhong

2011-09-15

Endogenous oestrogen deficiency after menopause is associated with high risk of acute cardiac events and the protection of exogenous oestrogen supplements remains uncertain. This study investigates whether oestrogen therapy protects the heart from ischemic injury in oophorectomised rats. Sexually mature female Sprague-Dawley rats (6 for each group) with bilateral oophorectomy underwent selective ligation (occlusion) of left coronary artery for 4 weeks. 17β-oestradiol (E2) supplements (10 μg, i.m., every other day) were started before (preventive-therapeutic supplement) or after coronary occlusion (therapeutic supplement). In oophorectomised rats plasma levels of E2 declined from 1301 ± 80 to 196 ± 48 pmol/L (p<0.01) and cardiac expression of oestrogen receptors (ER) decreased by ∼60%. E2 supplements recovered the ER expression. Selective ligation of left coronary led myocardial infarction in the left ventricle, with an increase in plasma cardiac troponin I (cTn-I), decrease in systolic blood pressure (SBP), and reduction of left ventricular pressures. Preventive-therapeutic but not therapeutic E2 supplement reduced cTn-I levels (from 21.9 ± 2.0 to 6.0 ± 0.3 ng/mL, p<0.01), minimised infarction (from 37.0 ± 1.2% to 18.1 ± 2.3%, p<0.05), increased SBP (from 82 ± 4.2 to 97 ± 4.4mm Hg, p<0.05), and improved left ventricular end pressures in the oophorectomised rats following coronary occlusion. Postmenopausal (ooporectomised) oestrogen supplement commenced before establishment of myocardial ischemia minimises myocardial infarction and ventricular dysfunction following the coronary artery occlusion. Cellular and molecular mechanisms underlying the cardiac protection of oestrogen therapy remain unclear, in which activation of cardiac ER expression and increasing in circulating CD90(+) stem cells may be involved. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Picture grammars in classification and semantic interpretation of 3D coronary vessels visualisations

NASA Astrophysics Data System (ADS)

Ogiela, M. R.; Tadeusiewicz, R.; Trzupek, M.

2009-09-01

The work presents the new opportunity for making semantic descriptions and analysis of medical structures, especially coronary vessels CT spatial reconstructions, with the use of AI graph-based linguistic formalisms. In the paper there will be discussed the manners of applying methods of computational intelligence to the development of a syntactic semantic description of spatial visualisations of the heart's coronary vessels. Such descriptions may be used for both smart ordering of images while archiving them and for their semantic searches in medical multimedia databases. Presented methodology of analysis can furthermore be used for attaining other goals related performance of computer-assisted semantic interpretation of selected elements and/or the entire 3D structure of the coronary vascular tree. These goals are achieved through the use of graph-based image formalisms based on IE graphs generating grammars that allow discovering and automatic semantic interpretation of irregularities visualised on the images obtained during diagnostic examinations of the heart muscle. The basis for the construction of 3D reconstructions of biological objects used in this work are visualisations obtained from helical CT scans, yet the method itself may be applied also for other methods of medical 3D images acquisition. The obtained semantic information makes it possible to make a description of the structure focused on the semantics of various morphological forms of the visualised vessels from the point of view of the operation of coronary circulation and the blood supply of the heart muscle. Thanks to these, the analysis conducted allows fast and — to a great degree — automated interpretation of the semantics of various morphological changes in the coronary vascular tree, and especially makes it possible to detect these stenoses in the lumen of the vessels that can cause critical decrease in blood supply to extensive or especially important fragments of the heart muscle.

PPIA rs6850: A > G single-nucleotide polymorphism is associated with raised plasma cyclophilin A levels in patients with coronary artery disease.

PubMed

Vinitha, A; Kutty, V Raman; Vivekanand, A; Reshmi, G; Divya, G; Sumi, S; Santosh, K R; Pratapachandran, N S; Ajit, Mullassari S; Kartha, C C; Ramachandran, Surya

2016-01-01

Plasma level of cyclophilin A is a promising marker of vascular disease in patients with type 2 diabetes. Genetic variants in the peptidylprolyl isomerase A gene, encoding human cyclophilin may alter protein synthesis thus affecting its activity, function, and circulating plasma levels. We examined the effect of single-nucleotide polymorphisms (SNPs) within the PPIA gene on plasma levels of cyclophilin A and coupled this with status of vascular disease in patients with and without type 2 diabetes in 212 South Indian subjects. The regulatory region of PPIA gene was sequenced for SNPs. The association of SNPs with known blood markers of type 2 diabetes and coronary artery disease such as HbA1c, low- and high-density lipoproteins, triglycerides, fasting and postprandial blood sugar levels, and cyclophilin A were probed. We identified three SNPs namely, rs6850: A > G; (AG/-) c.*227_*228delAG and (-/T) c.*318_*319insT. Welchs two-sample t test indicated an association of SNP rs6850: A > G, located at the 5' UTR region with increased plasma levels of cyclophilin A in patients with coronary artery disease and with coronary artery disease associated with diabetes. The presence of rs6850: A > G variant was significantly associated with coronary artery disease irrespective of whether the patients had diabetes or not. In silico analysis of the sequence using different tools and matrix libraries did not predict any significant differential binding sites for rs6850: A > G, c.*227_*228delAG and c.*318_*319insT. Our results indicate that the SNP rs6850: A > G is associated with increased risk for elevated plasma levels of cyclophilin A and coronary artery disease in patients with and without type 2 diabetes.

Immediate Percutaneous Coronary Intervention Is Associated With Improved Short- and Long-Term Survival After Out-of-Hospital Cardiac Arrest.

PubMed

Geri, Guillaume; Dumas, Florence; Bougouin, Wulfran; Varenne, Olivier; Daviaud, Fabrice; Pène, Frédéric; Lamhaut, Lionel; Chiche, Jean-Daniel; Spaulding, Christian; Mira, Jean-Paul; Empana, Jean-Philippe; Cariou, Alain

2015-10-01

Whether to perform or not an immediate percutaneous coronary intervention (PCI) after out-of-hospital cardiac arrest is still debated. We aimed to evaluate the impact of PCI on short- and long-term survival in out-of-hospital cardiac arrest patients admitted after successful resuscitation. Between 2000 and 2013, all nontrauma out-of-hospital cardiac arrest patients admitted in a Parisian cardiac arrest center after return of spontaneous circulation were prospectively included. The association between immediate PCI and short- and long-term mortality was analyzed using logistic regression and Cox multivariate analysis, respectively. Propensity score-matching method was used to assess the influence of PCI on short- and long-term survival. During the study period, 1722 patients (71.5% male, median age 60 [49.6, 72.2] years) were analyzed: 628 (35.6%) without coronary angiography, 615 (35.7%) with coronary angiography without PCI, and 479 (27.8%) with both. Among these groups, day 30 and year-10 survival rates were 21% and 11.9%, 35% and 29%, 43% and 38%, respectively (P<0.01 for each). PCI as compared with no coronary angiography was associated with a lower day-30 and long-term mortality (adjORcoro with PCI versus no coro 0.71, 95% confidence interval [0.54, 0.92]; P=0.02 and adjHRcoro with PCI versus no coro 0.44, 95% confidence interval [0.27, 0.71]; P<0.01, respectively). PCI remained associated with a lower risk of long-term mortality (adjHR 0.29; 95% confidence interval [0.14, 0.61]; P<0.01) in propensity score-matching analysis. Immediate PCI after out-of-hospital cardiac arrest was associated with significant reduced risk of short- and long-term mortality. These findings should suggest physicians to consider immediate coronary angiography and PCI if indicated in these patients. © 2015 American Heart Association, Inc.

Circulating irisin levels are lower in patients with either stable coronary artery disease (CAD) or myocardial infarction (MI) versus healthy controls, whereas follistatin and activin A levels are higher and can discriminate MI from CAD with similar to CK-MB accuracy.

PubMed

Anastasilakis, Athanasios D; Koulaxis, Dimitrios; Kefala, Nikoleta; Polyzos, Stergios A; Upadhyay, Jagriti; Pagkalidou, Eirini; Economou, Fotios; Anastasilakis, Chrysostomos D; Mantzoros, Christos S

2017-08-01

Several myokines are produced by cardiac muscle. We investigated changes in myokine levels at the time of acute myocardial infarction (MI) and following reperfusion in relation to controls. Patients with MI (MI Group, n=31) treated with percutaneous coronary intervention (PCI) were compared to patients with stable coronary artery disease (CAD) subjected to scheduled PCI (CAD Group, n=40) and controls with symptoms mimicking CAD without stenosis in angiography (Control Group, n=43). The number and degree of stenosis were recorded. Irisin, follistatin, follistatin-like 3, activin A and B, ALT, AST, CK and CK-MB were measured at baseline and 6 or 24h after the intervention. MI and CAD patients had lower irisin than controls (p<0.001). MI patients had higher follistatin, activin A, CK, CK-MB and AST than CAD patients and controls (all p≤0.001). None of the myokines changed following reperfusion. Circulating irisin was associated with the degree of stenosis in all patients (p=0.05). Irisin was not inferior to CK-MB in predicting MI while folistatin and activin A could discriminate MI from CAD patients with similar to CK-MB accuracy. None of these myokines was altered following PCI in contrast to CK-MB. Irisin levels are lower in MI and CAD implying that their production may depend on myocadial blood supply. Follistatin and activin A are higher in MI than in CAD suggesting increased release due to myocardial necrosis. They can predict MI with accuracy similar to CK-MB and their role in the diagnosis of MI remains to be confirmed by prospective large clinical studies. Copyright © 2017 Elsevier Inc. All rights reserved.

Cardio-Surgical Thermography

NASA Astrophysics Data System (ADS)

Fiorini, A. R.; Fumero, R.; Marchesi, R.

1983-03-01

Extracorporeal circulation allows direct access inside the chest: it may be used to carry out physiological research. The thermo-chemical protection of myocardium during heart surgery, called cardioplegy, is one of the latest outstanding techniques in patient safety. Thermocardiography monitoring during the infusion of the cardioplegic solution allows continuous assessment of rapid temperature distribution changes and shows exactly the extent of myocardium involved. Using a peculiar pseudocolor digital image enhancement, it is possible to emphasize involved areas coronary flow and to model the thermo-fluid-dynamical actions of inspected heart.

Cross-talk between cardiac muscle and coronary vasculature.

PubMed

Westerhof, Nico; Boer, Christa; Lamberts, Regis R; Sipkema, Pieter

2006-10-01

The cardiac muscle and the coronary vasculature are in close proximity to each other, and a two-way interaction, called cross-talk, exists. Here we focus on the mechanical aspects of cross-talk including the role of the extracellular matrix. Cardiac muscle affects the coronary vasculature. In diastole, the effect of the cardiac muscle on the coronary vasculature depends on the (changes in) muscle length but appears to be small. In systole, coronary artery inflow is impeded, or even reversed, and venous outflow is augmented. These systolic effects are explained by two mechanisms. The waterfall model and the intramyocardial pump model are based on an intramyocardial pressure, assumed to be proportional to ventricular pressure. They explain the global effects of contraction on coronary flow and the effects of contraction in the layers of the heart wall. The varying elastance model, the muscle shortening and thickening model, and the vascular deformation model are based on direct contact between muscles and vessels. They predict global effects as well as differences on flow in layers and flow heterogeneity due to contraction. The relative contributions of these two mechanisms depend on the wall layer (epi- or endocardial) and type of contraction (isovolumic or shortening). Intramyocardial pressure results from (local) muscle contraction and to what extent the interstitial cavity contracts isovolumically. This explains why small arterioles and venules do not collapse in systole. Coronary vasculature affects the cardiac muscle. In diastole, at physiological ventricular volumes, an increase in coronary perfusion pressure increases ventricular stiffness, but the effect is small. In systole, there are two mechanisms by which coronary perfusion affects cardiac contractility. Increased perfusion pressure increases microvascular volume, thereby opening stretch-activated ion channels, resulting in an increased intracellular Ca2+ transient, which is followed by an increase in Ca2+ sensitivity and higher muscle contractility (Gregg effect). Thickening of the shortening cardiac muscle takes place at the expense of the vascular volume, which causes build-up of intracellular pressure. The intracellular pressure counteracts the tension generated by the contractile apparatus, leading to lower net force. Therefore, cardiac muscle contraction is augmented when vascular emptying is facilitated. During autoregulation, the microvasculature is protected against volume changes, and the Gregg effect is negligible. However, the effect is present in the right ventricle, as well as in pathological conditions with ineffective autoregulation. The beneficial effect of vascular emptying may be reduced in the presence of a stenosis. Thus cardiac contraction affects vascular diameters thereby reducing coronary inflow and enhancing venous outflow. Emptying of the vasculature, however, enhances muscle contraction. The extracellular matrix exerts its effect mainly on cardiac properties rather than on the cross-talk between cardiac muscle and coronary circulation.

Coronary Artery Bypass Graft Surgery Cost Coverage by the Brazilian Unified Health System (SUS)

PubMed Central

da Silva, Gilmara Silveira; Colósimo, Flávia Cortez; de Sousa, Alexandre Gonçalves; Piotto, Raquel Ferrari; Castilho, Valéria

2017-01-01

Introduction Cost management has been identified as an essential tool for the general control and evaluation of health organizations. Objectives To identify the coverage percentage of transferred funds from the Unified Health System for coronary artery bypass grafts in a philanthropic hospital having a consolidated costing system in the municipality of São Paulo. Methods A quantitative, descriptive and cross-sectional research with information provided from a database composed of 1913 patients undergoing coronary artery bypass graft from March 13 to September 30, 2012, including isolated elective coronary artery bypass graft with the use of extracorporeal circulation. It excluded 551 (28.8%) patients, among them 76 (4.0%) deaths and 8 hospitalized patients, since the cost was compared according to the length of hospital stay. Therefore, the sample consisted of 1362 patients. Results The average total cost per patient was $7,992.55. The average fund transfer by the Unified Health System was $3,450.73 (48.66%), resulting in a deficit of $4,541.82 (51.34%). Conclusion The Unified Health System transfers covered 48.66% of the average total cost of hospitalization. Although the amount transferred increased with increasing costs, it was not proportional to the total cost, resulting in a percentage difference in revenue that was increasingly negative for each increase in cost and hospital stay. Those hospitalized for longer than seven days presented higher costs, older age, higher percentage of diabetics and chronic kidney disease patients and more postoperative complications. PMID:28977196

Endothelial Cell-Derived Microparticles from Patients with Obstructive Sleep Apnea Hypoxia Syndrome and Coronary Artery Disease Increase Aortic Endothelial Cell Dysfunction.

PubMed

Jia, Lixin; Fan, Jingyao; Cui, Wei; Liu, Sa; Li, Na; Lau, Wayne Bond; Ma, Xinliang; Du, Jie; Nie, Shaoping; Wei, Yongxiang

2017-01-01

Obstructive sleep apnea hypoxia syndrome (OSAHS) is an independent risk factor for coronary artery disease (CAD). Treatment of OSAHS improves clinical outcome in some CAD patients, but the relationship between OSAHS and CAD is complex. Microparticles (MPs) are shed by the plasma membrane by either physiologic or pathologic stimulation. In the current study, we investigated the role of MPs in the context of OSAHS. 54 patients with both suspected coronary artery stenosis and OSAHS were recruited and underwent both coronary arteriography and polysomnography. Circulating MPs were isolated and analyzed by flow cytometry. CAD+OSAHS patients exhibited greater levels of total MPs (Annexin V+), erythrocyte-derived MPs (CD235+ Annexin V+), platelet-derived MPs (CD41+ Annexin V+), and leukocyte-derived MPs (CD45+ Annexin V+) compared to CAD alone patients or control. CAD+OSAHS patients expressed the greatest level of endothelial-derived MPs of all cellular origin types (CD144+ Annexin V +). Treatment of human aortic endothelial cells (HAECs) with MPs isolated from CAD+OSAHS patients markedly increased HAEC permeability (as detected by FITC-dextran), and significantly upregulated mRNA levels of ICAM-1, VCAM-1, and MCP-1. OSAHS+CAD patients harbor increased levels of MPs, particularly the endothelial cell-derived subtype. When administered to HAECs, OSAHS+CAD patients MPs increase endothelial cell permeability and dysfunction. © 2017 The Author(s). Published by S. Karger AG, Basel.

Granulocyte colony-stimulating factor mobilizes functional endothelial progenitor cells in patients with coronary artery disease.

PubMed

Powell, Tiffany M; Paul, Jonathan D; Hill, Jonathan M; Thompson, Michael; Benjamin, Moshe; Rodrigo, Maria; McCoy, J Philip; Read, Elizabeth J; Khuu, Hanh M; Leitman, Susan F; Finkel, Toren; Cannon, Richard O

2005-02-01

Endothelial progenitor cells (EPCs) that may repair vascular injury are reduced in patients with coronary artery disease (CAD). We reasoned that EPC number and function may be increased by granulocyte colony-stimulating factor (G-CSF) used to mobilize hematopoietic progenitor cells in healthy donors. Sixteen CAD patients had reduced CD34(+)/CD133(+) (0.0224+/-0.0063% versus 0.121+/-0.038% mononuclear cells [MNCs], P<0.01) and CD133(+)/VEGFR-2(+) cells, consistent with EPC phenotype (0.00033+/-0.00015% versus 0.0017+/-0.0006% MNCs, P<0.01), compared with 7 healthy controls. Patients also had fewer clusters of cells in culture, with out-growth consistent with mature endothelial phenotype (2+/-1/well) compared with 16 healthy subjects at high risk (13+/-4/well, P<0.05) or 14 at low risk (22+/-3/well, P<0.001) for CAD. G-CSF 10 microg/kg per day for 5 days increased CD34(+)/CD133(+) cells from 0.5+/-0.2/microL to 59.5+/-10.6/microL and CD133(+)/ VEGFR-2(+) cells from 0.007+/-0.004/microL to 1.9+/-0.6/microL (both P<0.001). Also increased were CD133(+) cells that coexpressed the homing receptor CXCR4 (30.4+/-8.3/microL, P<0.05). Endothelial cell-forming clusters in 10 patients increased to 27+/-9/well after treatment (P<0.05), with a decline to 9+/-4/well at 2 weeks (P=0.06). Despite reduced EPCs compared with healthy controls, patients with CAD respond to G-CSF with increases in EPC number and homing receptor expression in the circulation and endothelial out-growth in culture. Endothelial progenitor cells (EPCs) are reduced in coronary artery disease. Granulocyte colony-stimulating factor (CSF) administered to patients increased: (1) CD133+/VEGFR-2+ cells consistent with EPC phenotype; (2) CD133+ cells coexpressing the chemokine receptor CXCR4, important for homing of EPCs to ischemic tissue; and (3) endothelial cell-forming clusters in culture. Whether EPCs mobilized into the circulation will be useful for the purpose of initiating vascular growth and myocyte repair in coronary artery disease patients must be tested in clinical trials.

[The relationship between fragmented QRS complex and coronary collateral circulation in patients with chronic total occlusion lesion without prior myocardial infarction].

PubMed

Gu, X J; Shan, S J; Liu, Z Z; Jin, G Z; Hu, Z Y; Zhu, L L; Zhang, J

2017-04-24

Objective: To explore the relationship between fragmented QRS complex(fQRS) and coronary collateral circulation(CCC) in patients with chronic total occlusion(CTO)lesion without prior myocardial infarction. Methods: This retrospective study analyzed 238 consecutive patients with CTO lesion in one of the major coronary arteries from May 2014 to October 2015 in our department. Patients were divided into poor CCC group (grade 0 and 1, 58 cases) and good CCC group(grade 2 and 3, 180 cases) based on Rentrop's classification of CCC. The fQRS was defined as the presence of an additional R wave or notching of R or S wave or the presence of fragmentation in two contiguous electrocardiogram leads corresponding to a major coronary artery territory. Multivariate logistic regression was used to analyze the relationship between CCC and fQRS on electrocardiogram. Results: Compared with good CCC group, patients in poor CCC group had older age((65.2±8.9)years old vs. (60.3±10.1) years old, P =0.03), higher plasma glucose ((7.22±3.00) mmol/L vs.(6.31±1.83)mmol/L, P =0.04), and lower left ventricular ejection fraction ((45.2±11.4)% vs. (51.2±13.5)%, P =0.02). None of patients had Rentrop grade 0, the presence of fQRS on ECG in patients with Rentrop grade 1, grade 2, and grade 3 CCC was 69.0% (40/58), 48.6% (35/72) , and 19.4% (21/108), respectively ( P <0.01). The presence of fQRS were higher in poor CCC group than in good CCC group (69.0%(40/58)vs. 31.1%(56/180), P <0.01), and number of leads with fQRS were higher in poor CCC group than in good CCC group (3(0, 4)vs.0(0, 3), P <0.01). Multivariate logistic regression analysis demonstrated that poor CCC growth in patients with CTO lesion without prior myocardial infarction was independently related to the presence of fQRS ( OR =3.659, 95% CI 1.619-8.217, P <0.01). Conclusion: Poor CCC in patients with CTO lesion without prior myocardial infarction is independently related to the presence of fQRS on electrocardiogram.

Nanotechnology for Synthetic High Density Lipoproteins

PubMed Central

Luthi, Andrea J.; Patel, Pinal C.; Ko, Caroline H.; Mutharasan, R. Kannan; Mirkin, Chad A.; Thaxton, C. Shad

2014-01-01

Atherosclerosis is the disease mechanism responsible for coronary heart disease (CHD), the leading cause of death worldwide. One strategy to combat atherosclerosis is to increase the amount of circulating high density lipoproteins (HDL), which transport cholesterol from peripheral tissues to the liver for excretion. The process, known as reverse cholesterol transport, is thought to be one of the main reasons for the significant inverse correlation observed between HDL blood levels and the development of CHD. This article highlights the most common strategies for treating atherosclerosis using HDL. We further detail potential treatment opportunities that utilize nanotechnology to increase the amount of HDL in circulation. The synthesis of biomimetic HDL nanostructures that replicate the chemical and physical properties of natural HDL provides novel materials for investigating the structure-function relationships of HDL and for potential new therapeutics to combat CHD. PMID:21087901

Are Elevated Levels of IGF-1 Caused by Coronary Arteriesoclerosis?: Molecular and Clinical Analysis

PubMed Central

Gozdzicka-Jozefiak, Anna; Zurawski, Jakub; Nowak, Witold; Durzynska, Julia; Link, Rafał; Grotowski, Tomasz; Siminiak, Tomasz

2010-01-01

The importance of insulin-like growth factor-1 (IGF-1) in coronary artery disease (CAD) due to wide range of its biological effects and its therapeutic potential, has already been described. Our aim was to evaluate possible influence of IGF-1 serum level changes on coronary atherosclerosis. In case of existence of such association our further aim was to verify and explain this phenomenon by examination of promoter P1 of IGF-1gene and receptor gene for IGF-1. The study was performed in 101 consecutive patients undergo for routine coronary angiography. Quantitative and qualitative assessment of coronary atherosclerosis was performed respectively by estimation of the number of culprit lesions in coronary arteries and by Gensini score calculation. IGF-1, IGFBP3 and plasma lipoproteins were measured in all patients. In addition, we evaluated DNA from 101 patients, isolated from blood cells, which was amplified by using PCR with sophisticated primers for P1 promoter of IGF-1 gene and IGF-1 receptor gene, then analyzed utilizing SSCP technique and automatically sequenced. We observed significant increase of serum IGF-1 levels in patients with “3 vessel disease” and with high score in Gensini scale when compared to those without any narrowing lesions in coronary arteries and 0 Gensini score (in group with 3 vessel disease 215.0 ± 71.3 versuss 176.7 ± 34.2 ng/ml p = 0.04 and with high Gensini score 231.4 ± 59.3 versus 181.0 ± 37.8 ng/ml p = 0.01).We found different genotypes for five P1 promoter polymorphisms of IGF-1 gene (RS35767, RS5742612, RS228837, RS11829693, RS17879774). There were no significant associations between the observed single nucleotide polymorphism (SNP) and coronary atherosclerosis nor with levels of circulating IGF-1. We found no structural polymorphism in receptor gene for IGF-1 nor in its extracellular domain(exon 2–4) nor in internal domain (exon 16–21). The effect of increased IGF-1 serum level in our study was probably independent from structural polymorphism in promoter P1 for IGF-1 or in receptor gene for IGF-1. PMID:21046444

Are elevated levels of IGF-1 caused by coronary arteriesoclerosis?: Molecular and clinical analysis.

PubMed

Burchardt, Pawel; Gozdzicka-Jozefiak, Anna; Zurawski, Jakub; Nowak, Witold; Durzynska, Julia; Link, Rafał; Grotowski, Tomasz; Siminiak, Tomasz

2010-11-01

The importance of insulin-like growth factor-1 (IGF-1) in coronary artery disease (CAD) due to wide range of its biological effects and its therapeutic potential, has already been described. Our aim was to evaluate possible influence of IGF-1 serum level changes on coronary atherosclerosis. In case of existence of such association our further aim was to verify and explain this phenomenon by examination of promoter P1 of IGF-1gene and receptor gene for IGF-1. The study was performed in 101 consecutive patients undergo for routine coronary angiography. Quantitative and qualitative assessment of coronary atherosclerosis was performed respectively by estimation of the number of culprit lesions in coronary arteries and by Gensini score calculation. IGF-1, IGFBP3 and plasma lipoproteins were measured in all patients. In addition, we evaluated DNA from 101 patients, isolated from blood cells, which was amplified by using PCR with sophisticated primers for P1 promoter of IGF-1 gene and IGF-1 receptor gene, then analyzed utilizing SSCP technique and automatically sequenced. We observed significant increase of serum IGF-1 levels in patients with "3 vessel disease" and with high score in Gensini scale when compared to those without any narrowing lesions in coronary arteries and 0 Gensini score (in group with 3 vessel disease 215.0 ± 71.3 versuss 176.7 ± 34.2 ng/ml p = 0.04 and with high Gensini score 231.4 ± 59.3 versus 181.0 ± 37.8 ng/ml p = 0.01).We found different genotypes for five P1 promoter polymorphisms of IGF-1 gene (RS35767, RS5742612, RS228837, RS11829693, RS17879774). There were no significant associations between the observed single nucleotide polymorphism (SNP) and coronary atherosclerosis nor with levels of circulating IGF-1. We found no structural polymorphism in receptor gene for IGF-1 nor in its extracellular domain(exon 2-4) nor in internal domain (exon 16-21). The effect of increased IGF-1 serum level in our study was probably independent from structural polymorphism in promoter P1 for IGF-1 or in receptor gene for IGF-1.

Reduced progression of atherosclerosis in apolipoprotein E-deficient mice with phenylhydrazine-induced anemia.

PubMed

Paul, A; Calleja, L; Vilella, E; Martínez, R; Osada, J; Joven, J

1999-11-01

Epidemiological and experimental studies suggest that circulating erythrocytes play a role in the incidence of coronary heart disease. We investigated the influence of phenylhydrazine (PHZ)-induced anemia on the formation of atherosclerotic lesions in apo E-deficient mice on regular chow and on a high-fat, high-cholesterol diet during 10 weeks. The repeated doses of PHZ caused sustained anemia throughout the study, changes in the physical characteristics of erythrocytes and increased reticulocyte count. The lesions of the anemic animals were smaller than in the controls and this was even more evident in mice fed with the atherogenic diet. A positive correlation was found between circulating red blood cells at the end of the experiment and the area of aortic lesion. There was also a negative association between the lesion and the reticulocyte count. This reduced progression of atherosclerotic lesions is independent of nutritional status or the lipoprotein cholesterol distribution. The results suggest that mechanisms related to the number of circulating red blood cells may have a significant influence on the development of atherosclerosis.

Tissue-associated self-antigens containing exosomes: Role in allograft rejection.

PubMed

Sharma, Monal; Ravichandran, Ranjithkumar; Bansal, Sandhya; Bremner, Ross M; Smith, Michael A; Mohanakumar, T

2018-06-15

Exosomes are extracellular vesicles that express self-antigens (SAgs) and donor human leukocyte antigens. Tissue-specific exosomes can be detected in the circulation following lung, heart, kidney and islet cell transplantations. We collected serum samples from patients who had undergone lung (n = 30), heart (n = 8), or kidney (n = 15) transplantations to isolate circulating exosomes. Exosome purity was analyzed by Western blot, using CD9 exosome-specific markers. Tissue-associated lung SAgs, collagen V (Col-V) and K-alpha 1 tubulin (Kα1T), heart SAgs, myosin and vimentin, and kidney SAgs, fibronectin and collagen IV (Col-IV), were identified using western blot. Lung transplant recipients diagnosed with bronchiolitis obliterans syndrome had exosomes with higher expression of Col-V (4.2-fold) and Kα1T (37.1-fold) than stable. Exosomes isolated from heart transplant recipients diagnosed with coronary artery vasculopathy had a 3.9-fold increase in myosin and a 4.7-fold increase in vimentin compared with stable. Further, Kidney transplant recipients diagnosed with transplant glomerulopathy had circulating exosomes with a 2-fold increased expression of fibronectin and 2.5-fold increase in Col-IV compared with stable. We conclude that circulating exosomes with tissue associated SAgs have the potential to be a noninvasive biomarker for allograft rejection. Copyright © 2018. Published by Elsevier Inc.

Dietary intake of phytoestrogen is associated with increased circulating endothelial progenitor cells in patients with cardiovascular disease.

PubMed

Chan, Yap-Hang; Lam, Tai-Hing; Lau, Kui-Kai; Yiu, Kai-Hang; Siu, Chung-Wah; Li, Sheung-Wai; Chan, Hiu-Ting; Tam, Sidney; Lau, Chu-Pak; Tse, Hung-Fat

2011-06-01

Endogenous estrogen is known to positively influence the level and functionality of endothelial progenitor cells (EPC). However, the effect of phytoestrogen on EPC is unknown. Isoflavone is a major component of phytoestrogen. This study aims to investigate if the intake of isoflavone has any impact on the circulating level of EPC. We studied 102 consecutive patients (mean age: 66.5 ± 9.5 years, 78% male, all female post-menopausal) with cardiovascular disease (atherothrombotic stroke 62%, coronary artery disease 38%). Circulating levels of CD133(+) EPC were determined by flow cytometry. Non-invasive pulse wave velocity (PWV) was measured. Long-term intake of isoflavone was determined by a validated food frequency questionnaire. Isoflavone intake was positively associated with circulating CD133(+) EPC (r = 0.31, p = 0.001). Patients with circulating CD133(+) EPC <10th percentile had significantly lower isoflavone intake than patients with CD133(+)EPC ≥10th percentile (4.6 ± 3.7 mg/day versus 19.3 ± 30.2 mg/day, p < 0.001). A significant overall linear trend of circulating EPC across increasing tertiles of isoflavone intake was observed (p = 0.004). Adjusted for potential confounders, increased isoflavone intake from the 1st to the 3rd tertile independently predicted increased circulating CD133(+) EPC level by 221 cells/µl (95%CI: 71.4 to 369.8, relative increase 160%, p = 0.004). Gender was not a significant factor (p > 0.05). Furthermore, circulating CD133(+) EPC <10th percentile was independently predictive of increased PWV by 261.7 cm/s (95% CI: 37.1 to 486.2, p = 0.024). The study demonstrated that circulating EPC increased by more than one fold in patients with cardiovascular disease who had higher intake of isoflavone, suggesting that isoflavone may confer vascular protection through enhanced endothelial repair.

Microvascular and mitochondrial dysfunction in the female F1 generation after gestational TiO2 nanoparticle exposure

PubMed Central

Stapleton, Phoebe A.; Nichols, Cody E.; Yi, Jinghai; McBride, Carroll R.; Minarchick, Valerie C.; Shepherd, Danielle L.; Hollander, John M.; Nurkiewicz, Timothy R.

2016-01-01

Due to the ongoing evolution of nanotechnology, there is a growing need to assess the toxicological outcomes in under-studied populations in order to properly consider the potential of engineered nanomaterials (ENM) and fully enhance their safety. Recently, we and others have explored the vascular consequences associated with gestational nanomaterial exposure, reporting microvascular dysfunction within the uterine circulation of pregnant dams and the tail artery of fetal pups. It has been proposed (via work derived by the Barker Hypothesis) that mitochondrial dysfunction and subsequent oxidative stress mechanisms as a possible link between a hostile gestational environment and adult disease. Therefore, in this study, we exposed pregnant Sprague-Dawley rats to nanosized titanium dioxide aerosols after implantation (gestational day 6). Pups were delivered, and the progeny grew into adulthood. Microvascular reactivity, mitochondrial respiration and hydrogen peroxide production of the coronary and uterine circulations of the female offspring were evaluated. While there were no significant differences within the maternal or litter characteristics, endothelium-dependent dilation and active mechanotransduction in both coronary and uterine arterioles were significantly impaired. In addition, there was a significant reduction in maximal mitochondrial respiration (state 3) in the left ventricle and uterus. These studies demonstrate microvascular dysfunction and coincide with mitochondrial inefficiencies in both the cardiac and uterine tissues, which may represent initial evidence that prenatal ENM exposure produces microvascular impairments that persist throughout multiple developmental stages. PMID:25475392

miR-22-5p revealed as a potential biomarker involved in the acute phase of myocardial infarction via profiling of circulating microRNAs.

PubMed

Maciejak, Agata; Kiliszek, Marek; Opolski, Grzegorz; Segiet, Agnieszka; Matlak, Krzysztof; Dobrzycki, Slawomir; Tulacz, Dorota; Sygitowicz, Grazyna; Burzynska, Beata; Gora, Monika

2016-09-01

Acute myocardial infarction (AMI) is a life-threatening episode of coronary artery disease. Recently, circulating myocardial-derived microRNAs (miRNAs) have been reported as potential biomarkers of infarction. The present study aimed to identify differentially expressed miRNAs in patients with ST-segment elevation myocardial infarction that could be potentially dysregulated in response to early myocardial damage. miRNA expression profile analysis was performed using the Serum/Plasma Focus miRNA Polymerase Chain Reaction (PCR) panel of Exiqon A/S (Vedbaek, Denmark) on plasma samples of patients on the first day of AMI (admission) and on samples from the identical patients collected six months following AMI. Selected miRNAs were validated by reverse transcription‑quantitative PCR (RT‑qPCR) using independent patients with AMI and a control group of patients with a stable coronary artery disease. Thirty‑two species of plasma miRNA were differentially expressed (P<0.05) on admission compared with six months following AMI. Subsequent validation in an independent patient group confirmed that miR‑133b and miR‑22‑5p were significantly up‑regulated in the serum of patients with AMI. The receiver operating characteristic (ROC) curve analysis demonstrated a diagnostic utility for miR-22-5p, which has not previously been reported to be associated with AMI. Among the selected miRNAs, miR‑22‑5p represents a novel promising biomarker for the diagnosis of AMI.

Embracing the heart: perioperative management of patients undergoing off-pump coronary artery bypass grafting using the octopus tissue stabilizer.

PubMed

Nierich, A P; Diephuis, J; Jansen, E W; van Dijk, D; Lahpor, J R; Borst, C; Knape, J T

1999-04-01

To describe hemodynamic alterations during coronary artery bypass grafting (CABG) without extracorporeal circulation using the Octopus Tissue Stabilizer, and to describe the two anesthetic management protocols based on either general anesthesia with opioids (34 patients) or general anesthesia with high thoracic epidural anesthesia (TEA; 66 patients). A prospective observational report. An academic university heart center. First 100 patients undergoing CABG using the Octopus Tissue Stabilizer. None. Current management provided satisfactory results in preventing hypoperfusion of the heart and inadequate systemic circulation without the use of major pharmacologic interventions. Movement of the heart to reach the target site of anastomosis caused hemodynamic alterations. These could easily be corrected by anesthetic interventions, such as fluid load and low doses of inotropes. High TEA allows earlier extubation compared with the opioid anesthesia technique (0.9 v 4.5 hours). Perioperative management and the incidence of postoperative complications did not differ between anesthetic techniques. Major complications, such as death, intraoperative myocardial infarction, and stroke, did not occur. Both anesthetic protocols are safe and effective in handling these patients. Off-pump CABG surgery requires anesthetic interventions because hemodynamic alterations are caused by the presentation of the heart to the surgeon. The complication rate is low but needs to be evaluated, compared with conventional CABG, in a prospective randomized study. High thoracic epidural anesthesia allows early recovery, but improved outcome could not be proved in this patient group.

Using information theory to assess the communicative capacity of circulating microRNA.

PubMed

Finn, Nnenna A; Searles, Charles D

2013-10-11

The discovery of extracellular microRNAs (miRNAs) and their transport modalities (i.e., microparticles, exosomes, proteins and lipoproteins) has sparked theories regarding their role in intercellular communication. Here, we assessed the information transfer capacity of different miRNA transport modalities in human serum by utilizing basic principles of information theory. Zipf Statistics were calculated for each of the miRNA transport modalities identified in human serum. Our analyses revealed that miRNA-mediated information transfer is redundant, as evidenced by negative Zipf's Statistics with magnitudes greater than one. In healthy subjects, the potential communicative capacity of miRNA in complex with circulating proteins was significantly lower than that of miRNA encapsulated in circulating microparticles and exosomes. Moreover, the presence of coronary heart disease significantly lowered the communicative capacity of all circulating miRNA transport modalities. To assess the internal organization of circulating miRNA signals, Shannon's zero- and first-order entropies were calculated. Microparticles (MPs) exhibited the lowest Shannon entropic slope, indicating a relatively high capacity for information transfer. Furthermore, compared to the other miRNA transport modalities, MPs appeared to be the most efficient at transferring miRNA to cultured endothelial cells. Taken together, these findings suggest that although all transport modalities have the capacity for miRNA-based information transfer, MPs may be the simplest and most robust way to achieve miRNA-based signal transduction in sera. This study presents a novel method for analyzing the quantitative capacity of miRNA-mediated information transfer while providing insight into the communicative characteristics of distinct circulating miRNA transport modalities. Published by Elsevier Inc.

Circulating Branched-Chain Amino Acids and Incident Cardiovascular Disease in a Prospective Cohort of US Women.

PubMed

Tobias, Deirdre K; Lawler, Patrick R; Harada, Paulo H; Demler, Olga V; Ridker, Paul M; Manson, JoAnn E; Cheng, Susan; Mora, Samia

2018-04-01

Circulating branched-chain amino acids (BCAAs; isoleucine, leucine, and valine) are strong predictors of type 2 diabetes mellitus (T2D), but their association with cardiovascular disease (CVD) is uncertain. We hypothesized that plasma BCAAs are positively associated with CVD risk and evaluated whether this was dependent on an intermediate diagnosis of T2D. Participants in the Women's Health Study prospective cohort were eligible if free of CVD at baseline blood collection (n=27 041). Plasma metabolites were measured via nuclear magnetic resonance spectroscopy. Multivariable Cox regression models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for BCAAs with incident CVD (myocardial infarction, stroke, and coronary revascularization). We confirmed 2207 CVD events over a mean 18.6 years of follow-up. Adjusting for age, body mass index, and other established CVD risk factors, total BCAAs were positively associated with CVD (per SD: HR, 1.13; 95% CI, 1.08-1.18), comparable to LDL-C (low-density lipoprotein cholesterol) with CVD (per SD: HR, 1.12; 95% CI, 1.07-1.17). BCAAs were associated with coronary events (myocardial infarction: HR, 1.16; 95% CI, 1.06-1.26; revascularization: HR, 1.17; 95% CI, 1.11-1.25), and borderline significant association with stroke (HR, 1.07; 95% CI, 0.99-1.15). The BCAA-CVD association was greater ( P interaction=0.036) among women who developed T2D before CVD (HR, 1.20; 95% CI, 1.08-1.32) versus women without T2D (HR, 1.08; 95% CI, 1.03-1.14). Adjusting for LDL-C, an established CVD risk factor, did not attenuate these findings; however, adjusting for HbA1c and insulin resistance eliminated the associations of BCAAs with CVD. Circulating plasma BCAAs were positively associated with incident CVD in women. Impaired BCAA metabolism may capture the long-term risk of the common cause underlying T2D and CVD. © 2018 American Heart Association, Inc.

[Flowmetric assessment of coronary bypass grafts in the conditions of artificial circulation and on the beating heart].

PubMed

Bazylev, V V; Nemchenko, E V; Karnakhin, V A; Pavlov, A A; Mikulyak, A I

2016-01-01

Advantages and shortcomings of aortocoronary bypass grafting on the beating heart and in the conditions of artificial circulation (AC) have long been discussed. The data on patency of bypass grafts in the remote period are indicative of comparable results of operations with and without AC or advantages of using AC. In order to determine benefits of each method it is necessary to reveal intraoperative predictors of bypass grafts occlusion in the remote period. We analyzed the results of ultrasound flowmetry of the blood flow through the left internal thoracic artery during bypass grafting of the anterior descending artery with the use of AC and on the beating heart. A retrospective study included a total of 352 patients subdivided into 2 groups: Group One was composed of 120 patients undergoing surgery in the conditions of AC and Group Two comprised 232 patients subjected to similar operations on the beating heart. Blood flow was measured with the help of flowmeter VeryQ MediStim® after termination of AC and inactivation of heparin by protamine, with systolic pressure of 100-110 mm Hg. There were no statistically significant differences between the groups by the diameter and degree of stenosis of the anterior descending artery, diameter of the left internal thoracic artery. The mean volumetric blood flow velocity (Qmean) along the shunts in Group One was higher (p=0.01). No statistically significant differences by the pulsatility index (PI) between the groups were revealed (p=0.2). A conclusion was drawn that coronary bypass grafting of the anterior descending artery by the left internal thoracic artery in the conditions of artificial circulation made it possible to achieve higher volumetric velocity of blood flow through the conduit as compared with operations on the beating heart, with similar resistance index. The immediate results of the operations with the use of the both techniques did not differ.

Circulating brain-derived neurotrophic factor concentrations and the risk of cardiovascular disease in the community.

PubMed

Kaess, Bernhard M; Preis, Sarah R; Lieb, Wolfgang; Beiser, Alexa S; Yang, Qiong; Chen, Tai C; Hengstenberg, Christian; Erdmann, Jeanette; Schunkert, Heribert; Seshadri, Sudha; Vasan, Ramachandran S; Assimes, Themistocles L; Deloukas, Panos; Holm, Hilma; Kathiresan, Sekar; König, Inke R; McPherson, Ruth; Reilly, Muredach P; Roberts, Robert; Samani, Nilesh J; Stewart, Alexandre F R

2015-03-11

Brain-derived neurotrophic factor (BDNF) is a pleiotropic peptide involved in maintaining endothelial integrity. It is unknown if circulating BDNF levels are associated with risk of cardiovascular disease (CVD). We prospectively investigated the association of circulating BDNF levels with cardiovascular events and mortality in 3687 participants (mean age 65 years, 2068 women) from the Framingham Heart Study (FHS). Using a common nonsynonomous single nucleotide polymorphism (SNP) in the BDNF gene (rs6265), we then performed a Mendelian randomization experiment in the CARDIoGRAM (Coronary ARtery DIsease Genome-Wide Replication And Meta-Analysis) consortium (>22,000 coronary artery disease [CAD] cases, >60,000 controls) to investigate whether SNP rs6265 was associated with CAD in CARDIoGRAM and, if so, whether the effect estimate differed from that predicted based on FHS data. On follow-up (median 8.9 years), 467 individuals (261 women) in FHS experienced a CVD event, and 835 (430 women) died. In multivariable-adjusted Cox regression, serum BDNF was associated inversely with CVD risk (hazard ratio [HR] per 1-SD increase 0.88, 95% CI 0.80 to 0.97, P=0.01) and with mortality (HR 0.87, 95% CI 0.80 to 0.93, P=0.0002). SNP rs6265 was associated with BDNF concentrations (0.772 ng/mL increase per minor allele copy) in FHS. In CARDIoGRAM, SNP rs6265 was associated with CAD (odds ratio 0.957, 95% CI 0.923 to 0.992), a magnitude consistent with the predicted effect (HR per minor allele copy 0.99, 95% CI 0.98 to 1.0; P=0.06 for difference between predicted and observed effect). Higher serum BDNF is associated with a decreased risk of CVD and mortality. Mendelian randomization suggests a causal protective role of BDNF in the pathogenesis of CVD. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

A Case Report of Recurrent Takotsubo Cardiomyopathy in a Patient during Myasthenia Crisis

PubMed Central

Battineni, Anusha; Mullaguri, Naresh; Thanki, Shail; Chockalingam, Anand

2017-01-01

Introduction Patients with myasthenia crisis can develop Takotsubo stress cardiomyopathy (SC) due to emotional or physical stress and high level of circulating catecholamines. We report a patient who developed recurrent Takotsubo cardiomyopathy during myasthenia crisis. Coexisting autoimmune disorders known to precipitate stress cardiomyopathy like Grave's disease need to be evaluated. Case Report A 69-year-old female with seropositive myasthenia gravis (MG), Grave's disease, and coronary artery disease on monthly infusion of intravenous immunoglobulin (IVIG), prednisone, pyridostigmine, and methimazole presented with shortness of breath and chest pain. Electrocardiogram (ECG) showed ST elevation in anterolateral leads with troponemia. Coronary angiogram was unremarkable for occlusive coronary disease with left ventriculogram showing reduced wall motion with apical and mid left ventricle (LV) hypokinesis suggestive of Takotsubo stress cardiomyopathy. Her symptoms were attributed to MG crisis. Her symptoms, ECG, and echocardiographic findings resolved after five cycles of plasma exchange (PLEX). She had another similar episode one year later during myasthenia crisis with subsequent resolution in 10 days after PLEX. Conclusion Takotsubo cardiomyopathy can be one of the manifestations of myasthenia crisis with or without coexisting Grave's disease. These patients might benefit from meticulous fluid status and cardiac monitoring while administering rescue treatments like IVIG and PLEX. PMID:29201468

Lower Plasma Fetuin-A Levels Are Associated With a Higher Mortality Risk in Patients With Coronary Artery Disease.

PubMed

Chen, Xuechen; Zhang, Yuan; Chen, Qian; Li, Qing; Li, Yanping; Ling, Wenhua

2017-11-01

The present study was designed to evaluate the association of circulating fetuin-A with cardiovascular disease (CVD) and all-cause mortality. We measured plasma fetuin-A in 1620 patients using an enzyme-linked immunosorbent assay kit. The patients were members of the Guangdong coronary artery disease cohort and were recruited between October 2008 and December 2011. Cox regression models were used to estimate the association between plasma fetuin-A and the risk of mortality. A total of 206 deaths were recorded during a median follow-up of 5.9 years, 146 of whom died from CVD. The hazard ratios for the second and third tertiles of the fetuin-A levels (using the first tertile as a reference) were 0.65 (95% confidence interval, 0.44-0.96) and 0.51 (95% confidence interval, 0.33-0.78) for CVD mortality ( P =0.005) and 0.65 (95% confidence interval, 0.47-0.91) and 0.48 (95% confidence interval, 0.33-0.70) for all-cause mortality ( P <0.001), respectively. Lower plasma fetuin-A levels were associated with an increased risk of all-cause and CVD mortality in patients with coronary artery disease independently of traditional CVD risk factors. © 2017 American Heart Association, Inc.

Pathway-related modules involved in the application of sevoflurane or propofol in off-pump coronary artery bypass graft surgery.

PubMed

Bu, Xiangmei; Wang, Bo; Wang, Yaoqi; Wang, Zhigang; Gong, Chunzhi; Qi, Feng; Zhang, Caixia

2017-07-01

Off-pump coronary artery bypass graft (CABG) surgery has recently emerged as a means to avoid the sequelae of extracorporeal circulation, including the whole-body inflammatory response, coagulation disorders and multiple organ dysfunction. At present, gas anesthesia, sevoflurane and intravenous anesthesia and propofol have been widely used during the CABG. To further understand the underlying mechanisms of these anesthetics on the gene level, the present study conducted pathway-related module analysis based on a co-expression network. This was performed in order to identify significant pathways in coronary artery disease patients who had undergone off-pump CABG surgery before and after applying sevoflurane or propofol. A total of 269 and 129 differentially expressed genes were obtained in the sevoflurane and propofol groups, respectively. In total, eight and seven pathways (P<0.05) in the sevoflurane and propofol groups were separately obtained via Kyoto Encyclopedia of Genes and Genome pathway analysis. Finally, eight and seven pathway-related modules in the sevoflurane and propofol groups were obtained, respectively. Furthermore, the mean degree of complement and coagulation cascades pathway-related module in both of the groups was the highest. It was predicted that during the CABG, the anesthetics might activate the complement and coagulation systems in order to possess some cardioprotective properties.

Reliable porcine coronary model of chronic total occlusion using copper wire stents and bioabsorbable levo-polylactic acid polymer.

PubMed

Sim, Doo Sun; Jeong, Myung Ho; Cha, Kyoung Rae; Park, Suk Ho; Park, Jong Oh; Shin, Young Min; Shin, Heungsoo; Hong, Young Joon; Ahn, Youngkeun; Schwartz, Robert S; Kang, Jung Chaee

2012-12-01

Chronic total occlusion (CTO) remains a challenge in interventional cardiology. We investigated the feasibility and reliability of copper wire stents and levo-polylactic acid (l-PLA) as a means of CTO induction in a porcine model. In one group of 20 swine, copper stents were crimped on a 3.0mm angioplasty balloon and inserted into the mid-left anterior descending coronary artery (LAD). In the other group of 20 swine, l-PLA was wrapped on a guidewire and pushed into the distal LAD with a 3.0mm balloon catheter to induce embolization. Of 20 swine which underwent copper stent implantation, 13 died of stent thrombosis. In the remaining 7 swine, total or near total occlusion with collateral circulation was observed at 5 weeks. Of 20 swine which underwent l-PLA embolization, 4 died of ventricular fibrillation during or shortly after the procedure. Serial histopathologic studies showed complete absorption of the polymer with replacement by fibrotic tissue approximately 4 weeks following the polymer implantation. CTO could be reliably induced in porcine coronary arteries by copper stents and l-PLA. These models may support investigation of new percutaneous devices to facilitate CTO interventions. Copyright © 2012 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Atheroprotective Properties of Serum IGF-1 in the Carotid and Coronary Territories and Beneficial Role on the Physical Fitness of the Oldest Old.

PubMed

Córdova, Claudio; Boullosa, Daniel A; Custódio, Misael R M; Quaglia, Luiz A; Santos, Simone N; Freitas, Wladimir M; Sposito, Andrei C; Nóbrega, Otávio T

2016-10-01

Our aim was to investigate whether physiological levels of soluble insulin-like growth factor-1 (IGF-1) associate with coronary and carotid atherosclerotic burden and physical fitness in the oldest old by means of a cross-sectional study including 100 community-dwelling individuals with no previous cardiovascular events. Linear correlation was found between IGF-1 and intima-media thickness, number of carotid plaques, and walking speed. Individuals in the upper IGF-1 tertile had smaller right and left intima-media thickness compared with the intermediate and lower tertiles, along with reduced atherosclerotic plaques. Also, walking speed was greater in the upper IGF-1 tertile. On the other hand, a nonlinear correlation was observed between IGF-1 and coronary calcification scores, with the intermediate IGF-1 tertile associated to the lowest scores of calcification and participants with lower circulating levels of IGF-1 showing higher frequency of high-risk morphology plaques. All in all, our report supports a territory-dependent, atherorefractory phenotype in the oldest old carrying middle and/or higher serum levels of IGF-1. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Serum levels of chemerin, apelin, vaspin, and omentin-1 in obese type 2 diabetic Egyptian patients with coronary artery stenosis.

PubMed

Motawi, Tarek M K; Mahdy, Soliman G; El-Sawalhi, Maha M; Ali, Eman N; El-Telbany, Rania Farag A

2018-01-01

Cardiovascular diseases (CVD) are the leading cause of death in the diabetic population. Obesity is a serious problem that has been linked with CVD and diabetes via a variety of adipokines. The aims of this study were to evaluate and correlate circulating chemerin, apelin, vaspin, and omentin-1 levels in obese type 2 diabetic Egyptian patients with coronary artery stenosis (CAS), and to assess their usefulness as noninvasive diagnostic biomarkers. Chemerin, apelin, vaspin, and omentin-1 levels were determined by enzyme immunoassay in coronary artery disease (CAD) I patients (45 non-obese, nondiabetic with CAS), CAD II patients (45 obese, diabetic with CAS), and 30 controls. Patients in CAD I and CAD II groups exhibited higher levels of chemerin and apelin together with lower levels of vaspin and omentin-1 than in controls. These alterations were more significant in CAD II than in CAD I patients. Additionally, adipokine levels were individually correlated with each other and with certain biochemical variables. Moreover, chemerin and vaspin levels could differentiate CAD II patients from CAD I and controls. Alterations of these adipokines may play a crucial role in the pathogenesis of CAS in obese type 2 diabetic Egyptian patients. Chemerin and vaspin could be used as markers to support diagnosis of CAS.

[Mortality following cardiac surgery in the National Health Service Hospitals of the Community of Valencia in 2007: a descriptive analysis].

PubMed

Vicente, R; Pajares, A; Vicente, J L; Aparicio, R; Loro, J M; Moreno, I; Soria, A; López, A; Porta, J; de la Fuente, C; Herrera, P; Tur, A; Osseyran, F; Guillén, A; Martí, F; Llagunes, J; Mateo, E; Aguar, F; Peña, J J; Marqués, J I; Ripoll, A; Reina, C; Ferrandis, P; Muedra, V; Llopis, E; Cantó, M; García, C

2010-02-01

To analyze clinical records of cardiac surgery patients in an attempt to identify factors associated with mortality in the postoperative critical care units of the public health service hospitals in the Community of Valencia, Spain, in 2007. Retrospective study of cases from January 1, 2007 to December 31, 2007. The charts of all patients who underwent cardiac surgery with or without extracorporeal circulation were reviewed. A data collection protocol was followed to obtain information on age, sex, body mass index (BMI), presurgical risk factors, type of surgery, duration of extracorporeal circulation, duration of ischemia, cause of death, and length of stay in the postoperative critical care unit. The study population consisted of 2113 patients at 5 public hospitals; 124 patients (70 men, 54 women) died. The mean (SD) age was 70 (9.43) years (range, 36-91 years). The mean BMI was 28.19 kg/m2 (maximum, 42 kg/m2). The mean Euroscore was 21.92 (maximum, 94.29). Hypertension was present as a preoperative risk factor in most patients (74.2%); dyslipidemia was present in 51.6%, diabetes mellitus in 38.7%, stroke in 73%, and renal failure in 2.4%. It was noteworthy was that the group who underwent coronary revascularization had the highest mortality rate (nearly 35% of the 124 patients). The next highest mortality rate (19.4%) was in patients who had combined procedures (valve repair or substitution plus coronary revascularization). Mortality was 18.5% in the group undergoing aortic valve surgery and 11.3% in those undergoing mitral valve surgery. The mean duration of extracorporeal circulation was 148.63 minutes. The mean duration of myocardial ischemia was 94.91 minutes. The most frequent cause of death was cardiogenic shock (54.8%). This was followed by distributive shock (29.8%) and hemorrhagic shock (8.9%). The mean length of stay in the postoperative critical care unit was 13.6 days. Overall mortality was 5.87%. The highest mortality rate among cardiac surgery patients in postoperative critical care units in hospitals in the Community of Valencia in 2007 was in patients who underwent coronary revascularization. The most prevalent preoperative risk factor was hypertension. Cardiogenic shock and distributive shock were the most frequent causes of death in these patients. A system for classifying risk is needed in order to predict mortality in critical care units and improve perioperative care.

PCSK9 inhibition fails to alter hepatic LDLR, circulating cholesterol, and atherosclerosis in the absence of ApoE.

PubMed

Ason, Brandon; van der Hoorn, José W A; Chan, Joyce; Lee, Edward; Pieterman, Elsbet J; Nguyen, Kathy Khanh; Di, Mei; Shetterly, Susan; Tang, Jie; Yeh, Wen-Chen; Schwarz, Margrit; Jukema, J Wouter; Scott, Rob; Wasserman, Scott M; Princen, Hans M G; Jackson, Simon

2014-11-01

LDL cholesterol (LDL-C) contributes to coronary heart disease. Proprotein convertase subtilisin/kexin type 9 (PCSK9) increases LDL-C by inhibiting LDL-C clearance. The therapeutic potential for PCSK9 inhibitors is highlighted by the fact that PCSK9 loss-of-function carriers exhibit 15-30% lower circulating LDL-C and a disproportionately lower risk (47-88%) of experiencing a cardiovascular event. Here, we utilized pcsk9(-/-) mice and an anti-PCSK9 antibody to study the role of the LDL receptor (LDLR) and ApoE in PCSK9-mediated regulation of plasma cholesterol and atherosclerotic lesion development. We found that circulating cholesterol and atherosclerotic lesions were minimally modified in pcsk9(-/-) mice on either an LDLR- or ApoE-deficient background. Acute administration of an anti-PCSK9 antibody did not reduce circulating cholesterol in an ApoE-deficient background, but did reduce circulating cholesterol (-45%) and TGs (-36%) in APOE*3Leiden.cholesteryl ester transfer protein (CETP) mice, which contain mouse ApoE, human mutant APOE3*Leiden, and a functional LDLR. Chronic anti-PCSK9 antibody treatment in APOE*3Leiden.CETP mice resulted in a significant reduction in atherosclerotic lesion area (-91%) and reduced lesion complexity. Taken together, these results indicate that both LDLR and ApoE are required for PCSK9 inhibitor-mediated reductions in atherosclerosis, as both are needed to increase hepatic LDLR expression. Copyright © 2014 by the American Society for Biochemistry and Molecular Biology, Inc.

Cardiac Gene Therapy: Optimization of Gene Delivery Techniques In Vivo

PubMed Central

Katz, Michael G.; Swain, JaBaris D.; White, Jennifer D.; Low, David; Stedman, Hansell

2010-01-01

Abstract Vector-mediated cardiac gene therapy holds tremendous promise as a translatable platform technology for treating many cardiovascular diseases. The ideal technique is one that is efficient and practical, allowing for global cardiac gene expression, while minimizing collateral expression in other organs. Here we survey the available in vivo vector-mediated cardiac gene delivery methods—including transcutaneous, intravascular, intramuscular, and cardiopulmonary bypass techniques—with consideration of the relative merits and deficiencies of each. Review of available techniques suggests that an optimal method for vector-mediated gene delivery to the large animal myocardium would ideally employ retrograde and/or anterograde transcoronary gene delivery,extended vector residence time in the coronary circulation, an increased myocardial transcapillary gradient using physical methods, increased endothelial permeability with pharmacological agents, minimal collateral gene expression by isolation of the cardiac circulation from the systemic, and have low immunogenicity. PMID:19947886

Clinical experience with the mini-extracorporeal circulation system: an evolution or a revolution?

PubMed

Remadi, Jean-Paul; Marticho, Paul; Butoi, Irina; Rakotoarivelo, Zava; Trojette, Faouzi; Benamar, Amar; Beloucif, Sadek; Foure, Dominique; Poulain, Henri J

2004-06-01

We studied a cohort of 150 patients operated on with a new cardiopulmonary bypass (CPB) system. This is the mini-extracorporeal circulation (MECC) system. The MECC is a fully heparin coated closed-loop CPB system that includes a centrifugal pump and has a priming volume of 450 mL. Between March 2001 and September 2002, 150 consecutive patients were operated on using the mini-CPB (MECC) method. This includes 105 coronary artery bypass graft and 45 aortic valve replacement patients. The median age was 66.7 +/- 10.7 years with a gender ratio of 3.27 males to 1 female. The 30-day operative mortality was 1.3%. The hemoglobin concentration was stable and perioperative transfusion was needed in only 6% of all patients. The renal and neuropsychiatric complications were less than 1%. In our experience, the MECC system is a reliable new concept for CPB with good clinical results.

Adiponectin as a routine clinical biomarker.

PubMed

Kishida, Ken; Funahashi, Tohru; Shimomura, Iichiro

2014-01-01

Adiponectin is a protein synthesized and secreted predominantly by adipocytes into the peripheral blood. However, circulating adiponectin level is inversely related with body weight, especially visceral fat accumulation. The mechanism of this paradoxical relation remains obscure. Low circulating adiponectin concentrations (hypoadiponectinemia; <4 μg/mL) are associated with a variety of diseases, including dysmetabolism (type 2 diabetes, insulin resistance, hypertension, dyslipidemia, metabolic syndrome, hyperuricemia), atherosclerosis (coronary artery disease, stroke, peripheral artery disease), sleep apnea, non-alcoholic fatty liver disease, gastritis and gastro-esophageal reflux disease, inflammatory bowel diseases, pancreatitis, osteoporosis, and cancer (endometrial cancer, postmenopausal breast cancer, leukemia, colon cancer, gastric cancer, prostate cancer). On the other hand, hyperadiponectinemia is associated with cardiac, renal and pulmonary diseases. This review article focuses on the significance of adiponectin as a clinical biomarker of obesity-related diseases. Routine measurement of adiponectin in patients with lifestyle-related diseases is highly recommended. Copyright © 2013 Elsevier Ltd. All rights reserved.

Non-invasive detection of human cardiomyocyte death using methylation patterns of circulating DNA.

PubMed

Zemmour, Hai; Planer, David; Magenheim, Judith; Moss, Joshua; Neiman, Daniel; Gilon, Dan; Korach, Amit; Glaser, Benjamin; Shemer, Ruth; Landesberg, Giora; Dor, Yuval

2018-04-24

Detection of cardiomyocyte death is crucial for the diagnosis and treatment of heart disease. Here we use comparative methylome analysis to identify genomic loci that are unmethylated specifically in cardiomyocytes, and develop these as biomarkers to quantify cardiomyocyte DNA in circulating cell-free DNA (cfDNA) derived from dying cells. Plasma of healthy individuals contains essentially no cardiomyocyte cfDNA, consistent with minimal cardiac turnover. Patients with acute ST-elevation myocardial infarction show a robust cardiac cfDNA signal that correlates with levels of troponin and creatine phosphokinase (CPK), including the expected elevation-decay dynamics following coronary angioplasty. Patients with sepsis have high cardiac cfDNA concentrations that strongly predict mortality, suggesting a major role of cardiomyocyte death in mortality from sepsis. A cfDNA biomarker for cardiomyocyte death may find utility in diagnosis and monitoring of cardiac pathologies and in the study of normal human cardiac physiology and development.

Two congenital coronary abnormalities affecting heart function: anomalous origin of the left coronary artery from the pulmonary artery and congenital left main coronary artery atresia.

PubMed

Xiao, Yanyan; Jin, Mei; Han, Ling; Ding, Wenhong; Zheng, Jianyong; Sun, Chufan; Lyu, Zhenyu

2014-01-01

The anomalous origin of the left coronary artery (LCA) from the pulmonary artery (ALCAPA) and congenital left main coronary artery atresia (CLMCA-A) are two kinds of very rare coronary heart diseases which affect heart function profoundly. This study aimed to retrospectively illustrate the clinical features and therapy experience of ALCAPA and CLMCA-A patients. From April 1984 to July 2012, in Beijing Anzhen Hospital, 23 patients were diagnosed with ALCAPA and 4 patients with CLMCA-A. We summarized the clinical data of the 27 cases and retrospectively analyzed the clinical manifestation, diagnosis, and treatments of these two kinds of congenital coronary abnormalities. The 23 patients (13 males and 10 females, aged ranging from 2.5 months to 65 years) identified with ALCAPA were classified into infantile type (age of onset younger than 12 months, 16 cases) and adult type (age of onset older than 12 months, 7 cases). Four patients were diagnosed with CLMCA-A (three males and one female, aged ranging from 3 months to 2 years). The main clinical manifestations of infantile-type ALCAPA and CLMCA-A include repeated respiratory tract infection, heart failure, dyspnea, feeding intolerance, diaphoresis, and failure to thrive. And these two congenital coronary abnormalities might be misdiagnosed as endocardial fibroelastosis, dilated cardiomyopathy, and acute myocardial infarction. As for the adult-type ALCAPA, cardiac murmurs and discomfort of the precordial area are the most common presentations and might be misdiagnosed as coronary heart disease, myocarditis, or patent ductus arteriosus. In ECG examination: Infantile-type ALCAPA and CLMCA-A showed abnormal Q waves with T wave inversion in leads I, avL, and V4-V6, especially in lead avL. However, ECG of adult-type ALCAPA lacked distinct features. In chest radiography: pulmonary congestion and cardiomegaly were the most common findings in infantile-type ALCAPA and CLMCA-A, while pulmonary artery segment dilation was more common in adult type. In echocardiography, the common features of infantile-type ALCAPA and CLMCA-A included left ventricular enlargement, left ventricular systolic function normal or mildly reduced in CLMCA-A or significantly reduced in ALCAPA, and moderate to large mitral valve. It was performed in 9 of 23 cases of ALCAPA and showed the origin of the dilated right coronary artery (RCA) from the right sinus of the aortic root and absence of LCA origin in angiography. After opacification of RCA, reverse flow in the LCA and pulmonary artery was visualized through coronary artery collateral circulation. Angio was performed in three of the four cases of CLMCA-A and showed left main coronary artery was a blind end, with diameter of only 1.1-2.0 mm. Treatment and prognosis: 21 patients with ALCAPA had cardiac surgery and 6 of them died postoperatively. Fifteen postoperative patients survived without overt symptoms within the follow-up period of 6-166 months (median 17 months). As for treatment of CLMCA-A, four patients took digoxin and diuretics without undergoing cardiac surgery. Their clinical symptoms improved during the close follow-ups. ALCAPA and CLMCA-A are two rare coronary artery abnormalities that affect cardiac function in infants and children. In younger patients with cardiomegaly and heart dysfunction these two congenital coronary diseases should be noticed.

Efficacy of a new intraaortic propeller pump vs the intraaortic balloon pump: an animal study.

PubMed

Dekker, André; Reesink, Koen; van der Veen, Erik; Van Ommen, Vincent; Geskes, Gijs; Soemers, Cecile; Maessen, Jos

2003-06-01

To compare the efficacy of a new intraaortic propeller pump (PP) to provide hemodynamic support to the intraaortic balloon pump (IABP) in an acute mitral regurgitation (MR) animal model. A new intraaortic PP (Reitan catheter pump; Jomed; Helsingborg, Sweden) recently has been introduced. The pump's aim is a reduction in afterload via a deployable propeller that is placed in the high descending aorta and can be set at rotational speeds of

Serum amyloid A induction of cytokines in monocytes/macrophages and lymphocytes.

PubMed

Song, Changjie; Hsu, Kenneth; Yamen, Eric; Yan, Weixing; Fock, Jianyi; Witting, Paul K; Geczy, Carolyn L; Freedman, S Ben

2009-12-01

Serum amyloid A (SAA) is a biomarker of inflammation. Elevated blood levels in cardiovascular disease and local deposition in atheroma implies a role of SAA as a mediator rather than just a marker of inflammation. This study explored SAA-induced cytokine production and secretion by mononuclear cells. RT-PCR showed that SAA time-dependently induced cytokine mRNAs in peripheral blood mononuclear cells (PBMC) and THP-1 monocytoid cells, and dramatically increased IL-1beta, MCP-1, IL-6, IL-8, IL-10, GM-CSF, TNF, and MIP-1alpha secretion by PBMC to levels 28 to 25,000 fold above baseline, as measured with Bio-Plex kits; monocytes were the principle source. SAA induction of cytokines in monocyte-derived macrophages (MDM) was significantly higher than from monocytes from the same donors. SAA time-dependently induced transient and significant upregulation of NF-kappaB1 mRNA; inhibitor studies indicate that activation of NF-kappaB through the ERK1/2, p38 and JNK MAPKs and the PI3K pathway was involved. PBMC from 10 patients with coronary artery disease (CAD) spontaneously secreted higher levels of IL-6 and MIP-1alpha after 24h incubation than PBMC from normal controls, whereas SAA-induced levels of all cytokines were similar to controls. Aortic and coronary sinus sampling in 23 CAD patients indicated significant SAA release into the coronary circulation, not evident in 11 controls. SAA can increase monocyte and macrophage cytokine production, possibly at sites of atherosclerosis, thereby contributing to the pro-inflammatory state in coronary artery disease.

Serum total bilirubin levels and coronary heart disease--Causal association or epiphenomenon?

PubMed

Kunutsor, Setor K

2015-12-01

Observational epidemiological evidence supports a linear inverse and independent association between serum total bilirubin levels and coronary heart disease (CHD) risk, but whether this association is causal remains to be ascertained. A Mendelian randomization approach was employed to test whether serum total bilirubin is causally linked to CHD. The genetic variant rs6742078--well known to specifically modify levels of serum total bilirubin and accounting for up to 20% of the variance in circulating serum total bilirubin levels--was used as an instrumental variable. In pooled analysis of estimates reported from published genome-wide association studies, every copy of the T allele of rs6742078 was associated with 0.42 standard deviation (SD) higher levels of serum total bilirubin (95% confidence interval, 0.40 to 0.43). Based on combined data from the Coronary Artery Disease Genome wide Replication and Meta-analyses and the Coronary Artery Disease (C4D) Genetics Consortium involving a total of 36,763 CHD cases and 76,997 controls, the odds ratio for CHD per copy of the T allele was 1.01 (95% confidence interval, 0.99 to 1.04). The odds ratio of CHD for a 1 SD genetically elevated serum total bilirubin level was 1.03 (95% confidence interval, 0.98 to 1.09). The current findings casts doubt on a strong causal association of serum total bilirubin levels with CHD. The inverse associations demonstrated in observational studies may be driven by biases such as unmeasured confounding and/or reverse causation. However, further research in large-scale consortia is needed. Copyright © 2015 Elsevier Inc. All rights reserved.

Heart fatty acid binding protein (H-FABP) as a diagnostic biomarker in patients with acute coronary syndrome.

PubMed

Gururajan, Priya; Gurumurthy, Prema; Nayar, Pradeep; Srinivasa Nageswara Rao, G; Babu, Sai; Cherian, K M

2010-11-01

Diagnosis of myocardial ischaemia at an early stage in the emergency department is often difficult. A recently proposed biomarker, heart fatty acid binding protein (H-FABP) has been found to appear in the circulation superior to that of cardiac troponins in the early hours of acute coronary syndrome. We proposed to evaluate the levels of H-FABP and ascertain its utility as an early biomarker for acute coronary syndrome (ACS). The present study was carried out in 485 subjects, of whom 297 were diagnosed as patients with ACS, 89 were diagnosed as non-cardiac chest pain (NCCP) and 99 people served as healthy controls. H-FABP levels were measured in comparison with standard markers such as troponin I and CK-MB in all subjects enrolled in the study. The levels of H-FABP were significantly raised in patients when compared to controls and NCCP (P<0.001). Receiver Operator Characteristic Curve (ROC) analysis showed H-FABP to be a good discriminator between patients with ischaemic heart disease and patients without ischaemic heart disease. The area under the curve was found to be 0.965 with 95% CI (0.945-0.979). The cut-off value above which H-FABP can be considered positive was found to be 17.7ng/ml. H-FABP is a promising biomarker for the early detection of patients with acute coronary syndrome. Copyright © 2010 Australasian Society of Cardiac and Thoracic Surgeons and the Cardiac Society of Australia and New Zealand. Published by Elsevier B.V. All rights reserved.

Neutralization of heparin activity.

PubMed

Pai, Menaka; Crowther, Mark A

2012-01-01

Heparin is the mainstay in the treatment and prevention of thrombosis in such diverse clinical settings as venous thromboembolism, acute coronary syndrome, cardiopulmonary bypass, and hemodialysis. However, the major complication of heparin - like that of all anticoagulants - is bleeding. Heparin may need to be reversed in the following settings: clinically significant bleeding; prior to an invasive procedure; at the conclusion of a procedure involving extracorporeal circulation (e.g., cardiopulmonary bypass, dialysis). This chapter discusses protamine sulfate, as well as several other agents that are able to neutralize heparin, including their pharmacological properties, indications, dosing, and efficacy.

Assessment of the rs4340 ACE gene polymorphism in acute coronary syndrome in a Western Mexican population.

PubMed

Valdez-Haro, A; Valle, Y; Valdes-Alvarado, E; Casillas-Muñoz, F; Muñoz-Valle, J F; Reynoso-Villalpando, G L; Flores-Salinas, H E; Padilla-Gutiérrez, J R

2017-09-27

Acute coronary syndrome (ACS) is considered one of the main causes of death worldwide. Contradictory findings concerning the impact of the angiotensin-converting enzyme (ACE) gene on cardiovascular diseases have been reported. Previous conclusions point out that the variability in results depends on ethnicity and genetic polymorphisms to determine the association of rs4340 polymorphisms of the ACE gene and ACE circulating levels in ACS. Genotyping of rs4340 polymorphisms was performed in a total of 600 individuals from Western Mexico divided into two groups: the ACS and the control group (CG). The polymorphisms were identified by polymerase chain reaction. Serum ACE concentration was determined by enzyme-linked immunosorbent assay. D/D carriers had higher ACE levels than I/I carriers (3.6 vs 2.8 ng/mL, P < 0.0021) in the CG. The D/D genotype of the rs4340 polymorphism is associated with higher ACE concentration levels; however, the polymorphism was not associated with ACS.

[Current radionuclear methods in the diagnosis of regional myocardial circulation disorders].

PubMed

Felix, R; Winkler, C

1977-01-29

Among nuclear medical diagnostic procedures a distinction can be made between non-invasive and invasive methods. The non-invasive methods serve either to image the still viable myocardium ("cold spot" technique) or for direct visualization of recently infarcted myocardial tissue ("hot spot" technique). These methods have the advantage of simple handling and good reproducibility. Side effects and risks are thus far unknown. Improvement of local dissolution should be aimed at in the future and wound greatly increase diagnostic and topographic security. The invasive procedures always require catheterization of the coronary arteries. This is the reason why they can be performed only with coronary arteriography. The Xenon "wash out" technique permits, with some restrictions, quantitative measurement of the regional flow rate. The "inflow technique" permits determination of perfusion distribution. The possibilities of the "double-radionuclide" scintigramm are discussed. For measurement of activity distribution, sationary detectors are generally preferred. In the case of the time-activity curves with the Xenon "wash out" technique, single detectors offer certain advantages.

Influence of Drugs Carried in Lipid Nanoparticles in Coronary Disease of Rabbit Transplanted Heart.

PubMed

Barbieri, Lucas R; Lourenço-Filho, Domingos D; Tavares, Elaine R; Carvalho, Priscila O; Gutierrez, Paulo S; Maranhão, Raul C; Stolf, Noedir A G

2017-08-01

Coronary allograft vasculopathy is an inflammatory-proliferative process that compromises the long-term success of heart transplantation and currently has no effective prevention and treatment. Lipid nanoparticles, termed LDE can carry chemotherapeutic agents in the circulation and concentrates them in the heart. Twenty-eight rabbits fed a cholesterol-rich diet and submitted to heterotopic heart transplantation were treated with cyclosporine A (10 mg/kg daily) and allocated to four groups of 7 animals treated with intravenous LDE-methotrexate (MTX; 4 mg/kg weekly), with LDE-paclitaxel (PACLI; 4 mg/kg weekly), or with LDE-PACLI (4 mg/kg weekly) and LDE-MTX (4 mg/kg weekly). A control group was treated with only weekly intravenous saline solution. Animals were euthanized 6 weeks later for morphometric, histologic, immunohistochemical, and gene expression analysis of the graft and native hearts. Compared with controls, grafts of rabbits treated with LDE-PACLI showed 50% reduction of coronary stenosis, and in the LDE-MTX and LDE-MTX/PACLI stenosis was approximately 18% less than in control, but this difference was not statistically significant. In the three treatment groups, macrophage infiltration was decreased. In the LDE-MTX group, gene expression of proinflammatory factors tumor necrosis factor-α, monocyte chemoattractant protein 1, interleukin 18, vascular cellular adhesion molecule 1, and matrix metalloproteinase 12 was strongly diminished, whereas expression of antiinflammatory interleukin 10 increased. In the LDE-PACLI and LDE-PACLI/MTX groups, proinflammatory and antiinflammatory gene expressions were not consistently changed by the treatments. LDE-PACLI promoted strong improvement of cardiac allograft vasculopathy, but the decrease in coronary stenosis by LDE-MTX and LDE-MTX/PACLI was not significant. All three treatments decreased macrophage infiltration in the graft. These results may encourage future clinical trials to test this new therapeutic approach to coronary allograft vasculopathy. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Decline in Cardiovascular Mortality: Possible Causes and Implications.

PubMed

Mensah, George A; Wei, Gina S; Sorlie, Paul D; Fine, Lawrence J; Rosenberg, Yves; Kaufmann, Peter G; Mussolino, Michael E; Hsu, Lucy L; Addou, Ebyan; Engelgau, Michael M; Gordon, David

2017-01-20

If the control of infectious diseases was the public health success story of the first half of the 20th century, then the decline in mortality from coronary heart disease and stroke has been the success story of the century's past 4 decades. The early phase of this decline in coronary heart disease and stroke was unexpected and controversial when first reported in the mid-1970s, having followed 60 years of gradual increase as the US population aged. However, in 1978, the participants in a conference convened by the National Heart, Lung, and Blood Institute concluded that a significant recent downtick in coronary heart disease and stroke mortality rates had definitely occurred, at least in the US Since 1978, a sharp decline in mortality rates from coronary heart disease and stroke has become unmistakable throughout the industrialized world, with age-adjusted mortality rates having declined to about one third of their 1960s baseline by 2000. Models have shown that this remarkable decline has been fueled by rapid progress in both prevention and treatment, including precipitous declines in cigarette smoking, improvements in hypertension treatment and control, widespread use of statins to lower circulating cholesterol levels, and the development and timely use of thrombolysis and stents in acute coronary syndrome to limit or prevent infarction. However, despite the huge growth in knowledge and advances in prevention and treatment, there remain many questions about this decline. In fact, there is evidence that the rate of decline may have abated and may even be showing early signs of reversal in some population groups. The National Heart, Lung, and Blood Institute, through a request for information, is soliciting input that could inform a follow-up conference on or near the 40th anniversary of the original landmark conference to further explore these trends in cardiovascular mortality in the context of what has come before and what may lie ahead. © 2017 American Heart Association, Inc.

The significance of adiponectin as a biomarker in metabolic syndrome and/or coronary artery disease.

PubMed

Stojanović, Sanja; Ilić, Marina Deijanin; Ilić, Stevan; Petrović, Dejan; Djukić, Svetlana

2015-09-01

BACKGROUND/AIM. Adiponectin exerts profound protective actions during insulin resistence or prediabetes progression towards more severe clinical entities such as metabolic syndrome and/or cardiovascular disease. Since hypoadiponectinaemia contributes to the pathophysiology of the metabolic syndrome and coronary artery disease the level of circulating adiponectin may be an early marker of cardiovascular events. The aim of this study was to determine the relationships between serum adiponectin levels and parameters of both insulin sensitivity and obesity in patients with the metabolic syndrome and/or coronary artery disease, as well as to assess predictive value of adiponectin serum levels as a biomarker of these entitetis. The study included 100 patients with metabolic syndrome and/or coronary artery disease with different degree of insulin resistance and healthy, normoglycemic individuals. The control group comprising healthy, normoglycemic individuals was used for comparison. Serum level of adiponectin, fasting glucose, fasting insulinemia Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) index and anthropometric parameters were determined in all the subjects. Adiponectin was measured by using the ultrasensitive ELISA method. Insulinemia was measured by the radioimmunoassay (RIA) method. The presence of glycemic disorders was assessed on the basis of oral glucose tolerance test (OGTT). Results. Adiponectin level was inversely correlated with age (ρ = -0.015), parameters of both obesity (R = 0.437;p < 0.001) and insulin resistance (R = 0.374; p < 0.01). Decreasing in the level of adiponecrin was strongly implicated in the development of insulin resistance. Most importantly, a statistically significant rapid decrease ih adiponectin was in the prediabetic stages (p < 0.01). The predictor value of adiponectin was 1,356.32 ± 402.65 pg/mL. The obtained resultats suggest that adiponectin may be a useful marker in identification of individuals with risk of developing metabolic syndrome and coronary artery disease, as well as a predictor of prediabetes.

10 GY TOTAL BODY IRRADIATION INCREASES RISK OF CORONARY SCLEROSIS, DEGENERATION OF HEART STRUCTURE AND FUNCTION IN A RAT MODEL

PubMed Central

Baker, John E; Fish, Brian L; Su, Jidong; Haworth, Steven T; Strande, Jennifer L; Komorowski, Richard A; Migrino, Raymond Q; Doppalapudi, Anil; Harmann, Leanne; Li, X Allen; Hopewell, John W; Moulder, John E

2009-01-01

Purpose To determine the impact of 10 Gy total body irradiation (TBI) or local thorax irradiation, a dose relevant to a radiological terrorist threat, on lipid and liver profile, coronary microvasculature and ventricular function. Materials and methods WAG/RijCmcr rats received 10 Gy TBI followed by bone marrow transplantation, or 10 Gy local thorax irradiation. Age-matched, non-irradiated rats served as controls. The lipid profile and liver enzymes, coronary vessel morphology, nitric oxide synthase (NOS) isoforms, protease activated receptor (PAR)-1 expression and fibrinogen levels were compared. Two dimensional strain echocardiography assessed global radial and circumferential strain on the heart. Results TBI resulted in a sustained increase in total and low density lipoprotein (LDL) cholesterol (190±8 vs. 58±6; 82±8 vs. 13±3 mg/dL, respectively). The density of small coronary arterioles was decreased by 32%. Histology revealed complete blockage of some vessels while cardiomyocytes remained normal. TBI resulted in cellular peri-arterial fibrosis whereas control hearts had symmetrical penetrating vessels with less collagen and fibroblasts. TBI resulted in a 32±4% and 28±3% decrease in endothelial NOS and inducible NOS protein respectively, and a 21±4% and 35±5% increase in fibrinogen and PAR-1 protein respectively, after 120 days. TBI reduced radial strain (19±8 vs. 46±7%) and circumferential strain (-8±3 vs. −15±3%) compared to controls. Thorax-only irradiation produced no changes over the same time frame. Conclusions TBI with 10 Gy, a dose relevant to radiological terrorist threats, worsened lipid profile, injured coronary microvasculature, altered endothelial physiology and myocardial mechanics. These changes were not manifest with local thorax irradiation. Non-thoracic circulating factors may be promoting radiation-induced injury to the heart. PMID:19995235

Loss-of-function mutations in APOC3, triglycerides, and coronary disease.

PubMed

Crosby, Jacy; Peloso, Gina M; Auer, Paul L; Crosslin, David R; Stitziel, Nathan O; Lange, Leslie A; Lu, Yingchang; Tang, Zheng-zheng; Zhang, He; Hindy, George; Masca, Nicholas; Stirrups, Kathleen; Kanoni, Stavroula; Do, Ron; Jun, Goo; Hu, Youna; Kang, Hyun Min; Xue, Chenyi; Goel, Anuj; Farrall, Martin; Duga, Stefano; Merlini, Pier Angelica; Asselta, Rosanna; Girelli, Domenico; Olivieri, Oliviero; Martinelli, Nicola; Yin, Wu; Reilly, Dermot; Speliotes, Elizabeth; Fox, Caroline S; Hveem, Kristian; Holmen, Oddgeir L; Nikpay, Majid; Farlow, Deborah N; Assimes, Themistocles L; Franceschini, Nora; Robinson, Jennifer; North, Kari E; Martin, Lisa W; DePristo, Mark; Gupta, Namrata; Escher, Stefan A; Jansson, Jan-Håkan; Van Zuydam, Natalie; Palmer, Colin N A; Wareham, Nicholas; Koch, Werner; Meitinger, Thomas; Peters, Annette; Lieb, Wolfgang; Erbel, Raimund; Konig, Inke R; Kruppa, Jochen; Degenhardt, Franziska; Gottesman, Omri; Bottinger, Erwin P; O'Donnell, Christopher J; Psaty, Bruce M; Ballantyne, Christie M; Abecasis, Goncalo; Ordovas, Jose M; Melander, Olle; Watkins, Hugh; Orho-Melander, Marju; Ardissino, Diego; Loos, Ruth J F; McPherson, Ruth; Willer, Cristen J; Erdmann, Jeanette; Hall, Alistair S; Samani, Nilesh J; Deloukas, Panos; Schunkert, Heribert; Wilson, James G; Kooperberg, Charles; Rich, Stephen S; Tracy, Russell P; Lin, Dan-Yu; Altshuler, David; Gabriel, Stacey; Nickerson, Deborah A; Jarvik, Gail P; Cupples, L Adrienne; Reiner, Alex P; Boerwinkle, Eric; Kathiresan, Sekar

2014-07-03

Plasma triglyceride levels are heritable and are correlated with the risk of coronary heart disease. Sequencing of the protein-coding regions of the human genome (the exome) has the potential to identify rare mutations that have a large effect on phenotype. We sequenced the protein-coding regions of 18,666 genes in each of 3734 participants of European or African ancestry in the Exome Sequencing Project. We conducted tests to determine whether rare mutations in coding sequence, individually or in aggregate within a gene, were associated with plasma triglyceride levels. For mutations associated with triglyceride levels, we subsequently evaluated their association with the risk of coronary heart disease in 110,970 persons. An aggregate of rare mutations in the gene encoding apolipoprotein C3 (APOC3) was associated with lower plasma triglyceride levels. Among the four mutations that drove this result, three were loss-of-function mutations: a nonsense mutation (R19X) and two splice-site mutations (IVS2+1G→A and IVS3+1G→T). The fourth was a missense mutation (A43T). Approximately 1 in 150 persons in the study was a heterozygous carrier of at least one of these four mutations. Triglyceride levels in the carriers were 39% lower than levels in noncarriers (P<1×10(-20)), and circulating levels of APOC3 in carriers were 46% lower than levels in noncarriers (P=8×10(-10)). The risk of coronary heart disease among 498 carriers of any rare APOC3 mutation was 40% lower than the risk among 110,472 noncarriers (odds ratio, 0.60; 95% confidence interval, 0.47 to 0.75; P=4×10(-6)). Rare mutations that disrupt APOC3 function were associated with lower levels of plasma triglycerides and APOC3. Carriers of these mutations were found to have a reduced risk of coronary heart disease. (Funded by the National Heart, Lung, and Blood Institute and others.).

Reactive Oxygen Metabolites are Closely Associated With the Diagnosis and Prognosis of Coronary Artery Disease

PubMed Central

Hirata, Yoshihiro; Yamamoto, Eiichiro; Tokitsu, Takanori; Kusaka, Hiroaki; Fujisue, Koichiro; Kurokawa, Hirofumi; Sugamura, Koichi; Maeda, Hirofumi; Tsujita, Kenichi; Kaikita, Koichi; Hokimoto, Seiji; Sugiyama, Seigo; Ogawa, Hisao

2015-01-01

Background Reactive oxygen species (ROS) are associated with development of coronary artery disease (CAD). However, there's no useful biomarker of ROS in CAD. Methods and Results We recruited 395 consecutive CAD patients who were performed coronary angiography (262 male and 133 female, age 70.2±10), and we measured serum derivatives of reactive oxidative metabolites (DROM) were measured. Two hundred twenty‐seven non‐CAD patients were also enrolled. We performed follow‐up study in these 395 CAD patients and case‐control study after risk factor and 1:1 pair matching (both, n=163). As subgroup analysis, DROM were also measured at the aortic root and the coronary sinus in 59 CAD patients. DROM were significantly higher in CAD patients (n=163, median [inter‐quartile range, IQR]=338 [302 to 386]) than in risk factor‐matched non‐CAD patients (n=163, 311 [282 to 352.5], effect size=0.33, P<0.001). During a mean follow‐up period of 20 months of 395 CAD patients, 83 cardiovascular events were recorded. Kaplan‐Meier analysis showed a higher probability of cardiovascular events in the high‐DROM group (>346 U.CARR) than in the low‐DROM group (≤346 U.CARR) (P=0.001 [log‐rank test]). Multivariate Cox hazard analysis identified ln‐DROM as an independent predictor for cardiovascular events (hazard ratio: 10.8, 95% confidence interval: 2.76 to 42.4, P=0.001). The transcardiac gradient of DROM was significantly higher in CAD patients than in non‐CAD patients (−2.0 [−9.0 to 9.0] versus 8 [−8.0 to 28.3], effect size=0.21, P=0.04), indicating that DROM production in coronary circulation is associated with development of CAD. Conclusion DROM are increased in CAD patients and associated with future cardiovascular events. DROM might provide clinical benefits for risk stratification of CAD. Clinical Trial Registration URL: http://www.umin.ac.jp/ctr/. Unique identifier: UMIN000012990. PMID:25630910

Loss-of-Function Mutations in APOC3, Triglycerides, and Coronary Disease

PubMed Central

2014-01-01

Background Plasma triglyceride levels are heritable and are correlated with the risk of coronary heart disease. Sequencing of the protein-coding regions of the human genome (the exome) has the potential to identify rare mutations that have a large effect on phenotype. Methods We sequenced the protein-coding regions of 18,666 genes in each of 3734 participants of European or African ancestry in the Exome Sequencing Project. We conducted tests to determine whether rare mutations in coding sequence, individually or in aggregate within a gene, were associated with plasma triglyceride levels. For mutations associated with triglyceride levels, we subsequently evaluated their association with the risk of coronary heart disease in 110,970 persons. Results An aggregate of rare mutations in the gene encoding apolipoprotein C3 (APOC3) was associated with lower plasma triglyceride levels. Among the four mutations that drove this result, three were loss-of-function mutations: a nonsense mutation (R19X) and two splice-site mutations (IVS2+1G→A and IVS3+1G→T). The fourth was a missense mutation (A43T). Approximately 1 in 150 persons in the study was a heterozygous carrier of at least one of these four mutations. Triglyceride levels in the carriers were 39% lower than levels in noncarriers (P<1×10−20), and circulating levels of APOC3 in carriers were 46% lower than levels in noncarriers (P = 8×10−10). The risk of coronary heart disease among 498 carriers of any rare APOC3 mutation was 40% lower than the risk among 110,472 noncarriers (odds ratio, 0.60; 95% confidence interval, 0.47 to 0.75; P = 4×10−6). Conclusions Rare mutations that disrupt APOC3 function were associated with lower levels of plasma triglycerides and APOC3. Carriers of these mutations were found to have a reduced risk of coronary heart disease. (Funded by the National Heart, Lung, and Blood Institute and others.) PMID:24941081

Augmented TLR2 expression on monocytes in both human Kawasaki disease and a mouse model of coronary arteritis.

PubMed

Lin, I-Chun; Kuo, Ho-Chang; Lin, Ying-Jui; Wang, Feng-Shen; Wang, Lin; Huang, Shun-Chen; Chien, Shao-Ju; Huang, Chien-Fu; Wang, Chih-Lu; Yu, Hong-Ren; Chen, Rong-Fu; Yang, Kuender D

2012-01-01

Kawasaki disease (KD) of unknown immunopathogenesis is an acute febrile systemic vasculitis and the leading cause of acquired heart diseases in childhood. To search for a better strategy for the prevention and treatment of KD, this study compared and validated human KD immunopathogenesis in a mouse model of Lactobacillus casei cell wall extract (LCWE)-induced coronary arteritis. Recruited subjects fulfilled the criteria of KD and were admitted for intravenous gamma globulin (IVIG) treatment at the Kaohsiung Chang Gung Memorial Hospital from 2001 to 2009. Blood samples from KD patients were collected before and after IVIG treatment, and cardiovascular abnormalities were examined by transthoracic echocardiography. Wild-type male BALB/c mice (4-week-old) were intraperitoneally injected with LCWE (1 mg/mL) to induce coronary arteritis. The induced immune response in mice was examined on days 1, 3, 7, and 14 post injections, and histopathology studies were performed on days 7 and 14. Both human KD patients and LCWE-treated mice developed coronary arteritis, myocarditis, valvulitis, and pericarditis, as well as elevated plasma levels of interleukin (IL)-2, IL-6, IL-10, monocyte chemoattractant protein (MCP)-1, and tumor necrosis factor (TNF)-α in acute phase. Most of these proinflammatory cytokines declined to normal levels in mice, whereas normal levels were achieved in patients only after IVIG treatment, with a few exceptions. Toll-like receptor (TLR)-2, but not TLR4 surface enhancement on circulating CD14+ monocytes, was augmented in KD patients before IVIG treatment and in LCWE-treated mice, which declined in patients after IVIG treatment. This result suggests that that not only TLR2 augmentation on CD14+ monocytes might be an inflammatory marker for both human KD patients and LCWE-induced CAL mouse model but also this model is feasible for studying therapeutic strategies of coronary arteritis in human KD by modulating TLR2-mediated immune activation on CD14+ monocytes.

Augmented TLR2 Expression on Monocytes in both Human Kawasaki Disease and a Mouse Model of Coronary Arteritis

PubMed Central

Lin, I-Chun; Kuo, Ho-Chang; Lin, Ying-Jui; Wang, Feng-Shen; Wang, Lin; Huang, Shun-Chen; Chien, Shao-Ju; Huang, Chien-Fu; Wang, Chih-Lu; Yu, Hong-Ren; Chen, Rong-Fu; Yang, Kuender D.

2012-01-01

Background Kawasaki disease (KD) of unknown immunopathogenesis is an acute febrile systemic vasculitis and the leading cause of acquired heart diseases in childhood. To search for a better strategy for the prevention and treatment of KD, this study compared and validated human KD immunopathogenesis in a mouse model of Lactobacillus casei cell wall extract (LCWE)-induced coronary arteritis. Methods Recruited subjects fulfilled the criteria of KD and were admitted for intravenous gamma globulin (IVIG) treatment at the Kaohsiung Chang Gung Memorial Hospital from 2001 to 2009. Blood samples from KD patients were collected before and after IVIG treatment, and cardiovascular abnormalities were examined by transthoracic echocardiography. Wild-type male BALB/c mice (4-week-old) were intraperitoneally injected with LCWE (1 mg/mL) to induce coronary arteritis. The induced immune response in mice was examined on days 1, 3, 7, and 14 post injections, and histopathology studies were performed on days 7 and 14. Results Both human KD patients and LCWE-treated mice developed coronary arteritis, myocarditis, valvulitis, and pericarditis, as well as elevated plasma levels of interleukin (IL)-2, IL-6, IL-10, monocyte chemoattractant protein (MCP)-1, and tumor necrosis factor (TNF)-α in acute phase. Most of these proinflammatory cytokines declined to normal levels in mice, whereas normal levels were achieved in patients only after IVIG treatment, with a few exceptions. Toll-like receptor (TLR)-2, but not TLR4 surface enhancement on circulating CD14+ monocytes, was augmented in KD patients before IVIG treatment and in LCWE-treated mice, which declined in patients after IVIG treatment. Conclusion This result suggests that that not only TLR2 augmentation on CD14+ monocytes might be an inflammatory marker for both human KD patients and LCWE-induced CAL mouse model but also this model is feasible for studying therapeutic strategies of coronary arteritis in human KD by modulating TLR2-mediated immune activation on CD14+ monocytes. PMID:22737215

A Small Nonerythropoietic Helix B Surface Peptide Based upon Erythropoietin Structure Is Cardioprotective against Ischemic Myocardial Damage

PubMed Central

Ahmet, Ismayil; Tae, Hyun-Jin; Juhaszova, Magdalena; Riordon, Daniel R; Boheler, Kenneth R; Sollott, Steven J; Brines, Michael; Cerami, Anthony; Lakatta, Edward G; Talan, Mark I

2011-01-01

Strong cardioprotective properties of erythropoietin (EPO) reported over the last 10 years have been difficult to translate to clinical applications for ischemic cardioprotection owing to undesirable parallel activation of erythropoiesis and thrombogenesis. A pyroglutamate helix B surface peptide (pHBP), recently engineered to include only a part of the EPO molecule that does not bind to EPO receptor and thus, is not erythropoietic, retains tissue protective properties of EPO. Here we compared the ability of pHBP and EPO to protect cardiac myocytes from oxidative stress in vitro and cardiac tissue from ischemic damage in vivo. HBP, similar to EPO, increased the reactive oxygen species (ROS) threshold for induction of the mitochondrial permeability transition by 40%. In an experimental model of myocardial infarction induced by permanent ligation of a coronary artery in rats, a single bolus injection of 60 μg/kg of pHBP immediately after coronary ligation, similar to EPO, reduced apoptosis in the myocardial area at risk, examined 24 h later, by 80% and inflammation by 34%. Myocardial infarction (MI) measured 24 h after coronary ligation was similarly reduced by 50% in both pHBP- and EPO-treated rats. Two wks after surgery, left ventricular remodeling (ventricular dilation) and functional decline (fall in ejection fraction) assessed by echocardiography were significantly and similarly attenuated in pHBP- and EPO-treated rats, and MI size was reduced by 25%. The effect was retained during the 6-wk follow-up. A single bolus injection of pHBP immediately after coronary ligation was effective in reduction of MI size in a dose as low as 1 μg/kg, but was ineffective at a 60 μg/kg dose if administered 24 h after MI induction. We conclude that pHBP is equally cardioprotective with EPO and deserves further consideration as a safer alternative to rhEPO in the search for therapeutic options to reduce myocardial damage following blockade of the coronary circulation. PMID:21170473

On a sparse pressure-flow rate condensation of rigid circulation models

PubMed Central

Schiavazzi, D. E.; Hsia, T. Y.; Marsden, A. L.

2015-01-01

Cardiovascular simulation has shown potential value in clinical decision-making, providing a framework to assess changes in hemodynamics produced by physiological and surgical alterations. State-of-the-art predictions are provided by deterministic multiscale numerical approaches coupling 3D finite element Navier Stokes simulations to lumped parameter circulation models governed by ODEs. Development of next-generation stochastic multiscale models whose parameters can be learned from available clinical data under uncertainty constitutes a research challenge made more difficult by the high computational cost typically associated with the solution of these models. We present a methodology for constructing reduced representations that condense the behavior of 3D anatomical models using outlet pressure-flow polynomial surrogates, based on multiscale model solutions spanning several heart cycles. Relevance vector machine regression is compared with maximum likelihood estimation, showing that sparse pressure/flow rate approximations offer superior performance in producing working surrogate models to be included in lumped circulation networks. Sensitivities of outlets flow rates are also quantified through a Sobol’ decomposition of their total variance encoded in the orthogonal polynomial expansion. Finally, we show that augmented lumped parameter models including the proposed surrogates accurately reproduce the response of multiscale models they were derived from. In particular, results are presented for models of the coronary circulation with closed loop boundary conditions and the abdominal aorta with open loop boundary conditions. PMID:26671219

Circulating endothelial and progenitor cells: Evidence from acute and long-term exercise effects

PubMed Central

Koutroumpi, Matina; Dimopoulos, Stavros; Psarra, Katherini; Kyprianou, Theodoros; Nanas, Serafim

2012-01-01

Circulating bone-marrow-derived cells, named endothelial progenitor cells (EPCs), are capable of maintaining, generating, and replacing terminally differentiated cells within their own specific tissue as a consequence of physiological cell turnover or tissue damage due to injury. Endothelium maintenance and restoration of normal endothelial cell function is guaranteed by a complex physiological procedure in which EPCs play a significant role. Decreased number of peripheral blood EPCs has been associated with endothelial dysfunction and high cardiovascular risk. In this review, we initially report current knowledge with regard to the role of EPCs in healthy subjects and the clinical value of EPCs in different disease populations such as arterial hypertension, obstructive sleep-apnea syndrome, obesity, diabetes mellitus, peripheral arterial disease, coronary artery disease, pulmonary hypertension, and heart failure. Recent studies have introduced the novel concept that physical activity, either performed as a single exercise session or performed as part of an exercise training program, results in a significant increase of circulating EPCs. In the second part of this review we provide preliminary evidence from recent studies investigating the effects of acute and long-term exercise in healthy subjects and athletes as well as in disease populations. PMID:23272272

A Double-Blinded Randomized Study Investigating a Possible Anti-Inflammatory Effect of Saxagliptin versus Placebo as Add-On Therapy in Patients with Both Type 2 Diabetes And Stable Coronary Artery Disease.

PubMed

Njerve, Ida Unhammer; Åkra, Sissel; Weiss, Thomas W; Solheim, Svein; Øvstebø, Reidun; Aass, Hans Christian D; Byrkjeland, Rune; Arnesen, Harald; Seljeflot, Ingebjørg

2017-01-01

Promising results regarding potential anti-inflammatory and antiatherosclerotic effects of gliptins have been reported. Our aim was to investigate whether saxagliptin treatment modifies expression of inflammatory markers, primarily in peripheral blood mononuclear cells (PBMCs) and in circulating leukocytes in patients with stable coronary artery disease (CAD) and T2DM. Patients ( n = 12) were randomized to saxagliptin 5 mg daily or placebo for 3 months. Samples were taken at baseline and end of study in fasting state prior to intake of medications. PBMCs were isolated and cryopreserved at -150°C until ex vivo exposed to 1 ng/mL of lipopolysaccharide (LPS) for 4 hours. Gene expression was performed with custom-designed TaqMan® Arrays and relative quantification by real-time PCR (RT-qPCR). HbA1c was reduced in the saxagliptin-treated group compared to that in the change with placebo ( p = 0.042). In unstimulated PBMCs and in circulating leukocytes, we observed a significant increase in IL-10 expression in the saxagliptin group ( p = 0.043, both), significantly different from that in the placebo ( p = 0.009 and p = 0.032, resp.). No between group differences in changes were observed in any of the selected proinflammatory markers. In our small cohort of patients with combined T2DM and CAD, a possible anti-inflammatory effect of saxagliptin, observed in the present study by upregulation of IL-10 in leukocytes, needs to be confirmed in larger studies.

Hepatocyte growth factor is associated with progression of atherosclerosis: The Multi-Ethnic Study of Atherosclerosis (MESA).

PubMed

Bell, Elizabeth J; Decker, Paul A; Tsai, Michael Y; Pankow, James S; Hanson, Naomi Q; Wassel, Christina L; Larson, Nicholas B; Cohoon, Kevin P; Budoff, Matthew J; Polak, Joseph F; Stein, James H; Bielinski, Suzette J

2018-05-01

Hepatocyte growth factor (HGF) has previously been associated with risk of stroke, coronary heart disease, and atherosclerosis. We hypothesized that higher circulating HGF is associated with greater progression of measures of atherosclerosis: coronary artery calcium (CAC) and carotid plaque. Participants aged 45-84 years from the prospective cohort study Multi-Ethnic Study of Atherosclerosis had HGF measured at baseline (between 2000 and 2002) and were followed for progression of atherosclerosis for up to 12 years. CAC was measured at all five exams using the Agatston method. Mixed-effects models were used to examine the association of HGF and CAC progression among 6695 participants with available data. Relative risk regression was used to assess the association between HGF and new or additional carotid plaque between exams 1 and 5 in 3400 participants with available data. All point estimates were adjusted for potential confounding variables. Each standard deviation higher HGF at baseline was associated with 2.9 Agatston units/year greater CAC progression (95% CI: 1.6-4.2, p < 0.0001), and the magnitude of this association differed by race/ethnicity (p value for interaction by race = 0.003). Each standard deviation higher HGF at baseline was associated with a 4% higher risk of new or additional carotid plaque (95% CI: 1.01-1.08, p = 0.005). Higher levels of HGF were significantly associated with greater progression of atherosclerosis in this large and diverse population. Circulating HGF continues to show promise as a potential clinical biomarker for cardiovascular disease. Copyright © 2018 Elsevier B.V. All rights reserved.

Plasma complement and vascular complement deposition in patients with coronary artery disease with and without inflammatory rheumatic diseases

PubMed Central

2017-01-01

Purpose Inflammatory rheumatic diseases (IRD) are associated with accelerated coronary artery disease (CAD), which may result from both systemic and vascular wall inflammation. There are indications that complement may be involved in the pathogenesis of CAD in Systemic Lupus Erythematosus (SLE) and Rheumatoid Arthritis (RA). This study aimed to evaluate the associations between circulating complement and complement activation products with mononuclear cell infiltrates (MCI, surrogate marker of vascular inflammation) in the aortic media and adventitia in IRDCAD and non-IRDCAD patients undergoing coronary artery bypass grafting (CABG). Furthermore, we compared complement activation product deposition patterns in rare aorta adventitial and medial biopsies from SLE, RA and non-IRD patients. Methods We examined plasma C3 (p-C3) and terminal complement complexes (p-TCC) in 28 IRDCAD (SLE = 3; RA = 25), 52 non-IRDCAD patients, and 32 IRDNo CAD (RA = 32) from the Feiring Heart Biopsy Study. Aortic biopsies taken from the CAD only patients during CABG were previously evaluated for adventitial MCIs. The rare aortic biopsies from 3 SLE, 3 RA and 3 non-IRDCAD were assessed for the presence of C3 and C3d using immunohistochemistry. Results IRDCAD patients had higher p-TCC than non-IRDCAD or IRDNo CAD patients (p<0.0001), but a similar p-C3 level (p = 0.42). Circulating C3 was associated with IRD duration (ρ, p-value: 0.46, 0.03). In multiple logistic regression analysis, IRD remained significantly related to the presence and size of MCI (p<0.05). C3 was present in all tissue samples. C3d was detected in the media of all patients and only in the adventitia of IRD patients (diffuse in all SLE and focal in one RA). Conclusion The independent association of IRD status with MCI and the observed C3d deposition supports the unique relationship between rheumatic disease, and, in particular, SLE with the complement system. Exaggerated systemic and vascular complement activation may accelerate CVD, serve as a CVD biomarker, and represent a target for new therapies. PMID:28362874

Current evidence for the safety and efficacy of the bio-engineered dual therapy COMBO stent.

PubMed

Kalkman, Deborah N; Chandrasekhar, Jaya; de Winter, Robbert J; Mehran, Roxana

2018-06-01

The novel dual-therapy COMBO stent aims to promote vessel healing after percutaneous coronary intervention (PCI) in patients with coronary artery disease. The pro-healing technique consists of an anti-CD34+ antibody layer that attracts circulating endothelial progenitor cells (EPCs), which bind to the stent surface and allow rapid endothelialization by differentiation of the EPCs into normal endothelial cells. The COMBO stent combines this pro-healing technique with an abluminal drug elution of sirolimus. The promise of this dual-therapy stent is that it may safely allow a shortened duration of dual-antiplatelet therapy (DAPT) after stent placement. Moreover, with a mature endothelial layer, lower rates of in-stent restenosis may be expected. Clinical outcomes after COMBO stent implantation have been recently evaluated in both randomized trials and large, prospective, multicenter registries, showing low clinical event rates of in-stent restenosis and stent thrombosis. Randomized clinical trials (HARMONEE and RECOVERY) have demonstrated the non-inferiority of COMBO versus "first in class" second generation and newer generation drug-eluting stents. Safety and efficacy of 3 months of DAPT after COMBO stent placement in patients presenting with acute coronary syndrome has been evaluated in the large REDUCE randomized controlled trial, showing non-inferiority to standard duration of 12-month DAPT. In this review we provide an overview of the current pre-clinical and clinical evidence for the performance of the COMBO stent.

Report of the American Heart Association (AHA) Scientific Sessions 2012, Los Angeles.

PubMed

Fujita, Jun

2013-01-01

The American Heart Association (AHA) Scientific Sessions were held for the first time in Los Angeles in 2012, with the most up-to-date basic and clinical science in the field presented and heard by physicians, research scientists, students, and paramedical personnel from 100 countries. Japan accounted for the second highest number of submitted abstracts and the Japanese Circulation Society actively contributed to the success of the AHA Scientific Sessions this year. The Late-Breaking Clinical Trial sessions comprised 27 clinical studies presented in the main hall. The FREEDOM study revealed the superiority of using a coronary artery bypass graft for diabetic multivessel coronary artery diseases over percutaneous coronary intervention using a drug-eluting stent. A new peptide hormone, serelaxin, improved dyspnea in heart failure patients and significantly reduced mortality rates according to the RELAX-AHF study. In the basic sciences, primary necrosis in mitochondria was the hot topic, while genetics, including genome-wide association studies, and epigenetics were strong features of the basic and clinical cardiovascular (CV) science. It was also clear that regenerative medicine is now part of mainstream CV research, with several clinical trials underway and many basic research projects ongoing around the world. Induced pluripotent stem cells in particular have the potential to change CV medicine, and will underpin the next era of regenerative medicine and personal therapies for heart diseases.

Haplotypes in the CRP gene associated with increased BMI and levels of CRP in subjects with type 2 diabetes or obesity from Southwestern Mexico.

PubMed

Martínez-Calleja, América; Quiróz-Vargas, Irma; Parra-Rojas, Isela; Muñoz-Valle, José Francisco; Leyva-Vázquez, Marco A; Fernández-Tilapa, Gloria; Vences-Velázquez, Amalia; Cruz, Miguel; Salazar-Martínez, Eduardo; Flores-Alfaro, Eugenia

2012-01-01

We evaluated the association between four polymorphisms in the CRP gene with circulating levels of C-reactive protein (CRP), type 2 diabetes (T2D), obesity, and risk score of coronary heart disease. We studied 402 individuals and classified them into four groups: healthy, obese, T2D obese, and T2D without obesity, from Guerrero, Southwestern Mexico. Blood levels of CRP, glucose, cholesterol, triglycerides, and leukocytes were measured. Genotyping was performed by PCR/RFLP, and the risk score for coronary heart disease was determined by the Framingham's methodology. The TT genotype of SNP rs1130864 was associated with increased body mass index and T2D patients with obesity. We found that the haplotype 2 (TGAG) was associated with increased levels of CRP (β = 0.3; 95%CI: 0.1, 0.5; P = 0.005) and haplotype 7 (TGGG) with higher body mass index (BMI) (β = 0.2; 95%CI: 0.1, 0.3; P < 0.001). The risk score for coronary heart disease was associated with increased levels of CRP, but not with any polymorphism or haplotype. The association between the TT genotype of SNP rs1130864 with obesity and the haplotype 7 with BMI may explain how obesity and genetic predisposition increase the risk of diseases such as T2D in the population of Southwestern Mexico.

Lipid-Altering Therapies and the Progression of Atherosclerotic Disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wierzbicki, Anthony S.

2007-04-15

Lipids play a key role in the progression of atherosclerosis, and lipid-lowering therapies have been studied for 30 years in coronary disease. Measurement of the progression of atherosclerosis through carotid intima-media thickness, coronary mean lumen diameter, and, mostly recently, intravascular ultrasound is generally accepted. This article reviews the role of lipid-lowering therapies in changing the rate of atherosclerosis progression in the coronary and carotid circulations. Statins are the primary therapy used to reduce atherosclerosis and cardiovascular events, including strokes and transient ischemic attacks, and have benefits in reducing events in patients undergoing carotid endarterectomy. In contrast, data for other agents,more » including fibrates and nicotinic acid, in reducing the progression of atherosclerosis are less extensive and not as well known. There is increasing interest in optimizing the whole lipid profile, as this might deliver extra benefits over and above statin therapy alone. Initial proof of this concept has recently come from studies that measured the progression of atherosclerosis and showed that adding nicotinic acid to statin therapy and, more directly, infusion of high-density lipoprotein-like particles reduced progression and indeed might induce regression of the disease. It is likely that the management of significant carotid stenosis will become ever more drug focused and will be customized to the lipid profile of each patient with intervention reserved only for late-stage symptomatic disease.« less

[Coronary disease extension determines mobilization of endothelial progenitor cells and cytokines after a first myocardial infarction with ST elevation].

PubMed

Jiménez-Navarro, Manuel F; González, Francisco Jesús; Caballero-Borrego, Juan; Marchal, Juan Antonio; Rodríguez-Losada, Noela; Carrillo, Esmeralda; García-Pinilla, José Manuel; Hernández-García, José M; Pérez-González, Rita; Ramírez, Gemma; Aránega, Antonia; de Teresa Galván, Eduardo

2011-12-01

Multivessel coronary disease is still a postinfarction prognostic marker despite new forms of reperfusion, such as primary angioplasty. The aim of this study was to determine the time sequence of various sets of endothelial progenitor cells and angiogenic cytokines (vascular endothelial growth factor, hepatocyte growth factor) according to the degree of extension of the postinfarction coronary disease. We studied the release kinetics in 32 patients admitted for a first myocardial infarction with ST elevation, grouped according to whether they had single or multivessel disease, and 26 controls. The patients had a higher number of endothelial progenitor cells and angiogenic cytokines than the controls at all 3 measurements (admission, day 3, and day 7) of the following subsets: CD34, CD34+CD133+, CD34+KDR+, and CD34+CD133+KDR+CD45+(weak); this latter was higher on day 7. The levels of these cell subsets were all higher in the patients with single-vessel disease and at all 3 measurements. The vascular endothelial growth factor levels were raised during the first week and the hepatocyte growth factor showed an early peak on admission for infarction. No significant differences were seen in the cytokines according to coronary disease extension. Although the release kinetics of different subsets of endothelial progenitor cells in patients with a first acute myocardial infarction with ST elevation was similar in those with single vessel disease to those with multivessel disease, the number of circulating endothelial progenitor cells was greater in the patients with single vessel disease. The vascular endothelial growth factor levels were raised during the first postinfarction week and the hepatocyte growth factor were higher on admission. Copyright © 2011 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

Race-Specific Associations of Myeloperoxidase with Atherosclerosis in a Population-Based Sample: The Dallas Heart Study

PubMed Central

Chen, Lu; Rohatgi, Anand; Ayers, Colby R.; Das, Sandeep R.; Khera, Amit; Berry, Jarett D.; McGuire, Darren K.; de Lemos, James A.

2011-01-01

Objective Myeloperoxidase (MPO) is a leukocyte-derived enzyme that appears to be directly involved in atherosclerosis development. We evaluated the association of circulating MPO with coronary and aortic atherosclerosis in a large, multiethnic population. Methods and Results Plasma levels of MPO were measured in 3294 subjects participating in the Dallas Heart Study, a probability-based population sample. Coronary artery calcification (CAC) was measured by EBCT, and abdominal aorta plaque prevalence (AP) and burden (APB), as well as abdominal aorta wall thickness (AWT) were determined by MRI. Associations between MPO and atherosclerosis phenotypes were assessed in multivariable analyses adjusting for traditional atherosclerosis risk factors. MPO levels in the 4th compared with 1st quartile independently associated with prevalent AP (OR 1.41, 95% CI 1.08–1.84), APB (beta coefficient 0.23, p=0.02), and AWT (beta coefficient 0.04, p=0.03), but not with prevalent CAC (OR 0.84, 95% CI 0.61–1.17). MPO remained associated with aortic atherosclerosis phenotypes but not coronary calcification after adjustment for other inflammatory biomarkers. A significant interaction was observed between race/ethnicity, MPO and AP (pinteraction=0.038), such that MPO levels in the 4th vs 1st quartile associated with prevalent AP in African Americans, (OR 1.81, 95% CI 1.23–2.65) but not in White or Hispanic participants (OR 0.99, 95% CI 0.68–1.44). Conclusion Higher levels of MPO associated with aortic but not coronary atherosclerosis, with significant associations limited to African American participants. These findings suggest that MPO might be a novel risk factor contributing to racial disparities in peripheral vascular disease. PMID:21917261

Differences between perivascular adipose tissue surrounding the heart and the internal mammary artery: possible role for the leptin-inflammation-fibrosis-hypoxia axis.

PubMed

Drosos, Ioannis; Chalikias, Georgios; Pavlaki, Maria; Kareli, Dimitra; Epitropou, Grigorios; Bougioukas, Georgios; Mikroulis, Dimitrios; Konstantinou, Fotios; Giatromanolaki, Alexandra; Ritis, Konstantinos; Münzel, Thomas; Tziakas, Dimitrios; Konstantinides, Stavros; Schäfer, Katrin

2016-11-01

The factors mediating the paracrine effects of perivascular adipose tissue (PVAT) in atherosclerosis are largely unknown. The adipokine leptin has been implicated in the increased cardiovascular risk in obesity and may locally promote neointima formation independently of circulating leptin levels. In patients with established coronary artery disease, we examined the expression of leptin as well as of its possible inducers in 'cardiac' PVAT surrounding the aortic root and coronary arteries (C-PVAT), and compared it to the PVAT surrounding the internal mammary artery (IMA-PVAT), a vessel resistant to atherosclerosis. Tissue specimens collected from male patients undergoing coronary artery bypass surgery were processed for real-time PCR, ELISA, in situ hybridization, and immunohistochemistry analysis. Leptin protein expression was elevated in C-PVAT compared to IMA-PVAT, independent of serum leptin levels. Compared to IMA-PVAT, C-PVAT exhibited more pronounced angiogenesis and inflammation, as indicated by significantly higher numbers of PECAM1-positive vessels and CD68-positive macrophages, and was characterized by a greater extent of fibrosis and hypoxia. Increased expression of hypoxia-inducible factor-1α and Fos-like antigen (FOSL)2, factors known to enhance leptin gene transcription, was observed in C-PVAT. As a proof of concept, exposure of human adipocytes to chemical hypoxia resulted in significantly increased FOSL2 and leptin mRNA levels. A higher degree of local tissue hypoxia and up-regulation of leptin expression in the perivascular adipose tissue, along with increased vascularization, inflammation, and fibrosis, may contribute to the increased atherosclerotic plaque burden in the coronary arteries compared to the IMA.

Accelerated collagen turnover in women with angina pectoris without obstructive coronary artery disease: An iPOWER substudy.

PubMed

Nielsen, Signe H; Mygind, Naja D; Michelsen, Marie M; Bechsgaard, Daria F; Suhrs, Hannah E; Genovese, Federica; Nielsen, Henning B; Brix, Susanne; Karsdal, Morten; Prescott, Eva; Kastrup, Jens

2018-05-01

Aim Collagens are major cardiac extracellular matrix components, known to be actively remodelled and accumulated during diffuse myocardial fibrosis. We evaluated whether accelerated collagen turnover described by neo-epitope biomarkers reflecting collagen formation and degradation separates patients with diffuse myocardial fibrosis from asymptomatic controls. Methods and results Seventy-one women with angina pectoris without significant coronary artery disease assessed by invasive coronary angiogram were included. Competitive enzyme-linked immunosorbent assays (ELISAs) measuring circulating protein fragments in serum assessed the formation and degradation of collagen type III (Pro-C3, C3M and C3C), IV (P4NP7S and C4M), V (Pro-C5 and C5M) and VI (Pro-C6 and C6M), and degradation of collagen type I (C1M). Serum samples from 32 age-matched asymptomatic women were included as controls. Symptomatic women presented significantly elevated levels of Pro-C6, C3C, C3M, C4M and C8-C ( p < 0.0001-0.0058) and significantly decreased levels of Pro-C3, C5M and C6M ( p < 0.0001-0.041), reflecting accelerated collagen turnover and an imbalanced collagen formation and degradation compared to controls. Cardiac magnetic resonance T1 mapping was performed to determine extracellular volume fraction and thus diffuse myocardial fibrosis. A significant association was identified between C5M and extracellular volume fraction by cardiac magnetic resonance ( p = 0.01). Conclusion Women with angina pectoris, but without significant obstructive coronary artery disease, showed an imbalanced collagen turnover compared to asymptomatic controls. The examined biomarkers are tools to monitor active collagen remodelling in patients with angina pectoris, in risk of developing myocardial fibrosis.

Kv7 channels critically determine coronary artery reactivity: left-right differences and down-regulation by hyperglycaemia.

PubMed

Morales-Cano, Daniel; Moreno, Laura; Barreira, Bianca; Pandolfi, Rachele; Chamorro, Virginia; Jimenez, Rosario; Villamor, Eduardo; Duarte, Juan; Perez-Vizcaino, Francisco; Cogolludo, Angel

2015-04-01

Voltage-gated potassium channels encoded by KCNQ genes (Kv7 channels) are emerging as important regulators of vascular tone. In this study, we analysed the contribution of Kv7 channels to the vasodilation induced by hypoxia and the cyclic AMP pathway in the coronary circulation. We also assessed their regional distribution and possible impairment by diabetes. We examined the effects of Kv7 channel modulators on K+ currents and vascular reactivity in rat left and right coronary arteries (LCAs and RCAs, respectively). Currents from LCA were more sensitive to Kv7 channel inhibitors (XE991, linopirdine) and activators (flupirtine, retigabine) than those from RCA. Accordingly, LCAs were more sensitive than RCAs to the relaxation induced by Kv7 channel enhancers. Likewise, relaxation induced by the adenylyl cyclase activator forskolin and hypoxia, which were mediated through Kv7 channel activation, were greater in LCA than in RCA. KCNQ1 and KCNQ5 expression was markedly higher in LCA than in RCA. After incubation with high glucose (HG, 30 mmol/L), myocytes from LCA, but not from RCA, were more depolarized and showed reduced Kv7 currents. In HG-incubated LCA, the effects of Kv7 channel modulators and forskolin were diminished, and the expression of KCNQ1 and KCNQ5 was reduced. Finally, vascular responses induced by Kv7 channel modulators were impaired in LCA, but not in RCA, from type 1 diabetic rats. Our results reveal that the high expression and function of Kv7 channels in the LCA and their down-regulation by diabetes critically determine the sensitivity to key regulators of coronary tone. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

New imaging technology: measurement of myocardial perfusion by contrast echocardiography

NASA Technical Reports Server (NTRS)

Rubin, D. N.; Thomas, J. D.

2000-01-01

Myocardial perfusion imaging has long been a goal for the non-invasive echocardiographic assessment of the heart. However, many factors at play in perfusion imaging have made this goal elusive. Harmonic imaging and triggered imaging with newer contrast agents have made myocardial perfusion imaging potentially practical in the very near future. The application of indicator dilution theory to the coronary circulation and bubble contrast agents is fraught with complexities and sources of error. Therefore, quantification of myocardial perfusion by non-invasive echocardiographic imaging requires further investigation in order to make this technique clinically viable.

Association of adiponectin gene polymorphism (+T45G) with acute coronary syndrome and circulating adiponectin levels.

PubMed

Rizk, Nasser M; El-Menyar, Ayman; Marei, Isra; Sameer, Maha; Musad, Tasneem; Younis, Dima; Farag, Fathi; Basem, Nora; Al-Ali, Khalid; Al Suwaidi, Jassim

2013-05-01

We investigated the association of adiponectin gene polymorphisms (+T45G and +G276T) and adiponectin levels with acute coronary syndrome (ACS) among Arabs in Qatar. A case-control study was performed in 142 Arab patients with ACS and 122 controls. Genotypes were determined using TaqMan real-time polymerase chain reaction assay. The TT, TG, and GG genotype frequencies of the T45G variant were significantly different among cases and controls (P = .023) but not significant for G276T genotypic frequencies. It was found that only the +45G allele was significantly associated with 3-fold increased risk of ACS (odds ratio = 2.77; 1.03-6.96; P = .043) among patients, using the genetic recessive model. Carriers of GG alleles had significantly lower adiponectin levels compared to TT/TG carriers of T45G in patients with ACS. The present study suggests that only T45G single-nucleotide polymorphism in the adiponectin gene is associated with higher odds for ACS events and has an effect on serum adiponectin levels among Arab populations.

Cardiac Intensive Care Unit Management of Patients After Cardiac Arrest: Now the Real Work Begins.

PubMed

Randhawa, Varinder K; Grunau, Brian E; Debicki, Derek B; Zhou, Jian; Hegazy, Ahmed F; McPherson, Terry; Nagpal, A Dave

2018-02-01

Survival with a good quality of life after cardiac arrest continues to be abysmal. Coordinated resuscitative care does not end with the effective return of spontaneous circulation (ROSC)-in fact, quite the contrary is true. Along with identifying and appropriately treating the precipitating cause, various components of the post-cardiac arrest syndrome also require diligent observation and management, including post-cardiac arrest neurologic injury and myocardial dysfunction, systemic ischemia-reperfusion phenomenon with potential consequent multiorgan failure, and the various sequelae of critical illness. There is growing evidence that an early invasive approach to coronary reperfusion with percutaneous coronary intervention, together with active targeted temperature management and optimization of hemodynamic, ventilator, and metabolic parameters, may improve survival and neurologic outcomes in cardiac arrest survivors. Neuroprognostication is complex, as are survivorship issues and long-term rehabilitation. Our paramedics, emergency physicians, and resuscitation specialists are all to be congratulated for ever-increasing success with ROSC… but now the real work begins. Copyright © 2017 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

From debulking to delivery: sequential use of rotational atherectomy and Guidezilla™ for complex saphenous vein grafts intervention.

PubMed

Pellicano, Mariano; Floré, Vincent; Barbato, Emanuele; De Bruyne, Bernard

2018-06-19

Percutaneous coronary interventions (PCI) of old calcified saphenous vein grafts (SVGs) is challenging and is associated with a considerably high risk of adverse ischemic events in the short- and long-term as compared to native coronary arteries. We report a case in which a non-dilatable, calcified SVG lesion is successfully treated with rotational atherectomy followed by PCI and stenting with local stent delivery (LSD) technique using the Guidezilla™ guide extension catheter (5-in-6 Fr) in the "child-in-mother" fashion. A 70 years-old man with a dilated ischemic cardiomyopathy, triple coronary artery bypass grafting (CABG) in 1990 and chronic renal failure (baseline GFR: 45 ml/min/1.73 m 2 ) underwent a coronary angiography for a Non-ST segment elevation myocardial infarction (NSTEMI). Native coronary circulation was completely occluded at the proximal segments. Grafts angiography showed a tandem calcified lesions of SVG on distal right coronary artery (RCA) and an ostial stenosis of the SVG on first obtuse marginal branch (OM1). Left internal mammary artery on the mid left anterior descending artery was patent. Ad Hoc PCI of SVG on RCA was attempted. The proximal calcified stenosis has been crossed with a 1.5 x 12 mm balloon only with the support of Guidezilla™, however the non-compliant (NC) balloon 2.5 x 15 mm was unable to break the hard and calcified plaque. After several attempts, the procedure was interrupted with a suboptimal result. An elective transradial PCI of SVG on RCA with rotational atherectomy was performed. Two runs with 1.25 mm burr and 2 runs with 1.5 mm burr were carried out. Then, the use of distal anchoring balloon warranted support and tracking, made as centring rail for the advance of the tip of the "mother-and-child" catheter into the SVG. During slow deflation of the balloon, the Guidezilla™ was advanced distal to the stenoses to be stented, thus allowing the placement of two long drug eluting stents according to a LSD technique. Rotational atherectomy is a feasible option for non-dilatable stenoses in old SVGs when there is no evidence of thrombus or vessel dissection and the subsequent use of "mother-and-child" catheter has a key role, especially in case of radial approach, for long stents delivery.

A Double-Blinded Randomized Study Investigating a Possible Anti-Inflammatory Effect of Saxagliptin versus Placebo as Add-On Therapy in Patients with Both Type 2 Diabetes And Stable Coronary Artery Disease

PubMed Central

Åkra, Sissel; Weiss, Thomas W.; Øvstebø, Reidun; Aass, Hans Christian D.; Byrkjeland, Rune; Arnesen, Harald

2017-01-01

Background Promising results regarding potential anti-inflammatory and antiatherosclerotic effects of gliptins have been reported. Our aim was to investigate whether saxagliptin treatment modifies expression of inflammatory markers, primarily in peripheral blood mononuclear cells (PBMCs) and in circulating leukocytes in patients with stable coronary artery disease (CAD) and T2DM. Methods Patients (n = 12) were randomized to saxagliptin 5 mg daily or placebo for 3 months. Samples were taken at baseline and end of study in fasting state prior to intake of medications. PBMCs were isolated and cryopreserved at −150°C until ex vivo exposed to 1 ng/mL of lipopolysaccharide (LPS) for 4 hours. Gene expression was performed with custom-designed TaqMan® Arrays and relative quantification by real-time PCR (RT-qPCR). Results HbA1c was reduced in the saxagliptin-treated group compared to that in the change with placebo (p = 0.042). In unstimulated PBMCs and in circulating leukocytes, we observed a significant increase in IL-10 expression in the saxagliptin group (p = 0.043, both), significantly different from that in the placebo (p = 0.009 and p = 0.032, resp.). No between group differences in changes were observed in any of the selected proinflammatory markers. Conclusion In our small cohort of patients with combined T2DM and CAD, a possible anti-inflammatory effect of saxagliptin, observed in the present study by upregulation of IL-10 in leukocytes, needs to be confirmed in larger studies. PMID:28596642

Emotional Processes in Patients Undergoing Coronary Artery Bypass Graft Surgeries with Extracorporeal Circulation in View of Selected Indicators of the Inflammatory Condition

PubMed Central

Płotek, Włodzimierz; Pielok, Joanna; Cybulski, Marcin; Samborska, Regina

2015-01-01

Background The aim of this study was to describe positive and negative emotions in patients undergoing coronary artery bypass graft (CABG) surgeries with extracorporeal circulation and the correlations between emotions and basic indicators of the inflammatory condition: C-reactive protein (CRP) concentration, body temperature, and leukocyte count. Material/Methods Standardized tools were used to select 52 patients (aged 47–63 years, 6 women – 11.5% and 46 men – 88.5%) without dementia or depression. The Positive and Negative Affect Schedule (PANAS) was used to examine positive affect (PA) and negative affect (NA) and the State-Trait Anxiety Inventory (STAI X1 and X2) was used to examine the anxiety level. The patients underwent CABG surgery according to a common anesthesia protocol and for 5 consecutive days they were observed in the ward, where selected indicators of the inflammatory condition were monitored. Results A detailed description of the results of examinations of emotions was presented. The patients with low PA-trait level, high NA-trait level, and high anxiety-trait level (STAI X2) exhibited statistically significantly higher body temperatures than the other patients in the postoperative period. The patients with high NA-trait and anxiety-state levels (STAI X1) had statistically significantly lower CRP levels in the postoperative period than the patients with low NA-trait and anxiety-state levels (STAI X1). Conclusions Patients undergoing CABG operations express both positive and negative affects. The changes in the inflammatory markers are expressed mostly by CRP concentration. There exist relationships between the result of tests assessing emotions and the markers of the inflammatory condition. PMID:25573296

Prospective randomized study comparing coronary artery bypass grafting with the new mini-extracorporeal circulation Jostra System or with a standard cardiopulmonary bypass.

PubMed

Remadi, Jean Paul; Rakotoarivelo, Zava; Marticho, Paul; Benamar, Amar

2006-01-01

To assess the potential benefits of a new concept of cardiopulmonary bypass (CPB), the mini-extracorporeal circulation (MECC) Jostra System, we conducted a prospective randomized study among patients who underwent coronary artery bypass grafting (CABG) with a MECC Jostra System or with a standard CPB. In a prospective randomized study, 400 patients underwent elective CABG using a standard CPB (200 patients) or a Jostra MECC System (200 patients). The patients were randomly assigned to have preoperative data similar for both groups. The operative mortality rate (< 30 days) was 1.5% for the MECC group and 2.5% for the CPB group (P = NS). Low-cardiac-output syndrome occurred in 0.66% and 4% for the CPB group (P < .001.). The inflammatory response was significantly reduced with the MECC. Likewise, C-reactive protein release was significantly higher in group B at 24 hours (69.6 +/- 38.5 vs 40.8 +/- 21.8 mg/L for the group A, P < .01) and at 48 hours (116.7 +/- 47.0 vs 65.4 +/- 39.5 mg/L, P < .05) postoperatively. In the CPB group, there was a significantly higher decrease of hematocrit and hemoglobin rate. So, the intraoperative transfusion rate amounted to 6% for the MECC group and 12.8% for the CPB group (P < .001). Patients in the CPB group had significantly higher levels of postoperative blood creatinine and urea. The MECC system is a new concept of CPB that seems to be reliable and safe. To perform CABG, the MECC provides an excellent surgical exposure like a standard CPB and a better biologic profile like CABG without CPB.

The ACE2 gene: its potential as a functional candidate for cardiovascular disease.

PubMed

Burrell, Louise M; Harrap, Stephen B; Velkoska, Elena; Patel, Sheila K

2013-01-01

The RAS (renin-angiotensin system) plays an important role in the pathophysiology of CVD (cardiovascular disease), and RAS blockade is an important therapeutic strategy in the management of CVD. A new counterbalancing arm of the RAS is now known to exist in which ACE (angiotensin-converting enzyme) 2 degrades Ang (angiotensin) II, the main effector of the classic RAS, and generates Ang-(1-7). Altered ACE2 expression is associated with cardiac and vascular disease in experimental models of CVD, and ACE2 is increased in failing human hearts and atherosclerotic vessels. In man, circulating ACE2 activity increases with coronary heart disease, as well as heart failure, and a large proportion of the variation in plasma ACE2 levels has been attributed to hereditary factors. The ACE2 gene maps to chromosome Xp22 and this paper reviews the evidence associating ACE2 gene variation with CVD and considers clues to potential functional ACE2 variants that may alter gene expression or transcriptional activity. Studies to date have investigated ACE2 gene associations in hypertension, left ventricular hypertrophy and coronary artery disease, but the results have been inconsistent. The discrepancies may reflect the sample size of the studies, the gender or ethnicity of subjects, the cardiovascular phenotype or the ACE2 SNP investigated. The frequent observation of apparent sex-dependence might be of special importance, if confirmed. As yet, there are no studies to concurrently assess ACE2 gene polymorphisms and circulating ACE2 activity. Large-scale carefully conducted clinical studies are urgently needed to clarify more precisely the potential role of ACE2 in the CVD continuum.

Presurgical levels of circulating cell-derived microparticles discriminate between patients with and without transfusion in coronary artery bypass graft surgery.

PubMed

Jy, Wenche; Gómez-Marín, Orlando; Salerno, Tomas A; Panos, Anthony L; Williams, Donald; Horstman, Lawrence L; Ahn, Yeon S

2015-01-01

Improved understanding of presurgical risk factors for transfusions will lead to reduction in their number and related complications. The goal of this study is to identify these factors in coronary artery bypass graft (CABG) surgery. Presented herein are results of analyses of data from an ongoing study of transfusion in CABG surgery. Of 122 patients, 81 received transfusion (Tx) and 41 did not (NoTx). In addition to routine tests, presurgical levels of microparticles from platelets (PMPs), red cells (RMPs), and other lineages were assayed. The Tx and NoTx groups were similar with respect to most presurgical variables but differed in distribution of gender, blood type, diabetes prevalence, activated partial thromboplastin time (aPTT), hemoglobin (HGB), and microparticle levels. Stepwise multiple logistic regression was used to evaluate presurgical variables and to develop a model to assess risk factors for transfusion. CD41(+) PMP and CD235(+) RMP levels were found to be the main risk factors for transfusion. The Model's discriminating ability was assessed using receiver operating characteristic curve analysis, which showed that the area under the model curve (± standard error) was 0.86 ± 0.04 (95% confidence interval, 0.77-0.94). According to the model, patients with higher presurgical levels of circulating CD41(+) PMP, CD235a(+) RMP, and HGB, as well as a shorter aPTT, are less likely to receive transfusion(s). Presurgical levels of CD41(+) PMPs and CD235a(+) RMPs are the main risk factors for transfusion in CABG, followed by HGB and aPTT. Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Particulate matter air pollution exposure promotes recruitment of monocytes into atherosclerotic plaques.

PubMed

Yatera, Kazuhiro; Hsieh, Joanne; Hogg, James C; Tranfield, Erin; Suzuki, Hisashi; Shih, Chih-Horng; Behzad, Ali R; Vincent, Renaud; van Eeden, Stephan F

2008-02-01

Epidemiologic studies have shown an association between exposure to ambient particulate air pollution <10 microm in diameter (PM(10)) and increased cardiovascular morbidity and mortality. We previously showed that PM(10) exposure causes progression of atherosclerosis in coronary arteries. We postulate that the recruitment of monocytes from the circulation into atherosclerotic lesions is a key step in this PM(10)-induced acceleration of atherosclerosis. The study objective was to quantify the recruitment of circulating monocytes into vessel walls and the progression of atherosclerotic plaques induced by exposure to PM(10). Female Watanabe heritable hyperlipidemic rabbits, which naturally develop systemic atherosclerosis, were exposed to PM(10) (EHC-93) or vehicle by intratracheal instillation twice a week for 4 wk. Monocytes, labeled with 5-bromo-2'-deoxyuridine (BrdU) in donors, were transfused to recipient rabbits as whole blood, and the recruitment of BrdU-labeled cells into vessel walls and plaques in recipients was measured by quantitative histological methodology. Exposure to PM(10) caused progression of atherosclerotic lesions in thoracic and abdominal aorta. It also decreased circulating monocyte counts, decreased circulating monocytes expressing high levels of CD31 (platelet endothelial cell adhesion molecule-1) and CD49d (very late antigen-4 alpha-chain), and increased expression of CD54 (ICAM-1) and CD106 (VCAM-1) in plaques. Exposure to PM(10) increased the number of BrdU-labeled monocytes adherent to endothelium over plaques and increased the migration of BrdU-labeled monocytes into plaques and smooth muscle underneath plaques. We conclude that exposure to ambient air pollution particles promotes the recruitment of circulating monocytes into atherosclerotic plaques and speculate that this is a critically important step in the PM(10)-induced progression of atherosclerosis.

A human APOC3 missense variant and monoclonal antibody accelerate apoC-III clearance and lower triglyceride-rich lipoprotein levels.

PubMed

Khetarpal, Sumeet A; Zeng, Xuemei; Millar, John S; Vitali, Cecilia; Somasundara, Amritha Varshini Hanasoge; Zanoni, Paolo; Landro, James A; Barucci, Nicole; Zavadoski, William J; Sun, Zhiyuan; de Haard, Hans; Toth, Ildikó V; Peloso, Gina M; Natarajan, Pradeep; Cuchel, Marina; Lund-Katz, Sissel; Phillips, Michael C; Tall, Alan R; Kathiresan, Sekar; DaSilva-Jardine, Paul; Yates, Nathan A; Rader, Daniel J

2017-09-01

Recent large-scale genetic sequencing efforts have identified rare coding variants in genes in the triglyceride-rich lipoprotein (TRL) clearance pathway that are protective against coronary heart disease (CHD), independently of LDL cholesterol (LDL-C) levels. Insight into the mechanisms of protection of these variants may facilitate the development of new therapies for lowering TRL levels. The gene APOC3 encodes apoC-III, a critical inhibitor of triglyceride (TG) lipolysis and remnant TRL clearance. Here we report a detailed interrogation of the mechanism of TRL lowering by the APOC3 Ala43Thr (A43T) variant, the only missense (rather than protein-truncating) variant in APOC3 reported to be TG lowering and protective against CHD. We found that both human APOC3 A43T heterozygotes and mice expressing human APOC3 A43T display markedly reduced circulating apoC-III levels. In mice, this reduction is due to impaired binding of A43T apoC-III to lipoproteins and accelerated renal catabolism of free apoC-III. Moreover, the reduced content of apoC-III in TRLs resulted in accelerated clearance of circulating TRLs. On the basis of this protective mechanism, we developed a monoclonal antibody targeting lipoprotein-bound human apoC-III that promotes circulating apoC-III clearance in mice expressing human APOC3 and enhances TRL catabolism in vivo. These data reveal the molecular mechanism by which a missense variant in APOC3 causes reduced circulating TG levels and, hence, protects from CHD. This protective mechanism has the potential to be exploited as a new therapeutic approach to reduce apoC-III levels and circulating TRL burden.

A human APOC3 missense variant and monoclonal antibody accelerate apoC-III clearance and lower triglyceride-rich lipoprotein levels

PubMed Central

Khetarpal, Sumeet A; Zeng, Xuemei; Millar, John S; Vitali, Cecilia; Somasundara, Amritha Varshini Hanasoge; Zanoni, Paolo; Landro, James A; Barucci, Nicole; Zavadoski, William J; Sun, Zhiyuan; de Haard, Hans; Toth, Ildikó V; Peloso, Gina M; Natarajan, Pradeep; Cuchel, Marina; Lund-Katz, Sissel; Phillips, Michael C; Tall, Alan R; Kathiresan, Sekar; DaSilva-Jardine, Paul; Yates, Nathan A; Rader, Daniel J

2017-01-01

Recent large-scale genetic sequencing efforts have identified rare coding variants in genes in the triglyceride-rich lipoprotein (TRL) clearance pathway that are protective against coronary heart disease (CHD), independently of LDL cholesterol (LDL-C) levels1. Insight into the mechanisms of protection of these variants may facilitate the development of new therapies for lowering TRL levels. The gene APOC3 encodes apoC-III, a critical inhibitor of triglyceride (TG) lipolysis and remnant TRL clearance2. Here we report a detailed interrogation of the mechanism of TRL lowering by the APOC3 Ala43Thr (A43T) variant, the only missense (rather than protein-truncating) variant in APOC3 reported to be TG lowering and protective against CHD3–5. We found that both human APOC3 A43T heterozygotes and mice expressing human APOC3 A43T display markedly reduced circulating apoC-III levels. In mice, this reduction is due to impaired binding of A43T apoC-III to lipoproteins and accelerated renal catabolism of free apoC-III. Moreover, the reduced content of apoC-III in TRLs resulted in accelerated clearance of circulating TRLs. On the basis of this protective mechanism, we developed a monoclonal antibody targeting lipoprotein-bound human apoC-III that promotes circulating apoC-III clearance in mice expressing human APOC3 and enhances TRL catabolism in vivo. These data reveal the molecular mechanism by which a missense variant in APOC3 causes reduced circulating TG levels and, hence, protects from CHD. This protective mechanism has the potential to be exploited as a new therapeutic approach to reduce apoC-III levels and circulating TRL burden. PMID:28825717

Micro RNAs from DNA Viruses are Found Widely in Plasma in a Large Observational Human Population.

PubMed

Koupenova, Milka; Mick, Eric; Corkrey, Heather A; Huan, Tianxiao; Clancy, Lauren; Shah, Ravi; Benjamin, Emelia J; Levy, Daniel; Kurt-Jones, Evelyn A; Tanriverdi, Kahraman; Freedman, Jane E

2018-04-23

Viral infections associate with disease risk and select families of viruses encode miRNAs that control an efficient viral cycle. The association of viral miRNA expression with disease in a large human population has not been previously explored. We sequenced plasma RNA from 40 participants of the Framingham Heart Study (FHS, Offspring Cohort, Visit 8) and identified 3 viral miRNAs from 3 different human Herpesviridae. These miRNAs were mostly related to viral latency and have not been previously detected in human plasma. Viral miRNA expression was then screened in the plasma of 2763 participants of the remaining cohort utilizing high-throughput RT-qPCR. All 3 viral miRNAs associated with combinations of inflammatory or prothrombotic circulating biomarkers (sTNFRII, IL-6, sICAM1, OPG, P-selectin) but did not associate with hypertension, coronary heart disease or cancer. Using a large observational population, we demonstrate that the presence of select viral miRNAs in the human circulation associate with inflammatory biomarkers and possibly immune response, but fail to associate with overt disease. This study greatly extends smaller singular observations of viral miRNAs in the human circulation and suggests that select viral miRNAs, such as those for latency, may not impact disease manifestation.

Protective effects of circulating microvesicles derived from myocardial ischemic rats on apoptosis of cardiomyocytes in myocardial ischemia/reperfusion injury.

PubMed

Wang, Yao; Wei, Su; Wang, Yi-Lu; Liu, Miao; Shang, Man; Zhang, Qi; Wu, Yan-Na; Liu, Ming-Lin; Song, Jun-Qiu; Liu, Yan-Xia

2017-08-15

To investigate the effects of circulating microvesicles derived from myocardial ischemia (I-MVs) on apoptosis in myocardial ischemia/reperfusion (I/R) injury in rats. I-MVs from rats undergoing myocardial left anterior descending (LAD) coronary artery ligation were isolated by ultracentrifugation from circulating blood and characterized by flow cytometry. I-MVs were administered intravenously (4.8 mg/kg) at 5 min before reperfusion procedure in I/R injury model which was induced by 30-min of ischemia and 120-min of reperfusion of LAD in rats. Treatment with I-MVssignificantly reduced the size of myocardial infarction, the activities of serum CK-MB and LDH, and the number of apoptotic cardiomyocytes. The activities of caspase 3, caspase 9 and caspase 12 in myocardium were also decreased significantly with I-MVs treatment. Moreover, the expression of Bax was decreased but Bcl-2 was increased. The expression of glucose regulated protein 78 (GRP78), sarco/endoplasmic reticulum Ca 2+ -ATPase 2 (SERCA2) and phosphorylated phospholamban (p-PLB) were increased after being treated with I-MVs. I-MVs could protect hearts from I/R injury in rats through SERCA2 and p-PLB of calcium regulatory proteins to alleviate intrinsic myocardial apoptosis including mitochondrial and endoplasmic reticulum pathways.

Haplotypes in the CRP Gene Associated with Increased BMI and Levels of CRP in Subjects with Type 2 Diabetes or Obesity from Southwestern Mexico

PubMed Central

Martínez-Calleja, América; Quiróz-Vargas, Irma; Parra-Rojas, Isela; Muñoz-Valle, José Francisco; Leyva-Vázquez, Marco A.; Fernández-Tilapa, Gloria; Vences-Velázquez, Amalia; Cruz, Miguel; Salazar-Martínez, Eduardo; Flores-Alfaro, Eugenia

2012-01-01

Objective. We evaluated the association between four polymorphisms in the CRP gene with circulating levels of C-reactive protein (CRP), type 2 diabetes (T2D), obesity, and risk score of coronary heart disease. Methods. We studied 402 individuals and classified them into four groups: healthy, obese, T2D obese, and T2D without obesity, from Guerrero, Southwestern Mexico. Blood levels of CRP, glucose, cholesterol, triglycerides, and leukocytes were measured. Genotyping was performed by PCR/RFLP, and the risk score for coronary heart disease was determined by the Framingham's methodology. Results. The TT genotype of SNP rs1130864 was associated with increased body mass index and T2D patients with obesity. We found that the haplotype 2 (TGAG) was associated with increased levels of CRP (β = 0.3; 95%CI: 0.1, 0.5; P = 0.005) and haplotype 7 (TGGG) with higher body mass index (BMI) (β = 0.2; 95%CI: 0.1, 0.3; P < 0.001). The risk score for coronary heart disease was associated with increased levels of CRP, but not with any polymorphism or haplotype. Conclusions. The association between the TT genotype of SNP rs1130864 with obesity and the haplotype 7 with BMI may explain how obesity and genetic predisposition increase the risk of diseases such as T2D in the population of Southwestern Mexico. PMID:23049543

Resveratrol combined with total flavones of hawthorn alleviate the endothelial cells injury after coronary bypass graft surgery.

PubMed

Zhu, Ying; Feng, Bing; He, Songmin; Su, Zuqing; Zheng, Guangjuan

2018-02-01

To explore the preventive and therapeutic effects of Resveratrol combined with total flavones of hawthorn, compatibility of traditional Chinese medicines, on the endothelial cells injury after artery bypass graft surgery. The animal model of coronary artery bypass grafting (CABG) was prepared by transplanting a segment of autologous jugular vein onto the transected common carotid artery in rabbits. After CABG surgery, the rabbits were administrated with saline (model group), aspirin (Aspirin group), resveratrol (Res group), total flavones of hawthorn (Haw group) and resveratrol combined with total flavones of hawthorn (Res+Haw group) once a day for eight weeks, respectively. Eight weeks later, the grafting arteries from all group were obtained for the pathomorphism observation, peripheral blood was collected to detect circulating endothelial cells (CECs) by flow cytometry. And the concentration of albumen and mRNA of ICAM-1 in the serum were measured by western blot and quantitative real-time polymerase chain reaction, respectively. Compared with the model group, the level of CECs density and the expressions of albumen and mRNA of ICAM-1 were significantly decreased in the aspirin,resveratrol,total flavones of hawthorn and resveratrol combined with total flavones of hawthorn groups (P < .05). Of note, above all parameters were lower in Res group than aspirin group. The Resveratrol combined with total flavones of hawthorn could protect the endothelial cells after coronary artery bypass graft. Copyright © 2018 Elsevier GmbH. All rights reserved.

Downregulated Expression of TRPV2 in Peripheral Blood Cells following Acute Myocardial Infarction Is Inversely Correlated with Serum Levels of CRP and Troponin I.

PubMed

Rozenbaum, Zach; Cohen, Lena; Bigelman, Einat; Shacham, Yacov; Keren, Gad; Entin-Meer, Michal

We have recently shown that the transient receptor potential vanilloid 2 (TRPV2) channel is exclusively upregulated in rat/murine peri-infarct monocytes/macrophages following an acute myocardial infarction (AMI), and that this overexpression might be detrimental for cardiac recovery. We aimed to characterize the expression levels of TRPV2 in peripheral blood mononuclear cells (PBMCs) of AMI patients relative to individuals with normal coronaries, and to analyze potential associations with inflammatory and cardiac ischemic markers. Patients who underwent coronary angiography due to AMI or chest pain were prospectively included. PBMCs were isolated from whole blood by Ficoll gradient centrifugation. TRPV2 expression was analyzed by real-time PCR. C-reactive protein (CRP) and troponin I (TpI) levels were determined at the central chemistry laboratory; interleukin 6 and insulin-like growth factor (IGF)-1 levels were tested by ELISA. Following AMI, the number of TRPV2-expressing PBMCs was reduced when compared to in patients with normal coronaries. An inverse correlation was documented between the numbers of circulating macrophages and TRPV2 expression. Additionally, TRPV2 expression was inversely correlated with CRP and TpI and directly correlated with serum IGF-1. We assume that peripheral TRPV2 downregulation occurs concomitantly with the accumulation of TRPV2-white blood cells in the peri-infarct zone. TRPV2 may thus represent a novel target for treatment in the acute phase after MI. © 2018 S. Karger AG, Basel.

Plasma level of cyclophilin A is increased in patients with type 2 diabetes mellitus and suggests presence of vascular disease.

PubMed

Ramachandran, Surya; Venugopal, Anila; Kutty, V Raman; A, Vinitha; G, Divya; Chitrasree, V; Mullassari, Ajit; Pratapchandran, N S; Santosh, K R; Pillai, M Radhakrishna; Kartha, C C

2014-02-07

Cyclophilin A, an immunophilin is secreted from human monocytes activated by high glucose. Given its role as an inflammatory mediator of vascular tissue damage associated with inflammation and oxidative stress, we examined plasma levels of cyclophilin A in normal healthy volunteers and patients with type 2 diabetes (DM), with or without coronary artery disease (CAD). Study subjects comprised of 212 patients with DM and CAD,101 patients with diabetes, 122 patients with CAD and 121 normal healthy volunteers. Diabetes was assessed by HbA1c levels while coronary artery disease was established by a positive treadmill test and/or coronary angiography. Plasma cyclophilin A was measured using a cyclophilin A ELISA Kit. Relationship of plasma cyclophilin A levels with blood markers of type 2 diabetes, blood lipid levels and medication for diabetes and coronary artery disease were also explored. Plasma Cyclophilin levels were higher in diabetes patients with or without CAD compared to normal subjects (P < 0.001). Age, fasting blood sugar levels and HbA1C levels were positively associated with increased plasma cyclophilin. Patients using metformin had reduced levels of plasma cyclophilin (p < 0.001).Serum levels of total cholesterol, LDL cholesterol and triglycerides had no significant association with plasma cyclophilin levels. In patients with increased serum CRP levels, plasma cyclophilin A was also elevated (p = 0.016). Prevalence odds for DM, DM + CAD and CAD are higher in those with high cyclophilin values, compared to those with lower values, after adjusting for age and sex, indicating strong association of high cyclophilin values with diabetes and vascular disease. Our study demonstrates that patients with type 2 diabetes have higher circulating levels of cyclophilin A than the normal population. Plasma cyclophilin levels were increased in patients with diabetes and coronary artery disease suggesting a role of this protein in accelerating vascular disease in type 2 diabetes. Considering the evidence that Cyclophilin A is an inflammatory mediator in atherogenesis, the mechanistic role of cyclophilin A in diabetic vascular disease progression deserves detailed investigation.

Plasma level of cyclophilin A is increased in patients with type 2 diabetes mellitus and suggests presence of vascular disease

PubMed Central

2014-01-01

Aims/hypothesis Cyclophilin A, an immunophilin is secreted from human monocytes activated by high glucose. Given its role as an inflammatory mediator of vascular tissue damage associated with inflammation and oxidative stress, we examined plasma levels of cyclophilin A in normal healthy volunteers and patients with type 2 diabetes (DM), with or without coronary artery disease (CAD). Methods Study subjects comprised of 212 patients with DM and CAD,101 patients with diabetes, 122 patients with CAD and 121 normal healthy volunteers. Diabetes was assessed by HbA1c levels while coronary artery disease was established by a positive treadmill test and/or coronary angiography. Plasma cyclophilin A was measured using a cyclophilin A ELISA Kit. Relationship of plasma cyclophilin A levels with blood markers of type 2 diabetes, blood lipid levels and medication for diabetes and coronary artery disease were also explored. Results Plasma Cyclophilin levels were higher in diabetes patients with or without CAD compared to normal subjects (P < 0.001). Age, fasting blood sugar levels and HbA1C levels were positively associated with increased plasma cyclophilin. Patients using metformin had reduced levels of plasma cyclophilin (p < 0.001).Serum levels of total cholesterol, LDL cholesterol and triglycerides had no significant association with plasma cyclophilin levels. In patients with increased serum CRP levels, plasma cyclophilin A was also elevated (p = 0.016). Prevalence odds for DM, DM + CAD and CAD are higher in those with high cyclophilin values, compared to those with lower values, after adjusting for age and sex, indicating strong association of high cyclophilin values with diabetes and vascular disease. Conclusions/interpretations Our study demonstrates that patients with type 2 diabetes have higher circulating levels of cyclophilin A than the normal population. Plasma cyclophilin levels were increased in patients with diabetes and coronary artery disease suggesting a role of this protein in accelerating vascular disease in type 2 diabetes. Considering the evidence that Cyclophilin A is an inflammatory mediator in atherogenesis, the mechanistic role of cyclophilin A in diabetic vascular disease progression deserves detailed investigation. PMID:24502618

Low-dose copper infusion into the coronary circulation induces acute heart failure in diabetic rats: New mechanism of heart disease.

PubMed

Cheung, Carlos Chun Ho; Soon, Choong Yee; Chuang, Chia-Lin; Phillips, Anthony R J; Zhang, Shaoping; Cooper, Garth J S

2015-09-01

Diabetes impairs copper (Cu) regulation, causing elevated serum Cu and urinary Cu excretion in patients with established cardiovascular disease; it also causes cardiomyopathy and chronic cardiac impairment linked to defective Cu homeostasis in rats. However, the mechanisms that link impaired Cu regulation to cardiac dysfunction in diabetes are incompletely understood. Chronic treatment with triethylenetetramine (TETA), a Cu²⁺-selective chelator, improves cardiac function in diabetic patients, and in rats with heart disease; the latter displayed ∼3-fold elevations in free Cu²⁺ in the coronary effluent when TETA was infused into their coronary arteries. To further study the nature of defective cardiac Cu regulation in diabetes, we employed an isolated-perfused, working-heart model in which we infused micromolar doses of Cu²⁺ into the coronary arteries and measured acute effects on cardiac function in diabetic and non-diabetic-control rats. Infusion of CuCl₂ solutions caused acute dose-dependent cardiac dysfunction in normal hearts. Several measures of baseline cardiac function were impaired in diabetic hearts, and these defects were exacerbated by low-micromolar Cu²⁺ infusion. The response to infused Cu²⁺ was augmented in diabetic hearts, which became defective at lower infusion levels and underwent complete pump failure (cardiac output = 0 ml/min) more often (P < 0.0001) at concentrations that only moderately impaired function of control hearts. To our knowledge, this is the first report describing the acute effects on cardiac function of pathophysiological elevations in coronary Cu²⁺. The effects of Cu²⁺ infusion occur within minutes in both control and diabetic hearts, which suggests that they are not due to remodelling. Heightened sensitivity to the acute effects of small elevations in Cu²⁺ could contribute substantively to impaired cardiac function in patients with diabetes and is thus identified as a new mechanism of heart disease. Copyright © 2015 Elsevier Inc. All rights reserved.

Recovery of distal coronary flow reserve in LAD and LCx after Y-Graft intervention assessed by transthoracic echocardiography

PubMed Central

2010-01-01

Background Y- graft (Y-G) is a graft formed by the Left Internal Mammary Artery (LIMA) connected to the Left Anterior Descending Artery (LAD) and by a free Right Internal Mammary Artery (RIMA) connected to LIMA and to a Marginal artery of Left Circumflex Artery (LCx). Aim of the work was to study the flow of this graft during a six months follow-up to assess whether the graft was able to meet the request of all the left coronary circulation, and to assess whether it could be done by evaluation of coronary flow reserve (CFR). Methods In 13 consecutive patients submitted to Y-G (13 men), CFR was measured in distal LAD and in distal LCx from 1 week after , every two months, up to six months after operation (a total of 8 tests for each patient) by means of transthoracic echocardiography (TTE) and Adenosine infusion (140 mcg/kg/min for 3-6 min). A Sequoia 256, Acuson-Siemens, was used. Contrast was used when necessary (Levovist 300 mg/ml solution at a rate of 0,5-1 ml/min). Max coronary flow diastolic velocity post-/pre-test ≥2 was considered normal CFR. Results Coronary arteriography revealed patency of both branches of Y-G after six months. Accuracy of TTE was 100% for LAD and 85% for LCx. Feasibility was 100% for LAD and 85% for LCx. CFR improved from baseline in LAD (2.21 ± 0.5 to 2.6 ± 0.5, p = 0.03) and in LCx (1.7 ± 1 to 2.12 ± 1, p = 0.05). CFR was under normal at baseline in 30% of patients vs 8% after six months in LAD (p = 0.027), and in 69% of patients vs 30% after six months in LCx (p = 0.066). Conclusion CFR in Y-G is sometimes reduced in both left territories postoperatively but it improves at six months follow-up. A follow-up can be done non-invasively by TTE and CFR evaluation. PMID:20716357

Coronary heart disease-associated variation in TCF21 disrupts a miR-224 binding site and miRNA-mediated regulation.

PubMed

Miller, Clint L; Haas, Ulrike; Diaz, Roxanne; Leeper, Nicholas J; Kundu, Ramendra K; Patlolla, Bhagat; Assimes, Themistocles L; Kaiser, Frank J; Perisic, Ljubica; Hedin, Ulf; Maegdefessel, Lars; Schunkert, Heribert; Erdmann, Jeanette; Quertermous, Thomas; Sczakiel, Georg

2014-03-01

Genome-wide association studies (GWAS) have identified chromosomal loci that affect risk of coronary heart disease (CHD) independent of classical risk factors. One such association signal has been identified at 6q23.2 in both Caucasians and East Asians. The lead CHD-associated polymorphism in this region, rs12190287, resides in the 3' untranslated region (3'-UTR) of TCF21, a basic-helix-loop-helix transcription factor, and is predicted to alter the seed binding sequence for miR-224. Allelic imbalance studies in circulating leukocytes and human coronary artery smooth muscle cells (HCASMC) showed significant imbalance of the TCF21 transcript that correlated with genotype at rs12190287, consistent with this variant contributing to allele-specific expression differences. 3' UTR reporter gene transfection studies in HCASMC showed that the disease-associated C allele has reduced expression compared to the protective G allele. Kinetic analyses in vitro revealed faster RNA-RNA complex formation and greater binding of miR-224 with the TCF21 C allelic transcript. In addition, in vitro probing with Pb2+ and RNase T1 revealed structural differences between the TCF21 variants in proximity of the rs12190287 variant, which are predicted to provide greater access to the C allele for miR-224 binding. miR-224 and TCF21 expression levels were anti-correlated in HCASMC, and miR-224 modulates the transcriptional response of TCF21 to transforming growth factor-β (TGF-β) and platelet derived growth factor (PDGF) signaling in an allele-specific manner. Lastly, miR-224 and TCF21 were localized in human coronary artery lesions and anti-correlated during atherosclerosis. Together, these data suggest that miR-224 interaction with the TCF21 transcript contributes to allelic imbalance of this gene, thus partly explaining the genetic risk for coronary heart disease associated at 6q23.2. These studies implicating rs12190287 in the miRNA-dependent regulation of TCF21, in conjunction with previous studies showing that this variant modulates transcriptional regulation through activator protein 1 (AP-1), suggests a unique bimodal level of complexity previously unreported for disease-associated variants.

Mature proprotein convertase subtilisin/kexin type 9, coronary atheroma burden, and vessel remodeling in heterozygous familial hypercholesterolemia.

PubMed

Kataoka, Yu; Harada-Shiba, Mariko; Nakao, Kazuhiro; Nakashima, Takahiro; Kawakami, Shoji; Fujino, Masashi; Kanaya, Tomoaki; Nagai, Toshiyuki; Tahara, Yoshio; Asaumi, Yasuhide; Hori, Mika; Ogura, Masatsune; Goto, Yoichi; Noguchi, Teruo; Yasuda, Satoshi

Proprotein convertase subtilisin/kexin type 9 (PCSK9), an important contributor to low-density lipoprotein metabolism in heterozygous familial hypercholesterolemia (HeFH), exhibits direct proatherogenic effects. PCSK9 circulates as mature and furin-cleaved forms, which differ in its biological activity. However, it remains to be elucidated whether each PCSK9 subtype has different atherogenic properties. To investigate the association of each PCSK9 subtype with coronary atherosclerosis in HeFH. About 204 nonculprit segments in 138 HeFH subjects with coronary artery disease were evaluated by using intravascular ultrasound. Mature, furin-cleaved PCSK9 and total concentration of PCSK9 subtypes were measured by using enzyme-linked immunosorbent assay (BML Inc., Tokyo, Japan). The relationship of these PCSK9 values with intravascular ultrasound measures was investigated. Mature PCSK9 level was positively associated with percent atheroma volume (PAV: r = 0.78, P = .003). Despite extensive atheroma under a higher mature PCSK9 level, vessel volume did not change across any mature PCSK9 levels (r = 0.05, P = .78). These responses resulted in smaller lumen volume, which was negatively correlated to mature PCSK9 level (r = 0.65, P = .009). By contrast, there were no significant relationships of PAV with furin-cleaved (r = 0.12, P = .45) and total PCSK9 (r = 0.37, P = .25) levels. On multivariate analysis, mature PCSK9 level independently contributed to PAV (odds ratio: 1.45, 95% confidence interval: 1.11-1.67, P = .01). Even in subjects with low-density lipoprotein cholesterol level <2.6 mmol/L, greater PAV was still observed in association with an elevated mature PCSK9 level (P = .003). Mature PCSK9 associated with atheroma volume and impaired vessel remodeling in HeFH patients with coronary artery disease. These findings suggest the potential role of mature PCSK9 in propagation of coronary atherosclerosis in HeFH. Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Vascular extracellular vesicles in comorbidities of heart failure with preserved ejection fraction in men and women: The hidden players. A mini review.

PubMed

Gohar, Aisha; de Kleijn, Dominique P V; Hoes, Arno W; Rutten, Frans H; Hilfiker-Kleiner, Denise; Ferdinandy, Péter; Sluijter, Joost P G; den Ruijter, Hester M

2018-05-25

Left ventricular diastolic dysfunction, the main feature of heart failure with preserved ejection fraction (HFpEF), is thought to be primarily caused by comorbidities affecting the endothelial function of the coronary microvasculature. Circulating extracellular vesicles, released by the endothelium have been postulated to reflect endothelial damage. Therefore, we reviewed the role of extracellular vesicles, in particularly endothelium microparticles, in these comorbidities, including obesity and hypertension, to identify if they may be potential markers of the endothelial dysfunction underlying left ventricular diastolic dysfunction and HFpEF. Copyright © 2017. Published by Elsevier Inc.

[Studies on the pharmacological effects of saffron(Crocus sativus L.)--a review].

PubMed

Deng, Ying; Guo, Zhi-gang; Zeng, Zhao-lin; Wang, Zhao

2002-08-01

Reviewing the studies on the chemical components and medicinal value. Philological method. Saffron is a conventional effective medicine in improving blood circulation and curing the bruise. The late of evidesnces indicate that saffron possesses anticancer activity against a wide spectrum of tumors, such as leukemia, ovarian carcinoma, colon adenocarcinoma, rhabdomyosarcoma, papilloma, squamous cell carcinoma, and soft tissue sarcoma. It has low biochemical toxic effects on animals. In addition, saffron can be used to cure coronary heart disease and hepatitis, and to promote immunity. Saffron is a highly valuable medicine. And producing it in a large quantity has a wide application prosperity.

[Current ideas of a complex relationship between atrial fibrillation and ischemic heart disease and of optimum tactics for anticoagulant therapy to prevent embolism in systemic circulation].

PubMed

Golshmid, M V; Gilyarevskiy, S R; Kuzmina, I M; Sinitsina, I I

The article discusses the issue of searching for optimum oral anticoagulants to prevent thrombosis and embolism induced by heart disease both in patients with atrial fibrillation and sinus rhythm. A complex bidirectional relationship between atrial fibrillation and coronary atherosclerosis is considered along with possible mechanisms for development of myocardial infarction in patients with atrial fibrillation. The authors provided evidence-based data which can be used in selecting an anticoagulant for prevention of heart disease induced thrombosis and embolism taking into account both the efficacy and safety established in randomized clinical studies.

[Unintended cooling, active warming, and microcirculation in cardiosurgical patients].

PubMed

Aksel'rod, B A; Trekova, N A; Guleshov, V A; Tolstova, I A; Gus'kov, D A; Babaev, M A

2010-01-01

The study was undertaken to compare various methods to maintain a patient's body temperature and to evaluate their impact on microcirculation during myocardial revascularization under normothermal extracorporeal circulation (NTEC). The study enrolled 50 patients with NYHA Functional Classes III-IV coronary heart disease, who underwent aortocoronary bypass surgery under NTEC. A HICO-AQUATHERM 660 water-warming unit (Hirtz, Germany) was used in Group 1 patients (n=30). A Bair Hugger air-warming unit (Arizant, U.S.A.) with a mattress located under a patient was employed in Group 2 (n=20). Intraoperative microcirculation monitoring was carried out by a laser analyzer (Lazma, Moscow).

The effect of short-term antiorthostatic hypokinesia on central and intracardiac hemodynamics and metabolism of a healthy person

NASA Technical Reports Server (NTRS)

Katkov, V. Y.; Chesturkhin, V. V.; Zybin, O. K.; Sukhotskiy, S. S.; Abrosimov, S. V.; Utkin, V. N.

1981-01-01

The right parts of the heart and the radial artery were catheterized in healthy male volunteers before and 5 days after strict bedrest in antiorthostatic position of the body (-4.5 deg). After immobilization, most values of central circulation showed no essential changes; the only exceptions were indicates characterizing the inotropic myocardial condition. A shift in the direction of acidosis of a mixed character was noted in mixed venous blood, the beta lipoprotein content increased. A decrease in the arteriovenous difference in oxygen was encountered in blood draining from the heart (from the coronary sinus).

Blood magnesium concentration and dopamine or dobutamine infusion demand in patients during CABG (coronary artery bypass grafting) with normovolemic haemodilution.

PubMed

Pasternak, K; Wrońska, J; Dabrowski, W; Sztanke, M

2006-12-01

It is well known that magnesium (Mg) plays an essential role in cardiac protection. Mg has many beneficial effects on the myocardium and cardiac function, e.g. it improves contractility and reduces the number of cardiac arrhythmia episodes. The inotropically positive effects of Mg are interesting and worth stressing. High blood Mg concentration may result in an increase in cardiac contraction strength, which may be important for haemodynamic stabilization, and thus it is likely to decrease the demand for dopamine and dobutamine infusions. However, the exact determination of correlation between blood Mg concentrations and dopamine or dobutamine infusion demand is still unknown. The aim of the study was to assess the demand for dopamine or dobutamine infusion in relation to changes in blood magnesium concentrations in patients undergoing CABG (Coronary artery bypass graft) with extracorporeal circulation and normovolemic haemodilution. The study included 20 male patients, aged 53-70 (61.1 +/- 6.9) who underwent general anaesthesia and coronary artery bypass grafting (CABG) with extracorporeal circulation (ECC) and normovolemic haemodilution (NH) due to stable angina pectoris. The patients were retrospectively divided into three groups: A--patients who did not receive dopamine or dobutamine infusion, B--those receiving only D infusion in the doses dependent on their clinical state and C--those receiving DB infusion in the doses dependent on their clinical state. Mg was measured in 7 stages: 1) just before anaesthesia after the radial artery cannulation, 2) during normovolemic haemodilution and ECC, 3) immediately after surgery, 4) in the evening of the surgery day, 5) in the morning of the lst postoperative day, 6) in the evening of 1st postoperative day, 7) in the morning of the 2nd postoperative day. The spectrophotometric methods were used to determine Mg. The CABG procedure resulted in a decrease in Mg. Its level returned to normal in the evening of surgery day. The NH caused a similar Mg decrease in groups A, B and C, but these significantly low values of Mg were observed only in stage 2. There was no correlation between blood Mg concentrations and dopamine or dobutamine infusion demand. 1) The CABG procedure resulted in decreased blood magnesium concentrations. 2) The Mg changes do not correlate with dopamine or dobutamine infusion demand.

Ten-year experience of an invasive cardiology centre with out-of-hospital cardiac arrest patients admitted for urgent coronary angiography.

PubMed

Zeliaś, Aleksander; Stępińska, Janina; Andres, Janusz; Trąbka-Zawicki, Aleksander; Sadowski, Jerzy; Żmudka, Krzysztof

2014-01-01

The aim of the study was to evaluate survival and neurological function of out-of-hospital cardiac arrest (OHCA) patients admitted for urgent coronary angiography (UCA) with a view to percutaneous coronary intervention (PCI). Hospital records of OHCA patients admitted to an invasive cardiology centre (providing 24 h a day/7 days a week service) in 2000-2010 were reviewed retrospectively, and similar data collected in 2011 were reviewed prospectively. Reports from the pre-hospital phase from emergency medical services (EMS) in Krakow were also analysed. Long-term follow-up data were collected by retrieving records from other hospitals (for patients transferred after UCA/PCI) and by phone calls to patients or their relatives. In 2000-2011, 405 OHCA patients were admitted for UCA/PCI. Most (78%) had ventricular fibrillation (VF) or ventricular tachycardia (VT) as the primary mechanism of cardiac arrest (asystole: 13%, pulseless electrical activity: 3%, unknown: 6%). The mean patient age was 61 (range 20-85) years, and 81% were males. On admission, about 70% of patients were unconscious and 11% were in cardiogenic shock. The mean resuscitation time (time to return of spontaneous circulation [ROSC]) was 26.7 (range 1-126) min. ST-T changes seen in an electrocardiogram recorded after ROSC included ST elevation and depression in 52% of cases, only ST depression in 21% of cases, only ST elevation in 17% of cases, unspecific changes (due to intraventricular conduction disturbances) in 7% of cases, negative T waves in 3% of cases, and no changes in 0.5% of cases. Coronary angiography revealed acute coronary occlusion in 48% of cases, critical coronary stenosis (> 90%) in 26% of cases, other significant coronary lesions (> 50% stenosis) in 15% of cases, and non-significant lesions in 11% of cases. An acute coronary syndrome (ACS) was diagnosed in 82% of patients (75% STEMI, 25% NSTEMI), and other cardiac cause (mostly ischaemic cardiomyopathy) was identified in 13% of patients. Among OHCA patients diagnosed with ACS, PCI was performed in 90% and additional 4% underwent coronary artery bypass grafting. Overall success rate of PCI, defined as TIMI 3 flow plus residual stenosis < 50% and resolution of ST elevation after PCI by > 30%, was 70%. Survival to hospital discharge in the entire group of OHCA patients was 63% and 30-day survival with good neurological outcomes (defined as Cerebral Performance Category 1 or 2) was 49%. Among patients who were initially unconscious, those figures were 52% and 33%, respectively. During long-term follow-up (up to 12 years), 49% of patients were alive and 42% had good neurological function (87% of those who survived). In multivariate analysis, independent predictors of survival with good neurological outcomes were preserved consciousness on admission, absence of shock, cardiac arrest witnessed by medical personnel, VF/VT as a primary mechanism of cardiac arrest, and preserved renal function. Successful PCI predicted survival until hospital discharge only when the neurological status of the patients was not taken into account. The most important cause of OHCA is coronary artery disease, in particular ACS. UCA and PCI seem to be important elements of appropriate post-resuscitation care because such treatment could improve survival but it is still unclear whether PCI might influence neurological outcomes as well.

Vertebral artery ostium atherosclerotic plaque as a potential source of posterior circulation ischemic stroke: result from borgess medical center vertebral artery ostium stenting registry.

PubMed

Al-Ali, Firas; Barrow, Tom; Duan, Li; Jefferson, Anne; Louis, Susan; Luke, Kim; Major, Kevin; Smoker, Sandy; Walker, Sarah; Yacobozzi, Margaret

2011-09-01

Although atherosclerotic plaque in the carotid and coronary arteries is accepted as a cause of ischemia, vertebral artery ostium (VAO) atherosclerotic plaque is not widely recognized as a source of ischemic stroke. We seek to demonstrate its implication in some posterior circulation ischemia. This is a nonrandomized, prospective, single-center registry on consecutive patients presenting with posterior circulation ischemia who underwent VAO stenting for significant atherosclerotic stenosis. Diagnostic evaluation and imaging studies determined the likelihood of this lesion as the symptom source (highly likely, probable, or highly unlikely). Patients were divided into 4 groups in decreasing order of severity of clinical presentation (ischemic stroke, TIA then stroke, TIA, asymptomatic), which were compared with the morphological and hemodynamic characteristics of the VAO plaque. Clinical follow-up 1 year after stenting assessed symptom recurrence. One hundred fourteen patients underwent stenting of 127 lesions; 35% of the lesions were highly likely the source of symptoms, 53% were probable, and 12% were highly unlikely. Clinical presentation correlated directly with plaque irregularity and presence of clot at the VAO, as did bilateral lesions and presence of tandem lesions. Symptom recurrence at 1 year was 2%. Thirty-five percent of the lesions were highly likely the source of the symptoms. A direct relationship between some morphological/hemodynamic characteristics and the severity of clinical presentation was also found. Finally, patients had a very low rate of symptom recurrence after treatment. These 3 observations point strongly to VAO plaque as a potential source of some posterior circulation stroke.

X-ray intravital microscopy for functional imaging in rat hearts using synchrotron radiation coronary microangiography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Umetani, K.; Fukushima, K.

2013-03-15

An X-ray intravital microscopy technique was developed to enable in vivo visualization of the coronary, cerebral, and pulmonary arteries in rats without exposure of organs and with spatial resolution in the micrometer range and temporal resolution in the millisecond range. We have refined the system continually in terms of the spatial resolution and exposure time. X-rays transmitted through an object are detected by an X-ray direct-conversion type detector, which incorporates an X-ray SATICON pickup tube. The spatial resolution has been improved to 6 {mu}m, yielding sharp images of small arteries. The exposure time has been shortened to around 2 msmore » using a new rotating-disk X-ray shutter, enabling imaging of beating rat hearts. Quantitative evaluations of the X-ray intravital microscopy technique were extracted from measurements of the smallest-detectable vessel size and detection of the vessel function. The smallest-diameter vessel viewed for measurements is determined primarily by the concentration of iodinated contrast material. The iodine concentration depends on the injection technique. We used ex vivo rat hearts under Langendorff perfusion for accurate evaluation. After the contrast agent is injected into the origin of the aorta in an isolated perfused rat heart, the contrast agent is delivered directly into the coronary arteries with minimum dilution. The vascular internal diameter response of coronary arterial circulation is analyzed to evaluate the vessel function. Small blood vessels of more than about 50 {mu}m diameters were visualized clearly at heart rates of around 300 beats/min. Vasodilation compared to the control was observed quantitatively using drug manipulation. Furthermore, the apparent increase in the number of small vessels with diameters of less than about 50 {mu}m was observed after the vasoactive agents increased the diameters of invisible small blood vessels to visible sizes. This technique is expected to offer the potential for direct investigation of mechanisms of vascular dysfunctions.« less

Reduced endothelial activation after exercise is associated with improved HbA1c in patients with type 2 diabetes and coronary artery disease.

PubMed

Byrkjeland, Rune; Njerve, Ida U; Arnesen, Harald; Seljeflot, Ingebjørg; Solheim, Svein

2017-03-01

We have previously reported insignificant changes in HbA 1c after exercise in patients with both type 2 diabetes and coronary artery disease. In this study, we investigated the effect of exercise on endothelial function and possible associations between changes in endothelial function and HbA 1c . Patients with type 2 diabetes and coronary artery disease ( n = 137) were randomised to 12 months exercise or standard follow-up. Endothelial function was assessed by circulating biomarkers (E-selectin, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, von Willebrand factor, tissue plasminogen activator antigen, asymmetric dimethylarginine and L-arginine/asymmetric dimethylarginine ratio). Differences between the randomised groups were analysed by analysis of covariance and correlations by Spearman's rho or Pearson's correlation. No effect of exercise on endothelial function was demonstrated. The changes in HbA 1c in the exercise group correlated with changes in E-selectin ( r = 0.56, p < 0.001), intercellular adhesion molecule-1 ( r = 0.27, p = 0.052), vascular cell adhesion molecule-1 ( r = 0.32, p = 0.022) and tissue plasminogen activator antigen ( r = 0.35, p =  0.011). HbA 1c decreased significantly more in patients with versus without a concomitant reduction in E-selectin ( p =  0.002), intercellular adhesion molecule-1 ( p =  0.011), vascular cell adhesion molecule-1 ( p =  0.028) and tissue plasminogen activator antigen ( p =  0.009). Exercise did not affect biomarkers of endothelial function in patients with both type 2 diabetes and coronary artery disease. However, changes in biomarkers of endothelial activation correlated with changes in HbA 1c , and reduced endothelial activation was associated with improved HbA 1c after exercise.

A novel workflow combining plaque imaging, plaque and plasma proteomics identifies biomarkers of human coronary atherosclerotic plaque disruption.

PubMed

Lee, Regent; Fischer, Roman; Charles, Philip D; Adlam, David; Valli, Alessandro; Di Gleria, Katalin; Kharbanda, Rajesh K; Choudhury, Robin P; Antoniades, Charalambos; Kessler, Benedikt M; Channon, Keith M

2017-01-01

Atherosclerotic plaque rupture is the culprit event which underpins most acute vascular syndromes such as acute myocardial infarction. Novel biomarkers of plaque rupture could improve biological understanding and clinical management of patients presenting with possible acute vascular syndromes but such biomarker(s) remain elusive. Investigation of biomarkers in the context of de novo plaque rupture in humans is confounded by the inability to attribute the plaque rupture as the source of biomarker release, as plaque ruptures are typically associated with prompt down-stream events of myocardial necrosis and systemic inflammation. We developed a novel approach to identify potential biomarkers of plaque rupture by integrating plaque imaging, using optical coherence tomography, with both plaque and plasma proteomic analysis in a human model of angioplasty-induced plaque disruption. We compared two pairs of coronary plaque debris, captured by a FilterWire Device, and their corresponding control samples and found matrix metalloproteinase 9 (MMP9) to be significantly enriched in plaque. Plaque contents, as defined by optical coherence tomography, affect the systemic changes of MMP9. Disruption of lipid-rich plaque led to prompt elevation of plasma MMP9, whereas disruption of non-lipid-rich plaque resulted in delayed elevation of plasma MMP9. Systemic MMP9 elevation is independent of the associated myocardial necrosis and systemic inflammation (measured by Troponin I and C-reactive protein, respectively). This information guided the selection of a subset of subjects of for further label free proteomics analysis by liquid chromatography tandem mass spectrometry (LC-MS/MS). We discovered five novel, plaque-enriched proteins (lipopolysaccharide binding protein, Annexin A5, eukaryotic translocation initiation factor, syntaxin 11, cytochrome B5 reductase 3) to be significantly elevated in systemic circulation at 5 min after plaque disruption. This novel approach for biomarker discovery in human coronary artery plaque disruption can identify new biomarkers related to human coronary artery plaque composition and disruption.

CArbon dioxide surgical field flooding and aortic NO-touch off-pump coronary artery bypass grafting to reduce Neurological injuries after surgical coronary revascularisation (CANON): protocol for a randomised, controlled, investigator and patient blinded single-centre superiority trial with three parallel arms.

PubMed

Krzysztof, Szwed; Wojciech, Pawliszak; Zbigniew, Serafin; Mariusz, Kowalewski; Remigiusz, Tomczyk; Damian, Perlinski; Magdalena, Szwed; Marta, Tomaszewska; Lech, Anisimowicz; Alina, Borkowska

2017-07-10

Neurological injuries remain a major concern following coronary artery bypass grafting (CABG) that offsets survival benefit of CABG over percutaneous coronary interventions. Among numerous efforts to combat this issue is the development of off-pump CABG (OPCABG) that obviates the need for extracorporeal circulation and is associated with improved neurological outcomes. The objective of this study is to examine whether the neuroprotective effect of OPCABG can be further pronounced by the use of two state-of-the-art operating techniques. In this randomised, controlled, investigator and patient blinded single-centre superiority trial with three parallel arms, a total of 360 patients will be recruited. They will be allocated in a 1:1:1 ratio to two treatment arms and one control arm. Treatment arms undergoing either aortic no-touch OPCABG or OPCABG with partial clamp applying carbon dioxide surgical field flooding will be compared against control arm undergoing OPCABG with partial clamp. The primary endpoint will be the appearance of new lesions on control brain MRI 3 days after surgery. Secondary endpoints will include the prevalence of new focal neurological deficits in the first 7 days after surgery, the occurrence of postoperative cognitive dysfunction at either 1 week or 3 months after surgery and the incidence of delirium in the first 7 days after surgery. Data will be analysed on intention-to-treat principles and a per protocol basis. Ethical approval has been granted for this study. Results will be disseminated through peer-reviewed media. NCT03074604; Pre-results. 10-Mar-2017 Original. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Incremental prognostic value of biomarkers beyond the GRACE (Global Registry of Acute Coronary Events) score and high-sensitivity cardiac troponin T in non-ST-elevation acute coronary syndrome.

PubMed

Widera, Christian; Pencina, Michael J; Bobadilla, Maria; Reimann, Ines; Guba-Quint, Anja; Marquardt, Ivonne; Bethmann, Kerstin; Korf-Klingebiel, Mortimer; Kempf, Tibor; Lichtinghagen, Ralf; Katus, Hugo A; Giannitsis, Evangelos; Wollert, Kai C

2013-10-01

Guidelines recommend the use of validated risk scores and a high-sensitivity cardiac troponin assay for risk assessment in non-ST-elevation acute coronary syndrome (NSTE-ACS). The incremental prognostic value of biomarkers in this context is unknown. We calculated the Global Registry of Acute Coronary Events (GRACE) score and measured the circulating concentrations of high-sensitivity cardiac troponin T (hs-cTnT) and 8 selected cardiac biomarkers on admission in 1146 patients with NSTE-ACS. We used an hs-cTnT threshold at the 99th percentile of a reference population to define increased cardiac marker in the score. The magnitude of the increase in model performance when individual biomarkers were added to GRACE was assessed by the change (Δ) in the area under the receiver-operating characteristic curve (AUC), integrated discrimination improvement (IDI), and category-free net reclassification improvement [NRI(>0)]. Seventy-eight patients reached the combined end point of 6-month all-cause mortality or nonfatal myocardial infarction. The GRACE score alone had an AUC of 0.749. All biomarkers were associated with the risk of the combined end point and offered statistically significant improvement in model performance when added to GRACE (likelihood ratio test P ≤ 0.015). Growth differentiation factor 15 [ΔAUC 0.039, IDI 0.049, NRI(>0) 0.554] and N-terminal pro-B-type natriuretic peptide [ΔAUC 0.024, IDI 0.027, NRI(>0) 0.438] emerged as the 2 most promising biomarkers. Improvements in model performance upon addition of a second biomarker were small in magnitude. Biomarkers can add prognostic information to the GRACE score even in the current era of high-sensitivity cardiac troponin assays. The incremental information offered by individual biomarkers varies considerably, however.

Pathway-Specific Aggregate Biomarker Risk Score Is Associated With Burden of Coronary Artery Disease and Predicts Near-Term Risk of Myocardial Infarction and Death

PubMed Central

Ghasemzadeh, Nima; Hayek, Salim S.; Ko, Yi-An; Eapen, Danny J.; Patel, Riyaz S.; Manocha, Pankaj; Kassem, Hatem Al; Khayata, Mohamed; Veledar, Emir; Kremastinos, Dimitrios; Thorball, Christian W.; Pielak, Tomasz; Sikora, Sergey; Zafari, A. Maziar; Lerakis, Stamatios; Sperling, Laurence; Vaccarino, Viola; Epstein, Stephen E.; Quyyumi, Arshed A.

2018-01-01

Background Inflammation, coagulation, and cell stress contribute to atherosclerosis and its adverse events. A biomarker risk score (BRS) based on the circulating levels of biomarkers C-reactive protein, fibrin degradation products, and heat shock protein-70 representing these 3 pathways was a strong predictor of future outcomes. We investigated whether soluble urokinase plasminogen activator receptor (suPAR), a marker of immune activation, is predictive of outcomes independent of the aforementioned markers and whether its addition to a 3-BRS improves risk reclassification. Methods and Results C-reactive protein, fibrin degradation product, heat shock protein-70, and suPAR were measured in 3278 patients undergoing coronary angiography. The BRS was calculated by counting the number of biomarkers above a cutoff determined using the Youden’s index. Survival analyses were performed using models adjusted for traditional risk factors. A high suPAR level ≥3.5 ng/mL was associated with all-cause death and myocardial infarction (hazard ratio, 1.83; 95% confidence interval, 1.43–2.35) after adjustment for risk factors, C-reactive protein, fibrin degradation product, and heat shock protein-70. Addition of suPAR to the 3-BRS significantly improved the C statistic, integrated discrimination improvement, and net reclassification index for the primary outcome. A BRS of 1, 2, 3, or 4 was associated with a 1.81-, 2.59-, 6.17-, and 8.80-fold increase, respectively, in the risk of death and myocardial infarction. The 4-BRS was also associated with severity of coronary artery disease and composite end points. Conclusions SuPAR is independently predictive of adverse outcomes, and its addition to a 3-BRS comprising C-reactive protein, fibrin degradation product, and heat shock protein-70 improved risk reclassification. The clinical utility of using a 4-BRS for risk prediction and management of patients with coronary artery disease warrants further study. PMID:28280039

Pathway-Specific Aggregate Biomarker Risk Score Is Associated With Burden of Coronary Artery Disease and Predicts Near-Term Risk of Myocardial Infarction and Death.

PubMed

Ghasemzedah, Nima; Hayek, Salim S; Ko, Yi-An; Eapen, Danny J; Patel, Riyaz S; Manocha, Pankaj; Al Kassem, Hatem; Khayata, Mohamed; Veledar, Emir; Kremastinos, Dimitrios; Thorball, Christian W; Pielak, Tomasz; Sikora, Sergey; Zafari, A Maziar; Lerakis, Stamatios; Sperling, Laurence; Vaccarino, Viola; Epstein, Stephen E; Quyyumi, Arshed A

2017-03-01

Inflammation, coagulation, and cell stress contribute to atherosclerosis and its adverse events. A biomarker risk score (BRS) based on the circulating levels of biomarkers C-reactive protein, fibrin degradation products, and heat shock protein-70 representing these 3 pathways was a strong predictor of future outcomes. We investigated whether soluble urokinase plasminogen activator receptor (suPAR), a marker of immune activation, is predictive of outcomes independent of the aforementioned markers and whether its addition to a 3-BRS improves risk reclassification. C-reactive protein, fibrin degradation product, heat shock protein-70, and suPAR were measured in 3278 patients undergoing coronary angiography. The BRS was calculated by counting the number of biomarkers above a cutoff determined using the Youden's index. Survival analyses were performed using models adjusted for traditional risk factors. A high suPAR level ≥3.5 ng/mL was associated with all-cause death and myocardial infarction (hazard ratio, 1.83; 95% confidence interval, 1.43-2.35) after adjustment for risk factors, C-reactive protein, fibrin degradation product, and heat shock protein-70. Addition of suPAR to the 3-BRS significantly improved the C statistic, integrated discrimination improvement, and net reclassification index for the primary outcome. A BRS of 1, 2, 3, or 4 was associated with a 1.81-, 2.59-, 6.17-, and 8.80-fold increase, respectively, in the risk of death and myocardial infarction. The 4-BRS was also associated with severity of coronary artery disease and composite end points. SuPAR is independently predictive of adverse outcomes, and its addition to a 3-BRS comprising C-reactive protein, fibrin degradation product, and heat shock protein-70 improved risk reclassification. The clinical utility of using a 4-BRS for risk prediction and management of patients with coronary artery disease warrants further study. © 2017 American Heart Association, Inc.

Integration of Wall Motion, Coronary Flow Velocity, and Left Ventricular Contractile Reserve in a Single Test: Prognostic Value of Vasodilator Stress Echocardiography in Patients with Diabetes.

PubMed

Cortigiani, Lauro; Huqi, Alda; Ciampi, Quirino; Bombardini, Tonino; Bovenzi, Francesco; Picano, Eugenio

2018-06-01

Coronary flow velocity reserve (CFVR) and left ventricular contractile reserve (LVCR) have demonstrated prognostic importance in patients with diabetes. The aim of this study was to investigate the prognostic contribution of combined evaluation of CFVR and LVCR in patients with diabetes with nonischemic stress echocardiography. Three hundred seventy-five patients with diabetes (mean age, 68 ± 9 years) with nonischemic dipyridamole stress echocardiography underwent assessment of CFVR of the left anterior descending coronary artery (prospectively) and LVCR with left ventricular force (retrospectively) in a multicenter study. On receiver operating characteristic analysis, LVCR ≤ 1.1 was the best prognostic predictor and was considered an abnormal value. CFVR was abnormal (≤2) in 139 patients (37%), LVCR in 156 (42%), neither in 157 (42%), and both in 77 (21%). During a median follow-up period of 16 months, 86 major adverse cardiac events occurred: 16 deaths, 13 myocardial infarctions, and 57 revascularizations. Multivariate prognostic indicators were CFVR ≤ 2 (P < .0001), age (P = .03), and LVCR ≤ 1.1 (P = .04). The 3-year rate of major adverse cardiac events was 63% in patients with both abnormal CFVR and LVCR, 42% in those with abnormal CFVR only, 19% in those with abnormal LVCR only, and 10% in patients with both normal CFVR and LVCR. The 3-year hard event rate was 3% in patients with both normal CFVR and LVCR, fivefold higher in patients with abnormal CFVR or LVCR only, and ninefold higher in patients with both abnormal CFVR and LVCR. Patients with diabetes with nonischemic dipyridamole stress echocardiography may still have significant risk in presence of abnormal CFVR and/or LVCR, which assess the underlying, largely unrelated, microvascular and myocardial components of coronary circulation. Copyright © 2017 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

Assessing the cost effectiveness of using prognostic biomarkers with decision models: case study in prioritising patients waiting for coronary artery surgery

PubMed Central

Henriksson, Martin; Palmer, Stephen; Chen, Ruoling; Damant, Jacqueline; Fitzpatrick, Natalie K; Abrams, Keith; Hingorani, Aroon D; Stenestrand, Ulf; Janzon, Magnus; Feder, Gene; Keogh, Bruce; Shipley, Martin J; Kaski, Juan-Carlos; Timmis, Adam; Sculpher, Mark

2010-01-01

Objective To determine the effectiveness and cost effectiveness of using information from circulating biomarkers to inform the prioritisation process of patients with stable angina awaiting coronary artery bypass graft surgery. Design Decision analytical model comparing four prioritisation strategies without biomarkers (no formal prioritisation, two urgency scores, and a risk score) and three strategies based on a risk score using biomarkers: a routinely assessed biomarker (estimated glomerular filtration rate), a novel biomarker (C reactive protein), or both. The order in which to perform coronary artery bypass grafting in a cohort of patients was determined by each prioritisation strategy, and mean lifetime costs and quality adjusted life years (QALYs) were compared. Data sources Swedish Coronary Angiography and Angioplasty Registry (9935 patients with stable angina awaiting coronary artery bypass grafting and then followed up for cardiovascular events after the procedure for 3.8 years), and meta-analyses of prognostic effects (relative risks) of biomarkers. Results The observed risk of cardiovascular events while on the waiting list for coronary artery bypass grafting was 3 per 10 000 patients per day within the first 90 days (184 events in 9935 patients). Using a cost effectiveness threshold of £20 000-£30 000 (€22 000-€33 000; $32 000-$48 000) per additional QALY, a prioritisation strategy using a risk score with estimated glomerular filtration rate was the most cost effective strategy (cost per additional QALY was <£410 compared with the Ontario urgency score). The impact on population health of implementing this strategy was 800 QALYs per 100 000 patients at an additional cost of £245 000 to the National Health Service. The prioritisation strategy using a risk score with C reactive protein was associated with lower QALYs and higher costs compared with a risk score using estimated glomerular filtration rate. Conclusion Evaluating the cost effectiveness of prognostic biomarkers is important even when effects at an individual level are small. Formal prioritisation of patients awaiting coronary artery bypass grafting using a routinely assessed biomarker (estimated glomerular filtration rate) along with simple, routinely collected clinical information was cost effective. Prioritisation strategies based on the prognostic information conferred by C reactive protein, which is not currently measured in this context, or a combination of C reactive protein and estimated glomerular filtration rate, is unlikely to be cost effective. The widespread practice of using only implicit or informal means of clinically ordering the waiting list may be harmful and should be replaced with formal prioritisation approaches. PMID:20085988

Comparative and Developmental Anatomy of Cardiac Lymphatics

PubMed Central

Ratajska, A.; Gula, G.; Flaht-Zabost, A.; Czarnowska, E.; Ciszek, B.; Jankowska-Steifer, E.; Niderla-Bielinska, J.; Radomska-Lesniewska, D.

2014-01-01

The role of the cardiac lymphatic system has been recently appreciated since lymphatic disturbances take part in various heart pathologies. This review presents the current knowledge about normal anatomy and structure of lymphatics and their prenatal development for a better understanding of the proper functioning of this system in relation to coronary circulation. Lymphatics of the heart consist of terminal capillaries of various diameters, capillary plexuses that drain continuously subendocardial, myocardial, and subepicardial areas, and draining (collecting) vessels that lead the lymph out of the heart. There are interspecies differences in the distribution of lymphatic capillaries, especially near the valves, as well as differences in the routes and number of draining vessels. In some species, subendocardial areas contain fewer lymphatic capillaries as compared to subepicardial parts of the heart. In all species there is at least one collector vessel draining lymph from the subepicardial plexuses and running along the anterior interventricular septum under the left auricle and further along the pulmonary trunk outside the heart and terminating in the right venous angle. The second collector assumes a different route in various species. In most mammalian species the collectors run along major branches of coronary arteries, have valves and a discontinuous layer of smooth muscle cells. PMID:24592145

Bilirubin and atherosclerotic diseases.

PubMed

Vítek, L

2017-04-05

Bilirubin is the final product of heme catabolism in the systemic circulation. For decades, increased serum/plasma bilirubin levels were considered an ominous sign of an underlying liver disease. However, data from recent years convincingly suggest that mildly elevated bilirubin concentrations are associated with protection against various oxidative stress-mediated diseases, atherosclerotic conditions being the most clinically relevant. Although scarce data on beneficial effects of bilirubin had been published also in the past, it took until 1994 when the first clinical study demonstrated an increased risk of coronary heart disease in subjects with low serum bilirubin levels, and bilirubin was found to be a risk factor for atherosclerotic diseases independent of standard risk factors. Consistent with these results, we proved in our own studies, that subjects with mild elevation of serum levels of unconjugated bilirubin (benign hyperbilirubinemia, Gilbert syndrome) have much lower prevalence/incidence of coronary heart as well as peripheral vascular disease. We have also demonstrated that this association is even more general, with serum bilirubin being a biomarker of numerous other diseases, often associated with increased risk of atherosclerosis. In addition, very recent data have demonstrated biological pathways modulated by bilirubin, which are responsible for observed strong clinical associations.

Comparative and developmental anatomy of cardiac lymphatics.

PubMed

Ratajska, A; Gula, G; Flaht-Zabost, A; Czarnowska, E; Ciszek, B; Jankowska-Steifer, E; Niderla-Bielinska, J; Radomska-Lesniewska, D

2014-01-01

The role of the cardiac lymphatic system has been recently appreciated since lymphatic disturbances take part in various heart pathologies. This review presents the current knowledge about normal anatomy and structure of lymphatics and their prenatal development for a better understanding of the proper functioning of this system in relation to coronary circulation. Lymphatics of the heart consist of terminal capillaries of various diameters, capillary plexuses that drain continuously subendocardial, myocardial, and subepicardial areas, and draining (collecting) vessels that lead the lymph out of the heart. There are interspecies differences in the distribution of lymphatic capillaries, especially near the valves, as well as differences in the routes and number of draining vessels. In some species, subendocardial areas contain fewer lymphatic capillaries as compared to subepicardial parts of the heart. In all species there is at least one collector vessel draining lymph from the subepicardial plexuses and running along the anterior interventricular septum under the left auricle and further along the pulmonary trunk outside the heart and terminating in the right venous angle. The second collector assumes a different route in various species. In most mammalian species the collectors run along major branches of coronary arteries, have valves and a discontinuous layer of smooth muscle cells.

CardioNet: a human metabolic network suited for the study of cardiomyocyte metabolism.

PubMed

Karlstädt, Anja; Fliegner, Daniela; Kararigas, Georgios; Ruderisch, Hugo Sanchez; Regitz-Zagrosek, Vera; Holzhütter, Hermann-Georg

2012-08-29

Availability of oxygen and nutrients in the coronary circulation is a crucial determinant of cardiac performance. Nutrient composition of coronary blood may significantly vary in specific physiological and pathological conditions, for example, administration of special diets, long-term starvation, physical exercise or diabetes. Quantitative analysis of cardiac metabolism from a systems biology perspective may help to a better understanding of the relationship between nutrient supply and efficiency of metabolic processes required for an adequate cardiac output. Here we present CardioNet, the first large-scale reconstruction of the metabolic network of the human cardiomyocyte comprising 1793 metabolic reactions, including 560 transport processes in six compartments. We use flux-balance analysis to demonstrate the capability of the network to accomplish a set of 368 metabolic functions required for maintaining the structural and functional integrity of the cell. Taking the maintenance of ATP, biosynthesis of ceramide, cardiolipin and further important phospholipids as examples, we analyse how a changed supply of glucose, lactate, fatty acids and ketone bodies may influence the efficiency of these essential processes. CardioNet is a functionally validated metabolic network of the human cardiomyocyte that enables theorectical studies of cellular metabolic processes crucial for the accomplishment of an adequate cardiac output.

Porphyromonas gingivalis-dendritic cell interactions: consequences for coronary artery disease.

PubMed

Zeituni, Amir E; Carrion, Julio; Cutler, Christopher W

2010-12-21

An estimated 80 million US adults have one or more types of cardiovascular diseases. Atherosclerosis is the single most important contributor to cardiovascular diseases; however, only 50% of atherosclerosis patients have currently identified risk factors. Chronic periodontitis, a common inflammatory disease, is linked to an increased cardiovascular risk. Dendritic cells (DCs) are potent antigen presenting cells that infiltrate arterial walls and may destabilize atherosclerotic plaques in cardiovascular disease. While the source of these DCs in atherosclerotic plaques is presently unclear, we propose that dermal DCs from peripheral inflamed sites such as CP tissues are a potential source. This review will examine the role of the opportunistic oral pathogen Porphyromonas gingivalis in invading DCs and stimulating their mobilization and misdirection through the bloodstream. Based on our published observations, combined with some new data, as well as a focused review of the literature we will propose a model for how P. gingivalis may exploit DCs to gain access to systemic circulation and contribute to coronary artery disease. Our published evidence supports a significant role for P. gingivalis in subverting normal DC function, promoting a semimature, highly migratory, and immunosuppressive DC phenotype that contributes to the inflammatory development of atherosclerosis and, eventually, plaque rupture.

Epigenetic Biomarkers and Cardiovascular Disease: Circulating MicroRNAs.

PubMed

de Gonzalo-Calvo, David; Iglesias-Gutiérrez, Eduardo; Llorente-Cortés, Vicenta

2017-09-01

MicroRNAs (miRNAs) are a class of small noncoding RNA (20-25 nucleotides) involved in gene regulation. In recent years, miRNAs have emerged as a key epigenetic mechanism in the development and physiology of the cardiovascular system. These molecular species regulate basic functions in virtually all cell types, and are therefore directly associated with the pathophysiology of a large number of cardiovascular diseases. Since their relatively recent discovery in extracellular fluids, miRNAs have been studied as potential biomarkers of disease. A wide array of studies have proposed miRNAs as circulating biomarkers of different cardiovascular pathologies (eg, myocardial infarction, coronary heart disease, and heart failure, among others), which may have superior physicochemical and biochemical properties than the conventional protein indicators currently used in clinical practice. In the present review, we provide a brief introduction to the field of miRNAs, paying special attention to their potential clinical application. This includes their possible role as new diagnostic or prognostic biomarkers in cardiovascular disease. Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Utility of Traditional Circulating and Imaging-Based Cardiac Biomarkers in Patients with Predialysis CKD

PubMed Central

Colbert, Gates; Jain, Nishank; de Lemos, James A.

2015-01-01

Cardiac biomarkers, such as cardiac troponin T (cTnT), brain natriuretic peptide (BNP), and N-terminal-pro-BNP (NT-pro-BNP), are commonly used to diagnose acute coronary syndrome and congestive heart failure exacerbation in symptomatic patients. Levels of these biomarkers are frequently chronically elevated in asymptomatic patients with ESRD who are receiving maintenance dialysis. Other imaging biomarkers commonly encountered in nephrologists’ clinical practice, such as coronary artery calcium measured by computed tomography, left ventricular hypertrophy, and carotid intima-media thickness, are also frequently abnormal in asymptomatic patients with ESRD. This article critically reviews the limited observational data on associations between cTnT, BNP, NT-pro-BNP, coronary artery calcium, left ventricular hypertrophy, and carotid intima-media thickness with cardiovascular events and death in non–dialysis-dependent patients with CKD. Although sufficient evidence suggests that these biomarkers may be used for prognostication, the diagnostic utility of cTnT, BNP, and NT-pro-BNP remain challenging in patients with CKD. Decreased renal clearance may affect the plasma levels of these biomarkers, and upper reference limits were originally derived in patients without CKD. Until better data are available, higher cutoffs, or a rise in level compared with previous values, have been proposed to help distinguish acute myocardial infarction from chronic elevations of cTnT in symptomatic patients with CKD. Additionally, it is not known whether these biomarkers are modifiable and amenable to interventions that could change hard clinical outcomes in patients with CKD not yet undergoing long-term dialysis. PMID:25403922

Platelet and leukocyte activation, atherosclerosis and inflammation in European and South Asian men.

PubMed

Dotsenko, O; Chaturvedi, N; Thom, S A McG; Wright, A R; Mayet, J; Shore, A; Schalkwijk, C; Hughes, A D

2007-10-01

Increased platelet activation occurs in ischemic heart disease (IHD), but increased platelet activation is also seen in cerebrovascular atherosclerosis and peripheral artery disease. It is not clear therefore whether platelet activation is an indicator of IHD or a marker of generalized atherosclerosis and inflammation. South Asian subjects are at high risk of IHD, but little is known regarding differences in platelet and leukocyte function between European and South Asian subjects. Fifty-four male subjects (age 49-79 years) had coronary artery calcification measured by multislice computed tomography (CT), aortic atherosclerosis assessed by measurement of carotid-femoral pulse wave velocity (aortic PWV), and femoral and carotid atherosclerosis measured by B-mode ultrasound. Platelet and leukocyte activation was assessed by flow cytometry of platelet-monocyte complexes (PMC), platelet expression of PAC-1 binding site and CD62P, and expression of L-selectin on leukocytes. Elevated circulating PMC correlated significantly with elevated aortic PWV and PMC were higher in subjects with femoral plaques. In contrast PMC did not differ by increasing coronary artery calcification category or presence of carotid plaques. Higher numbers of PMC were independently related to elevated levels of C-reactive protein (CRP), higher aortic PWV, hypertension and smoking in a multivariate model. Markers of platelet and leukocyte activation did not differ significantly by ethnicity. Increased PMC are related to the extent of aortic and femoral atherosclerosis rather than coronary or carotid atherosclerosis. The association between elevated CRP and increased PMC suggests that inflammation in relation to generalized atherosclerosis may play an important role in PMC activation.

Major Depression and Coronary Flow Reserve Detected by Positron Emission Tomography

PubMed Central

Vaccarino, Viola; Votaw, John; Faber, Tracy; Veledar, Emir; Murrah, Nancy V.; Jones, Linda R.; Zhao, Jinying; Su, Shaoyong; Goldberg, Jack; Raggi, J. Paolo; Quyyumi, Arshed A.; Sheps, David S.; Bremner, J. Douglas

2010-01-01

Background Major depressive disorder (MDD) is associated with coronary heart disease (CHD), but the mechanisms are unclear. The presence of MDD may increase CHD risk by affecting microvascular circulation. It is also plausible that genetic factors influencing MDD may overlap with those for CHD. We sought to examine the relationship between MDD and coronary flow reserve (CFR), the ratio of maximum flow during stress to flow at rest measured in milliliters per minute per gram of tissue. Methods We examined 289 male middle-aged twins, including 106 twins (53 twin pairs) discordant for a lifetime history of MDD and 183 control twins (unrelated to any twins in the experimental group) without MDD. To calculate CFR, we used positron emission tomography with nitrogen 13 (13N) ammonia to evaluate myocardial blood flow at rest and after adenosine stress. A standard perfusion defect score was also used to assess myocardial ischemia. Results There was no difference in myocardial ischemia between twins with and without MDD. Among the dizygotic twin pairs discordant for MDD, the CFR was 14% lower in the twins with MDD than in their brothers without MDD (2.36 vs 2.74) (P=.03). This association was not present in the monozygotic discordant pairs who were genetically matched (2.86 vs 2.64) (P = .19). The zygosity-MDD interaction after adjustment was significant (P=.006). The CFR in the dizygotic twins with MDD was also lower than in the control twins. Conclusions Our results provide evidence for a shared genetic pathway between MDD and microvascular dysfunction. Common pathophysiologic processes may link MDD and early atherosclerosis. PMID:19822823

Influence of isoflurane on the diastolic pressure-flow relationship and critical occlusion pressure during arterial CABG surgery: a randomized controlled trial.

PubMed

Hinz, José; Mansur, Ashham; Hanekop, Gerd G; Weyland, Andreas; Popov, Aron F; Schmitto, Jan D; Grüne, Frank F G; Bauer, Martin; Kazmaier, Stephan

2016-01-01

The effects of isoflurane on the determinants of blood flow during Coronary Artery Bypass Graft (CABG) surgery are not completely understood. This study characterized the influence of isoflurane on the diastolic Pressure-Flow (P-F) relationship and Critical Occlusion Pressure (COP) during CABG surgery. Twenty patients undergoing CABG surgery were studied. Patients were assigned to an isoflurane or control group. Hemodynamic and flow measurements during CABG surgery were performed twice (15 minutes after the discontinuation of extracorporeal circulation (T15) and again 15 minutes later (T30)). The zero flow pressure intercept (a measure of COP) was extrapolated from a linear regression analysis of the instantaneous diastolic P-F relationship. In the isoflurane group, the application of isoflurane significantly increased the slope of the diastolic P-F relationship by 215% indicating a mean reduction of Coronary Vascular Resistance (CVR) by 46%. Simultaneously, the Mean Diastolic Aortic Pressure (MDAP) decreased by 19% mainly due to a decrease in the systemic vascular resistance index by 21%. The COP, cardiac index, heart rate, Left Ventricular End-Diastolic Pressure (LVEDP) and Coronary Sinus Pressure (CSP) did not change significantly. In the control group, the parameters remained unchanged. In both groups, COP significantly exceeded the CSP and LVEDP at both time points. We conclude that short-term application of isoflurane at a sedative concentration markedly increases the slope of the instantaneous diastolic P-F relationship during CABG surgery implying a distinct decrease with CVR in patients undergoing CABG surgery.

Reversal of diabetic vasculopathy in a rat model of type 1 diabetes by opiorphin-related peptides

PubMed Central

Calenda, Giulia; Tong, Yuehong; Kanika, Nirmala D.; Tar, Moses T.; Suadicani, Sylvia O.; Zhang, Xinhua; Melman, Arnold; Rougeot, Catherine

2011-01-01

Diabetes results in a myriad of vascular complications, often referred to as diabetic vasculopathy, which encompasses both microvascular [erectile dysfunction (ED), retinopathy, neuropathy, and nephropathy] and macrovascular complications (hypertension, coronary heart disease, and myocardial infarction). In diabetic animals and patients with ED, there is decreased opiorphin or opiorphin-related gene expression in corporal tissue. Both opiorphin and the rat homologous peptide sialorphin are found circulating in the plasma. In the present study, we investigated if diabetes induced changes in plasma sialorphin levels and if changes in these levels could modulate the biochemistry and physiology of vascular smooth muscle. We show that circulating sialorphin levels are reduced in a rat model of type I diabetes. Intracorporal injection of plasmids expressing sialorphin into diabetic rats restores sialorphin levels to those seen in the blood of nondiabetic animals and results in both improved erectile function and blood pressure. Sialorphin modulated the ability of C-type natriuretic peptide to relax both corporal and aortic smooth muscle strips and of bradykinin to regulate intracellular calcium levels in both corporal and aortic smooth muscle cells. We have previously shown that expression of genes encoding opiorphins is increased when erectile function is improved. Our findings thus suggest that by affecting circulating levels of opiorphin-related peptides, proper erectile function is not only an indicator but also a modulator of overall vascular health of a man. PMID:21784987

Reversal of diabetic vasculopathy in a rat model of type 1 diabetes by opiorphin-related peptides.

PubMed

Calenda, Giulia; Tong, Yuehong; Kanika, Nirmala D; Tar, Moses T; Suadicani, Sylvia O; Zhang, Xinhua; Melman, Arnold; Rougeot, Catherine; Davies, Kelvin P

2011-10-01

Diabetes results in a myriad of vascular complications, often referred to as diabetic vasculopathy, which encompasses both microvascular [erectile dysfunction (ED), retinopathy, neuropathy, and nephropathy] and macrovascular complications (hypertension, coronary heart disease, and myocardial infarction). In diabetic animals and patients with ED, there is decreased opiorphin or opiorphin-related gene expression in corporal tissue. Both opiorphin and the rat homologous peptide sialorphin are found circulating in the plasma. In the present study, we investigated if diabetes induced changes in plasma sialorphin levels and if changes in these levels could modulate the biochemistry and physiology of vascular smooth muscle. We show that circulating sialorphin levels are reduced in a rat model of type I diabetes. Intracorporal injection of plasmids expressing sialorphin into diabetic rats restores sialorphin levels to those seen in the blood of nondiabetic animals and results in both improved erectile function and blood pressure. Sialorphin modulated the ability of C-type natriuretic peptide to relax both corporal and aortic smooth muscle strips and of bradykinin to regulate intracellular calcium levels in both corporal and aortic smooth muscle cells. We have previously shown that expression of genes encoding opiorphins is increased when erectile function is improved. Our findings thus suggest that by affecting circulating levels of opiorphin-related peptides, proper erectile function is not only an indicator but also a modulator of overall vascular health of a man.

Local Drug Delivery to Prevent Restenosis

PubMed Central

Seedial, Stephen M.; Ghosh, Soumojit; Saunders, R. Scott; Suwanabol, Pasithorn A.; Shi, Xudong; Liu, Bo; Kent, K. Craig

2013-01-01

Introduction Despite significant advances in vascular biology, bioengineering and pharmacology, restenosis remains a limitation to the overall efficacy of vascular reconstructions, both percutaneous and open. Although the pathophysiology of intimal hyperplasia is complex, a number of drugs and/or molecular tools have been identified that can prevent restenosis. Moreover, the focal nature of this process lends itself to treatment with local drug administration. In this article we provide a broad overview of current and future techniques for local drug delivery that have been developed to prevent restenosis following vascular intervention. Methods A systematic electronic literature search using PubMed was performed for all accessible published articles through September 2012. In an effort to remain current, additional searches were performed for abstracts presented at relevant societal meetings, filed patents, clinical trials and funded NIH awards. Results The efficacy of local drug delivery has been demonstrated in the coronary circulation with the current clinical use of drug-eluting stents (DES). Until recently, however, DES were not found to be efficacious in the peripheral circulation. Further pursuit of intraluminal devices has led to the development of balloon-based technologies with a recent surge in trials involving drug-eluting balloons. Early data appears encouraging, particularly for treatment of lesions in the superficial femoral artery, with several devices having recently received the CE mark in Europe. Investigators have also explored periadventitial application of biomaterials containing anti-restenotic drugs, an approach that could be particularly useful for surgical bypass or endarterectomy. In the past systemic drug delivery has been unsuccessful, however, there has been recent exploration of intravenous delivery of drugs designed specifically to target injured or reconstructed arteries. Our review revealed a multitude of additional interesting strategies including more than 65 new patents issued over the past two years for approaches to local drug delivery focused on preventing restenosis. Conclusion Restenosis following intraluminal or open vascular reconstruction remains an important clinical problem. Success in the coronary circulation has not translated into solutions for the peripheral arteries. However, our review of the literature reveals a number of promising approaches including drug-eluting balloons, periadventitial drug delivery as well as targeted systemic therapies. These innovations as well as others suggest that the future is bright and a solution for preventing restenosis in peripheral vessels will soon be at hand. PMID:23601595

[Agranulocytosis and acute coronary syndrome in apathetic hyperthyroidism].

PubMed

Ivović, Miomira; Radiojković, Biljena; Penezić, Zorana; Stojković, Mirjana; Tancić, Milina; Vujović, Svetlana; Bogdanović, Andrija; Drezgić, Milka

2003-01-01

Tissue expose to excessive levels of circulating thyroid hormones results in thyrotoxicosis. In most cases, thyrotoxicosis is due to hyperactivity of the thyroid gland. Cardiovascular and myopathic manifestations are predominant clinical features in most hyperthyroid patients, aged 60 years and older. Some of patients have apathetic hyperthyroidism which presents with weight loss, small goiter, severe depression and without clinical features of increased sympathetic activity [3, 6]. About 50% of patients with cardiovascular manifestations have no evidence of underlying heart disease. Cardiac problems resolve when euthyroid state is established [3]. Three treatment modalities are available in hyperthyroidism, namely medicament therapy, surgery and radioactive iodine. Antithyroid drug therapy complications, can be mild such as rash, which is managed without cessation of therapy by antihistamines administration. On the other hand, very serious complications such as agranulocytosis, necessitate immediate discontinuation of the medication and appropriate treatment. Although extremely rear, it is life-threatening with highly variable recovery time. A 62-year-old woman with recurrent hyperthyroidism was admitted after treatment of agranulocytosis due to antithyroid drugs in another institution with G-CSF. The patient presented with clinical features of apathetic hyperthyroidism with extremely elevated thyroid hormone levels (total and free T4) and suppressed TSH. Radioactive iodine (5 mCi) was administered after increased thyroid uptake was confirmed. Echocardiography on admission was normal. ECG revealed moderately inverted T waves in standard and V1, V2 precordial leads. Laboratory analysis revealed mild normocytic anemia with normal white blood cell count, hypokaliemia and normal concentration of creatine phosphokinase, lactic dehydrogenase and mildly elevated aspartate transminase in sera. Chest X-ray was consistent with pulmonary emphysema. Because the worsening of ECG changes she was transferred to Coronary unit. The diagnosis of non-Q myocardial infarction was confirmed and treatment with nitrates and beta-adrenergic antagonists was instituted. Four weeks later she became euthyroid and coronarography was performed. Subepicardial coronary arteries were normal (Figure 1). She was dismissed, and still euthyroid three months later. Agranulocytosis is very rare but very serious complication of antithyroid drug therapy. It can be detected in about 0.1-1% patients during the first three months of treatment. Sudden appearance, heralded by sore throat and fever, prompt physicians to seek white blood cell and differential count [1-3]. Confirmation of diagnosis urges cessation of drug therapy and appropriate antibiotic treatment. Recently, it was reported that recombinant human granulocyte colony-stimulating factor (rhG-CSF) is to be effective in shortening the recovery time in the neutropenic patients undergoing chemotherapy and also in patients with other types of neutropenia [5]. Tamai at al. [7] confirmed positive outcome in 34 patients treated with rhG-CSF compared to corticosteroid treatment. Hematologic laboratory abnormalities disappear 7-10 days after session of therapy. Patients completely recover two to three weeks later. Fatal outcome was also described [1-5]. Thyroid hormones have profound effects on cardiovascular physiology, especially on heart rate, cardiac output and systemic vascular resistance. In patients with hyperthyroidism, cardiac output is much higher than in normal persons. This is the result of direct effect of thyroid hormones on cardiac muscle contractility, heart rate and decrease in systemic vascular resistance. Excessive thyroid hormone secretion increases cardiac Na-K-activated plasma membrane ATP-ase and sarcoplasmic reticulum Ca-activated ATP-ase with resultant in increase myocardial contractility [6, 9]. Sinus tachycardia is the most common rhythm disorder in hyperthyroidism, but paroxysmal tachycardia and atrial fibrillation are not rare. This can be explained by increased heart rate, cardiac output, blood volume, coronary artery flow and peripheral oxygen consumption in thyrotoxicosis [9]. Patients with coronary arteriosclerosis can develop angina pectoris during thyrotoxic stage, which can be explained by imbalance between cardiac demand and supply. Myocardial damage is often in thyrotoxic patients with chronic hart failure, together with myocardial infarction in patients without coronary disease [2,6]. Congestive heart failure and atrial fibrillation are relatively resistant to digitalis treatment because of high metabolic turn over of medication and excessive myocardial irritability in hyperthyroidism [6]. Cardiovascular and myopathic manifestations predominate in older hyperthyroid patients (over 60 years) and some of them can have only few symptoms of hyperthyroidism [1-3]. Thyrotoxic state characterized by fatigue, apathy, extreme weakness, low-grade fever and sometimes congestive heart failure are designated as apathetic hyperthyroidism. Such patients have small goiters, mild tachycardia and often cool and dry skin with few eye signs [6]. Patients with subclinical hyperthyroidism are at increased risk for atrial fibrillation [9]. Unstable angina and non-Q myocardial infarction (non ST elevation) are acute manifestation of coronary artery disease. The acute coronary syndrome of unstable angina, non-Q myocardial infarction and Q-wave myocardial infarction have atherosclerotic lesions of the coronary arteries as a common pathogenic substrate. Erosions or ruptures of unstable atherosclerotic plaque triggered pathophysiologic processes, resulted in thrombus formation at the site of arterial injury. This leads to abrupt reduction or cessation through the affected vessel. Clinical manifestations of unstable angina and non-Q myocardial infarction are similar and diagnosis of non-Q myocardial infarction is made on the basis of elevated serum markers indicative of cardiac necrosis, detected in peripheral circulation. Acute coronary syndrome ranging from unstable angina to myocardial infarction an non-Q myocardial infarction represents increasingly severe manifestations of the same pathophysiologic processes [10,11]. In conclusion, these 62-year-old woman presented with apathetic form of recurrent hyperthyroidism associated with two serious complications, life-threatening agranulocytosis and acute coronary syndrome.

Circulating fibroblast growth factor-23 plasma levels predict adverse cardiovascular outcomes in patients with diabetes mellitus with coronary artery disease.

PubMed

Tuñón, José; Fernández-Fernández, Beatriz; Carda, Rocío; Pello, Ana M; Cristóbal, Carmen; Tarín, Nieves; Aceña, Álvaro; González-Casaus, María Luisa; Huelmos, Ana; Alonso, Joaquín; Lorenzo, Óscar; González-Parra, Emilio; Hernández-González, Ignacio; Mahíllo-Fernández, Ignacio; López-Bescós, Lorenzo; Egido, Jesús

2016-10-01

Abnormalities of fibroblast growth factor-23 (FGF-23) plasma levels predict adverse outcomes in patients with coronary artery disease. However, FGF-23 has a different behaviour in the presence of type 2 diabetes mellitus (T2D). We explored whether the presence of T2D affects the predictive power of FGF-23. In 704 patients with stable coronary artery disease, FGF-23, calcidiol, parathormone (PTH) and phosphate plasma levels were prospectively assessed. The primary outcome was the development of acute ischemic events (acute coronary syndrome, stroke or transient ischemic attack), heart failure or death. One hundred seventy-three (24.6%) patients had T2D, without differences in age, sex or estimated glomerular filtration rate as compared with non-diabetic patients. Serum PTH was lower and phosphate higher in T2D than in non-diabetic patients, without differences in FGF-23 or calcidiol levels. During follow-up (2.15 ± 0.99 years), 26 (15.2%) T2D and 51 (9.6%) non-diabetic patients developed the outcome (p = 0.048). T2D patients who developed the outcome had higher FGF-23 [112.0 (59.9, 167.6) vs 68.9 (54.2, 93.0) RU/mL; p = 0.002], PTH [71.3 (47.3, 106.6) vs 51.9 (40.8, 66.2) pg/mL; p = 0.004) and phosphate (3.53 ± 0.71 vs 3.25 ± 0.50 mg/dL; p = 0.017) levels than T2D subjects who remained stable. These differences were not significant in non-diabetic patients. By multivariable Cox proportional hazard model, FGF-23 predicted independently the outcome in T2D patients [hazard ratio = 1.277; 95% CI (1.132, 1.442)] but not in those without T2D. FGF-23 plasma levels predict adverse cardiovascular outcomes in coronary artery disease patients who have T2D but not in those without T2D. This finding should be confirmed in larger studies. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

[Prevention of cerebrovascular complications in coronary artery bypass grafting].

PubMed

Mialiuk, P A; Marchenko, A V; Arutiunian, V B; Chragian, V A; Alekseevich, G Iu; Vronskiĭ, A S

The authors carried out a comparative analysis of the incidence rate of cerebrovascular complications following coronary artery bypass grafting performed using either a differentiated approach to surgical policy depending on the findings of epiaortic ultrasonographic scanning or the standard conventional approach. A total of 3,454 operations of coronary artery bypass grafting were performed. All patients were divided into two groups. Patients of the Study Group (n=765) were subjected to obligatory intraoperative epiaortic scanning, with the variant of further surgical intervention depending on the obtained findings of the examination. The Control Group patients (n=2,689) underwent standard coronary artery bypass grafting in the conditions of artificial circulation (AC). In the Study Group patients, depending on the degree and localization of the atherosclerotic lesion of the aorta, determined by the findings of epiaortic scanning, one of the following techniques of coronary artery bypass grafting (CABG) was chosen: cases with no lesion were managed by CABG with AC (585 patients); a local solitary lesion was managed by altering the site of cannulation and application of the clamp (92 patients) or by the operation according to the 'single clamp' technique (43 patients); cases of manifested atherosclerosis of the ascending aorta were treated by the 'on-pump beating-heart' technique in the conditions of AC without placing clamps (27 patients); cases of massive involvement of the ascending aorta and aortic arch were managed by CABG performed according to the 'no-touch aorta' technique (18 patients). The total mortality rate amounted to 1.1%. Thirty-three (0.96%) patients in the postoperative period were found to have ischaemic stroke. The mortality rate in the Control Group amounted to 1.4% and that in the Study Group equalled 0.3%, with the number of cases of ischaemic strokes amounting to 33 (1.4%) and 0, respectively. Perioperative infarction was diagnosed in 16 (0.6%) cases in the Control Group and in 5 (0.7%) patients in the group treated using the differentiated approach. A conclusion was drawn that the differentiated approach to choosing the technique of CABG based on the findings obtained by means of epiaortic scanning was associated with a statistically significant decrease in both the number of ischaemic strokes and the mortality rate after CABG operations.

Testosterone and acute stress are associated with fibrinogen and von Willebrand factor in African men: the SABPA study.

PubMed

Malan, Nicolaas T; von Känel, Roland; Schutte, Alta E; Huisman, Hugo W; Schutte, Rudolph; Smith, Wayne; Mels, Carina M; Kruger, Ruan; Meiring, Muriel; van Rooyen, Johannes M; Malan, Leoné

2013-10-12

Low testosterone, acute and chronic stress and hypercoagulation are all associated with hypertension and hypertension-related diseases. The interaction between these factors and future risk for coronary artery disease in Africans has not been fully elucidated. In this study, associations of testosterone, acute cardiovascular and coagulation stress responses with fibrinogen and von Willebrand factor in African and Caucasian men in a South African cohort were investigated. Cardiovascular variables were studied by means of beat-to-beat and ambulatory blood pressure monitoring. Fasting serum-, salivary testosterone and citrate coagulation markers were obtained from venous blood samples. Acute mental stress responses were evoked with the Stroop test. The African group demonstrated a higher cardiovascular risk compared to Caucasian men with elevated blood pressure, low-grade inflammation, chronic hyperglycemia (HbA1c), lower testosterone levels, and elevated von Willebrand factor (VWF) and fibrinogen levels. Blunted testosterone acute mental stress responses were demonstrated in African males. In multiple regression analyses, higher circulating levels of fibrinogen and VWF in Africans were associated with a low T environment (R(2) 0.24-0.28; p≤0.01), but only circulating fibrinogen in Caucasians. Regarding endothelial function, a low testosterone environment and a profile of augmented α-adrenergic acute mental stress responses (diastolic BP, D-dimer and testosterone) were associated with circulating VWF levels in Africans (Adj R(2) 0.24; p<0.05). An interdependence between acute mental stress, salivary testosterone, D-dimer and vascular responses existed in African males in their association with circulating VWF but no interdependence of the independent variables occurred with fibrinogen levels. © 2013.

Circulating and dietary omega-3 and omega-6 polyunsaturated fatty acids and incidence of CVD in the Multi-Ethnic Study of Atherosclerosis.

PubMed

de Oliveira Otto, Marcia C; Wu, Jason H Y; Baylin, Ana; Vaidya, Dhananjay; Rich, Stephen S; Tsai, Michael Y; Jacobs, David R; Mozaffarian, Dariush

2013-12-18

Dietary guidelines support intake of polyunsaturated fatty acids (PUFAs) in fish and vegetable oils. However, some controversy remains about benefits of PUFAs, and most prior studies have relied on self-reported dietary assessment in relatively homogeneous populations. In a multiethnic cohort of 2837 US adults (whites, Hispanics, African Americans, Chinese Americans), plasma phospholipid PUFAs were measured at baseline (2000-2002) using gas chromatography and dietary PUFAs estimated using a food frequency questionnaire. Incident cardiovascular disease (CVD) events (including coronary heart disease and stroke; n=189) were prospectively identified through 2010 during 19 778 person-years of follow-up. In multivariable-adjusted Cox models, circulating n-3 eicosapentaenoic acid and docosahexaenoic acid were inversely associated with incident CVD, with extreme-quartile hazard ratios (95% CIs) of 0.49 for eicosapentaenoic acid (0.30 to 0.79; Ptrend=0.01) and 0.39 for docosahexaenoic acid (0.22 to 0.67; Ptrend<0.001). n-3 Docosapentaenoic acid (DPA) was inversely associated with CVD in whites and Chinese, but not in other race/ethnicities (P-interaction=0.01). No significant associations with CVD were observed for circulating n-3 alpha-linolenic acid or n-6 PUFA (linoleic acid, arachidonic acid). Associations with CVD of self-reported dietary PUFA were consistent with those of the PUFA biomarkers. All associations were similar across racial-ethnic groups, except those of docosapentaenoic acid. Both dietary and circulating eicosapentaenoic acid and docosahexaenoic acid, but not alpha-linolenic acid or n-6 PUFA, were inversely associated with CVD incidence. These findings suggest that increased consumption of n-3 PUFA from seafood may prevent CVD development in a multiethnic population.

Apolipoproteins E and CIII interact to regulate HDL metabolism and coronary heart disease risk

PubMed Central

Morton, Allyson M.; Koch, Manja; Mendivil, Carlos O.; Furtado, Jeremy D.; Tjønneland, Anne; Overvad, Kim; Wang, Liyun; Jensen, Majken K.; Sacks, Frank M.

2018-01-01

BACKGROUND. Subspecies of HDL contain apolipoprotein E (apoE) and/or apoCIII. Both proteins have properties that could affect HDL metabolism. The relation between HDL metabolism and risk of coronary heart disease (CHD) is not well understood. METHODS. Eighteen participants were given a bolus infusion of [D3]L-leucine to label endogenous proteins on HDL. HDL was separated into subspecies containing apoE and/or apoCIII and then into 4 sizes. Metabolic rates for apoA-I in HDL subspecies and sizes were determined by interactive modeling. The concentrations of apoE in HDL that contain or lack apoCIII were measured in a prospective study in Denmark including 1,949 incident CHD cases during 9 years. RESULTS. HDL containing apoE but not apoCIII is disproportionately secreted into the circulation, actively expands while circulating, and is quickly cleared. These are key metabolic steps in reverse cholesterol transport, which may protect against atherosclerosis. ApoCIII on HDL strongly attenuates these metabolic actions of HDL apoE. In the epidemiological study, the relation between HDL apoE concentration and CHD significantly differed depending on whether apoCIII was present. HDL apoE was associated significantly with lower risk of CHD only in the HDL subspecies lacking apoCIII. CONCLUSIONS. ApoE and apoCIII on HDL interact to affect metabolism and CHD. ApoE promotes metabolic steps in reverse cholesterol transport and is associated with lower risk of CHD. ApoCIII, when coexisting with apoE on HDL, abolishes these benefits. Therefore, differences in metabolism of HDL subspecies pertaining to reverse cholesterol transport are reflected in differences in association with CHD. TRIAL REGISTRATION. Clinicaltrials.gov NCT01399632. FUNDING. This work was supported by NIH grant R01HL095964 to FMS and by a grant to the Harvard Clinical and Translational Science Center (8UL1TR0001750) from the National Center for Advancing Translational Science. PMID:29467335

Novel circulating lipid measurements for current dyslipidemias in non-treated patients undergoing coronary angiography: PCSK9, apoC3 and sdLDL-C.

PubMed

Li, Sha; Zhao, Xi; Zhang, Yan; Zhu, Cheng-Gang; Guo, Yuan-Lin; Wu, Na-Qiong; Xu, Rui-Xia; Qing, Ping; Gao, Ying; Sun, Jing; Liu, Geng; Dong, Qian; Li, Jian-Jun

2017-02-14

Plasma levels of proprotein convertase subtilisin/kexin type 9 (PCSK9), apolipoprotein C-III (apoC3) and small dense low density lipoprotein cholesterol (sdLDL-C), have been recently recognized as circulating atherosclerosis-related lipid measurements. We aimed to elucidate their associations with current dyslipidemias, and identify their levels at increased risk to dyslipidemia. A total of 1,605 consecutive, non-treated patients undergoing diagnostic/interventional coronary angiography were examined. Plasma PCSK9 and apoC3 levels were determined using a validated ELISA assay, and sdLDL-C was measured by the Lipoprint LDL System. Plasma levels of PCSK9, apoC3, and sdLDL-C were associated with the current dyslipidemias classification (all p<0.001). PCSK9 significantly conferred prediction of both hypercholesterolemia and combined hyperlipidemia at a level of 235 ng/ml; apoC3 levels for hypertriglyceridemia, hypercholesterolemia and combined hyperlipidemia were 80.0, 71.5, and 86.4 μg/ml, respectively; and sdLDL-C for hypertriglyceridemia, hypercholesterolemia, combined hyperlipidemia and hypo high density lipoprotein (HDL) cholesterolemia 3.5, 2.5, 4.5, and 2.5 mg/dl, respectively (all p<0.001 for area under the receiver-operating characteristic curve). In a polytomous logistic model comparing increasing LDL-C categories, the interactions with high PCSK9, apoC3, and sdLDL-C elevated gradually. Similarly, apoC3 and sdLDL-C showed elevated interaction with increased triglyceride categories, and only sdLDL-C showed interaction with decreased HDL cholesterol (HDL-C) categories. Furthermore, discordances of PCSK9, apoC3, and sdLDL-C with current dyslipidemias were observed. PCSK9, apoC3, and sdLDL-C showed significant interactions with current dyslipidemias, and were predictive in the screening. The substantial discordances with current dyslipidemias might provide novel view in lipid management and further cardiovascular benefit.

Novel circulating lipid measurements for current dyslipidemias in non-treated patients undergoing coronary angiography: PCSK9, apoC3 and sdLDL-C

PubMed Central

Li, Sha; Zhao, Xi; Zhang, Yan; Zhu, Cheng-Gang; Guo, Yuan-Lin; Wu, Na-Qiong; Xu, Rui-Xia; Qing, Ping; Gao, Ying; Sun, Jing; Liu, Geng; Dong, Qian; Li, Jian-Jun

2017-01-01

Plasma levels of proprotein convertase subtilisin/kexin type 9 (PCSK9), apolipoprotein C-III (apoC3) and small dense low density lipoprotein cholesterol (sdLDL-C), have been recently recognized as circulating atherosclerosis-related lipid measurements. We aimed to elucidate their associations with current dyslipidemias, and identify their levels at increased risk to dyslipidemia. A total of 1,605 consecutive, non-treated patients undergoing diagnostic/interventional coronary angiography were examined. Plasma PCSK9 and apoC3 levels were determined using a validated ELISA assay, and sdLDL-C was measured by the Lipoprint LDL System. Plasma levels of PCSK9, apoC3, and sdLDL-C were associated with the current dyslipidemias classification (all p<0.001). PCSK9 significantly conferred prediction of both hypercholesterolemia and combined hyperlipidemia at a level of 235 ng/ml; apoC3 levels for hypertriglyceridemia, hypercholesterolemia and combined hyperlipidemia were 80.0, 71.5, and 86.4 g/ml, respectively; and sdLDL-C for hypertriglyceridemia, hypercholesterolemia, combined hyperlipidemia and hypo high density lipoprotein (HDL) cholesterolemia 3.5, 2.5, 4.5, and 2.5 mg/dl, respectively (all p<0.001 for area under the receiver-operating characteristic curve). In a polytomous logistic model comparing increasing LDL-C categories, the interactions with high PCSK9, apoC3, and sdLDL-C elevated gradually. Similarly, apoC3 and sdLDL-C showed elevated interaction with increased triglyceride categories, and only sdLDL-C showed interaction with decreased HDL cholesterol (HDL-C) categories. Furthermore, discordances of PCSK9, apoC3, and sdLDL-C with current dyslipidemias were observed. PCSK9, apoC3, and sdLDL-C showed significant interactions with current dyslipidemias, and were predictive in the screening. The substantial discordances with current dyslipidemias might provide novel view in lipid management and further cardiovascular benefit. PMID:27713142

Acute Multiple Organ Failure in Adult Mice Deleted for the Developmental Regulator Wt1

PubMed Central

Chau, You-Ying; Brownstein, David; Mjoseng, Heidi; Lee, Wen-Chin; Buza-Vidas, Natalija; Nerlov, Claus; Jacobsen, Sten Eirik; Perry, Paul; Berry, Rachel; Thornburn, Anna; Sexton, David; Morton, Nik; Hohenstein, Peter; Freyer, Elisabeth; Samuel, Kay; van't Hof, Rob; Hastie, Nicholas

2011-01-01

There is much interest in the mechanisms that regulate adult tissue homeostasis and their relationship to processes governing foetal development. Mice deleted for the Wilms' tumour gene, Wt1, lack kidneys, gonads, and spleen and die at mid-gestation due to defective coronary vasculature. Wt1 is vital for maintaining the mesenchymal–epithelial balance in these tissues and is required for the epithelial-to-mesenchyme transition (EMT) that generates coronary vascular progenitors. Although Wt1 is only expressed in rare cell populations in adults including glomerular podocytes, 1% of bone marrow cells, and mesothelium, we hypothesised that this might be important for homeostasis of adult tissues; hence, we deleted the gene ubiquitously in young and adult mice. Within just a few days, the mice suffered glomerulosclerosis, atrophy of the exocrine pancreas and spleen, severe reduction in bone and fat, and failure of erythropoiesis. FACS and culture experiments showed that Wt1 has an intrinsic role in both haematopoietic and mesenchymal stem cell lineages and suggest that defects within these contribute to the phenotypes we observe. We propose that glomerulosclerosis arises in part through down regulation of nephrin, a known Wt1 target gene. Protein profiling in mutant serum showed that there was no systemic inflammatory or nutritional response in the mutant mice. However, there was a dramatic reduction in circulating IGF-1 levels, which is likely to contribute to the bone and fat phenotypes. The reduction of IGF-1 did not result from a decrease in circulating GH, and there is no apparent pathology of the pituitary and adrenal glands. These findings 1) suggest that Wt1 is a major regulator of the homeostasis of some adult tissues, through both local and systemic actions; 2) highlight the differences between foetal and adult tissue regulation; 3) point to the importance of adult mesenchyme in tissue turnover. PMID:22216009

Independent no-reflow predictors in female patients with ST-elevation acute myocardial infarction treated with primary percutaneous coronary intervention.

PubMed

Chen, Yundai; Wang, Changhua; Yang, Xinchun; Wang, Lefeng; Sun, Zhijun; Liu, Hongbin; Chen, Lian

2012-05-01

Independent no-reflow predictors should be evaluated in female patients with ST-segment elevation acute myocardial infarction (STEMI) and successfully treated with primary percutaneous coronary intervention (PPCI) in the current interventional equipment and techniques, thus to be constructed a no-reflow predicting model. In this study, 320 female patients with STEMI were successfully treated with PPCI within 12 h after the onset of AMI from 2007 to 2010. All clinical, angiographic, and procedural data were collected. Multiple logistic regression analysis was used to identify independent no-reflow predictors. The no-reflow was found in 81 (25.3%) of 320 female patients. Univariate and multivariate stepwise logistic regression analysis identified that low SBP on admission <100 mmHg (OR 1.991, 95% CI 1.018-3.896; p = 0.004), target lesion length >20 mm (OR 1.948, 95% CI 1.908-1.990; p = 0.016), collateral circulation 0-1 (OR 1.952, 95% CI 1.914-1.992; p = 0.019), pre-PCI thrombus score ≥ 4 (OR 4.184, 95% CI 1.482-11.813; p = 0.007), and IABP use before PCI (OR 1.949, 95% CI 1.168-3.253; p = 0.011) were independent no-reflow predictors. The no-reflow incidence significantly increased as the numbers of independent predictors increased [0% (0/2), 10.8% (9/84), 14.5% (17/117), 37.7% (29/77), 56.7% (17/30), and 81.8% (9/11) in female patients with 0, 1, 2, 3, 4, and 5 independent predictors, respectively; p < 0.0001]. The five no-reflow predicting variables were admission SBP <100 mmHg, target lesion length >20 mm, collateral circulation 0-1, pre-PCI thrombus score ≥ 4, and IABP use before PCI in female patients with STEMI treated with PPCI.

Miniaturized extracorporeal circulation versus off-pump coronary artery bypass grafting: a meta-analysis of randomized controlled trials.

PubMed

Benedetto, Umberto; Ng, Colin; Frati, Giacomo; Biondi-Zoccai, Giuseppe; Vitulli, Piergiusto; Zeinah, Mohamed; Raja, Shahzad G

2015-02-01

Controversies exist whether off-pump coronary artery bypass (OPCAB) is superior to miniaturized extracorporeal circulation (MECC) in reducing deleterious effects of cardiopulmonary bypass as only a number of smaller randomized controlled trials (RCT) currently provide a limited evidence base. The main purpose of conducting the present meta-analysis was to overcome the expected low power in RCTs in an attempt to establish whether MECC is comparable to OPCAB. A MEDLINE/PubMed search was conducted to identify eligible RCTs. A pooled summary effect estimate was calculated by means of Mantel-Haenszel method. The search yielded 7 RCTs included in this meta-analysis enrolling 271 patients in the OPCAB group and 279 in the MECC group. The OPCAB and MECC groups were comparable in terms of incidence of in-hospital mortality (Risk Difference [RD] 0.01; 95%CI -0.02, 0.03; P = 0.55; I(2) = 0%), stroke (RD -0.01; 95%CI -0.05, 0.04; P = 0.69; I(2) = 0%), need for renal replacement therapy (RD 0.00; -0.06, 0.06; P = 1; I(2) = 0%), postoperative atrial fibrillation (RD -0.03; -0.17, 0.10; P = 0.64; I(2) = 0%), re-exploration for bleeding (RD -0.01; 95%CI -0.03, 0.02; P = 0.65; I(2) = 0%), transfusion rate (RD -0.01; 95%CI -0.03, 0.02; P = 0.65; I(2) = 0%) and the amount of blood loss (weighted mean difference -25 mL; 95%CI -71, 21; P = 0.28; I(2) = 0%). Using a meta-analytic approach, MECC achieves clinical results comparable to OPCAB including postoperative blood loss and blood transfusion requirement. On the basis of our findings, MECC should be considered as a valid alternative to OPCAB in order to reduce surgical morbidity of conventional cardiopulmonary bypass. Copyright © 2015 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

Mini-extracorporeal circulation technology, conventional bypass and prime displacement in isolated coronary and aortic valve surgery: a propensity-matched in-hospital and survival analysis.

PubMed

Ariyaratnam, Priyadharshanan; Mclean, Lindsay A; Cale, Alexander; Chaudhry, Mubarak A; Vijayan, Ajith; Richards, Neil; Jarvis, Martin A; Haqzad, Yama; Ngaage, Dumbor; Cowen, Michael E; Loubani, Mahmoud

2018-02-14

Conventional cardiopulmonary bypass is the most commonly used means of artificial circulation in cardiac surgery. However, it suffers from the effects of haemodilution and activation of inflammatory/coagulation cascades. Prime displacement (PD) can offset haemodilution and Mini-Extracorporeal Technology (MIECT) can offset both. So far, no study has compared all of these modalities together; hence, we compared the outcomes of these 3 modalities at our institution. This was a retrospective analysis of our cardiac surgical database. A total of 9626 patients underwent conventional bypass (CB), 3125 patients underwent a modification of CB, called PD, and 904 underwent MIECT. A 1:1 propensity-matching algorithm was employed using IBM SPSS 24 to match (i) 813 MIECT patients with 813 CB patients and (ii) 717 MIECT patients with 717 PD patients. The patients included coronary artery bypass grafting and valve surgery. MIECT had significantly (P < 0.05) longer bypass and cross-clamp times compared to CB and PD. MIECT had significantly higher rates of postoperative atrial fibrillation associated with it compared to CB. The mean red cell blood transfusion was significantly lower in the MIECT group compared to the CB group as was the mean platelet transfusion and fresh frozen plasma transfusion. The overall 5-year survival was higher in the MIECT group compared to the CB group (log-rank, P = 0.018). Between the MIECT and the PD groups, we found the incidence of renal failure and gastrointestinal complications to be significantly higher in the PD group compared to the MIECT group. MIECT has short-term advantages over CB and PD. However, due to the retrospective limitations of the study, including calendar time bias, a multicentre randomized controlled trial comparing all 3 modalities will be beneficial for the larger cardiac community. © The Author(s) 2018. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Role of Circulating Fibroblast Growth Factor 21 Measurement in Primary Prevention of Coronary Heart Disease Among Chinese Patients With Type 2 Diabetes Mellitus.

PubMed

Lee, Chi Ho; Woo, Yu Cho; Chow, Wing Sun; Cheung, Chloe Yu Yan; Fong, Carol Ho Yi; Yuen, Michele Mae Ann; Xu, Aimin; Tse, Hung Fat; Lam, Karen Siu Ling

2017-06-06

Fibroblast growth factor 21 (FGF21) has demonstrated beneficial effects on lipid and carbohydrate metabolism. In cross-sectional studies, an association of raised circulating FGF21 levels with coronary heart disease (CHD) was found in some but not all studies. Here we investigated prospectively whether baseline serum FGF21 levels could predict incident CHD in subjects with type 2 diabetes mellitus and no known cardiovascular diseases. Baseline serum FGF21 levels were measured in 3528 Chinese subjects with type 2 diabetes mellitus recruited from the Hong Kong West Diabetes Registry. The role of baseline serum FGF21 levels in predicting incident CHD over a median follow-up of 3.8 years was analyzed using Cox regression analysis. Among 3528 recruited subjects without known cardiovascular diseases, 147 (4.2%) developed CHD over a mean follow-up of 4 years. Baseline serum log-transformed FGF21 levels were significantly higher in those who had incident CHD than those who did not (222.7 pg/mL [92.8-438.4] versus 151.1 pg/mL [75.6-274.6]; P <0.001). On multivariable Cox regression analysis, baseline serum FGF21 levels, using an optimal cutoff of 206.22 pg/mL derived from our study, independently predicted incident CHD (hazard ratio, 1.55; 95% CI, 1.10-2.19; P =0.013) and significantly improved net reclassification index and integrated discrimination improvement after adjustment for conventional cardiovascular risk factors. We have demonstrated, for the first time, that serum FGF21 level is an independent predictor of incident CHD and might be usefully utilized as a biomarker for identifying type 2 diabetes mellitus subjects with raised CHD risk, for primary prevention. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Regulation of coronary blood flow during exercise.

PubMed

Duncker, Dirk J; Bache, Robert J

2008-07-01

Exercise is the most important physiological stimulus for increased myocardial oxygen demand. The requirement of exercising muscle for increased blood flow necessitates an increase in cardiac output that results in increases in the three main determinants of myocardial oxygen demand: heart rate, myocardial contractility, and ventricular work. The approximately sixfold increase in oxygen demands of the left ventricle during heavy exercise is met principally by augmenting coronary blood flow (~5-fold), as hemoglobin concentration and oxygen extraction (which is already 70-80% at rest) increase only modestly in most species. In contrast, in the right ventricle, oxygen extraction is lower at rest and increases substantially during exercise, similar to skeletal muscle, suggesting fundamental differences in blood flow regulation between these two cardiac chambers. The increase in heart rate also increases the relative time spent in systole, thereby increasing the net extravascular compressive forces acting on the microvasculature within the wall of the left ventricle, in particular in its subendocardial layers. Hence, appropriate adjustment of coronary vascular resistance is critical for the cardiac response to exercise. Coronary resistance vessel tone results from the culmination of myriad vasodilator and vasoconstrictors influences, including neurohormones and endothelial and myocardial factors. Unraveling of the integrative mechanisms controlling coronary vasodilation in response to exercise has been difficult, in part due to the redundancies in coronary vasomotor control and differences between animal species. Exercise training is associated with adaptations in the coronary microvasculature including increased arteriolar densities and/or diameters, which provide a morphometric basis for the observed increase in peak coronary blood flow rates in exercise-trained animals. In larger animals trained by treadmill exercise, the formation of new capillaries maintains capillary density at a level commensurate with the degree of exercise-induced physiological myocardial hypertrophy. Nevertheless, training alters the distribution of coronary vascular resistance so that more capillaries are recruited, resulting in an increase in the permeability-surface area product without a change in capillary numerical density. Maintenance of alpha- and ss-adrenergic tone in the presence of lower circulating catecholamine levels appears to be due to increased receptor responsiveness to adrenergic stimulation. Exercise training also alters local control of coronary resistance vessels. Thus arterioles exhibit increased myogenic tone, likely due to a calcium-dependent protein kinase C signaling-mediated alteration in voltage-gated calcium channel activity in response to stretch. Conversely, training augments endothelium-dependent vasodilation throughout the coronary microcirculation. This enhanced responsiveness appears to result principally from an increased expression of nitric oxide (NO) synthase. Finally, physical conditioning decreases extravascular compressive forces at rest and at comparable levels of exercise, mainly because of a decrease in heart rate. Impedance to coronary inflow due to an epicardial coronary artery stenosis results in marked redistribution of myocardial blood flow during exercise away from the subendocardium towards the subepicardium. However, in contrast to the traditional view that myocardial ischemia causes maximal microvascular dilation, more recent studies have shown that the coronary microvessels retain some degree of vasodilator reserve during exercise-induced ischemia and remain responsive to vasoconstrictor stimuli. These observations have required reassessment of the principal sites of resistance to blood flow in the microcirculation. A significant fraction of resistance is located in small arteries that are outside the metabolic control of the myocardium but are sensitive to shear and nitrovasodilators. The coronary collateral system embodies a dynamic network of interarterial vessels that can undergo both long- and short-term adjustments that can modulate blood flow to the dependent myocardium. Long-term adjustments including recruitment and growth of collateral vessels in response to arterial occlusion are time dependent and determine the maximum blood flow rates available to the collateral-dependent vascular bed during exercise. Rapid short-term adjustments result from active vasomotor activity of the collateral vessels. Mature coronary collateral vessels are responsive to vasodilators such as nitroglycerin and atrial natriuretic peptide, and to vasoconstrictors such as vasopressin, angiotensin II, and the platelet products serotonin and thromboxane A(2). During exercise, ss-adrenergic activity and endothelium-derived NO and prostanoids exert vasodilator influences on coronary collateral vessels. Importantly, alterations in collateral vasomotor tone, e.g., by exogenous vasopressin, inhibition of endogenous NO or prostanoid production, or increasing local adenosine production can modify collateral conductance, thereby influencing the blood supply to the dependent myocardium. In addition, vasomotor activity in the resistance vessels of the collateral perfused vascular bed can influence the volume and distribution of blood flow within the collateral zone. Finally, there is evidence that vasomotor control of resistance vessels in the normally perfused regions of collateralized hearts is altered, indicating that the vascular adaptations in hearts with a flow-limiting coronary obstruction occur at a global as well as a regional level. Exercise training does not stimulate growth of coronary collateral vessels in the normal heart. However, if exercise produces ischemia, which would be absent or minimal under resting conditions, there is evidence that collateral growth can be enhanced. In addition to ischemia, the pressure gradient between vascular beds, which is a determinant of the flow rate and therefore the shear stress on the collateral vessel endothelium, may also be important in stimulating growth of collateral vessels.

Postsurgical Acute Phase Reaction is Associated with Decreased Levels of Circulating Myostatin.

PubMed

Åkerfeldt, Torbjörn; Helmersson-Karlqvist, Johanna; Gunningberg, Lena; Swenne, Christine Leo; Larsson, Anders

2015-08-01

Muscle strength is of importance for postsurgical rehabilitation. Myostatin is a growth factor that regulates the size of muscles and could thus influence muscle mass and function in the postsurgical period. The aim of the present study was to study the changes in myostatin levels during the postsurgical inflammatory period. Myostatin was analysed in serum samples from two elective surgery groups, orthopaedic surgery (n = 24) and coronary bypass patients (n = 21). The samples were collected prior to surgery and 4 and 30 days after surgery. In the orthopaedic group, the median myostatin levels decreased from 3582 ng/L prior to surgery to 774 ng/L at day 4 (p < 0.001) and to 2016 ng/L at day 30 (p < 0.001). Median CRP increased from 2.35 mg/L preoperatively to 117 mg/L at day 4 and decreased to 5.5 mg/L at day 30 in the same group. The coronary bypass group showed a similar pattern with a decrease in myostatin from 4212 ng/L to 2574 ng/L at day 4 (p < 0.001) and to 2808 ng/L at day 30 (p = 0.002). Median CRP increased from 1.80 mg/L preoperatively to 136 mg/L at day 4 and returned to 6.12 mg/L at day 30 in the coronary bypass group. There was a significant decrease in myostatin concentrations both in the early and late postsurgical period. The lowest myostatin concentration time point coincided with the highest CRP concentration time point.

Hepatocyte growth factor demonstrates racial heterogeneity as a biomarker for coronary heart disease.

PubMed

Bielinski, Suzette J; Berardi, Cecilia; Decker, Paul A; Larson, Nicholas B; Bell, Elizabeth J; Pankow, James S; Sale, Michele M; Tang, Weihong; Hanson, Naomi Q; Wassel, Christina L; de Andrade, Mariza; Budoff, Matthew J; Polak, Joseph F; Sicotte, Hugues; Tsai, Michael Y

2017-08-01

To determine if hepatocyte growth factor (HGF), a promising biomarker of coronary heart disease (CHD) given its release into circulation in response to endothelial damage, is associated with subclinical and clinical CHD in a racial/ethnic diverse population. HGF was measured in 6738 participants of the Multi-Ethnic Study of Atherosclerosis (MESA). Highest mean HGF values (pg/mL) were observed in Hispanic, followed by African, non-Hispanic white, then Chinese Americans. In all races/ethnicities, HGF levels were associated with older age, higher systolic blood pressure (SBP) and body mass index, lower high-density lipoprotein, diabetes and current smoking. In fully adjusted models, each SD higher HGF was associated with an average increase in coronary artery calcium (CAC) of 55 Agatston units for non-Hispanic whites (p<0.001) and 51 Agatston units for African-Americans (p=0.007) but was not in the other race/ethnic groups (interaction p=0.02). There were 529 incident CHD events, and CHD risk was 41% higher in African (p<0.001), 17% in non-Hispanic white (p=0.026) and Chinese (p=0.36), and 6% in Hispanic Americans (p=0.56) per SD increase in HGF. In a large and diverse population-based cohort, we report that HGF is associated with subclinical and incident CHD. We demonstrate evidence of racial/ethnic heterogeneity within these associations, as the results are most compelling in African-Americans and non-Hispanic white Americans. We provide evidence that HGF is a biomarker of atherosclerotic disease that is independent of traditional risk factors. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Relationship of lipid oxidation with subclinical atherosclerosis and 10-year coronary events in general population.

PubMed

Gómez, Miquel; Vila, Joan; Elosua, Roberto; Molina, Lluís; Bruguera, Jordi; Sala, Joan; Masià, Rafel; Covas, Maria Isabel; Marrugat, Jaume; Fitó, Montserrat

2014-01-01

To assess 1) the association of lipid oxidation biomarkers with 10-year coronary artery disease (CAD) events and subclinical atherosclerosis, and 2) the reclassification capacity of these biomarkers over Framingham-derived CAD risk functions, in a general population. Within the framework of the REGICOR study, 4782 individuals aged between 25 and 74 years were recruited in a population-based cohort study. Follow-up of the 4042 who met the eligibility criteria was carried out. Plasma, circulating oxidized low-density lipoprotein (oxLDL) and oxLDL antibodies (OLAB) were measured in a random sample of 2793 participants. End-points included fatal and non-fatal acute myocardial infarction (AMI) and angina. Carotid intima-media thickness (IMT) in the highest quintile and ankle-brachial index <0.9 were considered indicators of subclinical atherosclerosis. Mean age was 50.0 (13.4) years, and 52.4% were women. There were 103 CAD events (34 myocardial infarction, 43 angina, 26 coronary deaths), and 306 subclinical atherosclerosis cases. Oxidized LDL was independently associated with higher incidence of CAD events (HR = 1.70; 95% Confidence Interval: 1.02-2.84), but not with subclinical atherosclerosis. The net classification index of the Framingham-derived CAD risk function was significantly improved when ox-LDL was included (NRI = 14.67% [4.90; 24.45], P = 0.003). No associations were found between OLAB and clinical or subclinical events. The reference values for oxLDL and OLAB are also provided (percentiles). OxLDL was independently associated with 10-year CAD events but not subclinical atherosclerosis in a general population, and improved the reclassification capacity of Framingham-derived CAD risk functions. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Endothelial ischemia-reperfusion injury in humans: association with age and habitual exercise.

PubMed

Devan, Allison E; Umpierre, Daniel; Harrison, Michelle L; Lin, Hsin-Fu; Tarumi, Takashi; Renzi, Christopher P; Dhindsa, Mandeep; Hunter, Stacy D; Tanaka, Hirofumi

2011-03-01

Advancing age is a major risk factor for coronary artery disease. Endothelial dysfunction accompanied by increased oxidative stress and inflammation with aging may predispose older arteries to greater ischemia-reperfusion (I/R) injury. Because coronary artery ischemia cannot be induced safely, the effects of age and habitual endurance exercise on endothelial I/R injury have not been determined in humans. Using the brachial artery as a surrogate model of the coronary arteries, endothelial function, assessed by brachial artery flow-mediated dilation (FMD), was measured before and after 20 min of continuous forearm occlusion in young sedentary (n = 10, 24 ± 2 yr) and middle-aged (n = 9, 48 ± 2 yr) sedentary adults to gain insight into the effects of primary aging on endothelial I/R injury. Young (n = 9, 25 ± 1 yr) and middle-aged endurance-trained (n = 9, 50 ± 2 yr) adults were also studied to determine whether habitual exercise provides protection from I/R injury. Fifteen minutes after ischemic injury, FMD decreased significantly by 37% in young sedentary, 35% in young endurance-trained, 68% in middle-aged sedentary, and 50% in middle-aged endurance-trained subjects. FMD returned to baseline levels within 30 min in young sedentary and endurance-trained subjects but remained depressed in middle-aged sedentary and endurance-trained subjects. Circulating markers of antioxidant capacity and inflammation were not related to FMD. In conclusion, advancing age is associated with a greater magnitude and delayed recovery from endothelial I/R injury in humans. Habitual endurance exercise may provide partial protection to the endothelium against this form of I/R injury with advancing age.

[Clinical and medicine characteristics of patients with Parkinson's syndrome].

PubMed

Liu, Huan; Xie, Yan-Ming; Yi, Dan-Hui; Wang, Yong-Yan

2014-09-01

This study analyze the characteristics and clinical medicine in 17 hospitals all over China, based on hospital information system diagnostic information database, including 4 497 cases of hospitalized patients with Parkinson's syndrome. Results indicate, the most common comorbidities are infarction, hypertension, coronary heart disease, diabetes and lung infections, including cerebral infarction, the combined incidence of hypertension in men reached 33.46% and 30.05%, respectively, it is slightly lower in the females. Men with coronary heart disease are more than women, women with diabetes and bone disease are more than men. Combined incidence of the disease increases with age, vascular factors occupy an important position. The most common combined diseases in patients with 90 years of age or older are coronary heart disease, lung infection, and often accompanied by metabolic disorders and nutritional emergency, critical care. Constipation, depression, anxiety, sleep disorders, cognitive impairment are common non-motor symptoms. The drug categories associated with Parkinson's core symptoms treatment are about 20% to 30% of clinical medicine, the others are associated with the treatment of combined disease, clinical medicine and disease spectrum consistent. Blood circulation topped Chinese agents applied frequency, reaching 44.52%; laxative drugs accounted for 11.66%; detoxification agent representing 9.46%. The first twenty Chinese medicine of the applying frequency reached 56.07% of the total utilization, including 12 kinds of traditional Chinese medicine injections, accounting for 60%. Therefore, in the diagnosis and treatment of Parkinsons syndrome, the treatment of comorbidities is very important, more attentions should be paid to vascular factors of the disease, Chinese medicine should be more concerned to improve the non-motor symptoms, give full play to the pharmaceutical multi-target, the overall regulation of advantages, integrative medicine, and improve the quality of life of patients.

Platelet factor XIIIa release during platelet aggregation and plasma clot strength measured by thrombelastography in patients with coronary artery disease treated with clopidogrel.

PubMed

Kreutz, Rolf P; Owens, Janelle; Lu, Deshun; Nystrom, Perry; Jin, Yan; Kreutz, Yvonne; Desta, Zeruesenay; Flockhart, David A

2015-01-01

It has been estimated that up to half of circulating factor XIIIa (FXIIIa) is stored in platelets. The release of FXIIIa from platelets upon stimulation with adenosine diphosphate (ADP) in patients with coronary artery disease treated with dual antiplatelet therapy has not been previously examined. Samples from 96 patients with established coronary artery disease treated with aspirin and clopidogrel were examined. Platelet aggregation was performed by light transmittance aggregometry in platelet-rich plasma (PRP), with platelet-poor plasma (PPP) as reference, and ADP 5 µM as agonist. Kaolin-activated thrombelastography (TEG) was performed in citrate PPP. PRP after aggregation was centrifuged and plasma supernatant (PSN) collected. FXIIIa was measured in PPP and PSN. Platelet aggregation after stimulation with ADP 5 µM resulted in 24% additional FXIIIa release in PSN as compared to PPP (99.3 ± 27 vs. 80.3 ± 24%, p < 0.0001). FXIIIa concentration in PSN correlated with maximal plasma clot strength (TEG-G) (r = 0.48, p < 0.0001), but not in PPP (r = 0.15, p = 0.14). Increasing quartiles of platelet-derived FXIIIa were associated with incrementally higher TEG-G (p = 0.012). FXIIIa release was similar between clopidogrel responders and non-responders (p = 0.18). In summary, platelets treated with aspirin and clopidogrel release a significant amount of FXIIIa upon aggregation by ADP. Platelet-derived FXIIIa may contribute to differences in plasma TEG-G, and thus, in part, provide a mechanistic explanation for high clot strength observed as a consequence of platelet activation. Variability in clopidogrel response does not significantly influence FXIIIa release from platelets.

Association of adiponectin with future cardiovascular events in patients after acute myocardial infarction.

PubMed

Huang, Shao-Sung; Huang, Po-Hsun; Chen, Ying-Hwa; Chiang, Kuang-Hsing; Chen, Jaw-Wen; Lin, Shing-Jong

2010-03-31

There is uncertainty about the association between circulating concentrations of adiponectin and coronary heart disease risk, particularly in patients after acute myocardial infarction (AMI). The goal of this study was to determine whether plasma adiponectin levels could predict future cardiovascular events in patients after AMI, and to elucidate the role of adiponectin in cardioprotection. A total of 102 patients with AMI were enrolled. Plasma adiponectin levels were examined from blood samples collected 18 months after AMI. All subjects were followed-up for 43+/-12 months. The primary endpoint was the combined occurrence of major adverse cardiovascular events (MACE), including rehospitalization due to unstable angina, nonfatal MI, revascularization with percutaneous coronary intervention or coronary artery bypass grafting, ischemic stroke, and cardiovascular death. A total of 30 MACE occurred, including one case of cardiovascular death, five cases of nonfatal MI, and nine cases of ischemic stroke. Patients with MACE had lower plasma adiponectin levels (p=0.013). In addition, adiponectin was positively associated with changes in left ventricular ejection fraction (p=0.005). All patients were divided into a high-adiponectin group (>or=6.46 microg/mL) and a low-adiponectin group (<6.46 microg/mL). The incidence of MACE was significantly reduced in the high-adiponectin group (p=0.021). In multivariate Cox regression analysis that included adiponectin, classical risk factors, and medications, adiponectin was an independent predictor of MACE in patients after AMI (HR, 0.821; 95% CI, 0.691 to 0.974; p=0.024). The results indicate a potential association between plasma adiponectin levels and future cardiovascular events in patients after AMI. Moreover, plasma adiponectin concentrations appear to play a pivotal role in atherothrombosis and cardioprotection.

Facilitatory effects of fetuin-A on atherosclerosis.

PubMed

Naito, Chisato; Hashimoto, Mio; Watanabe, Kaho; Shirai, Remina; Takahashi, Yui; Kojima, Miho; Watanabe, Rena; Sato, Kengo; Iso, Yoshitaka; Matsuyama, Taka-Aki; Suzuki, Hiroshi; Ishibashi-Ueda, Hatsue; Watanabe, Takuya

2016-03-01

Fetuin-A is a circulating glycoprotein that is produced by liver and adipose tissue. Fetuin-A is known to induce insulin resistance and suppress vascular calcification. There are conflicting reports that show increased or decreased serum fetuin-A levels in patients with coronary artery disease (CAD). Since the role of fetuin-A in atherosclerosis remains still controversial, we aimed to clarify it in this study. We investigated the expression of fetuin-A in atheromatous plaques in CAD patients and restenosis lesions in balloon-injured rat carotid arteries in vivo. We also assessed in vitro effects of fetuin-A on inflammatory molecules in human umbilical vein endothelial cells (HUVECs), oxidized low-density lipoprotein-induced foam cell formation in human monocyte-derived macrophages, and the migration, proliferation, and extracellular matrix expression in human aortic smooth muscle cells (HASMCs) in a serum-free culture system. Fetuin-A was abundantly expressed in cultured human monocytes, macrophages, fibroblasts, HASMCs, and human coronary artery SMCs, atheromatous plaques in human coronary arteries, and restenosis lesions in rat carotid arteries. In vitro experiments showed that fetuin-A stimulated interleukin-6, monocyte chemotactic protein-1, intercellular adhesion molecule-1, and E-selectin expression in HUVECs. Fetuin-A enhanced macrophage foam cell formation associated with scavenger receptors (CD36 and SR-A) and acyl-CoA:cholesterol acyltransferase-1 down-regulation and ATP-binding cassette transporter A1 up-regulation, and increased cell proliferation and collagen-1 and -3 expression via PI3K/AKT/c-Src/NF-κB/ERK1/2 pathways in HASMCs. Our results indicate that fetuin-A exerts the stimulatory effects on inflammatory responses in HUVECs, macrophage foam cell formation, and proliferation and collagen production in HASMCs, leading to the development of atherosclerosis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Anti-oxidative and anti-inflammatory vasoprotective effects of caloric restriction in aging: role of circulating factors and SIRT1

PubMed Central

Csiszar, Anna; Labinskyy, Nazar; Jimenez, Rosario; Pinto, John T.; Ballabh, Praveen; Losonczy, Gyorgy; Pearson, Kevin J.; de Cabo, Rafael; Ungvari, Zoltan

2009-01-01

Endothelial-dysfunction, oxidative stress and inflammation are associated with vascular aging and promote the development of cardiovascular-disease. Caloric restriction (CR) mitigates conditions associated with aging, but its effects on vascular dysfunction during aging remain poorly defined. To determine whether CR exerts vasoprotective effects in aging, aortas of ad libitum (AL) fed young and aged and CR-aged F344 rats were compared. Aging in AL-rats was associated with impaired acetylcholine-induced relaxation, vascular oxidative stress and increased NF-κB-activity. Lifelong CR significantly improved endothelial function, attenuated vascular ROS production, inhibited NF-κB activity and down-regulated inflammatory genes. To elucidate the role of circulating factors in mediation of the vasoprotective effects of CR, we determined whether sera obtained from CR-animals can confer anti-oxidant and anti-inflammatory effects in cultured coronary-arterial endothelial cells (CAECs), mimicking the effects of CR. In CAECs cultured in the presence of AL-serum TNFα elicited oxidative-stress, NF-κB-activation and inflammatory gene expression. By contrast, treatment of CAECs with CR-serum attenuated TNFα-induced ROS generation and prevented NF-κB-activation and induction of inflammatory genes. siRNA-knockdown of SIRT1 mitigated the anti-oxidant and anti-inflammatory effects of CR-serum. CR exerts anti-oxidant and anti-inflammatory vascular effects, which are likely mediated by circulating factors, in part, via a SIRT1-dependent pathway. PMID:19549533

Chronic laminitis: strategic hoof wall resection.

PubMed

Rucker, Amy

2010-04-01

In the chronic-laminitic foot, severe soft-tissue compression and compromised circulation can result in osteitis and sepsis at the margin of the distal phalanx. Resultant inflammation and sepsis may cause the coronary corium to swell, drain, or separate from the hoof capsule, usually within 8 weeks of laminitis onset. Slow-onset cases of soft-tissue impingement can develop secondary to distal phalanx displacement due to lack of wall attachment. With either presentation, partial upper wall resection is required to reverse compression and vascular impingement by the hoof capsule. If the pathology is not overwhelming, the area reepithelializes and grows attached tubular horn. Firm bandaging and restricted exercise until tubular horn has regrown enhances recovery and the return of a strong hoof. Copyright 2010 Elsevier Inc. All rights reserved.

Where Does Inflammation Fit?

PubMed

Biasucci, Luigi M; La Rosa, Giulio; Pedicino, Daniela; D'Aiello, Alessia; Galli, Mattia; Liuzzo, Giovanna

2017-09-01

This review focuses on the complex relationship between inflammation and the onset of acute coronary syndrome and heart failure. In the last few years, two important lines of research brought new and essential information to light in the pathogenesis of acute coronary syndrome: a) the understanding of the immune mediate mechanisms of inflammation in Ischemic Heart Disease (IHD) and b) evidence that the inflammatory mechanisms associated with atherosclerosis and its complications can be modulated by anti-inflammatory molecules. A large amount of data also suggests that inflammation is a major component in the development and exacerbation of heart failure (HF), in a symbiotic relationship. In particular, recent evidence underlies peculiar aspects of the phenomenon: oxidative stress and autophagy; DAMPS and TLR-4 signaling activation; different macrophages lineage and the contribution of NLRP-3 inflammasome; adaptive immune system. A possible explanation that could unify the pathogenic mechanism of these different conditions is the rising evidence that increased bowel permeability may allow translation of gut microbioma product into the circulation. These findings clearly establish the role of inflammation as the great trigger for two of the major cardiovascular causes of death and morbidity. Further studies are needed, to better clarify the issue and to define more targeted approaches to reduce pathological inflammation while preserving the physiological one.

Hemodynamic and metabolic effects of para- versus intraaortic counterpulsatile circulation supports.

PubMed

Lu, Pong-Jeu; Lin, Pao-Yen; Yang, Chi-Fu Jeffrey; Hung, Chun-Hao; Chan, Ming-Yao; Hsu, Tzu-Cheng

2011-01-01

Despite the success of intraaortic balloon counterpulsation, data on physiologic indices and optimal inflation/deflation timing control of chronic counterpulsation devices are unclear. This study explored the acute hemodynamic and metabolic efficacy of a novel 40-ml stroke volume paraaortic blood pump (PABP) versus a standard intraaortic balloon pump (IABP). Acute porcine model was used with eight pigs randomly divided into PABP (n = 4) and IABP (n = 4) groups. Hemodynamic and metabolic measurements were obtained with and without mechanical assistance. In one pig, the inflation/deflation control was adjusted to different settings, with corresponding performance indices measured. The PABP significantly improved classical counterpulsation indices (p ≤ 0.05) and achieved an average beneficial effect on these indices 1.5-3.5 times greater than that of the IABP. Classical metabolic indices (tension time index and endocardial viability ratio [EVR]), and indices new to chronic counterpulsation research (coronary perfusion, left ventricular stroke work (SW), and a newly derived EVR) were also used in assessment. Both IABP assistance and PABP assistance improved these physiologic indices, with a trend toward PABP superiority in reducing left ventricular SW (p = 0.08). An optimal PABP deflation timing occurs during systole (25 milliseconds after the R-wave) and can minimize coronary regurgitation.

The Role of TLR2, TLR4, and TLR9 in the Pathogenesis of Atherosclerosis

PubMed Central

2016-01-01

Toll-like receptors (TLRs) are key players in the pathogenesis of inflammatory conditions including coronary arterial disease (CAD). They are expressed by a variety of immune cells where they recognize pathogen-associated molecular patterns (PAMPs). TLRs recruit adaptor molecules, including myeloid differentiation primary response protein (MYD88) and TIRF-related adaptor protein (TRAM), to mediate activation of MAPKs and NF-kappa B pathways. They are associated with the development of CAD through various mechanisms. TLR4 is expressed in lipid-rich and atherosclerotic plaques. In TLR2−/− and TLR4−/− mice, atherosclerosis-associated inflammation was diminished. Moreover, TLR2 and TLR4 may induce expression of Wnt5a in advanced staged atheromatous plaque leading to activation of the inflammatory processes. TLR9 is activated by CpG motifs in nucleic acids and have been implicated in macrophage activation and the uptake of oxLDL from the circulation. Furthermore, TLR9 also stimulates interferon-α (INF-α) secretion and increases cytotoxic activity of CD4+ T-cells towards coronary artery tunica media smooth muscle cells. This review outlines the pathophysiological role of TLR2, TLR4, and TLR9 in atherosclerosis, focusing on evidence from animal models of the disease. PMID:27795867

Trans-Ethnic Meta-Analysis Identifies Common and Rare Variants Associated with Hepatocyte Growth Factor Levels in the Multi-Ethnic Study of Atherosclerosis (MESA)

PubMed Central

Larson, Nicholas B.; Berardi, Cecilia; Decker, Paul A.; Wassel, Christina L.; Kirsch, Phillip S.; Pankow, James S.; Sale, Michele M.; de Andrade, Mariza; Sicotte, Hugues; Tang, Weihong; Hanson, Naomi Q.; Tsai, Michael Y.; Taylor, Kent D.; Bielinski, Suzette J.

2015-01-01

Summary Hepatocyte growth factor (HGF) is a mesenchyme-derived pleiotropic factor that regulates cell growth, motility, mitogenesis, and morphogenesis in a variety of cells, and increased serum levels of HGF have been linked to a number of clinical and subclinical cardiovascular disease phenotypes. However, little is currently known regarding what genetic factors influence HGF levels, despite evidence of substantial genetic contributions to HGF variation. Based upon ethnicity-stratified single-variant association analysis and trans-ethnic meta-analysis of 6201 participants of the Multi-Ethnic Study of Atherosclerosis (MESA), we discovered five statistically significant common and low-frequency variants: HGF missense polymorphism rs5745687 (p.E299K) as well as four variants (rs16844364, rs4690098, rs114303452, rs3748034) within or in proximity to HGFAC. We also identified two significant ethnicity-specific gene-level associations (A1BG in African Americans; FASN in Chinese Americans) based upon low-frequency/rare variants, while meta-analysis of gene-level results identified a significant association for HGFAC. However, identified single-variant associations explained modest proportions of the total trait variation and were not significantly associated with coronary artery calcium or coronary heart disease. Our findings indicate genetic factors influencing circulating HGF levels may be complex and ethnically diverse. PMID:25998175

Interhospital air transport of a blind patient on extracorporeal life support with consecutive and successful left ventricular assist device implantation.

PubMed

Bauer, Adrian; Schaarschmidt, Jan; Grosse, F Oliver; Al Alam, Nidal; Hausmann, Harald; Krämer, Klaus; Strüber, Martin; Mohr, Friedrich W

2014-06-01

The use of extracorporeal life support systems (ECLS) in patients with postcardiotomy low cardiac output syndrome (LCO) as a bridge to recovery and bridge to implantation of ventricular assist device (VAD) is common nowadays. A 59-year-old patient with acute myocardial infarction received a percutaneous transluminal angioplasty and stenting of the circumflex artery. During catheterization of the left coronary artery (LAD), the patient showed ventricular fibrillation and required defibrillation and cardiopulmonary resuscitation. After implantation of an intra-aortic balloon pump, the patient immediately was transmitted to the operating room. He received emergency coronary artery bypass grafting in a beating heart technique using pump-assisted minimal extracorporeal circulation circuit (MECC). Two bypass grafts were performed to the LAD and the right posterior descending artery. Despite initial successful weaning off cardiopulmonary bypass with high-dose inotropic support, the patient presented postcardiotomy LCO and an ECLS was implanted. The primary setup of the heparin-coated MECC system was modified and used postoperatively. As a result of the absence of an in-house VAD program, the patient was switched to a transportable ECLS the next day and was transferred by helicopter to the nearest VAD center where the patient received a successful insertion of a left VAD 3 days later.

The CD4/CD8 ratio is associated with coronary artery disease (CAD) in elderly Chinese patients.

PubMed

Gao, Pan; Rong, Hong-Hui; Lu, Ting; Tang, Gang; Si, Liang-Yi; Lederer, James A; Xiong, Wei

2017-01-01

The aim of this study was to investigate the relationship between number of circulating T cells and coronary artery disease (CAD) in an elderly Chinese population. A total of 295 elderly inpatients (age≥60) were included in this cross-sectional study. Their clinical and biochemical characteristics were recorded. Patients were divided to two groups: control patients and CAD patients. The risk factors of CAD were explored by binary logistic regression analysis. Compared with control patients, the ratio of CD4 to CD8 T cells was significantly increased in CAD patients. There was no difference in the number of CD3, CD4, and CD8 T cells between the two groups. Multiple logistic regression analysis showed that CAD was independently associated with age, gender, body mass index (BMI), systolic blood pressure (SBP), chronic heart failure (CHF) and the CD4/CD8 ratio. In addition, after adjusting for different clinical parameters (including gender, age, CHF, hypertension, arrhythmia, SBP, and BMI), the risk of CAD was significantly increased in patients with a CD4/CD8 ratio>1.5. There was a strong and independent association between the ratio of CD4/CD8 and CAD in elderly Chinese population. Copyright © 2016. Published by Elsevier B.V.

Effects of Olive Oil Phenolic Compounds on Inflammation in the Prevention and Treatment of Coronary Artery Disease

PubMed Central

de Souza, Priscilla Azambuja Lopes; Marcadenti, Aline; Portal, Vera Lúcia

2017-01-01

Coronary artery disease (CAD) is responsible for more than 7 million deaths worldwide. In the early stages of the development of atherosclerotic plaques, cardiovascular risk factors stimulate vascular endothelial cells, initiating an inflammatory process, fundamental in the pathogenesis of CAD. The inclusion of potentially cardioprotective foods, such as olive oil, to the diet, may aid in the control of these risk factors, and in the reduction of cytokines and inflammatory markers. The present review aims to address the interaction between phenolic compounds present in olive oil, and inflammation, in the prevention and treatment of CAD. In vitro and in vivo studies suggest that phenolic compounds, such as hydroxytyrosol, tyrosol, and their secoiridoid derivatives, may reduce the expression of adhesion molecules and consequent migration of immune cells, modify the signaling cascade and the transcription network (blocking the signal and expression of the nuclear factor kappa B), inhibit the action of enzymes responsible for the production of eicosanoids, and consequently, decrease circulating levels of inflammatory markers. Daily consumption of olive oil seems to modulate cytokines and inflammatory markers related to CAD in individuals at risk for cardiovascular diseases. However, clinical studies that have evaluated the effects of olive oil and its phenolic compounds on individuals with CAD are still scarce. PMID:28973999

Physiology of Angina and Its Alleviation With Nitroglycerin

PubMed Central

Williams, Rupert; Lockie, Timothy; Khawaja, Muhammed Z.; De Silva, Kalpa; Lumley, Matthew; Patterson, Tiffany; Arri, Satpal; Ihsan, Sana; Ellis, Howard; Guilcher, Antoine; Clapp, Brian; Chowienczyk, Philip J.; Plein, Sven; Perera, Divaka; Marber, Michael S.; Redwood, Simon R.

2017-01-01

Background: The mechanisms governing exercise-induced angina and its alleviation by the most commonly used antianginal drug, nitroglycerin, are incompletely understood. The purpose of this study was to develop a method by which the effects of antianginal drugs could be evaluated invasively during physiological exercise to gain further understanding of the clinical impact of angina and nitroglycerin. Methods: Forty patients (mean age, 65.2±7.6 years) with exertional angina and coronary artery disease underwent cardiac catheterization via radial access and performed incremental exercise using a supine cycle ergometer. As they developed limiting angina, sublingual nitroglycerin was administered to half the patients, and all patients continued to exercise for 2 minutes at the same workload. Throughout exercise, distal coronary pressure and flow velocity and central aortic pressure were recorded with sensor wires. Results: Patients continued to exercise after nitroglycerin administration with less ST-segment depression (P=0.003) and therefore myocardial ischemia. Significant reductions in afterload (aortic pressure, P=0.030) and myocardial oxygen demand were seen (tension-time index, P=0.024; rate-pressure product, P=0.046), as well as an increase in myocardial oxygen supply (Buckberg index, P=0.017). Exercise reduced peripheral arterial wave reflection (P<0.05), which was not further augmented by the administration of nitroglycerin (P=0.648). The observed increases in coronary pressure gradient, stenosis resistance, and flow velocity did not reach statistical significance; however, the diastolic velocity–pressure gradient relation was consistent with a significant increase in relative stenosis severity (k coefficient, P<0.0001), in keeping with exercise-induced vasoconstriction of stenosed epicardial segments and dilatation of normal segments, with trends toward reversal with nitroglycerin. Conclusions: The catheterization laboratory protocol provides a model to study myocardial ischemia and the actions of novel and established antianginal drugs. Administration of nitroglycerin causes changes in the systemic and coronary circulation that combine to reduce myocardial oxygen demand and to increase supply, thereby attenuating exercise-induced ischemia. Designing antianginal therapies that exploit these mechanisms may provide new therapeutic strategies. PMID:28468975

Physiology of Angina and Its Alleviation With Nitroglycerin: Insights From Invasive Catheter Laboratory Measurements During Exercise.

PubMed

Asrress, Kaleab N; Williams, Rupert; Lockie, Timothy; Khawaja, Muhammed Z; De Silva, Kalpa; Lumley, Matthew; Patterson, Tiffany; Arri, Satpal; Ihsan, Sana; Ellis, Howard; Guilcher, Antoine; Clapp, Brian; Chowienczyk, Philip J; Plein, Sven; Perera, Divaka; Marber, Michael S; Redwood, Simon R

2017-07-04

The mechanisms governing exercise-induced angina and its alleviation by the most commonly used antianginal drug, nitroglycerin, are incompletely understood. The purpose of this study was to develop a method by which the effects of antianginal drugs could be evaluated invasively during physiological exercise to gain further understanding of the clinical impact of angina and nitroglycerin. Forty patients (mean age, 65.2±7.6 years) with exertional angina and coronary artery disease underwent cardiac catheterization via radial access and performed incremental exercise using a supine cycle ergometer. As they developed limiting angina, sublingual nitroglycerin was administered to half the patients, and all patients continued to exercise for 2 minutes at the same workload. Throughout exercise, distal coronary pressure and flow velocity and central aortic pressure were recorded with sensor wires. Patients continued to exercise after nitroglycerin administration with less ST-segment depression ( P =0.003) and therefore myocardial ischemia. Significant reductions in afterload (aortic pressure, P =0.030) and myocardial oxygen demand were seen (tension-time index, P =0.024; rate-pressure product, P =0.046), as well as an increase in myocardial oxygen supply (Buckberg index, P =0.017). Exercise reduced peripheral arterial wave reflection ( P <0.05), which was not further augmented by the administration of nitroglycerin ( P =0.648). The observed increases in coronary pressure gradient, stenosis resistance, and flow velocity did not reach statistical significance; however, the diastolic velocity-pressure gradient relation was consistent with a significant increase in relative stenosis severity (k coefficient, P <0.0001), in keeping with exercise-induced vasoconstriction of stenosed epicardial segments and dilatation of normal segments, with trends toward reversal with nitroglycerin. The catheterization laboratory protocol provides a model to study myocardial ischemia and the actions of novel and established antianginal drugs. Administration of nitroglycerin causes changes in the systemic and coronary circulation that combine to reduce myocardial oxygen demand and to increase supply, thereby attenuating exercise-induced ischemia. Designing antianginal therapies that exploit these mechanisms may provide new therapeutic strategies. © 2017 The Authors.

Radial Artery as a Coronary Artery Bypass Conduit: 20-Year Results.

PubMed

Gaudino, Mario; Tondi, Paolo; Benedetto, Umberto; Milazzo, Valentina; Flore, Roberto; Glieca, Franco; Ponziani, Francesca Romana; Luciani, Nicola; Girardi, Leonard N; Crea, Filippo; Massetti, Massimo

2016-08-09

There is a lack of evidence for the choice of the second conduit in coronary surgery. The radial artery (RA) is a possible option, but few data on very-long-term outcomes exist. This study describes 20-year results of RA grafts used for coronary artery bypass grafting and the effects of RA removal on forearm circulation. We report the results of the prospective 20-year follow-up of the first 100 consecutive patients who received the RA as a coronary bypass conduit at our institution. Follow-up was 100% complete. There were 64 deaths, 23 (35.9%) from cardiovascular causes. Kaplan-Meier 20-year survival was 31%. Of the 36 survivors, 33 (91.6%) underwent RA graft control at a mean of 19.0 ± 2.5 years after surgery. The RA was found to be patent in 24 cases (84.8% patency). In the overall population, probability of graft failure at 20 years was 19.0 ± 0.2% for the left internal thoracic artery (ITA), 25.0 ± 0.2% for the RA, and 55.0 ± 0.2% for the saphenous vein (p = 0.002 for RA vs. saphenous vein, 0.11 for RA vs. ITA, and p < 0.001 for ITA vs. saphenous vein). Target vessel stenosis >90%, but not location of distal anastomosis, significantly influenced long-term RA graft patency. No patients reported hand or forearm symptoms. The ulnar artery diameter was increased in the operated arm (2.44 ± 0.43 mm vs. 2.01 ± 0.47 mm; p < 0.05) and correlated with the peak systolic velocity of the second palmar digital artery (Pearson coefficient: 0.621; p < 0.05). The 20-year patency rate of RA grafts is good, and not inferior to the ITA, especially when the conduit is used to graft a vessel with >90% stenosis. RA harvesting does not lead to hand or forearm symptoms, even at a very-long-term follow-up. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Cardiovascular RiskprofilE - IMaging and gender-specific disOrders (CREw-IMAGO): rationale and design of a multicenter cohort study.

PubMed

Zoet, Gerbrand A; Meun, Cindy; Benschop, Laura; Boersma, Eric; Budde, Ricardo P J; Fauser, Bart C J M; de Groot, Christianne J M; van der Lugt, Aad; Maas, Angela H E M; Moons, Karl G M; Roeters van Lennep, Jeanine E; Roos-Hesselink, Jolien W; Steegers, Eric A P; van Rijn, Bas B; Laven, Joop S E; Franx, Arie; Velthuis, Birgitta K

2017-08-07

Reproductive disorders, such as polycystic ovary syndrome (PCOS), primary ovarian insufficiency (POI) and hypertensive pregnancy disorders (HPD) like pre-eclampsia (PE), are associated with an increased risk of cardiovascular disease (CVD). Detection of early signs of cardiovascular disease (CVD), as well as identification of risk factors among women of reproductive age which improve cardiovascular risk prediction, is a challenge and current models might underestimate long-term health risks. The aim of this study is to assess cardiovascular disease in patients with a history of a reproductive disorder by low-dose computed tomography (CT). Women of 45 - 55 years, who experienced a reproductive disorder (PCOS, POI, HPD), are invited to participate in this multicenter, prospective, cohort study. Women will be recruited after regular cardiovascular screening, including assessment of classical cardiovascular risk factors. CT of the coronary arteries (both coronary artery calcium scoring (CACS), and contrast-enhanced coronary CT angiography (CCTA)) and carotid siphon calcium scoring (CSC) is planned in 300 women with HPD and 300 women with PCOS or POI. In addition, arterial stiffness (non-invasive pulse wave velocity (PWV)) measurement and cell-based biomarkers (inflammatory circulating cells) will be obtained. Initial inclusion is focused on women of 45 - 55 years. However, the age range (40 - 45 years and/or ≥ 55 years) and group composition may be adjusted based on the findings of the interim analysis. Participants can potentially benefit from information obtained in this study concerning their current cardiovascular health and expected future risk of cardiovascular events. The results of this study will provide insights in the development of CVD in women with a history of reproductive disorders. Ultimately, this study may lead to improved cardiovascular prediction models and will provide an opportunity for timely adjustment of preventive strategies. Limitations of this study include the possibility of overdiagnosis and the average radiation dose of 3.5 mSv during coronary and carotid siphon CT, although the increased lifetime malignancy risk is negligible. Netherlands Trial Register, NTR5531 . Date registered: October 21st, 2015.

Apolipoprotein(a) isoform size, lipoprotein(a) concentration, and coronary artery disease: a mendelian randomisation analysis.

PubMed

Saleheen, Danish; Haycock, Philip C; Zhao, Wei; Rasheed, Asif; Taleb, Adam; Imran, Atif; Abbas, Shahid; Majeed, Faisal; Akhtar, Saba; Qamar, Nadeem; Zaman, Khan Shah; Yaqoob, Zia; Saghir, Tahir; Rizvi, Syed Nadeem Hasan; Memon, Anis; Mallick, Nadeem Hayyat; Ishaq, Mohammad; Rasheed, Syed Zahed; Memon, Fazal-Ur-Rehman; Mahmood, Khalid; Ahmed, Naveeduddin; Frossard, Philippe; Tsimikas, Sotirios; Witztum, Joseph L; Marcovina, Santica; Sandhu, Manjinder; Rader, Daniel J; Danesh, John

2017-07-01

The lipoprotein(a) pathway is a causal factor in coronary heart disease. We used a genetic approach to distinguish the relevance of two distinct components of this pathway, apolipoprotein(a) isoform size and circulating lipoprotein(a) concentration, to coronary heart disease. In this mendelian randomisation study, we measured lipoprotein(a) concentration and determined apolipoprotein(a) isoform size with a genetic method (kringle IV type 2 [KIV2] repeats in the LPA gene) and a serum-based electrophoretic assay in patients and controls (frequency matched for age and sex) from the Pakistan Risk of Myocardial Infarction Study (PROMIS). We calculated odds ratios (ORs) for myocardial infarction per 1-SD difference in either LPA KIV2 repeats or lipoprotein(a) concentration. In a genome-wide analysis of up to 17 503 participants in PROMIS, we identified genetic variants associated with either apolipoprotein(a) isoform size or lipoprotein(a) concentration. Using a mendelian randomisation study design and genetic data on 60 801 patients with coronary heart disease and 123 504 controls from the CARDIoGRAMplusC4D consortium, we calculated ORs for myocardial infarction with variants that produced similar differences in either apolipoprotein(a) isoform size in serum or lipoprotein(a) concentration. Finally, we compared phenotypic versus genotypic ORs to estimate whether apolipoprotein(a) isoform size, lipoprotein(a) concentration, or both were causally associated with coronary heart disease. The PROMIS cohort included 9015 patients with acute myocardial infarction and 8629 matched controls. In participants for whom KIV2 repeat and lipoprotein(a) data were available, the OR for myocardial infarction was 0·93 (95% CI 0·90-0·97; p<0·0001) per 1-SD increment in LPA KIV2 repeats after adjustment for lipoprotein(a) concentration and conventional lipid concentrations. The OR for myocardial infarction was 1·10 (1·05-1·14; p<0·0001) per 1-SD increment in lipoprotein(a) concentration, after adjustment for LPA KIV2 repeats and conventional lipids. Genome-wide analysis identified rs2457564 as a variant associated with smaller apolipoprotein(a) isoform size, but not lipoprotein(a) concentration, and rs3777392 as a variant associated with lipoprotein(a) concentration, but not apolipoprotein(a) isoform size. In 60 801 patients with coronary heart disease and 123 504 controls, OR for myocardial infarction was 0·96 (0·94-0·98; p<0·0001) per 1-SD increment in apolipoprotein(a) protein isoform size in serum due to rs2457564, which was directionally concordant with the OR observed in PROMIS for a similar change. The OR for myocardial infarction was 1·27 (1·07-1·50; p=0·007) per 1-SD increment in lipoprotein(a) concentration due to rs3777392, which was directionally concordant with the OR observed for a similar change in PROMIS. Human genetic data suggest that both smaller apolipoprotein(a) isoform size and increased lipoprotein(a) concentration are independent and causal risk factors for coronary heart disease. Lipoprotein(a)-lowering interventions could be preferentially effective in reducing the risk of coronary heart disease in individuals with smaller apolipoprotein(a) isoforms. British Heart Foundation, US National Institutes of Health, Fogarty International Center, Wellcome Trust, UK Medical Research Council, UK National Institute for Health Research, and Pfizer. Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND license. Published by Elsevier Ltd.. All rights reserved.

Association of Rare and Common Variation in the Lipoprotein Lipase Gene with Coronary Artery Disease

PubMed Central

Khera, Amit V.; Won, Hong-Hee; Peloso, Gina M.; O’Dushlaine, Colm; Liu, Dajiang; Stitziel, Nathan O.; Natarajan, Pradeep; Nomura, Akihiro; Emdin, Connor A.; Gupta, Namrata; Borecki, Ingrid B.; Asselta, Rosanna; Duga, Stefano; Merlini, Piera Angelica; Correa, Adolfo; Kessler, Thorsten; Wilson, James G.; Bown, Matthew J.; Hall, Alistair S.; Braund, Peter S.; Carey, David J.; Murray, Michael F.; Kirchner, H. Lester; Leader, Joseph B.; Lavage, Daniel R.; Manus, J. Neil; Hartzel, Dustin N.; Samani, Nilesh J.; Schunkert, Heribert; Marrugat, Jaume; Elosua, Roberto; McPherson, Ruth; Farrall, Martin; Watkins, Hugh; Lander, Eric S.; Rader, Daniel J.; Danesh, John; Ardissino, Diego; Gabriel, Stacey; Willer, Cristen; Abecasis, Gonçalo R.; Saleheen, Danish; Dewey, Frederick E.; Kathiresan, Sekar

2017-01-01

Importance The activity of lipoprotein lipase (LPL) is the rate-determining step in clearing triglyceride-rich lipoproteins from the circulation. Mutations that damage the LPL gene lead to lifelong deficiency in enzymatic activity and can provide insight into the relationship of LPL to human disease. Objective Determine if rare and/or common variants in the LPL gene are associated with early-onset coronary artery disease (CAD). Design, Setting, and Participants Cross-sectional study. The LPL gene was sequenced in 10 CAD case-control cohorts of the multinational Myocardial Infarction Genetics Consortium and a nested CAD case-control cohort of the Geisinger Health System DiscovEHR cohort between 2010 and 2015. Common variants were genotyped in up to 305,699 individuals of the Global Lipids Genetics Consortium and up to 120,600 individuals of the CARDIoGRAM Exome Consortium between 2012 and 2014. Study-specific estimates were pooled via meta-analysis. Exposure Rare damaging mutations in LPL included loss-of-function variants and missense variants annotated as pathogenic in a human genetics database or predicted to be damaging by computer prediction algorithms trained to identify mutations that impair protein function. Common variants in the LPL gene region included those independently associated with circulating triglyceride levels. Main Outcomes and Measures Circulating lipid levels and CAD. Results Among 46,891 individuals with LPL gene sequencing data available, mean age was 50 years (SD 12.6) and 51% were female. 188 participants (0.40%; 95%CI 0.35–0.46) carried a damaging mutation in the LPL gene – 105 of 32,646 control participants (0.32%) and 83 of 14,245 (0.58%) early-onset CAD cases. Compared to 46,703 non-carriers, the 188 heterozygous carriers of a LPL damaging mutation displayed higher plasma triglycerides (Beta coefficient= +19.6 mg/dL; 95%CI 4.6–34.6) and higher odds of CAD (odds ratio 1.84; 95%CI 1.35–2.51; P<0.001). An analysis of 6 common LPL variants noted an odds ratio for CAD of 1.51 (95%CI 1.39–1.64; P=1.1×10−22) per standard deviation increase in triglycerides. Conclusions and Relevance The presence of rare damaging mutations in the LPL gene was significantly associated with higher triglyceride levels and presence of CAD. However, further research is needed to assess causal mechanisms by which heterozygous LPL deficiency could lead to CAD. PMID:28267856

The effects of nitroglycerin during cardiopulmonary resuscitation.

PubMed

Stefaniotou, Antonia; Varvarousi, Giolanda; Varvarousis, Dimitrios P; Xanthos, Theodoros

2014-07-05

The outcome for both in-hospital and out-of hospital cardiac arrest remains dismal. Vasopressors are used to increase coronary perfusion pressure and thus facilitate return of spontaneous circulation during cardiopulmonary resuscitation. However, they are associated with a number of potential adverse effects and may decrease endocardial and cerebral organ blood flow. Nitroglycerin has a favourable haemodynamic profile which promotes forward blood flow. Several studies suggest that combined use of nitroglycerin with vasopressors during resuscitation, is associated with increased rates of resuscitation and improved post-resuscitation outcome. This article reviews the effects of nitroglycerin during cardiopulmonary resuscitation and postresuscitation period, as well as the beneficial outcomes of a combination regimen consisting of a vasopressor and a vasodilator, such as nitroglycerin. Copyright © 2014 Elsevier B.V. All rights reserved.

Stress in surgeons.

PubMed

Green, A; Duthie, H L; Young, H L; Peters, T J

1990-10-01

A sample of 1000 members of the Association of Surgeons of Great Britain and Ireland was circulated with a postal questionnaire relating to their occupational stressors, their type A coronary-prone behaviour and their mental health. Six hundred and seventy-two (67 per cent) useable forms were returned anonymously. The major individual stressors were: (1) the interference of the job with personal life, (2) general administration, and (3) the number of patients in clinics. Type A behaviour was similar to that of other professional groups. Surgeons showed mean scores significantly higher than the general population on two subscales of the mental health index (free-floating anxiety and hysterical anxiety). The findings for the few female surgeons (2 per cent) were similar to those in men but they did not exhibit raised free-floating anxiety levels.

MicroRNAs Expression Profiles in Cardiovascular Diseases

PubMed Central

Bronze-da-Rocha, Elsa

2014-01-01

The current search for new markers of cardiovascular diseases (CVDs) is explained by the high morbidity and mortality still observed in developed and developing countries due to cardiovascular events. Recently, microRNAs (miRNAs or miRs) have emerged as potential new biomarkers and are small sequences of RNAs that regulate gene expression at posttranscriptional level by inhibiting translation or inducing degradation of the target mRNAs. Circulating miRNAs are involved in the regulation of signaling pathways associated to aging and can be used as novel diagnostic markers for acute and chronic diseases such as cardiovascular pathologies. This review summarizes the biogenesis, maturation, and stability of miRNAs and their use as potential biomarkers for coronary artery disease (CAD), myocardial infarction (MI), and heart failure (HF). PMID:25013816

The heart as a self-regulating system: integration of homeodynamic mechanisms.

PubMed

Kresh, J Y; Armour, J A

1997-04-01

In the past the study of mechanical and electrical properties of the heart has been disjointed with minimal overlap and unification. The fact remains that these features are tightly coupled and central to the functioning heart. The maintenance of adequate cardiac output relies upon the highly integrated autoregulatory mechanisms and modulation of cardiac myocyte function. Regional ventricular mechanics and energetics are dependent upon muscle fiber stress-strain rate, the passive properties of myocardial collagen matrix, adequate vascular perfusion, transcapillary transport and electrical activation pattern. Intramural hydraulic "loading" is regulated by coronary arterial and venous dynamics. All of these components are under the constant influence of intrinsic cardiac and extracardiac autonomic neurons, as well as circulating hormones. A brief overview of the putative regulation of these various components is presented in this paper.

Association of socioeconomic stratification with plasmatic markers of lipoperoxidation and antioxidants in Venezuelan school-age children.

PubMed

Ruiz-Fernández, Nelina; Bosch, Virgilio; Giacopini, Maria Isabel

2016-12-30

To establish association between socioeconomic status and plasmatic markers of lipoperoxidation and antioxidants in Venezuelan school-age children from the middle-class and in critical poverty. Cross-sectional study with a sample of 114 school-age children (aged 7-9). The socioeconomic status, dietary intake of macro and micro-nutrients, weight, height, lipid profile, indicators of lipid peroxidation and enzymatic and non-enzymatic antioxidants were determined. The daily average intake of energy, carbohydrates and vitamin A, and the percentage of energy obtained from carbohydrates was significantly higher in middle-class children compared to critical poverty children ( p <0.05). The circulating oxidized low density lipoprotein ( p <0.001) and the susceptibility of low density lipoproteins and very low density lipoproteins to oxidation in vitro ( p <0.05) were significantly higher in middle-class children, while the critical poverty children showed significantly lower levels of Vitamin C and E in plasma ( p <0.05). Non-enzymatic antioxidant levels were frequently deficient in both strata. The concentrations of circulating oxidized low density lipoprotein (OR: 1.09, CI 95% : 1.016-1.179; p = 0.017) and Vitamin C (OR: 3.21, CI 95% : 1.104-9.938; p = 0.032) were associated to the socioeconomic status independently of gender, family history of premature coronary artery disease, triglicerides, Vitamin C and E dietary intake and count of white blood cells. The socioeconomic status was associated to circulating oxidized low density lipoprotein and Vitamin C in Venezuelan school-age children, The results suggested the need to improve the dietary intake of antioxidants in both studied socioeconomic groups.

Severe respiratory depression and bradycardia before induction of anesthesia and onset of Takotsubo cardiomyopathy after cardiopulmonary resuscitation.

PubMed

Furuichi, Yuko; Hamada, Ayaka; Nakazato, Keiko; Kobayashi, Katsuya; Sakamoto, Atsuhiro

2016-12-01

A 69-year-old woman undergoing treatment for hypertension and epilepsy was scheduled to undergo cataract surgery. All preoperative examination results were within normal limits. Despite being tense, she walked to the operating room. Approximately 2 minutes after an intravenous line was established by an anesthesia resident, severe hypoxia and bradycardia developed, and she lost consciousness. Cardiopulmonary resuscitation was initiated immediately, and after 1 minute, she regained consciousness, and her breathing and circulation recovered. After admission to the intensive care unit, emergency coronary angiography was performed. The blood flow in all the coronary arteries was normal. However, a decrease in the apical left ventricular wall motion and an increase in the basal wall motion were observed. Based on these findings, Takotsubo cardiomyopathy was diagnosed. The wall motion gradually improved and the patient was discharged from the hospital on postoperative day 15. The respiratory depression and bradycardia were thought to be due to an inadvertent bolus of remifentanil. We surmised that the patient had received a slight amount of retained medication when the anesthesia resident established the intravenous line, which caused severe respiratory depression. It is important to note that adverse effects such as severe respiratory depression and bradycardia can be caused by even small doses of remifentanil. Copyright © 2016 Elsevier Inc. All rights reserved.

Metabolic Syndrome and Sexual Function in Postmenopausal Women.

PubMed

Trompeter, Susan E; Bettencourt, Ricki; Barrett-Connor, Elizabeth

2016-12-01

Limited literature suggests that sexual dysfunction in women covaries with the metabolic syndrome. This study examined the association of sexual function with metabolic syndrome and cardiovascular disease in healthy older women. There were 376 postmenopausal, community-dwelling women from the Rancho Bernardo Study (mean baseline age = 73 years) that completed a clinic visit during 1999-2002 and returned the Female Sexual Function Index (FSFI) questionnaire mailed in 2002. Thirty-nine percent reported being sexually active; 41.5% met a diagnosis of metabolic syndrome. The number of metabolic syndrome components was strongly associated with decreased sexual activity, desire, and low sexual satisfaction. Waist girth, diabetes, and hypertension were associated with decreased sexual activity. Elevated triglycerides were associated with low desire. Among the cardiovascular endpoints, heart attack, coronary artery bypass, and angina were associated with decreased sexual activity, but not with sexual desire or satisfaction. Past diagnosis of heart failure, poor circulation, and stroke were not associated with sexual function. Sexually active women with metabolic syndrome met criteria for sexual dysfunction in desire, arousal, orgasm, and satisfaction domains. The FSFI Total Score did not differ significantly between sexually active and inactive women. Metabolic syndrome was associated with decreased sexual activity, desire, and satisfaction in all women and with sexual dysfunction in most domains in sexually active women. Coronary artery disease was more prevalent in women with low sexual activity. Copyright © 2016 Elsevier Inc. All rights reserved.

Coronary reconnection in emergency "conduit operation" for acute type-a aortic dissection with aortic insufficiency: experience with 24 cases.

PubMed

Massimo, C G; Presenti, L F; Favi, P P; Duranti, A; Poma, A G; Marranci, P; Modiano, C

1987-12-01

Twenty-four cases of acute type-A aortic dissection with aortic valvular insufficiency were treated in our institution by means of an emergency operation in which the aortic valve, ascending aorta, and aortic arch were resected and replaced with a valved conduit that had been lengthened with a tubular Dacron graft. The procedure included the use of deep hypothermia for cerebral protection, as well as extracorporeal circulation. Aortic resection was performed from the aortic valve to the origin of the descending thoracic aorta; the aortic graft was anastomosed proximally to the valve annulus and distally to the descending aorta. The carotid orifices were connected to the side of the graft in a single tissue button. The coronary arteries were then reconnected by means of double venous bypass grafts to the innominate artery, to allow for inclusion of the graft. Within 1 month after operation, four patients died of the consequences of dissection. Six months postoperatively, one patient succumbed to an infarction. Six months to 5 years after operation, the remaining 19 patients are still alive. On the basis of this experience, we believe that acute type-A aortic dissection with aortic valvular insufficiency should be treated during the first hours after the onset of symptoms. The above-described procedure proved effective in the control of bleeding, which is the major risk in emergency operations of this type.

Marked Acceleration of Atherosclerosis following Lactobacillus casei induced Coronary Arteritis in a Mouse Model of Kawasaki Disease

PubMed Central

Chen, Shuang; Lee, Young Ho; Crother, Timothy R.; Fishbein, Michael; Zhang, Wenxuan; Yilmaz, Atilla; Shimada, Kenichi; Schulte, Danica J; Lehman, Thomas J.A.; Shah, Prediman K.; Arditi, Moshe

2012-01-01

Objective To investigate if Lactobacillus casei cell wall extract (LCWE)-induced Kawasaki Disease (KD) accelerates atherosclerosis in hypercholesterolemic mice. Method and Resuslts Apoe−/− or Ldlr−/− mice were injected with LCWE (KD mice) or PBS, fed high fat diet for 8 weeks, and atherosclerotic lesions in aortic sinuses (AS), arch (AC) and whole aorta were assessed. KD mice had larger, more complex aortic lesions with abundant collagen, and both extracellular and intracellular lipid and foam cells, compared to lesions in control mice despite similar cholesterol levels. Both Apoe−/− KD and Ldlr−/− KD mice showed dramatic acceleration in atherosclerosis vs. controls, with increases in en face aortic atherosclerosis and plaque size in both the AS and AC plaques. Accelerated atherosclerosis was associated with increased circulating IL-12p40, IFN-γ, TNF-α, and increased macrophage, DC, and T cell recruitment in lesions. Furthermore, daily injections of the IL-1Ra, which inhibits LCWE induced KD vasculitis, prevented the acceleration of atherosclerosis. Conclusions Our results suggest an important pathophysiologic link between coronary arteritis/vasculitis in the KD mouse model and subsequent atherosclerotic acceleration, supporting the concept that a similar relation may also be present in KD patients. These results also suggest that KD in childhood may predispose to accelerated and early atherosclerosis as adults. PMID:22628430

Physical and mathematical aspects of blood-glucose- and insulin-level kinetics in patients with coronary heart disease and high risk of its development

NASA Astrophysics Data System (ADS)

Denisova, Tatyana P.; Malinova, Lidia I.; Malinov, Igor A.

2001-05-01

The intravenous glucose tolerance test was performed to estimate the kinetics of blood glucose and insulin levels. Glucose was injected in individual standardized dose (0.5 g. per 1 kg of body weight). Three groups of patients were checked up: 1) patients with coronary heart disease verified by cicatricial alterations in myocardium found by electrocardiographic and echocardiographic methods; 2) children of patients with transmural myocardial infarction practically healthy at the moment of study; 3) persons practically healthy at the moment of study without any indications on cardiovascular diseases and non-insulin dependent diabetes mellitus among all ancestors and relatives who frequently were long-livers. Last groups didn't differ by age and sex. Peripheral blood glucose level, immunoreactive and free insulin (tested by muscular tissue) were studied just before glucose injection (on an empty stomach) and 4 times after it. The received discrete data were approximated by high degree polynomials, the estimation of blood glucose and insulin time functions symmetric was performed. The deceleration of degradation of insulin circulating in peripheral blood and the time decrease of second phase of insulin secretion were analytically established. This fact proves the complicated mechanism of insulin alterations in atherosclerosis, consisting not only of insulin resistance of peripheral tissues but of decrease of plastic processes in insulin- generating cells.

Small vessel hematocrit in ischemic myocardium

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gumm, D.C.; Cooper, S.M.; Marcus, M.L.

1986-03-01

As blood enters the microvasculature of normally perfused myocardium, there is a progressive decrease in small vessel hematocrit (SV Hct) due to RBC streaming in smaller branching vessels and the Fahraeus-Lindqvist effect. We hypothesized that if the coronary collateral circulation was composed of very small vessels branching from large parent vessels, plasma streaming would result in a further decrease of SV Hct in ischemic myocardium. Six open chest anesthetized dogs were studied. Plasma was labelled with /sup 59/FeCl siderophilin and RBC's with /sup 99/mTc to estimate SV Hct from myocardial biopsies. The LAD was occluded and cannulated for measurement ofmore » retrograde flow (arising presumably from proximal collaterals). The ischemic region was identified using the microsphere shadow technique. Collateral flow after LAD occlusion was 30 +- 12 ml/min 100g (x +- SE). Systemic Hct was 40 +- 1%. The Hct of blood from retrograde flow was 39 +- 1% (p = NS). Activity of /sup 59/FeCl and /sup 99/mTc in known quantities of blood were compared to myocardial biopsies to estimate SV Hct. Ischemic SV Hct was 23 +- 2% and non-ischemic SV Hct was 21 +- 1% (p = NS). We conclude that the size and branching pattern of coronary collaterals is such that plasma streaming in collaterals does not result in an additional decrease in SV Hct in ischemic myocardium.« less

An organic khorasan wheat-based replacement diet improves risk profile of patients with acute coronary syndrome: a randomized crossover trial.

PubMed

Whittaker, Anne; Sofi, Francesco; Luisi, Maria Luisa Eliana; Rafanelli, Elena; Fiorillo, Claudia; Becatti, Matteo; Abbate, Rosanna; Casini, Alessandro; Gensini, Gian Franco; Benedettelli, Stefano

2015-05-11

Khorasan wheat is an ancient grain with previously reported health benefits in clinically healthy subjects. The aim of this study was to examine whether a replacement diet, thereby substituting all other cereal grains, with products made with organic khorasan wheat could provide additive protective effects in reducing lipid, oxidative and inflammatory risk factors, in patients with Acute Coronary Syndromes (ACS) in comparison to a similar replacement diet using products made from organic modern wheat. A randomized double-blinded crossover trial with two intervention phases was conducted on 22 ACS patients (9 F; 13 M). The patients were assigned to consume products (bread, pasta, biscuits and crackers) made either from organic semi-whole khorasan wheat or organic semi-whole control wheat for eight weeks in a random order. On average, patients ingested 62.0 g dry weight (DW) day-1 khorasan or control semolina; and 140.5 g DW day-1 khorasan or control flour, respectively. An eight-week washout period was implemented between the respective interventions. Blood analyses were performed both at the beginning and end of each intervention phase; thereby permitting a comparison of both the khorasan and control intervention phases, respectively, on circulatory risk factors for the same patient. Consumption of products made with khorasan wheat resulted in a significant amelioration in total cholesterol (-6.8%), low-density lipoprotein cholesterol (LDL-C) (-8.1%) glucose (-8%) and insulin (-24.6%) from baseline levels, independently of age, sex, traditional risk factors, medication and diet quality. Moreover, there was a significant reduction in reactive oxygen species (ROS), lipoperoxidation of circulating monocytes and lymphocytes, as well as in the levels of Tumor Necrosis Factor-alpha. No significant differences from baseline in the same patients were observed after the conventional control wheat intervention phase. The present results suggest that a replacement diet with cereal products made from organic khorasan wheat provides additional protection in patients with ACS. Circulating cardiovascular risk factors, including lipid parameters, and markers of both oxidative stress and inflammatory status, were reduced, irrespective of the number and combination of medicinal therapies with proven efficacy in secondary prevention.

Isolated coronary artery bypass grafting in extracorporeal circulation in patients over 65 years old – does age still matter?

PubMed Central

Walczak, Andrzej; Ostrowski, Stanisław; Wrona, Ewa; Bartczak, Karol; Jaszewski, Ryszard

2014-01-01

Introduction Coronary artery bypass grafting (CABG) is conducted more and more commonly in patients in advanced age. Aim of the study To analyze the influence of age and concurrent risk factors on the complications and early mortality after CABG. Material and methods Medical records of 2194 patients were analyzed retrospectively. A group of 1303 patients who had undergone isolated CABG was selected. 106 (4.8%) patients were excluded due to missing data in their medical records. The remaining 1197 patients were divided into two subgroups by age: 1st group < 65 years (n = 662; 55.3%); 2nd group ≥ 65 years (n = 535; 44.7%). Results The total 30-day mortality was 3.93% and was six times higher in the older group (1.21 vs. 7.29%; p < 0.001). Complications were observed in 176 (14.70%) patients, more often in the older group (10.42% vs. 20.0%; p < 0.001). In this group all kinds of complications were noted more often and in particular: postoperative myocardial infarction (1.96% vs. 5.42%; p = 0.001), respiratory dysfunction (1.36% vs. 4.11%; p = 0.005), neurological complications (1.81% vs. 3.74%; p = 0.04) and multi-organ dysfunction syndrome (0.30% vs. 1.68%, p = 0.03). The older patients required longer time under mechanical ventilation (24.0 ± 27.9 vs. 37.0 ± 74.1 hours; p = 0.004) and stayed longer in the intensive care unit: 2.5 ± 3.0 vs. 4.1 ± 7.84 days; p < 0.001. Independent predictors of death were: female sex [OR (95% CI) = 2.4 (1.2-4.5)], age ≥ 65 years [OR = 4.9 (2.1-11.1)], eGFR < 60 mL/min/1.73 m2 [OR = 2.2 (1.0-4.7)], time at extracorporeal circulation > 72 minutes [OR = 5.5 (2.7-10.9)] and left main stem stenosis (> 50%) [OR = 2.4 (1.3-4.6)]. Conclusions Age still significantly influences postoperative complications and mortality after isolated CABG. PMID:26336419

Isolated coronary artery bypass grafting in extracorporeal circulation in patients over 65 years old - does age still matter?

PubMed

Miśkowiec, Dawid; Walczak, Andrzej; Ostrowski, Stanisław; Wrona, Ewa; Bartczak, Karol; Jaszewski, Ryszard

2014-06-01

Coronary artery bypass grafting (CABG) is conducted more and more commonly in patients in advanced age. To analyze the influence of age and concurrent risk factors on the complications and early mortality after CABG. Medical records of 2194 patients were analyzed retrospectively. A group of 1303 patients who had undergone isolated CABG was selected. 106 (4.8%) patients were excluded due to missing data in their medical records. The remaining 1197 patients were divided into two subgroups by age: 1(st) group < 65 years (n = 662; 55.3%); 2(nd) group ≥ 65 years (n = 535; 44.7%). The total 30-day mortality was 3.93% and was six times higher in the older group (1.21 vs. 7.29%; p < 0.001). Complications were observed in 176 (14.70%) patients, more often in the older group (10.42% vs. 20.0%; p < 0.001). In this group all kinds of complications were noted more often and in particular: postoperative myocardial infarction (1.96% vs. 5.42%; p = 0.001), respiratory dysfunction (1.36% vs. 4.11%; p = 0.005), neurological complications (1.81% vs. 3.74%; p = 0.04) and multi-organ dysfunction syndrome (0.30% vs. 1.68%, p = 0.03). The older patients required longer time under mechanical ventilation (24.0 ± 27.9 vs. 37.0 ± 74.1 hours; p = 0.004) and stayed longer in the intensive care unit: 2.5 ± 3.0 vs. 4.1 ± 7.84 days; p < 0.001. Independent predictors of death were: female sex [OR (95% CI) = 2.4 (1.2-4.5)], age ≥ 65 years [OR = 4.9 (2.1-11.1)], eGFR < 60 mL/min/1.73 m(2) [OR = 2.2 (1.0-4.7)], time at extracorporeal circulation > 72 minutes [OR = 5.5 (2.7-10.9)] and left main stem stenosis (> 50%) [OR = 2.4 (1.3-4.6)]. Age still significantly influences postoperative complications and mortality after isolated CABG.

Microfluidic assay of circulating endothelial cells in coronary artery disease patients with angina pectoris

PubMed Central

Chen, Shuiyu; Sun, Yukun; Neoh, Kuang Hong; Chen, Anqi; Li, Weiju; Yang, Xiaorui

2017-01-01

Background Circulating endothelial cells (CECs) are widely reported as a promising biomarker of endothelial damage/dysfunction in coronary artery disease (CAD). The two popular methods of CEC quantification include the use of immunomagnetic beads separation (IB) and flow cytometry analysis (FC); however, they suffer from two main shortcomings that affect their diagnostic and prognostic responses: non-specific bindings of magnetic beads to non-target cells and a high degree of variability in rare cell identification, respectively. We designed a microfluidic chip with spatially staggered micropillars for the efficient harvesting of CECs with intact cellular morphology in an attempt to revisit the diagnostic goal of CEC counts in CAD patients with angina pectoris. Methods A label-free microfluidic assay that involved an in-situ enumeration and immunofluorescent identification (DAPI+/CD146+/VEGFR1+/CD45-) of CECs was carried out to assess the CEC count in human peripheral blood samples. A total of 55 CAD patients with angina pectoris [16 with chronic stable angina (CSA) and 39 with unstable angina (UA)], together with 15 heathy controls (HCs) were enrolled in the study. Results CEC counts are significantly higher in both CSA and UA groups compared to the HC group [respective medians of 6.9, 10.0 and 1.5 cells/ml (p < 0.01)]. Further, a significant elevation of CEC count was observed in the three UA subgroups [low risk (5.3) vs. intermediate risk (10.8) vs. high risk (18.0) cells/ml, p < 0.001) classified in accordance to the TIMI NSTEMI/UA risk score system. From the receiver-operating characteristic curve analysis, the AUCs for distinguishing CSA and UA from HC were 0.867 and 0.938, respectively. The corresponding sensitivities were 87.5% and 84.6% and the specificities were 66.7% and 86.7%, respectively. Conclusions Our microfluidic assay system is efficient and stable for CEC capture and enumeration. The results showed that the CEC count has the potential to be a promising clinical biomarker for the assessment of endothelial damage/dysfunction in CAD patients with angina pectoris. PMID:28704506

Microfluidic assay of circulating endothelial cells in coronary artery disease patients with angina pectoris.

PubMed

Chen, Shuiyu; Sun, Yukun; Neoh, Kuang Hong; Chen, Anqi; Li, Weiju; Yang, Xiaorui; Han, Ray P S

2017-01-01

Circulating endothelial cells (CECs) are widely reported as a promising biomarker of endothelial damage/dysfunction in coronary artery disease (CAD). The two popular methods of CEC quantification include the use of immunomagnetic beads separation (IB) and flow cytometry analysis (FC); however, they suffer from two main shortcomings that affect their diagnostic and prognostic responses: non-specific bindings of magnetic beads to non-target cells and a high degree of variability in rare cell identification, respectively. We designed a microfluidic chip with spatially staggered micropillars for the efficient harvesting of CECs with intact cellular morphology in an attempt to revisit the diagnostic goal of CEC counts in CAD patients with angina pectoris. A label-free microfluidic assay that involved an in-situ enumeration and immunofluorescent identification (DAPI+/CD146+/VEGFR1+/CD45-) of CECs was carried out to assess the CEC count in human peripheral blood samples. A total of 55 CAD patients with angina pectoris [16 with chronic stable angina (CSA) and 39 with unstable angina (UA)], together with 15 heathy controls (HCs) were enrolled in the study. CEC counts are significantly higher in both CSA and UA groups compared to the HC group [respective medians of 6.9, 10.0 and 1.5 cells/ml (p < 0.01)]. Further, a significant elevation of CEC count was observed in the three UA subgroups [low risk (5.3) vs. intermediate risk (10.8) vs. high risk (18.0) cells/ml, p < 0.001) classified in accordance to the TIMI NSTEMI/UA risk score system. From the receiver-operating characteristic curve analysis, the AUCs for distinguishing CSA and UA from HC were 0.867 and 0.938, respectively. The corresponding sensitivities were 87.5% and 84.6% and the specificities were 66.7% and 86.7%, respectively. Our microfluidic assay system is efficient and stable for CEC capture and enumeration. The results showed that the CEC count has the potential to be a promising clinical biomarker for the assessment of endothelial damage/dysfunction in CAD patients with angina pectoris.

The systemic factor: the comparative roles of cardiopulmonary bypass and off-pump surgery in the genesis of patient injury during and following cardiac surgery.

PubMed

Menasché, P

2001-12-01

There is compelling evidence that off-pump coronary artery bypass operations are associated with reduced circulating levels of inflammatory mediators. Whereas complement activation and release of acute-phase reactants such as interleukin-6 are still expected to occur as consequences of a nonbypass-related general surgical trauma, a major feature of off-pump surgery seems to be a decreased production of interleukin-8, which may have important practical implications because of the participation of this cytokine in neutrophil trafficking and myocardial injury. The scarcity of carefully controlled, randomized trials precludes firm conclusions regarding the extent to which these biological changes translate into meaningful improvements in clinical outcomes. The problem is further complicated by the fact that the adverse effects of cardiopulmonary bypass largely depend on a genetically controlled balance between proinflammatory and antiinflammatory mediators. Currently, it is still impossible to predict, in a given patient, the side toward which this balance will be shifted. Nevertheless, accumulating experience identifies patient subgroups who may greatly benefit from avoiding extracorporeal circulation. These subsets include patients with severe extracardiac comorbidities (in particular, renal failure) and, possibly, patients with advanced left ventricular dysfunction, who may poorly tolerate superimposed, bypass-related, inflammatory tissue injuries.

Partial IGF-1 deficiency is sufficient to reduce heart contractibility, angiotensin II sensibility, and alter gene expression of structural and functional cardiac proteins.

PubMed

González-Guerra, José Luis; Castilla-Cortazar, Inma; Aguirre, Gabriel A; Muñoz, Úrsula; Martín-Estal, Irene; Ávila-Gallego, Elena; Granado, Miriam; Puche, Juan E; García-Villalón, Ángel Luis

2017-01-01

Circulating levels of IGF-1 may decrease under several circumstances like ageing, metabolic syndrome, and advanced cirrhosis. This reduction is associated with insulin resistance, dyslipidemia, progression to type 2 diabetes, and increased risk for cardiovascular diseases. However, underlying mechanisms between IGF-1 deficiency and cardiovascular disease remain elusive. The specific aim of the present work was to study whether the partial IGF-1 deficiency influences heart and/or coronary circulation, comparing vasoactive factors before and after of ischemia-reperfusion (I/R). In addition, histology of the heart was performed together with cardiac gene expression for proteins involved in structure and function (extracellular matrix, contractile proteins, active peptides); carried out using microarrays, followed by RT-qPCR confirmation of the three experimental groups. IGF-1 partial deficiency is associated to a reduction in contractility and angiotensin II sensitivity, interstitial fibrosis as well as altered expression pattern of genes involved in extracellular matrix proteins, calcium dynamics, and cardiac structure and function. Although this work is descriptive, it provides a clear insight of the impact that partial IGF-1 deficiency on the heart and establishes this experimental model as suitable for studying cardiac disease mechanisms and exploring therapeutic options for patients under IGF-1 deficiency conditions.

Partial IGF-1 deficiency is sufficient to reduce heart contractibility, angiotensin II sensibility, and alter gene expression of structural and functional cardiac proteins

PubMed Central

Aguirre, Gabriel A.; Muñoz, Úrsula; Martín-Estal, Irene; Ávila-Gallego, Elena; Granado, Miriam; Puche, Juan E.; García-Villalón, Ángel Luis

2017-01-01

Circulating levels of IGF-1 may decrease under several circumstances like ageing, metabolic syndrome, and advanced cirrhosis. This reduction is associated with insulin resistance, dyslipidemia, progression to type 2 diabetes, and increased risk for cardiovascular diseases. However, underlying mechanisms between IGF-1 deficiency and cardiovascular disease remain elusive. The specific aim of the present work was to study whether the partial IGF-1 deficiency influences heart and/or coronary circulation, comparing vasoactive factors before and after of ischemia-reperfusion (I/R). In addition, histology of the heart was performed together with cardiac gene expression for proteins involved in structure and function (extracellular matrix, contractile proteins, active peptides); carried out using microarrays, followed by RT-qPCR confirmation of the three experimental groups. IGF-1 partial deficiency is associated to a reduction in contractility and angiotensin II sensitivity, interstitial fibrosis as well as altered expression pattern of genes involved in extracellular matrix proteins, calcium dynamics, and cardiac structure and function. Although this work is descriptive, it provides a clear insight of the impact that partial IGF-1 deficiency on the heart and establishes this experimental model as suitable for studying cardiac disease mechanisms and exploring therapeutic options for patients under IGF-1 deficiency conditions. PMID:28806738

The Emerging Role of miR-223 in Platelet Reactivity: Implications in Antiplatelet Therapy

PubMed Central

Shi, Rui; Zhou, Xin; Ji, Wen-Jie; Zhang, Ying-Ying; Ma, Yong-Qiang; Zhang, Jian-Qi

2015-01-01

Platelets are anuclear cells and are devoid of genomic DNA, but they are capable of de novo protein synthesis from mRNA derived from their progenitor cells, megakaryocytes. There is mounting evidence that microRNA (miRNA) plays an important role in regulating gene expression in platelets. miR-223 is the most abundant miRNAs in megakaryocytes and platelets. One of the miR-223-regulated genes is ADP P2Y12, a key target for current antiplatelet drug therapy. Recent studies showed that a blunted response to P2Y12 antagonist, that is, high on-treatment platelet reactivity (HTPR), is a strong predictor of major cardiovascular events (MACEs) in coronary heart disease (CHD) patients receiving antiplatelet treatment. Recent clinical cohort study showed that the level of circulating miR-223 is inversely associated with MACE in CHD patients. In addition, our recent data demonstrated that the level of both intraplatelet and circulating miR-223 is an independent predictor for HTPR, thus providing a link between miR-223 and MACE. These lines of evidence indicate that miR-223 may serve as a potential regulatory target for HTPR, as well as a diagnostic tool for identification of HTPR in clinical settings. PMID:26221610

New congenital coronary artery anomaly - double supply of single left anterior descending coronary artery from the left and right coronary sinuses: a case report.

PubMed

Daralammouri, Yunis; Ghannam, Malik; Lauer, Bernward

2016-08-02

A normal anatomy of coronary arteries is important to have adequate cardiac muscle blood supply especially during extraneous physical activities. This case report describes a rare coronary anomaly in which the accessory coronary artery arose from the right coronary artery, reentered the left anterior descending coronary artery, and then ran as a single vessel. We present a case of a coronary anomaly in a 47-year-old white man who presented with atypical angina. Computed tomographic angiography and coronary angiography showed a variant of dual left anterior descending coronary artery not previously described. Our patient's accessory coronary artery arose from his right coronary artery. It took an intramuscular course beneath the right ventricular outflow tract in the interventricular septal area to the anterior interventricular sulcus, giving off septal perforators that reentered his medial left anterior descending coronary artery. Both vessels ran after the anastomosis in the anterior interventricular sulcus as a single vessel. We propose that this anomaly represents a new variant of coronary artery anomaly. This coronary artery anomaly does not cause ischemia. Recognition of this coronary anomaly is important in patients undergoing percutaneous coronary intervention or coronary artery bypass graft operations.

EXCEL Clinical Trial

ClinicalTrials.gov

2018-03-01

Chronic Coronary Occlusion; Unprotected Left Main Coronary Artery Disease; Stent Thrombosis; Vascular Disease; Myocardial Ischemia; Coronary Artery Stenosis; Coronary Disease; Coronary Artery Disease; Coronary Restenosis

Causal Associations of Adiposity and Body Fat Distribution With Coronary Heart Disease, Stroke Subtypes, and Type 2 Diabetes Mellitus: A Mendelian Randomization Analysis.

PubMed

Dale, Caroline E; Fatemifar, Ghazaleh; Palmer, Tom M; White, Jon; Prieto-Merino, David; Zabaneh, Delilah; Engmann, Jorgen E L; Shah, Tina; Wong, Andrew; Warren, Helen R; McLachlan, Stela; Trompet, Stella; Moldovan, Max; Morris, Richard W; Sofat, Reecha; Kumari, Meena; Hyppönen, Elina; Jefferis, Barbara J; Gaunt, Tom R; Ben-Shlomo, Yoav; Zhou, Ang; Gentry-Maharaj, Aleksandra; Ryan, Andy; Mutsert, Renée de; Noordam, Raymond; Caulfield, Mark J; Jukema, J Wouter; Worrall, Bradford B; Munroe, Patricia B; Menon, Usha; Power, Chris; Kuh, Diana; Lawlor, Debbie A; Humphries, Steve E; Mook-Kanamori, Dennis O; Sattar, Naveed; Kivimaki, Mika; Price, Jacqueline F; Davey Smith, George; Dudbridge, Frank; Hingorani, Aroon D; Holmes, Michael V; Casas, Juan P

2017-06-13

The implications of different adiposity measures on cardiovascular disease etiology remain unclear. In this article, we quantify and contrast causal associations of central adiposity (waist-to-hip ratio adjusted for body mass index [WHRadjBMI]) and general adiposity (body mass index [BMI]) with cardiometabolic disease. Ninety-seven independent single-nucleotide polymorphisms for BMI and 49 single-nucleotide polymorphisms for WHRadjBMI were used to conduct Mendelian randomization analyses in 14 prospective studies supplemented with coronary heart disease (CHD) data from CARDIoGRAMplusC4D (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics; combined total 66 842 cases), stroke from METASTROKE (12 389 ischemic stroke cases), type 2 diabetes mellitus from DIAGRAM (Diabetes Genetics Replication and Meta-analysis; 34 840 cases), and lipids from GLGC (Global Lipids Genetic Consortium; 213 500 participants) consortia. Primary outcomes were CHD, type 2 diabetes mellitus, and major stroke subtypes; secondary analyses included 18 cardiometabolic traits. Each one standard deviation (SD) higher WHRadjBMI (1 SD≈0.08 U) associated with a 48% excess risk of CHD (odds ratio [OR] for CHD, 1.48; 95% confidence interval [CI], 1.28-1.71), similar to findings for BMI (1 SD≈4.6 kg/m 2 ; OR for CHD, 1.36; 95% CI, 1.22-1.52). Only WHRadjBMI increased risk of ischemic stroke (OR, 1.32; 95% CI, 1.03-1.70). For type 2 diabetes mellitus, both measures had large effects: OR, 1.82 (95% CI, 1.38-2.42) and OR, 1.98 (95% CI, 1.41-2.78) per 1 SD higher WHRadjBMI and BMI, respectively. Both WHRadjBMI and BMI were associated with higher left ventricular hypertrophy, glycemic traits, interleukin 6, and circulating lipids. WHRadjBMI was also associated with higher carotid intima-media thickness (39%; 95% CI, 9%-77% per 1 SD). Both general and central adiposity have causal effects on CHD and type 2 diabetes mellitus. Central adiposity may have a stronger effect on stroke risk. Future estimates of the burden of adiposity on health should include measures of central and general adiposity. © 2017 American Heart Association, Inc.

Association of single Nucleotide Missence Polymorphism Val109Asp of Omentin-1 gene and coronary artery disease in Pakistani population: Multicenter study

PubMed Central

Nazar, Shazia; Zehra, Sitwat; Azhar, Abid

2017-01-01

Background & Objective: Coronary artery disease (CAD) is a most important cause of morbidity and mortality worldwide as well as in Pakistan. Recent studies have shown that the combination of obesity, insulin resistance and fluctuation in circulating adipocytokines levels is associated with the pathogenesis of coronary artery disease. Omentin-1 is recently found adipocytokine that is highly expressed in visceral adipose tissue. It has anti- inflammatory properties and is negatively correlated with ischemic heart disease. Therefore, this study was designed to investigate the relationship between omentin-1 Val109Asp polymorphism and CAD in Pakistani population. Methods: A total of 350 subjects were included in the study. Two hundred fifty were diagnosed with coronary artery disease while 100 served as healthy controls. PCR-RFLP was performed at Dr. A Q. Khan Institute of Biotechnology (KIBGE) to analyze Val109Asp polymorphism. In this, case control study SPSS software version 16 (Chicago, IL, USA) was used for data analysis. Continuous variables and categorical variables were presented as mean±SD or in percentage. Independent sample test and chi-square test was performed to compare the differences in means between cases and controls. Genotype distribution was analyzed by chi-square test and results were presented as percentage and frequency. Multivarible regression analysis indicated that Val109Asp SNP might be an independent risk factor for CAD susceptibility after adjustment for some well- known CAD risk factors including age, gender, body mass index, smoking, hypertension, diabetes mellitus and lipid abnormalities. There was estimation of odd ratios (OR) and 95% confidence intervals (CIs) to determine the correlation between genotypes and the risk of CAD. (p> 0.05). Genotype frequencies were compared by Chi-square test. Results: There was prevalence of Omentin-1 Val109Asp polymorphism in both case and control groups. However, Val/Asp (heterozygous mutant) genotype was detected more frequently in patients with CAD, OR(95%)=1.921; CI=1.173-3.1469 in comparison of Asp/Asp and Val/Val genotypes. Conclusion: Individuals having Val/Asp heterozygous gemotype of omentin-1 gene polymorphism are at more risk of developing CAD in Pakistani population, further studies are required in different populations and ethnicities to confirm our findings. PMID:29142551

microRNA expression profile in human coronary smooth muscle cell-derived microparticles is a source of biomarkers.

PubMed

de Gonzalo-Calvo, David; Cenarro, Ana; Civeira, Fernando; Llorente-Cortes, Vicenta

2016-01-01

microRNA (miRNA) expression profile of extracellular vesicles is a potential tool for clinical practice. Despite the key role of vascular smooth muscle cells (VSMC) in cardiovascular pathology, there is limited information about the presence of miRNAs in microparticles secreted by this cell type, including human coronary artery smooth muscle cells (HCASMC). Here, we tested whether HCASMC-derived microparticles contain miRNAs and the value of these miRNAs as biomarkers. HCASMC and explants from atherosclerotic or non-atherosclerotic areas were obtained from coronary arteries of patients undergoing heart transplant. Plasma samples were collected from: normocholesterolemic controls (N=12) and familial hypercholesterolemia (FH) patients (N=12). Both groups were strictly matched for age, sex and cardiovascular risk factors. Microparticle (0.1-1μm) isolation and characterization was performed using standard techniques. VSMC-enriched miRNAs expression (miR-21-5p, -143-3p, -145-5p, -221-3p and -222-3p) was analyzed using RT-qPCR. Total RNA isolated from HCASMC-derived microparticles contained small RNAs, including VSMC-enriched miRNAs. Exposition of HCASMC to pathophysiological conditions, such as hypercholesterolemia, induced a decrease in the expression level of miR-143-3p and miR-222-3p in microparticles, not in cells. Expression levels of miR-222-3p were lower in circulating microparticles from FH patients compared to normocholesterolemic controls. Microparticles derived from atherosclerotic plaque areas showed a decreased level of miR-143-3p and miR-222-3p compared to non-atherosclerotic areas. We demonstrated for the first time that microparticles secreted by HCASMC contain microRNAs. Hypercholesterolemia alters the microRNA profile of HCASMC-derived microparticles. The miRNA signature of HCASMC-derived microparticles is a source of cardiovascular biomarkers. Copyright © 2016 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

Minnesota Resuscitation Consortium's Advanced Perfusion and Reperfusion Cardiac Life Support Strategy for Out-of-Hospital Refractory Ventricular Fibrillation.

PubMed

Yannopoulos, Demetris; Bartos, Jason A; Martin, Cindy; Raveendran, Ganesh; Missov, Emil; Conterato, Marc; Frascone, R J; Trembley, Alexander; Sipprell, Kevin; John, Ranjit; George, Stephen; Carlson, Kathleen; Brunsvold, Melissa E; Garcia, Santiago; Aufderheide, Tom P

2016-06-13

In 2015, the Minnesota Resuscitation Consortium (MRC) implemented an advanced perfusion and reperfusion life support strategy designed to improve outcome for patients with out-of-hospital refractory ventricular fibrillation/ventricular tachycardia (VF/VT). We report the outcomes of the initial 3-month period of operations. Three emergency medical services systems serving the Minneapolis-St. Paul metro area participated in the protocol. Inclusion criteria included age 18 to 75 years, body habitus accommodating automated Lund University Cardiac Arrest System (LUCAS) cardiopulmonary resuscitation (CPR), and estimated transfer time from the scene to the cardiac catheterization laboratory of ≤30 minutes. Exclusion criteria included known terminal illness, Do Not Resuscitate/Do Not Intubate status, traumatic arrest, and significant bleeding. Refractory VF/VT arrest was defined as failure to achieve sustained return of spontaneous circulation after treatment with 3 direct current shocks and administration of 300 mg of intravenous/intraosseous amiodarone. Patients were transported to the University of Minnesota, where emergent advanced perfusion strategies (extracorporeal membrane oxygenation; ECMO), followed by coronary angiography and primary coronary intervention (PCI), were performed, when appropriate. Over the first 3 months of the protocol, 27 patients were transported with ongoing mechanical CPR. Of these, 18 patients met the inclusion and exclusion criteria. ECMO was placed in 83%. Seventy-eight percent of patients had significant coronary artery disease with a high degree of complexity and 67% received PCI. Seventy-eight percent of patients survived to hospital admission and 55% (10 of 18) survived to hospital discharge, with 50% (9 of 18) achieving good neurological function (cerebral performance categories 1 and 2). No significant ECMO-related complications were encountered. The MRC refractory VF/VT protocol is feasible and led to a high functionally favorable survival rate with few complications. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Anatomy of Atrioventricular Node Artery and Pattern of Dominancy in Normal Coronary Subject: A Comparison between Individuals with and without Isolated Right Bundle Branch Block

PubMed Central

Kazemisaeid, Ali; Pakbaz, Marziyeh; Yaminisharif, Ahmad; Davoodi, Gholamreza; Lotfi Tokaldany, Masoumeh; Hakki Kazazi, Elham

2012-01-01

Background: Isolated right bundle branch block (RBBB) is a common finding in the general population. The atrioventricular node (AVN) artery contributes to the blood supply of the right bundle branch. Our hypothesis was that the anatomy of the AVN artery and the pattern of dominancy differ between subjects with and without RBBB. Methods: We retrospectively studied the coronary angiography of 92 patients with RBBB and 184 age- and gender-matched controls without RBBB. All the subjects had angiographically proven normal coronary arteries. The dominant circulation and precise origin of the AVN artery were determined in each subject. Obtained data were compared between the two study groups. Results: There was no significant difference between the two groups in terms of dominancy (p value = 0.200). Origination of the AVN artery from the right circulatory system was more common in both groups, but this pattern was more prevalent in the cases than in the controls (p value = 0.021). There was a great variation of the AVN artery origin. In the total study population, the AVN artery was more commonly separated from a non crux origin than from the crux area. The prevalence of the non-crux origination of the AVN artery was significantly higher in the cases than in the controls (p value < 0.001). While the origination of the AVN artery from the right circulatory system was more common in both groups, the prevalence of the right origin of the AVN artery was significantly higher in the cases than in the controls. We observed that the AVN artery most commonly originated from the dominant artery but not necessarily from the crux. Conclusion: The anatomy of the AVN artery but not the pattern of dominancy is somewhat different in subjects with RBBB compared with normal individuals. PMID:23323077

Anatomy of Atrioventricular Node Artery and Pattern of Dominancy in Normal Coronary Subject: A Comparison between Individuals with and without Isolated Right Bundle Branch Block.

PubMed

Kazemisaeid, Ali; Pakbaz, Marziyeh; Yaminisharif, Ahmad; Davoodi, Gholamreza; Lotfi Tokaldany, Masoumeh; Hakki Kazazi, Elham

2012-11-01

Isolated right bundle branch block (RBBB) is a common finding in the general population. The atrioventricular node (AVN) artery contributes to the blood supply of the right bundle branch. Our hypothesis was that the anatomy of the AVN artery and the pattern of dominancy differ between subjects with and without RBBB. We retrospectively studied the coronary angiography of 92 patients with RBBB and 184 age- and gender-matched controls without RBBB. All the subjects had angiographically proven normal coronary arteries. The dominant circulation and precise origin of the AVN artery were determined in each subject. Obtained data were compared between the two study groups. There was no significant difference between the two groups in terms of dominancy (p value = 0.200). Origination of the AVN artery from the right circulatory system was more common in both groups, but this pattern was more prevalent in the cases than in the controls (p value = 0.021). There was a great variation of the AVN artery origin. In the total study population, the AVN artery was more commonly separated from a non crux origin than from the crux area. The prevalence of the non-crux origination of the AVN artery was significantly higher in the cases than in the controls (p value < 0.001). While the origination of the AVN artery from the right circulatory system was more common in both groups, the prevalence of the right origin of the AVN artery was significantly higher in the cases than in the controls. We observed that the AVN artery most commonly originated from the dominant artery but not necessarily from the crux. The anatomy of the AVN artery but not the pattern of dominancy is somewhat different in subjects with RBBB compared with normal individuals.

Epigenetic Patterns in Blood Associated With Lipid Traits Predict Incident Coronary Heart Disease Events and Are Enriched for Results From Genome-Wide Association Studies.

PubMed

Hedman, Åsa K; Mendelson, Michael M; Marioni, Riccardo E; Gustafsson, Stefan; Joehanes, Roby; Irvin, Marguerite R; Zhi, Degui; Sandling, Johanna K; Yao, Chen; Liu, Chunyu; Liang, Liming; Huan, Tianxiao; McRae, Allan F; Demissie, Serkalem; Shah, Sonia; Starr, John M; Cupples, L Adrienne; Deloukas, Panos; Spector, Timothy D; Sundström, Johan; Krauss, Ronald M; Arnett, Donna K; Deary, Ian J; Lind, Lars; Levy, Daniel; Ingelsson, Erik

2017-01-01

Genome-wide association studies have identified loci influencing circulating lipid concentrations in humans; further information on novel contributing genes, pathways, and biology may be gained through studies of epigenetic modifications. To identify epigenetic changes associated with lipid concentrations, we assayed genome-wide DNA methylation at cytosine-guanine dinucleotides (CpGs) in whole blood from 2306 individuals from 2 population-based cohorts, with replication of findings in 2025 additional individuals. We identified 193 CpGs associated with lipid levels in the discovery stage ( P <1.08E-07) and replicated 33 (at Bonferroni-corrected P <0.05), including 25 novel CpGs not previously associated with lipids. Genes at lipid-associated CpGs were enriched in lipid and amino acid metabolism processes. A differentially methylated locus associated with triglycerides and high-density lipoprotein cholesterol (HDL-C; cg27243685; P =8.1E-26 and 9.3E-19) was associated with cis -expression of a reverse cholesterol transporter ( ABCG1; P =7.2E-28) and incident cardiovascular disease events (hazard ratio per SD increment, 1.38; 95% confidence interval, 1.15-1.66; P =0.0007). We found significant cis -methylation quantitative trait loci at 64% of the 193 CpGs with an enrichment of signals from genome-wide association studies of lipid levels ( P TC =0.004, P HDL-C =0.008 and P triglycerides =0.00003) and coronary heart disease ( P =0.0007). For example, genome-wide significant variants associated with low-density lipoprotein cholesterol and coronary heart disease at APOB were cis -methylation quantitative trait loci for a low-density lipoprotein cholesterol-related differentially methylated locus. We report novel associations of DNA methylation with lipid levels, describe epigenetic mechanisms related to previous genome-wide association studies discoveries, and provide evidence implicating epigenetic regulation of reverse cholesterol transport in blood in relation to occurrence of cardiovascular disease events. © 2017 The Authors.

The Effects of On-Pump and Off-Pump Coronary Artery Bypass Surgery on Respiratory Function in the Early Postoperative Period.

PubMed

Chiarenza, Federica; Tsoutsouras, Theodoros; Cassisi, Cesare; Santonocito, Cristina; Gerry, Stephen; Astuto, Marinella; George, Shane; Sanfilippo, Filippo

2017-01-01

Respiratory complications are common after cardiac surgery and the use of extracorporeal circulation is one of the main causes of lung injury. We hypothesized a better postoperative respiratory function in off-pump coronary artery bypass grafting (OPCABG) as compared with "on-pump coronary artery bypass grafting" (ONCABG). This is a retrospective, single-center study at a cardiothoracic intensive care unit (ICU) in a tertiary university hospital. Consecutive data on 339 patients undergoing elective CABG (n = 215 ONCABG, n = 124 OPCABG) were collected for 1 year from the ICU electronic medical records. We compared respiratory variables (Pao 2 , Pao 2 /Fio 2 ratio, Sao 2 , and Paco 2 ) at 7 predefined time points (ICU admission, postoperative hours 1, 3, 6, 12, 18, and 24). We also evaluated time to extubation, rates of reintubation, and use of noninvasive ventilation (NIV). We used mixed-effects linear regression models (with time as random effect for clustering of repeated measures) adjusted for a predetermined set of covariates. The values of Pao 2 and Pao 2 /Fio 2 were significantly higher in the OPCABG group only at ICU admission (mean differences: 9.7 mm Hg, 95% confidence interval [CI] 3.1-16.2; and 27, 95% CI 6.1-47.7, respectively). The OPCABG group showed higher Paco 2 , overall ( P = .02) and at ICU admission (mean difference 1.8 mm Hg, 95% CI: 0.6-3), although mean values were always within normal range in both groups. No differences were seen in Sao 2 values, time to extubation, rate of reintubation rate, and use of postoperative NIV. Extubation rate was higher in OPCABG only at postoperative hour 12 (92% vs ONCABG 82%, P = .02). The OPCABG showed only marginal improvements of unlikely clinical meaning in oxygenation as compared to ONCABG in elective low-risk patients.

Editor's Choice-Is the pre-hospital ECG after out-of-hospital cardiac arrest accurate for the diagnosis of ST-elevation myocardial infarction?

PubMed

Salam, Idrees; Hassager, Christian; Thomsen, Jakob Hartvig; Langkjær, Sandra; Søholm, Helle; Bro-Jeppesen, John; Bang, Lia; Holmvang, Lene; Erlinge, David; Wanscher, Michael; Lippert, Freddy K; Køber, Lars; Kjaergaard, Jesper

2016-08-01

Current guidelines recommend that comatose out-of-hospital cardiac arrest patients with ST-segment elevations (STEs) following return of spontaneous circulation (ROSC) should be referred for an acute coronary angiography. We sought to investigate the diagnostic value of the pre-hospital ROSC-ECG in predicting ST-elevation myocardial infarction (STEMI). ROSC-ECGs of 145 comatose survivors of out-of-hospital cardiac arrest, randomly assigned in the Target Temperature Management trial, were classified according to the current STEMI ECG criteria (third universal definition of myocardial infarction). STEs were present in the pre-hospital ROSC-ECG of 78 (54%) patients. A final diagnosis revealed that 69 (48%) patients had STEMI, 31 (21%) patients had non-STEMI and 45 (31%) patients had no myocardial infarction. STE in ROSC-ECGs had a sensitivity of 74% (95% confidence interval (CI) 62-84), specificity of 65% (95% CI 53-75) and a positive and negative predictive value of 65% (95% CI 54-76) and 73% (95% CI 61-83) in predicting STEMI. Time to ROSC was significantly longer (24 minutes vs. 19 minutes, P=0.02) in STE compared with no STE patients. Percutaneous coronary intervention was successful in 68% versus 36% (P<0.001) of STE compared to no STE patients. No significant difference was found in 180-day mortality rates between STE and no STE patients (36% vs. 30%, Plogrank=0.37). The pre-hospital ROSC-ECG is a suboptimal diagnostic tool to predict STEMI and therefore not a sensitive tool for triage to cardiac centres. This supports the incentive of referring all comatose survivors of out-of-hospital cardiac arrest of suspected cardiac origin to a tertiary heart centre with the availability of acute coronary angiography, even in the absence of STEs. © The European Society of Cardiology 2015.

Caffeine reduces dipyridamole-induced myocardial ischemia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smits, P.; Aengevaeren, W.R.; Corstens, F.H.

1989-10-01

The mechanism of action of coronary vasodilation after dipyridamole may be based on inhibition of cellular uptake of circulating endogenous adenosine. Since caffeine has been reported to be a competitive antagonist of adenosine we studied the effect of caffeine on the outcome of dipiridamole-{sup 201}Tl cardiac imaging in one patient. During caffeine abstinence dipyridamole induced myocardial ischemia with down-slope ST depressions on the ECG, and reversible perfusion defects on the scintigrams. When the test was repeated 1 wk later on similar conditions, but now shortly after infusion of caffeine (4 mg/kg), the ECG showed nodepressions, and the scintigrams only slightmore » signs of ischemia. We conclude that when caffeine abstinence is not sufficient, the widespread use of coffee and related products may be responsible for false-negative findings in dipyridamole-201Tl cardiac imaging.« less

[Metalloproteases, vascular remodeling and atherothrombotic syndromes].

PubMed

Rodríguez, José A; Orbe, Josune; Páramo, José A

2007-09-01

Defects in the synthesis and breakdown of the extracellular matrix (ECM) are now seen as key processes in the development of atherosclerosis and its thrombotic complications. Correlations have been observed between circulating levels of ECM biomarkers and the clinical manifestations of and risk factors for atherosclerosis. Several matrix metalloproteinases (MMPs), endopeptidases that can degrade the ECM, such as MMP-9 and MMP-10, play important roles in the pathophysiology of atherothrombosis and contribute to the expansion of abdominal aortic aneurysms. Moreover, they may also be useful biomarkers of atherosclerotic risk and serve as predictors of coronary and cerebrovascular disease recurrence. Although at present the effect of tissue inhibitors of MMPs (TIMPs) on cardiovascular disease prognosis is still uncertain, the ECM could be a promising therapeutic target in atherothrombotic disease, and several MMP inhibitors are currently undergoing clinical trials.

An Overview of FGF19 and FGF21: The Therapeutic Role in the Treatment of the Metabolic Disorders and Obesity.

PubMed

Babaknejad, Nasim; Nayeri, Hashem; Hemmati, Roohullah; Bahrami, Somaye; Esmaillzadeh, Ahmad

2018-06-01

Fibroblast growth factors (FGFs) are responsible for the regulation of a wide range of biological functions, among which cellular proliferation, survival, migration, and differentiation could be pointed out. FGF19 controls the enterohepatic bile acid/cholesterol system, and FGF21 modulates fatty acid/glucose metabolism. Obesity, type 2 diabetes, coronary artery disease, and cancer, all can alter FGF21 circulating concentrations. In contrast to FGF21, metabolic diseases exhibit reduced serum FGF19 levels. Accordingly, FGF19 and FGF21 play important roles in regulating glucose and lipid metabolism. Hence, we present here a timely review on the relationship between FGF19/21 and metabolic diseases, especially obesity, and their probable role in development and treatment of obesity seems necessary. © Georg Thieme Verlag KG Stuttgart · New York.

[Selected pages of history of vascular surgery in Russia (contribution of Russian surgeons to world vascular surgery)].

PubMed

Pokrovskiĭ, A V; Gliantsev, S P

2014-01-01

The article describes the most significant for Russian surgery personalities, facts, and events of the last 180years. An emphasis is placed upon those works, discoveries or operations made by Russians for the first timein the world's practice. To such we refer N.J. Pirogov's topographical anatomy of vessels (1837), N. V. Ekk's portocaval anastomosis (1877), A.A. Yanovsky's lateral arterial suture (1889), S.S. Bryukhonenko's artificial circulation unit (1923-1924), Yu. Yu. Voronoy's renal replantation onto femoral vessels (1933), V.P. Demikhov'stransplantation of vital organs (1946-1959), V.I. Kolesov's mammary-coronary anastomosis (1964),F.A. Serbinenko's endovascular neurosurgery ( 1979), E. I. Chasov's intracoronary thrombolysis by E.I. Chazov( 1974), endovascular prosthetic repair of the thoracic aorta by N.L. Volodos ( 1985) and a series of other facts.

Coronary vasodilation by the use of sublingual nitroglycerin using 64-slice dual-source coronary computed tomography angiography.

PubMed

Okada, Munemasa; Nakashima, Yoshiteru; Nomura, Takafumi; Miura, Toshiro; Nao, Tomoko; Yoshimura, Masayuki; Sano, Yuichi; Matsunaga, Naofumi

2015-03-01

Sublingual nitroglycerin capsules or spray is routinely used to treat anginal attacks and to maximally dilate the epicardial coronary arteries during coronary angiography. These dilated coronary vessels have an advantage, but increased heart rates were disadvantageous for coronary computed tomography angiography (CTA). The influence of applying nitroglycerin was analyzed regarding the coronary diameter, coronary luminal attenuation, evaluable number of coronary segments, heart rate (HR), HR variability, the optimal reconstruction phase, and image scoring of CTA in the same patients using a 64-slice dual-source CT. Fifty-two patients with atypical chest pain underwent coronary CTA before and after the administration of sublingual nitroglycerin without heart rate control. The coronary diameter and luminal attenuation were measured on short-axial images in each coronary segment. The coronary vasodilation ratios (VRs) were calculated from the coronary diameters at the same location before and after the use of nitroglycerin. The local institutional review board approved this study and written informed consent was obtained from all the patients. No significant differences were noted in the HR variability or optimal reconstruction phase, despite an increase in HR after the use of nitroglycerin. Nitroglycerin significantly enlarged the coronary artery diameter, and VRs of each coronary segment ranged from 7.54% to 22.26%. As compared with baseline coronary diameter, VRs of minor segments (16.91%) were significantly larger than those of major segments (11.35%), and the magnitude of VR correlated with the baseline coronary diameter (r=-0.48, p<0.001). Coronary luminal attenuation significantly increased due to additional administration of contrast material after the use of nitroglycerin (p<0.01), but no significant difference was noted in the image quality after the use of nitroglycerin. Sublingual nitroglycerin significantly enlarged the coronary diameters, especially in peripheral small coronary arteries, and increased the evaluable number of coronary segments on coronary CTA. Copyright © 2014 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Coronary responses to endothelin-1 and acetylcholine during partial coronary ischaemia and reperfusion in anaesthetized goats.

PubMed

Martínez, Maria Angeles; Fernández, Nuria; Monge, Luis; García-Villalón, Angel Luis; Sanz, Elena; Diéguez, Godofredo

2002-08-01

To examine coronary reactivity to acetylcholine and endothelin-1 (ET-1) during partial ischaemia and reperfusion, flow in the left circumflex coronary artery was measured electromagnetically, and coronary partial ischaemia was induced by stenosis of this artery in anaesthetized goats. In eight animals not treated with N(G)-nitro-l-arginine methyl ester (l-NAME), coronary stenosis reduced coronary flow by 45%, mean arterial pressure by 16% and coronary vascular conductance by 34%. During this ischaemia, coronary vasodilatation to acetylcholine (0.003-0.1 microg) and sodium nitroprusside (SNP; 1-10 microg) was markedly reduced, and coronary vasoconstriction to ET-1 (0.01-0.3 nmol) was attenuated. After 30 min of reperfusion, coronary flow, mean arterial pressure and coronary vascular conductance remained decreased, and the effects of acetylcholine, SNP and ET-1 were as in control animals. In six goats treated with N(G)-nitro-l-arginine methyl ester, coronary stenosis reduced coronary flow by 26% and coronary vascular conductance by 24%, but did not affect mean arterial pressure. During this ischaemia, coronary vasodilatation to acetylcholine and SNP was also markedly reduced, but vasoconstriction to ET-1 was unaffected. After 30 min of reperfusion, coronary flow and coronary vascular conductance remained decreased and mean arterial pressure was normal; in addition, the effects of acetylcholine were lower, those of SNP were similar and those of ET-1 were higher than in control animals. Therefore partial ischaemia reduces the coronary vasodilator reserve and blunts coronary vasoconstriction to ET-1, and reperfusion does not alter the endothelium-dependent and -independent coronary vasodilatation or vasoconstriction to ET-1.

Coronary Artery Anomalies in Animals

PubMed Central

Scansen, Brian A.

2017-01-01

Coronary artery anomalies represent a disease spectrum from incidental to life-threatening. Anomalies of coronary artery origin and course are well-recognized in human medicine, but have received limited attention in veterinary medicine. Coronary artery anomalies are best described in the dog, hamster, and cow though reports also exist in the horse and pig. The most well-known anomaly in veterinary medicine is anomalous coronary artery origin with a prepulmonary course in dogs, which limits treatment of pulmonary valve stenosis. A categorization scheme for coronary artery anomalies in animals is suggested, dividing these anomalies into those of major or minor clinical significance. A review of coronary artery development, anatomy, and reported anomalies in domesticated species is provided and four novel canine examples of anomalous coronary artery origin are described: an English bulldog with single left coronary ostium and a retroaortic right coronary artery; an English bulldog with single right coronary ostium and transseptal left coronary artery; an English bulldog with single right coronary ostium and absent left coronary artery with a prepulmonary paraconal interventricular branch and an interarterial circumflex branch; and a mixed-breed dog with tetralogy of Fallot and anomalous origin of all coronary branches from the brachiocephalic trunk. Coronary arterial fistulae are also described including a coronary cameral fistula in a llama cria and an English bulldog with coronary artery aneurysm and anomalous shunting vessels from the right coronary artery to the pulmonary trunk. These examples are provided with the intent to raise awareness and improve understanding of such defects. PMID:29056679

Emergency coronary artery bypass grafting using minimized versus standard extracorporeal circulation – a propensity score analysis

PubMed Central

2013-01-01

Background The impact of minimized extracorporeal circulation (MECC) for emergency revascularization remains controversial. Methods A total of 348 patients underwent emergency CABG with MECC (n=146) or conventional extracorporeal circulation (CECC; n=175) between January 2005 and December 2010. Using propensity score matching after binary logistic regression, 100 patients, who underwent CABG with MECC could be matched with 100 patients, who underwent CABG with CECC. Primary outcome was 30-day mortality. Results Unadjusted 30-day mortality was 14.8% in patients with CECC and 6.9% in those with MECC (mean difference −7.9%; p=0.03). The adjusted mean difference (average treatment effect of the treated, ATT) after matching was −1.0% (95% CI −8.6 to 7.6; p=1.0). Intensive care unit stay (adjusted mean difference 1.0; 95% CI −0.2 to 3.2; p=0.70) and hospital stay (adjusted mean difference 1.0; 95% CI −2.0 to 3.6; p=0.40) did not show significant differences between both groups. The adjusted mean difference for postoperative low cardiac output syndrome was −1.1% (95% CI −7.3 to 7.1; p=0.83) without significant differences between CECC and MECC. Postoperative mechanical ventilation time, drain loss, postoperative rethoracotomy, postoperative neurological events, new onset renal replacement therapy and respiratory failure also had insignificant average treatment effects of the treated. In addition, all average treatment effects (ATEs) did not significantly differ between both groups. Conclusion Using propensity score estimation and matching, we did not observe significant differences in terms of survival and further outcomes in patients who undergo emergency CABG with CECC or MECC, but our results call for further analysis. PMID:23547910

Circulating SIRT1 inversely correlates with epicardial fat thickness in patients with obesity.

PubMed

Mariani, S; Costantini, D; Lubrano, C; Basciani, S; Caldaroni, C; Barbaro, G; Poggiogalle, E; Donini, L M; Lenzi, A; Gnessi, L

2016-11-01

Obesity is increasing worldwide and is related to undesirable cardiovascular outcomes. Epicardial fat (EF), the heart visceral fat depot, increases with obesity and correlates with cardiovascular risk. SIRT1, an enzyme regulating metabolic circuits linked with obesity, has a cardioprotective effect and is a predictor of cardiovascular events. We aimed to assess the relationship of EF thickness (EFT) with circulating SIRT1 in patients with obesity. Sixty-two patients affected by obesity and 23 lean controls were studied. Plasma SIRT1 concentration was determined by enzyme-linked immunosorbent assay (ELISA). EFT was measured by echocardiography. Body mass index (BMI), waist circumference, heart rate (HR), blood pressure, and laboratory findings (fasting glucose, insulin, HbA1c, cholesterol, and triglycerides) were assessed. SIRT1 was significantly lower (P = 0.002) and EFT was higher (P < 0.0001) in patients with obesity compared with lean controls. SIRT1 showed a negative correlation with EFT and HR in the obesity group (ρ = -0.350, P = 0.005; ρ = -0.303, P = 0.008, respectively). After adjustment for obesity-correlated variables, multiple linear regression analysis showed that EFT remained the best correlate of SIRT1 (β = -0.352, P = 0.016). Circulating SIRT1 correlates with the visceral fat content of the heart. Serum SIRT1 levels might provide additional information for risk assessment of coronary artery disease in patients with obesity. Copyright © 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Plasma circulating fibrinogen stability and moderate beer consumption.

PubMed

Gorinstein, Shela; Caspi, Abraham; Zemser, Marina; Libman, Imanuel; Goshev, Ivan; Trakhtenberg, Simon

2003-12-01

MODERATE BEER CONSUMPTION (MBC) IS CARDIOPROTECTIVE: it positively influences plasma lipid levels and plasma antioxidant activity in beer-consuming individuals. The connection between MBC and blood coagulation is not clearly defined. Forty-two volunteers were equally divided into experimental (EG) and control (CG) groups following coronary bypass surgery. For 30 consecutive days, only patients of the EG consumed 330 mL of beer per day (about 20 g of alcohol). A comprehensive clinical investigation of 42 patients was done. Blood samples were collected before and after the investigation for a wide range of laboratory tests. The plasma fibrinogen was denatured with 8 M urea and intrinsic fluorescence (IF), hydrophobicity and differential scanning calorimetry (DSC) were used to reveal possible qualitative changes. After 30 days of moderate beer consumption, positive changes in the plasma lipid levels, plasma anticoagulant and plasma antioxidant activities were registered in patients of the EG group. In 17 out of 21 patients of the same group, differences in plasma circulating fibrinogen's (PCF), secondary and tertiary structures were found. The stability of fibrinogen, expressed in thermodynamic parameters, has shown that the loosening of the structure takes place under ethanol and urea denaturation. Also fluorescence stability of PCF was decreased. No changes in the lipid levels, anticoagulant and antioxidant activity or changes in PCF were detected in patients of CG. In conclusion, for the first time after a short term of moderate beer consumption some qualitative changes in the plasma circulating fibrinogen were detected: differences in the emission peak response, fluorescence intensity and all thermodynamic data. Together, with the decrease in the PCF concentration it may lead to an elevation of the blood anticoagulant activity.

Vaspin plasma concentrations and mRNA expressions in patients with stable and unstable angina pectoris.

PubMed

Li, Hai Ling; Peng, Wen Hui; Cui, Shi Tao; Lei, Hou; Wei, Yi Dong; Li, Wei Ming; Xu, Ya Wei

2011-09-01

Vaspin was a recently identified adipokine, playing a protective role in many metabolic diseases. The present study aimed to investigate the association between vaspin plasma level and stable angina pectoris (SAP) and unstable angina pectoris (UAP). A total of 88 patients with angiographically-proved coronary artery disease (CAD) (SAP 47, UAP 41) and 103 control subjects without cardiovascular diseases were enrolled in this study. Circulating vaspin, mRNA expression of vaspin in peripheral blood mononuclear cells (PBMC), clinical parameters, lipid profile and high-sensitivity C-reactive protein (hsCRP) were assayed. The severity of CAD was also assessed according to the number of vessels diseased. There are significant differences in circulating vaspin levels and mRNA levels of PBMC between SAP and UAP groups (SAP 0.91±0.95 ng/mL and UAP 0.43±0.38 ng/mL, p<0.01 in circulating vaspin level; SAP 1.19±0.85 and UAP 0.82±0.56, p<0.05 in mRNA level of PBMC). An inverse correlation between the number of diseased vessels and plasma vaspin concentration was observed (r=-0.350, p<0.01) in the CAD group. Construction of receiver operating characteristic curves confirmed that vaspin plasma concentrations significantly differentiated CAD patients (area under the curve=0.684, p<0.001), as well as UAP (area under the curve=0.640, p<0.05). Decreased vaspin plasma levels and mRNA levels in PBMC were observed in patients with UAP. Low vaspin concentrations correlate with CAD severity. The findings suggested that vaspin could serve as a novel biomarker of CAD as well as UAP.

PCSK9 inhibition: the dawn of a new age in cholesterol lowering?

PubMed

Preiss, David; Mafham, Marion

2017-03-01

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a circulating enzyme of hepatic origin that plays a key role in LDL receptor turnover. Genetic studies have confirmed that individuals with gain-of-function PCSK9 mutations have increased PCSK9 activity, elevated LDL-cholesterol levels and a severe form of familial hypercholesterolaemia. Those with variants leading to reduced PCSK9 have lower LDL-cholesterol levels and a reduced risk of coronary heart disease, and this has led to the development of various strategies aimed at reducing circulating PCSK9. Monoclonal antibodies to PCSK9, given every 2-4 weeks by subcutaneous injection, have been shown to reduce LDL-cholesterol by 50-60% compared with placebo in individuals with and without diabetes. PCSK9 inhibition also reduces lipoprotein(a), an atherogenic lipid particle, by around 20-30%. Major cardiovascular outcome trials for two agents, evolocumab and alirocumab, are expected to report from 2017. These trials involve over 45,000 participants and are likely to include about 15,000 individuals with diabetes. PCSK9-binding adnectins have been employed as an alternative method of removing circulating PCSK9. Small interfering RNA targeting messenger RNA for PCSK9, which acts by reducing hepatic production of PCSK9, is also under investigation. These agents may only need to be given by subcutaneous injection once every 4-6 months. Ongoing trials will determine whether anti-PCSK9 antibody therapy safely reduces cardiovascular risk, although high cost may limit its use. Development of PCSK9-lowering technologies cheaper than monoclonal antibodies will be necessary for large numbers of individuals to benefit from this approach to lowering cholesterol.

Association of socioeconomic stratification with plasmatic markers of lipoperoxidation and antioxidants in Venezuelan school-age children

PubMed Central

Bosch, Virgilio; Giacopini, Maria Isabel

2016-01-01

Abstract Objetive: To establish association between socioeconomic status and plasmatic markers of lipoperoxidation and antioxidants in Venezuelan school-age children from the middle-class and in critical poverty. Methods: Cross-sectional study with a sample of 114 school-age children (aged 7-9). The socioeconomic status, dietary intake of macro and micro-nutrients, weight, height, lipid profile, indicators of lipid peroxidation and enzymatic and non-enzymatic antioxidants were determined. Results: The daily average intake of energy, carbohydrates and vitamin A, and the percentage of energy obtained from carbohydrates was significantly higher in middle-class children compared to critical poverty children (p <0.05). The circulating oxidized low density lipoprotein (p <0.001) and the susceptibility of low density lipoproteins and very low density lipoproteins to oxidation in vitro (p <0.05) were significantly higher in middle-class children, while the critical poverty children showed significantly lower levels of Vitamin C and E in plasma (p <0.05). Non-enzymatic antioxidant levels were frequently deficient in both strata. The concentrations of circulating oxidized low density lipoprotein (OR: 1.09, CI 95%: 1.016-1.179; p= 0.017) and Vitamin C (OR: 3.21, CI 95%: 1.104-9.938; p= 0.032) were associated to the socioeconomic status independently of gender, family history of premature coronary artery disease, triglicerides, Vitamin C and E dietary intake and count of white blood cells. Conclusion: The socioeconomic status was associated to circulating oxidized low density lipoprotein and Vitamin C in Venezuelan school-age children, The results suggested the need to improve the dietary intake of antioxidants in both studied socioeconomic groups. PMID:28293041

[THE INFLUENCE OF MONO- AND MULTIVASCULAR LESIONS OF CORONARY ARTERIES ON THE COURSE OF CORONARY HEART DISEASE IN PATIENTS WITH DIABETES MELLITUS TYPE 2].

PubMed

Sypalo, A; Kravchun, P; Kadykova, O

2017-03-01

The article assesses the influence of mono- and multivascular lesions of coronary arteries on the course of coronary heart disease at patients with diabetes mellitus type 2. For this purpose, a comprehensive survey of 75 patients with coronary heart disease and diabetes mellitus type 2 was arranged. Depending on the number of vascular lesions of the coronary arteries, according to the data of coronary arteries computer tomography, all patients were divided into two subgroups. The first subgroup included 27 patients with coronary heart disease and diabetes mellitus type 2 with monovascular lesions of coronary arteries. To the second subgroup were included 48 patients with coronary heart disease and diabetes mellitus type 2 with multivascular lesions of coronary arteries. During the analysis of carbohydrate metabolism in cases of coronary heart disease and diabetes mellitus type 2 the HOMA index increase by 25.40% and insulin level increase by 17.05% were revealed at patients with multivascular lesions of coronary arteries in comparison with patients with monovascular lesions of coronary arteries, respectively. The combination of coronary heart disease and diabetes mellitus type 2 with multivascular lesions of coronary arteries was associated with an increase of sortilin level (233,47±47,85 ng/l). A significant increase in triglycerides, lipoprotein cholesterol of very low density influences greatly on the progression of coronary atherosclerosis with lesions of greater number of coronary arteries at patients surveyed. At patients with coronary heart disease and diabetes mellitus type 2 with multivascular lesions of coronary arteries the left ventricle myocardial re-modeling occurred through the increase of left ventricle's size and cavity.

Angioplasty and stent placement - heart

MedlinePlus

PCI; Percutaneous coronary intervention; Balloon angioplasty; Coronary angioplasty; Coronary artery angioplasty; Percutaneous transluminal coronary angioplasty; Heart artery dilatation; Angina - stent placement; Acute coronary ...

Coronary microvascular dysfunction equivalent to left main coronary artery disease.

PubMed

Panç, Cafer; Kocaağa, Mehmet; Erdoğan, Onur; Sarıkaya, Remzi; Umman, Sabahattin

2017-04-01

Coronary microvascular dysfunction, also known as cardiac syndrome X, is a clinical syndrome presenting with typical angina and evidence of myocardial ischemia in the absence of flow-limiting stenosis on coronary angiography. Of patients undergoing coronary angiography due to suspected myocardial ischemia, 50% are found to have normal or near-normal coronary arteries. Described in this case report is a patient who developed hypotension and ST segment depressions during treadmill exercise test. Left main coronary artery or multivessel disease was suspected. Coronary angiography was normal, but coronary flow reserve measurement revealed severe microvascular dysfunction.

Narrowing the gap: early and intermediate outcomes after percutaneous coronary intervention and coronary artery bypass graft procedures in California, 1997 to 2006.

PubMed

Carey, Joseph S; Danielsen, Beate; Milliken, Jeffrey; Li, Zhongmin; Stabile, Bruce E

2009-11-01

Percutaneous coronary intervention is increasingly used to treat multivessel coronary artery disease. Coronary artery bypass graft procedures have decreased, and as a result, percutaneous coronary intervention has increased. The overall impact of this treatment shift is uncertain. We examined the in-hospital mortality and complication rates for these procedures in California using a combined risk model. The confidential dataset of the Office of Statewide Health Planning and Development patient discharge database was queried for 1997 to 2006. A risk model was developed using International Classification of Diseases, Ninth Revision, Clinical Modification procedures and diagnostic codes from the combined pool of isolated coronary artery bypass graft and percutaneous coronary intervention procedures performed during 2005 and 2006. In-hospital mortality was corrected for "same-day" transfers to another health care institution. Early failure rate was defined as in-hospital mortality rate plus reintervention for another percutaneous coronary intervention or cardiac surgery procedure within 90 days. Coronary artery bypass graft volume decreased from 28,495 (1997) to 15,520 (2006), whereas percutaneous coronary intervention volume increased from 38,098 to 53,703. Risk-adjusted mortality rate decreased from 4.7% to 2.1% for coronary artery bypass graft procedures and from 3.4% to 1.9% for percutaneous coronary intervention. Expected mortality rate increased for both procedures. Early failure rate decreased from 13.1% to 8.0% for percutaneous coronary intervention and from 6.5% to 5.4% for coronary artery bypass graft. For the years 2004 and 2005, the risk of recurrent myocardial infarction or need for coronary artery bypass graft during the first postoperative year was 12% for percutaneous coronary intervention and 6% for coronary artery bypass grafts. This study shows that as volume shifted from coronary artery bypass grafts to percutaneous coronary intervention, expected mortality increased for both procedures. Risk-adjusted mortality rate decreased for both procedures, more so for coronary artery bypass grafts, so that corrected in-hospital mortality rates essentially equalized at approximately 2.0% in 2006. The post-procedural risk of reintervention, death, or myocardial infarction within the first year was twice as high for percutaneous coronary intervention as for coronary artery bypass grafts.

Coronary artery dimensions: Iranian population versus Indo-Asians and Caucasians.

PubMed

Ghaffari, Samad; Mehdizadeh-Lame, Mohammad-Bagher; Sepehrvand, Nariman; Aslanabadi, Naser; Sohrabi, Bahram; Separham, Ahmad; Jamshidi, Peiman

2015-10-01

The dimensions of the coronary arteries have been shown to vary among ethnic groups. There are no data available regarding the normal size of coronary arteries in Iranians. This study aimed to investigate normal coronary artery dimensions in a Northwestern Iranian population and to compare it with pooled data of Indo-Asians and Caucasians in previous studies. The study included 200 adults with suspected coronary disease who were referred for elective coronary angiography between June 2012 and March 2013 and were found to have normal epicardial flow in the coronary arteries. Quantitative coronary angiography was carried out on the longest atheroma-free part of the proximal segment of each coronary artery in all patients. Two Indo-Asian and Caucasian groups were selected and pooled for comparison with the available reports on individuals without coronary artery disease. The mean diameters of the left main coronary artery, proximal left anterior descending artery, proximal left circumflex, and proximal right coronary artery were 4.58 ± 0.80, 3.69 ± 0.64, 3.37 ± 0.73, and 3.47 ± 0.68 mm, respectively. The dimensions of the proximal part of the left main coronary artery and right coronary artery were significantly greater in the Northwestern Iranian population compared to the pooled Caucasian group. This difference was maintained even after correction for body surface area. Our data indicate larger coronary diameters in the Iranian population compared to Caucasians or South-Asians. Hence the high prevalence of coronary artery disease in Iran cannot be explained by coronary dimensions. © The Author(s) 2015.

The Genetic Architecture of Coronary Artery Disease: Current Knowledge and Future Opportunities

PubMed Central

Hartiala, Jaana; Schwartzman, William S.; Gabbay, Julian; Ghazalpour, Anatole; Bennett, Brian J.; Allayee, Hooman

2018-01-01

Purpose of review We provide an overview of our current understanding of the genetic architecture of coronary artery disease (CAD)and discuss areas of research that provide excellent opportunities for further exploration. Recent findings Large-scale studies in human populations, coupled with rapid advances in genetic technologies over the last decade, have clearly established the association of common genetic variation with risk of CAD. However, the effect sizes of the susceptibility alleles are for the most part modest and collectively explain only a small fraction of the overall heritability. By comparison, evidence that rare variants make a substantial contribution to risk of CAD has been somewhat disappointing thus far, suggesting that other biological mechanisms have yet to be discovered. Emerging data suggests that novel pathways involved in the development of CAD can be identified through complementary and integrative systems genetics strategies in mice or humans. There is also convincing evidence that gut bacteria play a previously unrecognized role in the development of CAD, particularly through metabolism of certain dietary nutrients that lead to proatherogenic metabolites in the circulation. Summary A major effort is now underway to functionally understand the newly discovered genetic and biological associations for CAD, which could lead to the development of potentially novel therapeutic strategies. Other important areas of investigation for understanding the pathophysiology of CAD, including epistatic interactions between genes or with either sex and environmental factors, have not been studied on a broad scope and represent additional opportunities for future studies. PMID:28130654

Increased levels of markers of vascular inflammation in patients with coronary heart disease.

PubMed

Schumacher, A; Seljeflot, I; Sommervoll, L; Christensen, B; Otterstad, J E; Arnesen, H

2002-01-01

Elevated levels of soluble cell adhesion molecules (sCAMs), inflammatory cytokines and C-reactive protein (CRP) have been associated with atherosclerotic disease states. The aim of the present study was to evaluate whether circulating levels of vascular cell adhesion molecule-1 (sVCAM-1), intercellular adhesion molecule-1 (sICAM-1), E- and P-selectin were significantly elevated in patients with coronary heart disease (CHD) compared with healthy controls, and to study possible associations between these sCAMs, tumour necrosis factor alpha (TNFalpha). interleukin-6 (IL-6), CRP and major CHD risk factors. The study included 193 patients in various stages of CHD and 193 matched controls. To evaluate any possible influence of acute phase reaction, reinvestigation was performed after 6 months. After adjustment for major CHD risk factors, sVCAM-1, sICAM-1, P-selectin, IL-6 and CRP remained significantly elevated in the CHD patients (p for all <0.001). In multivariate analysis sVCAM-1 was predicted by age (p=0.015), sICAM-1 by smoking (p<0.001) and total cholesterol (p=0.026), E-selectin by body mass index (BMI) (p=0.004) and P-selectin by male gender (p=0.015). TNFalpha significantly predicted sICAM-1 and E-selectin levels, while IL-6 predicted CRP but none of the sCAMs measured. This might indicate that TNFalpha, but not IL-6, plays a major role in the regulation of sCAM levels in vivo.

Magnetizable stent-grafts enable endothelial cell capture

NASA Astrophysics Data System (ADS)

Tefft, Brandon J.; Uthamaraj, Susheil; Harburn, J. Jonathan; Hlinomaz, Ota; Lerman, Amir; Dragomir-Daescu, Dan; Sandhu, Gurpreet S.

2017-04-01

Emerging nanotechnologies have enabled the use of magnetic forces to guide the movement of magnetically-labeled cells, drugs, and other therapeutic agents. Endothelial cells labeled with superparamagnetic iron oxide nanoparticles (SPION) have previously been captured on the surface of magnetizable 2205 duplex stainless steel stents in a porcine coronary implantation model. Recently, we have coated these stents with electrospun polyurethane nanofibers to fabricate prototype stent-grafts. Facilitated endothelialization may help improve the healing of arteries treated with stent-grafts, reduce the risk of thrombosis and restenosis, and enable small-caliber applications. When placed in a SPION-labeled endothelial cell suspension in the presence of an external magnetic field, magnetized stent-grafts successfully captured cells to the surface regions adjacent to the stent struts. Implantation within the coronary circulation of pigs (n=13) followed immediately by SPION-labeled autologous endothelial cell delivery resulted in widely patent devices with a thin, uniform neointima and no signs of thrombosis or inflammation at 7 days. Furthermore, the magnetized stent-grafts successfully captured and retained SPION-labeled endothelial cells to select regions adjacent to stent struts and between stent struts, whereas the non-magnetized control stent-grafts did not. Early results with these prototype devices are encouraging and further refinements will be necessary in order to achieve more uniform cell capture and complete endothelialization. Once optimized, this approach may lead to more rapid and complete healing of vascular stent-grafts with a concomitant improvement in long-term device performance.

Demographic and cardiovascular risk factors modify association of fasting insulin with incident coronary heart disease and ischemic stroke (from the Atherosclerosis Risk In Communities Study).

PubMed

Rasmussen-Torvik, Laura J; Yatsuya, Hiroshi; Selvin, Elizabeth; Alonso, Alvaro; Folsom, Aaron R

2010-05-15

Previous studies have reported an association between circulating insulin and incident cardiovascular disease, but limited knowledge is available on the association across subgroups. We examined the associations of fasting insulin with incident coronary heart disease (CHD) and ischemic stroke in multiple subgroups of a biracial, middle-age cohort. A total of 12,323 subjects were included in the analysis. The incidence of CHD (n = 960) and ischemic stroke (n = 445) through 2005 was determined through annual interviews, repeat examinations, and community surveillance. Serum insulin was measured at baseline. Cox regression analysis was used to estimate the hazard ratios by quintile of fasting insulin at baseline and to determine the significance of effect modification. In the minimally adjusted models (age, gender, race, and field center), the baseline fasting insulin quintile was positively associated with both incident CHD (hazard ratio per quintile insulin = 1.12, p-trend <0.0001) and ischemic stroke (hazard ratio per quintile insulin = 1.11, p = 0.0018). The adjustment for high-density lipoprotein completely attenuated the association of insulin with CHD but not with stroke. The associations of insulin with CHD were stronger in nonsmokers (p-interaction = 0.018) and in those without hypertension (p-interaction = 0.0087). The associations of insulin with stroke were stronger in women (p-interaction = 0.037), whites (compared to blacks; p-interaction = 0.036), and those without hypertension (p-interaction = 0.0027). Copyright 2010 Elsevier Inc. All rights reserved.

Effects of diaspirin cross-linked hemoglobin (DCLHb) during and post-CPR in swine.

PubMed

Chow, M S; Fan, C; Tran, H; Zhao, H; Zhou, L

2001-04-01

The purpose of the study was to test the hypothesis that diaspirin cross-linked hemoglobin (DCLHb) can produce improved resuscitation during cardiac arrest. DCLHb, a derivative of human hemoglobin, has previously been demonstrated to produce a vasopressor response that is associated with increased blood flow to vital organs. In addition, it is an oxygen carrier. These effects may be beneficial to extreme low flow states, such as that during cardiac arrest and cardiopulmonary resuscitation (CPR). Experimental cardiac arrest and CPR were carried out in 32 anesthetized immature pigs. In each animal, ventricular fibrillation was induced for 5 min, followed by 10 min of standard CPR with a pneumatic device and room air ventilation. High (15 ml/kg) and low (5 ml/kg) doses of DCLHb or equivalent volume of normal saline were infused at the beginning of CPR in a random and blind manner. Cardiac output, organ blood flow, aortic pressure, coronary perfusion pressure, blood gases, and lactate concentrations were obtained before and during CPR. Following the 10-min CPR, the animals were defibrillated and the return of spontaneous circulation (ROSC) determined. DCLHb treatment achieved 75% ROSC compared with 25% in the saline group (p < 0.05). In addition, a better (p < 0.05) myocardial O(2) delivery, venous blood O(2) content, and myocardial and cerebral perfusion pressure were observed in the DCLHb group. DCLHb treatment during cardiac arrest and CPR significantly improves ROSC. This is most likely related to its improvement in coronary perfusion and myocardial oxygen delivery.

Laser blood irradiation effect on electrophysiological characteristics of acute coronary syndrome patients

NASA Astrophysics Data System (ADS)

Khotiaintsev, Sergei N.; Doger-Guerrero, E.; Glebova, L.; Svirid, V.; Sirenko, Yuri

1996-11-01

This paper treats electro-physiological effects of the low- level laser irradiation of blood (LBI). The data presented here are based on the observation of almost 200 patients suffering from the acute disruption of coronary blood circulation, unstable angina pectoris and myocardial infarction. Statistically significant changes of the electro-physiological characteristics were observed in the group of 65 patients, treated by the LBI. In particular, the significant 6 percent extension of the effective refractory period was observed. The electrical situation threshold has increased by 20.6 percent. The significant changes of some other important electro-physiological characteristics were within the range of 5-15 percent. In this paper, the data obtained on the LBI effectiveness are compared also with the results obtained on 94 patients who in addition to the standard anti-angina therapy were treated by the autohaemo- transfusion performed simultaneously with the UV-light irradiation of the transfused blood. The results obtained demonstrate the significant positive effect of the low energy LBI. The electrophysiological data obtained have good correlation with observed anti-arrhythmic effect of the LBI. This is proved by the data obtained on the electro- physiological characteristics of the cardiovascular system and by other clinical data on the experimental and control group of patients. In the course of this research the exact effect of the low level LBI was established. LBI led to the pronounced positive changes in electro-physiological characteristics of the cardiovascular system of the patients, it also led to the pronounced anti-arrhythmic effect.

Magnetizable stent-grafts enable endothelial cell capture.

PubMed

Tefft, Brandon J; Uthamaraj, Susheil; Harburn, J Jonathan; Hlinomaz, Ota; Lerman, Amir; Dragomir-Daescu, Dan; Sandhu, Gurpreet S

2017-04-01

Emerging nanotechnologies have enabled the use of magnetic forces to guide the movement of magnetically-labeled cells, drugs, and other therapeutic agents. Endothelial cells labeled with superparamagnetic iron oxide nanoparticles (SPION) have previously been captured on the surface of magnetizable 2205 duplex stainless steel stents in a porcine coronary implantation model. Recently, we have coated these stents with electrospun polyurethane nanofibers to fabricate prototype stent-grafts. Facilitated endothelialization may help improve the healing of arteries treated with stent-grafts, reduce the risk of thrombosis and restenosis, and enable small-caliber applications. When placed in a SPION-labeled endothelial cell suspension in the presence of an external magnetic field, magnetized stent-grafts successfully captured cells to the surface regions adjacent to the stent struts. Implantation within the coronary circulation of pigs (n=13) followed immediately by SPION-labeled autologous endothelial cell delivery resulted in widely patent devices with a thin, uniform neointima and no signs of thrombosis or inflammation at 7 days. Furthermore, the magnetized stent-grafts successfully captured and retained SPION-labeled endothelial cells to select regions adjacent to stent struts and between stent struts, whereas the non-magnetized control stent-grafts did not. Early results with these prototype devices are encouraging and further refinements will be necessary in order to achieve more uniform cell capture and complete endothelialization. Once optimized, this approach may lead to more rapid and complete healing of vascular stent-grafts with a concomitant improvement in long-term device performance.

Assessment of the nickel-albumin binding assay for diagnosis of acute coronary syndrome.

PubMed

da Silva, Sandra Huber; Pereira, Renata da Silva; Hausen, Bruna dos Santos; Signor, Cristiane; Gomes, Patrícia; de Campos, Marli Matiko Anraku; Moresco, Rafael Noal

2011-03-01

Myocardial ischemia may alter the metal binding capacity of circulating serum albumin. Thus, the aim of this study was to describe an automated method to measure ischemia-induced alterations in the binding capacity of serum albumin for exogenous nickel, and to evaluate the diagnostic characteristics of this assay for the assessment of acute coronary syndrome (ACS) in patients presenting to the emergency room (ER) with acute chest pain. We assessed the concentrations of cardiac troponin I (cTnI), serum albumin, ischemia-modified albumin (IMA) measured by the cobalt-albumin binding assay (CABA), and by an automated nickel-albumin binding assay (NABA) in the following groups: ACS (n=63) and non-ischemic chest pain (NICP, n=26). Biochemical markers were determined in blood samples obtained from patients within 3 h of ER admission. cTnI, CABA and NABA concentrations were higher in ACS group in comparison to the NICP group. A significant correlation between NABA and CABA was observed (r=0.5387, p<0.001). Areas under the curve for CABA and NABA were 0.7289 and 0.7582, respectively. Both CABA and NABA have the ability to discriminate patients with ACS. However, NABA has a slightly higher ability to discriminate ACS compared with CABA. Patients with ACS have reduced nickel binding to human serum albumin, and NABA may have an important role as an early marker of myocardial ischemia, particularly in patients presenting to the ER with acute chest pain.

The ASSURE ROT Registry: Bioresorbable Vascular Scaffold Following Rotablation for Complex Coronary Lesions

ClinicalTrials.gov

2015-02-05

Cardiovascular Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Coronary Restenosis; Heart Diseases; Coronary Stenosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Heart bypass surgery

MedlinePlus

Off-pump coronary artery bypass; OPCAB; Beating heart surgery; Bypass surgery - heart; CABG; Coronary artery bypass graft; Coronary artery bypass surgery; Coronary bypass surgery; Coronary artery disease - CABG; CAD - CABG; Angina - ...

A comparison of hybrid coronary revascularization and off-pump coronary revascularization.

PubMed

Umakanthan, Ramanan; Leacche, Marzia; Gallion, Anna H; Byrne, John G

2013-04-01

Minimally invasive approaches to treat vascular disease have been accruing significant popularity over the last several decades. Due to progressive advances in technology, a variety of techniques are being now utilized in the field of cardiovascular surgery. The objectives of minimally invasive techniques are to curtail operative trauma and minimize perioperative morbidity without decreasing the quality of the treatment. The standard surgical approach for the treatment of coronary artery disease has traditionally been coronary artery bypass grafting surgery via median sternotomy. Off-pump coronary artery bypass grafting surgery offers a less invasive alternative and enables coronary revascularization to be performed without cardiopulmonary bypass. Hybrid coronary revascularization offers an even less invasive option in which minimally invasive direct coronary artery bypass can be combined with percutaneous coronary intervention. In this article, the authors review a recent publication comparing hybrid coronary revascularization and off-pump coronary artery bypass grafting surgery.

Effect of Red Blood Cell Storage on Cardiac Performance. Improved Myocardial Oxygen Delivery and Function during Constant Flow Coronary Perfusion with Low Oxy-Hemoglobin Affinity Human Red Blood Cells in Normothermic and Hypothermic Rabbit Hearts.

DTIC Science & Technology

1983-02-01

with an isovolumic left ven- tricular balloon. Coronary flow was held constant to simulate the physiolog of coronary atherosclerosis and other...erythrocyte DPG content can potentially benefit patients with coronary atherosclerosis , or other states with a limited coronary vasodilator reserve, who...Coronary flow was held constant to simulate the physiology of coronary atherosclerosis and other conditions of limited coronary vasodilator reserve

Coronary tortuosity: a long and winding road

PubMed Central

Zegers, E.S.; Meursing, B.T.J.; Zegers, E.B.; Oude Ophuis, A.J.M.

2007-01-01

Coronary tortuosity is a phenomenon often encountered by cardiologists performing coronary angiography. The aetiology and clinical importance of coronary tortuosity are still unclear. Coronary tortuosity without fixed atherosclerotic stenosis in patients with angina pectoris and an abnormal exercise stress test has never been described in the literature. This article describes three cases of patients with anginal complaints, an abnormal exercise stress test and coronary angiography without the presence of a fixed atherosclerotic lesion. It is hypothesised that coronary tortuosity leads to flow alteration resulting in a reduction in coronary pressure distal to the tortuous segment of the coronary artery, subsequently leading to ischaemia. Future studies will be necessary to elucidate the actual mechanism of coronary tortuosity and its clinical significance. (Neth Heart J 2007;15:191-5.17612682) PMID:17612682

Coronary artery anomalies in Turner Syndrome.

PubMed

Viuff, Mette H; Trolle, Christian; Wen, Jan; Jensen, Jesper M; Nørgaard, Bjarne L; Gutmark, Ephraim J; Gutmark-Little, Iris; Mortensen, Kristian H; Gravholt, Claus Højbjerg; Andersen, Niels H

Congenital heart disease, primarily involving the left-sided structures, is often seen in patients with Turner Syndrome. Moreover, a few case reports have indicated that coronary anomalies may be more prevalent in Turner Syndrome than in the normal population. We therefore set out to systematically investigate coronary arterial anatomy by computed tomographic coronary angiography (coronary CTA) in Turner Syndrome patients. Fifty consecutive women with Turner Syndrome (mean age 47 years [17-71]) underwent coronary CTA. Patients were compared with 25 gender-matched controls. Coronary anomaly was more frequent in patients with Turner Syndrome than in healthy controls [20% vs. 4% (p = 0.043)]. Nine out of ten abnormal cases had an anomalous left coronary artery anatomy (absent left main trunk, n = 7; circumflex artery originating from the right aortic sinus, n = 2). One case had a tubular origin of the right coronary artery above the aortic sinus. There was no correlation between the presence of coronary arterial anomalies and karyotype, bicuspid aortic valve, or other congenital heart defects. Coronary anomalies are highly prevalent in Turner Syndrome. The left coronary artery is predominantly affected, with an absent left main coronary artery being the most common anomaly. No hemodynamically relevant coronary anomalies were found. Copyright © 2016 Society of Cardiovascular Computed Tomography. All rights reserved.