Effect of PFDA on Cardiac Membrane Function.

DTIC Science & Technology

1983-03-01

NO. 3. RECIPIENT’S CATALOG NUMBER AFOS-TR - / .... 4. TITLE (and Subtitle) 5. TVPF nF REPORT & PERIOD COVERED EFFECT OF PFDA ON CARDIAC MEMBRANE...Continue on reverse side II necessary and Identify by block number) Heart, Thyroxine, Triiodothyronine, PFDA 0t C) 20, ABSTRACT (Continue on revereD...eide If neceesary and Identify by block number) LTJ "Yihe in vivo and in vitro heart rates of rats treated with 75 mg/kg PFDA was __j significantly

Nonemergency PCI at hospitals with or without on-site cardiac surgery.

PubMed

Jacobs, Alice K; Normand, Sharon-Lise T; Massaro, Joseph M; Cutlip, Donald E; Carrozza, Joseph P; Marks, Anthony D; Murphy, Nancy; Romm, Iyah K; Biondolillo, Madeleine; Mauri, Laura

2013-04-18

Emergency surgery has become a rare event after percutaneous coronary intervention (PCI). Whether having cardiac-surgery services available on-site is essential for ensuring the best possible outcomes during and after PCI remains uncertain. We enrolled patients with indications for nonemergency PCI who presented at hospitals in Massachusetts without on-site cardiac surgery and randomly assigned these patients, in a 3:1 ratio, to undergo PCI at that hospital or at a partner hospital that had cardiac surgery services available. A total of 10 hospitals without on-site cardiac surgery and 7 with on-site cardiac surgery participated. The coprimary end points were the rates of major adverse cardiac events--a composite of death, myocardial infarction, repeat revascularization, or stroke--at 30 days (safety end point) and at 12 months (effectiveness end point). The primary end points were analyzed according to the intention-to-treat principle and were tested with the use of multiplicative noninferiority margins of 1.5 (for safety) and 1.3 (for effectiveness). A total of 3691 patients were randomly assigned to undergo PCI at a hospital without on-site cardiac surgery (2774 patients) or at a hospital with on-site cardiac surgery (917 patients). The rates of major adverse cardiac events were 9.5% in hospitals without on-site cardiac surgery and 9.4% in hospitals with on-site cardiac surgery at 30 days (relative risk, 1.00; 95% one-sided upper confidence limit, 1.22; P<0.001 for noninferiority) and 17.3% and 17.8%, respectively, at 12 months (relative risk, 0.98; 95% one-sided upper confidence limit, 1.13; P<0.001 for noninferiority). The rates of death, myocardial infarction, repeat revascularization, and stroke (the components of the primary end point) did not differ significantly between the groups at either time point. Nonemergency PCI procedures performed at hospitals in Massachusetts without on-site surgical services were noninferior to procedures performed at hospitals with on-site surgical services with respect to the 30-day and 1-year rates of clinical events. (Funded by the participating hospitals without on-site cardiac surgery; MASS COM ClinicalTrials.gov number, NCT01116882.).

Long-term mortality from cardiac causes after adjuvant hypofractionated vs. conventional radiotherapy for localized left-sided breast cancer.

PubMed

Chan, Elisa K; Woods, Ryan; Virani, Sean; Speers, Caroline; Wai, Elaine S; Nichol, Alan; McBride, Mary L; Tyldesley, Scott

2015-01-01

Ongoing concern remains regarding cardiac injury with hypofractionated whole breast/chest-wall radiotherapy (HF-WBI) compared to conventional radiotherapy (CF-WBI) in left-sided breast cancer patients. The purpose was to determine if cardiac mortality increases with HF-WBI relative to CF-WBI. Between 1990 and 1998, 5334 women with early-stage breast cancer received post-operative radiotherapy to the breast/chest wall alone. A population-based database recorded baseline patient, tumor and treatment factors. Baseline cardiovascular risk factors were identified from hospital administrative records. A propensity-score model balanced risk factors between radiotherapy groups. Cause of death was coded as breast cancer, cardiac or other cause. Cumulative mortality from each cause after radiotherapy was estimated using a competing risk approach. For left-sided cases, median follow-up was 14.2 years. 485 women received CF-WBI, 2221 women received HF-WBI. There was no difference in 15-year mortality from cardiac causes: 4.8% with HF-WBI and 4.2% with CF-WBI (p=0.74), even after propensity-score adjustment (p=0.45). There was no difference in breast cancer mortality or other cause mortality. For right-sided cases, there was no difference in mortality for the three causes of death. At 15-years follow-up, cardiac mortality is not statistically different among left-sided breast cancer patients treated with HF-WBI or CF-WBI. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Therapeutic trial of granulocyte-colony stimulating factor for dilated cardiomyopathy in three dogs.

PubMed

Park, Chul; Yoo, Jong-Hyun; Jeon, Hyo-Won; Kang, Byeong-Teck; Kim, Jung-Hyun; Jung, Dong-In; Lim, Chae-Young; Lee, Hye-Jung; Hahm, Dae-Hyun; Woo, Eung-Je; Park, Hee-Myung

2007-09-01

Three dogs were presented to us for evaluation of cardiac problems. Electrocardiographic recordings revealed severe tachyarrhythmia and atrial fibrillation with ventricular tachycardia in 2 of the 3 dogs. The echocardiographic findings of the 3 dogs revealed markedly decreased fractional shortening and a marked increase in E-point septal separation. Based on the results of electrocardiographic and echocardiographic evaluation, the 3 dogs were diagnosed as dilated cardiomyopathy (DCM). The dogs were treated with conventional cardiac medication, but cardiac function did not improve and the clinical signs remained. We subsequently attempted treatment with granulocyte-colony stimulating factor (G-CSF; 10 microg/kg, subcutaneously). The specific purpose of G-CSF therapy for DCM was to improve cardiac function and a significant improvement in cardiac function was confirmed. The three dogs had no treatment side effects. This case report suggests that G-CSF might have therapeutic effects for medically refractory DCM in dogs.

Beta-blocker-induced psoriasis: a rare side effect--a case report.

PubMed

Yilmaz, Mehmet Birhan; Turhan, Hasan; Akin, Yesim; Kisacik, Halil L; Korkmaz, Sule

2002-01-01

Beta blockers are one of the oral agents shown to decrease cardiovascular morbidity and mortality rates in randomized, controlled trials, and hence, they are widely used for the management of many cardiovascular situations. In terms of side effects there are 3 major modes of action: (1) contraction of smooth muscles, particularly of bronchi with nonselective agents; (2) exaggerated cardiac effects; and (3) central nervous system effects. There are also some rare side effects of beta blockers, some of which are unpredictable, but the others are related to mode of action at the cellular level. Beta-blocking agents may cause psoriaform eruptions and worsen existing psoriasis. Psoriasis may be an inconvenient side effect of beta blockade. Herein, we report a case of beta-blocker-induced psoriasis.

Side differences in cerebrovascular accidents after cardiac surgery: a statistical analysis of neurologic symptoms and possible implications for anatomic mechanisms of aortic particle embolization.

PubMed

Boivie, Patrik; Edström, Cecilia; Engström, Karl Gunnar

2005-03-01

Aortic manipulation and particle embolization have been identified to cause cerebrovascular accidents in cardiac surgery. Recent data suggest that left-hemispheric cerebrovascular accident (right-sided symptoms) is more common, and this has been interpreted as being caused by aortic cannula stream jets. Our aim was to evaluate symptoms of cerebrovascular accident and side differences from a retrospective statistical analysis. During a 2-year period, 2641 consecutive cardiac surgery cases were analyzed. Patients positive for cerebrovascular accident were extracted from a database designed to monitor clinical symptoms. A protocol was used to confirm symptom data with the correct diagnosis in patient records. Patients were subdivided into 3 groups: control, immediate cerebrovascular accident, and delayed cerebrovascular accident. Among pooled patients, immediate and delayed cerebrovascular accidents were 3.0% and 0.9%, respectively. The expected predisposing factors behind immediate cerebrovascular accidents were significant, although the type of operation affected this search. Aortic quality was a strong predictor ( P < .001). The rate of delayed cerebrovascular accident was unaffected by surgery group. Left-sided symptoms of immediate cerebrovascular accident were approximately twice as frequent ( P = .016) as on the contralateral side. This phenomenon was observed for pooled patients and for isolated coronary bypass procedures (n = 1882; P = .025). Immediate cerebrovascular accident and aortic calcifications are linked. The predominance of left-sided symptoms may suggest that aortic manipulation and anatomic mechanisms in the aortic arch are more likely to cause cerebrovascular accidents than effects from cannula stream jets.

Unilateral dampening of Bmp activity by nodal generates cardiac left-right asymmetry.

PubMed

Veerkamp, Justus; Rudolph, Franziska; Cseresnyes, Zoltan; Priller, Florian; Otten, Cécile; Renz, Marc; Schaefer, Liliana; Abdelilah-Seyfried, Salim

2013-03-25

Signaling by Nodal and Bmp is essential for cardiac laterality. How activities of these pathways translate into left-right asymmetric organ morphogenesis is largely unknown. We show that, in zebrafish, Nodal locally reduces Bmp activity on the left side of the cardiac field. This effect is mediated by the extracellular matrix enzyme Hyaluronan synthase 2, expression of which is induced by Nodal. Unilateral reduction of Bmp signaling results in lower expression of nonmuscle myosin II and higher cell motility on the left, driving asymmetric displacement of the entire cardiac field. In silico modeling shows that left-right differences in cell motility are sufficient to induce a robust, directional migration of cardiac tissue. Thus, the mechanism underlying the formation of cardiac left-right asymmetry involves Nodal modulating an antimotogenic Bmp activity. Copyright © 2013 Elsevier Inc. All rights reserved.

Cardiopulmonary manifestations of isolated pulmonary valve infective endocarditis demonstrated with cardiac CT.

PubMed

Passen, Edward; Feng, Zekun

2015-01-01

Right-sided infective endocarditis involving the pulmonary valve is rare. This pictorial essay discusses the use and findings of cardiac CT combined with delayed chest CT and noncontrast chest CT of pulmonary valve endocarditis. Cardiac CT is able to show the full spectrum of right-sided endocarditis cardiopulmonary features including manifestations that cannot be demonstrated by echocardiography. Copyright © 2015 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.

Framing effects on expectations, decisions, and side effects experienced: the case of influenza immunization.

PubMed

O'Connor, A M; Pennie, R A; Dales, R E

1996-11-01

To examine the effects of using positive or negative frames to describe influenza vaccine benefits and side effects on patients' expectations, decisions, decisional conflict, and reported side effects. 292 previously unimmunized patients with chronic respiratory or cardiac disease were randomly assigned to receive benefit/risk information that was framed: (1) positively as the percentage who remain free of influenza and have no vaccine side effects, or (2) negatively as the percentage who acquire influenza and have vaccine side effects. Questionnaires elicited expectations, decisions, and decisional conflict. Vaccines were telephoned 3 days later for a self-report of local and systemic side effects and work absenteeism. Both groups had similar immunization rates and decisional conflict scores. The positive frame group had lower and more realistic expectations of vaccine side effects, fewer systemic side effects, and less work absenteeism (p < 0.05). In contrast to previous studies of health care workers, framing did not influence patients' decisions, possibly due to the patients' awareness of their higher risk of influenza complications and greater desire to follow recommendations. The common practice of using negative frames when describing probabilities of side effects may need to be reexamined, considering its deleterious influence on self-reported side effects and work absenteeism.

Synergistic effects of Isatis tinctoria L. and tacrolimus in the prevention of acute heart rejection in mice.

PubMed

Wang, Yongzhi; Qin, Qing; Chen, Jibing; Kuang, Xiaocong; Xia, Junjie; Xie, Baiyi; Wang, Feng; Liang, Hua; Qi, Zhongquan

2009-12-01

Although immunosuppressive treatments are available for acute cardiac rejection no viable treatment exists for long-term cardiac graft failure. Moreover, the extended use of calcineurin inhibitor immunosuppressants, the mainstay of current treatment for cardiac transplantation, leads to significant side effects such as nephrotoxicity and an increased risk of cardiac disease. Because some agents used in Traditional Chinese Medicine (TCM) have strong immunosuppressive effects coupled with low toxicity, we investigated the effect of Compound K (K), the synthesized analogue of highly unsaturated fatty acids from Isatis tinctoria L., either as a single treatment or combined with tacrolimus (FK-506) on acute cardiac allograft rejection. We compared the ability of K alone, or in combination with FK-506, to inhibit acute heart transplant rejection both in vitro and in vivo. We found that the inhibition of lymphocyte proliferation was positively correlated with K concentration. K significantly reduced IL-2 and IFN-gamma expression levels and significantly inhibited lymphocyte proliferation in both a lymphocyte transformation test and a mixed lymphocyte reaction (MLR). We also found that the inhibitory effect of a combination of K and a sub-therapeutic dose of FK-506 (SubFK-506) was stronger than that of full-dose FK-506 alone. Oral administration of K reduced acute cardiac allograft rejection in mice and had no apparent toxicity. In vivo, the immunosuppressive effect of K combined with a half-dose of FK-506 was equivalent to that of a full-dose of FK-506 alone. K combined with a half-dose of FK-506 reduced the expression levels of IL-2 and IFN-gamma (both within the graft and in the recipients' serum) more effectively than a full-dose of FK-506. These results show that K has significant immunosuppressive effects both in vitro and in vivo. When used as a combination therapy with FK-506 we see a powerful inhibition of rejection with no obvious toxic side effects. The mechanism of action is postulated to involve the inhibition of IL-2 and IFN-gamma expressions by lymphocytes, rather than the activation of Tr1 cells via the production of IL-10.

White matter changes in comatose survivors of anoxic ischemic encephalopathy and traumatic brain injury: comparative diffusion-tensor imaging study.

PubMed

van der Eerden, Anke W; Khalilzadeh, Omid; Perlbarg, Vincent; Dinkel, Julien; Sanchez, Paola; Vos, Pieter E; Luyt, Charles-Edouard; Stevens, Robert D; Menjot de Champfleur, Nicolas; Delmaire, Christine; Tollard, Eleonore; Gupta, Rajiv; Dormont, Didier; Laureys, Steven; Benali, Habib; Vanhaudenhuyse, Audrey; Galanaud, Damien; Puybasset, Louis

2014-02-01

To analyze white matter pathologic abnormalities by using diffusion-tensor (DT) imaging in a multicenter prospective cohort of comatose patients following cardiac arrest or traumatic brain injury (TBI). Institutional review board approval and informed consent from proxies and control subjects were obtained. DT imaging was performed 5-57 days after insult in 49 cardiac arrest and 40 TBI patients. To control for DT imaging-processing variability, patients' values were normalized to those of 111 control subjects. Automated segmentation software calculated normalized axial diffusivity (λ1) and radial diffusivity (λ⊥) in 19 predefined white matter regions of interest (ROIs). DT imaging variables were compared by using general linear modeling, and side-to-side Pearson correlation coefficients were calculated. P values were corrected for multiple testing (Bonferroni). In central white matter, λ1 differed from that in control subjects in six of seven TBI ROIs and five of seven cardiac arrest ROIs (all P < .01). The λ⊥ differed from that in control subjects in all ROIs in both patient groups (P < .01). In hemispheres, λ1 was decreased compared with that in control subjects in three of 12 TBI ROIs (P < .05) and nine of 12 cardiac arrest ROIs (P < .01). The λ⊥ was increased in all TBI ROIs (P < .01) and in seven of 12 cardiac arrest ROIs (P < .05). Cerebral hemisphere λ1 was lower in cardiac arrest than in TBI in six of 12 ROIs (P < .01), while λ⊥ was higher in TBI than in cardiac arrest in eight of 12 ROIs (P < .01). Diffusivity values were symmetrically distributed in cardiac arrest (P < .001 for side-to-side correlation) but not in TBI patients. DT imaging findings are consistent with the known predominance of cerebral hemisphere axonal injury in cardiac arrest and chiefly central myelin injury in TBI. This consistency supports the validity of DT imaging for differentiating axon and myelin damage in vivo in humans. © RSNA, 2013

Resveratrol Co-Treatment Attenuates the Effects of HIV Protease Inhibitors on Rat Body Weight and Enhances Cardiac Mitochondrial Respiration

PubMed Central

Symington, Burger; Mapanga, Rudo F.; Norton, Gavin R.

2017-01-01

Since the early 1990s human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) emerged as a global health pandemic, with sub-Saharan Africa the hardest hit. While the successful roll-out of antiretroviral (ARV) therapy provided significant relief to HIV-positive individuals, such treatment can also elicit damaging side-effects. Here especially HIV protease inhibitors (PIs) are implicated in the onset of cardio-metabolic complications such as type-2 diabetes and coronary heart disease. As there is a paucity of data regarding suitable co-treatments within this context, this preclinical study investigated whether resveratrol (RSV), aspirin (ASP) or vitamin C (VitC) co-treatment is able to blunt side-effects in a rat model of chronic PI exposure (Lopinavir/Ritonavir treatment for 4 months). Body weights and weight gain, blood metabolite levels (total cholesterol, HDL, LDL, triglycerides), echocardiography and cardiac mitochondrial respiration were assessed in PI-treated rats ± various co-treatments. Our data reveal that PI treatment significantly lowered body weight and cardiac respiratory function while no significant changes were found for heart function and blood metabolite levels. Moreover, all co-treatments ameliorated the PI-induced decrease in body weight after 4 months of PI treatment, while RSV co-treatment enhanced cardiac mitochondrial respiratory capacity in PI-treated rats. This pilot study therefore provides novel hypotheses regarding RSV co-treatment that should be further assessed in greater detail. PMID:28107484

Sci—Thur AM: YIS - 01: Dosimetric Analysis of Respiratory Induced Cardiac Intrafraction Motion in Left-sided Breast Cancer Radiotherapy

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

El-Sherif, O; Xhaferllari, I; Patrick, J

2014-08-15

Introduction: Long-term cardiac side effects in left-sided breast cancer patients (BREL) after post-operative radiotherapy has become one of the most debated issues in radiation oncology. Through breathing-adapted radiotherapy the volume of the heart exposed to radiation can be significantly reduced by delivering the radiation only at the end of inspiration phase of the respiratory cycle, this is referred to as inspiration gating (IG). The purpose of this study is to quantify the potential reduction in cardiac exposure during IG compared to conventional BREL radiotherapy and to assess the dosimetric impact of cardiac motion due to natural breathing. Methods: 24 BRELmore » patients treated with tangential parallel opposed photon beams were included in this study. All patients received a standard fast helical planning CT (FH-CT) and a 4D-CT. Treatment plans were created on the FH-CT using a clinical treatment planning system. The original treatment plan was then superimposed onto the end of inspiration CT and all 10 phases of the 4D-CT to quantify the dosimetric impact of respiratory motion and IG through 4D dose accumulation. Results: Through IG the mean dose to the heart, left ventricle, and left anterior descending artery (LAD) can be reduced in comparison to the clinical standard BREL treatment by as much as 8.39%, 10.11%, and 13.71% respectively (p < 0.05). Conclusion: Failure to account for respiratory motion can lead to under or overestimation in the calculated DVH for the heart, and it's sub-structures. IG can reduce cardiac exposure especially to the LAD during BREL radiotherapy.« less

Adjuvant Hypofractionated Versus Conventional Whole Breast Radiation Therapy for Early-Stage Breast Cancer: Long-Term Hospital-Related Morbidity From Cardiac Causes

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

Chan, Elisa K.; Woods, Ryan; McBride, Mary L.

Purpose: The risk of cardiac injury with hypofractionated whole-breast/chest wall radiation therapy (HF-WBI) compared with conventional whole-breast/chest wall radiation therapy (CF-WBI) in women with left-sided breast cancer remains a concern. The purpose of this study was to determine if there is an increase in hospital-related morbidity from cardiac causes with HF-WBI relative to CF-WBI. Methods and Materials: Between 1990 and 1998, 5334 women ≤80 years of age with early-stage breast cancer were treated with postoperative radiation therapy to the breast or chest wall alone. A population-based database recorded baseline patient, tumor, and treatment factors. Hospital administrative records identified baseline cardiacmore » risk factors and other comorbidities. Factors between radiation therapy groups were balanced using a propensity-score model. The first event of a hospital admission for cardiac causes after radiation therapy was determined from hospitalization records. Ten- and 15-year cumulative hospital-related cardiac morbidity after radiation therapy was estimated for left- and right-sided cases using a competing risk approach. Results: The median follow-up was 13.2 years. For left-sided cases, 485 women were treated with CF-WBI, and 2221 women were treated with HF-WBI. Mastectomy was more common in the HF-WBI group, whereas boost was more common in the CF-WBI group. The CF-WBI group had a higher prevalence of diabetes. The 15-year cumulative hospital-related morbidity from cardiac causes (95% confidence interval) was not different between the 2 radiation therapy regimens after propensity-score adjustment: 21% (19-22) with HF-WBI and 21% (17-25) with CF-WBI (P=.93). For right-sided cases, the 15-year cumulative hospital-related morbidity from cardiac causes was also similar between the radiation therapy groups (P=.76). Conclusions: There is no difference in morbidity leading to hospitalization from cardiac causes among women with left-sided early-stage breast cancer treated with HF-WBI or CF-WBI at 15-year follow-up.« less

[Orthostatic hypotension in the elderly].

PubMed

Ferrer-Gila, Teresa; Rízea, Cristian

2013-03-16

Orthostatic hypotension (OH) is defined as a decrease in systolic blood pressure of 20 mmHg, or a decrease in diastolic blood pressure of 10 mmHg within three minutes of standing. It results from an inadequate response to postural changes in blood pressure. Common symptoms include dizziness, light-headedness, blurred vision, weakness, fatigue, nausea, palpitations, sweating, head and neck ache, slow cognitive performance and transient loss of conscientiousness. OH is a common problem among elderly patients and its aetiology is diverse, including autonomic nervous system dysfunction, cardiac problems, medication side effects, ageing changes or transitory deregulation of blood volume. The instrumental diagnosis can be easily accomplished by the tilt-table test, with continuous monitoring of blood pressure and cardiac parameters. It is a non-invasive technique and needs minimal collaboration from the patient. In our experience, when reviewing 327 patients, aged over 40 years and examined because of clinical suspicion of OH, the prevalence thereof was 51% whereas if focused in subjects older than 70, OH was proven in 90% of the cases. The older the patients, the more frequently they presented general deterioration, neurological or cardiac problems as well as pharmacological side effects. Ruling out neurological or cardiac malfunction can drastically improve the prognosis with possible reversibility of symptoms. Some nonpharmacological and pharmacological approaches to improve management of OH and life quality are described for guidance.

On the subjective acceptance during cardiovascular magnetic resonance imaging at 7.0 Tesla.

PubMed

Klix, Sabrina; Els, Antje; Paul, Katharina; Graessl, Andreas; Oezerdem, Celal; Weinberger, Oliver; Winter, Lukas; Thalhammer, Christof; Huelnhagen, Till; Rieger, Jan; Mehling, Heidrun; Schulz-Menger, Jeanette; Niendorf, Thoralf

2015-01-01

This study examines the subjective acceptance during UHF-CMR in a cohort of healthy volunteers who underwent a cardiac MR examination at 7.0T. Within a period of two-and-a-half years (January 2012 to June 2014) a total of 165 healthy volunteers (41 female, 124 male) without any known history of cardiac disease underwent UHF-CMR. For the assessment of the subjective acceptance a questionnaire was used to examine the participants experience prior, during and after the UHF-CMR examination. For this purpose, subjects were asked to respond to the questionnaire in an exit interview held immediately after the completion of the UHF-CMR examination under supervision of a study nurse to ensure accurate understanding of the questions. All questions were answered with "yes" or "no" including space for additional comments. Transient muscular contraction was documented in 12.7% of the questionnaires. Muscular contraction was reported to occur only during periods of scanning with the magnetic field gradients being rapidly switched. Dizziness during the study was reported by 12.7% of the subjects. Taste of metal was reported by 10.1% of the study population. Light flashes were reported by 3.6% of the entire cohort. 13% of the subjects reported side effects/observations which were not explicitly listed in the questionnaire but covered by the question about other side effects. No severe side effects as vomiting or syncope after scanning occurred. No increase in heart rate was observed during the UHF-CMR exam versus the baseline clinical examination. This study adds to the literature by detailing the subjective acceptance of cardiovascular magnetic resonance imaging examinations at a magnetic field strength of 7.0T. Cardiac MR examinations at 7.0T are well tolerated by healthy subjects. Broader observational and multi-center studies including patient cohorts with cardiac diseases are required to gain further insights into the subjective acceptance of UHF-CMR examinations.

77 FR 3646 - Products Containing Imidazolines Equivalent to 0.08 Milligrams or More

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-25

... congestion and/or ophthalmic irritation. Products containing imidazolines can cause serious adverse reactions... unpredictable, idiosyncratic reaction (i.e., a drug effect that occurs in a small number of people due to age..., and death associated with cardiac reactions in adults. Other systemic side effects can include...

Intraperitoneal AAV9-shRNA inhibits target expression in neonatal skeletal and cardiac muscles.

PubMed

Mayra, Azat; Tomimitsu, Hiroyuki; Kubodera, Takayuki; Kobayashi, Masaki; Piao, Wenying; Sunaga, Fumiko; Hirai, Yukihiko; Shimada, Takashi; Mizusawa, Hidehiro; Yokota, Takanori

2011-02-11

Systemic injections of AAV vectors generally transduce to the liver more effectively than to cardiac and skeletal muscles. The short hairpin RNA (shRNA)-expressing AAV9 (shRNA-AAV9) can also reduce target gene expression in the liver, but not enough in cardiac or skeletal muscles. Higher doses of shRNA-AAV9 required for inhibiting target genes in cardiac and skeletal muscles often results in shRNA-related toxicity including microRNA oversaturation that can induce fetal liver failure. In this study, we injected high-dose shRNA-AAV9 to neonates and efficiently silenced genes in cardiac and skeletal muscles without inducing liver toxicity. This is because AAV is most likely diluted or degraded in the liver than in cardiac or skeletal muscle during cell division after birth. We report that this systemically injected shRNA-AAV method does not induce any major side effects, such as liver dysfunction, and the dose of shRNA-AAV is sufficient for gene silencing in skeletal and cardiac muscle tissues. This novel method may be useful for generating gene knockdown in skeletal and cardiac mouse tissues, thus providing mouse models useful for analyzing diseases caused by loss-of-function of target genes. Copyright © 2011 Elsevier Inc. All rights reserved.

AZT-induced mitochondrial toxicity: an epigenetic paradigm for dysregulation of gene expression through mitochondrial oxidative stress.

PubMed

Koczor, Christopher A; Jiao, Zhe; Fields, Earl; Russ, Rodney; Ludaway, Tomika; Lewis, William

2015-10-01

Mitochondrial dysfunction causes oxidative stress and cardiomyopathy. Oxidative stress also is a side effect of dideoxynucleoside antiretrovirals (NRTI) and is observed in NRTI-induced cardiomyopathy. We show here that treatment with the NRTI AZT {1-[(2R,4S,5S)-4-azido-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione} modulates cardiac gene expression epigenetically through production of mitochondrially derived reactive oxygen species. Transgenic mice with ubiquitous expression of mitochondrially targeted catalase (MCAT) and C57Bl/6 wild-type mice littermates (WT) were administered AZT (0.22 mg/day po, 35 days), and cardiac DNA and mRNA were isolated. In AZT-treated WT, 95 cardiac genes were differentially expressed compared with vehicle-treated WTs. When MCAT mice were treated with AZT, each of those 95 genes reverted toward the expression of vehicle-treated WTs. In AZT-treated WT hearts, Mthfr [5,10-methylenetetrahydrofolate reductase; a critical enzyme in synthesis of methionine cycle intermediates including S-adenosylmethionine (SAM)], was overexpressed. Steady-state abundance of SAM in cardiac extracts from AZT-treated MCAT mice increased 60% above that of vehicle-treated MCAT. No such change occurred in WT. AZT caused hypermethylation (47%) and hypomethylation (53%) of differentially methylated DNA regions in WT cardiac DNA. AZT-treated MCAT heart DNA exhibited greater hypermethylation (91%) and less hypomethylation (9%) compared with vehicle-treated MCAT controls. The gene encoding protein kinase C-α displayed multifocal epigenetic regulation caused by oxidative stress. Results show that mitochondrially derived oxidative stress in the heart hinders cardiac DNA methylation, alters steady-state abundance of SAM, alters cardiac gene expression, and promotes characteristic pathophysiological changes of cardiomyopathy. This mechanism for NRTI toxicity offers insight into long-term side effects from these commonly used antiviral agents. Copyright © 2015 the American Physiological Society.

Transdiaphragmatic resuscitative open cardiac massage: description of the technique and a first case-series of an alternative approach to the heart.

PubMed

Schnüriger, Beat; Studer, Peter; Candinas, Daniel; Seiler, Christian A

2014-07-01

The purpose of this paper is to describe the transdiaphragmatic approach to the heart for open CPR in patients that arrest at laparotomy and to present a first case series of patients that have undergone this procedure. All patients who had undergone intraperitoneal transdiaphragmatic open CPR between January 1, 2002 and December 31, 2012 were retrieved from the operation registry at Bern University Hospital, Switzerland. Transdiaphragmatic access to the heart is initiated with a 10-cm-long anterocaudal incision in the central tendon of the diaphragm--approximately at 2 o'clock. Internal cardiac compression through the diaphragmatic incision can be performed from both sides of the patient. From the right side of the patient, cardiac massage is performed with the right hand and vice versa. A total of six patients were identified that suffered cardiac arrest during laparotomy with open CPR performed through the transdiaphragmatic approach. Four patients suffered cardiac arrest during orthotopic liver transplantation and two trauma patients suffered cardiac arrest during damage control laparotomy. In three patients, cardiac activity was never reestablished. However, three patients regained a perfusion heart rhythm and two of these survived to the ICU. One patient ultimately survived to discharge. In patients suffering cardiac arrest during laparotomy, the transdiaphragmatic approach allows for a rapid, technically easy, and almost atraumatic access to the heart, with excellent CPR performance. After this potentially life-saving procedure, pulmonary or surgical site complications are expected to occur much less compared with the conventionally performed emergency department left-sided thoracotomy.

[Assessment of Tricuspid Insufficiency and the Function of Right Ventricle Using Cardiac Magnetic Resonance Imaging Combined with Echocardiography].

PubMed

Chen, Hui; Zhao, Yanling; Yu, Jianqun

2015-08-01

Right-sided cardiac valvular diseases have traditionally been considered less important than disease of mitral or aortic valve. However, severe tricuspid regurgitation could lead to right ventricle dysfunction and reduce patients' survival rate. In clinic setting, tricuspid valve disease should be paid more attention for patients with secondary tricuspid regurgitation caused by left-sided valvular surgery combined with irreversible annular dilatation increasing the risk of reoperation. In this review, we summarize the epidemiology, anatomy, pathology, diagnosis, ultrasound and cardiac magnetic resonance imaging findings in patients with tricuspid regurgitation.

[Psychopharmaceutical drugs in the mass media. Results of a systematic analysis of text contents and images].

PubMed

Hillert, A; Sandmann, J; Ehmig, S C; Weisbecker, H; Sobota, K; Kepplinger, H M; Benkert, O

1995-11-01

Mental diseases and psychopharmacological drugs are frequently discussed in newspapers and popular magazines. The representations are supposed to have a great impact on people's opinions on the subject. From 1 August 1991 to 31 July 1992 all articles about psychopharmacological drugs and cardiac drugs in 19 German newspapers were collected. All statements, effects and side effects, the reason for prescription, individual details about the patient and, according to this procedure, subjects and implications of the illustrations, were registered and classified according to a code book. In contrast to the articles about cardiac drugs, half of the psychopharmacological drug reports primarily deal with the problems of side effects the drugs may produce. There was much more critical comment and emotional emphasis used to characterize the psychopharmacological drugs. Only in 9% was their therapeutic efficacy mentioned. Cardiac drugs are generally discussed objectively in a medical context and their efficacy is emphasized. Psychopharmacological drugs are often mentioned in stories about prominent persons having a life crisis, taking drugs, or turning to alcoholism, in the sense of social decline. In only 3% of these articles could a serious mental diseases be identified as the reason for the prescription. Corresponding to the more prominent emotional emphasis of these articles, compared to the articles about cardiac drugs, more pictures, mainly of prominent persons or patients are used. However, the illustration seldom adds to information provided. The reasons for and implications of these findings and the significant differences between the distinct groups of newspapers are discussed.

Controversies in diagnosis and management of community-acquired pneumonia.

PubMed

Sparham, Sarah; Charles, Patrick Gp

2017-04-17

Community-acquired pneumonia (CAP) is a common condition; however, it appears to be overdiagnosed. Diagnosing CAP too frequently may be adding to the problems of overuse of antibiotics, such as bacterial resistance in the community and greater costs and complications in individuals. Data support that most patients with non-severe CAP can be treated for 3-5 days; however, most patients with CAP are receiving much longer courses of therapy. Macrolides such as azithromycin have the potential to prolong the QT interval, although large population studies show that this does not appear to result in excess cardiac mortality. CAP is associated with an increase in a variety of cardiac complications, most notably infarctions and worsening cardiac failure, so clinicians should be vigilant for signs and symptoms of these complications, particularly in patients with a history of ischaemic cardiac disease or the presence of cardiac risk factors. Cardiac risk factors should be assessed and managed in patients with CAP over 40 years of age, although there are yet to be data to show that this approach reduces deaths. Corticosteroids may have a slight effect on reducing deaths in patients with severe CAP, but this must be balanced against the significant potential for side effects.

Chromosomal abnormalities and copy number variations in fetal left-sided congenital heart defects.

PubMed

Jansen, Fenna A R; Hoffer, Mariette J V; van Velzen, Christine L; Plati, Stephani Klingeman; Rijlaarsdam, Marry E B; Clur, Sally-Ann B; Blom, Nico A; Pajkrt, Eva; Bhola, Shama L; Knegt, Alida C; de Boer, Marion A; Haak, Monique C

2016-02-01

To demonstrate the spectrum of copy number variants (CNVs) in fetuses with isolated left-sided congenital heart defects (CHDs), and analyse genetic content. Between 2003 and 2012, 200 fetuses were identified with left-sided CHD. Exclusion criteria were chromosomal rearrangements, 22q11.2 microdeletion and/or extra-cardiac malformations (n = 64). We included cases with additional minor anomalies (n = 39), such as single umbilical artery. In 54 of 136 eligible cases, stored material was available for array analysis. CNVs were categorized as either (likely) benign, (likely) pathogenic or of unknown significance. In 18 of the 54 isolated left-sided CHDs we found 28 rare CNVs (prevalence 33%, average 1.6 CNV per person, size 10.6 kb-2.2 Mb). Our interpretation yielded clinically significant CNVs in two of 54 cases (4%) and variants of unknown significance in three other cases (6%). In left-sided CHDs that appear isolated, with normal chromosome analysis and 22q11.2 FISH analysis, array analysis detects clinically significant CNVs. When counselling parents of a fetus with a left-sided CHD it must be taken into consideration that aside from the cardiac characteristics, the presence of extra-cardiac malformations and chromosomal abnormalities influence the treatment plan and prognosis. © 2015 John Wiley & Sons, Ltd.

Mitochondria-Targeted Antioxidant Prevents Cardiac Dysfunction Induced by Tafazzin Gene Knockdown in Cardiac Myocytes

PubMed Central

He, Quan; Harris, Nicole; Ren, Jun; Han, Xianlin

2014-01-01

Tafazzin, a mitochondrial acyltransferase, plays an important role in cardiolipin side chain remodeling. Previous studies have shown that dysfunction of tafazzin reduces cardiolipin content, impairs mitochondrial function, and causes dilated cardiomyopathy in Barth syndrome. Reactive oxygen species (ROS) have been implicated in the development of cardiomyopathy and are also the obligated byproducts of mitochondria. We hypothesized that tafazzin knockdown increases ROS production from mitochondria, and a mitochondria-targeted antioxidant prevents tafazzin knockdown induced mitochondrial and cardiac dysfunction. We employed cardiac myocytes transduced with an adenovirus containing tafazzin shRNA as a model to investigate the effects of the mitochondrial antioxidant, mito-Tempo. Knocking down tafazzin decreased steady state levels of cardiolipin and increased mitochondrial ROS. Treatment of cardiac myocytes with mito-Tempo normalized tafazzin knockdown enhanced mitochondrial ROS production and cellular ATP decline. Mito-Tempo also significantly abrogated tafazzin knockdown induced cardiac hypertrophy, contractile dysfunction, and cell death. We conclude that mitochondria-targeted antioxidant prevents cardiac dysfunction induced by tafazzin gene knockdown in cardiac myocytes and suggest mito-Tempo as a potential therapeutic for Barth syndrome and other dilated cardiomyopathies resulting from mitochondrial oxidative stress. PMID:25247053

A Study to Determine if Pharmaceutical Cost is Related to Diagnostic Complexity for the Treatment of Essential Hypertension Patients at Womack Army Community Hospital

DTIC Science & Technology

1987-05-01

angiotensin without actually measuring sodium electrolyte levels), and pancreatic disease (to remove potential confounding effects of diabetes ...side effects such as muscle weakness, polyuria and an increased propensity toward cardiac arrhythmias. When uric acid (UA) levels increase to 6.0 mg per

Roles of Sensory Nerves in the Regulation of Radiation-Induced Structural and Functional Changes in the Heart

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

Sridharan, Vijayalakshmi; Tripathi, Preeti; Sharma, Sunil

Purpose: Radiation-induced heart disease (RIHD) is a chronic severe side effect of radiation therapy of intrathoracic and chest wall tumors. The heart contains a dense network of sensory neurons that not only are involved in monitoring of cardiac events such as ischemia and reperfusion but also play a role in cardiac tissue homeostasis, preconditioning, and repair. The purpose of this study was to examine the role of sensory nerves in RIHD. Methods and Materials: Male Sprague-Dawley rats were administered capsaicin to permanently ablate sensory nerves, 2 weeks before local image-guided heart x-ray irradiation with a single dose of 21 Gy.more » During the 6 months of follow-up, heart function was assessed with high-resolution echocardiography. At 6 months after irradiation, cardiac structural and molecular changes were examined with histology, immunohistochemistry, and Western blot analysis. Results: Capsaicin pretreatment blunted the effects of radiation on myocardial fibrosis and mast cell infiltration and activity. By contrast, capsaicin pretreatment caused a small but significant reduction in cardiac output 6 months after irradiation. Capsaicin did not alter the effects of radiation on cardiac macrophage number or indicators of autophagy and apoptosis. Conclusions: These results suggest that sensory nerves, although they play a predominantly protective role in radiation-induced cardiac function changes, may eventually enhance radiation-induced myocardial fibrosis and mast cell activity.« less

Semiautomatic segmentation of the heart from CT images based on intensity and morphological features

NASA Astrophysics Data System (ADS)

Redwood, Abena B.; Camp, Jon J.; Robb, Richard A.

2005-04-01

The incidence of certain types of cardiac arrhythmias is increasing. Effective, minimally invasive treatment has remained elusive. Pharmacologic treatment has been limited by drug intolerance and recurrence of disease. Catheter based ablation has been moderately successful in treating certain types of cardiac arrhythmias, including typical atrial flutter and fibrillation, but there remains a relatively high rate of recurrence. Additional side effects associated with cardiac ablation procedures include stroke, perivascular lung damage, and skin burns caused by x-ray fluoroscopy. Access to patient specific 3-D cardiac images has potential to significantly improve the process of cardiac ablation by providing the physician with a volume visualization of the heart. This would facilitate more effective guidance of the catheter, increase the accuracy of the ablative process, and eliminate or minimize the damage to surrounding tissue. In this study, a semiautomatic method for faithful cardiac segmentation was investigated using Analyze - a comprehensive processing software package developed at the Biomedical Imaging Resource, Mayo Clinic. This method included use of interactive segmentation based on math morphology and separation of the chambers based on morphological connections. The external surfaces of the hearts were readily segmented, while accurate separation of individual chambers was a challenge. Nonetheless, a skilled operator could manage the task in a few minutes. Useful improvements suggested in this paper would give this method a promising future.

Deep Inspiration Breath Hold: Techniques and Advantages for Cardiac Sparing During Breast Cancer Irradiation.

PubMed

Bergom, Carmen; Currey, Adam; Desai, Nina; Tai, An; Strauss, Jonathan B

2018-01-01

Historically, heart dose from left-sided breast radiotherapy has been associated with a risk of cardiac injury. Data suggests that there is not a threshold for the deleterious effects from radiation on the heart. Over the past several years, advances in radiation delivery techniques have reduced cardiac morbidity due to treatment. Deep inspiration breath hold (DIBH) is a technique that takes advantage of a more favorable position of the heart during inspiration to minimize heart doses over a course of radiation therapy. In the accompanying review article, we outline several methods used to deliver treatment with DIBH, quantify the benefits of DIBH treatment, discuss considerations for patient selection, and identify challenges associated with DIBH techniques.

Pulmonary hypertension and isolated right heart failure complicating amiodarone induced hyperthyroidism.

PubMed

Wong, Sean-Man; Tse, Hung-Fat; Siu, Chung-Wah

2012-03-01

Hyperthyroidism is a common side effect encountered in patients prescribed long-term amiodarone therapy for cardiac arrhythmias. We previously studied 354 patients prescribed amiodarone in whom the occurrence of hyperthyroidism was associated with major adverse cardiovascular events including heart failure, myocardial infarction, ventricular arrhythmias, stroke and even death [1]. We now present a case of amiodarone-induced hyperthyroidism complicated by isolated right heart failure and pulmonary hypertension that resolved with treatment of hyperthyroidism. Detailed quantitative echocardiography enables improved understanding of the haemodynamic mechanisms underlying the condition. Copyright © 2011 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Successful resuscitation of cardiac arrest caused by CO2 embolism with intra-aortic injection of epinephrine during off-pump coronary bypass surgery -a case report-.

PubMed

Lee, Choon Soo; Yoon, Yeo Sam; Shim, Jae-Kwang; Lim, Hyun Kyoung

2013-12-01

Although compressed gas (CO2) blowers have been used safely to aid accurate grafting during off-pump coronary bypass surgery, hemodynamic collapse due to gas embolism into the right coronary artery may occur. Supportive measures to facilitate gas clearance by increasing the coronary perfusion pressure have been reported to be successful in restoring hemodynamic stability. However, right ventricular dysfunction and atrioventricular nodal ischemia may hinder effective systemic delivery of the vasoactive medications, even when performing resuscitative measures such as direct cardiac massage. We herein report a case of cardiac arrest that was caused by a right coronary gas embolism and that could not be restored by cardiac resuscitation. When supportive measures fail, direct aortic injection of epinephrine to increase the coronary perfusion pressure can be attempted before initiating cardiopulmonary bypass, and this approach may be life-saving in situations that limit systemic drug delivery from the venous side despite the performance of direct cardiac massage.

Successful resuscitation of cardiac arrest caused by CO2 embolism with intra-aortic injection of epinephrine during off-pump coronary bypass surgery -a case report-

PubMed Central

Lee, Choon Soo; Yoon, Yeo Sam; Shim, Jae-Kwang

2013-01-01

Although compressed gas (CO2) blowers have been used safely to aid accurate grafting during off-pump coronary bypass surgery, hemodynamic collapse due to gas embolism into the right coronary artery may occur. Supportive measures to facilitate gas clearance by increasing the coronary perfusion pressure have been reported to be successful in restoring hemodynamic stability. However, right ventricular dysfunction and atrioventricular nodal ischemia may hinder effective systemic delivery of the vasoactive medications, even when performing resuscitative measures such as direct cardiac massage. We herein report a case of cardiac arrest that was caused by a right coronary gas embolism and that could not be restored by cardiac resuscitation. When supportive measures fail, direct aortic injection of epinephrine to increase the coronary perfusion pressure can be attempted before initiating cardiopulmonary bypass, and this approach may be life-saving in situations that limit systemic drug delivery from the venous side despite the performance of direct cardiac massage. PMID:24427464

Effects of side lying on lung function in older individuals.

PubMed

Manning, F; Dean, E; Ross, J; Abboud, R T

1999-05-01

Body positioning exerts a strong effect on pulmonary function, but its effect on other components of the oxygen transport pathway are less well understood, especially the effects of side-lying positions. This study investigated the interrelationships between side-lying positions and indexes of lung function such as spirometry, alveolar diffusing capacity, and inhomogeneity of ventilation in older individuals. Nineteen nonsmoking subjects (mean age=62.8 years, SD=6.8, range=50-74) with no history of cardiac or pulmonary disease were tested over 2 sessions. The test positions were sitting and left side lying in one session and sitting and right side lying in the other session. In each of the positions, forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), single-breath pulmonary diffusing capacity (DLCO/VA), and the slope of phase III (DN2%/L) of the single-breath nitrogen washout test to determine inhomogeneity of ventilation were measured. Compared with measurements obtained in the sitting position, FVC and FEV1 were decreased equally in the side-lying positions, but no change was observed in DLCO/VA or DN2%/L. Side-lying positions resulted in decreases in FVC and FEV1, which is consistent with the well-documented effects of the supine position. These findings further support the need for prescriptive rather than routine body positioning of patients with risks of cardiopulmonary compromise and the need to use upright positions in which lung volumes and capacities are maximized.

Psychopharmacology of Attention-Deficit Hyperactivity Disorder: Effects and Side Effects.

PubMed

Golmirzaei, Javad; Mahboobi, Hamidreza; Yazdanparast, Maryam; Mushtaq, Gohar; Kamal, Mohammad A; Hamzei, Enayatollah

2016-01-01

Attention-deficit hyperactivity disorder (ADHD) is a common psychiatric disorder in children which manifests with hyperactivity, impulsivity, and/or inattention. Several drugs are used in treatment of ADHD. Stimulants, atomoxetine, anti-depressants, and bupropion are common medications used in the treatment of ADHD. Stimulants are widely used as the first line treatment in children with ADHD. Their mechanism of action is the release of dopamine and norepinephrine in central nervous system. Methylphenidate is the most common stimulant used for the treatment of ADHD. Methylphenidate significantly reduces ADHD symptoms in children both at home and school and improves their social skills. Methylphenidate is safe in healthy children and has shown to have no cardiac side effects in these patients. Other medications include: Atomoxetine, Amphetamines, Clonidine, Melatonin, and anti-depressants. Effects, side effects, and mechanism of action these drugs have been discussed in this paper.

Automated patch clamp on mESC-derived cardiomyocytes for cardiotoxicity prediction.

PubMed

Stoelzle, Sonja; Haythornthwaite, Alison; Kettenhofen, Ralf; Kolossov, Eugen; Bohlen, Heribert; George, Michael; Brüggemann, Andrea; Fertig, Niels

2011-09-01

Cardiovascular side effects are critical in drug development and have frequently led to late-stage project terminations or even drug withdrawal from the market. Physiologically relevant and predictive assays for cardiotoxicity are hence strongly demanded by the pharmaceutical industry. To identify a potential impact of test compounds on ventricular repolarization, typically a variety of ion channels in diverse heterologously expressing cells have to be investigated. Similar to primary cells, in vitro-generated stem cell-derived cardiomyocytes simultaneously express cardiac ion channels. Thus, they more accurately represent the native situation compared with cell lines overexpressing only a single type of ion channel. The aim of this study was to determine if stem cell-derived cardiomyocytes are suited for use in an automated patch clamp system. The authors show recordings of cardiac ion currents as well as action potential recordings in readily available stem cell-derived cardiomyocytes. Besides monitoring inhibitory effects of reference compounds on typical cardiac ion currents, the authors revealed for the first time drug-induced modulation of cardiac action potentials in an automated patch clamp system. The combination of an in vitro cardiac cell model with higher throughput patch clamp screening technology allows for a cost-effective cardiotoxicity prediction in a physiologically relevant cell system.

Oral theophylline in chronic heart failure

PubMed Central

Al-Damluji, S.; Johnston, A.; Spurrell, R. A. J.; Nathan, A. W.; Banim, S. O.; Camm, A. J.

1982-01-01

Theophylline choline 600 mg was given as a single oral dose to nine patients in chronic left ventricular failure due to myocardial dysfunction. Cardiac output, left ventricular filling pressure (LVFP) and right atrial pressure (RAP) were measured with a pulmonary artery thermodilution catheter for the following 3 hr. Continuous recordings of cardiac rhythm were made throughout the study. Mean cardiac index increased from 1·75 (±0·14 s.e. mean) to 2·04 (±0·11) 1/min/m2 (P<0·02), mean LVFP fell from 27 (±2·4) to 22 (±1·5) mmHg (P<0·01), mean RAP fell from 5 (±1·3) to 3 (±2·0) mmHg (P<0·05) and mean systemic arterial pressure rose from 80 (±3) to 86 (±3·5) mmHg (P<0·05). There were no significant changes in heart rate or systemic vascular resistance; thus the increase in cardiac output was probably due to a positive inotropic effect. Side effects were seen in two patients, both of whom proved to have toxic plasma theophylline concentrations. This study demonstrated a beneficial acute haemodynamic effect of oral theophylline in chronic cardiac failure. PMID:7111101

Effect of Statins on Skeletal Muscle: Exercise, Myopathy, and Muscle Outcomes

PubMed Central

Parker, Beth A.; Thompson, Paul D.

2012-01-01

Statins are effective for reducing low-density lipoprotein cholesterol and cardiac events, but can produce muscle side effects. We have hypothesized that statin-related muscle complaints are exacerbated by exercise and influenced by factors including mitochondrial dysfunction, membrane disruption and/or calcium handling. The interaction between statins, exercise and muscle symptoms may be more effectively diagnosed and treated as rigorous scientific studies accumulate. PMID:23000957

Deferiprone for the treatment of transfusional iron overload in thalassemia.

PubMed

Belmont, Ami; Kwiatkowski, Janet L

2017-06-01

Transfusional iron overload can lead to hepatic fibrosis, arrhythmias and congestive heart failure and a number of endocrinopathies. Deferiprone is an oral iron chelator approved for use in the United States as a second line agent for the treatment of transfusional iron overload in patients with thalassemia. Areas covered: This article will review the data regarding the efficacy of deferiprone for iron chelation and prevention and reversal of iron related complications, the drug's adverse effect profile, and the use of this drug in combination regimens. Expert commentary: Extensive data support that deferiprone is particularly efficacious at cardiac iron removal and therefore, a chelator regimen that contains deferiprone is generally recommended when there is significant cardiac iron loading and/or in the setting of iron-related cardiac disease. The most concerning side effects of deferiprone are agranulocytosis and milder forms of neutropenia, which require appropriate monitoring and patient/provider education.

PULMONARY ARTERIAL DISEASE ASSOCIATED WITH RIGHT-SIDED CARDIAC HYPERTROPHY AND CONGESTIVE HEART FAILURE IN ZOO MAMMALS HOUSED AT 2,100 M ABOVE SEA LEVEL.

PubMed

Juan-Sallés, Carles; Martínez, Liliana Sofía; Rosas-Rosas, Arely G; Parás, Alberto; Martínez, Osvaldo; Hernández, Alejandra; Garner, Michael M

2015-12-01

Subacute and chronic mountain sickness of humans and the related brisket disease of cattle are characterized by right-sided congestive heart failure in individuals living at high altitudes as a result of sustained hypoxic pulmonary hypertension. Adaptations to high altitude and disease resistance vary among species, breeds, and individuals. The authors conducted a retrospective survey of right-sided cardiac hypertrophy associated with pulmonary arterial hypertrophy or arteriosclerosis in zoo mammals housed at Africam Safari (Puebla, México), which is located at 2,100 m above sea level. Seventeen animals with detailed pathology records matched the study criterion. Included were 10 maras (Dolichotis patagonum), 2 cotton-top tamarins (Saguinus oedipus oedipus), 2 capybaras (Hydrochaeris hydrochaeris), and 1 case each of Bennet's wallaby (Macropus rufogriseus), nilgai antelope (Boselaphus tragocamelus), and scimitar-horned oryx (Oryx dammah). All had right-sided cardiac hypertrophy and a variety of arterial lesions restricted to the pulmonary circulation and causing arterial thickening with narrowing of the arterial lumen. Arterial lesions most often consisted of medial hypertrophy or hyperplasia of small and medium-sized pulmonary arteries. All maras also had single or multiple elevated plaques in the pulmonary arterial trunk consisting of fibrosis, accompanied by chondroid metaplasia in some cases. Both antelopes were juvenile and died with right-sided congestive heart failure associated with severe pulmonary arterial lesions. To the authors' knowledge, this is the first description of cardiac and pulmonary arterial disease in zoo mammals housed at high altitudes.

Toxicological Findings in 889 Fatally Injured Obese Pilots Involved in Aviation Accidents

DTIC Science & Technology

2010-05-01

fenfluramine has now been withdrawn from the drug markets due to its side effects , heart valve conditions, pulmonary hypertensions, and cardiac...adverse effects of excess visceral abdominal fat (4, 5, 34) . abdominal obesity has been linked with coronary heart disease (22) . the comorbidities...Methamphetamine Cocaine Δ9-Tetrahydrocannabinol (THC)/THC Carboxylic Acid Prescription Drugs Alprazolam Amitriptyline Amlodipine Atenolol Atropine

Side Effects to Antidepressant Treatment in Patients With Depression and Comorbid Panic Disorder.

PubMed

Shankman, Stewart A; Gorka, Stephanie M; Katz, Andrea C; Klein, Daniel N; Markowitz, John C; Arnow, Bruce A; Manber, Rachel; Rothbaum, Barbara O; Thase, Michael E; Schatzberg, Alan F; Keller, Martin B; Trivedi, Madhukar H; Kocsis, James H

2017-04-01

Side effects to antidepressant medication can affect the efficacy of treatment, but few predictors foretell who experiences side effects and which side effects they experience. This secondary data analysis examined whether depressed patients with comorbid panic disorder were more likely to experience side effects than those without panic disorder. The study also examined whether greater burden of side effects predicted a poorer treatment course for patients with panic disorder than those without panic disorder. To examine the specificity of these effects, analyses also examined 2 other anxiety disorders-social phobia and generalized anxiety disorder (GAD). Between 2002 and 2006, a large sample (N = 808) of chronically depressed individuals (assessed using the Structured Clinical Interview for DSM-IV-TR Axis I Disorders [SCID-IV]) received antidepressants according to a predetermined algorithm for 12 weeks. Every 2 weeks, depressive symptoms (per the Hamilton Depression Rating Scale) and side effects (specific side effects as well as several indicators of side effect burden) were assessed. Lifetime diagnosis of panic disorder (assessed using the SCID-IV) at baseline was associated with higher likelihood of gastrointestinal (OR = 1.6 [95% CI, 1.0-2.6]), cardiac (OR = 1.8 [95% CI, 1.1-3.1]), neurologic (OR = 2.6 [95% CI, 1.6-4.2]), and genitourinary side effects (OR = 3.0 [95% CI, 1.7-5.3]) during treatment. Increases in side effect frequency, intensity, and impairment over time were more strongly associated with increases in depressive symptoms for patients with panic disorder compared to those without panic disorder. Neither social phobia nor GAD was associated with these effects. Potentially due to heighte​ned interoceptive awareness of changes in their body, chronically depressed individuals with panic disorder may be at greater risk than those without panic disorder for antidepressant side effects and to experience a worsening of depressive symptoms as a result of these side effects over time. ClinicalTrials.gov identifier: NCT00057551​. © Copyright 2017 Physicians Postgraduate Press, Inc.

Doping with anabolic androgenic steroids (AAS): Adverse effects on non-reproductive organs and functions.

PubMed

Nieschlag, Eberhard; Vorona, Elena

2015-09-01

Since the 1970s anabolic androgenic steroids (AAS) have been abused at ever increasing rates in competitive athletics, in recreational sports and in bodybuilding. Exceedingly high doses are often consumed over long periods, in particular by bodybuilders, causing acute or chronic adverse side effects frequently complicated by additional polypharmacy. This review summarizes side effects on non-reproductive organs and functions; effects on male and female reproduction have been recently reviewed in a parallel paper. Among the most striking AAS side effects are increases in haematocrit and coagulation causing thromboembolism, intracardiac thrombosis and stroke as well as other cardiac disturbances including arrhythmias, cardiomyopathies and possibly sudden death. 17α-alkylated AAS are liver toxic leading to cholestasis, peliosis, adenomas and carcinomas. Hyperbilirubinaemia can cause cholemic nephrosis and kidney failure. AAS abuse may induce exaggerated self-confidence, reckless behavior, aggressiveness and psychotic symptoms. AAS withdrawal may be accompanied by depression and suicidal intentions. Since AAS abuse is not or only reluctantly admitted physicians should be aware of the multitude of serious side effects when confronted with unclear symptoms.

Acetazolamide-related life-threatening hypophosphatemia in a glaucoma patient.

PubMed

Hu, Ching-Yun; Lee, Bor-Jen; Cheng, Hsiang-Fan; Wang, Chen-Yu

2015-01-01

Acetazolamide-related hypophosphatemia leading to cardiac arrest is extremely rare. Herein we report a 78-year-old female glaucoma patient who developed general weakness and acute respiratory failure, followed by cardiac arrest 1 day after taking acetazolamide. The patient was successfully weaned from the ventilator after correction of hypophosphatemia and fully recovered. As acetazolamide was shown to have the potential to cause a lethal side effect in stable glaucoma, the risk of hypophosphatemia should be kept in mind by ophthalmologists. An examination of serum metabolic panels may be indicated in patients at risk of hypophosphatemia.

St. John's wort: a new alternative for depression?

PubMed

Josey, E S; Tackett, R L

1999-03-01

The primary purpose of this article is to review the existing literature concerning the therapeutic uses, adverse effects, and possible drug interactions of St. John's wort (Hypericum perforatum) as compared to other antidepressant medications. Reference material was obtained through database searches with time restrictions of 1985 to the present. Studies selected were those written in the English language which compared the role of St. John's wort, tricyclic antidepressants, monoamine oxidase inhibitors, and serotonin-selective reuptake inhibitors in the treatment of depression. Other studies were selected based on their evaluation of the safety and efficacy of St. John's wort as an antidepressant for a minimum of four weeks. A review of existing literature recognized nine clinical trials that reported the efficacy of St. John's wort as compared to placebo and to other antidepressant medications. Of these nine, four controlled studies were chosen based upon their large patient populations and their consistency in brand and dosage of St. John's wort used. These four studies demonstrated that St. John's wort was as effective as other antidepressant medications and more effective than placebo, as the clinical symptoms of depression greatly decreased upon administration of H. perforatum. The side-effect profile of H. perforatum at this time appears to be superior to any current U.S.-approved antidepressant medication. From the existing literature, St. John's wort appears to be a safe and effective alternative in the treatment of depression. Tricylic antidepressants and monoamine oxidase inhibitors can produce serious cardiac side-effects, such as tachycardia and postural hypotension, and many unwanted anticholinergic side-effects, including dry mouth and constipation. St. John's wort has proven to be free of any cardiac, as well as anticholinergic, side-effects normally seen with antidepressant medications. Based upon limited studies, St. John's wort appears to be an acceptable alternative to traditional antidepressant therapy, although trials on a larger scale are warranted in this area. Hypericum is available to the lay public as an over-the-counter preparation and may be misused if not fully understood.

Computational cardiology: the bidomain based modified Hill model incorporating viscous effects for cardiac defibrillation

NASA Astrophysics Data System (ADS)

Cansız, Barış; Dal, Hüsnü; Kaliske, Michael

2017-10-01

Working mechanisms of the cardiac defibrillation are still in debate due to the limited experimental facilities and one-third of patients even do not respond to cardiac resynchronization therapy. With an aim to develop a milestone towards reaching the unrevealed mechanisms of the defibrillation phenomenon, we propose a bidomain based finite element formulation of cardiac electromechanics by taking into account the viscous effects that are disregarded by many researchers. To do so, the material is deemed as an electro-visco-active material and described by the modified Hill model (Cansız et al. in Comput Methods Appl Mech Eng 315:434-466, 2017). On the numerical side, we utilize a staggered solution method, where the elliptic and parabolic part of the bidomain equations and the mechanical field are solved sequentially. The comparative simulations designate that the viscoelastic and elastic formulations lead to remarkably different outcomes upon an externally applied electric field to the myocardial tissue. Besides, the achieved framework requires significantly less computational time and memory compared to monolithic schemes without loss of stability for the presented examples.

New-onset third-degree atrioventricular block because of autoimmune-induced myositis under treatment with anti-programmed cell death-1 (nivolumab) for metastatic melanoma.

PubMed

Behling, Juliane; Kaes, Joachim; Münzel, Thomas; Grabbe, Stephan; Loquai, Carmen

2017-04-01

There has been considerable progress in treating malignant melanoma over the last few years. The immune-checkpoint-inhibitors nivolumab and pembrolizumab have been approved by the Food and Drug Administration in 2014 for the therapy of metastatic melanoma. Anti-programmed cell death-1-blocking antibodies are known to cause immune-related adverse events. Physicians should be aware of common and rare side effects and pay attention to new ones. We therefore report a severe and life-threatening side effect of anti-programmed cell death-1 immunotherapy with nivolumab that has not been previously reported: the development of a third-degree atrioventricular block. After a second infusion with nivolumab, our patient developed a troponin I-positive and autoantibody-positive myositis and a few days later a new-onset third-degree atrioventricular block. This is most likely because of an autoimmune-induced myositis with a cardiac impairment in terms of a myocarditis, which led to an impairment of the conduction of cardiac electrical stimuli.

Direct, Differential Effects of Tamoxifen, 4-Hydroxytamoxifen, and Raloxifene on Cardiac Myocyte Contractility and Calcium Handling

PubMed Central

Asp, Michelle L.; Martindale, Joshua J.; Metzger, Joseph M.

2013-01-01

Tamoxifen (Tam), a selective estrogen receptor modulator, is in wide clinical use for the treatment and prevention of breast cancer. High Tam doses have been used for treatment of gliomas and cancers with multiple drug resistance, but long QT Syndrome is a side effect. Tam is also used experimentally in mice for inducible gene knockout in numerous tissues, including heart; however, the potential direct effects of Tam on cardiac myocyte mechanical function are not known. The goal of this study was to determine the direct, acute effects of Tam, its active metabolite 4-hydroxytamoxifen (4OHT), and related drug raloxifene (Ral) on isolated rat cardiac myocyte mechanical function and calcium handling. Tam decreased contraction amplitude, slowed relaxation, and decreased Ca2+ transient amplitude. Effects were primarily observed at 5 and 10 μM Tam, which is relevant for high dose Tam treatment in cancer patients as well as Tam-mediated gene excision in mice. Myocytes treated with 4OHT responded similarly to Tam-treated cells with regard to both contractility and calcium handling, suggesting an estrogen-receptor independent mechanism is responsible for the effects. In contrast, Ral increased contraction and Ca2+ transient amplitudes. At 10 μM, all drugs had a time-dependent effect to abolish cellular contraction. In conclusion, Tam, 4OHT, and Ral adversely and differentially alter cardiac myocyte contractility and Ca2+ handling. These findings have important implications for understanding the Tam-induced cardiomyopathy in gene excision studies and may be important for understanding effects on cardiac performance in patients undergoing high-dose Tam therapy. PMID:24205315

2017 Multimodality Appropriate Use Criteria for Noninvasive Cardiac Imaging: Expert Consensus of the Asian Society of Cardiovascular Imaging.

PubMed

Beck, Kyongmin Sarah; Kim, Jeong A; Choe, Yeon Hyeon; Hian, Sim Kui; Hoe, John; Hong, Yoo Jin; Kim, Sung Mok; Kim, Tae Hoon; Kim, Young Jin; Kim, Yun Hyeon; Kuribayashi, Sachio; Lee, Jongmin; Leong, Lilian; Lim, Tae-Hwan; Lu, Bin; Park, Jae Hyung; Sakuma, Hajime; Yang, Dong Hyun; Yaw, Tan Swee; Wan, Yung-Liang; Zhang, Zhaoqi; Zhao, Shihua; Yong, Hwan Seok

2017-01-01

In 2010, the Asian Society of Cardiovascular Imaging (ASCI) provided recommendations for cardiac CT and MRI, and this document reflects an update of the 2010 ASCI appropriate use criteria (AUC). In 2016, the ASCI formed a new working group for revision of AUC for noninvasive cardiac imaging. A major change that we made in this document is the rating of various noninvasive tests (exercise electrocardiogram, echocardiography, positron emission tomography, single-photon emission computed tomography, radionuclide imaging, cardiac magnetic resonance, and cardiac computed tomography/angiography), compared side by side for their applications in various clinical scenarios. Ninety-five clinical scenarios were developed from eight selected pre-existing guidelines and classified into four sections as follows: 1) detection of coronary artery disease, symptomatic or asymptomatic; 2) cardiac evaluation in various clinical scenarios; 3) use of imaging modality according to prior testing; and 4) evaluation of cardiac structure and function. The clinical scenarios were scored by a separate rating committee on a scale of 1-9 to designate appropriate use, uncertain use, or inappropriate use according to a modified Delphi method. Overall, the AUC ratings for CT were higher than those of previous guidelines. These new AUC provide guidance for clinicians choosing among available testing modalities for various cardiac diseases and are also unique, given that most previous AUC for noninvasive imaging include only one imaging technique. As cardiac imaging is multimodal in nature, we believe that these AUC will be more useful for clinical decision making.

Tricuspid regurgitation

MedlinePlus

... enlargement of the right side of the heart. Doppler echocardiography or right-sided cardiac catheterization may be ... Carabello BA. Valvular heart disease. In: Goldman L, Schafer AI, eds. ... Saunders; 2016:chap 75. Nishimura. RA, Otto CM, Bownow RO, ...

Multiple Roles of Pitx2 in Cardiac Development and Disease

PubMed Central

2017-01-01

Cardiac development is a complex morphogenetic process initiated as bilateral cardiogenic mesoderm is specified at both sides of the gastrulating embryo. Soon thereafter, these cardiogenic cells fuse at the embryonic midline configuring a symmetrical linear cardiac tube. Left/right bilateral asymmetry is first detected in the forming heart as the cardiac tube bends to the right, and subsequently, atrial and ventricular chambers develop. Molecular signals emanating from the node confer distinct left/right signalling pathways that ultimately lead to activation of the homeobox transcription factor Pitx2 in the left side of distinct embryonic organ anlagen, including the developing heart. Asymmetric expression of Pitx2 has therefore been reported during different cardiac developmental stages, and genetic deletion of Pitx2 provided evidence of key regulatory roles of this transcription factor during cardiogenesis and thus congenital heart diseases. More recently, impaired Pitx2 function has also been linked to arrhythmogenic processes, providing novel roles in the adult heart. In this manuscript, we provide a state-of-the-art review of the fundamental roles of Pitx2 during cardiogenesis, arrhythmogenesis and its contribution to congenital heart diseases. PMID:29367545

A phase I study of human natural interferon-beta in cancer patients.

PubMed

Liberati, A M; Biscottini, B; Fizzotti, M; Schippa, M; De Angelis, V; Senatore, M; Vittori, O; Teggia, L; Natali, R; Palmisano, L

1989-06-01

In this phase I study 15 patients with metastatic tumors were given interferon (IFN)-beta by i.v. bolus injections. Twelve individual doses of 1, 2, 3.3, 5, 7, 9, 12, 16, 21, 27, 35, and 46 x 10(6) IU were administered every other day. The single maximal tolerated dose ranged from 9 to 46 x 10(6) IU. Eight patients tolerated the dose of 46 x 10(6) IU without side effects. Disturbances of cardiac rhythm were observed, but were closely related temporally to severe chills and appeared to be the consequence of adrenergic stimulation associated with this side-effect. In addition, no significant variations in the left ventricular function as assessed by nuclear stethoscope were observed. Neurotoxicity was not a major side-effect. The toxicity of IFN-beta given as scheduled in this study was significant, but acceptable.

Refractory Cardiogenic Shock During Tramadol Poisoning: A Case Report.

PubMed

Belin, Nicolas; Clairet, Anne-Laure; Chocron, Sidney; Capellier, Gilles; Piton, Gaël

2017-04-01

Tramadol is a weak opioid analgesic indicated for the treatment of moderate to severe pain. Tramadol intoxication can be lethal, and this drug is frequently involved in voluntary overdose. Classically, tramadol intoxication is associated with neurological and respiratory side effects. In contrast, cardiac effects are poorly documented in the literature. We report a case of severe tramadol intoxication, with plasma concentration 20 times the toxic threshold, complicated by refractory cardiogenic shock, successfully treated by extra corporeal life support (ECLS) with a favorable cardiac outcome and ECLS weaning at day 10. Seizure, clonus, and nonreactive mydriasis were present during 4 days, and complete awakening was delayed to day 15. Poisoning caused by high doses of tramadol can lead to refractory cardiogenic shock, and ECLS can be considered as effective rescue therapy in this context.

Utility of Deep Inspiration Breath Hold for Left-Sided Breast Radiation Therapy in Preventing Early Cardiac Perfusion Defects: A Prospective Study

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

Zagar, Timothy M., E-mail: zagar@med.unc.edu; Kaidar-Person, Orit; Tang, Xiaoli

Purpose: To evaluate early cardiac single photon computed tomography (SPECT) findings after left breast/chest wall postoperative radiation therapy (RT) in the setting of deep inspiration breath hold (DIBH). Methods and Materials: We performed a prospective single-institution single-arm study of patients who were planned for tangential RT with DIBH to the left breast/chest wall (± internal mammary nodes). The DIBH was done by use of a controlled surface monitoring technique (AlignRT, Vision RT Ltd, London, UK). The RT was given with tangential fields and a heart block. Radiation-induced cardiac perfusion and wall motion changes were assessed by pre-RT and 6-month post-RTmore » SPECT scans. A cumulative SPECT summed-rest score was used to quantify perfusion in predefined left ventricle segments. The incidence of wall motion abnormalities was assessed in each of these same segments. Results: A total of 20 patients with normal pre-RT scans were studied; their median age was 56 years (range, 39-72 years). Seven (35%) patients also received irradiation to the left internal mammary chain, and 5 (25%) received an additional RT field to supraclavicular nodes. The median heart dose was 94 cGy (range, 56-200 cGy), and the median V25{sub Gy} was zero (range, 0-0.1). None of the patients had post-RT perfusion or wall motion abnormalities. Conclusions: Our results suggest that DIBH and conformal cardiac blocking for patients receiving tangential RT for left-sided breast cancer is an effective means to avoid early RT-associated cardiac perfusion defects.« less

Interdepartmental conflict management and negotiation in cardiovascular imaging.

PubMed

Otero, Hansel J; Nallamshetty, Leelakrishna; Rybicki, Frank J

2008-07-01

Although the relationship between cardiologists and radiologists has a thorny history, advanced cardiac imaging technology and the promise of cardiac computed tomography are forcing both specialties back to the negotiation table. These discussions represent an opportunity for better communication, collaboration, and resource allocation. The authors address the aspects of interdepartmental conflict management and negotiation through their radiology department's ongoing efforts to provide high-quality advanced noninvasive cardiovascular imaging services at a large academic institution. The definition and causes of conflict are defined, with a specific focus on noninvasive cardiovascular imaging, followed by a description of steps used in the negotiation process. The authors encourage radiologists to entertain an open dialogue with cardiology, because in many cases, both sides can benefit. The benefits of a negotiated outcome include minimizing internal competitors, incorporating cardiologists' expertise to cardiac imaging algorithms, and more effective training opportunities.

Use of antiarrhythmic drugs in elderly patients.

PubMed

Lee, Hon-Chi; Tl Huang, Kristin; Shen, Win-Kuang

2011-09-01

Human aging is a global issue with important implications for current and future incidence and prevalence of health conditions and disability. Cardiac arrhythmias, including atrial fibrillation, sudden cardiac death, and bradycardia requiring pacemaker placement, all increase exponentially after the age of 60. It is important to distinguish between the normal, physiological consequences of aging on cardiac electrophysiology and the abnormal, pathological alterations. The age-related cardiac changes include ventricular hypertrophy, senile amyloidosis, cardiac valvular degenerative changes and annular calcification, fibrous infiltration of the conduction system, and loss of natural pacemaker cells and these changes could have a profound effect on the development of arrhythmias. The age-related cardiac electrophysiological changes include up- and down-regulation of specific ion channel expression and intracellular Ca(2+) overload which promote the development of cardiac arrhythmias. As ion channels are the substrates of antiarrhythmic drugs, it follows that the pharmacokinetics and pharmacodynamics of these drugs will also change with age. Aging alters the absorption, distribution, metabolism, and elimination of antiarrhythmic drugs, so liver and kidney function must be monitored to avoid potential adverse drug effects, and antiarrhythmic dosing may need to be adjusted for age. Elderly patients are also more susceptible to the side effects of many antiarrhythmics, including bradycardia, orthostatic hypotension, urinary retention, and falls. Moreover, the choice of antiarrhythmic drugs in the elderly patient is frequently complicated by the presence of co-morbid conditions and by polypharmacy, and the astute physician must pay careful attention to potential drug-drug interactions. Finally, it is important to remember that the use of antiarrhythmic drugs in elderly patients must be individualized and tailored to each patient's physiology, disease processes, and medication regimen.

2017 Multimodality Appropriate Use Criteria for Noninvasive Cardiac Imaging: Expert Consensus of the Asian Society of Cardiovascular Imaging

PubMed Central

Beck, Kyongmin Sarah; Kim, Jeong A; Choe, Yeon Hyeon; Hian, Sim Kui; Hoe, John; Hong, Yoo Jin; Kim, Sung Mok; Kim, Tae Hoon; Kim, Young Jin; Kim, Yun Hyeon; Kuribayashi, Sachio; Lee, Jongmin; Leong, Lilian; Lim, Tae-Hwan; Lu, Bin; Park, Jae Hyung; Sakuma, Hajime; Yang, Dong Hyun; Yaw, Tan Swee; Wan, Yung-Liang; Zhang, Zhaoqi; Zhao, Shihua

2017-01-01

In 2010, the Asian Society of Cardiovascular Imaging (ASCI) provided recommendations for cardiac CT and MRI, and this document reflects an update of the 2010 ASCI appropriate use criteria (AUC). In 2016, the ASCI formed a new working group for revision of AUC for noninvasive cardiac imaging. A major change that we made in this document is the rating of various noninvasive tests (exercise electrocardiogram, echocardiography, positron emission tomography, single-photon emission computed tomography, radionuclide imaging, cardiac magnetic resonance, and cardiac computed tomography/angiography), compared side by side for their applications in various clinical scenarios. Ninety-five clinical scenarios were developed from eight selected pre-existing guidelines and classified into four sections as follows: 1) detection of coronary artery disease, symptomatic or asymptomatic; 2) cardiac evaluation in various clinical scenarios; 3) use of imaging modality according to prior testing; and 4) evaluation of cardiac structure and function. The clinical scenarios were scored by a separate rating committee on a scale of 1–9 to designate appropriate use, uncertain use, or inappropriate use according to a modified Delphi method. Overall, the AUC ratings for CT were higher than those of previous guidelines. These new AUC provide guidance for clinicians choosing among available testing modalities for various cardiac diseases and are also unique, given that most previous AUC for noninvasive imaging include only one imaging technique. As cardiac imaging is multimodal in nature, we believe that these AUC will be more useful for clinical decision making. PMID:29089819

Multimodality Imaging in Cardiooncology

PubMed Central

Pizzino, Fausto; Vizzari, Giampiero; Qamar, Rubina; Bomzer, Charles; Carerj, Scipione; Khandheria, Bijoy K.

2015-01-01

Cardiotoxicity represents a rising problem influencing prognosis and quality of life of chemotherapy-treated patients. Anthracyclines and trastuzumab are the drugs most commonly associated with development of a cardiotoxic effect. Heart failure, myocardial ischemia, hypertension, myocarditis, and thrombosis are typical manifestation of cardiotoxicity by chemotherapeutic agents. Diagnosis and monitoring of cardiac side-effects of cancer treatment is of paramount importance. Echocardiography and nuclear medicine methods are widely used in clinical practice and left ventricular ejection fraction is the most important parameter to asses myocardial damage secondary to chemotherapy. However, left ventricular ejection decrease is a delayed phenomenon, occurring after a long stage of silent myocardial damage that classic imaging methods are not able to detect. New imaging techniques including three-dimensional echocardiography, speckle tracking echocardiography, and cardiac magnetic resonance have demonstrated high sensitivity in detecting the earliest alteration of left ventricular function associated with future development of chemotherapy-induced cardiomyopathy. Early diagnosis of cardiac involvement in cancer patients can allow for timely and adequate treatment management and the introduction of cardioprotective strategies. PMID:26300915

Spiral-Wave Dynamics in a Mathematical Model of Human Ventricular Tissue with Myocytes and Fibroblasts

PubMed Central

Nayak, Alok Ranjan; Shajahan, T. K.; Panfilov, A. V.; Pandit, Rahul

2013-01-01

Cardiac fibroblasts, when coupled functionally with myocytes, can modulate the electrophysiological properties of cardiac tissue. We present systematic numerical studies of such modulation of electrophysiological properties in mathematical models for (a) single myocyte-fibroblast (MF) units and (b) two-dimensional (2D) arrays of such units; our models build on earlier ones and allow for zero-, one-, and two-sided MF couplings. Our studies of MF units elucidate the dependence of the action-potential (AP) morphology on parameters such as , the fibroblast resting-membrane potential, the fibroblast conductance , and the MF gap-junctional coupling . Furthermore, we find that our MF composite can show autorhythmic and oscillatory behaviors in addition to an excitable response. Our 2D studies use (a) both homogeneous and inhomogeneous distributions of fibroblasts, (b) various ranges for parameters such as , and , and (c) intercellular couplings that can be zero-sided, one-sided, and two-sided connections of fibroblasts with myocytes. We show, in particular, that the plane-wave conduction velocity decreases as a function of , for zero-sided and one-sided couplings; however, for two-sided coupling, decreases initially and then increases as a function of , and, eventually, we observe that conduction failure occurs for low values of . In our homogeneous studies, we find that the rotation speed and stability of a spiral wave can be controlled either by controlling or . Our studies with fibroblast inhomogeneities show that a spiral wave can get anchored to a local fibroblast inhomogeneity. We also study the efficacy of a low-amplitude control scheme, which has been suggested for the control of spiral-wave turbulence in mathematical models for cardiac tissue, in our MF model both with and without heterogeneities. PMID:24023798

Forward Programming of Cardiac Stem Cells by Homogeneous Transduction with MYOCD plus TBX5

PubMed Central

Belian, Elisa; Noseda, Michela; Abreu Paiva, Marta S.; Leja, Thomas; Sampson, Robert; Schneider, Michael D.

2015-01-01

Adult cardiac stem cells (CSCs) express many endogenous cardiogenic transcription factors including members of the Gata, Hand, Mef2, and T-box family. Unlike its DNA-binding targets, Myocardin (Myocd)—a co-activator not only for serum response factor, but also for Gata4 and Tbx5—is not expressed in CSCs. We hypothesised that its absence was a limiting factor for reprogramming. Here, we sought to investigate the susceptibility of adult mouse Sca1+ side population CSCs to reprogramming by supplementing the triad of GATA4, MEF2C, and TBX5 (GMT), and more specifically by testing the effect of the missing co-activator, Myocd. Exogenous factors were expressed via doxycycline-inducible lentiviral vectors in various combinations. High throughput quantitative RT-PCR was used to test expression of 29 cardiac lineage markers two weeks post-induction. GMT induced more than half the analysed cardiac transcripts. However, no protein was detected for the induced sarcomeric genes Actc1, Myh6, and Myl2. Adding MYOCD to GMT affected only slightly the breadth and level of gene induction, but, importantly, triggered expression of all three proteins examined (α-cardiac actin, atrial natriuretic peptide, sarcomeric myosin heavy chains). MYOCD + TBX was the most effective pairwise combination in this system. In clonal derivatives homogenously expressing MYOCD + TBX at high levels, 93% of cardiac transcripts were up-regulated and all five proteins tested were visualized. In summary: (1) GMT induced cardiac genes in CSCs, but not cardiac proteins under the conditions used. (2) Complementing GMT with MYOCD induced cardiac protein expression, indicating a more complete cardiac differentiation program. (3) Homogeneous transduction with MYOCD + TBX5 facilitated the identification of differentiating cells and the validation of this combinatorial reprogramming strategy. Together, these results highlight the pivotal importance of MYOCD in driving CSCs toward a cardiac muscle fate. PMID:26047103

Forward Programming of Cardiac Stem Cells by Homogeneous Transduction with MYOCD plus TBX5.

PubMed

Belian, Elisa; Noseda, Michela; Abreu Paiva, Marta S; Leja, Thomas; Sampson, Robert; Schneider, Michael D

2015-01-01

Adult cardiac stem cells (CSCs) express many endogenous cardiogenic transcription factors including members of the Gata, Hand, Mef2, and T-box family. Unlike its DNA-binding targets, Myocardin (Myocd)-a co-activator not only for serum response factor, but also for Gata4 and Tbx5-is not expressed in CSCs. We hypothesised that its absence was a limiting factor for reprogramming. Here, we sought to investigate the susceptibility of adult mouse Sca1+ side population CSCs to reprogramming by supplementing the triad of GATA4, MEF2C, and TBX5 (GMT), and more specifically by testing the effect of the missing co-activator, Myocd. Exogenous factors were expressed via doxycycline-inducible lentiviral vectors in various combinations. High throughput quantitative RT-PCR was used to test expression of 29 cardiac lineage markers two weeks post-induction. GMT induced more than half the analysed cardiac transcripts. However, no protein was detected for the induced sarcomeric genes Actc1, Myh6, and Myl2. Adding MYOCD to GMT affected only slightly the breadth and level of gene induction, but, importantly, triggered expression of all three proteins examined (α-cardiac actin, atrial natriuretic peptide, sarcomeric myosin heavy chains). MYOCD + TBX was the most effective pairwise combination in this system. In clonal derivatives homogenously expressing MYOCD + TBX at high levels, 93% of cardiac transcripts were up-regulated and all five proteins tested were visualized. (1) GMT induced cardiac genes in CSCs, but not cardiac proteins under the conditions used. (2) Complementing GMT with MYOCD induced cardiac protein expression, indicating a more complete cardiac differentiation program. (3) Homogeneous transduction with MYOCD + TBX5 facilitated the identification of differentiating cells and the validation of this combinatorial reprogramming strategy. Together, these results highlight the pivotal importance of MYOCD in driving CSCs toward a cardiac muscle fate.

Life-threatening complications of ibogaine: three case reports.

PubMed

Paling, F P; Andrews, L M; Valk, G D; Blom, H J

2012-11-01

Ibogaine is a naturally occurring psychoactive alkaloid extracted from the roots of the Tabernanthe iboga plant, which in alternative medicine is used to treat drug dependency. However, this upcoming, online advocated therapy can be dangerous due to its potentially lethal adverse effects. We present three cases in which toxic side effects were noted. We used the Naranjo scale to estimate the probability of a causal relationship between these effects and ibogaine. Findings in these three cases are suggestive of a causal relationship between the use of ibogaine and serious respiratory and cardiac problems (including lengthening of the QT interval). In our opinion it is of great importance that clinicians are aware of these potentially serious side effects and realise that widespread online marketing practices will give many more people access to ibogaine.

Dietary supplement consumption among cardiac patients admitted to internal medicine and cardiac wards.

PubMed

Karny-Rahkovich, Orith; Blatt, Alex; Elbaz-Greener, Gabby Atalya; Ziv-Baran, Tomer; Golik, Ahuva; Berkovitch, Matityahu

2015-01-01

Dietary supplements may have adverse effects and potentially interact with conventional medications. They are perceived as "natural" products, free of side effects with no need for medical consultation. Little is known about consumption of dietary supplements by patients with cardiac diseases. The objective of this study was to investigate dietary supplement consumption among cardiac patients admitted to internal and cardiology wards. Potential drug-dietary supplement interactions were also assessed. During a period of 6 months, patients with cardiac disease hospitalized in the Internal Medicine and Cardiology Wards at Assaf Harofeh Medical Center were evaluated regarding their dietary supplement consumption. A literature survey examining possible drug-supplement interaction was performed. Out of 149 cardiac patients, 45% were dietary supplement consumers. Patients ad-mitted to the Internal Medicine Wards consumed more dietary supplements than those admit-ted to the Cardiology Division. Dietary supplement consumption was associated with older age (OR = 1.05, p = 0.022), female gender (OR = 2.94, p = 0.014) and routine physical activity (OR = 3.15, p = 0.007). Diabetes mellitus (OR = 2.68, p = 0.020), hematological diseases (OR = 13.29, p = 0.022), and the use of anti-diabetic medications (OR = 4.28, p = 0.001) were independently associated with dietary supplement intake. Sixteen potential moderate interactions between prescribed medications and dietary supplements were found. Consumption of dietary supplements is common among cardiac patients. It is more common in those admitted to Internal Medicine Departments than in those admitted to the Cardiology Wards. Due to the risk of various drug-supplement interactions consumed by patients with cardiac diseases, there is a need to increase awareness and knowledge among medical staff regarding the intake of dietary supplements.

Hsp20 Interacting with Phosphorylated Akt Reduces Doxorubicin-Triggered Oxidative Stress and Cardiotoxicity

PubMed Central

Fan, Guo-Chang; Zhou, Xiaoyang; Wang, Xiaohong; Song, Guojie; Qian, Jiang; Nicolaou, Persoulla; Chen, Guoli; Ren, Xiaoping; Kranias, Evangelia G.

2009-01-01

Doxorubicin (DOX) is a widely used antitumor drug, but its application is limited due to its cardiotoxic side effects. Hsp20 has been recently shown to protect cardiomyocytes against apoptosis, induced by ischemia/reperfusion injury or by prolonged β-agonist stimulation. However, it is not clear whether Hsp20 would exert similar protective effects against DOX-induced cardiac injury. Actually, DOX-treatment was associated with down-regulation of Hsp20 in the heart. To elucidate the role of Hsp20 in DOX-triggered cardiac toxicity, Hsp20 was first overexpressed ex vivo by adenovirus-mediated gene delivery. Increased Hsp20 levels conferred higher resistance to DOX-induced cell death, compared to GFP-control. Furthermore, cardiac-specific overexpression of Hsp20 in vivo significantly ameliorated acute DOX-triggered cardiomyocyte apoptosis and animal mortality. Hsp20-transgenic mice also showed improved cardiac function and prolonged survival after chronic administration of DOX. The mechanisms underlying these beneficial effects were associated with preserved Akt phosphorylation/activity and attenuation of DOX-induced oxidative stress. Co-immunoprecipitation studies revealed an interaction between Hsp20 and phosphorylated Akt. Accordingly, BAD phosphorylation was preserved and cleaved caspase-3 was decreased in DOX-treated Hsp20-TG hearts, consistent with the Hsp20's anti-apoptotic effects. Parallel ex vivo experiments showed that either infection with a dominant-negative Akt adenovirus or pre-incubation of cardiomyocytes with the PI3-kinase inhibitors significantly attenuated the protective effects of Hsp20. Taken together, our findings indicate that overexpression of Hsp20 inhibits DOX-triggered cardiac injury, and these beneficial effects appear to be dependent on Akt activation. Thus, Hsp20 may constitute a new therapeutic target in ameliorating the cardiotoxic effects of DOX-treatment in cancer patients. PMID:18948619

A Tocotrienol-Enriched Formulation Protects against Radiation-Induced Changes in Cardiac Mitochondria without Modifying Late Cardiac Function or Structure

PubMed Central

Sridharan, Vijayalakshmi; Tripathi, Preeti; Aykin-Burns, Nukhet; Krager, Kimberly J; Sharma, Sunil K.; Moros, Eduardo G.; Melnyk, Stepan B.; Pavliv, Oleksandra; Hauer-Jensen, Martin; Boerma, Marjan

2015-01-01

Radiation-induced heart disease (RIHD) is a common and sometimes severe late side effect of radiation therapy for intrathoracic and chest wall tumors. We have previously shown that local heart irradiation in a rat model caused prolonged changes in mitochondrial respiration and increased susceptibility to mitochondrial permeability transition pore (mPTP) opening. Because tocotrienols are known to protect against oxidative stress-induced mitochondrial dysfunction, in this study, we examined the effects of tocotrienols on radiation-induced alterations in mitochondria, and structural and functional manifestations of RIHD. Male Sprague-Dawley rats received image-guided localized X irradiation to the heart to a total dose of 21 Gy. Twenty-four hours before irradiation, rats received a tocotrienol-enriched formulation or vehicle by oral gavage. Mitochondrial function and mitochondrial membrane parameters were studied at 2 weeks and 28 weeks after irradiation. In addition, cardiac function and histology were examined at 28 weeks. A single oral dose of the tocotrienol-enriched formulation preserved Bax/Bcl2 ratios and prevented mPTP opening and radiation-induced alterations in succinate-driven mitochondrial respiration. Nevertheless, the late effects of local heart irradiation pertaining to myocardial function and structure were not modified. Our studies suggest that a single dose of tocotrienols protects against radiation-induced mitochondrial changes, but these effects are not sufficient against long-term alterations in cardiac function or remodeling. PMID:25710576

A tocotrienol-enriched formulation protects against radiation-induced changes in cardiac mitochondria without modifying late cardiac function or structure.

PubMed

Sridharan, Vijayalakshmi; Tripathi, Preeti; Aykin-Burns, Nukhet; Krager, Kimberly J; Sharma, Sunil K; Moros, Eduardo G; Melnyk, Stepan B; Pavliv, Oleksandra; Hauer-Jensen, Martin; Boerma, Marjan

2015-03-01

Radiation-induced heart disease (RIHD) is a common and sometimes severe late side effect of radiation therapy for intrathoracic and chest wall tumors. We have previously shown that local heart irradiation in a rat model caused prolonged changes in mitochondrial respiration and increased susceptibility to mitochondrial permeability transition pore (mPTP) opening. Because tocotrienols are known to protect against oxidative stress-induced mitochondrial dysfunction, in this study, we examined the effects of tocotrienols on radiation-induced alterations in mitochondria, and structural and functional manifestations of RIHD. Male Sprague-Dawley rats received image-guided localized X irradiation to the heart to a total dose of 21 Gy. Twenty-four hours before irradiation, rats received a tocotrienol-enriched formulation or vehicle by oral gavage. Mitochondrial function and mitochondrial membrane parameters were studied at 2 weeks and 28 weeks after irradiation. In addition, cardiac function and histology were examined at 28 weeks. A single oral dose of the tocotrienol-enriched formulation preserved Bax/Bcl2 ratios and prevented mPTP opening and radiation-induced alterations in succinate-driven mitochondrial respiration. Nevertheless, the late effects of local heart irradiation pertaining to myocardial function and structure were not modified. Our studies suggest that a single dose of tocotrienols protects against radiation-induced mitochondrial changes, but these effects are not sufficient against long-term alterations in cardiac function or remodeling.

Pleural effusion decreases left ventricular pre-load and causes haemodynamic compromise: an experimental porcine study.

PubMed

Wemmelund, K B; Lie, R H; Juhl-Olsen, P; Frederiksen, C A; Hermansen, J F; Sloth, E

2012-08-01

Although pleural effusion is a common complication in critically ill patients, detailed knowledge is missing about the haemodynamic impact and the underlining mechanisms. The aim of this study was to evaluate the haemodynamic effect of incremental pleural effusion by means of invasive haemodynamic parameters and transthoracic echocardiography. This experimental interventional study was conducted using 22 female piglets (17.5-21.5 kg) randomized for right-side (n = 9) and left-side (n = 9) pleural effusion, or sham operation (n = 4). Pleural effusion was induced by infusing incremental volumes of saline into the pleural cavity. Invasive haemodynamic measurements and echocardiographical images were obtained at baseline, a volume of 45 ml/kg, a volume of 75 ml/kg and 45 min after drainage. No difference (all P > 0.147) was found between right- and left-side pleural effusion, and the groups were thus pooled. At 45 ml/kg cardiac output, mean arterial pressure, stroke volume and mixed venous saturation decreased (all P < 0.003); central venous pressure and pulmonary arterial pressure increased (both P > 0.003) at this point. The changes accelerated at 75 ml/kg. At 45 ml/kg left ventricular pre-load in terms of end-diastolic area decreased significantly (P < 0.001). The effect on haemodynamics and cardiac dimensions changed dramatically at 75 ml/kg. Cardiac output, mean arterial pressure, central venous pressure and left ventricular end-diastolic area returned to normal during a recovery period of 45 min (all P > 0.061). Incremental volumes of unilateral pleural effusion induced a significant haemodynamic impact fully reversible after drainage. Pleural effusion causes a significant decrease of left ventricular pre-load in a diverse picture of haemodynamic compromise. © 2012 The Authors. Acta Anaesthesiologica Scandinavica © 2012 The Acta Anaesthesiologica Scandinavica Foundation.

Tranexamic Acid in cardiac surgery and postoperative seizures: a case report series.

PubMed

Bell, David; Marasco, Silvana; Almeida, Aubrey; Rowland, Michael

2010-08-01

With the recent withdrawal of the antifibrinolytic aprotinin from the market, tranexamic acid (TxA) has become more widely used. This change has led to increasing concern about the side-effect profile of TxA, particularly the incidence of postoperative seizures. In this case series, we describe 7 patients over an 18-month period who had open-chamber cardiac surgery and developed seizures in the postoperative period. This incidence is increased compared with that of a cohort of patients in the previous 36 months who did not receive TxA (0.66% versus 0%; P < .05). The exact mechanism of TxA-induced seizures is thought to be via inhibition of gamma-aminobutyric acid receptors in neurons. Data from the neurosurgical literature show a well-established link between this antifibrinolytic and seizures. There is now increasing awareness of this association in cardiac surgery, particularly when high TxA doses are used.

Sexuality and the middle-aged cardiac patient.

PubMed

Watts, R J

1976-06-01

Counseling for the resumption of sexual activity deserves as much attention in a cardiac rehabilitation program as walking or jogging. Research findings enable the counselor to give specific sexual advice. The energey expenditure during coitus for long-married couples is equivalent to that of climbing stairs, and consequently the risk of heart attack is low. However, clustering of psychosocial and physiologic demands, such as illicit affairs, outbursts of anger, alcohol, and hearty meals, may precipitate reinfarction or death. A sexual activities program is successful only if each partner is committed to give and receive pleasure. Knowledgeable and sensitive counseling will enable the couple to explore extra-coital options for lovemaking prior to the resumption of intercourse. This writer has observed that once couples are "turned on" to the pleasuring exercises, coital activity is attempted at an earlier date without untoward side effects in the cardiac patient.

Cardiac magnetic resonance imaging and computed tomography in ischemic cardiomyopathy: an update*

PubMed Central

Assunção, Fernanda Boldrini; de Oliveira, Diogo Costa Leandro; Souza, Vitor Frauches; Nacif, Marcelo Souto

2016-01-01

Ischemic cardiomyopathy is one of the major health problems worldwide, representing a significant part of mortality in the general population nowadays. Cardiac magnetic resonance imaging (CMRI) and cardiac computed tomography (CCT) are noninvasive imaging methods that serve as useful tools in the diagnosis of coronary artery disease and may also help in screening individuals with risk factors for developing this illness. Technological developments of CMRI and CCT have contributed to the rise of several clinical indications of these imaging methods complementarily to other investigation methods, particularly in cases where they are inconclusive. In terms of accuracy, CMRI and CCT are similar to the other imaging methods, with few absolute contraindications and minimal risks of adverse side-effects. This fact strengthens these methods as powerful and safe tools in the management of patients. The present study is aimed at describing the role played by CMRI and CCT in the diagnosis of ischemic cardiomyopathies. PMID:26929458

Recent technological advancements in cardiac ultrasound imaging.

PubMed

Dave, Jaydev K; Mc Donald, Maureen E; Mehrotra, Praveen; Kohut, Andrew R; Eisenbrey, John R; Forsberg, Flemming

2018-03-01

About 92.1 million Americans suffer from at least one type of cardiovascular disease. Worldwide, cardiovascular diseases are the number one cause of death (about 31% of all global deaths). Recent technological advancements in cardiac ultrasound imaging are expected to aid in the clinical diagnosis of many cardiovascular diseases. This article provides an overview of such recent technological advancements, specifically focusing on tissue Doppler imaging, strain imaging, contrast echocardiography, 3D echocardiography, point-of-care echocardiography, 3D volumetric flow assessments, and elastography. With these advancements ultrasound imaging is rapidly changing the domain of cardiac imaging. The advantages offered by ultrasound imaging include real-time imaging, imaging at patient bed-side, cost-effectiveness and ionizing-radiation-free imaging. Along with these advantages, the steps taken towards standardization of ultrasound based quantitative markers, reviewed here, will play a major role in addressing the healthcare burden associated with cardiovascular diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

C-SPECT - a Clinical Cardiac SPECT/Tct Platform: Design Concepts and Performance Potential

PubMed Central

Chang, Wei; Ordonez, Caesar E.; Liang, Haoning; Li, Yusheng; Liu, Jingai

2013-01-01

Because of scarcity of photons emitted from the heart, clinical cardiac SPECT imaging is mainly limited by photon statistics. The sub-optimal detection efficiency of current SPECT systems not only limits the quality of clinical cardiac SPECT imaging but also makes more advanced potential applications difficult to be realized. We propose a high-performance system platform - C-SPECT, which has its sampling geometry optimized for detection of emitted photons in quality and quantity. The C-SPECT has a stationary C-shaped gantry that surrounds the left-front side of a patient’s thorax. The stationary C-shaped collimator and detector systems in the gantry provide effective and efficient detection and sampling of photon emission. For cardiac imaging, the C-SPECT platform could achieve 2 to 4 times the system geometric efficiency of conventional SPECT systems at the same sampling resolution. This platform also includes an integrated transmission CT for attenuation correction. The ability of C-SPECT systems to perform sequential high-quality emission and transmission imaging could bring cost-effective high-performance to clinical imaging. In addition, a C-SPECT system could provide high detection efficiency to accommodate fast acquisition rate for gated and dynamic cardiac imaging. This paper describes the design concepts and performance potential of C-SPECT, and illustrates how these concepts can be implemented in a basic system. PMID:23885129

Ugly duckling or Nosferatu? Cardiac injury in endurance sport - screening recommendations.

PubMed

Leischik, R; Dworrak, B

2014-01-01

In the beginning sporting activity may be exhausting, but over time, physical activity turns out to have beneficial effects to the body and even extended cycling or running is an emotional and healthy enrichment in life. On the other hand, spectacular sudden deaths during marathon, football and, just recently, in the trend discipline triathlon seem to support the dark side of the sporting activity. Since years there are constantly appearing reports about a potential myocardial injury induced by intensive sporting activities. Cardiac hypertrophy is the heart's response to arterial hypertension and to physical activity, but can be associated with an unfavorable outcome - in worst case for example with sudden death. The question of the right dose of sporting activity, the question how to prevent cardiac death induced by physical activity and the question how to screen the athletes for the possible risk of sudden death or other cardiac complications during sporting activity are those that will be answered by this review article. In this review we summarize recent insights into the problem of endurance sport and possible negative cardiac remodeling as well as the question how to screen the athletes.

Biphasic Role of Chondroitin Sulfate in Cardiac Differentiation of Embryonic Stem Cells through Inhibition of Wnt/β-Catenin Signaling

PubMed Central

Prinz, Robert D.; Willis, Catherine M.; van Kuppevelt, Toin H.; Klüppel, Michael

2014-01-01

The glycosaminoglycan chondroitin sulfate is a critical component of proteoglycans on the cell surface and in the extracellular matrix. As such, chondroitin sulfate side chains and the sulfation balance of chondroitin play important roles in the control of signaling pathways, and have a functional importance in human disease. In contrast, very little is known about the roles of chondroitin sulfate molecules and sulfation patterns during mammalian development and cell lineage specification. Here, we report a novel biphasic role of chondroitin sulfate in the specification of the cardiac cell lineage during embryonic stem cell differentiation through modulation of Wnt/beta-catenin signaling. Lineage marker analysis demonstrates that enzymatic elimination of endogenous chondroitin sulfates leads to defects specifically in cardiac differentiation. This is accompanied by a reduction in the number of beating cardiac foci. Mechanistically, we show that endogenous chondroitin sulfate controls cardiac differentiation in a temporal biphasic manner through inhibition of the Wnt/beta-catenin pathway, a known regulatory pathway for the cardiac lineage. Treatment with a specific exogenous chondroitin sulfate, CS-E, could mimic these biphasic effects on cardiac differentiation and Wnt/beta-catenin signaling. These results establish chondroitin sulfate and its sulfation balance as important regulators of cardiac cell lineage decisions through control of the Wnt/beta-catenin pathway. Our work suggests that targeting the chondroitin biosynthesis and sulfation machinery is a novel promising avenue in regenerative strategies after heart injury. PMID:24667694

Biphasic role of chondroitin sulfate in cardiac differentiation of embryonic stem cells through inhibition of Wnt/β-catenin signaling.

PubMed

Prinz, Robert D; Willis, Catherine M; van Kuppevelt, Toin H; Klüppel, Michael

2014-01-01

The glycosaminoglycan chondroitin sulfate is a critical component of proteoglycans on the cell surface and in the extracellular matrix. As such, chondroitin sulfate side chains and the sulfation balance of chondroitin play important roles in the control of signaling pathways, and have a functional importance in human disease. In contrast, very little is known about the roles of chondroitin sulfate molecules and sulfation patterns during mammalian development and cell lineage specification. Here, we report a novel biphasic role of chondroitin sulfate in the specification of the cardiac cell lineage during embryonic stem cell differentiation through modulation of Wnt/beta-catenin signaling. Lineage marker analysis demonstrates that enzymatic elimination of endogenous chondroitin sulfates leads to defects specifically in cardiac differentiation. This is accompanied by a reduction in the number of beating cardiac foci. Mechanistically, we show that endogenous chondroitin sulfate controls cardiac differentiation in a temporal biphasic manner through inhibition of the Wnt/beta-catenin pathway, a known regulatory pathway for the cardiac lineage. Treatment with a specific exogenous chondroitin sulfate, CS-E, could mimic these biphasic effects on cardiac differentiation and Wnt/beta-catenin signaling. These results establish chondroitin sulfate and its sulfation balance as important regulators of cardiac cell lineage decisions through control of the Wnt/beta-catenin pathway. Our work suggests that targeting the chondroitin biosynthesis and sulfation machinery is a novel promising avenue in regenerative strategies after heart injury.

Unpinning of rotating spiral waves in cardiac tissues by circularly polarized electric fields

PubMed Central

Feng, Xia; Gao, Xiang; Pan, De-Bei; Li, Bing-Wei; Zhang, Hong

2014-01-01

Spiral waves anchored to obstacles in cardiac tissues may cause lethal arrhythmia. To unpin these anchored spirals, comparing to high-voltage side-effect traditional therapies, wave emission from heterogeneities (WEH) induced by the uniform electric field (UEF) has provided a low-voltage alternative. Here we provide a new approach using WEH induced by the circularly polarized electric field (CPEF), which has higher success rate and larger application scope than UEF, even with a lower voltage. And we also study the distribution of the membrane potential near an obstacle induced by CPEF to analyze its mechanism of unpinning. We hope this promising approach may provide a better alternative to terminate arrhythmia. PMID:24777360

[Lead compound optimization strategy(5) – reducing the hERG cardiac toxicity in drug development].

PubMed

Zhou, Sheng-bin; Wang, Jiang; Liu, Hong

2016-10-01

The potassium channel encoded by the human ether-a-go-go related gene(hERG) plays a very important role in the physiological and pathological processes in human. hERG potassium channel determines the outward currents which facilitate the repolarization of the myocardial cells. Some drugs were withdrawn from the market for the serious side effect of long QT interval and arrhythmia due to blockade of hERG channel. The strategies for lead compound optimization are to reduce inhibitory activity of hERG potassium channel and decrease cardiac toxicity. These methods include reduction of lipophilicity and basicity of amines, introduction of hydroxyl and acidic groups, and restricting conformation.

Assessment of large copy number variants in patients with apparently isolated congenital left-sided cardiac lesions reveals clinically relevant genomic events.

PubMed

Hanchard, Neil A; Umana, Luis A; D'Alessandro, Lisa; Azamian, Mahshid; Poopola, Mojisola; Morris, Shaine A; Fernbach, Susan; Lalani, Seema R; Towbin, Jeffrey A; Zender, Gloria A; Fitzgerald-Butt, Sara; Garg, Vidu; Bowman, Jessica; Zapata, Gladys; Hernandez, Patricia; Arrington, Cammon B; Furthner, Dieter; Prakash, Siddharth K; Bowles, Neil E; McBride, Kim L; Belmont, John W

2017-08-01

Congenital left-sided cardiac lesions (LSLs) are a significant contributor to the mortality and morbidity of congenital heart disease (CHD). Structural copy number variants (CNVs) have been implicated in LSL without extra-cardiac features; however, non-penetrance and variable expressivity have created uncertainty over the use of CNV analyses in such patients. High-density SNP microarray genotyping data were used to infer large, likely-pathogenic, autosomal CNVs in a cohort of 1,139 probands with LSL and their families. CNVs were molecularly confirmed and the medical records of individual carriers reviewed. The gene content of novel CNVs was then compared with public CNV data from CHD patients. Large CNVs (>1 MB) were observed in 33 probands (∼3%). Six of these were de novo and 14 were not observed in the only available parent sample. Associated cardiac phenotypes spanned a broad spectrum without clear predilection. Candidate CNVs were largely non-recurrent, associated with heterozygous loss of copy number, and overlapped known CHD genomic regions. Novel CNV regions were enriched for cardiac development genes, including seven that have not been previously associated with human CHD. CNV analysis can be a clinically useful and molecularly informative tool in LSLs without obvious extra-cardiac defects, and may identify a clinically relevant genomic disorder in a small but important proportion of these individuals. © 2017 Wiley Periodicals, Inc.

Calcium channel blockers: spectrum of side effects and drug interactions.

PubMed

Hedner, T

1986-01-01

Calcium antagonists are a chemically heterogenous group of agents with potent cardiovascular effects which are beneficial in the treatment of angina pectoris, arterial hypertension and cardiac arrhythmias. The main side effects for the group are dose-dependent and the result of the main action or actions of the calcium antagonists, i.e. vasodilatation, negative inotropic effects and antiarrhythmic effects. Pronounced hypotension is reported for the main calcium antagonist drugs; verapamil, diltiazem and nifedipine. While conduction disturbances and bradycardia are seen more often after verapamil and diltiazem, tachycardia, headache and flush are more frequent after nifedipine. Constipation is relatively frequent after verapamil while nifedipine is reported to induce diarrhea in som patients. Idiosyncratic side effects are rare but have been reported from the skin, mouth, musculoskeletal system, the liver and the central nervous system. These side effects include urticarial rashes, gingival hyperplasia, arthralgia, hepathotoxicity and transistory mental confusion or akathisia. Verapamil, diltiazem and possibly also nifedipine have been reported to increase serum digoxin concentrations but the clinical relevance of these drug interactions are not clear. Furthermore, verapamil and diltiazem may potentiate the effects of beta-adrenergic blocking drugs and verapamil may also potentiate the effects of neuromuscular blocking drugs. It is concluded that side effects after calcium antagonist drugs are mostly trivial and transient although they may sometimes be relatively common. Clinically relevant drug interactions are few. Judged from the point of efficacy and safety, calcium antagonists will have a major place in the future pharmacotherapy of several cardiovascular disorders.

Effect of alectinib on cardiac electrophysiology: results from intensive electrocardiogram monitoring from the pivotal phase II NP28761 and NP28673 studies.

PubMed

Morcos, Peter N; Bogman, Katrijn; Hubeaux, Stanislas; Sturm-Pellanda, Carolina; Ruf, Thorsten; Bordogna, Walter; Golding, Sophie; Zeaiter, Ali; Abt, Markus; Balas, Bogdana

2017-03-01

Alectinib, a central nervous system (CNS)-active ALK inhibitor, has demonstrated efficacy and safety in ALK+ non-small-cell lung cancer that has progressed following crizotinib treatment. Other ALK inhibitors have shown concentration-dependent QTc prolongation and treatment-related bradycardia. Therefore, this analysis evaluated alectinib safety in terms of electrophysiologic parameters. Intensive triplicate centrally read electrocardiogram (ECG) and matched pharmacokinetic data were collected across two alectinib single-arm trials. Analysis of QTcF included central tendency analysis [mean changes from baseline with one-sided upper 95% confidence intervals (CIs)], categorical analyses, and relationship between change in QTcF and alectinib plasma concentrations. Alectinib effects on other ECG parameters (heart rate, PR interval and QRS duration) were also evaluated. Alectinib did not cause a clinically relevant change in QTcF. The maximum mean QTcF change from baseline was 5.3 ms observed pre-dose at week 2. The upper one-sided 95% CI was <10 ms at all time points. There was no relevant relationship between change in QTcF and alectinib plasma concentrations. Alectinib treatment resulted in a generally asymptomatic exposure-dependent decrease in mean heart rate of ~11 to 13 beats per minute at week 2. No clinically relevant effects were seen on other ECG parameters. Approximately 5% of patients reported cardiac adverse events of bradycardia or sinus bradycardia; however, these were all grade 1-2. Alectinib does not prolong the QTc interval or cause changes in cardiac function to a clinically relevant extent, with the exception of a decrease in heart rate which was generally asymptomatic.

Racial differences in sudden cardiac death

PubMed Central

Fender, Erin A.; Henrikson, Charles A.; Tereshchenko, Larisa

2014-01-01

There is an increased risk of sudden cardiac death (SCD) and sudden cardiac arrest (SCA), in African Americans, the basis of which is likely multifactorial. African Americans have higher rates of traditional cardiac risk factors including hypertension, left ventricular hypertrophy, diabetes, coronary heart disease, and heart failure. There are also significant disparities in health care delivery. While these factors undoubtedly affect health outcomes, there is also growing evidence that genetics may have a significant impact as well. In this paper, we discuss data and hypotheses in support of both sides of the controversy around racial differences in SCD/SCA. PMID:25155390

Developmental origin and lineage plasticity of endogenous cardiac stem cells

PubMed Central

Santini, Maria Paola; Forte, Elvira; Harvey, Richard P.; Kovacic, Jason C.

2016-01-01

Over the past two decades, several populations of cardiac stem cells have been described in the adult mammalian heart. For the most part, however, their lineage origins and in vivo functions remain largely unexplored. This Review summarizes what is known about different populations of embryonic and adult cardiac stem cells, including KIT+, PDGFRα+, ISL1+ and SCA1+ cells, side population cells, cardiospheres and epicardial cells. We discuss their developmental origins and defining characteristics, and consider their possible contribution to heart organogenesis and regeneration. We also summarize the origin and plasticity of cardiac fibroblasts and circulating endothelial progenitor cells, and consider what role these cells have in contributing to cardiac repair. PMID:27095490

Accessory hepatic vein complicating extra-cardiac total cavopulmonary connection.

PubMed

Yoshii, Shinpei; Suzuki, Shoji; Osawa, Hiroshi; Hosaka, Shigeru; Honda, Yoshihiro; Abraham, Samuel J K; Tada, Yusuke; Sugiyama, Hisashi; Tan, Tetsushi; Kadono, Toshie; Hoshiai, Minako; Komai, Takayuki

2002-04-01

We encountered unexpected, severe hypoxia after the right heart bypass operation in a patient with isomerism. A 2-year-old girl with polysplenia had a complex cardiac anomaly consisting of a single atrium, single ventricle, pulmonary stenosis, absence of the right superior vena cava, hemiazygos continuation of the left inferior vena cava, and d-malposition of the great arteries. After a total cavopulmonary shunt, we performed an extra-cardiac total cavo-pulmonary connection with a 14 mm tube graft. The postoperative course was complicated by severe hypoxia. Angiography performed 20 days after the operation showed that contrast medium in the conduit poured into the hepatic vein, and through the intrahepatic communications, it passed into a left-sided accessory hepatic vein, which was connected directly to the left side of the aspect of the atrium. As the intrahepatic communication was adequate, we ligated the accessory hepatic vein within the pericardial cavity. The SpO2 returned to normal and no hepatic dysfunction was detected. We conclude that surgeons performing extra-cardiac total cavopulmonary connection need to pay closer attention to the possibility that an accessory hepatic vein might exist.

Bioenergetics in the pathogenesis, progression and treatment of cardiovascular disorders.

PubMed

Tanner, H A

1995-05-01

The aim of this manuscript is to review perturbations in bioenergetics that are redundant denominators in the diversity of factors mediating the pathogenesis and progression of coronary heart disease (CHD), congestive heart failure (CHF), hypertension and arrhythmias. This paper likewise assesses the pharmacodynamics of widely prescribed drugs that enhance cellular respiration, maintain positive inotropic, chronotropic, dromotropic cardiac effects, sustain myocardial biosynthesis, reverse the morbidity of heart disease, and assure low levels of toxicity commensurate with the agent's biocompatability. Conversely, it is essential to delineate the modality of xenobiotic drugs that inhibit energy transformations, enhance the pathogenesis of CHD, worsen survival in CHF, provoke arrhythmogenic effects, and induce serious side-effects. Documented evidence, derived from biochemical, physiological and pharmacological data sources, consistently links inhibited mitochondrial decarboxylation to aberrations in cholesterol metabolism, biosynthesis, and calcium balance. Underutilized citrates evolved from inhibited decarboxylation are degraded to acetyl CoA. The acetate is the source of steroid synthesis; its carbon atoms form the molecular basis for all endogenous cholesterol. Myocardial anoxia, a consequence of the atheromatous plaque, inhibits ATP production, impairs biosynthesis, induces negative cardiac inotropic and chronotropic effects, and enhances the pathogenesis of CHF. Inhibited decarboxylation is likewise a factor in the mobilization of in situ cardiac Ca2+, resulting in arrhythmias provoked by the cation's deficiency. The restoration of calcium homeostasis decreases peripheral vasotension, reducing hypertension. Parameters drawn from endocrinopathies and the new physiological dimension of microgravity are developed to illustrate the detrimental effect of inhibited bioenergetics on cardiac pathomorphism and cardiovascular dysfunction. In conclusion, anabolic agents, adjunctive to a productive life-style, can provide the rational basis for the prevention and treatment of cardiac diseases. Failure to understand mechanisms generating cardiovascular morbidity eventuates in ineffective and empirical treatment.

Multiple-dose safety study of ibuprofen/codeine and aspirin/codeine combinations.

PubMed

Friedman, H; Seckman, C; Stubbs, C; Oster, H; Royer, G

1990-01-01

This multiple-dose, double-blind, placebo-controlled, randomized, normal volunteer study compared formulations of ibuprofen/codeine and aspirin/codeine for systemic safety. Vital signs, hematologic, biochemical and urinary parameters, side effects, mood and mental alertness, were monitored. The placebo group had less gastrointestinal side effects and more frequent stools than the active treatment groups. There was statistical evidence for greater adverse effects of aspirin/codeine on mood and mental alertness in comparison to ibuprofen/codeine and placebo. Ibuprofen/codeine had a more favorable adverse effect profile than aspirin/codeine. A mild respiratory and cardiac depressant effect attributable to codeine was evident in all active treatment groups after 7 days of frequent therapy. More work needs to be done to elucidate the factors regulating the development of tolerance to the respiratory and cardiovascular depressant effects of opiates in general, and for codeine in particular.

Healthy aging and myocardium: A complicated process with various effects in cardiac structure and physiology.

PubMed

Nakou, E S; Parthenakis, F I; Kallergis, E M; Marketou, M E; Nakos, K S; Vardas, P E

2016-04-15

It is known that there is an ongoing increase in life expectancy worldwide, especially in the population older than 65years of age. Cardiac aging is characterized by a series of complex pathophysiological changes affecting myocardium at structural, cellular, molecular and functional levels. These changes make the aged myocardium more susceptible to stress, leading to a high prevalence of cardiovascular diseases (heart failure, atrial fibrillation, left ventricular hypertrophy, coronary artery disease) in the elderly population. The aging process is genetically programmed but modified by environmental influences, so that the rate of aging can vary widely among people. We summarized the entire data concerning all the multifactorial changes in aged myocardium and highlighting the recent evidence for the pathophysiological basis of cardiac aging. Keeping an eye on the clinical side, this review will explore the potential implications of the age-related changes in the clinical management and on novel therapeutic strategies potentially deriving from the scientific knowledge currently acquired on cardiac aging process. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Inaccuracy of transthoracic echocardiography for the identification of right-sided vegetation in patients with no history of intravenous drug abuse or cardiac device insertion.

PubMed

Xie, Jiang; Liu, Shuang; Yang, Jinghua; Xu, Jie; Zhu, Guangfa

2014-06-01

The use of transthoracic echocardiography (TTE) to identify right-sided infective endocarditis (RSIE) vegetation is controversial. Data are scarce for patients with no history of intravenous drug abuse (IVDA) or cardiac device insertion. This study analysed the consistency of presurgical echocardiographic results with surgical findings for vegetation identification, and the factors that influence accuracy of echocardiography. This retrospective trial divided infective endocarditis (IE) patients into three subgroups according to the results of their presurgical TTE: left-sided native IE (LSNIE), left-sided prosthetic valve IE (LSPIE) and RSIE. The accuracy of TTE was tested by comparing vegetation (number and location), detected presurgery by TTE, with actual findings during surgery. In total, 416 patients were analysed, 322 with LSNIE, 31 with LSPIE and 63 with RSIE. Consistency between TTE findings and surgical results was lower in the RSIE group compared with the LSPIE and LSNIE groups. Consistency was lowered by the presence of vegetation in multiple locations and atypical distribution--both of which were increased in the RSIE group. The chance of vegetation in both sides of the heart rose with increased numbers of vegetation locations in RSIE patients. A high proportion of RSIE patients had congenital heart defects, mostly ventricular septal defects. TTE may be unsuitable for RSIE patients with no history of IVDA or cardiac device insertion, because multifocal and atypically distributed vegetation may influence detection accuracy. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Spiral-wave dynamics in a mathematical model of human ventricular tissue with myocytes and fibroblasts.

PubMed

Nayak, Alok Ranjan; Shajahan, T K; Panfilov, A V; Pandit, Rahul

2013-01-01

Cardiac fibroblasts, when coupled functionally with myocytes, can modulate the electrophysiological properties of cardiac tissue. We present systematic numerical studies of such modulation of electrophysiological properties in mathematical models for (a) single myocyte-fibroblast (MF) units and (b) two-dimensional (2D) arrays of such units; our models build on earlier ones and allow for zero-, one-, and two-sided MF couplings. Our studies of MF units elucidate the dependence of the action-potential (AP) morphology on parameters such as [Formula: see text], the fibroblast resting-membrane potential, the fibroblast conductance [Formula: see text], and the MF gap-junctional coupling [Formula: see text]. Furthermore, we find that our MF composite can show autorhythmic and oscillatory behaviors in addition to an excitable response. Our 2D studies use (a) both homogeneous and inhomogeneous distributions of fibroblasts, (b) various ranges for parameters such as [Formula: see text], and [Formula: see text], and (c) intercellular couplings that can be zero-sided, one-sided, and two-sided connections of fibroblasts with myocytes. We show, in particular, that the plane-wave conduction velocity [Formula: see text] decreases as a function of [Formula: see text], for zero-sided and one-sided couplings; however, for two-sided coupling, [Formula: see text] decreases initially and then increases as a function of [Formula: see text], and, eventually, we observe that conduction failure occurs for low values of [Formula: see text]. In our homogeneous studies, we find that the rotation speed and stability of a spiral wave can be controlled either by controlling [Formula: see text] or [Formula: see text]. Our studies with fibroblast inhomogeneities show that a spiral wave can get anchored to a local fibroblast inhomogeneity. We also study the efficacy of a low-amplitude control scheme, which has been suggested for the control of spiral-wave turbulence in mathematical models for cardiac tissue, in our MF model both with and without heterogeneities.

Inhibiting Na+/K+ ATPase can impair mitochondrial energetics and induce abnormal Ca2+ cycling and automaticity in guinea pig cardiomyocytes.

PubMed

Li, Qince; Pogwizd, Steven M; Prabhu, Sumanth D; Zhou, Lufang

2014-01-01

Cardiac glycosides have been used for the treatment of heart failure because of their capabilities of inhibiting Na+/K+ ATPase (NKA), which raises [Na+]i and attenuates Ca2+ extrusion via the Na+/Ca2+ exchanger (NCX), causing [Ca2+]i elevation. The resulting [Ca2+]i accumulation further enhances Ca2+-induced Ca2+ release, generating the positive inotropic effect. However, cardiac glycosides have some toxic and side effects such as arrhythmogenesis, confining their extensive clinical applications. The mechanisms underlying the proarrhythmic effect of glycosides are not fully understood. Here we investigated the mechanisms by which glycosides could cause cardiac arrhythmias via impairing mitochondrial energetics using an integrative computational cardiomyocyte model. In the simulations, the effect of glycosides was mimicked by blocking NKA activity. Results showed that inhibiting NKA not only impaired mitochondrial Ca2+ retention (thus suppressed reactive oxygen species (ROS) scavenging) but also enhanced oxidative phosphorylation (thus increased ROS production) during the transition of increasing workload, causing oxidative stress. Moreover, concurrent blocking of mitochondrial Na+/Ca2+ exchanger, but not enhancing of Ca2+ uniporter, alleviated the adverse effects of NKA inhibition. Intriguingly, NKA inhibition elicited Ca2+ transient and action potential alternans under more stressed conditions such as severe ATP depletion, augmenting its proarrhythmic effect. This computational study provides new insights into the mechanisms underlying cardiac glycoside-induced arrhythmogenesis. The findings suggest that targeting both ion handling and mitochondria could be a very promising strategy to develop new glycoside-based therapies in the treatment of heart failure.

Milrinone ameliorates cardiac mechanical dysfunction after hypothermia in an intact rat model.

PubMed

Dietrichs, Erik Sveberg; Kondratiev, Timofei; Tveita, Torkjel

2014-12-01

Rewarming from hypothermia is often complicated by cardiac dysfunction, characterized by substantial reduction in stroke volume. Previously we have reported that inotropic agents, working via cardiac β-receptor agonism may exert serious side effects when applied to treat cardiac contractile dysfunction during rewarming. In this study we tested whether Milrinone, a phosphodiesterase III inhibitor, is able to ameliorate such dysfunction when given during rewarming. A rat model designed for circulatory studies during experimental hypothermia with cooling to a core temperature of 15°C, stable hypothermia at this temperature for 3h and subsequent rewarming was used, with a total of 3 groups: (1) a normothermic group receiving Milrinone, (2) a hypothermic group receiving Milrinone the last hour of hypothermia and during rewarming, and (3) a hypothermic saline control group. Hemodynamic function was monitored using a conductance catheter introduced to the left ventricle. After rewarming from 15°C, stroke volume and cardiac output returned to within baseline values in Milrinone treated animals, while these variables were significantly reduced in saline controls. Milrinone ameliorated cardiac dysfunction during rewarming from 15°C. The present results suggest that at low core temperatures and during rewarming from such temperatures, pharmacologic efforts to support cardiovascular function is better achieved by substances preventing cyclic AMP breakdown rather than increasing its formation via β-receptor stimulation. Copyright © 2014 Elsevier Inc. All rights reserved.

The Validity of Adding ECG to the Preparticipation Screening of Athletes An Evidence Based Literature Review

PubMed Central

Alattar, A; Maffulli, N

2015-01-01

Objective: To review the available evidence establishing the validity of adding electrocardiogram to the preparticipation cardiac screening in athletes. Data Sources: MEDLINE and CINAHL databases were searched. Additional references from the bibliographies of retrieved articles were also reviewed and experts in the area were contacted. Selection Criteria: Only original research articles seeking to establish the use of electrocardiography followed by second line investigations in athletes under 36 years of age were reviewed. Search Result and Quality Assessment: The initial literature search identified 226 papers. Of these, 16 original articles (all type II evidence—population-based clinical studies) met the selection criteria and directly related to the use of electrocardiography in athletes cardiac screening. The methodological qualities of included studies were assessed using the Downs and Black checklist. Conclusion: Screening with electrocardiography represents best clinical practice to prevent or reduce the risk of sudden cardiac death in athletes. It significantly improves the sensitivity of history and physical examination alone; it has reasonable specificity and excellent negative predictive value; and it is cost-effective. Future studies must be large, multicentre, multination, prospective trials powered to determine how different screening options affect the incidence of sudden cardiac death. Efforts should also be targeted toward secondary prevention of sudden cardiac death with pitch side cardiac resuscitation and the immediate use of defibrillator. PMID:25674543

Racial differences in sudden cardiac death.

PubMed

Fender, Erin A; Henrikson, Charles A; Tereshchenko, Larisa

2014-01-01

There is an increased risk of sudden cardiac death (SCD) and sudden cardiac arrest (SCA), in African Americans, the basis of which is likely multifactorial. African Americans have higher rates of traditional cardiac risk factors including hypertension, left ventricular hypertrophy, diabetes, coronary heart disease, and heart failure. There are also significant disparities in health care delivery. While these factors undoubtedly affect health outcomes, there is also growing evidence that genetics may have a significant impact as well. In this paper, we discuss data and hypotheses in support of both sides of the controversy around racial differences in SCD/SCA. Copyright © 2014 Elsevier Inc. All rights reserved.

Is There a Dose-Response Relationship for Heart Disease With Low-Dose Radiation Therapy?

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

Chung, Eugene; Corbett, James R.; Moran, Jean M.

Purpose: To quantify cardiac radiation therapy (RT) exposure using sensitive measures of cardiac dysfunction; and to correlate dysfunction with heart doses, in the setting of adjuvant RT for left-sided breast cancer. Methods and Materials: On a randomized trial, 32 women with node-positive left-sided breast cancer underwent pre-RT stress single photon emission computed tomography (SPECT-CT) myocardial perfusion scans. Patients received RT to the breast/chest wall and regional lymph nodes to doses of 50 to 52.2 Gy. Repeat SPECT-CT scans were performed 1 year after RT. Perfusion defects (PD), summed stress defects scores (SSS), and ejection fractions (EF) were evaluated. Doses tomore » the heart and coronary arteries were quantified. Results: The mean difference in pre- and post-RT PD was −0.38% ± 3.20% (P=.68), with no clinically significant defects. To assess for subclinical effects, PD were also examined using a 1.5-SD below the normal mean threshold, with a mean difference of 2.53% ± 12.57% (P=.38). The mean differences in SSS and EF before and after RT were 0.78% ± 2.50% (P=.08) and 1.75% ± 7.29% (P=.39), respectively. The average heart Dmean and D95 were 2.82 Gy (range, 1.11-6.06 Gy) and 0.90 Gy (range, 0.13-2.17 Gy), respectively. The average Dmean and D95 to the left anterior descending artery were 7.22 Gy (range, 2.58-18.05 Gy) and 3.22 Gy (range, 1.23-6.86 Gy), respectively. No correlations were found between cardiac doses and changes in PD, SSS, and EF. Conclusions: Using sensitive measures of cardiac function, no clinically significant defects were found after RT, with the average heart Dmean <5 Gy. Although a dose response may exist for measures of cardiac dysfunction at higher doses, no correlation was found in the present study for low doses delivered to cardiac structures and perfusion, SSS, or EF.« less

Attenuation-emission alignment in cardiac PET∕CT based on consistency conditions

PubMed Central

Alessio, Adam M.; Kinahan, Paul E.; Champley, Kyle M.; Caldwell, James H.

2010-01-01

Purpose: In cardiac PET and PET∕CT imaging, misaligned transmission and emission images are a common problem due to respiratory and cardiac motion. This misalignment leads to erroneous attenuation correction and can cause errors in perfusion mapping and quantification. This study develops and tests a method for automated alignment of attenuation and emission data. Methods: The CT-based attenuation map is iteratively transformed until the attenuation corrected emission data minimize an objective function based on the Radon consistency conditions. The alignment process is derived from previous work by Welch et al. [“Attenuation correction in PET using consistency information,” IEEE Trans. Nucl. Sci. 45, 3134–3141 (1998)] for stand-alone PET imaging. The process was evaluated with the simulated data and measured patient data from multiple cardiac ammonia PET∕CT exams. The alignment procedure was applied to simulations of five different noise levels with three different initial attenuation maps. For the measured patient data, the alignment procedure was applied to eight attenuation-emission combinations with initially acceptable alignment and eight combinations with unacceptable alignment. The initially acceptable alignment studies were forced out of alignment a known amount and quantitatively evaluated for alignment and perfusion accuracy. The initially unacceptable studies were compared to the proposed aligned images in a blinded side-by-side review. Results: The proposed automatic alignment procedure reduced errors in the simulated data and iteratively approaches global minimum solutions with the patient data. In simulations, the alignment procedure reduced the root mean square error to less than 5 mm and reduces the axial translation error to less than 1 mm. In patient studies, the procedure reduced the translation error by >50% and resolved perfusion artifacts after a known misalignment for the eight initially acceptable patient combinations. The side-by-side review of the proposed aligned attenuation-emission maps and initially misaligned attenuation-emission maps revealed that reviewers preferred the proposed aligned maps in all cases, except one inconclusive case. Conclusions: The proposed alignment procedure offers an automatic method to reduce attenuation correction artifacts in cardiac PET∕CT and provides a viable supplement to subjective manual realignment tools. PMID:20384256

Ischaemic heart disease following conventional and hypofractionated radiation treatment in a contemporary breast cancer series.

PubMed

James, Melissa; Swadi, Sami; Yi, Ma; Johansson, Lisa; Robinson, Bridget; Dixit, Ashutosh

2018-06-01

We report the incidence of ischaemic cardiac toxicity in a contemporary cohort of patients receiving conventional (CFRT) or hypofractionated (HFRT) radiation after surgery for early breast cancer and investigate the interplay of cardiac risk factors and fractionation. Included were patients receiving external beam radiation treatment from 2002 to 2006 at the Christchurch public hospital. Hospital coding databases, oncology databases and medical records were reviewed for baseline characteristics, treatment details and outcomes. The primary outcome was cardiac toxicity (including myocardial infarction, admission for cardiac chest pain, coronary angiogram positivity and ischaemic cardiac death). Kaplan-Meier methods were used to derive ischaemic cardiac event free and overall survival. Predefined univariate and multivariate analysis was performed to investigate interaction with radiation fraction size, cardiac risk factors, age and side of cancer. Standardised mortality ratios were constructed. Five hundred and one patients were identified, 220 treated with CFRT and 281 with HFRT. The median age was 56 and median follow-up 10.33 years. The 10-year breast cancer specific survival was 81.8% (95% CI %.78.1-85.0). The 10-year freedom from cardiac death was 98.6% (95% CI 96.9-99.4). There were 27 post radiation cardiac events including 5 cardiac deaths and 19 cases of acute myocardial infarction. 265 (53%) had at least one cardiac risk factor. Twenty five of the 27 patients with a cardiac event had cardiac risk factors. On univariate and multivariate analysis, fractionation schedule was not significantly associated with a post radiation ischaemic event, however, there was a significant relationship with age and the presence of a cardiac risk factor. The standardised mortality ratio was 0.89 (95% CI: 0-3.13). Our study has shown a low rate of ischaemic cardiac disease for both CFRT and HFRT in women treated for breast cancer with no evidence of an effect with fractionation schedule. Coexisting cardiac risk factors are common in the population. © 2018 The Royal Australian and New Zealand College of Radiologists.

[Oral tocolytic therapy with clenbuterol--clinical facts].

PubMed

Meinen, K; Rahn, M; Hermer, M; Rominger, K L; Kanitz, T

1988-01-01

Clenbuterol is a betamimetic agent with a marked effect on the adrenergic beta-2-receptors relevant for tocolysis. The influence on beta-1-receptors of the heart, resulting in cardiovascular side effects is far less. The substance is resorbed almost completely enterally and has a half-life of 34 hours. Consequently, ingestion intervals of 12 hours are possible, resulting in a good acceptance of the tocolytic, therapy and a noticeable improvement of the patients compliance. Clenbuterol was applied in 37 cases in the course of a clinical test. Initially, the dose was 0.04 mg b.i.d., after 24 hours 0.02 mg b.i.d. In cases of cervix-effective, premature labor, an objectively measureable tocolytic effect was achieved. Subjectively reported side effects, i.e. palpation, tachycardia and tremor, were noticeably weaker than under fenoterol therapy. There was no indication of clenbuterol-related cardiotoxicity regarding continuous measurement of heart-specific enzymes, i.e. CK-MB and serum myoglobin. No pathologic alterations were found in the EKGs. Therefore, regarding indications and contraindications for beta-adrenergic agents, clenbuterol appears to have good tocolytic properties, with the advantages of less cardiac side effects, better compliance and a better dose-effect-ratio compared with the common oral tocolysis with fenoterol.

Goldenhar syndrome: Cardiac anesthesiologist's perspective.

PubMed

Choudhury, Minati; Kapoor, Poonam Malhotra

2017-01-01

Goldenhar syndrome or oculo-auriculo-vertebral dysplasia was defined by Goldenhar in 1952 and redefined by Grolin et al. later. As the name denotes, children with this syndrome present with craniofacial and vertebral anomalies which increase the risk of airway compromise. Neonates and infants with this syndrome often have premature internal organs, low birth weight, and airway disorders. For this reason, safe anesthesia in such infants requires a complete knowledge regarding metabolism and side effects of the drugs. The association of cardiovascular abnormalities is not uncommon and possesses additional challenge for anesthetic management. The aim of this review is to draw attention to the various perioperative problems that can be faced in these infants when they undergo surgery or the correction of the underlying cardiac problem.

The Critically Ill Infant with Congenital Heart Disease.

PubMed

Strobel, Ashley M; Lu, Le N

2015-08-01

This article presents an approach for identification of infants with congenital heart disorders. These disorders are difficult to diagnose because of the complexity and variety of cardiac malformations; additionally presentation can be complicated by age-dependent physiology. By compiling data from the history and the physical examination, the emergency physician can identify lesion category and initiate stabilization procedures. Critical congenital cardiac lesions can be classified as left-sided obstructive ductal dependent, right-sided obstructive ductal dependent, and shunting or mixing. The simplified approach categorizes infants with these lesions respectively as "pink," "blue," or "gray." The emergency provider can provide life-saving stabilization until specialized care can be obtained. Copyright © 2015 Elsevier Inc. All rights reserved.

Breast Cancer Laterality Does Not Influence Survival in a Large Modern Cohort: Implications for Radiation-Related Cardiac Mortality

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

Rutter, Charles E., E-mail: charles.rutter@yale.edu; Chagpar, Anees B.; Cancer Outcomes, Public Policy and Effectiveness Research Center, Yale School of Medicine, New Haven, Connecticut

2014-10-01

Objectives: Radiation therapy for left-sided breast cancer has been associated with an elevated risk of cardiac mortality, based on studies predating treatment planning based on computed tomography. This study assessed the impact of tumor laterality on overall survival (OS) in a large cohort treated with modern techniques, to indirectly determine whether left-sided treatment remains associated with increased cardiac mortality. Methods and Materials: Patients treated for breast cancer with breast conserving surgery and adjuvant external beam radiation therapy were identified in the National Cancer Database, and OS was compared based on tumor laterality using Kaplan-Meier analysis. Separate analyses were performed formore » noninvasive and invasive carcinoma and for breast-only and breast plus regional nodal radiation therapy. Multivariate regression analysis of OS was performed with demographic, pathologic, and treatment variables as covariates to adjust for factors associated with breast cancer–specific survival. Results: We identified 344,831 patients whose cancer was diagnosed from 1998 to 2006 with a median follow-up time of 6.04 years (range, 0-14.17 years). Clinical, tumor, and treatment characteristics were similar between laterality groups. Regional nodal radiation was used in 14.2% of invasive cancers. No OS difference was noted based on tumor laterality for patients treated with breast-only (hazard ratio [HR] 0.984, P=.132) and breast plus regional nodal radiation therapy (HR 1.001, P=.957). In multivariate analysis including potential confounders, OS was identical between left and right sided cancers (HR 1.002, P=.874). No significant OS difference by laterality was observed when analyses were restricted to patients with at least 10 years of follow-up (n=27,725), both in patients treated with breast-only (HR 0.955, P=.368) and breast plus regional nodal radiation therapy (HR 0.859, P=.155). Conclusions: Radiation therapy for left-sided breast cancer does not appear to increase the risk of death in this national database relative to right-sided tumors. Consequently, radiation therapy–induced cardiac disease may be less prominent than previously demonstrated.« less

Continuous internal counterpulsation as a bridge to recovery in acute and chronic heart failure

PubMed Central

Kontogiannis, Christos D; Malliaras, Konstantinos; Kapelios, Chris J; Mason, Jay W; Nanas, John N

2016-01-01

Cardiac recovery from cardiogenic shock (CS) and end-stage chronic heart failure (HF) remains an often insurmountable therapeutic challenge. The counterpulsation technique exerts numerous beneficial effects on systemic hemodynamics and left ventricular mechanoenergetics, rendering it attractive for promoting myocardial recovery in both acute and chronic HF. Although a recent clinical trial has questioned the clinical effectiveness of short-term hemodynamic support with intra-aortic balloon pump (IABP, the main representative of the counterpulsation technique) in CS complicating myocardial infarction, the issue remains open to further investigation. Moreover, preliminary data suggest that long-term IABP support in patients with end-stage HF is safe and may mediate recovery of left- or/and right-sided cardiac function, facilitating long-term weaning from mechanical support or enabling the application of other permanent, life-saving solutions. The potential of long-term counterpulsation could possibly be enhanced by implementation of novel, fully implantable counterpulsation devices. PMID:27011909

A rare case of supraventricular tachycardia induced by Infliximab: a case report

PubMed Central

2009-01-01

Background Infliximab, a chimeric monoclonal immunoglobulin antibody to tumor necrosis factor-α, has been established as a safe and effective treatment of rheumatoid arthritis, active and fistulising crohn's disease. Infliximab is generally well tolerated drug. The commonly reported cardiac side effects of Infliximab include exacerbation of congestive heart failure, hypotension and syncope. Symptomatic disorders of cardiac rhythm have been reported only rarely in few case reports and to the best of our knowledge, no tachyarrhythmia has been reported in past. Case report We report the case of a supraventricular tachycardia that occurred within three hours of Infliximab infusion in a patient with rheumatoid arthritis. Conclusion It is interesting to note that prior infusions in this patient did not precipitate similar consequences, thus, emphasising the importance of careful monitoring of patients on Infliximab therapy for possible reactions, even if prior exposures have been uneventful. PMID:19946518

Does ketogenic diet have any negative effect on cardiac systolic and diastolic functions in children with intractable epilepsy?: One-year follow-up results.

PubMed

Ozdemir, Rahmi; Kucuk, Mehmet; Guzel, Orkide; Karadeniz, Cem; Yilmaz, Unsal; Mese, Timur

2016-10-01

The ketogenic diet (KD) has been referred to as an "effective therapy with side effects" for children with intractable epilepsy. Among the most recognized adverse effects, there are cardiac conduction abnormalities, vascular and myocardial dysfunction. However, very limited and controversial data are available regarding the effects of the KD on cardiac functions. We sought to analyze the mid-term effect of ketogenic diet on cardiac functions in patients with intractable epilepsy who received a ketogenic diet for at least 12months using conventional and relatively new imaging techniques. This prospective study included 61 patients with intractable epilepsy who received ketogenic diet for at least 12months. Clinical examinations, serum carnitine and selenium levels as well as electrocardiographic and echocardiographic examinations were scheduled prior to the procedure and at 1, 3, 6 and 12months. We utilized two-dimensional, M-mode, colored Doppler, spectral Doppler and pulsed wave tissue Doppler imaging techniques to investigate ventricular systolic and diastolic functions of this subgroup of patients. In our study, there was no significant difference after 1year of KD therapy compared to baseline values-except a significantly decreased A wave velocity-in terms of pulse wave Doppler echocardiographic measurements of the diastolic function. The tissue Doppler measurements obtained from the lateral wall of tricuspide and mitral annuli were not different at baseline and at month 12 of the treatment, as well. The ketogenic diet appears to have no disturbing effect on ventricular functions in epileptic children in the midterm. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Cardiac systolic dysfunction in doxorubicin-challenged rats is associated with upregulation of MuRF2 and MuRF3 E3 ligases

PubMed Central

da Silva, Marcia Gracindo; Mattos, Elisabete; Camacho-Pereira, Juliana; Domitrovic, Tatiana; Galina, Antonio; Costa, Mauro W; Kurtenbach, Eleonora

2012-01-01

Doxorubicin (DOXO) is an efficient and low-cost chemotherapeutic agent. The use of DOXO is limited by its side effects, including cardiotoxicity, that may progress to cardiac failure as a result of multifactorial events that have not yet been fully elucidated. In the present study, the effects of DOXO at two different doses were analyzed to identify early functional and molecular markers of cardiac distress. One group of rats received 7.5 mg/kg of DOXO (low-dose group) and was followed for 20 weeks. A subset of these animals was then subjected to an additional cycle of DOXO treatment, generating a cumulative dose of 20 mg/kg (high-dose group). Physiological and biochemical parameters were assessed in both treatment groups and in a control group that received saline. Systolic dysfunction was observed only in the high-dose group. Mitochondrial function analysis showed a clear reduction in oxidative cellular respiration for animals in both DOXO treatment groups, with evidence of complex I damage being observed. Transcriptional analysis by quantitative polymerase chain reaction revealed an increase in atrial natriuretic peptide transcript in the high-dose group, which is consistent with cardiac failure. Analysis of transcription levels of key components of the cardiac ubiquitin-proteasome system found that the ubiquitin E3 ligase muscle ring finger 1 (MuRF1) was upregulated in both the low- and high-dose DOXO groups. MuRF2 and MuRF3 were also upregulated in the high-dose group but not in the low-dose group. This molecular profile may be useful as an early physiological and energetic cardiac failure indicator for testing therapeutic interventions in animal models. PMID:23620696

Side Effects of Long-Term Continuous Intra-arterial Nimodipine Infusion in Patients with Severe Refractory Cerebral Vasospasm after Subarachnoid Hemorrhage.

PubMed

Kieninger, Martin; Flessa, Julia; Lindenberg, Nicole; Bele, Sylvia; Redel, Andreas; Schneiker, André; Schuierer, Gerhard; Wendl, Christina; Graf, Bernhard; Silbereisen, Vera

2018-02-01

Long-term continuous intra-arterial nimodipine infusion (CIAN) is a rescue therapy option in cases of severe refractory cerebral vasospasm (CV) following acute non-traumatic subarachnoid hemorrhage (SAH). However, CIAN therapy can be associated with relevant side effects. Available studies focus on intracerebral complications, whereas extracerebral side effects are rarely examined. Aim of the present study was to generate descriptive data on the clinical course during CIAN therapy and expectable extracerebral side effects. All patients treated with CIAN therapy for at least 5 days between May 2011 and December 2015 were included. We retrospectively extracted data from the patient data management system regarding the period between 2 days before the beginning and 5 days after the termination of CIAN therapy to analyze the course of ventilation parameters and pulmonary gas exchange, hemodynamic support, renal and liver function, integrity of the gastrointestinal tract, and the occurrence of infectious complications. In addition, we recorded the mean daily values of intracranial pressure (ICP) and intracerebral problems associated with CIAN therapy. Data from 28 patients meeting inclusion criteria were analyzed. The mean duration of long-term CIAN therapy was 10.5 ± 4.5 days. Seventeen patients (60.7%) reached a good outcome level (Glasgow Outcome Scale [GOS] 4-5) 6 months after SAH. An impairment of the pulmonary gas exchange occurred only at the very beginning of CIAN therapy. The required vasopressor support with norepinephrine was significantly higher on all days during and the first day after CIAN therapy compared to the situation before starting CIAN therapy. Two patients required short-time resuscitation due to cardiac arrest during CIAN therapy. Acute kidney injury was observed in four patients, and one of them required renal replacement therapy with sustained low-efficiency daily dialysis. During CIAN therapy, 23 patients (82.1%) needed the escalation of a previous antiinfective therapy or the onset of antibiotics which was in line with a significant increase of C-reactive protein and white blood cell count. Obstipation was observed in 22 patients (78.6%). Ten patients (35.7%) even showed insufficient defecation on at least seven consecutive days. Compared to the situation before, ICP was significantly higher during the whole period of CIAN therapy. Long-term CIAN therapy is associated with diverse side effects. The leading problems are an impairment of the hemodynamic situation and cardiac problems, an increase in infectious complications, a worsening of the motility of the gastrointestinal tract, and rising ICP values. Teams on neurointensive care units must be aware of these side effects to avoid that the beneficial effects of CIAN therapy on CV reported elsewhere are foiled by the problems this technique can be associated with.

The morphology of the coronary sinus in patients with congenitally corrected transposition: implications for cardiac catheterisation and re-synchronisation therapy.

PubMed

Aiello, Vera D; Ferreira, Flávia C N; Scanavacca, Mauricio I; Anderson, Robert H; D'Avila, André

2016-02-01

Patients with congenitally corrected transposition frequently benefit from re-synchronisation therapy or ablation procedures. This is likely to require catheterisation of the coronary sinus. Its anatomy, however, is not always appreciated, despite being well-described. With this caveat in mind, we have evaluated its location and structure in hearts with congenitally corrected transposition in order to reinforce the guidance needed by the cardiac interventionist. We dissected and inspected the coronary sinus, the oblique vein of the left atrium, and the left-sided-circumflex venous channel in eight heart specimens with corrected transposition and eight controls, measuring the orifice and length of the sinus and the atrioventricular valves. In two-thirds of the malformed hearts, the sinus deviated from its anticipated course in the atrioventricular groove, ascending obliquely on the left atrial inferior wall to meet the left oblique vein. The maximal deviation coincided in all hearts with the point where the left oblique vein joined the left-sided-circumflex vein to form the coronary sinus. We describe a circumflex vein, rather than the great cardiac vein, as the latter venous channel is right-sided in the setting of corrected transposition. The length of the sinus correlated positively with the diameter of the tricuspid valve (p=0.02). Compared with controls, the left oblique vein in the malformed hearts joined the circumflex venous channel significantly closer to the mouth of the sinus. The unexpected course of the coronary sinus in corrected transposition and the naming of the cardiac veins have important implications for venous cannulation and interpretation of images.

Tricuspid annuloplasty versus a conservative approach in patients with functional tricuspid regurgitation undergoing left-sided heart valve surgery: A study-level meta-analysis.

PubMed

Pagnesi, Matteo; Montalto, Claudio; Mangieri, Antonio; Agricola, Eustachio; Puri, Rishi; Chiarito, Mauro; Ancona, Marco B; Regazzoli, Damiano; Testa, Luca; De Bonis, Michele; Moat, Neil E; Rodés-Cabau, Josep; Colombo, Antonio; Latib, Azeem

2017-08-01

Tricuspid valve (TV) repair at the time of left-sided valve surgery is indicated in patients with either severe functional tricuspid regurgitation (TR) or mild-to-moderate TR with coexistent tricuspid annular dilation or right heart failure. We assessed the benefits of a concomitant TV repair strategy during left-sided surgical valve interventions, focusing on mortality and echocardiographic TR-related outcomes. A meta-analysis was performed of studies reporting outcomes of patients who underwent left-sided (mitral and/or aortic) valve surgery with or without concomitant TV repair. Primary endpoints were all-cause and cardiac-related mortality; secondary endpoints were the presence of more-than-moderate TR, TR progression, and TR severity grade. All endpoints were evaluated at the longest available follow-up. Fifteen studies were included for a total of 2840 patients. TV repair at the time of left-sided valve surgery was associated with a significantly lower risk of cardiac-related mortality (odds ratio [OR] 0.38; 95% confidence interval [CI]: 0.25-0.58; p<0.001), with a trend towards a lower risk of all-cause mortality (OR 0.57; 95% CI: 0.32-1.05; p=0.07) at a mean weighted follow-up of 6years. The presence of more-than-moderate TR (OR 0.19; 95% CI: 0.12-0.30; p<0.001), TR progression (OR 0.03; 95% CI: 0.01-0.05; p<0.001), and TR grade (standardized mean difference -1.11; 95% CI: -1.57 to -0.65; p<0.001) were significantly lower in the TV repair group at a mean weighted follow-up of 4.7years. A concomitant TV repair strategy during left-sided valve surgery is associated with a reduction in cardiac-related mortality and improved echocardiographic TR outcomes at follow-up. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Cardiac adaption during pregnancy in women with congenital heart disease and healthy women.

PubMed

Kampman, Marlies A M; Valente, Mattia A E; van Melle, Joost P; Balci, Ali; Roos-Hesselink, Jolien W; Mulder, Barbara J M; van Dijk, A P J; Oudijk, M A; Jongbloed, M R M; van Veldhuisen, Dirk J; Pieper, Petronella G

2016-08-15

Pregnancy in women with congenital heart disease (CHD) is associated with deterioration in cardiac function. However, longitudinal data are scarce. This study describes serial changes in cardiac dimensions and function during pregnancy in women with CHD and compares these with healthy pregnant women (controls). Eight tertiary centres prospectively enrolled 125 pregnant women with CHD (pregnancy duration <20 weeks). Controls (N=49) were recruited from low-risk midwife practices. Standardised echocardiography at 20 and 32 weeks gestation and 1 year postpartum was performed. Age and parity were comparable between both groups (p>0.1). Left ventricular ejection fraction (LVEF) <45% was present in 3.2% of women with CHD and 14.4% had tricuspid annular plane systolic excursion (TAPSE) <16 mm. Absolute values of ventricular function parameters and diameters were less favourable in women with CHD. No permanent changes occurred in right and left ventricular function parameters and dimensions in women with CHD. The patterns of change in cardiac function and dimensions were comparable between women with CHD and controls, except for LVEF (p=0.026). In women with right-sided CHD the pattern of TAPSE over time differed from controls (p=0.043) (no decrease in TAPSE postpregnancy in CHD). In women with left-sided CHD left ventricular end-diastolic diameter (LVEDD) tended to increase compared with controls (p=0.045). Absolute levels of ventricular function parameters and diameters differ between CHD and controls, but changes during and after pregnancy are generally comparable. However, different patterns over time seen for TAPSE and LVEDD in women with right-sided and left-sided CHD, respectively, compared with controls indicate the importance of echocardiographic follow-up during pregnancy in women with CHD. 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/

The Effect of Milrinone on Splanchnic and Cerebral Perfusion in Infants With Congenital Heart Disease Prior to Surgery: An Observational Study.

PubMed

Bianchi, Maria Otilia; Cheung, Po-Yin; Phillipos, Ernest; Aranha-Netto, Abimael; Joynt, Chloe

2015-08-01

Despite the advancement in the postoperative care of neonates with congenital heart disease (CHD), there is little information on preoperative management of systemic and regional hemodynamics, which may be related to outcomes. We aimed to determine the preoperative effect of milrinone, a phosphodiesterase III inhibitor, on cardiac output and splanchnic and cerebral perfusion in neonates with CHD. Neonates with CHD requiring cardiac surgery were enrolled in a prospective, single-blinded study once a clinical decision of starting milrinone (0.75 μg/kg per minute intravenously) using institutional criteria was made. Demographic and clinical variables and outcomes were recorded. Combined cardiac output and measures of splanchnic (superior mesenteric and celiac arteries) and cerebral (anterior and middle cerebral arteries) perfusion were determined by Doppler studies at 0, 6, 24, and 48 h after milrinone infusion. Investigators were unaware of intervention time points and patients in analyzing blood flow measurements. Seventeen term (39.2 ± 1.3 weeks) neonates were included with hypoplastic left-sided heart syndrome (78.5%) as the most common diagnosis. Combined cardiac output increased by 28% within 48 h (613 ± 154 vs. 479 ± 147 mL/kg per minute at baseline, P < 0.05). Superior mesenteric artery mean velocity increased at 6 h and throughout 48 h of milrinone infusion (P < 0.05). Peak and mean velocities at cerebral arteries increased with milrinone infusion (P < 0.05~0.08), and the corresponding changes at celiac artery were modest. There were no significant changes in splanchnic and cerebral resistive and pulsatility indices during milrinone infusion. Milrinone increases cardiac output with concurrent effects on splanchnic and cerebral blood flows during the short-term preoperative use in neonates with CHD.

Deconstructing Decisions to Initiate, Maintain, or Discontinue Adjuvant Endocrine Therapy in Breast Cancer Survivors: A Mixed-Methods Study

PubMed Central

Bluethmann, Shirley M.; Murphy, Caitlin C.; Tiro, Jasmin A.; Mollica, Michelle A.; Vernon, Sally W.; Bartholomew, Leona Kay

2017-01-01

Purpose/Objectives Adjuvant endocrine therapy (AET) has been shown to improve survival in hormone receptor–positive breast cancer survivors, but as many as half do not complete recommended treatment. Management of medication-related side effects and engagement with providers are two potentially modifiable factors, but their associations with adherence are not well understood. The aims were to build on survey results to qualitatively explore survivors’ experiences with prescribed AET to (a) describe appraisal and management of AET side effects and (b) deconstruct decisions to initiate, discontinue, or maintain AET. Research Approach The authors used a mixed-methods explanatory sequence research design with a qualitative emphasis. Setting Survivors were recruited from a clinical cancer registry maintained at the University of Texas Southwestern Medical Center, which includes the Harold C. Simmons Comprehensive Cancer Center (National Cancer Institute–designated), in Dallas. Participants 452 survivors completed a survey, and 30 took part in telephone interviews. Methodologic Approach Qualitative methods were used in which the authors recorded and transcribed interviews for analysis and used open coding to reduce data into themes. Findings Among adherent survivors, the themes of tolerance of side effects and perseverance were strong. Nonadherent survivors expressed more difficulty managing side effects and perceived fewer benefits when side effects were bothersome. The most common side effects mentioned by all survivors were menopausal symptoms and joint pain; less common side effects were cognitive decline and cardiac distress. Some sought advice from their oncology team. Nonadherent survivors appeared initially motivated to maintain AET but identified a tolerance limit for side effects after which a provider’s recommendation was less influential in their decision to maintain or discontinue AET. Interpretation This study elucidated adherence as a complex continuum of behaviors, appraisals, and decision points. These insights may be particularly useful in counseling survivors taking AET and promoting timely delivery of clinical interventions to enhance adherence. Implications for Nursing Nurses should be involved in the planning and implementation of clinical interventions to manage side effects and other barriers to AET adherence. PMID:28635973

Variations of circulating cardiac biomarkers during and after anthracycline-containing chemotherapy in breast cancer patients.

PubMed

Frères, Pierre; Bouznad, Nassim; Servais, Laurence; Josse, Claire; Wenric, Stéphane; Poncin, Aurélie; Thiry, Jérôme; Moonen, Marie; Oury, Cécile; Lancellotti, Patrizio; Bours, Vincent; Jerusalem, Guy

2018-01-29

Over time, the chance of cure after the diagnosis of breast cancer has been increasing, as a consequence of earlier diagnosis, improved diagnostic procedures and more effective treatment options. However, oncologists are concerned by the risk of long term treatment side effects, including congestive heart failure (CHF). In this study, we evaluated innovative circulating cardiac biomarkers during and after anthracycline-based neoadjuvant chemotherapy (NAC) in breast cancer patients. Levels of cardiac-specific troponins T (cTnT), N-terminal natriuretic peptides (NT-proBNP), soluble ST2 (sST2) and 10 circulating microRNAs (miRNAs) were measured. Under chemotherapy, we observed an elevation of cTnT and NT-proBNP levels, but also the upregulation of sST2 and of 4 CHF-related miRNAs (miR-126-3p, miR-199a-3p, miR-423-5p, miR-34a-5p). The elevations of cTnT, NT-proBNP, sST2 and CHF-related miRNAs were poorly correlated, suggesting that these molecules could provide different information. Circulating miRNA and sST2 are potential biomarkers of the chemotherapy-related cardiac dysfunction (CRCD). Nevertheless, further studies and long-term follow-up are needed in order to evaluate if these new markers may help to predict CRCD and to identify the patients at risk to later develop CHF.

The Effect of Antifibrinolytic Prophylaxis on Postoperative Outcomes in Patients Undergoing Cardiac Operations

PubMed Central

Koul, Abhinav; Ferraris, Victor; Davenport, Daniel L; Ramaiah, Chandrashekhar

2012-01-01

Antifibrinolytic agents such as aprotinin and epsilon aminocaproic acid limit postoperative bleeding and blood transfusion in patients undergoing cardiac operations using cardiopulmonary bypass (CPB). Recent evidence suggests that these agents have adverse side effects that influence operative mortality and morbidity. We studied postoperative bleeding, transfusion rates, and operative outcomes in our patients in order to assess the efficacy of these agents during cardiac operations requiring CPB. We reviewed records of 520 patients undergoing a variety of cardiac operations between January 2005 and May 2009. We measured multiple variables including pre-operative risk factors, antifibrinolytic agent used, and outcomes of operation, such as measures of bleeding and blood transfusion, as well as serious operative morbidity and mortality. Postoperative bleeding rates varied significantly between patients receiving aprotinin and those receiving aminocaproic acid (P < 0.05). There was an associated 12% decrease in operative site bleeding in aprotinin-treated patients compared with aminocaproic acid. There was no significant difference in the transfusion rates of packed red blood cells between patients receiving aminocaproic acid or aprotinin (P > 0.05), though individuals in the aprotinin group did receive FFP more frequently than patients in the aminocaproic acid group (P < 0.05). There was no significant difference in morbidity and mortality rates between patients in either drug group (P > 0.05). Our study shows that aprotinin is more effective at controlling operative site bleeding than aminocaproic acid. Reduced operative site bleeding did not portend better outcome or differences in transfusion requirements. Aminocaproic acid remains a safe and cost-effective option for antifibrinolytic prophylaxis because of unavailability of aprotinin. PMID:23101999

Trichostatin A accentuates doxorubicin-induced hypertrophy in cardiac myocytes

PubMed Central

Karagiannis, Tom C; Lin, Ann JE; Ververis, Katherine; Chang, Lisa; Tang, Michelle M; Okabe, Jun; El-Osta, Assam

2010-01-01

Histone deacetylase inhibitors represent a new class of anticancer therapeutics and the expectation is that they will be most effective when used in combination with conventional cancer therapies, such as the anthracycline, doxorubicin. The dose-limiting side effect of doxorubicin is severe cardiotoxicity and evaluation of the effects of combinations of the anthracycline with histone deacetylase inhibitors in relevant models is important. We used a well-established in vitro model of doxorubicin-induced hypertrophy to examine the effects of the prototypical histone deacetylase inhibitor, Trichostatin A. Our findings indicate that doxorubicin modulates the expression of the hypertrophy-associated genes, ventricular myosin light chain-2, the alpha isoform of myosin heavy chain and atrial natriuretic peptide, an effect which is augmented by Trichostatin A. Furthermore, we show that Trichostatin A amplifies doxorubicin-induced DNA double strand breaks, as assessed by γH2AX formation. More generally, our findings highlight the importance of investigating potential side effects that may be associated with emerging combination therapies for cancer. PMID:20930262

Trichostatin A accentuates doxorubicin-induced hypertrophy in cardiac myocytes.

PubMed

Karagiannis, Tom C; Lin, Ann J E; Ververis, Katherine; Chang, Lisa; Tang, Michelle M; Okabe, Jun; El-Osta, Assam

2010-10-01

Histone deacetylase inhibitors represent a new class of anticancer therapeutics and the expectation is that they will be most effective when used in combination with conventional cancer therapies, such as the anthracycline, doxorubicin. The dose-limiting side effect of doxorubicin is severe cardiotoxicity and evaluation of the effects of combinations of the anthracycline with histone deacetylase inhibitors in relevant models is important. We used a well-established in vitro model of doxorubicin-induced hypertrophy to examine the effects of the prototypical histone deacetylase inhibitor, Trichostatin A. Our findings indicate that doxorubicin modulates the expression of the hypertrophy-associated genes, ventricular myosin light chain-2, the alpha isoform of myosin heavy chain and atrial natriuretic peptide, an effect which is augmented by Trichostatin A. Furthermore, we show that Trichostatin A amplifies doxorubicin-induced DNA double strand breaks, as assessed by γH2AX formation. More generally, our findings highlight the importance of investigating potential side effects that may be associated with emerging combination therapies for cancer.

Cardiac Dysfunction and Oxidative Stress in the Metabolic Syndrome: an Update on Antioxidant Therapies

PubMed Central

Ilkun, Olesya; Boudina, Sihem

2013-01-01

The metabolic syndrome (MetS) is a cluster of risk factors including obesity, insulin resistance, dyslipidemia, elevated blood pressure and glucose intolerance. The MetS increases the risk for cardiovascular disease (CVD) and type 2 diabetes. Each component of the MetS causes cardiac dysfunction and their combination carries additional risk. The mechanisms underlying cardiac dysfunction in the MetS are complex and might include lipid accumulation, increased fibrosis and stiffness, altered calcium homeostasis, abnormal autophagy, altered substrate utilization, mitochondrial dysfunction and increased oxidative stress. Mitochondrial and extra-mitochondrial sources of reactive oxygen species (ROS) and reduced antioxidant defense mechanisms characterize the myocardium of humans and animals with the MetS. The mechanisms for increased cardiac oxidative stress in the MetS are not fully understood but include increased fatty acid oxidation, mitochondrial dysfunction and enhanced NADPH oxidase activity. Therapies aimed to reduce oxidative stress and enhance antioxidant defense have been employed to reduce cardiac dysfunction in the MetS in animals. In contrast, large scale clinical trials using antioxidants therapies for the treatment of CVD have been disappointing because of the lack of efficacy and undesired side effects. The focus of this review is to summarize the current knowledge about the mechanisms underlying cardiac dysfunction in the MetS with a special interest in the role of oxidative stress. Finally, we will update the reader on the results obtained with natural antioxidant and mitochondria-targeted antioxidant therapies for the treatment of CVD in the MetS. PMID:23323621

[Ingestion of anabolic steroids and ischaemic stroke. A clinical case report and review of the literature].

PubMed

García-Esperón, Carlos; Hervás-García, José Vicente; Jiménez-González, Marta; Pérez de la Ossa-Herrero, Natalia; Gomis-Cortina, Meritxell; Dorado-Bouix, Laura; López-Cancio Martinez, Elena; Castaño-Duque, Carlos H; Millán-Torné, Mónica; Dávalos, Antonio

2013-03-16

INTRODUCTION. Anabolic-androgenic steroids are synthetic substances derived from testosterone that are employed for their trophic effect on muscle tissue, among other uses. Their consumption can give trigger a series of adverse side effects on the body, including the suppression of the hypothalamus-pituitary-gonadal axis as well as liver, psychiatric and cardiovascular disorders. The most common effects are altered fat profiles and blood pressure values, cardiac remodelling, arrhythmias or myocardial infarcts. CASE REPORT. We report the case of a young male, with a background of anabolic-androgenic steroids abuse, who visited because of an acute neurological focus in the right hemisphere related with an ischaemic stroke. The aetiological study, including cardiac monitoring, echocardiograph and imaging studies (magnetic resonance and arteriography) and lab findings (thrombophilia, serology, autoimmunity, tumour markers) showed no alterations. CONCLUSIONS. The association between consumption of anabolic-androgenic steroids and cardiovascular pathologies is known, but its relation with cerebrovascular disease has not received so much attention from researchers.

Effects of single low-temperature sauna bathing in patients with severe motor and intellectual disabilities

NASA Astrophysics Data System (ADS)

Iiyama, Junichi; Matsushita, Kensuke; Tanaka, Nobuyuki; Kawahira, Kazumi

2008-07-01

We have previously reported that thermal vasodilation following warm-water bathing and low-temperature sauna bathing (LTSB) at 60 °C for 15 min improves the cardiac function in patients with congestive heart failure. Through a comparative before-and-after study, we studied the hemodynamic and clinical effects of single exposure to LTSB in cerebral palsy (CP) patients who usually suffer from chilled extremities and low cardiac output. The study population comprised 16 patients ranging between 19 and 53 years with severe motor and intellectual disabilities. Noninvasive methods were used to estimate the systemic and peripheral circulatory changes before and after LTSB. Using blood flow velocity analysis, the pulsatile and resistive indexes of the peripheral arteries of the patients’ lower limbs were calculated. Following LTSB, the patients’ deep body temperature increased significantly by 1°C. Their heart rates increased and blood pressure decreased slightly. The total peripheral resistance decreased by 11%, and the cardiac output increased by 14%. There was significant improvement in the parameters that are indicative of the peripheral circulatory status, including the skin blood flow, blood flow velocity, pulsatile index, and resistive index. Numbness and chronic myalgia of the extremities decreased. There were no adverse side effects. Thus, it can be concluded that LTSB improves the peripheral circulation in CP patients.

Effects of single low-temperature sauna bathing in patients with severe motor and intellectual disabilities.

PubMed

Iiyama, Junichi; Matsushita, Kensuke; Tanaka, Nobuyuki; Kawahira, Kazumi

2008-07-01

We have previously reported that thermal vasodilation following warm-water bathing and low-temperature sauna bathing (LTSB) at 60 degrees C for 15 min improves the cardiac function in patients with congestive heart failure. Through a comparative before-and-after study, we studied the hemodynamic and clinical effects of single exposure to LTSB in cerebral palsy (CP) patients who usually suffer from chilled extremities and low cardiac output. The study population comprised 16 patients ranging between 19 and 53 years with severe motor and intellectual disabilities. Noninvasive methods were used to estimate the systemic and peripheral circulatory changes before and after LTSB. Using blood flow velocity analysis, the pulsatile and resistive indexes of the peripheral arteries of the patients' lower limbs were calculated. Following LTSB, the patients' deep body temperature increased significantly by 1 degrees C. Their heart rates increased and blood pressure decreased slightly. The total peripheral resistance decreased by 11%, and the cardiac output increased by 14%. There was significant improvement in the parameters that are indicative of the peripheral circulatory status, including the skin blood flow, blood flow velocity, pulsatile index, and resistive index. Numbness and chronic myalgia of the extremities decreased. There were no adverse side effects. Thus, it can be concluded that LTSB improves the peripheral circulation in CP patients.

Reversible pulmonary hypertension in a cat.

PubMed

Baron Toaldo, M; Guglielmini, C; Diana, A; Giunti, M; Dondi, F; Cipone, M

2011-05-01

A 13-year-old, neutered female domestic shorthair cat was presented for sudden respiratory distress following palliative radiotherapy and the combined administration of a single dose of carboplatin for the treatment of recurrent fibrosarcoma. Clinical and radiographic findings were suggestive of pleural effusion. Echocardiography revealed marked right-sided cardiac enlargement associated with tricuspid regurgitation and Doppler evidence of pulmonary hypertension. After 25 days of treatment for congestive heart failure and suspected pulmonary thromboembolism, clinical signs and echocardiographic and Doppler evidence of right-sided cardiac enlargement and pulmonary hypertension had completely resolved. To the best of the authors' knowledge, this is the first report of reversible pulmonary hypertension, likely secondary to pulmonary thromboembolism, in a cat. © 2011 British Small Animal Veterinary Association.

Brucellosis With Multi-Organ Involvement in a Patient With History of Composite Aortic Graft and Hepatitis B.

PubMed

Dehghan Manshadi, Seyed Ali; Rezahosseini, Omid; Abdi Liaei, Zahra

2016-11-01

The brucellosis with multi-organ involvement in a patient with a history of the composite aortic graft (Bentall procedure) and Hepatitis B infection is rare. A 35-year-old man presented to us with fever and loss of consciousness. Four years ago, he was IDU and underwent cardiac surgery because of endocarditis. Recently lumbar spondylodiscitis was diagnosed. The Wright (1/320) and Coombs Wright tests (1/640) were positive. After CNS imaging, lumbar puncture was done. The CSF pleocytosis was lymphocyte dominant. In cardiac echocardiography, large vegetation on prosthetic aortic valve leaflets was seen. The brain MRI was reported abnormal. Treatment of brucellosis started with Ceftriaxone, Doxycycline, Rifampin and Gentamycin. After 4 days, he became oriented, and fever was disappeared then we continued the treatment for 16 days. The patient discharged and followed by daily phone calls. As symptoms of abdominal pain and jaundice were presented on the fifth day, he re-admitted. The patient expired because of hepatorenal and cardiac insufficiency. Drug side effects, activation of Hepatitis B and embolism of cardiac vegetation to other organs were suspected causes of death. We do not suggest medical therapy without cardiac surgery in such cases. When combination therapy is necessary for brucellosis in an HBsAg-positive patient, hepatitis virus activity should be assess by HBV-DNA PCR and the dose of drugs with known hepatotoxic effects such as rifampin and co-trimoxazole should be adjust. Combination therapy with quinolones instead of hepatoxic drugs is one of our suggustions.

Bilateral pneumothorax, surgical emphysema and pneumomediastinum in a young male patient following MDMA intake.

PubMed

Obiechina, Nonyelum Evangeline; Jayakumar, Ahrane; Khan, Yusra; Bass, James

2018-04-07

MDMA (3,4-methylenedioxymethamphetamine) or 'Ecstasy' is an illicit drug frequently used by young people at parties and 'raves'. It is readily available in spite of the fact that it is illegal. 1 It is perceived by a lot of young people as being 'harmless', but there have been a few high-profile deaths associated with its use. 2 Known side effects of MDMA include hyperthermia, rhabdomyolysis, coagulopathy and cardiac arrhythmias. 3 Rarer side effects include surgical emphysema and pneumomediastinum, which have been better described with cocaine abuse. 4-6 We present a case of bilateral pneumothorax, surgical emphysema and pneumomediastinum in a young man after taking ecstasy. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Thoracentesis-reverting cardiac tamponade physiology in a patient with myxedema coma and large pleural effusion.

PubMed

Werlang, Monia E; Pimentel, Mario R; Diaz-Gomez, Jose L

2017-07-01

A large pleural effusion causing cardiac tamponade physiology and severe hemodynamic compromise is an uncommon event. We report a case of a 53-year-old woman with severe hypothyroidism presenting with myxedema coma and refractory shock. Her hemodynamic status failed to respond to fluid resuscitation and vasopressors. A transthoracic echocardiogram and chest radiograph demonstrated a pericardial fluid accumulation associated with a large left-sided pleural effusion. Thoracostomy tube insertion resulted in prompt improvement of the patient's hemodynamic status. Our finding demonstrates that a large pleural effusion may play an important role in cardiac tamponade physiology.

Complete A-V block: incidental or a part of cor triatriatum dexter.

PubMed

Guler, Y; Akgun, T; Toprak, C; Guler, A; Esen, A M

2014-05-01

Cor triatriatum dexter (CTD) is an extremely rare cardiac anomaly in which the right atrium is divided into two distinct chambers by a membrane. The persistence of the right valve of sinus venosus results in a complete septation of the right atrium. This anomaly is frequently associated with other right-sided cardiac abnormalities. Its clinical manifestation and the need for intervention are determined by the number and the size of the fenestrations on the membrane, associated cardiac anomalies and arrhythmias. We describe a case of CTD in a patient with complete atrioventricular (A-V) block.

Management of a hyperactive teen and cardiac safety.

PubMed

Sowinski, Heather; Karpawich, Peter P

2014-02-01

Since the earliest descriptions of the condition, controversy has prevailed as to the existence of as well as appropriate management of attention deficit hyperactivity disorder. Often diagnosed in childhood, symptoms of attention deficit hyperactivity disorder can continue into adolescence and adulthood, requiring lifelong therapy. Effective therapeutic interventions include stimulant medications with all their respective potential side effects, including the cardiovascular system. However, although initial studies raised concerns for an increase in serious adverse cardiovascular effects among children receiving these drugs, more recent and extensive reports have failed to substantiate those findings among young patients. Copyright © 2014 Elsevier Inc. All rights reserved.

[Effects of red ginseng on the congestive heart failure and its mechanism].

PubMed

Ding, D Z; Shen, T K; Cui, Y Z

1995-06-01

Forty-five patients with class IV cardiac function were divided into three groups: group I (digoxin group), group II (Red Ginseng group) and group III (Red Ginseng plus digoxin group). Each group consisted of 15 cases. After treatment, the improvement of the hemodynamical and biochemical indexes of group II and group III were greater than those of group I, and group III was the most significant amongst all. The results suggested that Red Ginseng and digoxin had synergism for treatment of congestive heart failure, and Red Ginseng was an effective and safe adjuvant without any side effects.

Rational and timely haemostatic interventions following cardiac surgery - coagulation factor concentrates or blood bank products.

PubMed

Tang, Mariann; Fenger-Eriksen, Christian; Wierup, Per; Greisen, Jacob; Ingerslev, Jørgen; Hjortdal, Vibeke; Sørensen, Benny

2017-06-01

Cardiac surgery may cause a serious coagulopathy leading to increased risk of bleeding and transfusion demands. Blood bank products are commonly first line haemostatic intervention, but has been associated with hazardous side effect. Coagulation factor concentrates may be a more efficient, predictable, and potentially a safer treatment, although prospective clinical trials are needed to further explore these hypotheses. This study investigated the haemostatic potential of ex vivo supplementation of coagulation factor concentrates versus blood bank products on blood samples drawn from patients undergoing cardiac surgery. 30 adults were prospectively enrolled (mean age=63.9, females=27%). Ex vivo haemostatic interventions (monotherapy or combinations) were performed in whole blood taken immediately after surgery and two hours postoperatively. Fresh-frozen plasma, platelets, cryoprecipitate, fibrinogen concentrate, prothrombin complex concentrate (PCC), and recombinant FVIIa (rFVIIa) were investigated. The haemostatic effect was evaluated using whole blood thromboelastometry parameters, as well as by thrombin generation. Immediately after surgery the compromised maximum clot firmness was corrected by monotherapy with fibrinogen or platelets or combination therapy with fibrinogen. At two hours postoperatively the coagulation profile was further deranged as illustrated by a prolonged clotting time, a reduced maximum velocity and further diminished maximum clot firmness. The thrombin lagtime was progressively prolonged and both peak thrombin and endogenous thrombin potential were compromised. No monotherapy effectively corrected all haemostatic abnormalities. The most effective combinations were: fibrinogen+rFVIIa or fibrinogen+PCC. Blood bank products were not as effective in the correction of the coagulopathy. Coagulation factor concentrates appear to provide a more optimal haemostasis profile following cardiac surgery compared to blood bank products. Copyright © 2017 Elsevier Ltd. All rights reserved.

hERG K+ channel-associated cardiac effects of the antidepressant drug desipramine.

PubMed

Staudacher, Ingo; Wang, Lu; Wan, Xiaoping; Obers, Sabrina; Wenzel, Wolfgang; Tristram, Frank; Koschny, Ronald; Staudacher, Kathrin; Kisselbach, Jana; Koelsch, Patrick; Schweizer, Patrick A; Katus, Hugo A; Ficker, Eckhard; Thomas, Dierk

2011-02-01

Cardiac side effects of antidepressant drugs are well recognized. Adverse effects precipitated by the tricyclic drug desipramine include prolonged QT intervals, torsade de pointes tachycardia, heart failure, and sudden cardiac death. QT prolongation has been primarily attributed to acute blockade of hERG/I(Kr) currents. This study was designed to provide a more complete picture of cellular effects associated with desipramine. hERG channels were expressed in Xenopus laevis oocytes and human embryonic kidney (HEK 293) cells, and potassium currents were recorded using patch clamp and two-electrode voltage clamp electrophysiology. Ventricular action potentials were recorded from guinea pig cardiomyocytes. Protein trafficking and cell viability were evaluated in HEK 293 cells and in HL-1 mouse cardiomyocytes by immunocytochemistry, Western blot analysis, or colorimetric MTT assay, respectively. We found that desipramine reduced hERG currents by binding to a receptor site inside the channel pore. hERG protein surface expression was reduced after short-term treatment, revealing a previously unrecognized mechanism. When long-term effects were studied, forward trafficking was impaired and hERG currents were decreased. Action potential duration was prolonged upon acute and chronic desipramine exposure. Finally, desipramine triggered apoptosis in cells expressing hERG channels. Desipramine exerts at least four different cellular effects: (1) direct hERG channel block, (2) acute reduction of hERG surface expression, (3) chronic disruption of hERG trafficking, and (4) induction of apoptosis. These data highlight the complexity of hERG-associated drug effects.

Pulmonary Hypertension, Hyperthyroidism, and Fenfluramine: A Case Report and Review

PubMed Central

Ying, Leung Ying; Shing, Tang Kam; Chi, Tsang Chiu; Kin, Chan Chi; Keung, Wong Kwan; Wai-yin, Yu Alex

2006-01-01

We report a case of pulmonary hypertension presenting with sudden cardiac arrest, hyperthyroidism and fenfluramine usage. This fatal case of pulmonary hypertension and valvular heart disease is associated with the use of an anorectic drug that had been withdrawn from the market more than eight years ago. Clinicians should alert to the side effects of appetite suppressant and slimming agents. The association between pulmonary hypertension in relation to hyperthyroidism and fenfluramine usage is reviewed. PMID:17415311

Mesalamine-induced myopericarditis - A case report.

PubMed

Bernardo, Sónia; Fernandes, Samuel Raimundo; Araújo-Correia, Luís

2016-11-01

Myopericarditis has occasionally been reported as a side effect of mesalamine in patients with inflammatory bowel disease. We present a 20-year-old woman with ulcerative colitis admitted with chest pain. After thorough investigation she was diagnosed with myopericarditis potentially related to mesalamine. There was complete clinical and laboratorial recovery following drug withdrawal. Although uncommon, the possibility of myopericarditis should be considered in patients with inflammatory bowel disease presenting with cardiac complaints. Early recognition can avoid potential life-threatening complications.

Evaluation of the effects of patient arm attenuation in SPECT cardiac perfusion imaging

NASA Astrophysics Data System (ADS)

Luo, Dershan; King, M. A.; Pan, Tin-Su; Xia, Weishi

1996-12-01

It was hypothesized that the use of attenuation correction could compensate for degradation in the uniformity of apparent localization of imaging agents seen in cardiac walls when patients are imaged with arms at their sides. Noise-free simulations of the digital MCAT phantom were employed to investigate this hypothesis. Four variations in camera size and collimation scheme were investigated. We observed that: 1) without attenuation correction, the arms had little additional influences on the uniformity of the heart for 180/spl deg/ reconstructions and caused a small increase in nonuniformity for 360/spl deg/ reconstructions, where the impact of both arms was included; 2) change in patient size had more of an impact on count uniformity than the presence of the arms, either with or without attenuation correction; 3) for a low number of iterations and large patient size, slightly better uniformity was obtained from parallel emission data than from fan-beam emission data, independent of whether parallel or fan-beam transmission data was used to reconstruct the attenuation maps; and 4) for all camera configurations, uniformity was improved with attenuation correction and, given sufficient number of iterations, it was compatible among different imaging geometry combinations. Thus, iterative algorithms can compensate for the additional attenuation imposed by larger patients or having the arms on the sides. When the arms are at the sides of the patient, however, a larger radius of rotation may be required, resulting in decreased spatial resolution.

Evaluation of the effects of patient arm attenuation in SPECT cardiac perfusion imaging

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

Luo, D.; King, M.A.; Pan, T.S.

1996-12-01

It was hypothesized that the use of attenuation correction could compensate for degradation in the uniformity of apparent localization of imaging agents seen in cardiac walls when patients are imaged with arms at their sides. Noise-free simulations of the digital MCAT phantom were employed to investigate this hypothesis. Four variations in camera size and collimation scheme were investigated. The authors observed that: (1) without attenuation correction, the arms had little additional influences on the uniformity of the heart for 180{degree} reconstructions and caused a small increase in nonuniformity for 360{degree} reconstructions, where the impact of both arms was included; (2)more » change in patient size had more of an impact on count uniformity than the presence of the arms, either with or without attenuation correction; (3) for a low number of iterations and large patient size, slightly better uniformity was obtained from parallel emission data than from fan-beam emission data, independent of whether parallel or fan-beam transmission data was used to reconstruct the attenuation maps; and (4) for all camera configurations, uniformity was improved with attenuation correction and, given sufficient number of iterations, it was compatible among different imaging geometry combinations. Thus, iterative algorithms can compensate for the additional attenuation imposed by larger patients or having the arms on the sides. When the arms are at the sides of the patient, however, a larger radius of rotation may be required, resulting in decreased spatial resolution.« less

RhNRG-1β Protects the Myocardium against Irradiation-Induced Damage via the ErbB2-ERK-SIRT1 Signaling Pathway

PubMed Central

Gu, Anxin; Jie, Yamin; Sun, Liang; Zhao, Shuping; E, Mingyan; You, Qingshan

2015-01-01

Radiation-induced heart disease (RIHD), which is a serious side effect of the radiotherapy applied for various tumors due to the inevitable irradiation of the heart, cannot be treated effectively using current clinical therapies. Here, we demonstrated that rhNRG-1β, an epidermal growth factor (EGF)-like protein, protects myocardium tissue against irradiation-induced damage and preserves cardiac function. rhNRG-1β effectively ameliorated irradiation-induced myocardial nuclear damage in both cultured adult rat-derived cardiomyocytes and rat myocardium tissue via NRG/ErbB2 signaling. By activating ErbB2, rhNRG-1β maintained mitochondrial integrity, ATP production, respiratory chain function and the Krebs cycle status in irradiated cardiomyocytes. Moreover, the protection of irradiated cardiomyocytes and myocardium tissue by rhNRG-1β was at least partly mediated by the activation of the ErbB2-ERK-SIRT1 signaling pathway. Long-term observations further showed that rhNRG-1β administered in the peri-irradiation period exerts continuous protective effects on cardiac pump function, the myocardial energy metabolism, cardiomyocyte volume and interstitial fibrosis in the rats receiving radiation via NRG/ErbB2 signaling. Our findings indicate that rhNRG-1β can protect the myocardium against irradiation-induced damage and preserve cardiac function via the ErbB2-ERK-SIRT1 signaling pathway. PMID:26332771

Adult Bone Marrow Mesenchymal Stem Cells Primed for fhe Repair of Damaged Cardiac Tissue After Myocardial Infarction

NASA Astrophysics Data System (ADS)

Marks, Edward D.

The burden of cardiovascular disease around the world is growing, despite improvements in hospital care and time to treatment. As more people survive an initial myocardial infarction (MI), the decompensated heart tissue is strained, leading to heart failure (HF) and an increased risk for a second MI. While extensive progress has been made in treating the symptoms after MI, including HF and angina, little success has come from repairing the damaged heart tissue to alleviate the progression to these end- stage symptoms. One promising area of regenerative research has been the use of adult stem cells, particularly from the bone marrow (BMSCs). These cells can differentiate towards the cardiac cell lineage in vitro while producing trophic factors that can repair damaged tissue. When placed in the heart after MI though, BMSCs have mixed results, producing profound changes in some patients but zero or even negative effects in others. In this report, we used BMSCs as a stem cell base for a regenerative medicine system for the repair of damaged cardiac tissue. These cells are seeded on a polycaprolactone nanoscaffolding support system, which provides a growth substrate for in vitro work, as well as a housing system for protected in vivo delivery. When the nanoscaffold is pre-coated with a novel combination of a cardiac protein, thymosin beta4 (Tbeta4), and a small molecule effector of the WNT protein pathway, IWP-2, BMSCs differentiated towards the cardiac lineage in as little as 24hours. When injected into rat hearts that have been given an ischemic MI, the nanoscaffolding system slowly dissolves, leaving the cells in place of the damaged cardiac tissue. After two weeks of monitoring, BMSCs are present within the damaged hearts, as evidenced by immunofluorescence and nanoparticle tracking. Injections of the nanoscaffolding/cell system led to robust healing of the rat hearts that had been given small- and medium- damage heart attacks, outperforming PBS sham and cell culture media injections. Significant improvements in cardiac metrics, including ejection fraction and left ventricular end systolic volume, were seen compared to untreated animals, and were comparable to healthy controls. To our knowledge this is the first side-by-side comparison of cell culture media and stem cells to heal a predefined range of MI damage. We believe this simple, inexpensive treatment option is a new beneficial step towards healing damaged patient tissue after MI.

Clozapine Associated with Autoimmune Reaction, Fever and Low Level Cardiotoxicity – A Case Report

PubMed Central

GERASIMOU, CHARILAOS; PHAEDRA VITALI, GEORGIA; D. VAVOUGIOS, GEORGE; PAPAGEORGIOU, CHARALABOS; DOUZENIS, ATHANASIOS; I. KOKORIS, STYLIANI; LIAPPAS, IOANNIS; RIZOS, EMMANOUIL

2017-01-01

Background: Clozapine is a second-generation antipsychotic drug used in treatment-resistant schizophrenia. Fever induced by clozapine is a rather frequent side-effect which usually occurs in the first 4 weeks of treatment. Despite its effectiveness, there are potentially life-threatening adverse effects, such as cardiotoxicity. Case Report: We present the case of a 31- year-old caucasian male with refractory schizophrenia who developed benign fever, increase of C-reactive protein and high troponin levels, without presenting any other signs to myocarditis, on the 13th day under clozapine treatment, which declined progressively upon discontinuation of the drug. Discussion: This case hints at the presence of initially subclinical cardiotoxicity as an underlying factor in patients developing fever. Conclusion: Taking advantage of more sensitive methods for measuring troponin, clinicians would be promptly aware of this possible side-effect. This would allow for significant reduction of the risk of cardiac dysfunction, further attained by carefully monitoring the patient. PMID:28064233

Clozapine Associated with Autoimmune Reaction, Fever and Low Level Cardiotoxicity - A Case Report.

PubMed

Gerasimou, Charilaos; Vitali, Georgia Phaedra; Vavougios, George D; Papageorgiou, Charalabos; Douzenis, Athanasios; Kokoris, Styliani I; Liappas, Ioannis; Rizos, Emmanouil

2017-01-02

Clozapine is a second-generation antipsychotic drug used in treatment-resistant schizophrenia. Fever induced by clozapine is a rather frequent side-effect which usually occurs in the first 4 weeks of treatment. Despite its effectiveness, there are potentially life-threatening adverse effects, such as cardiotoxicity. We present the case of a 31-year-old caucasian male with refractory schizophrenia who developed benign fever, increase of C-reactive protein and high troponin levels, without presenting any other signs to myocarditis, on the 13th day under clozapine treatment, which declined progressively upon discontinuation of the drug. This case hints at the presence of initially subclinical cardiotoxicity as an underlying factor in patients developing fever. Taking advantage of more sensitive methods for measuring troponin, clinicians would be promptly aware of this possible side-effect. This would allow for significant reduction of the risk of cardiac dysfunction, further attained by carefully monitoring the patient. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

The Role of Intralipid Emulsion in the Rat Model of Digoxin Intoxication.

PubMed

Turan, Cansu Arslan; Ozturk, Tuba Cimilli; Akoglu, Ebru Unal; Ak, Rohat; Aygun, Kemal; Sahiner, Ali; Sumer, Engin; Somay, Adnan; Onur, Ozge Ecmel

2018-02-03

Although the mechanism of action is not well known, intravenous lipid emulsion (ILE) has been shown to be effective in the treatment of lipophilic drug intoxications. It is thought that, ILE probably separates the lipophilic drugs from target tissue by creating a lipid-rich compartment in the plasma. The second theory is that ILE provides energy to myocardium with high-dose free fatty acids activating the voltage-gated calcium channels in the myocytes. In this study, effects of ILE treatment on digoxin overdose were searched in an animal model in terms of cardiac side effects and survival. Forty Sprague-Dawley rats were divided into five groups. As the pre-treatment, the groups were administered saline, ILE, DigiFab and DigiFab and ILE. Following that, digoxin was infused to all groups until death except the control group. First arrhythmia and cardiac arrest observation times were recorded. According to the results, there was no statistically significant difference among the group in terms of first arrhythmia time and cardiac arrest times. However, when the saline group compared with ILE-treated group separately, significant difference was observed. DigiFab, ILE or ILE-DigiFab treatment make no significant difference in terms of the first arrhythmia and cardiac arrest duration in digoxin-intoxicated rats. However, it is not possible to say that at the given doses, ILE treatment might be successful at least as a known antidote. The fact that the statistical significance between the two groups is not observed in the subgroup analysis, the study should be repeated with larger groups.

Long-QT Syndrome and Therapy for Attention Deficit/Hyperactivity Disorder.

PubMed

Zhang, Claire; Kutyifa, Valentina; Moss, Arthur J; McNitt, Scott; Zareba, Wojciech; Kaufman, Elizabeth S

2015-10-01

Stimulants are the mainstay therapy for attention deficit/hyperactivity disorder (ADHD) and are associated with adrenergic side effects. There are limited data on the clinical course of patients treated for ADHD who have long-QT syndrome (LQTS), for which β-blockade is the goal of therapy. LQTS patients from the Rochester-based LQTS Registry (open-enrollment between 1979 and 2003; follow-up from 1979 to present) treated with stimulant or nonstimulant ADHD medications (n = 48) were compared to a 2:1 age-, gender-, and QTc-duration matched LQTS control group not exposed to ADHD medications (n = 96). Kaplan-Meier and Cox proportional hazards regression analyses were used to evaluate risk of cardiac events (syncope, aborted cardiac arrest, and sudden cardiac death) in LQTS patients treated with ADHD medications. During a mean follow-up of 7.9 ± 5.4 years after initiation of ADHD medication at a mean age 10.7 ±7.3 years, there was a 62% cumulative probability of cardiac events in the ADHD treatment group compared to 28% in the matched LQTS control group (P < 0.001). Time-dependent use of ADHD medication was associated with an increased risk for cardiac events (HR = 3.07; P = 0.03) in the multivariate Cox model adjusted for time-dependent β-blocker use and prior cardiac events. Subgroup gender analyses showed that time-dependent ADHD medication was associated with an increased risk in male LQTS patients (HR = 6.80, P = 0.04). LQTS patients treated with ADHD medications have increased risk for cardiac events, particularly syncope, and this risk is augmented in males. The findings highlight the importance of heightened surveillance for LQTS patients on ADHD medications. © 2015 Wiley Periodicals, Inc.

Switch from aprotinin to ε-aminocaproic acid: impact on blood loss, transfusion, and clinical outcome in neonates undergoing cardiac surgery.

PubMed

Martin, K; Gertler, R; Liermann, H; Mayr, N P; MacGuill, M; Schreiber, C; Vogt, M; Tassani, P; Wiesner, G

2011-12-01

With the withdrawal of aprotinin from worldwide marketing in November 2007, many institutions treating patients at high risk for hyperfibrinolysis had to update their therapeutic protocols. At our institution, the standard was switched from aprotinin to ε-aminocaproic acid (EACA) in all patients undergoing cardiac surgery with extracorporeal circulation including neonates. Although both antifibrinolytic medications have been used widely for many years, there are few data directly comparing their blood-sparing effect and their side-effects especially in neonates. Perioperative data from 235 neonates aged up to 30 days undergoing primary cardiac surgery were analysed. Between July 1, 2006 and November 5, 2007, all patients (n=95) received aprotinin. Starting November 6, 2007 until December 31, 2009, all patients (n=140) were treated with EACA. The primary outcome criterion was blood loss; secondary outcome criteria were transfusion requirements, renal, vascular, and neurological complications and also in-hospital mortality. All descriptive and intraoperative data variable were similar. Blood loss was significantly higher in the EACA group (P=0.001), but there was no difference in the rate of re-operation for bleeding (P=0.218) nor the number of transfusions. There were no differences in the incidences of postoperative renal, neurological, and vascular events or in-hospital mortality. In neonatal patients undergoing cardiac surgery, the switch to EACA treatment led to a higher postoperative blood loss. However, there were no differences in transfusion requirements or major clinical outcomes.

An integrative view of cisplatin-induced renal and cardiac toxicities: molecular mechanisms, current treatment challenges and potential protective measures

PubMed Central

Dugbartey, George J.; Peppone, Luke J.; de Graaf, Inge A.M.

2017-01-01

Cisplatin is currently one of the most widely-used chemotherapeutic agents against various malignancies. Its clinical application is limited, however, by inherent renal and cardiac toxicities and other side effects, of which the underlying mechanisms are only partly understood. Experimental studies show cisplatin generates reactive oxygen species, which impair the cell’s antioxidant defense system, causing oxidative stress and potentiating injury, thereby culminating in kidney and heart failure. Understanding the molecular mechanisms of cisplatin-induced renal and cardiac toxicities may allow clinicians to prevent or treat this problem better and may also provide a model for investigating drug-induced organ toxicity in general. This review discusses some of the major molecular mechanisms of cisplatin-induced renal and cardiac toxicities including disruption of ionic homeostasis and energy status of the cell leading to cell injury and cell death. We highlight clinical manifestations of both toxicities as well as (novel)biomarkers such as kidney injury molecule-1 (KIM-1), tissue inhibitor of metalloproteinase-1 (TIMP-1) and N-terminal pro-B-type natriuretic peptide (NT-proBNP). We also present some current treatment challenges and propose potential protective strategies with novel pharmacological compounds that might mitigate or prevent these toxicities, which include the use of hydrogen sulfide. PMID:27717837

Cardioselective K(ATP) channel blockers derived from a new series of m-anisamidoethylbenzenesulfonylthioureas.

PubMed

Englert, H C; Gerlach, U; Goegelein, H; Hartung, J; Heitsch, H; Mania, D; Scheidler, S

2001-03-29

Sulfonylthioureas exhibiting cardioselective blockade of ATP-sensitive potassium channels (K(ATP) channels) were discovered by stepwise structural variations of the antidiabetic sulfonylurea glibenclamide. As screening assays, reversal of rilmakalim-induced shortening of the cardiac action potential in guinea pig papillary muscles was used to probe for activity on cardiac K(ATP) channels as the target, and membrane depolarization in CHO cells stably transfected with hSUR1/hKir6.2 was used to probe for unwanted side effects on pancreatic K(ATP) channels. Changing glibenclamide's para-arrangement of substituents in the central aromatic ring to a meta-pattern associated with size reduction of the substituent at the terminal nitrogen atom of the sulfonylurea moiety was found to achieve cardioselectivity. An additional change from a sulfonylurea moiety to a sulfonylthiourea moiety along with an appropriate substituent in the ortho-position of the central aromatic system was a successful strategy to further improve potency on the cardiac K(ATP) channel. Among this series of sulfonylthioureas HMR1883, 1-[5-[2-(5-chloro-o-anisamido)ethyl]-2-methoxyphenyl]sulfonyl-3-methylthiourea, and its sodium salt HMR1098 were selected for development and represent a completely new therapeutic approach toward the prevention of life-threatening arrhythmias and sudden cardiac death in patients with coronary heart disease.

Tricuspid valve dysplasia: A retrospective study of clinical features and outcome in dogs in the UK

PubMed Central

Navarro-Cubas, Xavier; Palermo, Valentina; French, Anne; Sanchis-Mora, Sandra; Culshaw, Geoff

2017-01-01

The objective of this study was to determine the demographic, clinical and survival characteristics and to identify risk factors for mortality due to tricuspid valve dysplasia in UK dogs. Records of client-owned dogs diagnosed with tricuspid valve dysplasia at a referral centre were retrospectively reviewed. Only dogs diagnosed with tricuspid valve dysplasia based on the presence of a right-sided heart murmur identified prior to one year of age, and confirmed with Doppler echocardiography, were included. Dogs with concomitant cardiac diseases, pulmonary hypertension and/or trivial tricuspid regurgitation were excluded. Analysed data included signalment, reason for presentation, clinical signs, electrocardiographic and echocardiographic features, survival status and cause of death. Survival times and risk factors for mortality were evaluated using Kaplan-Meier curves and Cox regression. Eighteen dogs met inclusion criteria. Border collies were over-represented (p= 0.014). Dogs were most frequently referred for investigation of heart murmur. The most common arrhythmia was atrial fibrillation (n=3). Median survival time from diagnosis of tricuspid valve dysplasia was 2775 days (range 1-3696 days; 95% CI 1542.41-4007.59) and from onset of right-sided congestive heart failure was 181 days (range 1-2130 days; 95% CI 0-455.59). Syncope was the sole risk factor for cardiac death. In this population of UK dogs, tricuspid valve dysplasia was uncommon but, when severe, frequently led to right-sided congestive heart failure. Prognosis was favourable for mild and moderate tricuspid dysplasia. Survival time was reduced with right-sided congestive heart failure but varied widely. Risk of cardiac death was significantly increased if syncope had occurred. PMID:29296595

Sudden Death in a Patient with Carney's Complex

PubMed Central

Rothschild, James Adam; Kreso, Melissa; Slodzinski, Martin

2013-01-01

Carney’s complex is a rare autosomal dominantly inherited multiple endocrine neoplasia syndrome that involves spotty skin pigmentations, recurrent cardiac myxomas, endocrine hyperactivity, pituitary adenomas, peripheral nerve tumors, testicular tumors, and ovarian lesions. We present a case of sudden cardiac death in a 40 year old female with a history of Carney’s complex with recurrent cardiac myxomas presenting for exploratory laparotomy and enblock adnexal resection of a slowly enlarging right sided ovarian mass. This case highlights the risk for sudden death in these patients as well as the preoperative assessment that should be undertaken by the anesthesiologist as it relates to Carney’s complex. PMID:24223358

Light-sheet fluorescence imaging to localize cardiac lineage and protein distribution

PubMed Central

Ding, Yichen; Lee, Juhyun; Ma, Jianguo; Sung, Kevin; Yokota, Tomohiro; Singh, Neha; Dooraghi, Mojdeh; Abiri, Parinaz; Wang, Yibin; Kulkarni, Rajan P.; Nakano, Atsushi; Nguyen, Thao P.; Fei, Peng; Hsiai, Tzung K.

2017-01-01

Light-sheet fluorescence microscopy (LSFM) serves to advance developmental research and regenerative medicine. Coupled with the paralleled advances in fluorescence-friendly tissue clearing technique, our cardiac LSFM enables dual-sided illumination to rapidly uncover the architecture of murine hearts over 10 by 10 by 10 mm3 in volume; thereby allowing for localizing progenitor differentiation to the cardiomyocyte lineage and AAV9-mediated expression of exogenous transmembrane potassium channels with high contrast and resolution. Without the steps of stitching image columns, pivoting the light-sheet and sectioning the heart mechanically, we establish a holistic strategy for 3-dimentional reconstruction of the “digital murine heart” to assess aberrant cardiac structures as well as the spatial distribution of the cardiac lineages in neonates and ion-channels in adults. PMID:28165052

Challenges, needs, and experiences of recently hospitalized cardiac patients and their informal caregivers.

PubMed

Blair, Judith; Volpe, Marie; Aggarwal, Brooke

2014-01-01

Cardiovascular disease (CVD) is the leading cause of death in the United States. Unpaid family caregivers of patients who experienced a cardiac event may occupy a key position in disseminating continuous health messages to these patients, yet more information is needed to guide the development of educational and behavioral interventions targeting caregivers. The purpose of this qualitative study was to assess the challenges, needs, and personal experiences of cardiac patients and their informal caregivers to explore the types of programs and services that would be most beneficial in promoting adherence to national CVD guidelines among cardiac patients and their caregivers. Patients who had been admitted to the cardiovascular service line of a large urban academic medical center and their informal caregivers (N = 38, 63% women, 74% white) participated in semistructured interviews and focus groups. Participants were asked to speak about 4 major categories of their personal experiences: support, challenges, coping, and program delivery, to determine their needs, the kind of educational interventions that would be most helpful to them, and how they would prefer this information/education to be delivered. Both patients and caregivers ranked diet as the most pressing challenge (91% and 78%, respectively). The Internet, television, and social media were the preferred methods of delivery of such programs. Challenges most commonly cited by caregivers and patients included issues related to taking/administering prescribed medications and medication side effects, and mental stress. Caregivers expressed that not knowing what to expect after the patient's discharge from the hospital was a major stressor. These findings may inform the development of educational interventions targeted to cardiac caregivers so that they may be more effective in assisting the patients in their care to adhere to national CVD prevention guidelines.

Cardiac dose-sparing effects of deep-inspiration breath-hold in left breast irradiation : Is IMRT more beneficial than VMAT?

PubMed

Sakka, Mazen; Kunzelmann, Leonie; Metzger, Martin; Grabenbauer, Gerhard G

2017-10-01

Given the reduction in death from breast cancer, as well as improvements in overall survival, adjuvant radiotherapy is considered the standard treatment for breast cancer. However, left-sided breast irradiation was associated with an increased rate of fatal cardiovascular events due to incidental irradiation of the heart. Recently, considerable efforts have been made to minimize cardiac toxicity of left-sided breast irradiation by new treatment methods such as deep-inspiration breath-hold (DIBH) and new radiation techniques, particularly intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT). The primary aim of this study was to evaluate the effect of DIBH irradiation on cardiac dose compared with free-breathing (FB) irradiation, while the secondary objective was to compare the advantages of IMRT versus VMAT plans in both the FB and the DIBH position for left-sided breast cancer. In all, 25 consecutive left-sided breast cancer patients underwent CT simulation in the FB and DIBH position. Five patients were excluded with no cardiac displacement following DIBH-CT simulation. The other 20 patients were irradiated in the DIBH position using respiratory gating. Four different treatment plans were generated for each patient, an IMRT and a VMAT plan in the DIBH and in the FB position, respectively. The following parameters were used for plan comparison: dose to the heart, left anterior descending coronary artery (mean dose, maximum dose, D25% and D45%), ipsilateral, contralateral lung (mean dose, D20%, D30%) and contralateral breast (mean dose). The percentage in dose reduction for organs at risk achieved by DIBH for both IMRT and VMAT plans was calculated and compared for each patient by each treatment plan. DIBH irradiation significantly reduced mean dose to the heart and left anterior descending coronary artery (LADCA) using both IMRT (heart -20%; p = 0.0002, LADCA -9%; p = 0.001) and VMAT (heart -23%; p = 0.00003, LADCA -16%; p = 0.01) techniques as compared with FB radiation. There were no significant changes in left lung dose by IMRT; however, with VMAT planning, mean dose to the left lung was reduced by -4% (p = 0.0004). In addition, DIBH significantly increased the mean dose to the contralateral breast with IMRT (+14%, p = 0.002) and significantly reduced the dose to the contralateral breast with VMAT planning (-9%, p = 0.003) compared with the FB position. Additionally, in comparison with VMAT, the IMRT technique reduced mean heart dose both in the FB and the DIBH-position by -30% (p = 0.0004) and -26% (p = 0.002), respectively. Furthermore, IMRT increased the mean dose to the left lung in both the FB and the DIBH position (+5%, p = 0.003, p = 0.006), respectively. There were no significant changes in dose to the right lung and contralateral breast either in the FB or DIBH position between IMRT and VMAT techniques. Left-sided breast irradiation is best performed in the DIBH position, since a considerable dose sparing to the heart and LADCA can be achieved by using either IMRT or VMAT techniques. A significant additional decrease in heart and LADCA dose by IMRT in both FB and DIBH irradiation was seen compared with VMAT.

Fluctuations in Cerebral Hemodynamics

DTIC Science & Technology

2003-12-01

Determination of scaling properties Detrended Fluctuations Analysis (see (28) and references therein) is commonly used to determine scaling...pressure (averaged over a cardiac beat) of a healthy subject. First 1000 values of the time series are shown. (b) Detrended fluctuation analysis (DFA...1000 values of the time series are shown. (b) Detrended fluctuation analysis of the time series shown in (a). Fig . 3 Side-by-side boxplot for the

[Perioperative betablockade].

PubMed

Skarvan, K

2007-01-01

Adverse cardiac outcomes continue to be an important cause of perioperative morbidity and mortality in the non-cardiac surgery. This is related to the high prevalence of coronary artery disease in the aging surgical population. Beta-blockers were proved useful and efficacious in the treatment of perioperative myocardial ischaemia and arrhythmia. Early studies suggested that the prophylactic perioperative beta-blockade could also reduce perioperative and long-term morbidity and mortality. The administration of beta-blockers to patients with coronary artery disease or with risk factors who undergo major noncardiac surgery is now recommended in the published guidelines. However, one recent meta-analysis and several new studies have not confirmed the postulated beneficial effects of perioperative betablockade and gave rise to an animated controversy. Until the finalization of ongoing large trials in the next two years, the decision to start prophylactic perioperative beta-blockade remains at the discretion of the responsible physicians. This decision should be based on the patient's risk, the type of surgery and on the consideration of potential interactions and side-effects of the selected beta-blocker.

Therapeutic potential of functional selectivity in the treatment of heart failure.

PubMed

Christensen, Gitte Lund; Aplin, Mark; Hansen, Jakob Lerche

2010-10-01

Adrenergic and angiotensin receptors are prominent targets in pharmacological alleviation of cardiac remodeling and heart failure, but their use is associated with cardiodepressant side effects. Recent advances in our understanding of seven transmembrane receptor signaling show that it is possible to design ligands with "functional selectivity," acting as agonists on certain signaling pathways while antagonizing others. This represents a major pharmaceutical opportunity to separate desired from adverse effects governed by the same receptor. Accordingly, functionally selective ligands are currently pursued as next-generation drugs for superior treatment of heart failure. Copyright © 2010 Elsevier Inc. All rights reserved.

Echocardiography of the normal camel (Camelus dromedaries) heart: technique and cardiac dimensions

PubMed Central

2012-01-01

Background Echocardiography and intra-cardiac dimensions have not previously been reported in adult camels despite its potential application for medical purpose. The aim of this study was to describe the results of a prospective study, aiming to report normal cardiac appearance and normal chamber dimensions in adult camels (Camelus dromedarius). Results On the right side, when the probe was placed in the 5th or 4th intercostal space (ICS), the caudal long-axis four-chamber view of the ventricles, atria, and the interventricular septum was obtained. Placing the probe slightly more cranially in the 4th ICS, the caudal long-axis four-chamber view and the caudal long-axis view of the left ventricular outflow tract (LVOT) were imaged. In 7 camels, a hybrid view between a “four-chamber” and “LVOT view” was imaged from the same position. The short-axis view of the ventricles was obtained in the 4th ICS where the transducer was rotated between 0° and 25°. Placement of the transducer in the 3rd ICS allowed visualisation of the right ventricular outflow tract (RVOT). On the left side, when the probe was placed in the 5th or 4th ICS, a four-chamber view was obtained. The LVOT is imaged in the 4th ICS and the RVOT was seen from the 3rd ICS. Conclusions This study showed that it is possible to obtain good-quality echocardiograms in adult camels and provide normal cardiac dimensions. This study could be used as a reference for further studies concerning camels with cardiac diseases. PMID:22862855

Three-dimensional engineered heart tissue from neonatal rat cardiac myocytes.

PubMed

Zimmermann, W H; Fink, C; Kralisch, D; Remmers, U; Weil, J; Eschenhagen, T

2000-04-05

A technique is presented that allows neonatal rat cardiac myocytes to form spontaneously and coherently beating 3-dimensional engineered heart tissue (EHT) in vitro, either as a plane biconcaval matrix anchored at both sides on Velcro-coated silicone tubes or as a ring. Contractile activity was monitored in standard organ baths or continuously in a CO(2) incubator for up to 18 days (=26 days after casting). Long-term measurements showed an increase in force between days 8 and 18 after casting and stable forces thereafter. At day 10, the twitch amplitude (TA) of electrically paced EHTs (average length x width x thickness, 11 x 6 x 0.4 mm) was 0.51 mN at length of maximal force development (L(max)) and a maximally effective calcium concentration. EHTs showed typical features of neonatal rat heart: a positive force-length and a negative force-frequency relation, high sensitivity to calcium (EC(50) 0.24 mM), modest positive inotropic (increase in TA by 46%) and pronounced positive lusitropic effect of isoprenaline (decrease in twitch duration by 21%). Both effects of isoprenaline were sensitive to the muscarinic receptor agonist carbachol in a pertussis toxin-sensitive manner. Adenovirus-mediated gene transfer of beta-galactosidase into EHTs reached 100% efficiency. In summary, EHTs retain many of the physiological characteristics of rat cardiac tissue and allow efficient gene transfer with subsequent force measurement. Copyright 2000 John Wiley & Sons, Inc.

Cardiac Metabolic Deregulation Induced by the Tyrosine Kinase Receptor Inhibitor Sunitinib is rescued by Endothelin Receptor Antagonism

PubMed Central

Sourdon, Joevin; Lager, Franck; Viel, Thomas; Balvay, Daniel; Moorhouse, Rebecca; Bennana, Evangeline; Renault, Gilles; Tharaux, Pierre-Louis; Dhaun, Neeraj; Tavitian, Bertrand

2017-01-01

The growing field of cardio-oncology addresses the side effects of cancer treatment on the cardiovascular system. Here, we explored the cardiotoxicity of the antiangiogenic therapy, sunitinib, in the mouse heart from a diagnostic and therapeutic perspective. We showed that sunitinib induces an anaerobic switch of cellular metabolism within the myocardium which is associated with the development of myocardial fibrosis and reduced left ventricular ejection fraction as demonstrated by echocardiography. The capacity of positron emission tomography with [18F]fluorodeoxyglucose to detect the changes in cardiac metabolism caused by sunitinib was dependent on fasting status and duration of treatment. Pan proteomic analysis in the myocardium showed that sunitinib induced (i) an early metabolic switch with enhanced glycolysis and reduced oxidative phosphorylation, and (ii) a metabolic failure to use glucose as energy substrate, similar to the insulin resistance found in type 2 diabetes. Co-administration of the endothelin receptor antagonist, macitentan, to sunitinib-treated animals prevented both metabolic defects, restored glucose uptake and cardiac function, and prevented myocardial fibrosis. These results support the endothelin system in mediating the cardiotoxic effects of sunitinib and endothelin receptor antagonism as a potential therapeutic approach to prevent cardiotoxicity. Furthermore, metabolic and functional imaging can monitor the cardiotoxic effects and the benefits of endothelin antagonism in a theranostic approach. PMID:28824714

Potential effectiveness of traditional Chinese medicine for cardiac syndrome X (CSX): a systematic review and meta-analysis

PubMed Central

2013-01-01

Background Treatment of cardiac syndrome X with unknown pathological mechanism remains a big challenge for clinicians. Complementary and alternative medicine may bring a new choice for its management. The aim of this study is to evaluate the clinical effects of traditional Chinese medicine on cardiac syndrome X patients. Methods We systematically searched databases such as Cochrane CENTRAL, PubMed, EMBASE, CBM, Chinese National Knowledge Infrastructure (CNKI), WanFang and VIP, and handsearched relevant journals to identify randomized controlled trials. Following the steps of systematic review recommended by the Cochrane group, we assessed the quality of included studies, extracted valid data and undertook meta-analysis. Results Twenty one moderate-to low-quality randomized controlled trials involving 1143 patients were included. The results showed that traditional Chinese medicine could improve angina [OR=1.34, 95% CI: 1.2 to 1.50], electrocardiogram (ECG), endothelin-1 (ET-1) levels, prolong exercise duration in treadmill tests, and reduce angina frequency per week compared with routine treatment. No other side effect was reported except two cases of stomach pain. Conclusion Compared with conventional treatment, traditional Chinese medicine shows the potential of optimizing symptomatic outcomes and improving ECG and exercise duration. The efficacy of TCM may find explanation in its pharmacological activity of adjusting the endothelial function. TCM, as a kind of alternative and complementary medicine, may provide another choice for CSX patients. PMID:23497135

Subvalvular pannus and thrombosis in a mitral valve prosthesis.

PubMed

Kim, Gun Ha; Yang, Dong Hyun; Kang, Joon-Won; Kim, Dae-Hee; Jung, Sung-Ho; Lim, Tae-Hwan

2016-01-01

A 69-year-old female underwent cardiac CT to evaluate prosthetic valve (PHV) dysfunction detected on echocardiography. A CT coronal and en face views of the mitral annular plane showed a low-density, mass-like lesion on the left atrial side of the PHV and a high-density, plate-like lesion on the left ventricular side of PHV. A repeat of the mitral valve replacement was performed, and preoperative CT findings of both the thrombus on the left atrial side and pannus formation on the LV side were confirmed in the operative findings. Copyright © 2016 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.

Direct measurement of a patient's entrance skin dose during pediatric cardiac catheterization

PubMed Central

Sun, Lue; Mizuno, Yusuke; Iwamoto, Mari; Goto, Takahisa; Koguchi, Yasuhiro; Miyamoto, Yuka; Tsuboi, Koji; Chida, Koichi; Moritake, Takashi

2014-01-01

Children with complex congenital heart diseases often require repeated cardiac catheterization; however, children are more radiosensitive than adults. Therefore, radiation-induced carcinogenesis is an important consideration for children who undergo those procedures. We measured entrance skin doses (ESDs) using radio-photoluminescence dosimeter (RPLD) chips during cardiac catheterization for 15 pediatric patients (median age, 1.92 years; males, n = 9; females, n = 6) with cardiac diseases. Four RPLD chips were placed on the patient's posterior and right side of the chest. Correlations between maximum ESD and dose–area products (DAP), total number of frames, total fluoroscopic time, number of cine runs, cumulative dose at the interventional reference point (IRP), body weight, chest thickness, and height were analyzed. The maximum ESD was 80 ± 59 (mean ± standard deviation) mGy. Maximum ESD closely correlated with both DAP (r = 0.78) and cumulative dose at the IRP (r = 0.82). Maximum ESD for coiling and ballooning tended to be higher than that for ablation, balloon atrial septostomy, and diagnostic procedures. In conclusion, we directly measured ESD using RPLD chips and found that maximum ESD could be estimated in real-time using angiographic parameters, such as DAP and cumulative dose at the IRP. Children requiring repeated catheterizations would be exposed to high radiation levels throughout their lives, although treatment influences radiation dose. Therefore, the radiation dose associated with individual cardiac catheterizations should be analyzed, and the effects of radiation throughout the lives of such patients should be followed. PMID:24968708

Muscle wasting and sarcopenia in heart failure and beyond: update 2017

PubMed Central

Springer, Joshua‐I.; Anker, Stefan D.

2017-01-01

Abstract Sarcopenia (loss of muscle mass and muscle function) is a strong predictor of frailty, disability and mortality in older persons and may also occur in obese subjects. The prevalence of sarcopenia is increased in patients suffering from chronic heart failure. However, there are currently few therapy options. The main intervention is resistance exercise, either alone or in combination with nutritional support, which seems to enhance the beneficial effects of training. Also, testosterone has been shown to increased muscle power and function; however, a possible limitation is the side effects of testosterone. Other investigational drugs include selective androgen receptor modulators, growth hormone, IGF‐1, compounds targeting myostatin signaling, which have their own set of side effects. There are abundant prospective targets for improving muscle function in the elderly with or without chronic heart failure, and the continuing development of new treatment strategies and compounds for sarcopenia and cardiac cachexia makes this field an exciting one. PMID:29154428

Clinical Classification and Prognosis of Isolated Right-Sided Infective Endocarditis

PubMed Central

Ortiz, Carlos; López, Javier; García, Héctor; Sevilla, Teresa; Revilla, Ana; Vilacosta, Isidre; Sarriá, Cristina; Olmos, Carmen; Ferrera, Carlos; García, Pablo Elpidio; Sáez, Carmen; Gómez, Itziar; San Román, José Alberto

2014-01-01

Abstract From an epidemiologic point of view, right-sided infective endocarditis (RSIE) affects different types of patients: intravenous drug users (IDUs), cardiac device carriers (pacemakers and implantable automatic defibrillators), and the “3 noes” endocarditis group: no left-sided, no IDUs, no cardiac devices. Our objective is to describe and compare the clinical profile and outcome of these groups of patients. Every episode of infective endocarditis (IE) consecutively diagnosed in 3 tertiary centers from 1996 to 2012 was included in an ongoing multipurpose database. We assessed 85 epidemiologic, clinical, echocardiographic, and outcome variables in patients with isolated RSIE. A bivariated comparative analysis between the 3 groups was conducted. Among 866 IE episodes, 121 were classified as isolated RSIE (14%): 36 IDUs (30%), 65 cardiac device carriers (54%), and 20 “3 noes” group (16%). IDUs were mainly young men (36 ± 7 years) without previous heart disease, few comorbidities, and frequent previous endocarditis episodes (28%). Human immunodeficiency virus infection was frequent (69%). Cardiac device carriers were older (66 ± 15 years) and had less comorbidities (34%). Removal of the infected device was performed in 91% of the patients without any death. The “3 noes” endocarditis group was composed mainly by middle-age men (56 ± 18 years), health care related infections (50%), and had many comorbidities (75%). Whereas Staphylococcus aureus were the most frequent cause in IDUs (72% vs 34% in device carriers and 34% in the “3 noes” group, P = 0.001), coagulase negative Staphylococci predominated in the device carriers (58% vs 11% in drug users and 35% in the “3 noes”, P < 0.001). Significant differences in mortality were found (17% in drug users, 3% in device carriers, and 30% in the “3 noes” group; P < 0.001). These results suggest that RSIE should be separated into 3 groups (IDUs, cardiac device carriers, and the “3 noes”) and considered as independent entities as there are relevant epidemiologic, clinical, microbiological, echocardiographic, and prognostic differences among them. PMID:25501052

Repeatability, variability and reference values of pulsed wave Doppler echocardiographic measurements in healthy Saanen goats

PubMed Central

2012-01-01

Background Pulsed wave (PW) Doppler echocardiography has become a routine non invasive cardiac diagnostic tool in most species. However, evaluation of intracardiac blood flow requires reference values, which are poorly documented in goats. The aim of this study was to test the repeatability, the variability, and to establish the reference values of PW measurements in healthy adult Saanen goats. Using a standardised PW Doppler echocardiographic protocol, 10 healthy adult unsedated female Saanen goats were investigated three times at one day intervals by the same observer. Mitral, tricuspid, aortic and pulmonary flows were measured from a right parasternal view, and mitral and aortic flows were also measured from a left parasternal view. The difference between left and right side measurements and the intra-observer inter-day repeatability were tested and then the reference values of PW Doppler echocardiographic parameters in healthy adult female Saanen goats were established. Results As documented in other species, all caprine PW Doppler parameters demonstrated a poor inter-day repeatability and a moderate variability. Tricuspid and pulmonary flows were best evaluated on the right side whereas mitral and aortic flows were best obtained on the left side, and reference values are reported for healthy adult Saanen goats. Conclusions PW Doppler echocardiography allows the measurement of intracardiac blood flow indices in goats. The reference values establishment will help interpreting these indices of cardiac function in clinical cardiac cases and developing animal models for human cardiology research. PMID:23067875

Cardio-Metabolic Effects of HIV Protease Inhibitors (Lopinavir/Ritonavir)

PubMed Central

Reyskens, Kathleen M. S. E.; Fisher, Tarryn-Lee; Schisler, Jonathan C.; O'Connor, Wendi G.; Rogers, Arlin B.; Willis, Monte S.; Planesse, Cynthia; Boyer, Florence; Rondeau, Philippe; Bourdon, Emmanuel; Essop, M. Faadiel

2013-01-01

Although antiretroviral treatment decreases HIV-AIDS morbidity/mortality, long-term side effects may include the onset of insulin resistance and cardiovascular diseases. However, the underlying molecular mechanisms responsible for highly active antiretroviral therapy (HAART)-induced cardio-metabolic effects are poorly understood. In light of this, we hypothesized that HIV protease inhibitor (PI) treatment (Lopinavir/Ritonavir) elevates myocardial oxidative stress and concomitantly inhibits the ubiquitin proteasome system (UPS), thereby attenuating cardiac function. Lopinavir/Ritonavir was dissolved in 1% ethanol (vehicle) and injected into mini-osmotic pumps that were surgically implanted into Wistar rats for 8 weeks vs. vehicle and sham controls. We subsequently evaluated metabolic parameters, gene/protein markers and heart function (ex vivo Langendorff perfusions). PI-treated rats exhibited increased serum LDL-cholesterol, higher tissue triglycerides (heart, liver), but no evidence of insulin resistance. In parallel, there was upregulation of hepatic gene expression, i.e. acetyl-CoA carboxylase β and 3-hydroxy-3-methylglutaryl-CoA-reductase, key regulators of fatty acid oxidation and cholesterol synthesis, respectively. PI-treated hearts displayed impaired cardiac contractile function together with attenuated UPS activity. However, there was no significant remodeling of hearts exposed to PIs, i.e. lack of ultrastructural changes, fibrosis, cardiac hypertrophic response, and oxidative stress. Western blot analysis of PI-treated hearts revealed that perturbed calcium handling may contribute to the PI-mediated contractile dysfunction. Here chronic PI administration led to elevated myocardial calcineurin, nuclear factor of activated T-cells 3 (NFAT3), connexin 43, and phosphorylated phospholamban, together with decreased calmodulin expression levels. This study demonstrates that early changes triggered by PI treatment include increased serum LDL-cholesterol levels together with attenuated cardiac function. Furthermore, PI exposure inhibits the myocardial UPS and leads to elevated calcineurin and connexin 43 expression that may be associated with the future onset of cardiac contractile dysfunction. PMID:24098634

A Retrospective Review: Significance of Vegetation Size in Injection Drug Users with Right-Sided Infective Endocarditis.

PubMed

Otome, Ohide; Guy, Stephen; Tramontana, Adrian; Lane, Garry; Karunajeewa, Harin

2016-05-01

Previously described prognostic markers in right-sided infective endocarditis (RSIE) include vegetation size ≥1cm, fever for more than three weeks, cardiac failure and severe sepsis. This study aimed to evaluate effectiveness of medical therapy for vegetations ≥1cm and explore determinants of outcome in a representative population of intravenous drug users (IDUs) at a metropolitan Australian health service. Retrospective review of consecutive IDUs presenting to our institution with native-valve RSIE (by modified Duke criteria) over seven years (2005-2011). Data recorded included echocardiographic estimation of maximal vegetation diameter (classified as < or ≥1cm). Relationships between vegetation size and specified outcomes of death, septic shock, recurrence and relapse were examined by Chi-squared testing. Of 49 episodes five (10%) were managed surgically and a further four (8%) were lost to follow-up and excluded from the analysis. Of the remaining 40 evaluable medically treated patients (median age 28, range 20-55), 37 (93%) cultured methicillin-sensitive S. aureus and all had tricuspid valve involvement. Of 24 with vegetations ≥1cm, three died (mortality 13%) compared with one (6%) in 16 medically treated patients with vegetations <1cm (p=0.63). A Pittsburgh (PITT) bacteraemia score of ≥4 at presentation was associated with a mortality of 24% (four of 17 patients died) compared with 0 in 23 patients with PITT scores <4 (p=0.026). Medical therapy alone can be effective for RSIE when large vegetations are present. However a high sepsis score at presentation may increase risk of death. Larger studies are required to determine optimal indications for early surgical intervention. Copyright © 2015 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Isatis tinctoria L. combined with co-stimulatory molecules blockade prolongs survival of cardiac allografts in alloantigen-primed mice.

PubMed

Kang, Xiangpeng; Chen, Jibing; Qin, Qing; Wang, Feng; Wang, Yongzhi; Lan, Tianshu; Xu, Shuo; Wang, Feiyu; Xia, Junjie; Ekberg, Henrik; Qi, Zhongquan; Liu, Zhongchen

2010-05-01

Memory T cells present a unique challenge in transplantation. Although memory T cells express robust immune responses to invading pathogens, they may be resistant to the effects of immunosuppressive therapies used to prolong graft survival. In previous studies, we found that compound K, the synthesized analogue of highly unsaturated fatty acids from Isatis tinctoria L., reduced acute cardiac allograft rejection in mice (Wang et al., 2009 [1]). Here, we further investigated the effect of compound K on cardiac allograft rejection in alloantigen-primed mice. We found that compound K significantly inhibited CD4(+) and CD8(+) memory T cells proliferation in a mixed lymphocyte reaction (MLR). In vivo, compound K combined with anti-CD154 and anti-LFA-1 monoclonal antibodies (mAbs) significantly extended the survival time of heart grafts in alloantigen-primed mice with no obvious toxic side effects. Furthermore, our data suggests that compound K works by reducing the expression of both IL-2 and IFN-gamma within the graft rather than enhancing expression of regulatory T cells (Tregs). Compound K can also inhibit the alloresponses of memory T cells, while increasing the proportion of CD4(+) memory T cells in the spleen of the recipients and significantly reducing the level of alloantibodies in the serum. Our study highlights the unique immune effects of compound K that may be further explored for clinical use in extending the survival of transplant grafts. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Dexmedetomidine and general anesthesia: a narrative literature review of its major indications for use in adults undergoing non-cardiac surgery.

PubMed

Davy, Arthur; Fessler, Julien; Fischler, Marc; LE Guen, Morgan

2017-12-01

In Europe, dexmedetomidine has marketing approval only for sedation in intensive care units. However, its use during general anesthesia has been widely reported. The aim of this narrative review is to draw a picture of potential indications in anesthesia. We searched in MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials using the keywords "Dexmedetomidine, Dexdor, Precedex and Dexdomitor." The research ended in December 2016. Studies were eligible for inclusion if they reported the use of dexmedetomidine in adults receiving general anesthesia. We excluded studies related to cardiac surgery and studies reporting the use of dexmedetomidine as an adjuvant of locoregional anesthesia. Several potential uses for dexmedetomidine during general anesthesia are described, especially: awake fiber optic intubation, the sparing effect of dexmedetomidine on hypnotic and opioid drugs, prevention of postoperative pain, nausea and vomiting and shivering, improvement of postoperative sleep and postoperative recovery, opioid-free anesthesia, use in craniotomy, endovascular stroke treatment and drug-induced sleep endoscopy. A protective effect against cardiac complications, an anti-inflammatory effect, and side effects, particularly bradycardia, are also described. The properties of dexmedetomidine lead to its use for elective indications such as awake fiberoptic intubation and neurosurgical anesthesia. New topics are under debate. These subjects must be studied thoroughly because of their implication in the patients' surgical course. These advantages must be weighed against the major drawback of dexmedetomidine administration which is the potential for hemodynamic abnormalities.

Lung volumes, ventricular function and pulmonary arterial flow in children operated on for left-sided congenital diaphragmatic hernia: long-term results.

PubMed

Abolmaali, Nasreddin; Koch, Arne; Götzelt, Knut; Hahn, Gabriele; Fitze, Guido; Vogelberg, Christian

2010-07-01

To compare MRI-based functional pulmonary and cardiac measurements in the long-term follow-up of children operated on for left-sided congenital diaphragmatic hernia (CDH) with age- and body size-matched healthy controls. Twelve children who received immediate postnatal surgery for closure of isolated left-sided CDH were included and received basic medical examinations, pulmonary function testing and echocardiography. MRI included measurement of lung volume, ventricular function assessment and velocity-encoded imaging of the pulmonary arteries and was compared with the data for 12 healthy children matched for age and body size. While patients' clinical test results were not suspicious, comparison between the MRI data for patients and those for healthy controls revealed significant differences. In patients, the volumes of the left lungs were increased and the tidal volume was larger on the right side. While the stroke volumes of both ventricles were reduced, heart rate and ejection fraction were increased. Flow, acceleration time and cross-sectional area of the left pulmonary artery were reduced. Functional MRI detected pulmonary and cardiac findings in the late follow-up of CDH children which may be missed by standard clinical methods and might be relevant for decisions regarding late outcome and treatment.

Tranexamic acid versus ɛ-aminocaproic acid: efficacy and safety in paediatric cardiac surgery.

PubMed

Martin, Klaus; Breuer, Tamás; Gertler, Ralph; Hapfelmeier, Alexander; Schreiber, Christian; Lange, Rüdiger; Hess, John; Wiesner, Gunther

2011-06-01

Tranexamic acid (TXA) and ɛ-aminocaproic acid (EACA) are used for antifibrinolytic therapy in cardiac surgery, although data directly comparing their blood sparing effect and their side effects, especially in paediatric cardiac surgical patients, are still missing. We analysed perioperative data of 234 paediatric patients weighing less than 20 kg undergoing cardiac surgery. In a 5-month period, all patients (n=114) received TXA (group TXA). During a second 5-month period, all patients (n=120) were treated with EACA (group EACA). Primary outcome was blood loss at 24h postoperatively; secondary outcome criteria were transfusion requirement, rate of revision for bleeding, postoperative complications and in-hospital mortality. All descriptive and intra-operative parameters were well comparable. There was no evidence for a difference in blood loss at 24h postoperatively (TXA 21 ml kg(-1) (14-38) (median (interquartile range)) vs EACA 29 ml kg(-1) (14-40), p=0.242), rate of re-operation for bleeding (TXA 9.6% vs EACA 8.3%, p=0.725) and transfusion of blood products. The incidence of postoperative complications such as seizures (TXA 3.5% vs EACA 0.8%, p=0.203) and other neurological complications (TXA 2.6% vs EACA 1.7%, p=0.677), renal injury (TXA 9.6% vs EACA 13.3%, p=0.378), renal failure (TXA 1.8% vs EACA 4.2%, p=0.447), low cardiac output syndrome (TXA 12.3% vs EACA 10.8%, p=0.729), and vascular thrombosis (TXA 4.4% vs EACA 5.0%, p=0.824), as well as the in-hospital mortality (TXA 2.6% vs EACA 3.3%, p>0.999) did not show any statistically significant difference. TXA and EACA are well comparable in their effect on perioperative blood loss as well as in major clinical outcome criteria. Although the fourfold risk for seizures using TXA was not significant, we currently use EACA in paediatric cardiac surgery. Copyright © 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Is chronic inhibition of phosphodiesterase type 5 cardioprotective and safe? A meta-analysis of randomized controlled trials.

PubMed

Giannetta, Elisa; Feola, Tiziana; Gianfrilli, Daniele; Pofi, Riccardo; Dall'Armi, Valentina; Badagliacca, Roberto; Barbagallo, Federica; Lenzi, Andrea; Isidori, Andrea M

2014-10-20

The myocardial effects of phosphodiesterase type 5 inhibitors (PDE5i) have recently received consideration in several preclinical studies. The risk/benefit ratio in humans remains unclear. We performed a meta-analysis of randomized, placebo-controlled trials (RCTs) to evaluate the efficacy and safety of PDE5i on cardiac morphology and function. From March 2012 to December 2013 (update: May 2014), we searched English-language studies from MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and SCOPUS-selecting RCTs of continuous PDE5i administration that reported cardiovascular outcomes: cardiac geometry and performance, afterload, endothelial function and safety. The pooled estimate of a weighted mean difference between treatment and placebo was obtained for all outcomes using a random effects model. A test for heterogeneity was performed and the I2 statistic calculated. Overall, 1,622 subjects were treated, with 954 randomized to PDE5i and 772 to placebo in 24 RCTs. According to our analysis, sustained PDE5 inhibition produced: (1) an anti-remodeling effect by reducing cardiac mass (-12.21 g/m2, 95% confidence interval (CI): -18.85; -5.57) in subjects with left ventricular hypertrophy (LVH) and by increasing end-diastolic volume (5.00 mL/m2; 95% CI: 3.29; 6.71) in non-LVH patients; (2) an improvement in cardiac performance by increasing cardiac index (0.30 L/min/m2, 95% CI: 0.202; 0.406) and ejection fraction (3.56%, 95% CI: 1.79; 5.33). These effects are parallel to a decline of N-terminal-pro brain natriuretic peptide (NT-proBNP) in subjects with severe LVH (-486.7 pg/ml, 95% CI: -712; -261). PDE5i administration also produced: (3) no changes in afterload parameters and (4) an improvement in flow-mediated vasodilation (3.31%, 95% CI: 0.53; 6.08). Flushing, headache, epistaxis and gastric symptoms were the commonest side effects. This meta-analysis suggests for the first time that PDE5i have anti-remodeling properties and improve cardiac inotropism, independently of afterload changes, with a good safety profile. Given the reproducibility of the findings and tolerability across different populations, PDE5i could be reasonably offered to men with cardiac hypertrophy and early stage heart failure. Given the limited gender data, a larger trial on the sex-specific response to long-term PDE5i treatment is required.

Terminal echocardiographic findings during death process in man and dogs.

PubMed

Wang, F S; Lien, W P; Fong, T E

1991-01-01

Serial echocardiographic imaging was performed to assess terminal mechanical changes of cardiac chambers and valves, as well as sequential echocardiographic features of blood stasis, inside the heart after mechanical asystole in 7 hospitalized adults who died without apparent cardiac disease and in 7 experimental dogs sacrificed by a means of asphyxia. Marked reduction of wall motion became manifest shortly after the electrocardiograms had generated into a slow junctional rhythm with intraventricular conduction defect, an idioventricular rhythm, or an extreme sinus bradycardia. Total cessation of cardiac wall and valve motion followed; the aortic valve remained closed, with mitral and tricuspid valves semiopen after total cardiac asystole. Liquid whole blood inside the heart became echogenic shortly before mechanical asystole had approached, and homogenous echogenicity usually first appeared on the right side of the heart. As the death process progressed and total asystole persisted, the acoustic intensity of the intracavitary echoes increased, tending to form amorphous masses, with some showing rather well-defined borders. Such echocardiographic features were noted to indicate red thrombi in experimental dogs. The cardiac dimensions (left ventricle and aorta) decreased after total cardiac asystole.

[Management of outpatients with cardiac disease: follow-up timing and modalities].

PubMed

Rossini, Roberta; Lina, Daniela; Ferlini, Marco; Belotti, Giuseppina; Caico, Salvatore Ivan; Caravati, Fabrizio; Faggiano, Pompilio; Iorio, Annamaria; Lauri, Davide; Lettieri, Corrado; Locati, Emanuela Teresa; Maggi, Antonio; Massari, Ferdinando; Mortara, Andrea; Moschini, Luigi; Musumeci, Giuseppe; Nassiacos, Daniele; Negri, Fabrizio; Pecora, Domenico; Pierini, Simona; Pedretti, Roberto; Ravizza, Pierfranco; Romano, Michele; Oliva, Fabrizio

2017-06-01

The increasing rate of cardiovascular diseases, the improved survival after the acute phase, the aging of the population and the implementation of primary prevention caused an exponential increase in outpatient cardiac performance, thereby making it difficult to maintain a balance between the citizen-patient request and the economic sustainability of the healthcare system. On the other side, the prescription of many diagnostic tests with a view to defensive medicine and the related growth of patients' expectations, has led several scientific societies to educational campaigns highlighting the concept that "less is more".The present document is aimed at providing the general practitioner with practical information about a prompt diagnosis of signs/symptoms (angina, dyspnea, palpitations, syncope) of the major cardiovascular diseases. It will also provide an overview about appropriate use of diagnostic exams (echocardiogram, stress test), about the appropriate timing of their execution, in order to ensure effectiveness, efficiency, and equity of the health system.

[Application of a shared interdisciplinary and multiprofessional cardio-oncology in-hospital pathway].

PubMed

Canale, Maria Laura; Camerini, Andrea; Magnacca, Massimo; Del Meglio, Jacopo; Lilli, Alessio; Donati, Sara; Belli, Lucia; Lencioni, Stefania; Amoroso, Domenico; Casolo, Giancarlo

2017-11-01

The burden of cardiac side effects in oncology patients will dramatically increase in the near future as a result of the widespread use of anticancer agents affecting the cardiovascular system, the general population aging, the heightened attention in the detection of cardiac toxicity and the absolute gain in terms of overall survival. The relationship between cardiologists and oncologists should therefore be closer leading to the definition of cardio-oncology. The increased number of such patients requires the creation of a dedicated patient assistance program in order to guarantee every patient the possibility of an interdisciplinary and multiprofessional approach. A dedicated care pathway needs a reorganization of internal resources to ensure high standards of care. The proposed pathway is actually active at our institution and has been implemented taking into account available facilities and planned work amount. Our patient cardio-oncology program could be adapted with minimal changes to different hospitals.

Cardio-oncology: the Nuclear Option.

PubMed

Alvarez, Jorge A; Russell, Raymond R

2017-04-01

Cardio-oncology focuses increased effort to decrease cancer treatment-related cardiotoxicity while continuing to improve outcomes. We sought to synthesize the latest in nuclear cardiology as it pertains to the assessment of left ventricular function in preventative guidelines and comparison to other modalities, novel molecular markers of pre-clinical cardiotoxicity, and its role in cardiac amyloid diagnosis. Planar ERNA (equilibrium radionuclide angiocardiography) provides a reliable and proven means of monitoring and preventing anthracycline cardiotoxicity, and SPECT ERNA using solid-state gamma cameras may provide reproducible assessments of left ventricular function with reduced radiation exposure. While certain chemotherapeutics have vascular side effects, the use of stress perfusion imaging has still not been adequately studied for routine use. Similarly, markers of apoptosis, inflammation, and sympathetic nerve dysfunction are promising, but are still not ready for uniform usage. SPECT tracers can assist in nonbiopsy diagnosis of cardiac amyloid. Nuclear cardiology is a significant contributor to the multimodality approach to cardio-oncology.

New concept of the contraction-extension property of the left ventricular myocardium.

PubMed

Tanaka, Motonao; Sakamoto, Tsuguya; Sugawara, Shigeo; Katahira, Yoshiaki; Tabuchi, Haruna; Nakajima, Hiroyuki; Kurokawa, Takafumi; Kanai, Hiroshi; Hasegawa, Hideyuki; Ohtsuki, Shigeo

2014-04-01

Using newly developed ultrasonic technology, we attempted to disclose the characteristics of the left ventricular (LV) contraction-extension (C-E) property, which has an important relationship to LV function. Strain rate (SR) distribution within the posterior wall and interventricular septum was microscopically measured with a high accuracy of 821μm in spatial resolution by using the phase difference tracking method. The subjects were 10 healthy men (aged 30-50 years). The time course of the SR distribution disclosed the characteristic C-E property, i.e. the contraction started from the apex and propagated toward the base on one hand, and from the epicardial side toward the endocardial side on the other hand. Therefore, the contraction of one area and the extension of another area simultaneously appeared through nearly the whole cardiac cycle, with the contracting part positively extending the latter part and vice versa. The time course of these propagations gave rise to the peristalsis and the bellows action of the LV wall, and both contributed to effective LV function. The LV contraction started coinciding in time with the P wave of the electrocardiogram, and the cardiac cycle was composed of 4 phases, including 2 types of transitional phase, as well as the ejection phase and slow filling phase. The sum of the measurement time duration of either the contraction or the extension process occupied nearly equal duration in normal conditions. The newly developed ultrasonic technology revealed that the SR distribution was important in evaluating the C-E property of the LV myocardium. The harmonious succession of the 4 cardiac phases newly identified seemed to be helpful in understanding the mechanism to keep long-lasting pump function of the LV. Copyright © 2013 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Structural and functional cardiac adaptations to a 10-week school-based football intervention for 9-10-year-old children.

PubMed

Krustrup, P; Hansen, P R; Nielsen, C M; Larsen, M N; Randers, M B; Manniche, V; Hansen, L; Dvorak, J; Bangsbo, J

2014-08-01

The present study investigated the cardiac effects of a 10-week football training intervention for school children aged 9-10 years using comprehensive transthoracic echocardiography as a part of a larger ongoing study. A total of 97 pupils from four school classes were cluster-randomized into a control group that maintained their usual activities (CON; two classes, n = 51, 21 boys and 30 girls) and a football training group that performed an additional 3 × 40 min of small-sided football training per week (FT; two classes, n = 46, 23 boys and 23 girls). No baseline differences were observed in age, body composition, or echocardiographic variables between FT and CON. After the 10-week intervention, left ventricular posterior wall diameter was increased in FT compared with CON [0.4 ± 0.7 vs -0.1 ± 0.6 (± SD) mm; P < 0.01] as was the interventricular septum thickness (0.2 ± 0.7 vs -0.2 ± 0.8 mm; P < 0.001). Global isovolumetric relaxation time increased more in FT than in CON (3.8 ± 10.4 vs -0.9 ± 6.6 ms, P < 0.05) while the change in ventricular systolic ejection fraction tended to be higher (1.4 ± 8.0 vs -1.1 ± 5.5%; P = 0.08). No changes were observed in resting heart rate or blood pressure. In conclusion, a short-term, school-based intervention comprising small-sided football sessions resulted in significant structural and functional cardiac adaptations in pre-adolescent children. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Systematic Review of the Side Effects Associated With Anti-HER2-Targeted Therapies Used in the Treatment of Breast Cancer, on Behalf of the EORTC Quality of Life Group.

PubMed

Sodergren, Samantha C; Copson, Ellen; White, Alice; Efficace, Fabio; Sprangers, Mirjam; Fitzsimmons, Deborah; Bottomley, Andrew; Johnson, Colin D

2016-06-01

Targeted therapies (TTs), notably trastuzumab, have improved outcomes for breast cancer characterised by overexpression of human epidermal growth factor receptors including HER2. Compared with chemotherapy treatments, TTs are more specific in their targets and are delivered over longer periods of time, thus presenting different side-effect profiles. The objective of this paper is to systematically review and describe the side effects associated with TTs used in the adjuvant and metastatic settings for HER2+ breast cancer. The MEDLINE, EMBASE, CINAHL, Web of Science and Cochrane Library databases were searched from January 2007 to March 2015 to identify clinical trials and prospective studies reporting toxicities associated with TTs (mainly trastuzumab and lapatinib) used without other therapies in the treatment of HER2-positive breast cancer. Two independent reviewers selected papers based on their titles and abstracts. All papers selected by either reviewer were included. A third reviewer extracted and tabulated the relevant data using a data extraction form. We identified 5478 papers, of which 299 were reviewed and 18 trials identified involving 6980 patients. A total of 66 side effects were identified, including 46 "patient-based" symptoms and 20 "medically defined" outcomes. Side effects were more common for patients treated with therapies other than trastuzumab or with dual-HER2 regimens and for patients with metastatic disease. Diarrhoea and skin rash were the most prevalent symptoms, experienced by 29 % and 22 % of patients overall, respectively. There were 119 (2 %) cardiac events reported, and these were not exclusive to trastuzumab-treated patients. The majority of side effects (n = 52) were experienced by 1 % or less of patients and were predominantly of grade 1/2 toxicity. This systematic review provides a detailed analysis of side effects of HER2+ therapies in a large number of patients included in trials, enabling an accurate estimate of prevalence and a complete understanding of the patients' experience. This will help clinicians and patients in treatment planning.

Total Artificial Heart Implantation after Excision of Right Ventricular Angiosarcoma.

PubMed

Bruckner, Brian A; Abu Saleh, Walid K; Al Jabbari, Odeaa; Copeland, Jack G; Estep, Jerry D; Loebe, Matthias; Reardon, Michael J

2016-06-01

Primary cardiac sarcomas, although rare, are aggressive and lethal, requiring thorough surgical resection and adjuvant chemotherapy for the best possible outcome. We report the case of a 32-year-old woman who underwent total artificial heart implantation for right-sided heart failure caused by right ventricular angiosarcoma. For the first several weeks in intensive care, the patient recovered uneventfully. However, a postoperative liver biopsy indicated hepatocellular injury consistent with preoperative chemotherapy. She developed continuing liver failure, from which she died despite good cardiac function.

Suppression of Arrhythmia by Enhancing Mitochondrial Ca2+ Uptake in Catecholaminergic Ventricular Tachycardia Models.

PubMed

Schweitzer, Maria K; Wilting, Fabiola; Sedej, Simon; Dreizehnter, Lisa; Dupper, Nathan J; Tian, Qinghai; Moretti, Alessandra; My, Ilaria; Kwon, Ohyun; Priori, Silvia G; Laugwitz, Karl-Ludwig; Storch, Ursula; Lipp, Peter; Breit, Andreas; Mederos Y Schnitzler, Michael; Gudermann, Thomas; Schredelseker, Johann

2017-12-01

Cardiovascular disease-related deaths frequently arise from arrhythmias, but treatment options are limited due to perilous side effects of commonly used antiarrhythmic drugs. Cardiac rhythmicity strongly depends on cardiomyocyte Ca 2+ handling and prevalent cardiac diseases are causally associated with perturbations in intracellular Ca 2+ handling. Therefore, intracellular Ca 2+ transporters are lead candidate structures for novel and safer antiarrhythmic therapies. Mitochondria and mitochondrial Ca 2+ transport proteins are important regulators of cardiac Ca 2+ handling. Here we evaluated the potential of pharmacological activation of mitochondrial Ca 2+ uptake for the treatment of cardiac arrhythmia. To this aim,we tested substances that enhance mitochondrial Ca 2+ uptake for their ability to suppress arrhythmia in a murine model for ryanodine receptor 2 (RyR2)-mediated catecholaminergic polymorphic ventricular tachycardia (CPVT) in vitro and in vivo and in induced pluripotent stem cell-derived cardiomyocytes from a CPVT patient. In freshly isolated cardiomyocytes of RyR2 R4496C/WT mice efsevin, a synthetic agonist of the voltage-dependent anion channel 2 (VDAC2) in the outer mitochondrial membrane, prevented the formation of diastolic Ca 2+ waves and spontaneous action potentials. The antiarrhythmic effect of efsevin was abolished by blockade of the mitochondrial Ca 2+ uniporter (MCU), but could be reproduced using the natural MCU activator kaempferol. Both mitochondrial Ca 2+ uptake enhancers (MiCUps), efsevin and kaempferol, significantly reduced episodes of stress-induced ventricular tachycardia in RyR2 R4496C/WT mice in vivo and abolished diastolic, arrhythmogenic Ca 2+ events in human iPSC-derived cardiomyocytes.

Risk factors for impaired respiratory function during nurse-administered procedural sedation and analgesia in the cardiac catheterisation laboratory: a matched case-control study.

PubMed

Conway, Aaron; Page, Karen; Rolley, John; Fulbrook, Paul

2013-08-01

Side effects of the medications used for procedural sedation and analgesia in the cardiac catheterisation laboratory are known to cause impaired respiratory function. Impaired respiratory function poses considerable risk to patient safety as it can lead to inadequate oxygenation. Having knowledge about the conditions that predict impaired respiratory function prior to the procedure would enable nurses to identify at-risk patients and selectively implement intensive respiratory monitoring. This would reduce the possibility of inadequate oxygenation occurring. To identify pre-procedure risk factors for impaired respiratory function during nurse-administered procedural sedation and analgesia in the cardiac catheterisation laboratory. Retrospective matched case-control. 21 cases of impaired respiratory function were identified and matched to 113 controls from a consecutive cohort of patients over 18 years of age. Conditional logistic regression was used to identify risk factors for impaired respiratory function. With each additional indicator of acute illness, case patients were nearly two times more likely than their controls to experience impaired respiratory function (OR 1.78; 95% CI 1.19-2.67; p = 0.005). Indicators of acute illness included emergency admission, being transferred from a critical care unit for the procedure or requiring respiratory or haemodynamic support in the lead up to the procedure. Several factors that predict the likelihood of impaired respiratory function were identified. The results from this study could be used to inform prospective studies investigating the effectiveness of interventions for impaired respiratory function during nurse-administered procedural sedation and analgesia in the cardiac catheterisation laboratory.

TU-EF-304-12: Proton Radiation Therapy for Left-Sided Breast Cancer: LET and RBE Considerations for Cardiac Toxicity

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

Giantsoudi, D; Jee, K; MacDonald, S

Purpose: Increased risk of coronary artery disease has been documented for patients treated with radiation for left-sided breast cancer. Proton therapy (PRT) has been shown to significantly decrease cardiac irradiation, however variations in relative biological effectiveness (RBE) have been ignored so far. In this study we evaluate the impact of accounting for RBE variations on sensitive structures located within high linear energy transfer (LET) areas (distal end) of the proton treatment fields, for this treatment site. Methods: Three patients treated in our institution with PRT for left-sided breast cancer were selected. All patients underwent reconstructive surgery after mastectomy and treatedmore » to a total dose of 50.4Gy with beam(s) vertical to the chest wall. Dose and LET distributions were calculated using Monte Carlo (MC-TOPAS - TOol for PArticle Simulation). The LET-based, variable-RBE-weighted dose was compared to the analytical calculation algorithm (ACA) and MC dose distributions for a constant RBE of 1.1, based on volume histograms and mean values for the target, heart and left anterior descending coronary artery (LAD). Results: Assuming a constant RBE and compared to the ACA dose, MC predicted lower mean target and heart doses by 0.5% to 2.7% of the prescription dose. For variable RBE, plan evaluation showed increased mean target dose by up to 5%. Mean variable-RBE-weighted doses for the LAD ranged from 2.7 to 5.9Gy(RBE) among patients increased by 41%–64.2% compared to constant RBE ACA calculation (absolute dose: 1.7–3.9Gy(RBE)). Smaller increase in mean heart doses was noticed. Conclusion: ACA overestimates the target mean dose by up to 2.7%. However, disregarding variations in RBE may lead to significant underestimation of the dose to sensitive structures at the distal end of the proton treatment field and could thus impact outcome modeling for cardiac toxicities after proton therapy. These results are subject to RBE model and parameter uncertainties.« less

Identification of Pulmonary Hypertension Caused by Left-Sided Heart Disease (World Health Organization Group 2) Based on Cardiac Chamber Volumes Derived From Chest CT Imaging.

PubMed

Aviram, Galit; Rozenbaum, Zach; Ziv-Baran, Tomer; Berliner, Shlomo; Topilsky, Yan; Fleischmann, Dominik; Sung, Yon K; Zamanian, Roham T; Guo, Haiwei Henry

2017-10-01

Evaluations of patients with pulmonary hypertension (PH) commonly include chest CT imaging. We hypothesized that cardiac chamber volumes calculated from the same CT scans can yield additional information to distinguish PH related to left-sided heart disease (World Health Organization group 2) from other PH subtypes. Patients who had PH confirmed by right heart catheterization and contrast-enhanced chest CT studies were enrolled in this retrospective multicenter study. Cardiac chamber volumes were calculated using automated segmentation software and compared between group 2 and non-group 2 patients with PH. This study included 114 patients with PH, 27 (24%) of whom were classified as group 2 based on their pulmonary capillary wedge pressure. Patients with group 2 PH exhibited significantly larger median left atrial (LA) volumes (118 mL vs 63 mL; P < .001), larger median left ventricular (LV) volumes (90 mL vs 76 mL; P = .02), and smaller median right ventricular (RV) volumes (173 mL vs 210 mL; P = .005) than did non-group 2 patients. On multivariate analysis adjusted for age, sex, and mean pulmonary arterial pressure, group 2 PH was significantly associated with larger median LA and LV volumes (P < .001 and P = .008, respectively) and decreased volume ratios of RA/LA, RV/LV, and RV/LA (P = .001, P = .004, and P < .001, respectively). Enlarged LA volumes demonstrated a high discriminatory ability for group 2 PH (area under the curve, 0.92; 95% CI, 0.870-0.968). Volumetric analysis of the cardiac chambers from nongated chest CT scans, particularly with findings of an enlarged left atrium, exhibited high discriminatory ability for identifying patients with PH due to left-sided heart disease. Copyright © 2017. Published by Elsevier Inc.

Prophylactic levosimendan for the prevention of low cardiac output syndrome and mortality in paediatric patients undergoing surgery for congenital heart disease.

PubMed

Hummel, Johanna; Rücker, Gerta; Stiller, Brigitte

2017-08-02

Low cardiac output syndrome remains a serious complication, and accounts for substantial morbidity and mortality in the postoperative course of paediatric patients undergoing surgery for congenital heart disease. Standard prophylactic and therapeutic strategies for low cardiac output syndrome are based mainly on catecholamines, which are effective drugs, but have considerable side effects. Levosimendan, a calcium sensitiser, enhances the myocardial function by generating more energy-efficient myocardial contractility than achieved via adrenergic stimulation with catecholamines. Thus potentially, levosimendan is a beneficial alternative to standard medication for the prevention of low cardiac output syndrome in paediatric patients after open heart surgery. To review the efficacy and safety of the postoperative prophylactic use of levosimendan for the prevention of low cardiac output syndrome and mortality in paediatric patients undergoing surgery for congenital heart disease. We identified trials via systematic searches of CENTRAL, MEDLINE, Embase, and Web of Science, as well as clinical trial registries, in June 2016. Reference lists from primary studies and review articles were checked for additional references. We only included randomised controlled trials (RCT) in our analysis that compared prophylactic levosimendan with standard medication or placebo, in infants and children up to 18 years of age, who were undergoing surgery for congenital heart disease. Two review authors independently extracted data and assessed risk of bias according to a pre-defined protocol. We obtained additional information from all but one of the study authors of the included studies. We used the five GRADE considerations (study limitations, consistency of effect, imprecision, indirectness, and publication bias) to assess the quality of evidence from the studies that contributed data to the meta-analyses for the prespecified outcomes. We created a 'Summary of findings' table to summarise the results and the quality of evidence for each outcome. We included five randomised controlled trials with a total of 212 participants in the analyses. All included participants were under five years of age. Using GRADE, we assessed there was low-quality evidence for all analysed outcomes. We assessed high risk of performance and detection bias for two studies due to their unblinded setting. Levosimendan showed no clear effect on risk of mortality (risk ratio (RR) 0.47, 95% confidence interval (CI) 0.12 to 1.82; participants = 123; studies = 3) and no clear effect on low cardiac output syndrome (RR 0.64, 95% CI 0.39 to 1.04; participants = 83; studies = 2) compared to standard treatments. Data on time-to-death were not available from any of the included studies.There was no conclusive evidence on the effect of levosimendan on the secondary outcomes. The length of intensive care unit stays (mean difference (MD) 0.33 days, 95% CI -1.16 to 1.82; participants = 188; studies = 4), length of hospital stays (MD 0.26 days, 95% CI -3.50 to 4.03; participants = 75; studies = 2), duration of mechanical ventilation (MD -0.04 days, 95% CI -0.08 to 0.00; participants = 208; studies = 5), and the risk of mechanical circulatory support or cardiac transplantation (RR 1.49, 95% CI 0.19 to 11.37; participants = 60; studies = 2) did not clearly differ between the groups. Published data about adverse effects of levosimendan were limited. A meta-analysis of hypotension, one of the most feared side effects of levosimendan, was not feasible because of the heterogeneous expression of blood pressure values. The current level of evidence is insufficient to judge whether prophylactic levosimendan prevents low cardiac output syndrome and mortality in paediatric patients undergoing surgery for congenital heart disease. So far, no significant differences have been detected between levosimendan and standard inotrope treatments in this setting.The authors evaluated the quality of evidence as low, using the GRADE approach. Reasons for downgrading were serious risk of bias (performance and detection bias due to unblinded setting of two RCTs), serious risk of inconsistency, and serious to very serious risk of imprecision (small number of included patients, low event rates).

Oxytocin-Gly-Lys-Arg stimulates cardiomyogenesis by targeting cardiac side population cells.

PubMed

Danalache, Bogdan A; Yu, Calvin; Gutkowska, Jolanta; Jankowski, Marek

2014-03-01

The functional oxytocin (OT) system is expressed in the human and rodent hearts. OT stimulates differentiation of cardiac stem cells into contracting cardiomyocytes (CM). In this study, we investigated OT receptors (OTR) expressed in the cells of cardiac side population (SP) and the abilities of these cells to differentiate into CM in response to the treatment with OT-Gly-Lys-Arg (OT-GKR), a dominant and biologically active form of OT, in the fetal rodent heart. Immunocytochemistry of whole rat embryo at mid gestation (E11) revealed parallel staining in the heart of OTR and the ATP-binding cassette sub-family G member 2 (brcp1) antigen the marker of the SP phenotype. Using flow cytometry, the SP cells were selected from the newborn CM stained with Höechst 33342: 5.32%±0.06% of SP and 15.2%±1.10 of main population expressed OTR on the cell surface. The OTR was detected in CD29 (6.6%) and then in CD31 (4.7%) but less frequently in CD45 (0.7%) positive SP cell subpopulations. Specifically, the phenotype of SP CD31- cell, but not SP CD31+ cells, proliferates in the presence of OT-GKR and develops large cell aggregates. Then, OT-GKR treatment induced the apparition of beating cell colonies after 11 days (10±2.78%), which increased until day 16 (52±1.21%). The cells in contractile colonies expressed the markers of a CM phenotype, such as troponin, cardiac myosin light chain-2, and actinin. Finally, SP cells stimulated by OT-GKR induced endothelial phenotype. These results suggest that the C-terminally extended OT molecule stimulates cardiac differentiation of SP CD31- cells and is involved in heart growth.

Cardiovascular consequences of sympathetic hyperactivity.

PubMed

Leenen, F H

1999-03-01

The sympathetic nervous system plays an integral role in many aspects of cardiovascular homeostasis. However, intermittent or chronic sympathetic hyperactivity can also initiate or accelerate cardiovascular pathology and provoke clinical events in the presence of cardiovascular disease. Both alpha- and beta-receptors mediate these responses. In the case of the heart, alpha- and beta- receptors contribute to ventricular arrhythmias and cardiac hypertrophy. Moreover, cardiac beta2-receptors mediate not only chronotropic and inotropic responses at the postsynaptic level, but also noradrenalin release at the presynaptic level. To block the adverse effects of sympathetic hyperactivity optimally, one would therefore need both alpha- and nonselective beta-receptor blockade. On the other hand, prevention or reversal of sympathetic hyperactivity at the central level appears to be an attractive alternative. Alpha2-agonists such as clonidine and alpha-methyldopa are clearly effective in this regard but are associated with side effects. More recent research indicates that in the central nervous systen (CNS) other classes such as dihydropyridines (eg, nifedipine) or angiotensin II type 1 receptor blockers (eg, losartan) also can decrease elevated sympathetic nerve activity. The therapeutic relevance of these CNS effects and differences between lipophilic and hydrophilic compounds provide intriguing new avenues for research in disorders such as hypertension and congestive heart failure.

[Organprotection in cardiac risk patients--rational of perioperative beta-adrenoceptor-antagonists and statins].

PubMed

Hanss, Robert; Bein, Berthold

2010-04-01

The number of patients with limited organ function is steadily increasing due to the aging of the population. Consequently, a growing number of patients needing surgery is accompanied by serious comorbidities. These patients are at high risk of perioperative organ dysfunction. In this context cardiac events (e.g. cardiac arrhythmias, angina or myocardial infarction) play a major role with significant impact on postoperative care, long term outcome and economic sequelae. Thus, anaesthesiologists must prevent such events in the perioperative period. Besides general measures such as adequate analgesia, protection from stressful events and sufficient volume replacement, medical intervention with beta-blockers or HMG-CoA-reductase-inhibitors (statins) are necessary to reduce the incidence of perioperative cardiac events. Both beta-blockers and HMG-CoA-reductase-inhibitors are known to exhibit pleiotropic effects (defined as additional cardioprotective effects) besides the primary blockade of the beta-adrenergic receptor or the inhibition of the synthesis of serum cholesterol, respectively. Both groups of drugs improve cardiac function, decrease inflammatory response, decrease activation of blood coagulation and stabilize endothelial plaques. Based on the current literature the following recommendations are published concerning the perioperative administration of beta-blockers: (i) Patients who are on beta-blockers on a regular basis following guidelines concerning chronic treatment of cardiovascular diseases should continue this medication throughout the perioperative period; (ii) a sufficient indicator of an adequate therapy is the baseline heart rate. It should not exceed 60-70bpm at rest; (iii) the Revised Cardiac Risk Index (RCRI) is a widely accepted score to estimate the patient's perioperative cardiac risk; (iv) patients with a RCRI > or =3 should not be scheduled for routine surgery without sufficient beta-adrenergic-receptor blockade; (v) in patients at high cardiac risk based on the RCRI who are scheduled for emergency surgery beta-blocker-therapy should not be initiated de novo perioperatively. However, for perioperative treatment of tachycardia or hypertension beta-blockers are the drug of first choice. Concerning perioperative statin-therapy the following recommendations are suggested: (i) chronic statin-therapy should be continued throughout surgery and the perioperative period; (ii) in patients without chronic statin-therapy scheduled for vascular surgery this treatment should be started perioperativly; (iii) no data is available concerning other patient populations; (iv) if statin-therapy is indicated it should be started independently from baseline serum LDL-C-concentration; (v) side effects of statin-therapy are rare and usually not live threatening, thus treatment is considered to be without serious risks to the patient. Georg Thieme Verlag Stuttgart. New York.

Cardiac Imaging System

NASA Technical Reports Server (NTRS)

1990-01-01

Although not available to all patients with narrowed arteries, balloon angioplasty has expanded dramatically since its introduction with an estimated further growth to 562,000 procedures in the U.S. alone by 1992. Growth has fueled demand for higher quality imaging systems that allow the cardiologist to be more accurate and increase the chances of a successful procedure. A major advance is the Digital Cardiac Imaging (DCI) System designed by Philips Medical Systems International, Best, The Netherlands and marketed in the U.S. by Philips Medical Systems North America Company. The key benefit is significantly improved real-time imaging and the ability to employ image enhancement techniques to bring out added details. Using a cordless control unit, the cardiologist can manipulate images to make immediate assessment, compare live x-ray and roadmap images by placing them side-by-side on monitor screens, or compare pre-procedure and post procedure conditions. The Philips DCI improves the cardiologist's precision by expanding the information available to him.

Conservative Management of an Epicardial Collateral Perforation During Retrograde Chronic Total Occlusion Percutaneous Coronary Intervention.

PubMed

Ngo, Christian; Christopoulos, George; Brilakis, Emmanouil S

2016-01-01

Coronary artery perforation is a highly feared complication of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) and can lead to pericardial effusion, tamponade, and, rarely, emergent cardiac surgery. Perforation of epicardial collaterals during retrograde CTO-PCI may be particularly challenging to treat, as embolization from both sides of the perforation may be required to control the bleeding. However, conservative measures can occasionally be effective. We present a case of epicardial collateral vessel perforation that was managed conservatively with anticoagulation reversal.

Differential control over postganglionic neurons in rat cardiac ganglia by NA and DmnX neurons: anatomical evidence.

PubMed

Cheng, Zixi; Zhang, Hong; Guo, Shang Z; Wurster, Robert; Gozal, David

2004-04-01

In previous single-labeling experiments, we showed that neurons in the nucleus ambiguous (NA) and the dorsal moto nucleus of the vagus (DmnX) project to intrinsic cardiac ganglia. Neurons in these two motor nuclei differ significantly in the size of their projection fields, axon caliber, and endings in cardiac ganglia. These differences in NA and DmnX axon cardiac projections raise the question as to whether they target the same, distinct, or overlapping populations of cardiac principal neurons. To address this issue, we examined vagal terminals in cardiac ganglia and trace injection sites in the brain stem using two different anterograde t ace s 1,1-dioleyl-3,3,3,3-tetramethylindocarbocyanine methanesulfonate and 4-[4-(dihexadecylamino)-styryl]-N-methylpyridinium iodide] and confocal microscopy in male Sprague-Dawley rats. We found that 1) NA and DmnX neurons innervate the same cardiac ganglia, but these axons target separate subpopulations of principal neurons and 2) axons arising from neurons in the NA and DmnX in the contralateral sides of the brain stem enter the cardiac ganglionic plexus through separate bundles and preferentially innervate principal neurons near their entry regions, providing topographic mapping of vagal motor neurons in left and right brain stem vagal nuclei. Because the NA and DmnX project to distinct populations of cardiac principal neurons, we propose that they may play different roles in controlling cardiac function.

Radiation-induced heart disease in lung cancer radiotherapy

PubMed Central

Ming, Xin; Feng, Yuanming; Yang, Chengwen; Wang, Wei; Wang, Ping; Deng, Jun

2016-01-01

Abstract Background: Radiation-induced heart disease (RIHD), which affects the patients’ prognosis with both acute and late side effects, has been published extensively in the radiotherapy of breast cancer, lymphoma and other benign diseases. Studies on RIHD in lung cancer radiotherapy, however, are less extensive and clear even though the patients with lung cancer are delivered with higher doses to the heart during radiation treatment. Methods: In this article, after extensive literature search and analysis, we reviewed the current evidence on RIHD in lung cancer patients after their radiation treatments and investigated the potential risk factors for RIHD as compared to other types of cancers. Result: Cardiac toxicity has been found highly relevant in lung cancer radiotherapy. So far, the crude incidence of cardiac complications in the lung cancer patients after radiotherapy has been up to 33%. Conclusion: The dose to the heart, the lobar location of tumor, the treatment modality, the history of heart and pulmonary disease and smoking were considered as potential risk factors for RIHD in lung cancer radiotherapy. As treatment techniques improve over the time with better prognosis for lung cancer survivors, an improved prediction model can be established to further reduce the cardiac toxicity in lung cancer radiotherapy. PMID:27741117

Radiation-induced heart disease in lung cancer radiotherapy: A dosimetric update.

PubMed

Ming, Xin; Feng, Yuanming; Yang, Chengwen; Wang, Wei; Wang, Ping; Deng, Jun

2016-10-01

Radiation-induced heart disease (RIHD), which affects the patients' prognosis with both acute and late side effects, has been published extensively in the radiotherapy of breast cancer, lymphoma and other benign diseases. Studies on RIHD in lung cancer radiotherapy, however, are less extensive and clear even though the patients with lung cancer are delivered with higher doses to the heart during radiation treatment. In this article, after extensive literature search and analysis, we reviewed the current evidence on RIHD in lung cancer patients after their radiation treatments and investigated the potential risk factors for RIHD as compared to other types of cancers. Cardiac toxicity has been found highly relevant in lung cancer radiotherapy. So far, the crude incidence of cardiac complications in the lung cancer patients after radiotherapy has been up to 33%. The dose to the heart, the lobar location of tumor, the treatment modality, the history of heart and pulmonary disease and smoking were considered as potential risk factors for RIHD in lung cancer radiotherapy. As treatment techniques improve over the time with better prognosis for lung cancer survivors, an improved prediction model can be established to further reduce the cardiac toxicity in lung cancer radiotherapy.

Elbasvir/Grazoprevir, an Alternative in Antiviral Hepatitis C Therapy in Patients under Amiodarone Treatment

PubMed Central

Weiss, Lina; Wustmann, Kerstin; Semmo, Mariam; Schwerzmann, Markus; Semmo, Nasser

2018-01-01

A sofosbuvir/ledipasvir combination is part of a first-line treatment of hepatitis C. However, in patients concurrently treated with amiodarone, cardiac side effects have been described, resulting in an official warning in 2015 by the American Food and Drug Administration and the European Medicines Agency when combining those substances. This deprived numerous hepatitis C patients with concurrent cardiovascular problems of receiving this highly effective treatment. Here we present a treatment alternative with an elbasvir/grazoprevir regimen, based on our successful treatment of a patient under concurrent amiodarone therapy. Our observations indicate that patients treated with amiodarone can finally benefit from effective antiviral therapy. PMID:29606942

Strain Analysis in the Assessment of a Mouse Model of Cardiotoxicity due to Chemotherapy: Sample for Preclinical Research.

PubMed

Rea, Domenica; Coppola, Carmela; Barbieri, Antonio; Monti, Maria Gaia; Misso, Gabriella; Palma, Giuseppe; Bimonte, Sabrina; Zarone, Mayra Rachele; Luciano, Antonio; Liccardo, Davide; Maiolino, Piera; Cittadini, Antonio; Ciliberto, Gennaro; Arra, Claudio; Maurea, Nicola

2016-01-01

In recent years, the development of more effective anticancer drugs has provided great benefits in patients' quality of life by improving both prognosis and disease-free survival. Nevertheless, the frequency and severity of side-effects, with particular reference to cardiac toxicity, have gained particular attention. The purpose of this study was to create a precise and sensitive preclinical model, able to identify early contractile dysfunction in mice treated with chemotherapy, through use of speckle-tracking echocardiography. We generated a mouse model of cardiotoxicity induced by doxorubicin. C57BL 6 mice were divided into two groups, treated for 7 days by intraperitoneal injections of placebo (vehicle) or doxorubicin (2.17 mg/kg), in order to characterize the cardiac phenotype in vivo. We demonstrated that doxorubicin caused ealy remodeling of the left ventricle: after two days of therapy, the radial, circumferential and strain rates were reduced respectively by 35%, 34%, and 39% (p-value ≤0.001). Moreover, histological analysis revealed that doxorubicin treatment increased fibrosis, cardiomyocyte diameter and apoptosis. In a murine model of doxorubicin-induced cardiac injury, we detected left ventricular dysfunction followed by alterations in conventional echocardiographic indices. Our study suggests that a change in strain could be an effective early marker of myocardial dysfunction for new anticancer treatments and, in preclinical studies, it might also be a valuable indicator for the assessment of activity of cardioprotective agents. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Voluntary Deep Inspiration Breath-hold Reduces the Heart Dose Without Compromising the Target Volume Coverage During Radiotherapy for Left-sided Breast Cancer.

PubMed

Al-Hammadi, Noora; Caparrotti, Palmira; Naim, Carole; Hayes, Jillian; Rebecca Benson, Katherine; Vasic, Ana; Al-Abdulla, Hissa; Hammoud, Rabih; Divakar, Saju; Petric, Primoz

2018-03-01

During radiotherapy of left-sided breast cancer, parts of the heart are irradiated, which may lead to late toxicity. We report on the experience of single institution with cardiac-sparing radiotherapy using voluntary deep inspiration breath hold (V-DIBH) and compare its dosimetric outcome with free breathing (FB) technique. Left-sided breast cancer patients, treated at our department with postoperative radiotherapy of breast/chest wall +/- regional lymph nodes between May 2015 and January 2017, were considered for inclusion. FB-computed tomography (CT) was obtained and dose-planning performed. Cases with cardiac V25Gy ≥ 5% or risk factors for heart disease were coached for V-DIBH. Compliant patients were included. They underwent additional CT in V-DIBH for planning, followed by V-DIBH radiotherapy. Dose volume histogram parameters for heart, lung and optimized planning target volume (OPTV) were compared between FB and BH. Treatment setup shifts and systematic and random errors for V-DIBH technique were compared with FB historic control. Sixty-three patients were considered for V-DIBH. Nine (14.3%) were non-compliant at coaching, leaving 54 cases for analysis. When compared with FB, V-DIBH resulted in a significant reduction of mean cardiac dose from 6.1 +/- 2.5 to 3.2 +/- 1.4 Gy (p < 0.001), maximum cardiac dose from 51.1 +/- 1.4 to 48.5 +/- 6.8 Gy (p = 0.005) and cardiac V25Gy from 8.5 +/- 4.2 to 3.2 +/- 2.5% (p < 0.001). Heart volumes receiving low (10-20 Gy) and high (30-50 Gy) doses were also significantly reduced. Mean dose to the left anterior coronary artery was 23.0 (+/- 6.7) Gy and 14.8 (+/- 7.6) Gy on FB and V-DIBH, respectively (p < 0.001). Differences between FB- and V-DIBH-derived mean lung dose (11.3 +/- 3.2 vs. 10.6 +/- 2.6 Gy), lung V20Gy (20.5 +/- 7 vs. 19.5 +/- 5.1 Gy) and V95% for the OPTV (95.6 +/- 4.1 vs. 95.2 +/- 6.3%) were non-significant. V-DIBH-derived mean shifts for initial patient setup were ≤ 2.7 mm. Random and systematic errors were ≤ 2.1 mm. These results did not differ significantly from historic FB controls. When compared with FB, V-DIBH demonstrated high setup accuracy and enabled significant reduction of cardiac doses without compromising the target volume coverage. Differences in lung doses were non-significant.

Impact of Age and Polytherapy on Fingolimod Induced Bradycardia: a Preclinical Study.

PubMed

Ritter, Christian; Svačina, Martin K R; Bobylev, Ilja; Joshi, Abhijeet; Schneider, Toni; Lehmann, Helmar C

2017-03-01

Fingolimod is a an oral disease modifying drug for relapsing remitting multiple sclerosis (MS) preventing egress of B and T cells from lymph nodes. Relevant first dose adverse events include bradycardia and atrioventricular conduction slowing. Cardiac side effects of fingolimod and combinational pharmacotherapy including duloxetine and tolterodine were monitored in mice of different age using implantable ECG telemetric systems. Cardiac tissue was assessed for S1P-receptor subtype (1 and 3), and for GIRK1 expression. Fingolimod led to a significant heart rate reduction within 60 min, which returned to baseline values within 24 h. In older mice bradycardia was more pronounced compared to younger mice. Atrioventricular conduction was not affected. Older mice showed a higher S1PR3 expression in a naïve state and receptor expression was reduced after fingolimod administration. Combination with duloxetine or tolterodine alleviated fingolimod induced heart rate decrease. Our data provide preclinical evidence that negative chronotropic effects of fingolimod might be age dependent, possibly due to an altered expression and internalization of cardiac S1PR3 in older animals. This data could be relevant for future clinical monitoring and patient selection in the aging MS population. Combinational therapies of fingolimod and duloxetine or tolterodine are well tolerated and safe without an increased risk for pronounced bradycardia or arrhythmia.

Cardiotoxicity and cancer therapy: treatment-related cardiac morbidity in patients presenting with symptoms suggestive of heart or lung disease.

PubMed

Wieshammer, Siegfried; Dreyhaupt, Jens; Müller, Dirk; Momm, Felix; Jakob, Andreas; Freund, Ulrich

2013-01-01

Cardiac injury is one of the complications of cancer treatment. This study aimed to investigate the relationships between the types of radiotherapy of the chest (RT), chemotherapy (CT), cancer surgery (CS) and endocrine therapy (ET), and the presence of heart disease, and their associations with the serum level of N-terminal pro-B-type natriuretic peptide (NT-proBNP). A consecutive series of 374 patients with cancer who were referred because of symptoms suggestive of heart or lung disease prospectively underwent a diagnostic workup. The prevalence of heart disease was 36.9%. RT administered before 1995 (n = 19) was associated with both increased odds of heart disease [adjusted odds ratio 10.3, 95% confidence interval 3.1-34.0] and higher ln-transformed NT-proBNP values (p < 0.01) compared to the control group (no RT or RT for right-sided breast cancer from 1995 onwards; n = 311). Anthracycline-treated patients (n = 54) had higher adjusted values for ln(NT-proBNP) compared to the control group (no CT; n = 243; p < 0.01) but no increased odds of heart disease. While pre-1995 RT and anthracycline-containing CT were associated with cardiac effects, there was no evidence that RT using modern cardioprotective techniques, CT in the absence of anthracyclines, CS or ET had detrimental effects on the heart. Copyright © 2013 S. Karger AG, Basel.

Accuracy of a step counter during treadmill and daily life walking by healthy adults and patients with cardiac disease

PubMed Central

Thorup, Charlotte Brun; Grønkjær, Mette; Dinesen, Birthe Irene

2017-01-01

Background Step counters have been used to observe activity and support physical activity, but there is limited evidence on their accuracy. Objective The purpose was to investigate the step accuracy of the Fitbit Zip (Zip) in healthy adults during treadmill walking and in patients with cardiac disease while hospitalised at home. Methods Twenty healthy adults aged 39±13.79 (mean ±SD) wore four Zips while walking on a treadmill at different speeds (1.7–6.1 km/hour), and 24 patients with cardiac disease (age 67±10.03) wore a Zip for 24 hours during hospitalisation and for 4 weeks thereafter at home. A Shimmer3 device was used as a criterion standard. Results At a treadmill speed of 3.6 km/hour, the relative error (±SD) for the Zips on the upper body was −0.02±0.67 on the right side and −0.09 (0.67) on the left side. For the Zips on the waist, this was 0.08±0.71 for the right side and -0.08 (0.47) on the left side. At a treadmill speed of 3.6 km/hour and higher, the average per cent of relative error was <3%. The 24-hour test for the hospitalised patients showed a relative error of −47.15±24.11 (interclass correlation coefficient (ICC): 0.60), and for the 24-hour test at home, the relative error was −27.51±28.78 (ICC: 0.87). Thus, none of the 24-hour tests had less than the expected 20% error. In time periods of evident walking during the 24 h test, the Zip had an average per cent relative error of <3% at 3.6 km/hour and higher speeds. Conclusions A speed of 3.6 km/hour or higher is required to expect acceptable accuracy in step measurement using a Zip, on a treadmill and in real life. Inaccuracies are directly related to slow speeds, which might be a problem for patients with cardiac disease who walk at a slow pace. PMID:28363918

Long-Term Haloperidol Treatment Prolongs QT Interval and Increases Expression of Sigma 1 and IP3 Receptors in Guinea Pig Hearts.

PubMed

Stracina, Tibor; Slaninova, Iva; Polanska, Hana; Axmanova, Martina; Olejnickova, Veronika; Konecny, Petr; Masarik, Michal; Krizanova, Olga; Novakova, Marie

2015-07-01

Haloperidol is a neuroleptic drug used for a medication of various psychoses and deliria. Its administration is frequently accompanied by cardiovascular side effects, expressed as QT interval prolongation and occurrence of even lethal arrhythmias. Despite these side effects, haloperidol is still prescribed in Europe in clinical practice. Haloperidol binds to sigma receptors that are coupled with inositol 1,4,5-trisphosphate (IP3) receptors. Sigma receptors are expressed in various tissues, including heart muscle, and they modulate potassium channels. Together with IP3 receptors, sigma receptors are also involved in calcium handling in various tissues. Therefore, the present work aimed to study the effects of long-term haloperidol administration on the cardiac function. Haloperidol (2 mg/kg once a day) or vehiculum was administered by intraperitoneal injection to guinea pigs for 21 consecutive days. We measured the responsiveness of the hearts isolated from the haloperidol-treated animals to additional application of haloperidol. Expression of the sigma 1 receptor and IP3 receptors was studied by real time-PCR and immunohistochemical analyses. Haloperidol treatment caused the significant decrease in the relative heart rate and the prolongation of QT interval of the isolated hearts from the haloperidol-treated animals, compared to the hearts isolated from control animals. The expression of sigma 1 and IP3 type 1 and type 2 receptors was increased in both atria of the haloperidol-treated animals but not in ventricles. The modulation of sigma 1 and IP3 receptors may lead to altered calcium handling in cardiomyocytes and thus contribute to changed sensitivity of cardiac cells to arrhythmias.

Application of Traditional Chinese Medicine in Treatment of Atrial Fibrillation

PubMed Central

Dong, Yan; Yao, Kuiwu; Jiang, Wenrui

2017-01-01

Atrial fibrillation (AF) is the most common cardiac arrhythmia, which is related to many cardiac and cerebral vascular diseases, especially stroke. It can therefore increase cardiovascular mortality and all-cause death. The current treatments of AF remain to be western drugs and radiofrequency ablation which are limited by the tolerance of patients, adverse side effects, and high recurrence rate, especially for the elderly. On the contrary, traditional Chinese medicine (TCM) with long history of use involves various treatment methods, including Chinese herbal medicines (CHMs) or bioactive ingredients, Chinese patent medicines, acupuncture, Qigong, and Tai Chi Chuan. With more and more researches reported, the active roles of TCM in AF management have been discovered. Then it is likely that TCM would be effective preventive means and valuable additional remedy for AF. The potential mechanisms further found by numerous experimental studies showed the distinct characteristics of TCM. Some CHMs or bioactive ingredients are atrial-selective, while others are multichannel and multifunctional. Therefore, in this review we summarized the treatment strategies reported in TCM, with the purpose of providing novel ideas and directions for AF management. PMID:28243308

The behavioral profile of spice and synthetic cannabinoids in humans.

PubMed

Müller, Helge H; Kornhuber, Johannes; Sperling, Wolfgang

2016-09-01

The use of synthetic cannabinoids (spice) is increasing. The number of descriptions of (new) clinical side effects is also increasing. We screened relevant publications for articles about spice with a focus on the clinical manifestations of the use of this drug. Spice creates diffuse psychiatric and somatic effects that are only partially similar to those of natural cannabinoids. Most of the observed effects are related to sympathomimetic-cardiac effects and neuropsychiatric manifestations. Clinical treatment is primarily based on intensive apparative and laboratory monitoring and supportive therapy. Because the exact active ingredients of spice are often difficult to determine with standard specific toxicology testing, the assessment and analysis of consumed substances by specialized laboratories is recommended. Copyright © 2015 Elsevier Inc. All rights reserved.

Mechanisms of cardiac cell damage due to catecholamines: significance of drugs regulating central sympathetic outflow.

PubMed

Rupp, H; Dhalla, K S; Dhalla, N S

1994-01-01

A chronically increased rate of catecholamine release has various deleterious actions. Isoproterenol injections (80 mg/kg body weight) resulted in depressed Ca2+ transport in the sarcolemma (ATP-dependent Ca2+ uptake, Na(+)-dependent Ca2+ uptake) and sarcoplasmic reticulum (Ca2+ uptake) of rat heart. The formation of malondialdehyde owing to lipid peroxidation was increased. Pretreatment with vitamin E (10-25 mg/kg/day) strongly inhibited the membrane damage. The toxic effects of catecholamines arise most probably from their oxidation, and it is therefore important either to reduce the central sympathetic outflow or to prevent the oxidation. An inappropriately high sympathetic outflow is a typical feature of Western affluent societies, and is linked to psychosocial stress and hypercaloric nutrition. However, established pharmacologic interventions to reduce sympathetic outflow have proven not practicable because of marked side effects. Using radiotelemetry for monitoring cardiovascular parameters of spontaneously hypertensive rats treated with clonidine or moxonidine, we showed that clonidine, unlike moxonidine, resulted in rebound hypertension after drug withdrawal. Because the rebound blood pressure and the typical side effects of clonidine associated with low patient compliance are mainly mediated by alpha-adrenoceptors, it can be inferred that the I1-imidazoline agonist moxonidine does not exhibit the side effects commonly seen with clonidine and therefore represents a promising approach for reducing an inappropriately high central sympathetic outflow.

Does a reduced glucose intake prevent hyperglycemia in children early after cardiac surgery? a randomized controlled crossover study

PubMed Central

2012-01-01

Introduction Hyperglycemia in children after cardiac surgery can be treated with intensive insulin therapy, but hypoglycemia is a potential serious side effect. The aim of this study was to investigate the effects of reducing glucose intake below standard intakes to prevent hyperglycemia, on blood glucose concentrations, glucose kinetics and protein catabolism in children after cardiac surgery with cardiopulmonary bypass (CPB). Methods Subjects received a 4-hour low glucose (LG; 2.5 mg/kg per minute) and a 4-hour standard glucose (SG; 5.0 mg/kg per minute) infusion in a randomized blinded crossover setting. Simultaneously, an 8-hour stable isotope tracer protocol was conducted to determine glucose and leucine kinetics. Data are presented as mean ± SD or median (IQR); comparison was made by paired samples t test. Results Eleven subjects (age 5.1 (20.2) months) were studied 9.5 ± 1.9 hours post-cardiac surgery. Blood glucose concentrations were lower during LG than SG (LG 7.3 ± 0.7 vs. SG 9.3 ± 1.8 mmol/L; P < 0.01), although the glycemic target (4.0-6.0 mmol/L) was not achieved. No hypoglycemic events occurred. Endogenous glucose production was higher during LG than SG (LG 2.9 ± 0.8 vs. SG 1.5 ± 1.1 mg/kg per minute; P = 0.02), due to increased glycogenolysis (LG 1.0 ± 0.6 vs. SG 0.0 ± 1.0 mg/kg per minute; P < 0.05). Leucine balance, indicating protein balance, was negative but not affected by glucose intake (LG -54.8 ± 14.6 vs. SG -58.8 ± 16.7 μmol/kg per hour; P = 0.57). Conclusions Currently recommended glucose intakes aggravated hyperglycemia in children early after cardiac surgery with CPB. Reduced glucose intake decreased blood glucose concentrations without causing hypoglycemia or affecting protein catabolism, but increased glycogenolysis. Trial registration Dutch trial register NTR2079. PMID:23031354

Muscle wasting and sarcopenia in heart failure and beyond: update 2017.

PubMed

Springer, Jochen; Springer, Joshua-I; Anker, Stefan D

2017-11-01

Sarcopenia (loss of muscle mass and muscle function) is a strong predictor of frailty, disability and mortality in older persons and may also occur in obese subjects. The prevalence of sarcopenia is increased in patients suffering from chronic heart failure. However, there are currently few therapy options. The main intervention is resistance exercise, either alone or in combination with nutritional support, which seems to enhance the beneficial effects of training. Also, testosterone has been shown to increased muscle power and function; however, a possible limitation is the side effects of testosterone. Other investigational drugs include selective androgen receptor modulators, growth hormone, IGF-1, compounds targeting myostatin signaling, which have their own set of side effects. There are abundant prospective targets for improving muscle function in the elderly with or without chronic heart failure, and the continuing development of new treatment strategies and compounds for sarcopenia and cardiac cachexia makes this field an exciting one. © 2017 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Visual assessment of CPR quality during pediatric cardiac arrest: does point of view matter?

PubMed

Jones, Angela; Lin, Yiqun; Nettel-Aguirre, Alberto; Gilfoyle, Elaine; Cheng, Adam

2015-05-01

In many clinical settings, providers rely on visual assessment when delivering feedback on CPR quality. Little is known about the accuracy of visual assessment of CPR quality. We aimed to determine how accurate pediatric providers are in their visual assessment of CPR quality and to identify the optimal position relative to the patient for accurate CPR assessment. We videotaped high-quality CPR (based on 2010 American Heart Association guidelines) and 3 variations of poor quality CPR in a simulated resuscitation, filmed from the foot, head and the side of the manikin. Participants watched 12 videos and completed a questionnaire to assess CPR quality. One hundred and twenty-five participants were recruited. The overall accuracy of visual assessment of CPR quality was 65.6%. Accuracy was better from the side (70.8%) and foot (68.8%) of the bed when compared to the head of the bed (57.2%; p<0.001). The side was the best position for assessing depth (p<0.001). Rate assessment was equivalent between positions (p=0.58). The side and foot of the bed were superior to the head when assessing chest recoil (p<0.001). Factors associated with increased accuracy in visual assessment of CPR quality included recent CPR course completion (p=0.034) and involvement in more cardiac arrests as a team member (p=0.003). Healthcare providers struggle to accurately assess the quality of CPR using visual assessment. If visual assessment is being used, providers should stand at the side of the bed. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Beneficial effects of the combination of amlodipine and losartan for lowering blood pressure in spontaneously hypertensive rats.

PubMed

Choi, Seul Min; Seo, Mi Jeong; Kang, Kyung Koo; Kim, Jeong Hoon; Ahn, Byoung Ok; Yoo, Moohi

2009-03-01

A combination of antihypertensive agents can better control blood pressure and reduce the number and severity of side effects than a monotherapy. Since both CCBs (calcium channel blockers) and ARBs (angiotensin II receptor type-1 blockers) are current and effective antihypertensive drugs, this study assessed the synergistic antihypertensive effects as well as the optimal combination ratio of these two drugs. Amlodipine (3 mg/kg) or losartan (30 mg/kg) alone or a combination of each drug at a ratio 1:10 and 1:20 was administered orally to spontaneously hypertensive rats (SHR). A four-week treatment of either 3 mg/kg amlodipine or 30 mg/kg losartan alone decreased the systolic blood pressure (SBP). However, their combination significantly lowered the SBP from the 3(rd) week, and there was a positive correlation between this reduction in blood pressure and the improvement in arterial endothelium-dependent relaxation. In addition, the combination therapy (1:20) decreased both the cardiac mass and left ventricular weight to a greater extent than with either amlodipine or losartan alone. The collagen content in the cardiac tissue was also significantly lower after the 4-week combination therapy (1:10). These results suggest that the combined use of amlodipine and losartan might be more effective in treating hypertension than a monotherapy.

Septic pulmonary arteriovenous fistula. An unusual conduit for systemic embolization in right-sided valvular endocarditis.

PubMed

Stagaman, D J; Presti, C; Rees, C; Miller, D D

1990-06-01

Right-sided valvular (tricuspid, pulmonic) endocarditis is frequently complicated by septic pulmonary embolization. Systemic embolization may also rarely occur due to associated left-sided endocarditis or right-to-left shunting in patients with septal defects. This report documents the occurrence of systemic embolization causing a cerebrovascular accident in an intravenous drug abuser with recurrent tricuspid valve endocarditis due to an isolated peripheral septic pulmonary arteriovenous fistula. Noninvasive diagnosis of the fistula by cardiac auscultation, contrast echocardiography, and nuclear magnetic resonance imaging was confirmed by selective pulmonary angiography. Subselective balloon embolization of the pulmonary arteries feeding this fistula was accomplished.

The changing face of antihistamines and cardiac adverse drug reactions: a clinical perspective.

PubMed

Shaikh, W A

2000-07-01

Recent times have witnessed a qualitative shift in the recognition and management of adverse drug effects. Many of them occur in organs that are unconnected to the primary target of pharmacological action. Out of these, cardiac side-effects have drawn particular attention because of their potential to cause death. Starting with the early observations on antibiotics such as macrolides, followed by fluoroquinolones and others, the focus has now shifted to the antihistamine class of drugs which are used extensively by patients all over the world, thanks to the ever increasing levels of environmental pollution. The occurrence of prolonged QTc interval following treatment with terfenadine leading to ventricular tachycardia of torsades de points variety with a potentially fatal outcome has forced many regulatory authorities of the world to clamp a ban the use of this drug. Alerted by these developments, studies on a new member, followed by fluoroquinolones and others, the focus has now shifted to the antihistamine class of drugs which are used extensively by patients all over the world, thanks to the ever incresing levels of envrionmental pollution. The occurrence of prolonged QTc interval following treatment with terfenadine leading to ventricular tachycardia of torsades de points variety with a potentially fatal outcome has forced many regulatory authorities of the world to clamp a ban use of this drug. Alerted by these developments, studies on a new member of non-sedating antihistamine class viz, fexofenadine, have been reviewed especially because of the structural similarity between terfenadine and fexofenadine. It is now clear that despite the closeness of its chemical structure to terfenadine fexofenadine behaves in a different manner and does not affect the electrophysiology of the heart muscle tissue, as proved by data from extensive clinical trials as well as membrane models in vitro. Interestingly, the solitary false alarm that was sounded on the drug by a group of workers in the Netherlands was later rectified by the same group. Clinically speaking, the cardiovascular safety of fexofenadine has been convincingly demonstrated at various dose levels and various time intervals, alone and together with other drugs of potential toxigenicity. All things put together, it appears reasonable to conclude that fexofenadine is free from cardiovascular ADRs of clinical significance. It could also be concluded that cardiac side-effects of antihistamines is not a class effect.

Safety and feasibility of xenon as an adjuvant to sevoflurane anaesthesia in children undergoing interventional or diagnostic cardiac catheterization: study protocol for a randomised controlled trial.

PubMed

Devroe, Sarah; Lemiere, Jurgen; Van de Velde, Marc; Gewillig, Marc; Boshoff, Derize; Rex, Steffen

2015-03-04

Xenon has minimal haemodynamic side effects when compared to volatile or intravenous anaesthetics. Moreover, in in vitro and in animal experiments, xenon has been demonstrated to convey cardio- and neuroprotective effects. Neuroprotection could be advantageous in paediatric anaesthesia as there is growing concern, based on both laboratory studies and retrospective human clinical studies, that anaesthetics may trigger an injury in the developing brain, resulting in long-lasting neurodevelopmental consequences. Furthermore, xenon-mediated neuroprotection could help to prevent emergence delirium/agitation. Altogether, the beneficial haemodynamic profile combined with its putative organ-protective properties could render xenon an attractive option for anaesthesia of children undergoing cardiac catheterization. In a phase-II, mono-centre, prospective, single-blind, randomised, controlled study, we will test the hypothesis that the administration of 50% xenon as an adjuvant to general anaesthesia with sevoflurane in children undergoing elective cardiac catheterization is safe and feasible. Secondary aims include the evaluation of haemodynamic parameters during and after the procedure, emergence characteristics, and the analysis of peri-operative neuro-cognitive function. A total of 40 children ages 4 to 12 years will be recruited and randomised into two study groups, receiving either a combination of sevoflurane and xenon or sevoflurane alone. Children undergoing diagnostic or interventional cardiac catheterization are a vulnerable patient population, one particularly at risk for intra-procedural haemodynamic instability. Xenon provides remarkable haemodynamic stability and potentially has cardio- and neuroprotective properties. Unfortunately, evidence is scarce on the use of xenon in the paediatric population. Our pilot study will therefore deliver important data required for prospective future clinical trials. EudraCT: 2014-002510-23 (5 September 2014).

Early administration of trimetazidine may prevent or ameliorate diabetic cardiomyopathy.

PubMed

Wenmeng, Wang; Qizhu, Tang

2011-02-01

Diabetic cardiomyopathy is a type of cardiac dysfunction resulting from diabetes, independent of vascular or valvular pathology. It clinically manifests initially as asymptomatic diastolic dysfunction and then progresses to symptomatic heart failure. Two major contributors to the development of diabetic cardiomyopathy, which are unique to diabetes, are hyperglycemia and diabetes-related alterations in myocardial metabolism. Diabetes mellitus is characterized by reduced glucose and lactate metabolism and enhanced fatty acid metabolism, which are the early consequences of the disease. Studies on the effect of intensive glucose control on heart failure events in patients with diabetes have been conducted with neutral results. However, no study on the effect of metabolic modulators on the prevention of heart failure has been reported. Trimetazidine, a 3-ketoacyl coenzyme A thiolase (3-KAT) inhibitor, shifts cardiac energy metabolism from free fatty acid oxidation to glucose oxidation by inhibiting mitochondrial long-chain 3-KAT, and is used clinically as an effective antianginal agent. Studies have shown that trimetazidine improves heart function in patients with idiopathic cardiomyopathy and in diabetic patients with cardiac ischemia or heart failure. In addition to being effective, trimetazidine has only mild side effects. Therefore, instead of routine administration of trimetazidine for the treatment of diabetic cardiomyopathy, we hypothesize that the early application of trimetazidine may prevent or ameliorate diabetic cardiomyopathy. In addition to life style modifications, ACEI, ARB, and beta-blockers, which have been recommended in the past, trimetazidine should be administered to those patients with impaired glucose tolerance or patients in the early course of diabetes. In this way, we may reduce the prevalence of heart failure and improve the long-term survival of patients with diabetes through early normalization of the myocardial substrate metabolism. Copyright © 2010 Elsevier Ltd. All rights reserved.

Evaluation of XIENCE V everolimus-eluting and Taxus Express2 paclitaxel-eluting coronary stents in patients with jailed side branches from the SPIRIT IV trial at 2 years.

PubMed

Forrest, John K; Lansky, Alexandra J; Meller, Stephanie M; Hou, Liming; Sood, Poornima; Applegate, Robert J; Wang, John C; Skelding, Kimberly A; Shah, Aakar; Kereiakes, Dean J; Sudhir, Krishnankutty; Cristea, Ecaterina; Yaqub, Manejeh; Stone, Gregg W

2013-06-01

The aim of this study was to determine whether patients from the Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System in the Treatment of Patients With de Novo Native Coronary Artery Lesions (SPIRIT) IV trial who underwent percutaneous coronary intervention, who had target lesions with jailed side branches, had improved clinical outcomes when treated with the XIENCE V versus Taxus Express(2) drug-eluting stent. In the SPIRIT III randomized trial, patients with target lesions with jailed side branches after XIENCE V compared with Taxus Express(2) implantation had lower 2-year rates of major adverse cardiac events. The SPIRIT IV trial represents a larger more diverse patient population compared with SPIRIT III. In the large-scale, prospective, multicenter, randomized SPIRIT IV trial, 3,687 patients who underwent coronary stenting with up to 3 de novo native coronary artery lesions were randomized 2:1 to receive XIENCE V versus Taxus Express(2) stents. Two-year clinical outcomes of patients with or without jailed side branches after stenting were compared. A jailed side branch was defined as any side branch >1.0 mm in diameter within the target segment being stented, excluding bifurcations deemed to require treatment. Of the 3,687 patients in SPIRIT IV, a total of 1,426 had side branches that were jailed during angioplasty of the target lesion. Patients with jailed side branches after XIENCE V compared with Taxus Express(2) implantation had significantly lower 2-year rates of target lesion failure (6.5% vs 11.9%, p = 0.001), major adverse cardiac events (6.6% vs 12.2%, p = 0.0008), ischemia-driven target vessel revascularization (4.1% vs 7.9%, p = 0.004), and stent thrombosis (0.6% vs 2.8%, p = 0.001). In conclusion, patients with jailed side branches after stenting with XIENCE V compared to Taxus Express(2) devices had superior clinical outcomes at 2 years in the large-scale randomized SPIRIT IV trial. Copyright © 2013 Elsevier Inc. All rights reserved.

Successful implementation of perioperative beta-blockade utilizing a multidisciplinary approach.

PubMed

Armanious, Samuel; Wong, David T; Etchells, Edward; Higgins, Patrick; Chung, Frances

2003-02-01

To describe how we implemented a protocol for perioperative beta-blockade in patients with or at risk of coronary artery disease (CAD) undergoing major non-cardiac surgery and to present our results. After institutional approval, from May 1999 to April 2001, patients with surgical and medical indications (CAD as indicated by previous myocardial infarction, typical angina or atypical angina with a positive stress test or at least two risk factors for CAD: age 65 yr, hypertension, smoking, high cholesterol, diabetes mellitus) for perioperative beta-blockade were identified preoperatively by anesthesiology and referred to the General Internal Medicine Service (MED). MED initiated patients on outpatient beta-blockers. The intraoperative anesthetic management was left to the discretion of the anesthesiologist. In the postanesthesia care unit (PACU), patients received iv metoprolol according to hemodynamic criteria. Postoperatively, patients were followed by MED for adverse cardiac events. Sixty-nine patients received perioperative beta-blockade. Preoperatively, 60% were started on metoprolol, 39% on atenolol and 1% on propranolol. In PACU, 42%, 9% and 38% of patients were given iv metoprolol 0, 5 and 10 mg respectively. One patient was given glycopyrrolate in the PACU for bradycardia and none received vasoactive or inotropic agents. Three patients (4.3%) had postoperative cardiac events. With close collaboration between anesthesiologists, internists, PACU nurses and family physicians, a strategy for perioperative beta-blockade was implemented successfully in patients with cardiac risks. Beta-blockade was associated with few side effects and morbidities.

Implementing international sexual counselling guidelines in hospital cardiac rehabilitation: development of the CHARMS intervention using the Behaviour Change Wheel.

PubMed

Mc Sharry, J; Murphy, P J; Byrne, M

2016-10-10

Decreased sexual activity and sexual problems are common among people with cardiovascular disease, negatively impacting relationship satisfaction and quality of life. International guidelines recommend routine delivery of sexual counselling to cardiac patients. The Cardiac Health and Relationship Management and Sexuality (CHARMS) baseline study in Ireland found, similar to international findings, limited implementation of sexual counselling guidelines in practice. The aim of the current study was to develop the CHARMS multi-level intervention to increase delivery of sexual counselling by healthcare professionals. We describe the methods used to develop the CHARMS intervention following the three phases of the Behaviour Change Wheel approach: understand the behaviour, identify intervention options, and identify content and implementation options. Survey (n = 60) and focus group (n = 14) data from two previous studies exploring why sexual counselling is not currently being delivered were coded by two members of the research team to understand staff's capability, opportunity, and motivation to engage in the behaviour. All potentially relevant intervention functions to change behaviour were identified and the APEASE (affordability, practicability, effectiveness, acceptability, side effects and equity) criteria were used to select the most appropriate. The APEASE criteria were then used to choose between all behaviour change techniques (BCTs) potentially relevant to the identified functions, and these BCTs were translated into intervention content. The Template for Intervention Description and Replication (TIDieR) checklist was used to specify details of the intervention including the who, what, how and where of proposed intervention delivery. Providing sexual counselling group sessions by cardiac rehabilitation staff to patients during phase III cardiac rehabilitation was identified as the target behaviour. Education, enablement, modelling, persuasion and training were selected as appropriate intervention functions. Twelve BCTs, linked to intervention functions, were identified for inclusion and translated into CHARMS intervention content. This paper details the use of Behaviour Change Wheel approach to develop an implementation intervention in an under-researched area of healthcare provision. The systematic and transparent development of the CHARMS intervention will facilitate the evaluation of intervention effectiveness and future replication and contribute to the advancement of a cumulative science of implementation intervention design.

Trastuzumab-induced cardiotoxicity and its risk factors in real-world setting of breast cancer patients.

PubMed

Moilanen, Tiina; Jokimäki, Anna; Tenhunen, Olli; Koivunen, Jussi P

2018-06-05

Cardiotoxicity is the most important side effect of trastuzumab treatment. Heart function monitoring is recommended during the treatment which has led to growing use of resources. The aim of this retrospective study was to determine the frequency and timing of trastuzumab cardiotoxicity and its risk factors in real-world setting. Single institute, retrospective collection of data on HER2+ breast cancer patients (n = 246) was carried out through a pharmacy search for patients who had received trastuzumab in 2006-2014. Clinical and pathological factors, treatment history, EF measurements, cardiac medications, cardiovascular disease history, cardiac symptoms, and survival data were collected from patient records. 32 patients (13%) had EF decline ≥ 10%, eleven (4.5%) had EF decline ≥ 20% within 1 year after trastuzumab initiation, and trastuzumab was discontinued due to suspected cardiotoxicity in six patients (2.4%). 49 patients (19.9%) experienced symptoms related to cardiotoxicity during therapy, which accumulated among those with EF drop. Underlying cardiovascular diseases and multiple (≥ 2) cardiac medications were related to EF drop (≥ 20%) and trastuzumab discontinuation. Majority of EF drops (≥ 10%) and trastuzumab discontinuations were seen within 6months of trastuzumab initiation and recovery of EF drop to < 10% of the baseline was seen in most cases (62.5%). There was no statistically significant difference in the survival of patients according to EF drop. Trastuzumab cardiotoxicity seems to accumulate among patients with underlying cardiac conditions. EF monitoring could be targeted to risk groups without compromising of the cardiac health or survival of HER2-positive breast cancer patients.

Oxidative Inactivation of the Lipid Phosphatase Phosphatase and Tensin Homolog on Chromosome Ten (PTEN) as a Novel Mechanism of Acquired Long QT Syndrome*

PubMed Central

Wan, Xiaoping; Dennis, Adrienne T.; Obejero-Paz, Carlos; Overholt, Jeffrey L.; Heredia-Moya, Jorge; Kirk, Kenneth L.; Ficker, Eckhard

2011-01-01

The most common cause of cardiac side effects of pharmaco-therapy is acquired long QT syndrome, which is characterized by abnormal cardiac repolarization and most often caused by direct blockade of the cardiac potassium channel human ether a-go-go-related gene (hERG). However, little is known about therapeutic compounds that target ion channels other than hERG. We have discovered that arsenic trioxide (As2O3), a very potent antineoplastic compound for the treatment of acute promyelocytic leukemia, is proarrhythmic via two separate mechanisms: a well characterized inhibition of hERG/IKr trafficking and a poorly understood increase of cardiac calcium currents. We have analyzed the latter mechanism in the present study using biochemical and electrophysiological methods. We find that oxidative inactivation of the lipid phosphatase PTEN by As2O3 enhances cardiac calcium currents in the therapeutic concentration range via a PI3Kα-dependent increase in phosphatidylinositol 3,4,5-triphosphate (PIP3) production. In guinea pig ventricular myocytes, even a modest reduction in PTEN activity is sufficient to increase cellular PIP3 levels. Under control conditions, PIP3 levels are kept low by PTEN and do not affect calcium current amplitudes. Based on pharmacological experiments and intracellular infusion of PIP3, we propose that in guinea pig ventricular myocytes, PIP3 regulates calcium currents independently of the protein kinase Akt along a pathway that includes a secondary oxidation-sensitive target. Overall, our report describes a novel form of acquired long QT syndrome where the target modified by As2O3 is an intracellular signaling cascade. PMID:21097842

Advantages, Disadvantages, and Trend of Integrative Medicine in the Treatment of Heart Failure.

PubMed

Zhang, PeiYing

2015-06-01

Integrative medicine therapy using traditional Chinese medicine (TCM) combined with western medicine has shown some advantages in treating heart failure (HF), such as holistic concept; multi-target treatment; dialectical logic; personalized therapy; formulae compatibility; and reduction of side effects of western medicine. However, problems still exist in TCM treatment of HF, including non-uniformed categorization of TCM, lack of standardized syndrome differentiation and lack of an evidence base. The future of treatment of HF seems to be focused on reversing ventricular remodeling, improving cardiac rehabilitation, and accelerating experimental research and drug discovery in TCM.

Extrasystoles: side effect of kangaroo care?

PubMed

Kluthe, Christof; Wauer, Roland R; Rüdiger, Mario

2004-09-01

To present an unpublished reason for an arrhythmic electrocardiogram (ECG) recording during kangaroo care in a preterm infant. Case report. Preterm infant. A preterm infant exhibited cardiac arrhythmia on the ECG monitor during kangaroo care, leading to interruption of kangarooing. Arrhythmia disappeared after placing the baby back into the incubator. The most likely reasons for arrhythmia were excluded. However, arrhythmia reappeared upon continuation of kangaroo care. ECG monitoring revealed the reason for the monitoring error. ECG monitoring during kangaroo care should cause error because of superimposed electric activity from the parent. Oxygen saturation represents a more reliable method of monitoring during kangaroo care.

Acetyl-lysine erasers and readers in the control of pulmonary hypertension and right ventricular hypertrophy

PubMed Central

Stratton, Matthew S.; McKinsey, Timothy A.

2016-01-01

Acetylation of lysine residues within nucleosomal histone tails provides a crucial mechanism for epigenetic control of gene expression. Acetyl groups are coupled to lysine residues by histone acetyltransferases (HATs) and removed by histone deacetylases (HDACs), which are also commonly referred to as “writers” and “erasers”, respectively. In addition to altering the electrostatic properties of histones, lysine acetylation often creates docking sites for bromodomain-containing “reader” proteins. This review focuses on epigenetic control of pulmonary hypertension (PH) and associated right ventricular (RV) cardiac hypertrophy and failure. Effects of small molecule HDAC inhibitors in pre-clinical models of PH are highlighted. Furthermore, we describe the recently discovered role of bromodomain and extraterminal (BET) reader proteins in the control of cardiac hypertrophy, and provide evidence suggesting that one member of this family, BRD4, contributes to the pathogenesis of RV failure. Together, the data suggest intriguing potential for pharmacological epigenetic therapies for the treatment of PH and right-sided heart failure. PMID:25707943

Laughter and MIRTH (Methodical Investigation of Risibility, Therapeutic and Harmful): narrative synthesis.

PubMed

Ferner, R E; Aronson, J K

2013-12-12

To review the beneficial and harmful effects of laughter. Narrative synthesis. We searched Medline (1946 to June 2013) and Embase (1974 to June 2013) for reports of benefits or harms from laughter in humans, and counted the number of papers in each category. Benefits of laughter include reduced anger, anxiety, depression, and stress; reduced tension (psychological and cardiovascular); increased pain threshold; reduced risk of myocardial infarction (presumably requiring hearty laughter); improved lung function; increased energy expenditure; and reduced blood glucose concentration. However, laughter is no joke-dangers include syncope, cardiac and oesophageal rupture, and protrusion of abdominal hernias (from side splitting laughter or laughing fit to burst), asthma attacks, interlobular emphysema, cataplexy, headaches, jaw dislocation, and stress incontinence (from laughing like a drain). Infectious laughter can disseminate real infection, which is potentially preventable by laughing up your sleeve. As a side effect of our search for side effects, we also list pathological causes of laughter, among them epilepsy (gelastic seizures), cerebral tumours, Angelman's syndrome, strokes, multiple sclerosis, and amyotrophic lateral sclerosis or motor neuron disease. Laughter is not purely beneficial. The harms it can cause are immediate and dose related, the risks being highest for Homeric (uncontrollable) laughter. The benefit-harm balance is probably favourable. It remains to be seen whether sick jokes make you ill or jokes in bad taste cause dysgeusia, and whether our views on comedians stand up to further scrutiny.

Gastroesophageal junction of Anatolian shepherd dog; a study by topographic anatomy, scanning electron and light microscopy.

PubMed

Alsafy, M A M; El-Gendy, S A A

2012-03-01

The aim of this study was to cast a spotlight on the topography and to point out the clinical importance of the gastroesophageal junction (GEJ) in Anatolian Shepherd dogs. Nine Anatolian Shepherd dogs were used to study the morphology of the GEJ. The esophagus was appeared has a portion within the thoracic cavity while no portion of the esophagus presented within the abdominal cavity that documented the absence of the intra-abdominal portion in all studied dogs. The topographic anatomy, scanning electron and light microscopic examinations revealed that the gastroesophageal junction was located at the level of the phrenico-esophageal ligament (PEL) inside the esophageal hiatus. Our results were distinguished the morphology of the esophageal and gastric cardiac mucosa at the level of the gastroesophageal junction by the scanning electron micrographs. The light microscopical examination was explained the PEL attached to the esophageal side in one dog and to the gastric cardiac side in three dogs.

Right Heart Failure in an African Penguin ( Spheniscus demersus ).

PubMed

Cusack, Lara; Field, Cara; McDermott, Alexa; Pogue, Brandon; Clauss, Tonya; Bossart, Gregory; Camus, Alvin

2016-09-01

A 19-year-old male African penguin ( Spheniscus demersus ) was presented with coelomic distention after a 6-week history of lethargy and decreased appetite. Results of radiographs showed loss of coelomic detail, and ultrasound and computed tomography results revealed coelomic fluid and dilated hepatic veins. Echocardiography revealed moderate right atrial enlargement. Findings were consistent with right-sided cardiac disease. Treatment with furosemide initially reduced ascites, but the clinical condition worsened weeks later and enalapril, pimobendan, and sildenafil were added to the medical therapy. At 12 weeks after presentation, results of an echocardiogram revealed persistent right atrioventricular valve regurgitation, moderate ascites, and dilation of hepatic veins. Clinical signs of right heart failure were managed through adjustments in medical therapy and coelomic fluid aspiration, but the bird died 18 weeks after initial presentation. Gross and microscopic findings were consistent with valvular insufficiency and right-sided heart failure. To our knowledge, this case is the first documented report of cardiac disease in an African penguin.

Loeffler endocarditis as a rare cause of heart failure with preserved ejection fraction: A case report and review of literature.

PubMed

Gao, Ming; Zhang, Weihua; Zhao, Waiou; Qin, Ling; Pei, Fei; Zheng, Yang

2018-03-01

Hypereosinophilic syndrome (HES) is a rare disease characterized by hypereosinophilia and its ensuing organ damage. Cardiac involvement is divided into 3 chronological stages: an acute necrotic stage; a thrombus formation stage; and a fibrotic stage. Infiltration of the myocardium by eosinophilic cells followed by endomyocardial fibrosis is known as "Loeffler endocarditis." We report a case of a 60-year-old man diagnosed with left-sided restrictive cardiomyopathy. The patient experienced heart failure with preserved ejection fraction. The cardiac MRI showed intense, linear, delayed gadolinium enhancement of the endocardium of the lateral wall of the left ventricle, and obliteration of the LV apex. He was ultimately identified as Loeffler endocarditis. A bone marrow smear and biopsy revealed the FIP1L1-PDGFRA fusion gene was positive in 82% of segmented nucleated cells. Our patient responded well to prednisone at 1 mg/kg/d. HES is a rare disease that often afflicts the heart. Cardiac involvement in hypereosinophilia, especially Loeffler endocarditis, carries a poor prognosis and significant mortality. Early detection and treatment of the disease is therefore essential. Further studies are needed to ascertain therapeutic corticosteroid dosages and develop targeted gene therapies, both important steps to ameliorate the effects of Loeffler endocarditis and improve patient outcomes.

Tricuspid regurgitation: contemporary management of a neglected valvular lesion.

PubMed

Irwin, Richard Bruce; Luckie, Matthew; Khattar, Rajdeep S

2010-11-01

Right-sided cardiac valvular disease has traditionally been considered less clinically important than mitral or aortic valve pathology. However, detectable tricuspid regurgitation (TR) is common and recent data suggest that significant TR can lead to functional impairment and reduced survival, particularly in patients with concomitant left-sided valvular disease. The tricuspid valve is a complex anatomical structure and advances in three dimensional echocardiography and cardiac MRI have contributed to a greater understanding of tricuspid valve pathology. These imaging techniques are invaluable in determining the aetiology and severity of TR, and provide an assessment of right ventricular function and pulmonary artery pressure. TR is more prevalent in women and those with a history of myocardial infarction and heart failure. It also occurs in about 10% of patients with rheumatic heart disease. Chronic severe TR may have a prolonged clinical course culminating in the development of fatigue and poor exercise tolerance due to a reduced cardiac output. Approximately 90% of cases of TR are secondary to either pulmonary hypertension or intrinsic right ventricular pathology and about 10% are due to primary tricuspid valve disease. Primary causes such as Ebstein's anomaly, rheumatic disease, myxomatous changes, carcinoid syndrome, endomyocardial fibrosis, and degenerative disease have characteristic morphological features readily identifiable by echocardiography. Ascertaining an accurate right ventricular systolic pressure is important in separating primary from secondary causes as significant TR with a pressure <40 mm Hg implies intrinsic valve disease. Cardiac MRI may be indicated in those with inadequate echocardiographic images and is also the gold standard for the evaluation of right ventricular function and morphology. The assessment of leaflet morphology, annular dimensions, and pulmonary artery pressure are particularly important for determining subsequent management. Along with appropriate treatment of the underlying cause of TR and pulmonary hypertension, management guidelines indicate a move towards more aggressive treatment of TR. In those undergoing left-sided valve surgery, tricuspid valve repair is universally recommended in the presence of severe coexistent TR; in those with isolated severe TR, surgery is recommended in the presence of symptoms or progressive right ventricular dilatation or dysfunction.

Acute peri-operative beta blockade in intermediate-risk patients.

PubMed

Biccard, B M; Sear, J W; Foëx, P

2006-10-01

Peri-operative beta-blockade has been shown to reduce the incidence of postoperative cardio- vascular complications including cardiac death in high-risk non-cardiac surgical patients. However, the recent analysis by Lindenauer et al. suggests that it is inappropriate to administer beta-blockers blindly to all surgical patients. In an attempt to determine the appropriateness of peri-operative beta-blocker administration across patients with a spectrum of cardiovascular risks, we have examined studies of intermediate-risk patient groups (that is those undergoing intermediate risk surgery or those with a Lee Revised Cardiac Risk Score of < or =2). We analysed data from randomised prospective studies of the effects of acute peri-operative beta-blockade on the incidence of peri-operative myocardial ischaemia. By examining the demographics and surgical interventions in these patients, we have compared these studies with other studies of peri-operative silent myocardial ischaemia representing patients of similar risk. We thus estimated the expected long-term postoperative cardiovascular complication rate associated with myocardial ischaemia in these patients in terms of number needed to treat for ischaemia prevention and for prevention of major cardiovascular complications. Prevention of peri-operative myocardial ischaemia with acute beta-blockade in non-cardiac surgical patients with 1-2 RCRI clinical risk factors can be achieved with a number needed to treat of 10. It is not associated with a significant increase in drug associated side-effects. However, acute beta-blockade shows no real benefit in the prevention of major cardiovascular complications in intermediate risk non-vascular surgical patients with a number-needed-to-treat of 833. Vascular surgical patients undergoing intermediate-risk surgery may benefit from the protective effects of acute peri-operative beta-blockade, however, with a number-needed-to-treat of 68 it would require a randomised clinical trial of over 24,000 patients to prove their efficacy.

A randomised clinical trial of comprehensive cardiac rehabilitation versus usual care for patients treated for infective endocarditis—the CopenHeartIE trial protocol

PubMed Central

Rasmussen, Trine Bernholdt; Zwisler, Ann-Dorthe; Sibilitz, Kirstine Lærum; Risom, Signe Stelling; Bundgaard, Henning; Gluud, Christian; Moons, Philip; Winkel, Per; Thygesen, Lau Caspar; Hansen, Jane Lindschou; Norekvål, Tone Merete; Berg, Selina Kikkenborg

2012-01-01

Introduction Infective endocarditis (IE) is among the most serious infectious diseases in the western world. Treatment requires lengthy hospitalisation, high-dosage antibiotic therapy and possible valve replacement surgery. Despite advances in treatment, the 1-year mortality remains at 20–40%. Studies indicate that patients experience persisting physical symptoms, diminished quality of life and difficulties returning to work up to a year postdischarge. No studies investigating the effects of rehabilitation have been published. We present the rationale and design of the CopenHeartIE trial, which investigates the effect of comprehensive cardiac rehabilitation versus usual care for patients treated for IE. Methods and analysis We will conduct a randomised clinical trial to investigate the effects of comprehensive cardiac rehabilitation versus usual care on the physical and psychosocial functioning of patients treated for IE. The trial is a multicentre, parallel design trial with 1 : 1 individual randomisation to either the intervention or control group. The intervention consists of five psychoeducational consultations provided by specialised nurses and a 12-week exercise training programme. The primary outcome is mental health (MH) measured by the standardised Short Form 36 (SF-36). The secondary outcome is peak oxygen uptake measured by the bicycle ergospirometry test. Furthermore, a number of exploratory analyses will be performed. Based on sample size calculation, 150 patients treated for left-sided (native or prosthetic valve) or cardiac device endocarditis will be included in the trial. A qualitative and a survey-based complementary study will be undertaken, to investigate postdischarge experiences of the patients. A qualitative postintervention study will explore rehabilitation participation experiences. Ethics and dissemination The study complies with the Declaration of Helsinki and was approved by the regional research ethics committee (no H-1-2011-129) and the Danish Data Protection Agency (no 2007-58-0015). Study findings will be disseminated widely through peer-reviewed publications and conference presentations. Registration Clinicaltrials.gov identifier: NCT01512615. PMID:23175738

A randomised clinical trial of comprehensive cardiac rehabilitation versus usual care for patients treated for infective endocarditis--the CopenHeartIE trial protocol.

PubMed

Rasmussen, Trine Bernholdt; Zwisler, Ann-Dorthe; Sibilitz, Kirstine Lærum; Risom, Signe Stelling; Bundgaard, Henning; Gluud, Christian; Moons, Philip; Winkel, Per; Thygesen, Lau Caspar; Hansen, Jane Lindschou; Norekvål, Tone Merete; Berg, Selina Kikkenborg

2012-01-01

Infective endocarditis (IE) is among the most serious infectious diseases in the western world. Treatment requires lengthy hospitalisation, high-dosage antibiotic therapy and possible valve replacement surgery. Despite advances in treatment, the 1-year mortality remains at 20-40%. Studies indicate that patients experience persisting physical symptoms, diminished quality of life and difficulties returning to work up to a year postdischarge. No studies investigating the effects of rehabilitation have been published. We present the rationale and design of the CopenHeart(IE) trial, which investigates the effect of comprehensive cardiac rehabilitation versus usual care for patients treated for IE. We will conduct a randomised clinical trial to investigate the effects of comprehensive cardiac rehabilitation versus usual care on the physical and psychosocial functioning of patients treated for IE. The trial is a multicentre, parallel design trial with 1 : 1 individual randomisation to either the intervention or control group. The intervention consists of five psychoeducational consultations provided by specialised nurses and a 12-week exercise training programme. The primary outcome is mental health (MH) measured by the standardised Short Form 36 (SF-36). The secondary outcome is peak oxygen uptake measured by the bicycle ergospirometry test. Furthermore, a number of exploratory analyses will be performed. Based on sample size calculation, 150 patients treated for left-sided (native or prosthetic valve) or cardiac device endocarditis will be included in the trial. A qualitative and a survey-based complementary study will be undertaken, to investigate postdischarge experiences of the patients. A qualitative postintervention study will explore rehabilitation participation experiences. The study complies with the Declaration of Helsinki and was approved by the regional research ethics committee (no H-1-2011-129) and the Danish Data Protection Agency (no 2007-58-0015). Study findings will be disseminated widely through peer-reviewed publications and conference presentations. Clinicaltrials.gov identifier: NCT01512615.

[Histopathological and immunohistochemical features of cardiac myxomas].

PubMed

Hernández-Bringas, Omar; Ortiz-Hidalgo, Carlos

2013-01-01

Mixomas are the most common primary cardiac tumors with an estimate incidence of 0,5-1 per 10(6) individuals per year. These tumors have generated interest due to their unique location (left side of the atrial septum near the fossa ovalis), variable clinical presentation and undefined histogenesis. Most cardiac myxomas occur sporadically while approximately 10% of diagnosed cases develop as part of Carney complex. This neoplasm is of uncertain histogenesis, however, endothelial, neurogenic, fibroblastic, and cardiac and smooth muscle cells differentiation has been proposed, and rarely glandular differentiation has been observed. Recently, due to the expression of certain cardiomyocyte-specific factors, an origin of mesenchymal cardiomyocytes progenitor cells has been suggested. Histologically cardiac myxomas are mainly composed of stellated, fusiform and polygonal cells, immersed in an amorphous myxoid matrix. Immunohistochemically some endothelial markers, such as CD31, CD34, FVIIIAg, are present. Positive staining has also been reported for S-100 protein, calretinin, vimentin, desmin, smooth muscle myosin, CD56, α1 antitrypsin and α 1antichymotrypsin. Surgical resection is currently the only treatment of choice. We present in this article a histopathological and immunohistochemical review of cardiac myxomas. Copyright © 2012 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

Cardiac risk index as a simple geometric indicator to select patients for the heart-sparing radiotherapy of left-sided breast cancer.

PubMed

Sung, KiHoon; Choi, Young Eun; Lee, Kyu Chan

2017-06-01

This is a dosimetric study to identify a simple geometric indicator to discriminate patients who meet the selection criterion for heart-sparing radiotherapy (RT). The authors proposed a cardiac risk index (CRI), directly measurable from the CT images at the time of scanning. Treatment plans were regenerated using the CT data of 312 consecutive patients with left-sided breast cancer. Dosimetric analysis was performed to estimate the risk of cardiac mortality using cardiac dosimetric parameters, such as the relative heart volumes receiving ≥25 Gy (heart V 25 ). For each CT data set, in-field heart depth (HD) and in-field heart width (HW) were measured to generate the geometric parameters, including maximum HW (HW max ) and maximum HD (HD max ). Seven geometric parameters were evaluated as candidates for CRI. Receiver operating characteristic (ROC) curve analyses were used to examine the overall discriminatory power of the geometric parameters to select high-risk patients (heart V 25  ≥ 10%). Seventy-one high-risk (22.8%) and 241 low-risk patients (77.2%) were identified by dosimetric analysis. The geometric and dosimetric parameters were significantly higher in the high-risk group. Heart V 25 showed the strong positive correlations with all geometric parameters examined (r > 0.8, p < 0.001). The product of HD max and HW max (CRI) revealed the largest area under the curve (AUC) value (0.969) and maintained 100% sensitivity and 88% specificity at the optimal cut-off value of 14.58 cm 2 . Cardiac risk index proposed as a simple geometric indicator to select high-risk patients provides useful guidance for clinicians considering optimal implementation of heart-sparing RT. © 2016 The Royal Australian and New Zealand College of Radiologists.

Niacin Promotes Cardiac Healing after Myocardial Infarction through Activation of the Myeloid Prostaglandin D2 Receptor Subtype 1

PubMed Central

Kong, Deping; Li, Juanjuan; Shen, Yujun; Liu, Guizhu; Zuo, Shengkai; Tao, Bo; Ji, Yong; Lu, Ankang; Lazarus, Michael; Breyer, Richard M.

2017-01-01

Niacin is a well established drug used to lower cholesterol and prevent cardiovascular disease events. However, niacin also causes cutaneous flushing side effects due to release of the proresolution mediator prostaglandin D2 (PGD2). Recent randomized clinical trials have demonstrated that addition of niacin with laropiprant [a PGD2 receptor subtype 1 (DP1) blocker] to statin-based therapies does not significantly decrease the risk of cardiovascular disease events, but increases the risk of serious adverse events. Here, we tested whether, and how, niacin beneficial effects on myocardial ischemia require the activation of the PGD2/DP1 axis. Myocardial infarction (MI) was reproduced by ligation of the left anterior descending branch of the coronary artery in mice. We found that niacin increased PGD2 release in macrophages and shifted macrophages to M2 polarization both in vitro and in vivo by activation of DP1 and accelerated inflammation resolution in zymosan-induced peritonitis in mice. Moreover, niacin treatment facilitated wound healing and improved cardiac function after MI through DP1-mediated M2 bias and timely resolution of inflammation in infarcted hearts. In addition, we found that niacin intake also stimulated M2 polarization of peripheral monocytes in humans. Collectively, niacin promoted cardiac functional recovery after ischemic myocardial infarction through DP1-mediated M2 polarization and timely resolution of inflammation in hearts. These results indicated that DP1 inhibition may attenuate the cardiovascular benefits of niacin. PMID:28057839

Single therapeutic and supratherapeutic doses of sacubitril/valsartan (LCZ696) do not affect cardiac repolarization.

PubMed

Langenickel, Thomas H; Jordaan, Pierre; Petruck, Jesika; Kode, Kiran; Pal, Parasar; Vaidya, Soniya; Chandra, Priya; Rajman, Iris

2016-08-01

Sacubitril/valsartan (LCZ696) is a first-in-class angiotensin receptor neprilysin inhibitor (ARNI) indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in patients with chronic heart failure (NYHA class II-IV) and reduced ejection fraction. This study was aimed to evaluate the effect of single oral therapeutic (400 mg) and supratherapeutic (1200 mg) doses of LCZ696 on cardiac repolarization. This randomized double-blind crossover study in healthy male subjects compared the effect of therapeutic and supratherapeutic doses of LCZ696 with placebo and moxifloxacin 400 mg (open-label treatment) as positive control. The primary assessment was mean baseline- and placebo-corrected QTcF (∆∆QTcF; Fridericia correction). Additional assessments included the ∆∆QTcB (Bazett's correction), PR interval, QRS duration, heart rate (HR), LCZ696 pharmacokinetics, pharmacokinetic/pharmacodynamic relationships, and safety. Of the 84 subjects enrolled, 81 completed the study. The maximum upper bound of the two-sided 90 % confidence interval for ∆∆QTcF for LCZ696 400 mg and 1200 mg were <10 ms, and assay sensitivity was confirmed with moxifloxacin. No relevant treatment-emergent changes were observed in any of the ECG-derived parameters with LCZ696 or placebo, and the incidence of adverse events was comparable among the treatment groups. Single therapeutic and supratherapeutic doses of LCZ696 did not affect cardiac repolarization as defined by the E14 ICH guidelines.

Intravenous Acetaminophen as an Adjunct Analgesic in Cardiac Surgery Reduces Opioid Consumption But Not Opioid-Related Adverse Effects: A Randomized Controlled Trial.

PubMed

Jelacic, Srdjan; Bollag, Laurent; Bowdle, Andrew; Rivat, Cyril; Cain, Kevin C; Richebe, Philippe

2016-08-01

The authors hypothesized that intravenous acetaminophen as an adjunct analgesic would significantly decrease 24-hour postoperative opioid consumption. Double-blind, randomized, placebo-controlled trial. A single academic medical center. The study was comprised of 68 adult patients undergoing cardiac surgery. Patients were assigned randomly to receive either 1,000 mg of intravenous acetaminophen or placebo immediately after anesthesia induction, at the end of surgery, and then every 6 hours for the first 24 hours in the intensive care unit, for a total of 6-1,000 mg doses. The primary outcome was 24-hour postoperative opioid consumption. The secondary outcomes included 48-hour postoperative opioid consumption, incisional pain scores, opioid-related adverse effects, length of mechanical ventilation, length of intensive care unit stay, and the extent of wound hyperalgesia assessed at 24 and 48 hours postoperatively. The mean±standard deviation postoperative 24-hour opioid consumption expressed in morphine equivalents was significantly less in the acetaminophen group (45.6±29.5 mg) than in the placebo group (62.3±29.5 mg), representing a 27% reduction in opioid consumption (95% CI, 2.3-31.1 mg; p = 0.024). There were no differences in pain scores and opioid-related adverse effects between the 2 groups. A significantly greater number of patients in the acetaminophen group responded "very much" and "extremely well" when asked how their overall pain experience met their expectation (p = 0.038). The administration of intravenous acetaminophen during cardiac surgery and for the first 24 hours postoperatively reduced opioid consumption and improved patient satisfaction with their overall pain experience but did not reduce opioid side effects. Copyright © 2016 Elsevier Inc. All rights reserved.

Conventional and right-sided screening for subcutaneous ICD in a population with congenital heart disease at high risk of sudden cardiac death.

PubMed

Alonso, Pau; Osca, Joaquín; Rueda, Joaquín; Cano, Oscar; Pimenta, Pedro; Andres, Ana; Sancho, María José; Martinez, Luis

2017-11-01

Information regarding suitability for subcutaneous defibrillator (sICD) implantation in tetralogy of Fallot (ToF) and systemic right ventricle is scarce and needs to be further explored. The main objective of our study was to determine the proportion of patients with ToF and systemic right ventricle eligible for sICD with both, standard and right-sided screening methods. Secondary objectives were: (i) to study sICD eligibility specifically in patients at high risk of sudden cardiac death, (ii) to identify independent predictors for sICD eligibility, and (iii) to compare the proportion of eligible patients in a nonselected ICD population. We recruited 102 patients with ToF, 33 with systemic right ventricle, and 40 consecutive nonselected patients. Conventional electrocardiographic screening was performed as usual. Right-sided alternative screening was studied by positioning the left-arm and right-arm electrodes 1 cm right lateral of the xiphoid midline. The Boston Scientific ECG screening tool was utilized. In high-risk patients with ToF, eligibility was higher with right-sided screening in comparison with standard screening (61% vs. 44%; p = .018). Eligibility in high-risk right ventricle population was identical with both screening methods (77%, p = ns). The only independent predictor for sICD eligibility was QRS duration. In high-risk patients with ToF, right-sided implantation of the sICD could be an alternative to a conventional ICD. In patients with a systemic right ventricle, implantation of a sICD is an alternative to a conventional sICD. © 2017 Wiley Periodicals, Inc.

Left ventricular inflow tract obstruction secondary to a myxoma in a dog.

PubMed

Fernandez-del Palacio, M Josefa; Sanchez, Joaquin; Talavera, Jesus; Martínez, Carlos

2011-01-01

This is the first description of a left ventricular inflow tract obstruction secondary to a myxoma in a dog. A 4 yr old, male fox terrier presented with a 1 mo history of cough and exercise intolerance. Expiratory dyspnea, pulmonary crackles, irregular cardiac rhythm, and a grade 4/6 pansystolic cardiac murmur over the left cardiac apex were the most important features on physical examination. The electrocardiogram revealed atrial fibrillation. Thoracic radiographs showed left-sided cardiac enlargement and mild pulmonary edema, especially in the hilar area. Two-dimensional transthoracic echocardiography showed severe left atrial dilation and a homogenous, echodense mass involving both leaflets of the mitral valve and the posteromedial papillary muscle, inducing mitral stenosis. Spectral Doppler echocardiography was consistent with severe left ventricular inflow tract obstruction secondary to a mass. Therapy for congestive heart failure was prescribed. Follow-up examinations of the dog 1 mo, 2 mo, and 6 mo after diagnosis showed an improvement in clinical signs, but similar echocardiographic features. Eleven months after diagnosis, the dog was euthanized at the owner's request because of recurrent congestive heart failure. The postmortem examination showed the cardiac tumor was consistent with a myxoma.

Quantifying the correlation between photoplethysmography and laser Doppler flowmetry microvascular low-frequency oscillations

NASA Astrophysics Data System (ADS)

Mizeva, Irina; Di Maria, Costanzo; Frick, Peter; Podtaev, Sergey; Allen, John

2015-03-01

Photoplethysmography (PPG) and laser Doppler flowmetry (LDF) are two recognized optical techniques that can track low-frequency perfusion changes in microcirculation. The aim of this study was to determine, in healthy subjects, the correlation between the techniques for specific low-frequency bands previously defined for microcirculation. Twelve healthy male subjects (age range 18 to 50 years) were studied, with PPG and LDF signals recorded for 20 min from their right and left index (PPG) and middle (LDF) fingers. Wavelet analysis comprised dividing the low-frequency integral wavelet spectrum (IWS) into five established physiological bands relating to cardiac, respiratory, myogenic, neurogenic, and endothelial activities. The correlation between PPG and LDF was quantified using wavelet correlation analysis and Spearman correlation analysis of the median IWS amplitude. The median wavelet correlation between signals (right-left side average) was 0.45 (cardiac), 0.49 (respiratory), 0.86 (myogenic), 0.91 (neurogenic), and 0.91 (endothelial). The correlation of IWS amplitude values (right-left side average) was statistically significant for the cardiac (ρ=0.64, p<0.05) and endothelial (ρ=0.62, p<0.05) bands. This pilot study has shown good correlation between PPG and LDF for specific physiological frequency bands. In particular, the results suggest that PPG has the potential to be a low-cost replacement for LDF for endothelial activity assessments.

Impact of Doxorubicin Treatment on the Physiological Functions of White Adipose Tissue

PubMed Central

Cruz, Maysa Mariana; Cunha, Roberta D. C.; Alonso-Vale, Maria Isabel; Oyama, Lila Missae; Nascimento, Claudia M. Oller; Pimentel, Gustavo Duarte; dos Santos, Ronaldo V. T.; Lira, Fabio Santos

2016-01-01

White adipose tissue (WAT) plays a fundamental role in maintaining energy balance and important endocrine functions. The loss of WAT modifies adipokine secretion and disrupts homeostasis, potentially leading to severe metabolic effects and a reduced quality of life. Doxorubicin is a chemotherapeutic agent used clinically because of its good effectiveness against various types of cancer. However, doxorubicin has deleterious effects in many healthy tissues, including WAT, liver, and skeletal and cardiac muscles. Our objective was to investigate the effects of doxorubicin on white adipocytes through in vivo and in vitro experiments. Doxorubicin reduced the uptake of glucose by retroperitoneal adipocytes and 3T3-L1 cells via the inhibition of AMP-activated protein kinase Thr172 phosphorylation and glucose transporter 4 content. Doxorubicin also reduced the serum level of adiponectin and, to a greater extent, the expression of genes encoding lipogenic (Fas and Acc) and adipogenic factors (Pparg, C/ebpa, and Srebp1c) in retroperitoneal adipose tissue. In addition, doxorubicin inhibited both lipogenesis and lipolysis and reduced the hormone-sensitive lipase and adipose tissue triacylglycerol lipase protein levels. Therefore, our results demonstrate the impact of doxorubicin on WAT. These results are important to understand some side effects observed in patients receiving chemotherapy and should encourage new adjuvant treatments that aim to inhibit these side effects. PMID:27015538

A Voluntary Breath-Hold Treatment Technique for the Left Breast With Unfavorable Cardiac Anatomy Using Surface Imaging

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

Gierga, David P., E-mail: dgierga@partners.org; Harvard Medical School, Boston, Massachusetts; Turcotte, Julie C.

2012-12-01

Purpose: Breath-hold (BH) treatments can be used to reduce cardiac dose for patients with left-sided breast cancer and unfavorable cardiac anatomy. A surface imaging technique was developed for accurate patient setup and reproducible real-time BH positioning. Methods and Materials: Three-dimensional surface images were obtained for 20 patients. Surface imaging was used to correct the daily setup for each patient. Initial setup data were recorded for 443 fractions and were analyzed to assess random and systematic errors. Real time monitoring was used to verify surface placement during BH. The radiation beam was not turned on if the BH position difference wasmore » greater than 5 mm. Real-time surface data were analyzed for 2398 BHs and 363 treatment fractions. The mean and maximum differences were calculated. The percentage of BHs greater than tolerance was calculated. Results: The mean shifts for initial patient setup were 2.0 mm, 1.2 mm, and 0.3 mm in the vertical, longitudinal, and lateral directions, respectively. The mean 3-dimensional vector shift was 7.8 mm. Random and systematic errors were less than 4 mm. Real-time surface monitoring data indicated that 22% of the BHs were outside the 5-mm tolerance (range, 7%-41%), and there was a correlation with breast volume. The mean difference between the treated and reference BH positions was 2 mm in each direction. For out-of-tolerance BHs, the average difference in the BH position was 6.3 mm, and the average maximum difference was 8.8 mm. Conclusions: Daily real-time surface imaging ensures accurate and reproducible positioning for BH treatment of left-sided breast cancer patients with unfavorable cardiac anatomy.« less

Exercise and the right ventricle: a potential Achilles' heel.

PubMed

La Gerche, Andre; Rakhit, Dhrubo J; Claessen, Guido

2017-10-01

Exercise is associated with unequivocal health benefits and results in many structural and functional changes of the myocardium that enhance performance and prevent heart failure. However, intense exercise also presents a significant hemodynamic challenge in which the right-sided heart chambers are exposed to a disproportionate increase in afterload and wall stress that can manifest as myocardial fatigue or even damage if intense exercise is sustained for prolonged periods. This review focuses on the physiological factors that result in a disproportionate load on the right ventricle during exercise and the long-term consequences. The changes in cardiac structure and function that define 'athlete's heart' disproportionately affect the right-sided heart chambers and this can raise important diagnostic overlap with some cardiac pathologies, particularly some inherited cardiomyopathies. The interaction between exercise and arrhythmogenic right ventricular cardiomyopathy (ARVC) will be highlighted as an important example of how hemodynamic stressors can combine with deficiencies in cardiac structural elements to cause cardiac dysfunction predisposing to arrhythmias. The extent to which extreme exercise can cause adverse remodelling in the absence of a genetic predisposition remains controversial. In the athlete with profound changes in heart structure, it can be extremely challenging to determine whether common symptoms such as palpitations may be a marker of more sinister arrhythmias. This review discusses some of the techniques that have recently been proposed to identify pathology in these circumstances. Finally, we will discuss recent evidence defining the role of exercise restriction as a therapeutic intervention in individuals predisposed to arrhythmogenic cardiomyopathy. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Mining relational paths in integrated biomedical data.

PubMed

He, Bing; Tang, Jie; Ding, Ying; Wang, Huijun; Sun, Yuyin; Shin, Jae Hong; Chen, Bin; Moorthy, Ganesh; Qiu, Judy; Desai, Pankaj; Wild, David J

2011-01-01

Much life science and biology research requires an understanding of complex relationships between biological entities (genes, compounds, pathways, diseases, and so on). There is a wealth of data on such relationships in publicly available datasets and publications, but these sources are overlapped and distributed so that finding pertinent relational data is increasingly difficult. Whilst most public datasets have associated tools for searching, there is a lack of searching methods that can cross data sources and that in particular search not only based on the biological entities themselves but also on the relationships between them. In this paper, we demonstrate how graph-theoretic algorithms for mining relational paths can be used together with a previous integrative data resource we developed called Chem2Bio2RDF to extract new biological insights about the relationships between such entities. In particular, we use these methods to investigate the genetic basis of side-effects of thiazolinedione drugs, and in particular make a hypothesis for the recently discovered cardiac side-effects of Rosiglitazone (Avandia) and a prediction for Pioglitazone which is backed up by recent clinical studies.

Nebivolol Induced Hyperkalemia: Case Report

PubMed

Altabas, Karmela; Altabas, Velimir; Gulin, Tonko

2016-12-01

In this article, we document a conclusive case of nebivolol-induced hyperkalemia for the first time in the known medical literature. Hyperkalemia is associated with serious conditions such as cardiac arrhythmias and sudden cardiac death. Nebivolol was not known to cause hyperkalemia, and this event is not listed in its summary of product characteristics (SmPC). For older beta blockers, hyperkalemia is recognized as a rare adverse event linked to cytochrome P450 2D6 (CYP2D6) polymorphism and poor drug degradation. Our patient, a 47-year-old woman taking nebivolol for hypertension developed persistent hyperkalemia, with serum potassium levels up to 6.4 mmol/L. After extensive diagnostic evaluation and exclusion of other known conditions leading to hyperkalemia, its cause remained occult. Since hyperkalemia coincided with increased doses of nebivolol, dose reduction and discontinuation were attempted, resulting in normalized serum potassium. Poor drug metabolism could not explain this adverse effect, since pharmacogenetic testing showed no relevant aberrations. In conclusion, hyperkalemia is a harmful adverse event with possible lethal outcome, and it may be caused by nebivolol. Therefore, medical professionals have to be aware of this side effect and hyperkalemia should be listed as an adverse event in nebivolol SmPC.

[Comparison of the effects of phosphodiesterase III inhibitors, milrinone and olprinone, in infant corrective cardiac surgery].

PubMed

Sakimura, Shotaro; Yoshino, Jun; Izumi, Kaoru; Jimi, Nobuo; Sumiyoshi, Rieko; Mizuno, Keiichiro

2013-05-01

Clinical characteristics of phosphodiesterase (PDE) III inhibitors, milrinone and olprinone, is not fully understood in infants. We therefore retrospectively examined the hemodynamics, metabolism, and oxygenation of two different PDE III inhibitors in infants undergoing radical correction of ventricular septal defect with pulmonary hypertension. Twenty-six infants with pulmonary hypertension undergoing ventricular septum defect repair were retrospectively allocated to milrinone group (n= 13)and olprinone group(n=13). Hemodynamic parameters, acid-base balance, oxygenation and postoperative mechanical ventilation period were compared between the two groups at induction of anesthesia, weaning from cardiopulmonary bypass and the end of the surgery. The patients' mean age was 4.4 +/- 2.5 months. Demographic data were almost similar between the two groups. Milrinone and olprinone were administered at the rates of 0.5 and 0.3 microg x kg-1 x min-1 at the end of surgery, respectively. Hemodynamic variables, acid-base balance, Pao2 /FIo2 ratio and mechanical ventilation period were not significantly different between the two groups. No adverse side effects were observed during the study period. The effects of the PDE III inhibitors, milrinone and olprinone, on hemodynamic parameters, acid-base balance and oxygenation were similar in these infants. Both milrinone and olprinone could be used safely in infant cardiac surgery.

Minimizing cardiac risk in perioperative practice - interdisciplinary pharmacological approaches.

PubMed

Bock, Matthias; Wiedermann, Christian J; Motsch, Johann; Fritsch, Gerhard; Paulmichl, Markus

2011-07-01

In an aging population, major surgery is often performed in patients with complex co-morbidities. These patients present new risk constellations so that cardiac and respiratory complications mainly contribute to perioperative morbidity. We composed a narrative review on pharmacological approaches to cardiovascular protection in the perioperative period including effects of central neuraxial blocks and hypothermia on cardiovascular outcome. The single chapters are structured as follows: pathophysiology-early studies-recent evidence-recommendations. In coping with this challenge, innovative concepts like fast track surgery and pharmacological treatment are being utilized with increasing frequency including perioperative cardioprotection, novel strategies of anticoagulation or antiplatelet therapy, and protocols for postoperative pain therapy. All the concepts described require an interdisciplinary approach in collaboration between operative physicians and physicians working in non-surgical disciplines like internal medicine, cardiology, and clinical pharmacology. The perioperative continuation of a pre-existing therapy with beta-blockers and other potentially cardioprotective agents like α(2)-agonists and statines is recommended. In the management of patients presenting for major surgery stratification of the perioperative risk is essential which considers both, invasiveness of the surgical procedure and conditions of the patient. Otherwise, side-effects might outweigh benefits of a potentially effective therapy as recently shown for the perioperative administration of beta-blockers that should be restricted to high-risk patients.

Trastuzumab-induced cardiotoxicity.

PubMed

Moss, Lisa Stegall; Starbuck, Mandy Fields; Mayer, Deborah K; Harwood, Elaine Brooks; Glotzer, Jana

2009-11-01

To review trastuzumab-related cardiotoxic effects in the breast cancer adjuvant setting, present a system for pretreatment screening for cardiovascular risk factors, describe monitoring recommendations, provide a tool to facilitate adherence to monitoring guidelines, and discuss implications for patient education. Literature regarding cardiotoxicity and trastuzumab in breast cancer. Trastuzumab was approved in 2006 for use in the adjuvant setting. A small percentage of women (approximately 4%) developed heart failure during or after treatment. However, the trials excluded women with cardiac disease. Current screening for cardiotoxicity relies on sequential left ventricular function measurements with either echocardiography or multigated acquisition scanning at baseline and every three months. Treatment modifications are recommended if changes from baseline are detected. Long-term and late effects have yet to be determined. Although a small number of women experienced cardiotoxicity in the adjuvant setting, an increase may be seen because women with preexisting heart disease receive this treatment. Guidelines and tools will be helpful for appropriate and consistent screening of cardiac risk factors and disease prior to initiation of trastuzumab and for monitoring during and after administration. Nurses are instrumental in assessing, monitoring, and treating women receiving trastuzumab. Implementing guidelines to promote adherence to recommended monitoring is important in the early detection of cardiotoxicity in this population. Educating women about their treatment and side effects is an important aspect of care.

Renal and cardiac effects of DPP4 inhibitors--from preclinical development to clinical research.

PubMed

Hocher, Berthold; Reichetzeder, Christoph; Alter, Markus L

2012-01-01

Inhibitors of type 4 dipeptidyl peptidase (DDP-4) were developed and approved for the oral treatment of type 2 diabetes. Its mode of action is to inhibit the degradation of incretins, such as type 1 glucagon like peptide (GLP-1), and GIP. GLP-1 stimulates glucose-dependent insulin secretion from pancreatic beta-cells and suppresses glucagon release from alpha-cells, thereby improving glucose control. Besides its action on the pancreas type 1 glucagon like peptide has direct effects on the heart, vessels and kidney mainly via the type 1 glucagon like peptide receptor (GLP-1R). Moreover, there are substrates of DPP-4 beyond incretins that have proven renal and cardiovascular effects such as BNP/ANP, NPY, PYY or SDF-1 alpha. Preclinical evidence suggests that DPP-4 inhibitors may be effective in acute and chronic renal failure as well as in cardiac diseases like myocardial infarction and heart failure. Interestingly, large cardiovascular meta-analyses of combined phase II/III clinical trials with DPP-4 inhibitors point all in the same direction: a potential reduction of cardiovascular events in patients treated with these agents. A pooled analysis of pivotal phase III, placebo-controlled, registration studies of linagliptin further showed a significant reduction of urinary albumin excretion after 24 weeks of treatment. The observation suggests direct renoprotective effects of DPP-4 inhibition that may go beyond its glucose-lowering potential. Type 4 dipeptidyl peptidase inhibitors have been shown to be very well tolerated in general, but for those excreted via the kidney dose adjustments according to renal function are needed to avoid side effects. In conclusion, the direct cardiac and renal effects seen in preclinical studies as well as meta-analysis of clinical trials may offer additional potentials - beyond improvement of glycemic control - for this newer class of drugs, such as acute kidney failure, chronic kidney failure as well as acute myocardial infarction and heart failure. Copyright © 2012 S. Karger AG, Basel.

[Clinical Experience of Beating Heart Atrial Septostomy Using a Device for Coronary Artery Anastomosis Site Creator].

PubMed

Takahashi, Goro; Sai, Sadahiro; Konishi, Akinobu

2015-09-01

Intra-atrial communication was mandatory for several congenital cardiac diseases, such as pulmonary atresia with intact ventricular septum (PA/IVS), and either sided aortoventricular valve atresia. We assessed whether the new methods of atrial septal defect(ASD)creation was effective. We experienced 4 cases of the surgical atrial septostomy performed under on-pump beating. We used a new device, a circular punch out defect creator. All cases were alive. The mean ASD diameter was enlarged from 4.37 mm to 5.55 mm and the mean ASD shunt flow was significantly decreased from 1.47 m/s to 1.11 m/s. We performed the surgical atrial septostomy using an aortic puncher under beating heart effectively and safely.

[Clonazepam in therapy of neurogenic syncopal states].

PubMed

Musaeva, Z A

2001-01-01

27 patients with frequent neurogenic syncopes (NS) resistant to conventional therapy were treated with clonazepam. The average age of the patients was 29.8 +/- 11.6 years. There were 1-2 syncopes in a month. Both before and after the treatment an active orthostatic test was performed with ECG registration and following analysis of variability of the cardiac rhythm. Clonazepam was administered in a dose of 2-2.5 mg/day during 8-9 weeks. Clinical improvement in the form of a lack of syncopes was observed in 20 patients (74%); 3 patients (10%) had isolated lipothymic states; 2 patients discontinued the treatment because of side-effects (dizziness). The results of the examination of 23 patients 6 months after clonazepam therapy testified the stability of the therapeutic effect.

Iodinated contrast media and contrast-induced nephropathy: is there a preferred cost-effective agent?

PubMed

Sharma, Samin K

2008-05-01

Over 20 years have passed since the introduction of the tri-iodinated low-osmolar nonionic contrast agents such as iopamidol, iohexol, ioversol and iopromide. During this time, most cardiology practices have switched to these nonionic agents to avoid the nuisance side effects and cardiac adverse events associated with the older ionic contrast agents. Although the improved tolerability of the nonionic agents is generally attributed to their decreased osmolality (approximately half that of the older ionic contrast agents), in fact, these contrast agents also differ from the older agents in their ionicity, viscosity and direct chemotoxicity. The impact of these properties on safety, together with cost differences, should be considered when selecting a contrast agent.

Joint Estimation of Cardiac Toxicity and Recurrence Risks After Comprehensive Nodal Photon Versus Proton Therapy for Breast Cancer

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

Stick, Line B., E-mail: line.bjerregaard.stick@regionh.dk; Niels Bohr Institute, Faculty of Science, University of Copenhagen, Copenhagen; Yu, Jen

Purpose: The study aims to perform joint estimation of the risk of recurrence caused by inadequate radiation dose coverage of lymph node targets and the risk of cardiac toxicity caused by radiation exposure to the heart. Delivered photon plans are compared with realistic proton plans, thereby providing evidence-based estimates of the heterogeneity of treatment effects in consecutive cases for the 2 radiation treatment modalities. Methods and Materials: Forty-one patients referred for postlumpectomy comprehensive nodal photon irradiation for left-sided breast cancer were included. Comparative proton plans were optimized by a spot scanning technique with single-field optimization from 2 en face beams.more » Cardiotoxicity risk was estimated with the model of Darby et al, and risk of recurrence following a compromise of lymph node coverage was estimated by a linear dose-response model fitted to the recurrence data from the recently published EORTC (European Organisation for Research and Treatment of Cancer) 22922/10925 and NCIC-CTG (National Cancer Institute of Canada Clinical Trials Group) MA.20 randomized controlled trials. Results: Excess absolute risk of cardiac morbidity was small with photon therapy at an attained age of 80 years, with median values of 1.0% (range, 0.2%-2.9%) and 0.5% (range, 0.03%-1.0%) with and without cardiac risk factors, respectively, but even lower with proton therapy (0.13% [range, 0.02%-0.5%] and 0.06% [range, 0.004%-0.3%], respectively). The median estimated excess absolute risk of breast cancer recurrence after 10 years was 0.10% (range, 0.0%-0.9%) with photons and 0.02% (range, 0.0%-0.07%) with protons. The association between age of the patient and benefit from proton therapy was weak, almost non-existing (Spearman rank correlations of −0.15 and −0.30 with and without cardiac risk factors, respectively). Conclusions: Modern photon therapy yields limited risk of cardiac toxicity in most patients, but proton therapy can reduce the predicted risk of cardiac toxicity by up to 2.9% and the risk of breast cancer recurrence by 0.9% in individual patients. Predicted benefit correlates weakly with age. Combined assessment of the risk from cardiac exposure and inadequate target coverage is desirable for rational consideration of competing photon and proton therapy plans.« less

Echocardiography-guided or "sided" pericardiocentesis.

PubMed

Degirmencioglu, Aleks; Karakus, Gultekin; Güvenc, Tolga Sinan; Pinhan, Osman; Sipahi, Ilke; Akyol, Ahmet

2013-10-01

Echocardiography-guided pericardiocentesis is the first choice method for relieving cardiac tamponade, but the exact role of the echocardiography at the moment of the puncture is still controversial. In this report, detailed echocardiographic evaluation was performed in 21 consecutive patients with cardiac tamponade just before the pericardiocentesis. Appropriate needle position was determined according to the probe position using imaginary x, y, and z axes. Pericardiocentesis was performed successfully using this technique without simultaneous echocardiography and no complications were observed. We concluded that bedside echocardiography with detailed evaluation of the puncture site and angle is enough for pericardiocentesis instead of real time guiding. © 2013, Wiley Periodicals, Inc.

Clinics in diagnostic imaging (160). Levocardia with abdominal situs inversus

PubMed Central

Abdullah, Nor Lenny; Quek, Swee Chye; Seto, Kar Yin; Teo, Lynette Li San

2015-01-01

Levocardia (left-sided cardiac apex) with abdominal situs inversus is extremely rare. This is also known as isolated levocardia and is almost always associated with severe forms of congenital heart defects with poor prognosis. We report isolated levocardia in a 13-year-old symptomatic male patient. The purpose of this paper is to outline the imaging features of isolated levocardia and to highlight the role of cardiovascular magnetic resonance imaging (CMR) in the diagnosis and management of such cases. Other forms of cardiac malposition, including dextrocardia, mesocardia and criss-cross heart, with chest radiograph and CMR correlation, are also discussed. PMID:25917470

Cardiac transplantation in situs inversus: two cases reports.

PubMed

Chang, Y L; Wei, J; Chang, C-Y; Chuang, Y-C; Sue, S-H

2008-10-01

The challenge of heart transplantation in patients with situs inversus is reconstruction of the systemic venous return. Herein we have presented 2 cases of complex congenital heart disease with atriovisceral situs inversus. Both of the patients shared many common cardiac anomalies, such as a single ventricle, a single AV valve with severe regurgitation, and severe pulmonary stenosis. We completed the venous connection in 2 different ways. In the first case, the donor inferior vena cava (IVC) was anastomosed to the recipient left-sided IVC directly, making the heart slightly counterclockwise rotated. In the second case, the IVC venous reconnection was accomplished by a composite conduit made of recipient right atrium.

Ensuring the effectiveness of community-wide emergency cardiac care.

PubMed

Becker, L B; Pepe, P E

1993-02-01

To improve emergency cardiac care (ECC) on the national or international level, we must translate to the rest of our communities the successes found in cities with high survival rates. In recent years, important developments have evolved in our understanding of the treatment and evaluation of cardiac arrest. Some of the most important of these developments include 1) recognition of the chain of survival, which is necessary to achieve high survival rates; 2) widespread acceptance that survival rates must be assessed routinely to ensure continuous quality improvements in the emergency medical services (EMS) system; and 3) development of improved methods for performing survival rate studies that will maximize the effectiveness of information gathering and analysis. While each community should determine how to optimize their own ECC services, some general guidelines are useful. Successful treatment of cardiac arrest starts in the community with prevention and education, including early recognition of the signs and symptoms of cardiovascular ischemia. Obtaining 911 service (and preferably enhanced 911) should be a top priority for all communities. EMS dispatchers should dispatch the unit to the scene in less than one minute, provide critical information to the responders regarding the type of emergency, and offer the caller telephone-assisted CPR instructions. The EMS first-responders should strive to arrive at the patient's side in less than four minutes, be able to immediately defibrillate if necessary, and begin basic CPR. An excellent strategy to accomplish this is to equip and train all fire-fighting units in the operation of automatic external defibrillators and dispatch them as a first-responder team. To manage the cardiac arrest patient, a minimum of two rescuers trained in advanced cardiac life support plus two or more rescuers trained in basic life support are needed. Furthermore, an EMS system is not complete without on-going evaluation. Therefore, the 1992 National Conference on CPR and ECC strongly endorses the position that all ECC systems assess their survival rates through an ongoing quality improvement process and that all members of the chain of providers should be represented in the outcome assessment team. We still have much to discover regarding optimal techniques of CPR, methods for data collection, and optimal structure of an EMS system. Research in these areas will provide the foundation for future changes in EMS systems development.

[Left-sided endocarditis due to gram-negative bacilli: epidemiology and clinical characteristics].

PubMed

Noureddine, Mariam; de la Torre, Javier; Ivanova, Radka; Martínez, Francisco José; Lomas, Jose María; Plata, Antonio; Gálvez, Juan; Reguera, Jose María; Ruiz, Josefa; Hidalgo, Carmen; Luque, Rafael; García-López, María Victoria; de Alarcón, Arístides

2011-04-01

The aim of this study is to describe the epidemiological, clinical characteristics, and outcome of patients with left-side endocarditis caused by gram-negative bacteria. Prospective multicenter study of left-sided infective endocarditis reported in the Andalusian Cohort for the Study of Cardiovascular Infections between 1984 and 2008. Among the 961 endocarditis, 24 (2.5%) were caused by gram-negative bacilli. The most common pathogens were Escherichia coli, Pseudomonas aeruginosa and Salmonella enterica. Native valves (85.7%) were mainly affected, most of them with previous valve damage (57%). Comorbidity was greater (90% vs 39%; P=.05) than in endocarditis due to other microorganism, the most frequent being, diabetes, hepatic cirrhosis and neoplasm. A previous manipulation was found in 47.6% of the cases, and 37% were considered hospital-acquired. Renal failure (41%), central nervous system involvement (33%) and ventricular dysfunction (45%) were the most frequent complications. Five cases (21%) required cardiac surgery, mostly due to ventricular dysfunction. More than 50% of cases were treated with aminoglycosides, but this did not lead to a better outcome or prognosis. Mortality (10 patients) was higher than that reported with other microorganisms (41% vs 35%; P=.05). Left-sided endocarditis due to gram-negative bacilli is a rare disease, which affects patients with major morbidities and often with a previous history of hospital manipulations. Cardiac, neurological and renal complications are frequent and associated with a high mortality. The association of aminoglycosides in the antimicrobial treatment did not involve a better outcome or prognosis. Copyright © 2010 Elsevier España, S.L. All rights reserved.

A hybrid surgical transcatheter strategy for treating severe para-right atrioventricular valvular regurgitation in a patient with left atrial isomerism.

PubMed

Kalantre, Atul; Vettukattil, Joseph; Haw, Marcus; Veldtman, Gruschen R

2007-12-01

Paravalvular leaks are a recognized complication of valve replacement surgery. We report a 47-year-old man with left atrial isomerism, interrupted left sided inferior caval vein with unilateral left sided superior caval vein, a common atrium, and anomalous pulmonary venous connection to the coronary sinus, who had recurrent severe para-right atrioventricular (AV) regurgitation with gross right heart failure following tricuspid valve (TCV) replacement. He underwent a hybrid surgery-transcatheter treatment strategy in the cardiac catheterization laboratory, which led to significant improvement in hemodynamics and symptoms. This to our knowledge is the first reported case of a minimally invasive approach to para-right sided AV valve regurgitation.

Combined usage of inhaled and intravenous milrinone in pulmonary hypertension after heart valve surgery.

PubMed

Carev, Mladen; Bulat, Cristijan; Karanović, Nenad; Lojpur, Mihajlo; Jercić, Antonio; Nenadić, Denis; Marovih, Zlatko; Husedzinović, Ino; Letica, Dalibor

2010-09-01

Secondary pulmonary hypertension is a frequent condition after heart valve surgery. It may significantly complicate the perioperative management and increase patients' morbidity and mortality. The treatment has not been yet completely defined principally because of lack of the selectivity of drugs for the pulmonary vasculature. The usage of inhaled milrinone could be the possible therapeutic option. Inodilator milrinone is commonly used intravenously for patients with pulmonary hypertension and ventricular dysfunction in cardiac surgery. The decrease in systemic vascular resistance frequently necessitates concomitant use of norepinephrine. Pulmonary vasodilators might be more effective and also devoid of potentially dangerous systemic side effects if applied by inhalation, thus acting predominantly on pulmonary circulation. There are only few reports of inhaled milrinone usage in adult post cardiac surgical patients. We reported 2 patients with severe pulmonary hypertension after valve surgery. Because of desperate clinical situation, we decided to use the combination of inhaled and intravenous milrinone. Inhaled milrinone was delivered by means of pneumatic medication nebulizer dissolved with saline in final concentration of 0.5 mg/ml. The nebulizer was attached to the inspiratory limb of the ventilator circuit, just before the Y-piece. We obtained satisfactory reduction in mean pulmonary artery pressure in both patients, and they were successfully extubated and discharged. Although it is a very small sample of patients, we conclude that the combination of inhaled and intravenous milrinone could be an effective treatment of secondary pulmonary hypertension in high-risk cardiac valve surgery patient. The exact indications for inhaled milrinone usage, optimal concentrations for this route, and the beginning and duration of treatment are yet to be determined.

Specific beta1-adrenergic receptor silencing with small interfering RNA lowers high blood pressure and improves cardiac function in myocardial ischemia.

PubMed

Arnold, Anne-Sophie; Tang, Yao Liang; Qian, Keping; Shen, Leping; Valencia, Valery; Phillips, Michael Ian; Zhang, Yuan Clare

2007-01-01

Beta-blockers are widely used and effective for treating hypertension, acute myocardial infarction (MI) and heart failure, but they present side-effects mainly due to antagonism of beta2-adrenergic receptor (AR). Currently available beta-blockers are at best selective but not specific for beta1 or beta2-AR. To specifically inhibit the expression of the beta1-AR, we developed a small interfering RNA (siRNA) targeted to beta1-AR. Three different sequences of beta1 siRNA were delivered into C6-2B cells with 90% efficiency. One of the three sequences reduced the level of beta1-AR mRNA by 70%. The siRNA was highly specific for beta1-AR inhibition with no overlap with beta2-AR. To test this in vivo, systemic injection of beta1 siRNA complexed with liposomes resulted in efficient delivery into the heart, lung, kidney and liver, and effectively reduced beta1-AR expression in the heart without altering beta2-AR. beta1 siRNA significantly lowered blood pressure of spontaneously hypertensive rats (SHR) for at least 12 days and reduced cardiac hypertrophy following a single injection. Pretreatment with beta1 siRNA 3 days before induction of MI in Wistar rats significantly improved cardiac function, as demonstrated by dP/dt and electrocardiogram following the MI. The protective mechanism involved reduction of cardiomyocyte apoptosis in the beta1 siRNA-treated hearts. The present study demonstrates the possibility of using siRNA for treating cardiovascular diseases and may represent a novel beta-blocker specific for beta1-AR.

A novel side branch protection technique in coronary stent implantation: Jailed Corsair technique.

PubMed

Numasawa, Yohei; Sakakura, Kenichi; Yamamoto, Kei; Yamamoto, Shingo; Taniguchi, Yousuke; Fujita, Hideo; Momomura, Shin-Ichi

2017-06-01

Side branch occlusion, which was one of the common complications in percutaneous coronary interventions, was closely associated with cardiac death and myocardial infarction. Clinical guidelines also support the importance of preservation of physiologic blood flow in SB during PCI to bifurcation lesions. In order to avoid side branch occlusion during stent implantation, we often performed the jailed wire technique, in which a conventional guide wire was inserted to the side branch before stent implantation to the main vessel. However, the jailed wire technique could not always prevent side branch occlusion. In this case report, we described a case of 72-year-old male suffering from angina pectoris. Coronary angiography revealed the diffuse calcified stenosis in the proximal and middle of left anterior descending coronary artery, and the large diagonal branch originated from the middle of the stenosis. To prevent side branch occlusion, we performed a novel side branch protection technique by using the Corsair microcatheter (Asahi Intecc, Nagoya, Japan). In this case report, we illustrated this "Jailed Corsair technique", and discussed the advantage compared to other side branch protection techniques such as the jailed balloon technique. Copyright © 2017 Elsevier Inc. All rights reserved.

Left-right asymmetry and cardiac looping: implications for cardiac development and congenital heart disease.

PubMed

Kathiriya, I S; Srivastava, D

2000-01-01

Proper morphogenesis and positioning of internal organs requires delivery and interpretation of precise signals along the anterior-posterior, dorsal-ventral, and left-right axes. An elegant signaling cascade determines left- versus right-sided identity in visceral organs in a concordant fashion, resulting in a predictable left-right (LR) organ asymmetry in all vertebrates. The complex morphogenesis of the heart and its connections to the vasculature are particularly dependent upon coordinated LR signaling pathways. Disorganization of LR signals can result in myriad congenital heart defects that are a consequence of abnormal looping and remodeling of the primitive heart tube into a multi-chambered organ. A framework for understanding how LR asymmetric signals contribute to normal organogenesis has emerged and begins to explain the basis of many human diseases of LR asymmetry. Here we review the impact of LR signaling pathways on cardiac development and congenital heart disease.

Congenital cardiac disease in dogs.

PubMed

McCaw, D; Aronson, E

1984-07-01

Pulmonic stenosis is caused by a malformed pulmonic valve, stricture of the right ventricular outflow tract or stricture of the pulmonary artery. English Bulldogs, Beagles, Samoyeds, Fox Terriers and Chihuahuas are predisposed. Clinical signs in severely affected dogs include exercise intolerance, stunting, dyspnea, syncope and ascites. Auscultation reveals a high-frequency, crescendo-decrescendo murmur during systole, loudest over the left side of the thorax, near the sternal cardiac border. An ECG may reveal a right-axis deviation of greater than 120 degrees, S waves in leads I, II and III, deep S waves in CV6LL, CV6LU and V10, Q waves deeper than 0.5 mv in leads II, III and AVF, and positive T waves in lead V10. Plain film LAT thoracic radiographs reveal an elevated carina, increased sternal contact of the heart, loss of the cranial cardiac waist and a widened cardiac silhouette, with normal pulmonary vasculature. A DV projection reveals an inverted "D" shape of the right ventricle and a pulmonary artery bulge. A nonselective angiocardiogram reveals poststenotic dilation of the main pulmonary artery. Treatment involves surgical correction of the stenosis.

Laughter and MIRTH (Methodical Investigation of Risibility, Therapeutic and Harmful): narrative synthesis

PubMed Central

Aronson, J K

2013-01-01

Objective To review the beneficial and harmful effects of laughter. Design Narrative synthesis. Data sources and review methods We searched Medline (1946 to June 2013) and Embase (1974 to June 2013) for reports of benefits or harms from laughter in humans, and counted the number of papers in each category. Results Benefits of laughter include reduced anger, anxiety, depression, and stress; reduced tension (psychological and cardiovascular); increased pain threshold; reduced risk of myocardial infarction (presumably requiring hearty laughter); improved lung function; increased energy expenditure; and reduced blood glucose concentration. However, laughter is no joke—dangers include syncope, cardiac and oesophageal rupture, and protrusion of abdominal hernias (from side splitting laughter or laughing fit to burst), asthma attacks, interlobular emphysema, cataplexy, headaches, jaw dislocation, and stress incontinence (from laughing like a drain). Infectious laughter can disseminate real infection, which is potentially preventable by laughing up your sleeve. As a side effect of our search for side effects, we also list pathological causes of laughter, among them epilepsy (gelastic seizures), cerebral tumours, Angelman’s syndrome, strokes, multiple sclerosis, and amyotrophic lateral sclerosis or motor neuron disease. Conclusions Laughter is not purely beneficial. The harms it can cause are immediate and dose related, the risks being highest for Homeric (uncontrollable) laughter. The benefit-harm balance is probably favourable. It remains to be seen whether sick jokes make you ill or jokes in bad taste cause dysgeusia, and whether our views on comedians stand up to further scrutiny. PMID:24336308

Dabigatran for anticoagulation in atrial fibrillation - early clinical experience in a hospital population and comparison to trial data.

PubMed

Michel, Jonathan; Mundell, David; Boga, Tau; Sasse, Alexander

2013-01-01

Dabigatran is a recently introduced direct thrombin inhibitor licensed for use as an oral anticoagulant for stroke prevention in non-valvular atrial fibrillation. Our prospective observational study aimed to assess the adverse effects, tolerability and patient satisfaction of dabigatran therapy in a hospital-practice population. Patients starting dabigatran, after its release in June 2011, were identified from clinical practice at two Wellington hospitals, New Zealand. Baseline characteristics were recorded from the clinical record and a telephone interview was performed in January 2012. Primary outcomes included adverse events, adherence, and satisfaction with treatment. Data were available for 70 patients: median age 71.9 years (IQR 62.7-79.0), weight 80 kg (IQR 71-95), CHA(2)DS(2)-VASc score 3 (IQR 2-4). Seventy-one percent of patients reported adverse events although the majority were minor. Twenty-four percent (16/70) had discontinued treatment with dabigatran; four due to predominantly gastrointestinal side effects, three due to bleeding (one severe), one as a result of adverse media coverage with the remainder comprising planned treatment discontinuation and undetermined. In total, 29% reported bleeding events, predominantly minor bleeding and bruising. There were no cerebrovascular events. Nineteen percent reported some difficulty with twice daily dosing adherence with 13 of 70 reporting missed doses. Seventy-seven percent reported treatment satisfaction and 79% of those previously treated with warfarin preferred dabigatran. In this population our study demonstrates a discontinuation rate of 10% due to side effects of dabigatran, similar to the rate reported in RE-LY. The majority of patients are satisfied with their treatment and preferred dabigatran to warfarin, mainly due to the reduced requirement for blood testing. Copyright © 2012 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Heart disease in patients with pulmonary embolism.

PubMed

Pesavento, Raffaele; Piovella, Chiara; Prandoni, Paolo

2010-09-01

Several heart diseases are promoters of left-side cardiac thrombosis and could lead to arterial embolism. The same mechanism may be responsible for right-side cardiac thrombosis and therefore be a direct source of pulmonary embolism. Yasuoka et al. showed a higher incidence of perfusion defects in lung scan in patients with spontaneous echocontrast in the right atrium than in those without it (40% and 7% respectively; P=0.006). We recently assessed the prevalence of heart diseases in 11.236 consecutive patients older than 60 years discharged from Venetian hospitals with a diagnosis of pulmonary embolism. We observed a higher prevalence of all-cause heart diseases (odds ratio 1.26; 95% confidence interval, 1.13-1.40) in patients with a diagnosis of pulmonary embolism alone (secondary or unprovoked) compared with those discharged with a diagnosis of pulmonary embolism associated with deep vein thrombosis, generating the hypothesis that some specific heart diseases in older patients could themselves be a possible source of pulmonary emboli. Further prospective studies are required to confirm these findings, which have the potential to open new horizons for the interpretation and management of venous thromboembolic disease.

Noninvasive diagnosis of right-sided extracardiac conduit obstruction by combined magnetic resonance imaging and continuous-wave Doppler echocardiography.

PubMed

Canter, C E; Gutierrez, F R; Molina, P; Hartmann, A F; Spray, T L

1991-04-01

Right-sided extracardiac conduits are frequently complicated by obstruction over time. We compared the utility of two-dimensional and Doppler echocardiography and magnetic resonance imaging in the diagnosis of postoperative right-sided obstruction with cardiac catheterization and angiography in 10 patients with xenograft or homograft conduits. Correlation (r = 0.95) between continuous-wave Doppler estimates and catheter pullback pressure gradients across the conduits was excellent. Echocardiography could only visualize five of 10 conduits in their entirety. Magnetic resonance imaging visualized all conduits and showed statistically significant (kappa = 0.58) agreement with angiography in the localization and estimation of severity of a variety of right-sided obstructions in these patients. However, flow voids created by the metallic ring around xenograft valves led to a false negative diagnosis of valvular stenosis in four patients when magnetic resonance imaging was used alone. Doppler studies correctly indicated obstruction in these patients. The combination of magnetic resonance imaging studies and continuous-wave Doppler echocardiography can be useful to noninvasively evaluate right-sided obstruction in postoperative patients with right-sided extracardiac conduits.

Histone deacetylase inhibitors augment doxorubicin-induced DNA damage in cardiomyocytes.

PubMed

Ververis, Katherine; Rodd, Annabelle L; Tang, Michelle M; El-Osta, Assam; Karagiannis, Tom C

2011-12-01

Histone deacetylase inhibitors have emerged as a new class of anticancer therapeutics with suberoylanilide hydroxamic acid (Vorinostat) and depsipeptide (Romidepsin) already being approved for clinical use. Numerous studies have identified that histone deacetylase inhibitors will be most effective in the clinic when used in combination with conventional cancer therapies such as ionizing radiation and chemotherapeutic agents. One promising combination, particularly for hematologic malignancies, involves the use of histone deacetylase inhibitors with the anthracycline, doxorubicin. However, we previously identified that trichostatin A can potentiate doxorubicin-induced hypertrophy, the dose-limiting side-effect of the anthracycline, in cardiac myocytes. Here we have the extended the earlier studies and evaluated the effects of combinations of the histone deacetylase inhibitors, trichostatin A, valproic acid and sodium butyrate on doxorubicin-induced DNA double-strand breaks in cardiomyocytes. Using γH2AX as a molecular marker for the DNA lesions, we identified that all of the broad-spectrum histone deacetylase inhibitors tested augment doxorubicin-induced DNA damage. Furthermore, it is evident from the fluorescence photomicrographs of stained nuclei that the histone deacetylase inhibitors also augment doxorubicin-induced hypertrophy. These observations highlight the importance of investigating potential side-effects, in relevant model systems, which may be associated with emerging combination therapies for cancer.

Building a knowledge base of severe adverse drug events based on AERS reporting data using semantic web technologies.

PubMed

Jiang, Guoqian; Wang, Liwei; Liu, Hongfang; Solbrig, Harold R; Chute, Christopher G

2013-01-01

A semantically coded knowledge base of adverse drug events (ADEs) with severity information is critical for clinical decision support systems and translational research applications. However it remains challenging to measure and identify the severity information of ADEs. The objective of the study is to develop and evaluate a semantic web based approach for building a knowledge base of severe ADEs based on the FDA Adverse Event Reporting System (AERS) reporting data. We utilized a normalized AERS reporting dataset and extracted putative drug-ADE pairs and their associated outcome codes in the domain of cardiac disorders. We validated the drug-ADE associations using ADE datasets from SIDe Effect Resource (SIDER) and the UMLS. We leveraged the Common Terminology Criteria for Adverse Event (CTCAE) grading system and classified the ADEs into the CTCAE in the Web Ontology Language (OWL). We identified and validated 2,444 unique Drug-ADE pairs in the domain of cardiac disorders, of which 760 pairs are in Grade 5, 775 pairs in Grade 4 and 2,196 pairs in Grade 3.

Protease-Activated Receptor 4 (PAR4): A Promising Target for Antiplatelet Therapy.

PubMed

Rwibasira Rudinga, Gamariel; Khan, Ghulam Jilany; Kong, Yi

2018-02-14

Cardiovascular diseases (CVDs) are currently among the leading causes of death worldwide. Platelet aggregation is a key cellular component of arterial thrombi and major cause of CVDs. Protease-activated receptors (PARs), including PAR1, PAR2, PAR3 and PAR4, fall within a subfamily of seven-transmembrane G-protein-coupled receptors (GPCR). Human platelets express PAR1 and PAR4, which contribute to the signaling transduction processes. In association with CVDs, PAR4 not only contributes to platelet activation but also is a modulator of cellular responses that serve as hallmarks of inflammation. Although several antiplatelet drugs are available on the market, they have many side effects that limit their use. Emerging evidence shows that PAR4 targeting is a safer strategy for preventing thrombosis and consequently may improve the overall cardiac safety profile. Our present review summarizes the PAR4 structural characteristics, activation mechanism, role in the pathophysiology of diseases and understanding the association of PAR4 targeting for improved cardiac protection. Conclusively, this review highlights the importance of PAR4 antagonists and its potential utility in different CVDs.

Radiation-related heart disease after breast cancer radiation therapy in Korean women.

PubMed

Chang, Jee Suk; Ko, Byung Kyun; Bae, Jeoung Won; Yu, Jong-Han; Park, Min Ho; Jung, Yongsik; Jeon, Ye Won; Kim, Kyung Hwan; Shin, Jaeyong; Suh, Chang-Ok; Kim, Yong Bae

2017-11-01

To study the late cardiac toxicity of breast radiation therapy (RT) in Asian women. Female breast cancer patients in Korea who underwent breast conservation surgery followed by RT from 1990-2012 were identified from two large registries at institution and population levels. Cumulative incidences of acute coronary events (ACE) or cardiac mortality were estimated in relation to the laterality of breast cancer using a competing risks analysis. In an analysis of 2577 women from a single institution, 3.7% were obese (body mass index ≥30), and 3.4% were ever-smokers. Patients with a history of hypertension, diabetes, or coronary artery disease were 17.5, 5.7, and 2.8%, respectively. The mean heart doses were 6.2 and 1.5 Gy for left- and right-sided tumors, respectively. With a median follow-up of 7 (range 1-23) years, the overall and breast cancer-specific survivals at 10 years were 94.9 and 96.5%, respectively. The 10-year cumulative incidence of ACE was 2.96%. The mean time to ACE was 5.2 ± 3.9 years (range 1-17). There was no clinically relevant difference in rates of ACE between left-sided and right-sided patients, with an adjusted hazard ratio of 1.16 (CI 0.59-2.29). An analysis of 24,235 women in a nationwide registry validated these negative findings with respect to cardiac mortality, with an adjusted hazard ratio of 1.52 (CI 0.37-6.25). Increasing age, a higher body mass index, and a history of hypertension or ischemic heart disease were identified as risk factors. Our findings reassure that excess risk from breast RT may be small in healthy women, most of who not smoke, weigh less, and have fewer risk factors. A validation using a larger data set of National Health Insurance Corporation is ongoing.

Phase analysis in the Wolff-Parkinson-White syndrome with surgically proven accessory conduction pathways: concise communication

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

Nakajima, K.; Bunko, H.; Tada, A.

1984-01-01

Twenty-one patients with the Wolff-Parkinson-White (WPW) syndrome who underwent surgical division of the accessory conduction pathway (ACP) were studied by gated blood-pool scintigraphy. In each case, a functional image of the phase was generated, based on the fundamental frequency of the Fourier transform. The location of the ACP was confirmed by electrophysiologic study, epicardial mapping, and surgery. Phase analysis identified the side of preexcitation correctly in 16 out of 20 patients with WPW syndrome with a delta wave. All patients with right-cardiac type (N=9) had initial contraction in the right ventricle (RV). In patients with left-cardiac type (N=10), six hadmore » initial movement in the left ventricle (LV); but in the other four the ACPs in the anterior or lateral wall of the left ventricle (LV) could not be detected. In patients with multiple ACPs (N=2), one right-cardiac type had initial contraction in the RV, while in the other (with an intermittent WPW syndrome) the ACP was not detected. These observations indicate that abnormal wall motion is associated with the conduction anomalies of the WPW syndrome. We conclude that phase analysis can correctly identify the side of initial contraction in the WPW syndrome before and after surgery. However, as a method of preoperative study, it seems difficult to determine the precise site of the ACP by phase analysis alone.« less

Evolving anatomic and electrophysiologic considerations associated with Fontan conversion.

PubMed

Mavroudis, Constantine; Backer, Carl Lewis; Deal, Barbara J; Stewart, Robert D; Franklin, Wayne H; Tsao, Sabrina; Ward, Kendra

2007-01-01

The principles of Fontan conversion with arrhythmia surgery are to restore the cardiac anatomy by converting the original atriopulmonary connection to a total cavopulmonary artery extracardiac connection and treat the underlying atrial arrhythmias. Successful outcomes of this procedure are dependent on a thorough understanding of several factors: the patient's fundamental diagnosis of single-ventricle anatomy, the resultant cardiac configuration from the original atriopulmonary Fontan connection, right atrial dilatation that leads to atrial flutter or fibrillation, and associated congenital cardiac anomalies. The purpose of this article is to present some of the more challenging anatomic and electrophysiologic problems we have encountered with Fontan conversion and arrhythmia surgery and the innovative solutions we have used to treat them. The cases reviewed herein include: takedown of a Bjork-Fontan modification, right ventricular hypertension and tricuspid regurgitation after atriopulmonary Fontan for pulmonary atresia and intact ventricular septum, takedown of atrioventricular valve isolation patch for right-sided maze procedure, resultant hemodynamic considerations leading to intraoperative pulmonary vein stenosis after Fontan conversion, unwanted inferior vena cava retraction during the extracardiac connection, right atrial cannulation in the presence of a right atrial clot, distended left superior vena cava causing left pulmonary vein stenosis, dropped atrial septum, and the modified right-sided maze procedure for various single-ventricle pathology. Since 1994 we have performed Fontan conversion with arrhythmia surgery on 109 patients with a 0.9% mortality rate. We attribute our program's success in no small measure to the strong collaborative efforts of the cardiothoracic surgery and cardiology teams.

Minimally invasive repair of pectus excavatum (MIRPE)--the Basel experience.

PubMed

Haecker, F M; Bielek, J; von Schweinitz, D

2003-01-01

Minimally invasive repair of pectus excavatum (MIRPE) was first reported in 1998 by D. Nuss. This technique has gained wide acceptance during the last 4-5 years. In the meantime, some modifications of the technique have been introduced by different authors. Our retrospective study reports our own experience over the last 36 months and modifications introduced due to a number of complications. From 3/2000 to 3/2003, 22 patients underwent MIRPE. Patients median age was 15.5 years (10.7 to 20.3 years). Standardised preoperative evaluation included 3D computerised tomography (CT) scan, pulmonary function tests, cardiac evaluation with electrocardiogram and echocardiography, and photo documentation. Indications for operation included at least two of the following: Haller CT index > 3.2, restrictive lung disease, cardiac compression, progression of the deformity and severe psychological alterations. In 22 patients (2 girls, 20 boys) undergoing MIRPE procedure, a single bar was used in 21 patients and two bars in one boy. Lateral stabilisers were fixed with non resorbable sutures on both sides. Overall, postoperative complications occurred in six patients (27.3%). In two patients (9.1%) a redo-procedure was necessary due to bar displacement. An additional median skin incision was performed in two patients to elevate the sternum. Pneumothorax or hematothorax in two patients resulted in routine use of a chest tube on both sides. Long-term favourable results were noted in all patients. The MIRPE procedure is an effective method with elegant cosmetic results. Modifications of the original method help to decrease the complication rate and to accelerate acquirement of expertise.

Cardiac Position Sensitivity Study in the Electrocardiographic Forward Problem Using Stochastic Collocation and Boundary Element Methods

PubMed Central

Swenson, Darrell J.; Geneser, Sarah E.; Stinstra, Jeroen G.; Kirby, Robert M.; MacLeod, Rob S.

2012-01-01

The electrocardiogram (ECG) is ubiquitously employed as a diagnostic and monitoring tool for patients experiencing cardiac distress and/or disease. It is widely known that changes in heart position resulting from, for example, posture of the patient (sitting, standing, lying) and respiration significantly affect the body-surface potentials; however, few studies have quantitatively and systematically evaluated the effects of heart displacement on the ECG. The goal of this study was to evaluate the impact of positional changes of the heart on the ECG in the specific clinical setting of myocardial ischemia. To carry out the necessary comprehensive sensitivity analysis, we applied a relatively novel and highly efficient statistical approach, the generalized polynomial chaos-stochastic collocation method, to a boundary element formulation of the electrocardiographic forward problem, and we drove these simulations with measured epicardial potentials from whole-heart experiments. Results of the analysis identified regions on the body-surface where the potentials were especially sensitive to realistic heart motion. The standard deviation (STD) of ST-segment voltage changes caused by the apex of a normal heart, swinging forward and backward or side-to-side was approximately 0.2 mV. Variations were even larger, 0.3 mV, for a heart exhibiting elevated ischemic potentials. These variations could be large enough to mask or to mimic signs of ischemia in the ECG. Our results suggest possible modifications to ECG protocols that could reduce the diagnostic error related to postural changes in patients possibly suffering from myocardial ischemia. PMID:21909818

Machine Learning of Three-dimensional Right Ventricular Motion Enables Outcome Prediction in Pulmonary Hypertension: A Cardiac MR Imaging Study.

PubMed

Dawes, Timothy J W; de Marvao, Antonio; Shi, Wenzhe; Fletcher, Tristan; Watson, Geoffrey M J; Wharton, John; Rhodes, Christopher J; Howard, Luke S G E; Gibbs, J Simon R; Rueckert, Daniel; Cook, Stuart A; Wilkins, Martin R; O'Regan, Declan P

2017-05-01

Purpose To determine if patient survival and mechanisms of right ventricular failure in pulmonary hypertension could be predicted by using supervised machine learning of three-dimensional patterns of systolic cardiac motion. Materials and Methods The study was approved by a research ethics committee, and participants gave written informed consent. Two hundred fifty-six patients (143 women; mean age ± standard deviation, 63 years ± 17) with newly diagnosed pulmonary hypertension underwent cardiac magnetic resonance (MR) imaging, right-sided heart catheterization, and 6-minute walk testing with a median follow-up of 4.0 years. Semiautomated segmentation of short-axis cine images was used to create a three-dimensional model of right ventricular motion. Supervised principal components analysis was used to identify patterns of systolic motion that were most strongly predictive of survival. Survival prediction was assessed by using difference in median survival time and area under the curve with time-dependent receiver operating characteristic analysis for 1-year survival. Results At the end of follow-up, 36% of patients (93 of 256) died, and one underwent lung transplantation. Poor outcome was predicted by a loss of effective contraction in the septum and free wall, coupled with reduced basal longitudinal motion. When added to conventional imaging and hemodynamic, functional, and clinical markers, three-dimensional cardiac motion improved survival prediction (area under the receiver operating characteristic curve, 0.73 vs 0.60, respectively; P < .001) and provided greater differentiation according to difference in median survival time between high- and low-risk groups (13.8 vs 10.7 years, respectively; P < .001). Conclusion A machine-learning survival model that uses three-dimensional cardiac motion predicts outcome independent of conventional risk factors in patients with newly diagnosed pulmonary hypertension. Online supplemental material is available for this article.

Recruitments of trained citizen volunteering for conventional cardiopulmonary resuscitation are necessary to improve the outcome after out-of-hospital cardiac arrests in remote time-distance area: A nationwide population-based study.

PubMed

Takei, Yutaka; Kamikura, Takahisa; Nishi, Taiki; Maeda, Tetsuo; Sakagami, Satoru; Kubo, Minoru; Inaba, Hideo

2016-08-01

To compare the factors associated with survival after out-of-hospital cardiac arrests (OHCAs) among three time-distance areas (defined as interquartile range of time for emergency medical services response to patient's side). From a nationwide, prospectively collected data on 716,608 OHCAs between 2007 and 2012, this study analyzed 193,914 bystander-witnessed OHCAs without pre-hospital physician involvement. Overall neurologically favourable 1-month survival rates were 7.4%, 4.1% and 1.7% for close, intermediate and remote areas, respectively. We classified BCPR by type (compression-only vs. conventional) and by dispatcher-assisted CPR (DA-CPR) (with vs. without); the effects on time-distance area survival were analyzed by BCPR classification. Association of each BCPR classification with survival was affected by time-distance area and arrest aetiology (p<0.05). The survival rates in the remote area were much higher with conventional BCPR than with compression-only BCPR (odds ratio; 95% confidence interval, 1.26; 1.05-1.51) and with BCPR without DA-CPR than with BCPR with DA-CPR (1.54; 1.29-1.82). Accordingly, we classified BCPR into five groups (no BCPR, compression-only with DA-CPR, conventional with DA-CPR, compression-only without DA-CPR, and conventional without DA-CPR) and analyzed for associations with survival, both cardiac and non-cardiac related, in each time-distance area by multivariate logistic regression analysis. In the remote area, conventional BCPR without DA-CPR significantly improved survival after OHCAs of cardiac aetiology, compared with all the other BCPR groups. Other correctable factors associated with survival were short collapse-to-call and call-to-first CPR intervals. Every effort to recruit trained citizens initiating conventional BCPR should be made in remote time-distance areas. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Endovascular Versus External Targeted Temperature Management for Patients With Out-of-Hospital Cardiac Arrest: A Randomized, Controlled Study.

PubMed

Deye, Nicolas; Cariou, Alain; Girardie, Patrick; Pichon, Nicolas; Megarbane, Bruno; Midez, Philippe; Tonnelier, Jean-Marie; Boulain, Thierry; Outin, Hervé; Delahaye, Arnaud; Cravoisy, Aurélie; Mercat, Alain; Blanc, Pascal; Santré, Charles; Quintard, Hervé; Brivet, François; Charpentier, Julien; Garrigue, Delphine; Francois, Bruno; Quenot, Jean-Pierre; Vincent, François; Gueugniaud, Pierre-Yves; Mira, Jean-Paul; Carli, Pierre; Vicaut, Eric; Baud, Frédéric J

2015-07-21

Targeted temperature management is recommended after out-of-hospital cardiac arrest. Whether advanced internal cooling is superior to basic external cooling remains unknown. The aim of this multicenter, controlled trial was to evaluate the benefit of endovascular versus basic surface cooling. Inclusion criteria were the following: age of 18 to 79 years, out-of-hospital cardiac arrest related to a presumed cardiac cause, time to return of spontaneous circulation <60 minutes, delay between return of spontaneous circulation and inclusion <240 minutes, and unconscious patient after return of spontaneous circulation and before the start of cooling. Exclusion criteria were terminal disease, pregnancy, known coagulopathy, uncontrolled bleeding, temperature on admission <30°C, in-hospital cardiac arrest, immediate need for extracorporeal life support or hemodialysis. Patients were randomized between 2 cooling strategies: endovascular femoral devices (Icy catheter, Coolgard, Zoll, formerly Alsius; n=203) or basic external cooling using fans, a homemade tent, and ice packs (n=197). The primary end point, that is, favorable outcome evaluated by survival without major neurological damage (Cerebral Performance Categories 1-2) at day 28, was not significantly different between groups (odds ratio, 1.41; 95% confidence interval, 0.93-2.16; P=0.107). Improvement in favorable outcome at day 90 in favor of the endovascular group did not reach significance (odds ratio, 1.51; 95% confidence interval, 0.96-2.35; P=0.07). Time to target temperature (33°C) was significantly shorter and target hypothermia was more strictly maintained in the endovascular than in the surface group (P<0.001). Minor side effects directly related to the cooling method were observed more frequently in the endovascular group (P=0.009). Despite better hypothermia induction and maintenance, endovascular cooling was not significantly superior to basic external cooling in terms of favorable outcome. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00392639. © 2015 American Heart Association, Inc.

Congenital portosystemic vascular malformations.

PubMed

Guérin, Florent; Blanc, Thomas; Gauthier, Frédéric; Abella, Stephanie Franchi; Branchereau, Sophie

2012-08-01

Congenital portosystemic shunts are developmental abnormalities of the portal venous system resulting in the diversion of portal blood away from the liver to the systemic venous system. Such malformations are believed to come from an insult occurring between the fourth and eighth week of gestation during the development of hepatic and systemic venous systems, and could explain their frequent association with cardiac and other vascular anomalies. They are currently categorized into end-to-side shunts (type I) or side-to-side shunts (type II). This article aims to review the common symptoms and complications encountered in congenital portosystemic shunts, the surgical and endovascular treatment, and the role of liver transplantation in this disease. We will also focus on the current controversies and the areas where there is potential for future studies. Copyright © 2012. Published by Elsevier Inc.

Pectoral Fascial (PECS) I and II Blocks as Rescue Analgesia in a Patient Undergoing Minimally Invasive Cardiac Surgery.

PubMed

Yalamuri, Suraj; Klinger, Rebecca Y; Bullock, W Michael; Glower, Donald D; Bottiger, Brandi A; Gadsden, Jeffrey C

Patients undergoing minimally invasive cardiac surgery have the potential for significant pain from the thoracotomy site. We report the successful use of pectoral nerve block types I and II (Pecs I and II) as rescue analgesia in a patient undergoing minimally invasive mitral valve repair. In this case, a 78-year-old man, with no history of chronic pain, underwent mitral valve repair via right anterior thoracotomy for severe mitral regurgitation. After extubation, he complained of 10/10 pain at the incision site that was minimally responsive to intravenous opioids. He required supplemental oxygen because of poor pulmonary mechanics, with shallow breathing and splinting due to pain, and subsequent intensive care unit readmission. Ultrasound-guided Pecs I and II blocks were performed on the right side with 30 mL of 0.2% ropivacaine with 1:400,000 epinephrine. The blocks resulted in near-complete chest wall analgesia and improved pulmonary mechanics for approximately 24 hours. After the single-injection blocks regressed, a second set of blocks was performed with 266 mg of liposomal bupivacaine mixed with bupivacaine. This second set of blocks provided extended analgesia for an additional 48 hours. The patient was weaned rapidly from supplemental oxygen after the blocks because of improved analgesia. Pectoral nerve blocks have been described in the setting of breast surgery to provide chest wall analgesia. We report the first successful use of Pecs blocks to provide effective chest wall analgesia for a patient undergoing minimally invasive cardiac surgery with thoracotomy. We believe that these blocks may provide an important nonopioid option for the management of pain during recovery from minimally invasive cardiac surgery.

Tricuspid regurgitation in patients with pacemakers and implantable cardiac defibrillators: a comprehensive review.

PubMed

Al-Bawardy, Rasha; Krishnaswamy, Amar; Bhargava, Mandeep; Dunn, Justin; Wazni, Oussama; Tuzcu, E Murat; Stewart, William; Kapadia, Samir R

2013-05-01

Implantable cardiac devices, including defibrillators and pacemakers, may be the cause of tricuspid regurgitation (TR) or may worsen existing TR. This review of the literature suggests that TR usually occurs over time after lead implantation. Diagnosis by clinical exam and 2-dimensional echocardiography may be augmented by 3-dimensional echocardiography and/or computed tomography. The mechanism may be mechanical perforation or laceration of leaflets, scarring and restriction of leaflets, or asynchronized activation of the right ventricle. Pacemaker-related TR might cause severe right-sided heart failure, but data regarding associated mortality are lacking. This comprehensive review summarizes the data regarding incidence, mechanism, and treatment of lead-related TR. © 2013 Wiley Periodicals, Inc.

Right heart on multidetector CT

PubMed Central

Gopalan, D

2011-01-01

Right ventricular function plays an integral role in the pathogenesis and outcome of many cardiovascular diseases. Imaging the right ventricle has long been a challenge because of its complex geometry. In recent years there has been a tremendous expansion in multidetector row CT (MDCT) and its cardiac applications. By judicious modification of contrast medium protocol, it is possible to achieve good opacification of the right-sided cardiac chambers, thereby paving the way for exploring the overshadowed right heart. This article will describe the key features of right heart anatomy, review MDCT acquisition techniques, elaborate the various morphological and functional information that can be obtained, and illustrate some important clinical conditions associated with an abnormal right heart. PMID:22723537

AMPD1 polymorphism and response to regadenoson.

PubMed

Saab, Rayan; Zouk, Aline N; Mastouri, Ronald; Skaar, Todd C; Philips, Santosh; Kreutz, Rolf P

2015-11-01

 AMPD1 c.34C > T (rs17602729) polymorphism results in AMPD1 deficiency. We examined the association of AMPD1 deficiency and variability of hemodynamic response to regadenoson. Genotyping for c.34C>T was performed in 267 patients undergoing regadenoson cardiac stress testing. Carriers of c.34C >T variant exhibited higher relative changes in systolic blood pressure (SBP) compared with wild-type subjects ([%] SBP change to peak: 12 ± 25 vs 5 ± 13%; p = 0.01) ([%] SBP change to nadir: -3 ± 15 vs -7 ± 11%; p = 0.04). Change in heart rate was similar between groups, but side effects were more common in carriers of the variant (+LR = 4.2; p = 0.04). AMPD1 deficiency may be involved in the modulation of regadenoson's systemic effects.

Adverse reactions and interactions with beta-adrenoceptor blocking drugs.

PubMed

Lewis, R V; McDevitt, D G

1986-01-01

beta-Blocking drugs are widely used throughout the world and serious adverse reactions are relatively uncommon. Most of those which do occur are pharmacologically predictable and may be avoided by ensuring that patients who are to be given beta-blockers do not have a predisposition to the development of bronchospasm, cardiac failure or peripheral ischaemia. In some situations, the use of a beta 1-selective blocking drug may reduce the risk of a severe adverse reaction, but there is little evidence that other ancillary properties such as partial agonist activity are of relevance in this context. Long term experience with many of the beta-blockers in current use suggests that unpredictable major adverse reactions such as the practolol oculomucocutaneous syndrome are unlikely to be repeated, although some of these drugs may be associated with immunological disturbances and some have been implicated in the development of retroperitoneal fibrosis. beta-Blocking drugs appear to be associated with a number of subjective side effects including muscle fatigue, peripheral coldness and some neurological symptoms. These side effects are highly subjective and are therefore difficult to quantify and it is not known whether they are of major importance in terms of their effect upon patients' overall well-being. It cannot be assumed that simply because such side effects can be elicited that they do, in fact, matter. However, because beta-blockers are often prescribed for patients who have no symptoms and for whom the benefits of therapy are generally small, such side effects would be of considerable importance if they had an overall effect upon quality of life. There are theoretical reasons to suppose that the incidence and severity of such side effects may be related to the ancillary properties of the individual drugs, but there is little evidence that parameters such as beta 1-selectivity, or partial agonist activity are clinically important determinants of the severity of these side effects. Lipophilicity, however, may be associated with an increased incidence of neurological symptoms. beta-Blocking drugs may cause a variety of metabolic disturbances including an increase in serum VLDL-cholesterol concentrations. However, long term studies have not shown that such disturbances are associated with an increased risk of cardiovascular disease, indicating that such metabolic changes may not be of major importance in practice. beta-Blocking drugs may be involved in a number of interactions with other drugs, but few of these have been shown to be of clinical significance.(ABSTRACT TRUNCATED AT 400 WORDS)

Vinpocetine Attenuates Pathological Cardiac Remodeling by Inhibiting Cardiac Hypertrophy and Fibrosis

PubMed Central

Wu, Mei-ping; Zhang, Yi-shuai; Xu, Xiangbin; Zhou, Qian

2017-01-01

Purpose Pathological cardiac remodeling, characterized by cardiac hypertrophy and fibrosis, is a pathological feature of many cardiac disorders that leads to heart failure and cardiac arrest. Vinpocetine, a derivative of the alkaloid vincamine, has been used for enhancing cerebral blood flow to treat cognitive impairment. However, its role in pathological cardiac remodeling remains unknown. The aim of this study is to examine the effect of vinpocetine on pathological cardiac remodeling induced by chronic stimulation with angiotensin II (Ang II). Methods Mice received Ang II infusion via osmotic pumps in the presence of vehicle or vinpocetine. Cardiac hypertrophy and fibrosis were assessed by morphological, histological, and biochemical analyses. Mechanistic studies were carried out in vitro with isolated mouse adult cardiac myocytes and fibroblasts. Results We showed that chronic Ang II infusion caused cardiac hypertrophy and fibrosis, which were all significantly attenuated by systemic administration of vinpocetine. In isolated adult mouse cardiomyocytes, vinpocetine suppressed Ang II-stimulated myocyte hypertrophic growth. In cultured cardiac fibroblasts, vinpocetine suppressed TGFβ-induced fibroblast activation and matrix gene expression, consistent with its effect in attenuating cardiac fibrosis. The effects of vinpocetine on cardiac myocyte hypertrophy and fibroblast activation are likely mediated by targeting cyclic nucleotide phosphodiesterase 1 (PDE1). Conclusions Our results reveal a novel protective effect of vinpocetine in attenuating pathological cardiac remodeling through suppressing cardiac myocyte hypertrophic growth and fibroblast activation and fibrotic gene expression. These studies may also shed light on developing novel therapeutic agents for antagonizing pathological cardiac remodeling. PMID:28321644

Vinpocetine Attenuates Pathological Cardiac Remodeling by Inhibiting Cardiac Hypertrophy and Fibrosis.

PubMed

Wu, Mei-Ping; Zhang, Yi-Shuai; Xu, Xiangbin; Zhou, Qian; Li, Jian-Dong; Yan, Chen

2017-04-01

Pathological cardiac remodeling, characterized by cardiac hypertrophy and fibrosis, is a pathological feature of many cardiac disorders that leads to heart failure and cardiac arrest. Vinpocetine, a derivative of the alkaloid vincamine, has been used for enhancing cerebral blood flow to treat cognitive impairment. However, its role in pathological cardiac remodeling remains unknown. The aim of this study is to examine the effect of vinpocetine on pathological cardiac remodeling induced by chronic stimulation with angiotensin II (Ang II). Mice received Ang II infusion via osmotic pumps in the presence of vehicle or vinpocetine. Cardiac hypertrophy and fibrosis were assessed by morphological, histological, and biochemical analyses. Mechanistic studies were carried out in vitro with isolated mouse adult cardiac myocytes and fibroblasts. We showed that chronic Ang II infusion caused cardiac hypertrophy and fibrosis, which were all significantly attenuated by systemic administration of vinpocetine. In isolated adult mouse cardiomyocytes, vinpocetine suppressed Ang II-stimulated myocyte hypertrophic growth. In cultured cardiac fibroblasts, vinpocetine suppressed TGFβ-induced fibroblast activation and matrix gene expression, consistent with its effect in attenuating cardiac fibrosis. The effects of vinpocetine on cardiac myocyte hypertrophy and fibroblast activation are likely mediated by targeting cyclic nucleotide phosphodiesterase 1 (PDE1). Our results reveal a novel protective effect of vinpocetine in attenuating pathological cardiac remodeling through suppressing cardiac myocyte hypertrophic growth and fibroblast activation and fibrotic gene expression. These studies may also shed light on developing novel therapeutic agents for antagonizing pathological cardiac remodeling.

[Dexrazoxane in anthracycline induced cardiotoxicity and extravasation].

PubMed

Goey, Andrew K L; Schellens, Jan H M; Beijnen, Jos H; Huitema, Alwin D R

2010-01-01

Cardiotoxicity and extravasation injuries are extremely serious complications of anthracycline use. Both complications are probably caused by oxidative stress. Dexrazoxane has been approved as a cardioprotective agent and as an antidote in extravasation of anthracyclines. Randomized clinical trials have shown that dexrazoxane is the only cardioprotective agent proven to be effective in the treatment of anthracycline-induced cardiotoxicity. In these clinical studies dexrazoxane decreased the incidence of cardiac events and heart failure. Possible adverse effects of dexrazoxane when administered as a cardioprotective agent are a decreased antitumor effect of anthracyclines and the onset of secondary malignancies in children. As an antidote in anthracycline extravasation, clinical studies showed dexrazoxane to be highly efficacious in preventing the need for surgical resection. Dexrazoxane can be considered as the treatment of first choice for this indication. Dexrazoxane is well tolerated in general. The most commonly reported side effects are leukopenia, thrombocytopenia and local reactions at the infusion site.

[Congenital portosystemic shunt. The Abernethy malformation].

PubMed

Avila, L F; Luis, A L; Encinas, J L; Hernández, F; Olivares, P; Fernández Cuadrado, J; Hierro, L; Jara, P; López Santamaría, M; Tovar, J A

2006-10-01

Congenital portosystemic shunt (CEPS) is a rare condition that was first reported by John Abernethy in 1793. Two types of CEPS are described: type I (side to end anastomosis) or congenital absence of the portal vein, and type II (side to side anastomosis) with portal vein supply partially conserved. Type I CEPS is usually seen in girls and associates multiple malformations as polysplenia, malrotation, and cardiac anomalies. Type II is even rarer with no sex preference and no malformations associated. Hepatic encephalopathy is a common complication of both types in adulthood. Liver transplantation is the only effective treatment for symptomatic type I CEPS. A therapeutic approach for type II could be surgical closure of the shunt. To analyse our experience in diagnosis and management of portosystemic shunts. We report 4 cases of CEPS (3 type I and 1 type II) diagnosed between January-1997 and March-2005 in our department. We present 4 patients with ages at diagnosis ranging from 0 to 28 months, 3 type I CEPS (2 boys and 1 girl) and 1 boy type II. The type I girl was prenatally diagnosed at 12 weeks of gestation. Initial clinical signs in type 1 boys were splenomegaly and hypersplenism, both with normal pondo-statural growth. No polysplenia or cardiac anomalies were assessed. One of them presented mild developmental delay, dismorphic features and facial telangiectasias. He had normal coagulation tests with chronic hepatic dysfunction (high transaminases) and regenerative nodular lesions were seen by imaging techniques. The other type I patient had hypoprothrombinemia, tendency to capillary bleeding (haematomas and epistaxis) with preserved liver function. Both patients have developed mild portal hypertension and present steatosis signs at liver biopsy. The type I girl presents a 21 trisomy and associates a cardiac anomaly (interauricular communication). Her hepatic function test are normal but liver calcifications can be seen by ultrasound. Type II child associates hypospadias but he has no clinical sigh or symptom related to the shunt. In our three cases diagnosis was suggested by conventional and Doppler ultrasound and confirmed by angio-resonance imaging. All our patients are included in a meticulous clinical and radiological follow-up with no need of surgical treatment for the shunt until now. Although diagnosis of these malformations could be casual we have to think about CEPS in children presenting unspecific liver disease. Magnetic angio-resonance imaging is actually the best diagnosis methods for CEPS. These patients have a high risk for developing hepatic encephalopathy and portal hypertension, so a careful follow-up is required although surgery is not usually needed until adulthood.

Effects of late administration of pentoxifylline and tocotrienols in an image-guided rat model of localized heart irradiation.

PubMed

Sridharan, Vijayalakshmi; Tripathi, Preeti; Sharma, Sunil; Corry, Peter M; Moros, Eduardo G; Singh, Awantika; Compadre, Cesar M; Hauer-Jensen, Martin; Boerma, Marjan

2013-01-01

Radiation-induced heart disease (RIHD) is a long-term side effect of radiotherapy of intrathoracic, chest wall and breast tumors when radiation fields encompass all or part of the heart. Previous studies have shown that pentoxifylline (PTX) in combination with α-tocopherol reduced manifestations of RIHD in rat models of local heart irradiation. The relative contribution of PTX and α-tocopherol to these beneficial effects are not known. This study examined the effects of PTX alone or in combination with tocotrienols, forms of vitamin E with potential potent radiation mitigation properties. Rats received localized X-irradiation of the heart with an image-guided irradiation technique. At 3 months after irradiation rats received oral treatment with vehicle, PTX, or PTX in combination with a tocotrienol-enriched formulation. At 6 months after irradiation, PTX-treated rats showed arrhythmia in 5 out of 14 animals. PTX alone or in combination with tocotrienols did not alter cardiac radiation fibrosis, left ventricular protein expression of the endothelial markers von Willebrand factor and neuregulin-1, or phosphorylation of the signal mediators Akt, Erk1/2, or PKCα. On the other hand, tocotrienols reduced cardiac numbers of mast cells and macrophages, but enhanced the expression of tissue factor. While this new rat model of localized heart irradiation does not support the use of PTX alone, the effects of tocotrienols on chronic manifestations of RIHD deserve further investigation.

Effects of Late Administration of Pentoxifylline and Tocotrienols in an Image-Guided Rat Model of Localized Heart Irradiation

PubMed Central

Sridharan, Vijayalakshmi; Tripathi, Preeti; Sharma, Sunil; Corry, Peter M.; Moros, Eduardo G.; Singh, Awantika; Compadre, Cesar M.; Hauer-Jensen, Martin; Boerma, Marjan

2013-01-01

Radiation-induced heart disease (RIHD) is a long-term side effect of radiotherapy of intrathoracic, chest wall and breast tumors when radiation fields encompass all or part of the heart. Previous studies have shown that pentoxifylline (PTX) in combination with α-tocopherol reduced manifestations of RIHD in rat models of local heart irradiation. The relative contribution of PTX and α-tocopherol to these beneficial effects are not known. This study examined the effects of PTX alone or in combination with tocotrienols, forms of vitamin E with potential potent radiation mitigation properties. Rats received localized X-irradiation of the heart with an image-guided irradiation technique. At 3 months after irradiation rats received oral treatment with vehicle, PTX, or PTX in combination with a tocotrienol-enriched formulation. At 6 months after irradiation, PTX-treated rats showed arrhythmia in 5 out of 14 animals. PTX alone or in combination with tocotrienols did not alter cardiac radiation fibrosis, left ventricular protein expression of the endothelial markers von Willebrand factor and neuregulin-1, or phosphorylation of the signal mediators Akt, Erk1/2, or PKCα. On the other hand, tocotrienols reduced cardiac numbers of mast cells and macrophages, but enhanced the expression of tissue factor. While this new rat model of localized heart irradiation does not support the use of PTX alone, the effects of tocotrienols on chronic manifestations of RIHD deserve further investigation. PMID:23894340

How to interpret liver function tests in heart failure patients?

PubMed

Çağlı, Kumral; Başar, Fatma Nurcan; Tok, Derya; Turak, Osman; Başar, Ömer

2015-05-01

Cardiac hepatopathy has generally been used to describe any liver damage caused by cardiac disorders in the absence of other possible causes of liver damage. Although there is no consensus on the terminology used, cardiac hepatopathy can be examined as congestive hepatopathy (CH) and acute cardiogenic liver injury (ACLI). CH is caused by passive venous congestion of the liver that generally occurs in the setting of chronic cardiac conditions such as chronic HF, constrictive pericarditis, tricuspid regurgitation, or right-sided heart failure (HF) of any cause, and ACLI is most commonly associated with acute cardiocirculatory failure resulting from acute myocardial infarction, acute decompensated HF, or myocarditis. Histologically, CH is characterized by sinusoidal dilation, replacement of hepatocytes with red blood cells extravasating from the sinusoids, and necrosis/apoptosis of zone 3 of the Rappaport acinus, and it could progress to cirrhosis in advanced cases. In ACLI, however, massive necrosis of zone 3 is the main histological finding. Primary laboratory findings of CH are elevated serum cholestasis markers including bilirubin, alkaline phosphatase, and γ-glutamyl-transpeptidase levels, whereas those of ACLI are a striking elevation in transaminase and lactate dehydrogenase levels. Both CH and ACLI have a prognostic value for identifying cardiovascular events and mortality and have some special implications in the management of patients undergoing ventricular assist device implantation or cardiac transplantation. There is no specific treatment for CH or ACLI other than treatment of the underlying cardiac disorder.

A pilot study of the relationship between Doppler-estimated carotid and brachial artery flow and cardiac index.

PubMed

Weber, U; Glassford, N J; Eastwood, G M; Bellomo, R; Hilton, A K

2015-10-01

We measured carotid and brachial artery blood flow by Doppler ultrasound in 11 human volunteers, and related these to cardiac index and to each other. The median (IQR [range]) carotid arterial blood flow was 0.334 (0.223-0.381 [0.052-0.563]) l.min(-1) on the right and 0.315 (0.223-0.369 [0.061-0.690]) l.min(-1) on the left. The brachial arterial blood flow was 0.049 (0.033-0.062 [0.015-0.204]) l.min(-1) on the right and 0.039 (0.027-0.054 [0.011-0.116]) on the left. Cardiac index was 3.2 (2.8-3.5 [1.9-5.4]) l.min(-1) .m(-2) . There was a moderate to good correlation between right-and left-sided flows (brachial: ρ = 0.45; carotid: ρ = 0.567). Brachial and carotid flow had no or a negative correlation with cardiac index (right brachial: ρ = -0.145, left brachial: ρ = -0.349; right carotid: ρ = -0.376, left carotid: ρ = -0.285). In contrast to some previous studies, we found that Doppler-estimated peripheral arterial blood flows only show a weak correlation with cardiac index and cannot be used to provide non-invasive estimates of cardiac index in man. © 2015 The Association of Anaesthetists of Great Britain and Ireland.

Effect of oxidative insult on young and adult cardiac muscle cells in vitro.

PubMed

Nag, A C; Sreepathi, P; Lee, M L; Reddan, J R

1996-01-01

The effect of hydrogen peroxide on cultured neonatal and adult cardiac myocytes was investigated. On neonatal cardiac myocytes the effect was very pronounced at a low concentration (0.03 mM), whereas the adult cardiac myocytes were resistant to the same concentration of H2O2. Dividing neonatal cardiac myocytes were more susceptible to H2O2 insult than the non-dividing adult cardiac myocytes. At a concentration of 0.1 mM H2O2, the neonatal cardiac myocytes were significantly damaged compared with the adult cardiac myocytes. Cardiac muscle cells from neonatal and adult hearts at high density culture were more tolerant to the oxidative insult by H2O2 than cells in low density culture. The damaging effect of H2O2 was very selective on F-actin in neonatal and adult cardiac muscle cells. The effect of H2O2 on myosin, titin, alpha-actinin, desmin or tubulin was not pronounced. Microscopical studies suggested a more marked protection by catalase than by glutathione reductase in the neonatal cells.

Lack of significant effect of bilastine administered at therapeutic and supratherapeutic doses and concomitantly with ketoconazole on ventricular repolarization: results of a thorough QT study (TQTS) with QT-concentration analysis.

PubMed

Tyl, Benoît; Kabbaj, Meriam; Azzam, Sara; Sologuren, Ander; Valiente, Román; Reinbolt, Elizabeth; Roupe, Kathryn; Blanco, Nathalie; Wheeler, William

2012-06-01

The effect of bilastine on cardiac repolarization was studied in 30 healthy participants during a multiple-dose, triple-dummy, crossover, thorough QT study that included 5 arms: placebo, active control (400 mg moxifloxacin), bilastine at therapeutic and supratherapeutic doses (20 mg and 100 mg once daily, respectively), and bilastine 20 mg administered with ketoconazole 400 mg. Time-matched, triplicate electrocardiograms (ECGs) were recorded with 13 time points extracted predose and 16 extracted over 72 hours post day 4 dosing. Four QT/RR corrections were implemented: QTcB; QTcF; a linear individual correction (QTcNi), the primary correction; and a nonlinear one (QTcNnl). Moxifloxacin was associated with a significant increase in QTcNi at all time points between 1 and 12 hours, inclusively. Bilastine administration at 20 mg and 100 mg had no clinically significant impact on QTc (maximum increase in QTcNi, 5.02 ms; upper confidence limit [UCL] of the 1-sided, 95% confidence interval, 7.87 ms). Concomitant administration of ketoconazole and bilastine 20 mg induced a clinically relevant increase in QTc (maximum increase in QTcNi, 9.3 ms; UCL, 12.16 ms). This result was most likely related to the cardiac effect of ketoconazole because for all time points, bilastine plasma concentrations were lower than those observed following the supratherapeutic dose.

Therapeutic vaccines for substance dependence.

PubMed

Kosten, Thomas R; Biegel, Diane

2002-10-01

Several immunotherapies are under development for nicotine, cocaine and phencyclidine and a cocaine vaccine has started human trials. These therapies promise a new approach to diseases that have had limited treatment success and tremendous morbidity. Both the cocaine and nicotine addiction immunotherapies have reduced 'relapse' to drug use in animal model systems. To date, the active cocaine vaccine has few side effects and induces considerable antibody titers after active immunization in humans. Studies with the monoclonal phencyclidine immunotherapy provide intriguing evidence of sustained protection for months after single-dose administration. Other immunotherapy may include treatment of drug overdose, prevention of brain or cardiac toxicity and protection of a fetus during pregnancy in a drug abuser.

Anaesthetics and analgesics; neurocognitive effects, organ protection and cancer reoccurrence an update.

PubMed

Sellbrant, I; Brattwall, M; Jildenstål, P; Warren-Stomberg, M; Forsberg, S; Jakobsson, J G

2016-10-01

Available general and local anaesthetics, third generation inhaled anaesthetics, propofol and amide class local anaesthetics are effective and reassuringly safe. They are all associated to low incidence of toxicology and or adverse-effects. There is however a debate whether anaesthetic drug and technique could exhibit effects beyond the primary effects; fully reversible depression of the central nervous system, dose dependent anaesthesia. Anaesthetics may be involved in the progression of neurocognitive side effects seen especially in the elderly after major surgery, so called Postoperative Cognitive Dysfunction. On the other hand anaesthetics may exhibit organ protective potential, reducing ischemia reperfusion injury and improving survival after cardiac surgery. Anaesthetics and anaesthetic technique may also have effects of cancer reoccurrence and risk for metastasis. The present paper provides an update around the evidence base around anaesthesia potential contributing effect on the occurrence of postoperative cognitive adverse-effects, organ protective properties and influence on cancer re-occurrence/metastasis. Copyright © 2016 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

Evaluation and Management of Right-Sided Heart Failure: A Scientific Statement From the American Heart Association.

PubMed

Konstam, Marvin A; Kiernan, Michael S; Bernstein, Daniel; Bozkurt, Biykem; Jacob, Miriam; Kapur, Navin K; Kociol, Robb D; Lewis, Eldrin F; Mehra, Mandeep R; Pagani, Francis D; Raval, Amish N; Ward, Carey

2018-05-15

The diverse causes of right-sided heart failure (RHF) include, among others, primary cardiomyopathies with right ventricular (RV) involvement, RV ischemia and infarction, volume loading caused by cardiac lesions associated with congenital heart disease and valvular pathologies, and pressure loading resulting from pulmonic stenosis or pulmonary hypertension from a variety of causes, including left-sided heart disease. Progressive RV dysfunction in these disease states is associated with increased morbidity and mortality. The purpose of this scientific statement is to provide guidance on the assessment and management of RHF. The writing group used systematic literature reviews, published translational and clinical studies, clinical practice guidelines, and expert opinion/statements to summarize existing evidence and to identify areas of inadequacy requiring future research. The panel reviewed the most relevant adult medical literature excluding routine laboratory tests using MEDLINE, EMBASE, and Web of Science through September 2017. The document is organized and classified according to the American Heart Association to provide specific suggestions, considerations, or reference to contemporary clinical practice recommendations. Chronic RHF is associated with decreased exercise tolerance, poor functional capacity, decreased cardiac output and progressive end-organ damage (caused by a combination of end-organ venous congestion and underperfusion), and cachexia resulting from poor absorption of nutrients, as well as a systemic proinflammatory state. It is the principal cause of death in patients with pulmonary arterial hypertension. Similarly, acute RHF is associated with hemodynamic instability and is the primary cause of death in patients presenting with massive pulmonary embolism, RV myocardial infarction, and postcardiotomy shock associated with cardiac surgery. Functional assessment of the right side of the heart can be hindered by its complex geometry. Multiple hemodynamic and biochemical markers are associated with worsening RHF and can serve to guide clinical assessment and therapeutic decision making. Pharmacological and mechanical interventions targeting isolated acute and chronic RHF have not been well investigated. Specific therapies promoting stabilization and recovery of RV function are lacking. RHF is a complex syndrome including diverse causes, pathways, and pathological processes. In this scientific statement, we review the causes and epidemiology of RV dysfunction and the pathophysiology of acute and chronic RHF and provide guidance for the management of the associated conditions leading to and caused by RHF. © 2018 American Heart Association, Inc.

Deep hypothermia therapy attenuates LPS-induced microglia neuroinflammation via the STAT3 pathway.

PubMed

Tong, G; Krauss, A; Mochner, J; Wollersheim, S; Soltani, P; Berger, F; Schmitt, K R L

2017-09-01

Deep hypothermia therapy (HT) is a standard method for neuroprotection during complex pediatric cardiac surgery involving extracorporeal circulation and deep hypothermic cardiac arrest. The procedure, however, can provoke systemic inflammatory response syndrome (SIRS), one of the most severe side effects associated with pediatric cardiac surgery. To date, the cellular inflammatory mechanisms induced by deep HT remain to be elucidated. Therefore, we investigated the effects of deep HT (17°C) and rewarming on the inflammatory response in lipopolysaccharide (LPS) stimulated BV-2 murine microglia. Additionally, we also investigated the application of Stattic, a signal transducer and activator of transcription 3 (STAT3) activation inhibitor, as an alternative to physical cooling to attenuate the LPS-induced inflammatory response. Deep HT had no cytotoxic effect but attenuated microglia migration. IκBα degradation was delayed by deep HT resulting in the attenuation of pNF-κB p65 migration into the nucleus and significant decreases in pro-inflammatory IL-6, TNF-α, and MCP-1 expressions and secretions, as well as decreased anti-inflammatory IL-10 and SOCS3 expressions. Additionally, pStat3 was significantly down regulated under deep hypothermic conditions, also corresponding with the significant reduction in IL-6 and TNF-α expressions. Similar to the effects of HT, the application of Stattic under normothermic conditions resulted in significantly reduced IL-6 and TNF-α expressions. Moreover, attenuation of the inflammatory response resulted in decreased apoptosis in a direct co-culture of microglia and neurons. HT reduces the inflammatory response in LPS-stimulated BV-2 microglial cells, alluding to a possible mechanism of therapeutic hypothermia-induced neuroprotection. In the future, attenuating the phospho-STAT3 pathway may lead to the development of a neuroprotectant with greater clinical efficacy. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Cardiorenal benefits of early versus late cyclosporine to sirolimus conversion in a rat model

PubMed Central

Sereno, José; Romão, Ana M.; Parada, Belmiro; Lopes, Patrícia; Carvalho, Eugénia; Teixeira, Frederico; Reis, Flávio

2012-01-01

Objective: To compare the cardiorenal effects of early versus late cyclosporine (CsA) to sirolimus (SRL) conversion, using a novel animal model that mimics these protocols used in the clinical practice, and focusing on blood pressure, heart rate (HR), biochemical data and heart and kidney lipid peroxidation. Materials and Methods: The study had five groups. Six male Wistar rats in each group were used during a 9-week study protocol: control, CsA (5 mg/kg/day), SRL (1 mg/kg/day); early conversion and late conversion. Cardiorenal evaluation was assessed by biochemical data, blood pressure, HR, and heart and kidney lipid peroxidation. Results: As expected, CsA promoted cardiorenal impairment, viewed by development of hypertension, tachycardia, increased urea, creatine kinase, and glucose levels, as well as heart and kidney oxidative stress. SRL, as expected, promoted less cardiorenal side effects, namely those related with nephrotoxicity. In agreement, both early and late conversions from CsA to SRL produced less side-effects, namely those related to the CsA-induced nephrotoxicity. Conclusions: In our model, both early and late CsA to SRL conversion promoted amelioration of the CsA -induced cardiorenal damage. However, early substitution seems to produce more benefits, in particular due to higher improvement of the cardiac profile. PMID:22629089

Real-time 3D visualization of cellular rearrangements during cardiac valve formation

PubMed Central

Pestel, Jenny; Ramadass, Radhan; Gauvrit, Sebastien; Helker, Christian; Herzog, Wiebke

2016-01-01

During cardiac valve development, the single-layered endocardial sheet at the atrioventricular canal (AVC) is remodeled into multilayered immature valve leaflets. Most of our knowledge about this process comes from examining fixed samples that do not allow a real-time appreciation of the intricacies of valve formation. Here, we exploit non-invasive in vivo imaging techniques to identify the dynamic cell behaviors that lead to the formation of the immature valve leaflets. We find that in zebrafish, the valve leaflets consist of two sets of endocardial cells at the luminal and abluminal side, which we refer to as luminal cells (LCs) and abluminal cells (ALCs), respectively. By analyzing cellular rearrangements during valve formation, we observed that the LCs and ALCs originate from the atrium and ventricle, respectively. Furthermore, we utilized Wnt/β-catenin and Notch signaling reporter lines to distinguish between the LCs and ALCs, and also found that cardiac contractility and/or blood flow is necessary for the endocardial expression of these signaling reporters. Thus, our 3D analyses of cardiac valve formation in zebrafish provide fundamental insights into the cellular rearrangements underlying this process. PMID:27302398

Resuscitation Outcomes Consortium (ROC) PRIMED cardiac arrest trial methods part 1: rationale and methodology for the impedance threshold device (ITD) protocol.

PubMed

Aufderheide, Tom P; Kudenchuk, Peter J; Hedges, Jerris R; Nichol, Graham; Kerber, Richard E; Dorian, Paul; Davis, Daniel P; Idris, Ahamed H; Callaway, Clifton W; Emerson, Scott; Stiell, Ian G; Terndrup, Thomas E

2008-08-01

The primary aim of this study is to compare survival to hospital discharge with a modified Rankin score (MRS)< or =3 between standard cardiopulmonary resuscitation (CPR) plus an active impedance threshold device (ITD) versus standard CPR plus a sham ITD in patients with out-of-hospital cardiac arrest. Secondary aims are to compare functional status and depression at discharge and at 3 and 6 months post-discharge in survivors. Prospective, double-blind, randomized, controlled, clinical trial. Patients with non-traumatic out-of-hospital cardiac arrest treated by emergency medical services (EMS) providers. EMS systems participating in the Resuscitation Outcomes Consortium. Based on a one-sided significance level of 0.025, power=0.90, a survival with MRS< or =3 to discharge rate of 5.33% with standard CPR and sham ITD, and two interim analyses, a maximum of 14,742 evaluable patients are needed to detect a 6.69% survival with MRS< or =3 to discharge with standard CPR and active ITD (1.36% absolute survival difference). If the ITD demonstrates the hypothesized improvement in survival, it is estimated that 2700 deaths from cardiac arrest per year would be averted in North America alone.

Real-time 3D visualization of cellular rearrangements during cardiac valve formation.

PubMed

Pestel, Jenny; Ramadass, Radhan; Gauvrit, Sebastien; Helker, Christian; Herzog, Wiebke; Stainier, Didier Y R

2016-06-15

During cardiac valve development, the single-layered endocardial sheet at the atrioventricular canal (AVC) is remodeled into multilayered immature valve leaflets. Most of our knowledge about this process comes from examining fixed samples that do not allow a real-time appreciation of the intricacies of valve formation. Here, we exploit non-invasive in vivo imaging techniques to identify the dynamic cell behaviors that lead to the formation of the immature valve leaflets. We find that in zebrafish, the valve leaflets consist of two sets of endocardial cells at the luminal and abluminal side, which we refer to as luminal cells (LCs) and abluminal cells (ALCs), respectively. By analyzing cellular rearrangements during valve formation, we observed that the LCs and ALCs originate from the atrium and ventricle, respectively. Furthermore, we utilized Wnt/β-catenin and Notch signaling reporter lines to distinguish between the LCs and ALCs, and also found that cardiac contractility and/or blood flow is necessary for the endocardial expression of these signaling reporters. Thus, our 3D analyses of cardiac valve formation in zebrafish provide fundamental insights into the cellular rearrangements underlying this process. © 2016. Published by The Company of Biologists Ltd.

Outcomes of surgical intervention for anomalous aortic origin of a coronary artery: A large contemporary prospective cohort study.

PubMed

Mery, Carlos M; De León, Luis E; Molossi, Silvana; Sexson-Tejtel, S Kristen; Agrawal, Hitesh; Krishnamurthy, Rajesh; Masand, Prakash; Qureshi, Athar M; McKenzie, E Dean; Fraser, Charles D

2018-01-01

The purpose of this study was to prospectively analyze the outcomes of patients with anomalous aortic origin of a coronary artery undergoing surgical intervention according to a standardized management algorithm. All patients aged 2 to 18 years undergoing surgical intervention for anomalous aortic origin of a coronary artery between December 2012 and April 2017 were prospectively included. Patients underwent stress nuclear perfusion imaging, stress cardiac magnetic resonance imaging, and retrospectively electrocardiogram-gated computed tomography angiography preoperatively. Patients were cleared for exercise at 3 months postoperatively if asymptomatic and repeat stress nuclear perfusion imaging, stress cardiac magnetic resonance imaging, and computed tomography angiography showed normal results. A total of 44 patients, with a median age of 14 years (8-18 years), underwent surgical intervention: 9 (20%) for the anomalous left coronary artery and 35 (80%) for the anomalous right coronary artery. Surgical procedures included unroofing in 35 patients (80%), translocation in 7 patients (16%), ostioplasty in 1 patient (2%), and side-side-anastomosis in 1 patient (2%). One patient who presented with aborted sudden cardiac death from an anomalous left coronary and underwent unroofing presented 1 year later with a recurrent episode and was found to have an unrecognized myocardial bridge and persistent compression of the coronary requiring reintervention. At last follow-up, 40 patients (91%) are asymptomatic and 4 patients have nonspecific chest pain; 42 patients (95%) have returned to full activity, and 2 patients are awaiting clearance. Surgical treatment for anomalous aortic origin of a coronary artery is safe and should aim to associate the coronary ostium with the correct sinus, away from the intercoronary pillar. After surgery, the majority of patients are cleared for exercise and remain asymptomatic. Longer follow-up is needed to assess the true efficacy of surgery in the prevention of sudden cardiac death. Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Proposed trial: safety and efficacy of resveratrol for the treatment of non-alcoholic fatty liver disease (NAFLD) and associated insulin resistance in adolescents who are overweight or obese adolescents - rationale and protocol.

PubMed

Wicklow, Brandy; Wittmeier, Kristy; T' Jong, Geert W; McGavock, Jonathon; Robert, Marni; Duhamel, Todd; Dolinsky, Vernon W

2015-10-01

Non-alcoholic fatty liver (NAFL) disease (NAFLD) affects 30% of overweight adolescents and increases the risk of type 2 diabetes mellitus (T2D). Resveratrol is a naturally occurring compound with potential to reverse NAFL and its associated insulin resistance in adults. The use of resveratrol to reduce risk for T2D through its effect on NAFL has not been examined to date in youth. This paper provides a literature review and protocol for a 30 day proof of principle trial of resveratrol in a population of adolescents at risk for T2D. This randomized double-blind controlled trial is designed with the primary objective of evaluating a twice daily supplementation of 75 mg of resveratrol for safety and tolerability in overweight and obese adolescent subjects (13 to <18 years of age) with NAFL. Secondary objectives are to determine the effect size of the intervention on hepatic steatosis and whole body insulin sensitivity. Adolescents in the intervention arm (n = 10) will receive oral supplementation of resveratrol 75 mg twice daily (with breakfast and dinner) for a total daily dose of 150 mg for the duration of 30 days. The comparison group (n = 10) will receive a placebo twice daily for 30 days. Both cases and controls will receive a standardized lifestyle intervention program. Subjects in both groups will be followed for an additional 30 days post intervention for total study duration of approximately 60 days. Primary outcome measures include a primary side effect profile determined by participant interview, a side effect profile determined by serum biochemistry and vital signs. Secondary outcome measures include an oral glucose tolerance test, liver and cardiac fat content measured by magnetic resonance spectroscopy, anthropometric measures of overweight/obesity, inflammatory markers, and cardiac function and morphology measured with ultrasonography. Additional outcome measures include serum concentrations of resveratrol, compliance to protocol, physical activity, and nutritional assessment. This study will determine the safety and tolerability of resveratrol in an overweight adolescent population and inform the design of a larger randomized controlled trial.

Double external jugular vein and other rare venous variations of the head and neck.

PubMed

Shenoy, Varsha; Saraswathi, Perumal; Raghunath, Gunapriya; Karthik, Jayakumar Sai

2012-12-01

Superficial veins of the head and neck are utilised for central venous cannulation, oral reconstruction and parenteral nutrition in debilitated patients. Clinical and sonological examinations of these veins may provide clues toward underlying cardiac pathology. Hence, although variations in these vessels are common, a sound knowledge of such variations becomes clinically important to surgeons, radiologists and interventional anaesthetists. We report a rare case of a left-sided double external jugular vein where the common facial vein continued as the second external jugular vein, and where there was a communicating channel between the internal jugular vein on the same side and the anterior jugular vein.

Enzyme replacement therapy in Fabry disease: influence on cardiac manifestations.

PubMed

Caballero, L; Climent, V; Hernández-Romero, D; Quintanilla, M A; de la Morena, G; Marín, F

2010-01-01

Fabry disease (FD) is an X-linked glycosphingolipid storage disorder caused by deficient activity of the lysosomal enzyme alpha-galactosidase A. This leads to a progressive accumulation of globotriaosylceramide (Gb3) in the lysosomes of different cells and tissues, causing principally ventricular hypertrophy, renal failure and cerebrovascular accidents, reducing lifespan both in hemizygous males and heterozygous females. Residual enzyme activity might lead to slow progression of the disease and result in the so-called cardiac or renal variants with delayed presentation. Two different forms of alpha-galactosidase A enzyme replacement therapies (ERT) are available for the treatment of FD, one genetically engineered in human cell line (agalsidase alfa, Replagal, Shire) and the other produced in a Chinese hamster ovary cell line (agalsidase beta, Fabrazyme, Genzyme). Although both proteins are structurally and functionally very similar, with the same amino acid sequence as the native human enzyme, they differ in the pattern of glycosilation of the protein depending on the originating cell line. Studies with both preparations have described a reduction in plasma, urinary sediment and tissue levels of Gb3, a decrease in the frequency of pain crisis and a reduction in left ventricular mass and improvement or stabilization of renal function. Studies have generally shown the greatest benefit when treatment is started at an early stage of the disease before extensive fibrosis or other irreversible tissue damage takes place. However, more data are needed to document long-term treatment outcomes. The aim of the present review is to provide an update overview of the two different forms of ERT for FD, their clinical effects in cardiac manifestations and their possible differences in terms of efficacy, side effects and safety profiles.

Left phrenic nerve anatomy relative to the coronary venous system: Implications for phrenic nerve stimulation during cardiac resynchronization therapy.

PubMed

Spencer, Julianne H; Goff, Ryan P; Iaizzo, Paul A

2015-07-01

The objective of this study was to quantitatively characterize anatomy of the human phrenic nerve in relation to the coronary venous system, to reduce undesired phrenic nerve stimulation during left-sided lead implantations. We obtained CT scans while injecting contrast into coronary veins of 15 perfusion-fixed human heart-lung blocs. A radiopaque wire was glued to the phrenic nerve under CT, then we created three-dimensional models of anatomy and measured anatomical parameters. The left phrenic nerve typically coursed over the basal region of the anterior interventricular vein, mid region of left marginal veins, and apical region of inferior and middle cardiac veins. There was large variation associated with the average angle between nerve and veins. Average angle across all coronary sinus tributaries was fairly consistent (101.3°-111.1°). The phrenic nerve coursed closest to the middle cardiac vein and left marginal veins. The phrenic nerve overlapped a left marginal vein in >50% of specimens. © 2015 Wiley Periodicals, Inc.

Use of contrast echocardiography in diagnosis of anomalous connection of right superior vena cava to left atrium.

PubMed Central

Truman, A T; Rao, P S; Kulangara, R J

1980-01-01

A 4-month-old infant with cyanosis but without other abnormal cardiac findings is presented in whom the diagnosis of anomalous systemic venous connection to the left atrium was made by contrast echocardiography. The diagnosis was later confirmed by cardiac catheterisation and selective cineangiography. When saline was injected into a vein on the dorsum of each hand while echocardiographically recording the cardiac structures, the left atrium, left ventricle, and aorta were opacified without visualisation of the right ventricle. Similar study with injection into the right foot produced opacification of the right ventricle without visualisation of the left-sided structures. These data suggested normal drainage of the inferior vena cava with anomalous connection of the superior vena cava to the left atrium. A review of the previously reported cases of anomalous connection of the right superior vena cava to the left atrium is presented together with the possible embryological origin of this anomaly. Images PMID:7459157

[Clinical epidemiological retro prospective studies on the incidence and prevalence of cardiac congenital abnormalities in a group of 1570 children, born in Iaşi between 2000-2009].

PubMed

Chiosac, Alina Andreea Andreescu; Gorduza, E V; Stamatin, Maria; Novac, Otilia; Ivan, A

2010-01-01

The study has been conducted on a period of ten years and it included 1570 children with congenital abnormalities (CA), of which 371 (24%) were cardiac abnormalities, 312 (20%) were skeletal abnormalities, 55 (3%) were Down Syndrome and 832 (53%) were other pathologies. 48% of the 371 children that were diagnosed with cardiac CA were males, while 52% were females; 52% of the children were from the city, while 48% were from the country-side; 42% of the children have been born prematurely, while 58% of them have been born at normal term. 38% of the children had an APGAR score lower than 7 and 62% of them had an APGAR score higher than 7. Of the total number of births, 72% were caesarian births and 28% were natural births. The different types of Cardiac CA that have been encountered in the study were atrioventricular canal (56%), transposition of the great vessels (18%), common arterial trunk (10%), atrial septal defect (8%), ventricular septal defect (5%) and tetralogy of Fallot (3%). 66% of the total number of deaths were represented by those with cardiac pathology, 21% were caused by hydrocephalus, 7% were caused by diaphragmatic hernia, 4% had renal CA, while 2% were caused by other pathologies.

Cardiac Safety of Ozanimod, a Novel Sphingosine‐1‐Phosphate Receptor Modulator: Results of a Thorough QT/QTc Study

PubMed Central

Hartung, Jeffrey P.; Olson, Allan D.; Mendzelevski, Boaz; Timony, Gregg A.; Boehm, Marcus F.; Peach, Robert J.; Gujrathi, Sheila; Frohna, Paul A.

2017-01-01

Abstract Ozanimod is a novel, selective, oral sphingosine‐1‐phosphate (1 and 5) receptor modulator in development for multiple sclerosis and inflammatory bowel disease. This randomized, double‐blind, placebo‐controlled, positive‐controlled, parallel‐group thorough QT study characterized the effects of ozanimod on cardiac repolarization in healthy subjects. Eligible subjects were randomized to 1 of 2 groups: ozanimod (escalated from 0.25 to 2 mg over 14 days) or placebo (for 14 days). A single dose of moxifloxacin 400 mg or placebo was administered on days 2 and 17. The primary end point was the time‐matched, placebo‐corrected, baseline‐adjusted mean QTcF (ΔΔQTcF). A total of 113/124 (91.1%) subjects completed the study. The upper limits of the 2‐sided 90% confidence intervals for ΔΔQTcF for both ozanimod 1 and 2 mg were below the 10‐millisecond regulatory threshold. No QTcF >480 milliseconds or postdose change in QTcF of >60 milliseconds was observed. There was no evidence of a positive relationship between concentrations of ozanimod and its active metabolites and ΔΔQTcF. Although ozanimod blunted the observed diurnal increase in heart rate, excursions below predose heart rates were no greater than with placebo. Results demonstrate that ozanimod does not prolong the QTc interval or cause clinically significant bradycardia, supporting ozanimod's evolving favorable cardiac safety profile. PMID:28783871

Getting to the heart of hERG K(+) channel gating.

PubMed

Perry, Matthew D; Ng, Chai-Ann; Mann, Stefan A; Sadrieh, Arash; Imtiaz, Mohammad; Hill, Adam P; Vandenberg, Jamie I

2015-06-15

Potassium ion channels encoded by the human ether-a-go-go related gene (hERG) form the ion-conducting subunit of the rapid delayed rectifier potassium current (IKr ). Although hERG channels exhibit a widespread tissue distribution they play a particularly important role in the heart. There has been considerable interest in hERG K(+) channels for three main reasons. First, they have very unusual gating kinetics, most notably rapid and voltage-dependent inactivation coupled to slow deactivation, which has led to the suggestion that they may play a specific role in the suppression of arrhythmias. Second, mutations in hERG are the cause of 30-40% of cases of congenital long QT syndrome (LQTS), the commonest inherited primary arrhythmia syndrome. Third, hERG is the molecular target for the vast majority of drugs that cause drug-induced LQTS, the commonest cause of drug-induced arrhythmias and cardiac death. Drug-induced LQTS has now been reported for a large range of both cardiac and non-cardiac drugs, in which this side effect is entirely undesired. In recent years there have been comprehensive reviews published on hERG K(+) channels (Vandenberg et al. 2012) and we will not re-cover this ground. Rather, we focus on more recent work on the structural basis and dynamics of hERG gating with an emphasis on how the latest developments may facilitate translational research in the area of stratifying risk of arrhythmias. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

Getting to the heart of hERG K+ channel gating

PubMed Central

Perry, Matthew D; Ng, Chai-Ann; Mann, Stefan A; Sadrieh, Arash; Imtiaz, Mohammad; Hill, Adam P; Vandenberg, Jamie I

2015-01-01

Potassium ion channels encoded by the human ether-a-go-go related gene (hERG) form the ion-conducting subunit of the rapid delayed rectifier potassium current (IKr). Although hERG channels exhibit a widespread tissue distribution they play a particularly important role in the heart. There has been considerable interest in hERG K+ channels for three main reasons. First, they have very unusual gating kinetics, most notably rapid and voltage-dependent inactivation coupled to slow deactivation, which has led to the suggestion that they may play a specific role in the suppression of arrhythmias. Second, mutations in hERG are the cause of 30–40% of cases of congenital long QT syndrome (LQTS), the commonest inherited primary arrhythmia syndrome. Third, hERG is the molecular target for the vast majority of drugs that cause drug-induced LQTS, the commonest cause of drug-induced arrhythmias and cardiac death. Drug-induced LQTS has now been reported for a large range of both cardiac and non-cardiac drugs, in which this side effect is entirely undesired. In recent years there have been comprehensive reviews published on hERG K+ channels (Vandenberg et al. 2012) and we will not re-cover this ground. Rather, we focus on more recent work on the structural basis and dynamics of hERG gating with an emphasis on how the latest developments may facilitate translational research in the area of stratifying risk of arrhythmias. PMID:25820318

Fatalities after taking ibogaine in addiction treatment could be related to sudden cardiac death caused by autonomic dysfunction.

PubMed

Maas, U; Strubelt, S

2006-01-01

Ibogaine is the most important alkaloid of the Central African Iboga-shrub. It is the central drug in Gabonian initiation ceremonies in which it is used to cause a near-death experience. In Western countries it is used in private clinics to treat addiction. However, in the United States and most European countries it is classified as an illegal drug because at least eight persons have died after having taken Ibogaine. These fatalities occurred in most cases several days after ingestion or following the intake of very small doses. There is no conclusive explanation at the present time for these deaths. We hypothesize, that these deaths may be a result of cardiac arrhythmias, caused by a dysregulation of the autonomic nervous system. Ibogaine affects the autonomic nervous system by influencing several neurotransmitter-systems and the fastigial nucleus. The cerebellar nucleus responds to small doses with a stimulation of the sympathetic system, leading to a fight or flight reaction. High doses, however, lead to a vagal dominance: a "feigned death". The risk of cardiac arrhythmias is increased in situations of sympathetic stimulation or coincidence of a high parasympathetic tonus and a left-sided sympathetic stimulation. This could occur under influence of small doses of ibogaine and also at times of exhaustion with a high vagal tonus, when sudden fear reactions could cause a critical left-sided sympathetic stimulation. Gabonian healers prevent these risks by isolating their patients from normal life and by inducing a trance-state with right-hemispheric and vagal dominance for several days.

Adjustable lead glass shielding device for use with an over-the-table x-ray tube.

PubMed

Eubig, C; Groves, B M; Davey, G

1978-12-01

Sources of scattered radiation exposure to personnel from a ceiling-mounted x-ray tube were examined at the side of cardiac catheterization patients. A fully adjustable mounting for a lead glass shield was designed to afford maximum radiation protection to the attending physician's head and neck area, while minimizing interference with the procedure.

Trimetazidine protects against cardiac ischemia/reperfusion injury via effects on cardiac miRNA-21 expression, Akt and the Bcl-2/Bax pathway

PubMed Central

Ma, Ning; Bai, Jingyun; Zhang, Weihua; Luo, Hong; Zhang, Xin; Liu, Donghai; Qiao, Chenhui

2016-01-01

Trimetazidine is a piperazine-derived metabolic agent, which exerts cell protective effects and has been reported to be efficient in the treatment of chronic stable angina pectoris. In addition, it has been shown to exert protection against acute myocardial infarction. The present study aimed to investigate whether trimetazidine protects against cardiac ischemia/reperfusion (I/R) injury, and to determine whether its curative effects are associated with microRNA (miRNA)-21 expression, Akt, and the B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein (Bax) pathway. Cardiac I/R injury was induced by ligating the left anterior descending coronary artery in adult rats. Subsequently, cardiac function was evaluated, and the expression levels of miRNA-21, Bcl-2, Bax and phosphorylated-Akt were detected using quantitative polymerase chain reaction and western blotting. The results indicated that trimetazidine was able to significantly protect cardiac function and reduce infarct size in rats following cardiac I/R injury. Furthermore, trimetazidine significantly promoted miRNA-21 expression and phosphorylated-Akt protein expression, and reduced the Bcl-2/Bax ratio in rats following cardiac I/R injury. Knockdown of miRNA-21 using anti-miR-21 plasmids was able to reverse the protective effects of trimetazidine against cardiac I/R injury. These results indicated that miRNA-21 serves a protective role in cardiac I/R injury via Akt and the Bcl-2/Bax pathway. In addition, trimetazidine exerts protective effects against cardiac I/R injury through cardiac miRNA-21 expression, Akt, and the Bcl-2/Bax pathway. Therefore, the present study provided evidence regarding the protective effects of miRNA-21 on cardiac I/R injury following treatment with trimetazidine in vivo. PMID:27666568

Drug insight: If inhibitors as specific heart-rate-reducing agents.

PubMed

Borer, Jeffrey S

2004-12-01

Heart rate is determined primarily by spontaneously repeating net inward current carried by sodium ions and potassium ions through hyperpolarization-activated cyclic-nucleotide-gated channels. Within the heart, these channels are found most abundantly in sinoatrial cardiomyocytes. The channels open in response to membrane hyperpolarization, modulated by local cAMP concentrations. They permit activation of the I(f) current, which can be blocked specifically by molecules characterized by linked benzazepinone and benzocyclobutane rings, and which are devoid of effects on cardiac conduction, inotropy or peripheral vascular tone. The resulting heart-rate reduction has been effective in angina prevention in clinical trials involving 4,000 patients, using the prototype I(f) inhibitor, ivabradine. No serious adverse events have been attributed to the treatment; the most prominent side-effect is dose-related, always reversible and often transient visual symptoms that seldom result in voluntary drug discontinuation.

Cimetidine: II. Adverse reactions and patterns of use.

PubMed

Freston, J W

1982-11-01

Numerous adverse reactions have been attributed to cimetidine, which is understandable in view of the attention and scrutiny the drug has received, its widespread use, and its systemic effects. The reported frequency of side effects has differed considerably but is surprisingly low in all studies. The drug has caused an array of central nervous system disturbances, gynecomastia, and, rarely, hepatotoxicity, interstitial nephritis, bradycardia, hypotension, and even cardiac arrest. The last complication has occurred with rapid-bolus intravenous injection. Blood dyscrasias have also been rare and usually associated with serious underlying disease or multiple drugs, making it difficult to establish cause and effect in most cases. The drug is used widely to treatment conditions for which it is not approved. Some of these conditions are now believed to respond to cimetidine (gastric ulcer); others are known not to respond (acute upper gastrointestinal bleeding and acute pancreatitis).

Doxorubicin Action on Mitochondria: Relevance to Osteosarcoma Therapy?

PubMed

Armstrong, Jo; Dass, Crispin R

2018-01-01

The mitochondria may very well determine the final commitment of the cell to death, particularly in times of energy stress. Cancer chemotherapeutics such as the anthracycline doxorubicin perturb mitochondrial structure and function in tumour cells, as evidenced in osteosarcoma, for which doxorubicin is used clinically as frontline therapy. This same mechanism of cell inhibition is also pertinent to doxorubicin's primary cause of side-effects, that to the cardiac tissue, culminating in such dire events as congestive heart failure. Reactive oxygen species are partly to blame for this effect on the mitochondria, which impact the electron transport chain. As this review highlights that, there is much more to be learnt about the mitochondria and how it is affected by such effective but toxic drugs as doxorubicin. Such information will aid researchers who search for cancer treatment able to preserve mitochondrial number and function in normal cells. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

[New Insights into Maternal Cardiopulmonary Resuscitation--Significance of Simulation Research and Training].

PubMed

Komasawa, Nobuyasu; Fujiwara, Shunsuke; Majima, Nozomi; Minami, Toshiaki

2015-08-01

Pregnancy-related mortality, estimated to occur in approximately 1: 50,000 deliveries, is rare in developed countries. The 2010 American Heart Association (AHA) Guidelines for Resuscitation emphasize the importance of high-quality chest compression as a key determinant of successful cardiopulmonary resuscitation. During pregnancy, the uterus can compress the inferior vena cava, impeding venous return and thereby reducing stroke volume and cardiac output. To maximize the effectiveness of chest compressions in pregnancy, the AHA guidelines recommend the 27-30 degrees left-lateral tilt (LLT) position. When CPR is performed on parturients in the LLT position, chest compressions will probably be more effective if performed with the operator standing on the left side of the patient. The videolaryngoscope Pentax-AWS Airwayscope (AWS) was found to be an effective tool for airway management during chest compressions in 27 LLT simulations, suggesting that the AWS may be a useful device for airway management during maternal resuscitation.

Deterioration of kidney function by the (pro)renin receptor blocker handle region peptide in aliskiren-treated diabetic transgenic (mRen2)27 rats.

PubMed

te Riet, Luuk; van den Heuvel, Mieke; Peutz-Kootstra, Carine J; van Esch, Joep H M; van Veghel, Richard; Garrelds, Ingrid M; Musterd-Bhaggoe, Usha; Bouhuizen, Angelique M; Leijten, Frank P J; Danser, A H Jan; Batenburg, Wendy W

2014-05-15

Dual renin-angiotensin system (RAS) blockade in diabetic nephropathy is no longer feasible because of the profit/side effect imbalance. (Pro)renin receptor [(P)RR] blockade with handle region peptide (HRP) has been reported to exert beneficial effects in various diabetic models in a RAS-independent manner. To what degree (P)RR blockade adds benefits on top of RAS blockade is still unknown. In the present study, we treated diabetic TGR(mREN2)27 rats, a well-established nephropathy model with high prorenin levels [allowing continuous (P)RR stimulation in vivo], with HRP on top of renin inhibition with aliskiren. Aliskiren alone lowered blood pressure and exerted renoprotective effects, as evidenced by reduced glomerulosclerosis, diuresis, proteinuria, albuminuria, and urinary aldosterone levels as well as diminished renal (P)RR and ANG II type 1 receptor expression. It also suppressed plasma and tissue RAS activity and suppressed cardiac atrial natriuretic peptide and brain natriuretic peptide expression. HRP, when given on top of aliskiren, did not alter the effects of renin inhibition on blood pressure, RAS activity, or aldosterone. However, it counteracted the beneficial effects of aliskiren in the kidney, induced hyperkalemia, and increased plasma plasminogen activator-inhibitor 1, renal cyclooxygenase-2, and cardiac collagen content. All these effects have been linked to (P)RR stimulation, suggesting that HRP might, in fact, act as a partial agonist. Therefore, the use of HRP on top of RAS blockade in diabetic nephropathy is not advisable. Copyright © 2014 the American Physiological Society.

Effect of hydration status on atrial and ventricular volumes and function in healthy adult volunteers.

PubMed

Schantz, Daryl I; Dragulescu, Andreea; Memauri, Brett; Grotenhuis, Heynric B; Seed, Mike; Grosse-Wortmann, Lars

2016-10-01

Assessment of cardiac chamber volumes is a fundamental part of cardiac magnetic resonance (CMR) imaging. While the effects of inter- and intraobserver variability have been studied and have a recognized effect on the comparability of serial cardiac MR imaging studies, the effect of differences in hydration status has not been evaluated. To evaluate the effects of volume administration on cardiac chamber volumes. Thirteen healthy adults underwent a baseline cardiac MR to evaluate cardiac chamber volumes after an overnight fast. They were then given two saline boluses of 10 ml/kg of body weight and the cardiac MR was repeated immediately after each bolus. From the baseline scan to the final scan there was a significant increase in all four cardiac chamber end-diastolic volumes. Right atrial volumes increased 8.0%, from 61.1 to 66.0 ml/m2 (P<0.001), and left atrial volumes increased 10.0%, from 50.0 to 55.0 ml/m2 (P<0.001). Right ventricular volumes increased 6.0%, from 91.1 to 96.5 ml/m2 (P<0.001), and left ventricular volumes increased 3.2%, from 87.0 to 89.8 ml/m2 (P<0.001). Hydration status has a significant effect on the end-diastolic volumes of all cardiac chambers assessed by cardiac MR. Thus, hydration represents a "variable" that should be taken into account when assessing cardiac chamber volumes, especially when performing serial imaging studies in a patient.

A Combination of Two Rare Coronary Anomalies Makes It Even Rarer: Right Sided Single Coronary Artery with Dual Left Anterior Descending Artery

PubMed Central

Addai, Theodore; Kola, Monahar; Raqeem, Muhammad Wajih; Barsamyan, Sergey; Mirrakhimov, Aibek E.

2016-01-01

An 82-year-old female with history of hyperlipidemia and hypertension presented to the clinic with chief complaint of nonradiating chest tightness accompanied by exertional dyspnea. Cardiac catheterization showed the absence of left coronary system; the entire coronary system originated from the right aortic sinus as a common trunk which then gave off the right coronary artery and the left main coronary artery. Cardiac catheterization demonstrated also another rare coronary anomaly: dual left anterior descending artery. Patient underwent percutaneous coronary intervention and subsequent multidetector computed tomography angiography confirmed the above angiography findings. Patient was subsequently discharged home on double antiplatelet therapy with aspirin and clopidogrel and has been asymptomatic since then. PMID:27293909

A cost-effectiveness analysis of hormone replacement therapy in the menopause.

PubMed

Cheung, A P; Wren, B G

1992-03-02

To evaluate the cost-effectiveness of hormone replacement therapy in the menopause with particular reference to osteoporotic fracture and myocardial infarction. The multiple-decrement form of the life table was the mathematical model used to follow women of age 50 through their lifetime under the "no hormone replacement" and "hormone replacement" assumptions. Standard demographic and health economic techniques were used to calculate the corresponding lifetime differences in direct health care costs (net costs in dollars) and health effects ("net effectiveness" in terms of life expectancy and quality, in "quality-adjusted life-years"). This was then expressed as a cost-effectiveness ratio or the cost ($) per quality-adjusted life-year (QALY) for each of the chosen hormone replacement regimens. All women of age 50 in New South Wales, Australia (n = 27,021). The analysis showed that the lifetime net increments in direct medical care costs were largely contributed by hormone drug and consultation costs. Hormone replacement was associated with increased quality-adjusted life expectancy, a large percentage of which was attributed to a relief of menopausal symptoms. Cost-effectiveness ratios ranged from under 10,000 to over a million dollars per QALY. Factors associated with improved cost-effectiveness were prolonged treatment duration, the presence of menopausal symptoms, minimum progestogen side effects (in the case of oestrogen with progestogen regimens), oestrogen use after hysterectomy and the inclusion of cardiac benefits in addition to fracture prevention. Hormone replacement therapy for symptomatic women is cost-effective when factors that enhance its efficiency are considered. Short-term treatment of asymptomatic women for prevention of osteoporotic fractures and myocardial infarction is an inefficient use of health resources. Cost-effectiveness of hormone replacement in asymptomatic women is dependent on the magnitude of cardiac benefits associated with hormone use and the treatment duration.

Effects of Ionizing Radiation on the Heart

PubMed Central

Boerma, Marjan; Sridharan, Vijayalakshmi; Mao, Xiao-Wen; Nelson, Gregory A.; Cheema, Amrita K.; Koturbash, Igor; Singh, Sharda P.; Tackett, Alan J.; Hauer-Jensen, Martin

2016-01-01

This article provides an overview of studies addressing effects of ionizing radiation on the heart. Clinical studies have identified early and late manifestations of radiation-induced heart disease, a side effect of radiation therapy to tumors in the chest when all or part of the heart is situated in the radiation field. Studies in preclinical animal models have contributed to our understanding of the mechanisms by which radiation may injure the heart. More recent observations in human subjects suggest that ionizing radiation may have cardiovascular effects at lower doses than was previously thought. This has led to examinations of low-dose photons and low-dose charged particle irradiation in animal models. Lastly, studies have started to identify noninvasive methods for detection of cardiac radiation injury and interventions that may prevent or mitigate these adverse effects. Altogether, this ongoing research should increase our knowledge of biological mechanisms of cardiovascular radiation injury, identify non-invasive biomarkers for early detection, and potential interventions that may prevent or mitigate these adverse effects. PMID:27919338

Comparative anatomy and evolution of the cardiac innervation in New World monkeys (Platyrrhini, e. Geoffroy, 1812).

PubMed

Kawashima, Tomokazu; Thorington, Richard W; Whatton, James F

2009-05-01

The morphology of the autonomic cardiac nervous system (ACNS) was examined in 24 sides of 12 New World monkeys (Platyrrhini) of all four families to document the morphology systematically and to study the evolutionary changes of the ACNS in this primate lineage. We report the following: (1) Although several trivial intra- and inter-specific variations are present, a family-dependent morphology of the ACNS does not exist in New World monkeys. (2) The sympathetic ganglia in New World monkeys consist of the superior cervical, the middle cervical, and the cervicothoracic which is composed of the inferior cervical and first and second thoracic, and the thoracic ganglia starting with the third thoracic. The general cardiac nervous system is the sympathetic middle and inferior cardiac nerves and all parasympathetic vagal cardiac branches. (3) The morphology of the ACNS in the New World monkeys is almost consistent regardless of the number of vertebrae, the cardiac position and deviation (axis), and the great arterial branching pattern of the aortic arch, and it is very similar to that in the Old World monkeys, with only one difference: the superior cervical ganglion in the New World monkeys tends to be relatively smaller, higher, and provides a narrower contribution to the spinal nerves than in the Old World monkeys. The ACNS morphology exhibits significant evolutionary changes within the primate lineage from New and Old World monkeys to humans. The comparative morphology within the lineage is concordant with the phylogeny, suggesting that the primate ACNS preserves its evolutionary history in close alignment with phylogeny.

Intrapericardial echocardiography: a novel catheter-based approach to cardiac imaging.

PubMed

Rodrigues, Ana Clara Tude; d'Avila, Andre; Houghtaling, Christopher; Ruskin, Jeremy N; Picard, Michael; Reddy, Vivek Y

2004-03-01

Transvascular catheter-based intracardiac echocardiography has been successfully used to help guide catheter ablation and electrophysiologic procedures. It has recently been demonstrated that catheters can be safely placed into the pericardial space to allow for epicardial cardiac mapping and ablation. We evaluated the feasibility of catheter-based intrapericardial echocardiography (IPE) during such procedures to identify cardiac structures and visualize intracardiac catheters. IPE was performed in 7 goats by placing a phased-array ultrasound transducer contained within a 10F steerable catheter into the pericardial space using the same transthoracic subxyphoid approach as used to map and ablate epicardial ventricular tachycardia. Images were obtained of cardiac structures and of intracardiac ablation catheters. After the procedure, the hearts were harvested to assess for possible IPE-related lesions. The IPE catheter could be easily placed inside the pericardial space in all animals. In 7 of 7 cases, longitudinal and short-axis views of right- and left-sided chambers and valves were obtained, similar in orientation to transesophageal echocardiography. Visualization of atrial appendages (6/7), pulmonary veins (6/7), coronary arteries (6/7), and coronary sinus (3/6) was also feasible. Assessment of intracardiac transvalvar and venous blood flow was achieved by spectral and color Doppler. The ablation catheter could be clearly visualized inside cardiac chambers. No arrhythmias were induced with IPE catheter manipulation. After harvesting the hearts, no lesions resulting from the procedure were observed. In this experimental setting, IPE was able to provide detailed images of cardiac structures and establish the relative position of the ablation catheter.

Vagal stimulation targets select populations of intrinsic cardiac neurons to control neurally induced atrial fibrillation

PubMed Central

Salavatian, Siamak; Beaumont, Eric; Longpré, Jean-Philippe; Armour, J. Andrew; Vinet, Alain; Jacquemet, Vincent; Shivkumar, Kalyanam

2016-01-01

Mediastinal nerve stimulation (MNS) reproducibly evokes atrial fibrillation (AF) by excessive and heterogeneous activation of intrinsic cardiac (IC) neurons. This study evaluated whether preemptive vagus nerve stimulation (VNS) impacts MNS-induced evoked changes in IC neural network activity to thereby alter susceptibility to AF. IC neuronal activity in the right atrial ganglionated plexus was directly recorded in anesthetized canines (n = 8) using a linear microelectrode array concomitant with right atrial electrical activity in response to: 1) epicardial touch or great vessel occlusion vs. 2) stellate or vagal stimulation. From these stressors, post hoc analysis (based on the Skellam distribution) defined IC neurons so recorded as afferent, efferent, or convergent (afferent and efferent inputs) local circuit neurons (LCN). The capacity of right-sided MNS to modify IC activity in the induction of AF was determined before and after preemptive right (RCV)- vs. left (LCV)-sided VNS (15 Hz, 500 μs; 1.2× bradycardia threshold). Neuronal (n = 89) activity at baseline (0.11 ± 0.29 Hz) increased during MNS-induced AF (0.51 ± 1.30 Hz; P < 0.001). Convergent LCNs were preferentially activated by MNS. Preemptive RCV reduced MNS-induced changes in LCN activity (by 70%) while mitigating MNS-induced AF (by 75%). Preemptive LCV reduced LCN activity by 60% while mitigating AF potential by 40%. IC neuronal synchrony increased during neurally induced AF, a local neural network response mitigated by preemptive VNS. These antiarrhythmic effects persisted post-VNS for, on average, 26 min. In conclusion, VNS preferentially targets convergent LCNs and their interactive coherence to mitigate the potential for neurally induced AF. The antiarrhythmic properties imposed by VNS exhibit memory. PMID:27591222

External cardiac compression may be harmful in some scenarios of pulseless electrical activity.

PubMed

Hogan, T S

2012-10-01

Pulseless electrical activity occurs when organised or semi-organised electrical activity of the heart persists but the product of systemic vascular resistance and the increase in systemic arterial flow generated by the ejection of the left venticular stroke volume is not sufficient to produce a clinically detectable pulse. Pulseless electrical activity encompasses a very heterogeneous variety of severe circulatory shock states ranging in severity from pseudo-cardiac arrest to effective cardiac arrest. Outcomes of cardiopulmonary resuscitation for pulseless electrical activity are generally poor. Impairment of cardiac filling is the limiting factor to cardiac output in many scenarios of pulseless electrical activity, including extreme vasodilatory shock states. There is no evidence that external cardiac compression can increase cardiac output when impaired cardiac filling is the limiting factor to cardiac output. If impaired cardiac filling is the limiting factor to cardiac output and the heart is effectively ejecting all the blood returning to it, then external cardiac compression can only increase cardiac output if it increases venous return and cardiac filling. Repeated cardiac compression asynchronous with the patient's cardiac cycle and raised mean intrathoracic pressure due to chest compression can be expected to reduce rather than to increase cardiac filling and therefore to reduce rather than to increase cardiac output in such circumstances. The hypothesis is proposed that the performance of external cardiac compression will have zero or negative effect on cardiac output in pulseless electrical activity when impaired cardiac filling is the limiting factor to cardiac output. External cardiac compression may be both directly and indirectly harmful to significant sub-groups of patients with pulseless electrical activity. We have neither evidence nor theory to provide comfort that external cardiac compression is not harmful in many scenarios of pulseless electrical activity. Investigation using a variety of animal models of pulseless electrical activity produced by different shock-inducing mechanisms is required to provide an evidence base for resuscitation guidelines. Copyright © 2012 Elsevier Ltd. All rights reserved.

TU-G-BRA-08: BEST IN PHYSICS (JOINT IMAGING-THERAPY): Hybrid PET-MRI Imaging of Acute Radiation Induced Cardiac Toxicity

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

El-Sherif, O; Xhaferllari, I; Gaede, S

Purpose: To identify the presence of low-dose radiation induced cardiac toxicity in a canine model using hybrid positron emission tomography (PET) and magnetic resonance imaging (MRI). Methods: Research ethics board approval was obtained for a longitudinal imaging study of 5 canines after cardiac irradiation. Animals were imaged at baseline, 1 week post cardiac irradiation, and 1 month post cardiac irradiation using a hybrid PET- MRI system (Biograph mMR, Siemens Healthcare). The imaging protocol was designed to assess acute changes in myocardial perfusion and inflammation. Myocardial perfusion imaging was performed using N13-ammonia tracer followed by a dynamic PET acquisition scan. Amore » compartmental tracer kinetic model was used for absolute perfusion quantification. Myocardial inflammation imaging was performed using F18-fluorodeoxyglucose (FDG) tracer. The standard uptake value (SUV) over a region encompassing the whole heart was used to compare FDG scans. All animals received a simulation CT scan (GE Medical Systems) for radiation treatment planning. Radiation treatment plans were created using the Pinncale3 treatment planning system (Philips Radiation Oncology Systems) and designed to resemble the typical cardiac exposure during left-sided breast cancer radiotherapy. Cardiac irradiations were performed in a single fraction using a TrueBeam linear accelerator (Varian Medical Systems). Results: The delivered dose (mean ± standard deviation) to heart was 1.8±0.2 Gy. Reductions in myocardial stress perfusion relative to baseline were observed in 2 of the 5 animals 1 month post radiation. A global inflammatory response 1 month post radiation was observed in 4 of the 5 animals. The calculated SUV at 1 month post radiation was significantly higher (p=0.05) than the baseline SUV. Conclusion: Low doses of cardiac irradiation (< 2 Gy) may lead to myocardial perfusion defects and a global inflammatory response that can be detectable as early as 1 month post irradiation using hybrid PET-MRI imaging techniques.« less

[Recurrent right atrial thrombus in a patient with atrial fibrillation and heart failure].

PubMed

Elikowski, Waldemar; Wróblewski, Dariusz; Małek-Elikowska, Małgorzata; Mazurek, Andrzej; Foremska-Iciek, Joanna; Łazowski, Stanisław

2015-11-01

Atrial fibrillation and heart failure are factors predisposing to locally formed intracardiac thrombosis, which is usually localized in left-sided chambers. A case report. The authors present a case of a 50-year-old male with permanent atrial fibrillation and dilated cardiomyopathy in whom recurrent right atrial thrombus was observed. Initially, the lesion was detected in echocardiography while he was hospitalized due to extensive right-sided pneumonia. The thrombus was successfully treated with heparin, followed by warfarin. Even though the patient continued warfarin use properly, there was recurrence of the thrombus two years later during a new episode of heart failure exacerbation. Because the thrombus was resistant to intensified anticoagulation, cardiac surgery was needed. A large (30 x 25 mm) pedunculated thrombus, as well as two smaller ones (each of 10 x 10 mm) attached closely to the atrial wall and previously not detected either by echocardiography or by magnetic resonance imaging, were excited. A partially organized pattern of the thrombi in histological examination can explain lack of anticoagulation effectiveness. © 2015 MEDPRESS.

Cardiac reactivity and preserved performance under stress: two sides of the same coin?

PubMed

Pattyn, Nathalie; Mairesse, Olivier; Cortoos, Aisha; Morais, José; Soetens, Eric; Roelands, Bart; van den Nest, Annick; Kolinsky, Régine

2014-07-01

In the present experiment, cognitive control under stress was investigated using a real-life paradigm, namely an evaluation flight for military student pilots. The magnitude of cognitive interference on color-word, numerical and emotional Stroop paradigms was studied during a baseline recording and right before the test flight. Cardio-respiratory parameters were simultaneously assessed during rest and the performance of the Stroop tasks. Cognitive data suggested a different speed/accuracy trade-off under stress, and no modulation of the interference effect for color words or numerical stimuli. However, we observed a major increase in error rates for specific emotional stimuli related to the evaluation situation in the stress condition. The increase in cognitive interference from emotional stimuli, expressed as an increase in error rates, was correlated to the decreased cardiac reactivity to challenge in the stress situation. This relationship is discussed in the framework of Sanders' (1983) model of stress and performance. In terms of future research, this link warrants a fruitful lead to be followed for investigating the causal mechanism of performance decrements under the influence of stress. Copyright © 2013 Elsevier B.V. All rights reserved.

Amiodaron in atrial fibrillation: post coronary artery bypass graft.

PubMed

Habibollahi, Paria; Jam, Shahrzad Hashemi; Vahdati, Samad Shams; Baghi, Hamidreza Morteza; Amiri, Hassan

2016-01-01

Atrial fibrilation (AF) is the most common complication following heart surgeries; it often occurs in patients after coronary artery bypass graft (CABG). The purpose of this review is to categorize prophylaxes or treatment by administration of Amiodaron in patients with CABG. We searched google scholar, pubmed, and Cochrane Library databases (the period 1970-2010) for articles on Amiodaron in CABG and cardiac surgery. A total of 1 561 articles were identified, and 30 articles met the criteria and were enrolled in this review. Most studies supported Amiodarone for prophylaxi purpose in patients who were performed with CABG; few papers supported Amiodaron as a drug for treating CABG. The prophylaxis can decrease the incidence rate of AF in CABG, but if it uses as a treatment, the side effect of Amiodaron will decrease because all of the patients will not get Amiodarone. In the other hand use of Amiodarone as a treatment does not influence the length of hospital stay significantly but these kinds of study are so few. No appropriate therapeutic method has been defined for AF. At present, the common way of treating AF following cardiac surgery is mainly based on prophylaxis in medical books and references.

Amiodaron in atrial fibrillation: post coronary artery bypass graft

PubMed Central

Habibollahi, Paria; Jam, Shahrzad Hashemi; Vahdati, Samad Shams; Baghi, Hamidreza Morteza; Amiri, Hassan

2016-01-01

BACKGROUND: Atrial fibrilation (AF) is the most common complication following heart surgeries; it often occurs in patients after coronary artery bypass graft (CABG). The purpose of this review is to categorize prophylaxes or treatment by administration of Amiodaron in patients with CABG. DATA RESOURCES: We searched google scholar, pubmed, and Cochrane Library databases (the period 1970–2010) for articles on Amiodaron in CABG and cardiac surgery. A total of 1 561 articles were identified, and 30 articles met the criteria and were enrolled in this review. RESULTS: Most studies supported Amiodarone for prophylaxi purpose in patients who were performed with CABG; few papers supported Amiodaron as a drug for treating CABG. The prophylaxis can decrease the incidence rate of AF in CABG, but if it uses as a treatment, the side effect of Amiodaron will decrease because all of the patients will not get Amiodarone. In the other hand use of Amiodarone as a treatment does not influence the length of hospital stay significantly but these kinds of study are so few. CONCLUSION: No appropriate therapeutic method has been defined for AF. At present, the common way of treating AF following cardiac surgery is mainly based on prophylaxis in medical books and references. PMID:27942340

A multichannel decision-level fusion method for T wave alternans detection

NASA Astrophysics Data System (ADS)

Ye, Changrong; Zeng, Xiaoping; Li, Guojun; Shi, Chenyuan; Jian, Xin; Zhou, Xichuan

2017-09-01

Sudden cardiac death (SCD) is one of the most prominent causes of death among patients with cardiac diseases. Since ventricular arrhythmia is the main cause of SCD and it can be predicted by T wave alternans (TWA), the detection of TWA in the body-surface electrocardiograph (ECG) plays an important role in the prevention of SCD. But due to the multi-source nature of TWA, the nonlinear propagation through thorax, and the effects of the strong noises, the information from different channels is uncertain and competitive with each other. As a result, the single-channel decision is one-sided while the multichannel decision is difficult to reach a consensus on. In this paper, a novel multichannel decision-level fusion method based on the Dezert-Smarandache Theory is proposed to address this issue. Due to the redistribution mechanism for highly competitive information, higher detection accuracy and robustness are achieved. It also shows promise to low-cost instruments and portable applications by reducing demands for the synchronous sampling. Experiments on the real records from the Physikalisch-Technische Bundesanstalt diagnostic ECG database indicate that the performance of the proposed method improves by 12%-20% compared with the one-dimensional decision method based on the periodic component analysis.

Effect of soluble guanylyl cyclase activator and stimulator therapy on nitroglycerin-induced nitrate tolerance in rats.

PubMed

Jabs, A; Oelze, M; Mikhed, Y; Stamm, P; Kröller-Schön, S; Welschof, P; Jansen, T; Hausding, M; Kopp, M; Steven, S; Schulz, E; Stasch, J-P; Münzel, T; Daiber, A

2015-08-01

Chronic nitroglycerin (GTN) anti-ischemic therapy induces side effects such as nitrate tolerance and endothelial dysfunction. Both phenomena could be based on a desensitization/oxidation of the soluble guanylyl cyclase (sGC). Therefore, the present study aims at investigating the effects of the therapy with the sGC activator BAY 60-2770 and the sGC stimulator BAY 41-8543 on side effects induced by chronic nitroglycerin treatment. Male Wistar rats were treated with nitroglycerin (100mg/kg/d for 3.5days, s.c. in ethanol) and BAY 60-2770 (0.5 or 2.5mg/kg/d) or BAY 41-8543 (1 and 5mg/kg/d) for 6days. Therapy with BAY 60-2770 but not with BAY 41-8543 improved nitroglycerin-triggered endothelial dysfunction and nitrate tolerance, corrected the decrease in aortic nitric oxide levels, improved the cGMP dependent activation of protein kinase I in aortic tissue and reduced vascular, cardiac and whole blood oxidative stress (fluorescence and chemiluminescence assays; 3-nitrotyrosine staining). In contrast to BAY 41-8543, the vasodilator potency of BAY 60-2770 was not impaired in isolated aortic ring segments from nitrate tolerant rats. sGC activator therapy improves partially the adverse effects of nitroglycerin therapy whereas sGC stimulation has only minor beneficial effects pointing to a nitroglycerin-dependent sGC oxidation/inactivation mechanism contributing to nitrate tolerance. Copyright © 2015 Elsevier Inc. All rights reserved.

Risks of on-pump coronary artery bypass grafting surgery in patients with chronic obstructive pulmonary disease due to sulfur mustard.

PubMed

Firoozabadi, Mehdi Dehghani; Sheikhi, Mohammad Ali; Rahmani, Hossein; Ebadi, Ahmad; Heidari, Amanollah; Gholizadeh, Behnam; Sharifi, Khosrow

2017-10-01

Sulfur mustard (SM) is a toxic chemical agent that belongs to a class of vesicant compounds. In the 1980s it was used by the Iraqi army against Iranian forces. Sulfur mustard severely irritates the skin, eyes and lungs. The highest side effects seen in patients affected by this gas are pulmonary complications including different types of lung diseases such as bronchiolitis. It has also led to a certain type of chronic obstructive pulmonary disease called mustard lung. Similar extra-pulmonary, molecular and hormonal effects can be observed in these patients and patients with chronic obstructive pulmonary disease. Here cardiovascular complications may be one of the most dangerous visible effects. And atherosclerosis is probable following the direct effects or consequential long-term effects of SM. The development of atherosclerosis in these patients is associated with an increased risk of cardiovascular and coronary artery disease. Coronary artery bypass grafting surgery is the treatment of coronary artery disease. Doing this surgery by bypass pump has its own morbidity and due to local and systemic inflammation changes in patients with SM pulmonary disorders it may have more side effects. Therefore, detailed knowledge of inflammatory diseases as well as the serum level or even the local lung fluid of the inflammatory factors in these patients before surgery are needed so that it would be possible to reduce the rate of morbidity and mortality by normalizing the inflammatory conditions of the patients before cardiac surgery.

Investigation of mechanisms and non-pharmacological therapy of cardiac arrhythmias

NASA Astrophysics Data System (ADS)

Vago, Hajnalka

Learning of mechanisms of arrhythmias may contribute substantially to the development of effective pharmacological and non-pharmacological therapeutic methods. Clinical relevance of endothelin-1 (ET-1), a strong vasoconstrictor and arrhythmogenic endogenous substrate, is not clarified yet. In our experimental studies, performed in the in situ canine heart, electrophysiological effects and the role in the pathomechanism of malignant ventricular tachyarrhythmias of endogenous and exogenous ET-1 was investigated. It has been proven in the in vivo ischaemia-reperfusion canine heart model, that during reperfusion ET-1 and big-ET levels increase in the coronary sinus, however there was no correlation between endothelin levels and electrophysiological changes. ET A-receptor antagonist darusentan does not prevent electrophysiological changes and development of ventricular tachyarrhythmias during ischaemia and reperfusion. On the contrary, during ischaemia endogenous ET-1 tends to show balancing effect. It has been proven that administration of high dose intracoronary ET-1 bolus has dual, ischaemic and direct, electrophysiological effect. It has been shown for the first time, that ET-1 causes monophasic action potential (MAP) and T-wave alternant. Our clinical study leads to the conclusion that previous atrial fibrillation, absence of preoperative beta-blocker treatment and combined heart surgery are strong predictors of atrial fibrillation following open heart surgery. The basis of new nonpharmacological therapies is the learning of pathomechanisms of arrhythmias and in some cases heart failure, which is an arrhythmogenic substrate. In our experimental study reliable MAP measurements, suitable for investigation of arrhythmogenesis, were performed for the first time using fractally coated ablation catheters during spontaneous rate and during stimulations. It has been proven that radiofrequency ablation affects significantly MAP parameters. In Hungary, we were the first to apply effectively biatrial pacemaker and biatrial cardioverter defibrillator for the prevention of paroxysmal atrial fibrillation. In the majority of patients frequency of paroxysmal atrial fibrillation decreased significantly due to biatrial stimulation or combined pharmacological and resynchronisation therapy. Parasymphathetic cardiac neurostimulation is a promising new non-pharmacological treatment option in certain types of arrhythmias. In our clinical study we were able to stimulate cardiac parasympathetic nerves innervating atrioventricular node achieving ventricular rate control during atrial tachyarrhythmias with chronically implanted coronary sinus lead. In our study biventricular pacemakers and cardioverter defibrillators were applied successfully in the treatment of drug refractory congestive heart failure combined with inter- and/or intraventricular conduction disturbances. AV sequential left sided chronic pacing using a single lead located in the coronary sinus has not been previously reported. Left sided DDD pacing was effective chronically in the improvement of the functional stage of patient suffering from congestive heart disease combined with left bundle branch block and binodal disease. Parallel with the investigation of pathomechanism of life-threatening ventricular tachyarrhythmias and the most common, clinically relevant atrial fibrillation due to recent technical development, we were able to support nonpharmacological therapeutic modalities, gaining popularity in clinical management, with novel observations.

Model-based approach for quantitative estimates of skin, heart, and lung toxicity risk for left-side photon and proton irradiation after breast-conserving surgery.

PubMed

Tommasino, Francesco; Durante, Marco; D'Avino, Vittoria; Liuzzi, Raffaele; Conson, Manuel; Farace, Paolo; Palma, Giuseppe; Schwarz, Marco; Cella, Laura; Pacelli, Roberto

2017-05-01

Proton beam therapy represents a promising modality for left-side breast cancer (BC) treatment, but concerns have been raised about skin toxicity and poor cosmesis. The aim of this study is to apply skin normal tissue complication probability (NTCP) model for intensity modulated proton therapy (IMPT) optimization in left-side BC. Ten left-side BC patients undergoing photon irradiation after breast-conserving surgery were randomly selected from our clinical database. Intensity modulated photon (IMRT) and IMPT plans were calculated with iso-tumor-coverage criteria and according to RTOG 1005 guidelines. Proton plans were computed with and without skin optimization. Published NTCP models were employed to estimate the risk of different toxicity endpoints for skin, lung, heart and its substructures. Acute skin NTCP evaluation suggests a lower toxicity level with IMPT compared to IMRT when the skin is included in proton optimization strategy (0.1% versus 1.7%, p < 0.001). Dosimetric results show that, with the same level of tumor coverage, IMPT attains significant heart and lung dose sparing compared with IMRT. By NTCP model-based analysis, an overall reduction in the cardiopulmonary toxicity risk prediction can be observed for all IMPT compared to IMRT plans: the relative risk reduction from protons varies between 0.1 and 0.7 depending on the considered toxicity endpoint. Our analysis suggests that IMPT might be safely applied without increasing the risk of severe acute radiation induced skin toxicity. The quantitative risk estimates also support the potential clinical benefits of IMPT for left-side BC irradiation due to lower risk of cardiac and pulmonary morbidity. The applied approach might be relevant on the long term for the setup of cost-effectiveness evaluation strategies based on NTCP predictions.

High dose rivastigmine in the symptom management of Lewy body dementia.

PubMed

Nour, Joseph Marwan; Chouliaras, Leonidas; Hickey, Lilian

2016-11-29

A man presented in late 2004 at the age of 65 with a decline in memory. He was diagnosed with Lewy body dementia and started on 3 mg rivastigmine a day, which made a marked clinical improvement. He lived with the illness for 10 years, over which time the dose of acetylcholinesterase inhibitors (ChEI) he took rose to two 9.5 mg rivastigmine patches and 7.5 mg donepezil, significantly above British National Formulary (BNF) limits. He demonstrated clear clinical response to ChEI and showed improvements in alertness and functioning. He did not exhibit life-threatening cardiac side effects and his death in 2014 was not related to the ChEI. 2016 BMJ Publishing Group Ltd.

Comparison of Safety and Effectiveness Between Right Versus Left Radial Arterial Access in Primary Percutaneous Coronary Intervention for Acute ST Segment Elevation Myocardial Infarction.

PubMed

Elmahdy, Mahmoud Farouk; ElMaghawry, Mohamed; Hassan, Mohamed; Kassem, Hussien Heshmat; Said, Karim; Elfaramawy, Amr AbdelAziz

2017-01-01

Transradial approach (TRA) is now considered the standard of care in many centres for elective and primary percutaneous intervention (PCI). The use of the radial approach in ST segment elevation myocardial infarction (STEMI) patients has been associated with a significant reduction in major adverse cardiac events. However, it is still unclear if the side of radial access (right vs. left) has impact on safety and effectiveness of TRA in primary PCI. So this study was conducted to compare the safety, feasibility, and outcomes of right radial access (RRA) vs. left radial access (LRA) in the setting of primary PCI. We retrospectively analysed the data of 400 consecutive patients presenting to our institution with STEMI for whom primary PCIs were performed via RRA and LRA. Mean age of the whole studied population was 57±12.8 years, with male predominance (77.2%). There were 202 cases in the RRA group and 198 in the LRA group, with no significant difference in demographics and clinical characteristics for patients included in both groups. There was no significant difference in procedure success rate (97.5% for RRA vs. 98.4% for LRA; P=0.77). In addition, no significant difference between both approaches was observed in the contrast volume, number of catheters, fluoroscopy time (FT), needle-to-balloon time, post-procedure vascular complications, in hospital reinfarction, stroke/transient ischaemic attack (TIA) or death. Right radial access and LRA are equally safe and effective in the setting of primary PCI. Both approaches have a high success rate and comparable needle-to-balloon time. Copyright © 2016 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

[High-dose Crataegus extract WS 1442 in the treatment of NYHA stage II heart failure].

PubMed

Tauchert, M; Gildor, A; Lipinski, J

1999-10-01

The efficacy and tolerance of the standardized hawthorn (crataegus) extract WS 1442 were tested in a multicenter utilization observational study. We monitored 1,011 patients with cardiac insufficiency stage NYHA II, treated with this extract (Crataegutt novo 450, 1 tablet b.i.d.) over a period of 24 weeks. During and at the end of the observation period a significant improvement in clinical symptoms (reduced performance in the exercise tolerance test, fatigue, palpitation and exercise dyspnea) was observed. Ankle edema and nocturia disappeared by 83%, and by half of the patients respectively manifesting these symptoms before treatment. The improvement and economization of cardiac performance were additionally shown by a reduction in blood pressure, an increased maximal exercise tolerance and a reduction in the difference in the pressure/heart rate product (PHRP). The positive effects of WS 1442 were further demonstrated by an improved ejection fraction and an increased percentile shortening fraction measured using M-mode echocardiography. The stabilizing effect of the hawthorn extract on the heart rate was shown by a slower rest pulse, as well as by an increase in the number of day and night normorhythmic patients, as documented by long-term ECG. The reduction in the number of patients showing ST depressions, arrhythmias and ventricular extrasystoles at the maximum exercise level is regarded as an indication for an improved myocardial perfusion. Fourteen side effects were noted. In two cases (abdominal discomfort and facial pains accompanied by tachycardia) a possible relationship with the hawthorn therapy, was postulated which however was considered unlikely by the treating physicians. Almost 2/3 of the patients felt better or much better following the 24 weeks of treatment. More than 3/4 of the participating physicians noted a good or a very good efficacy, and 98.7% noted a good or a very good tolerance. High-dose hawthorn therapy is an efficient, well-tolerated and easily regulated therapeutic alternative for patients suffering from cardiac insufficiency stage NYHA II.

Induction of a chronic myocardial infarction in the laboratory animal - experimental model

PubMed Central

POP, IONEL CIPRIAN; GRAD, NICOLAE-OVIDIU; PESTEAN, COSMIN; TAULESCU, MARIAN; MIRCEAN, MIRCEA; MIRONIUC, ION-AUREL

2013-01-01

Introduction Ischemic heart disease is a major public health problem in western countries. Appropriate animal experimental models of chronic myocardial infarction is an essential first step in order to investigate and develop new therapeutic interventions. Aim The aim of this study was to find an optimal place for a coronary artery ligation to induce an optimal chronic myocardial infarction and also a new heart approach that will not require oro-tracheal intubation. Material and methods To achieve these goals we used a group of rabbits and after induction of anesthesia and cardiac exposure by rib osteotomy (rib III, IV and V) at the costo-sternal junction level on the right side we performed three different left anterior descending artery (LAD) ligation at different distances (5, 10 and 15 mm) in relation to the apex. Thirty days after the acute myocardial infarction, we correlated laboratory investigations (serology, ECG, cardiac ultrasound) with histopathological findings. Results Heart approach achieved by rib osteotomy (rib III, IV and V) at the costo-sternal junction level on the right side, maintains the integrity of the ribcage, allowing it to take part in respiratory movements and the animal model does not need oro-tracheal intubation. Ligation of LAD at 15 mm from the apex was incompatible with life; ligation of LAD at 5 mm from the apex does not achieved transmural myocardial infarction and ligation of LAD at 10 mm from the apex achieved a transmural myocardial infarction of the left ventricle which also involved the distal part of the interventricular septum. Conclusion Ligation of LAD at 10 mm from the apex achieved a transmural myocardial infarction of the left ventricle, is in an easily accessible area from technical point of view, it is sufficiently expanded to induce hemodynamic effects that can be quantified with paraclinical examination and also it is compatible with the experimental animal life. If the heart is approached by rib III, IV and V osteotomy at the costo-sternal junction level on the right side combined with neuroleptic anaesthesia, the animal does not need assisted ventilation. PMID:26527973

Automated external defibrillation training on the left or the right side - a randomized simulation study.

PubMed

Stærk, Mathilde; Bødtker, Henrik; Lauridsen, Kasper G; Løfgren, Bo

2017-01-01

Correct placement of the left automated external defibrillator (AED) electrode is rarely achieved. AED electrode placement is predominantly illustrated and trained with the rescuer sitting on the right side of the patient. Placement of the AED electrodes from the left side of the patient may result in a better overview of and access to the left lateral side of the thorax. This study aimed to investigate if training in automated external defibrillation on the left side compared to the right side of a manikin improves left AED electrode placement. Laypeople attending basic life support training were randomized to learn automated external defibrillation from the left or right side of a manikin. After course completion, participants used an AED and placed AED electrodes in a simulated cardiac arrest scenario. In total, 40 laypersons were randomized to AED training on the left (n=19 [missing data =1], 63% female, mean age: 47.3 years) and right (n=20, 75% female, mean age: 48.7 years) sides of a manikin. There was no difference in left AED electrode placement when trained on the left or right side: the mean (SD) distances to the recommended left AED electrode position were 5.9 (2.1) cm vs 6.9 (2.2) cm ( p =0.15) and to the recommended right AED electrode position were 2.6 (1.5) cm vs 1.8 (0.8) cm ( p =0.06), respectively. Training in automated external defibrillation on the left side of a manikin does not improve left AED electrode placement compared to training on the right side.

Right massive haemothorax as the presentation of blunt cardiac rupture: the pitfall of coexisting pericardial laceration

PubMed Central

Chen, Shao-Wei; Huang, Yao-Kuang; Liao, Chien-Hung; Wang, Shang-Yu

2014-01-01

A 74-year old female was transferred to our institution because of blunt chest trauma. Chest X-ray and computed tomography (CT) revealed right haemothorax and little pericardial effusion. She was taken to the operating theatre for emergent operation because of hypotension and massive bleeding from the right-sided chest tube. Cardiopulmonary resuscitation was started during surgical exploration. There were three 1-cm lacerations actively bleeding from the right atrium and inferior vena cava junction, which were repaired successfully. Furthermore, we identified a 10 cm laceration in the right-side pleuropericardium and a communication existing between the pericardial space and the right pleural space. PMID:24218497

Right massive haemothorax as the presentation of blunt cardiac rupture: the pitfall of coexisting pericardial laceration.

PubMed

Chen, Shao-Wei; Huang, Yao-Kuang; Liao, Chien-Hung; Wang, Shang-Yu

2014-02-01

A 74-year old female was transferred to our institution because of blunt chest trauma. Chest X-ray and computed tomography (CT) revealed right haemothorax and little pericardial effusion. She was taken to the operating theatre for emergent operation because of hypotension and massive bleeding from the right-sided chest tube. Cardiopulmonary resuscitation was started during surgical exploration. There were three 1-cm lacerations actively bleeding from the right atrium and inferior vena cava junction, which were repaired successfully. Furthermore, we identified a 10 cm laceration in the right-side pleuropericardium and a communication existing between the pericardial space and the right pleural space.

Resuscitation Outcomes Consortium (ROC) PRIMED Cardiac Arrest Trial Methods, Part 1: Rationale and Methodology for the Impedance Threshold Device (ITD) Protocol

PubMed Central

Aufderheide, Tom P.; Kudenchuk, Peter J.; Hedges, Jerris R.; Nichol, Graham; Kerber, Richard E.; Dorian, Paul; Davis, Daniel P.; Idris, Ahamed H.; Callaway, Clifton W.; Emerson, Scott; Stiell, Ian G.; Terndrup, Thomas E.

2013-01-01

Aim The primary aim of this study is to compare survival to hospital discharge with a modified Rankin score (MRS) ≤3 between standard cardiopulmonary resuscitation (CPR) plus an active impedance threshold device (ITD) versus standard CPR plus a sham ITD in patients with out-of-hospital cardiac arrest. Secondary aims are to compare functional status and depression at discharge and at 3 and 6 months post discharge in survivors. Materials and Methods Design Prospective, double-blind, randomized, controlled, clinical trial. Population Patients with non-traumatic out-of-hospital cardiac arrest treated by emergency medical services (EMS) providers. Setting EMS systems participating in the Resuscitation Outcomes Consortium. Sample Size Based on a one-sided significance level of 0.025, power = 0.90, a survival with MRS ≤ 3 to discharge rate of 5.33% with standard CPR and sham ITD, and two interim analyses, a maximum of 14,742 evaluable patients are needed to detect a 6.69% survival with MRS ≤ 3 to discharge with standard CPR and active ITD (1.36% absolute survival difference). Conclusion If the ITD demonstrates the hypothesized improvement in survival, it is estimated that2,700 deaths from cardiac arrest per year would be averted in North America alone. PMID:18487005

Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells

PubMed Central

Jackson, Kathyjo A.; Majka, Susan M.; Wang, Hongyu; Pocius, Jennifer; Hartley, Craig J.; Majesky, Mark W.; Entman, Mark L.; Michael, Lloyd H.; Hirschi, Karen K.; Goodell, Margaret A.

2001-01-01

Myocyte loss in the ischemically injured mammalian heart often leads to irreversible deficits in cardiac function. To identify a source of stem cells capable of restoring damaged cardiac tissue, we transplanted highly enriched hematopoietic stem cells, the so-called side population (SP) cells, into lethally irradiated mice subsequently rendered ischemic by coronary artery occlusion for 60 minutes followed by reperfusion. The engrafted SP cells (CD34–/low, c-Kit+, Sca-1+) or their progeny migrated into ischemic cardiac muscle and blood vessels, differentiated to cardiomyocytes and endothelial cells, and contributed to the formation of functional tissue. SP cells were purified from Rosa26 transgenic mice, which express lacZ widely. Donor-derived cardiomyocytes were found primarily in the peri-infarct region at a prevalence of around 0.02% and were identified by expression of lacZ and α-actinin, and lack of expression of CD45. Donor-derived endothelial cells were identified by expression of lacZ and Flt-1, an endothelial marker shown to be absent on SP cells. Endothelial engraftment was found at a prevalence of around 3.3%, primarily in small vessels adjacent to the infarct. Our results demonstrate the cardiomyogenic potential of hematopoietic stem cells and suggest a therapeutic strategy that eventually could benefit patients with myocardial infarction. PMID:11390421

Comparative effects of torasemide and furosemide on gap junction proteins and cardiac fibrosis in a rat model of dilated cardiomyopathy.

PubMed

Watanabe, Kenichi; Sreedhar, Remya; Thandavarayan, Rajarajan A; Karuppagounder, Vengadeshprabhu; Giridharan, Vijayasree V; Antony, Shanish; Harima, Meilei; Nakamura, Masahiko; Suzuki, Kenji; Suzuki, Hiroshi; Sone, Hirohito; Arumugam, Somasundaram

2017-03-01

Cardiac fibrosis is the major hallmark of adverse cardiac remodeling in chronic heart failure (CHF) and its therapeutic targeting might help against cardiac dysfunction during chronic conditions. Diuretic agents are potentially useful in these cases, but their effects on the cardiac fibrosis pathogenesis are yet to be identified. This study was designed to identify and compare the effects of diuretic drugs torasemide and furosemide on cardiac fibrosis in a rat model of dilated cardiomyopathy induced by porcine cardiac myosin mediated experimental autoimmune myocarditis. Gap junction proteins, connexin-43 and N-cadherin, expressions were downregulated in the hearts of CHF rats, while torasemide treatment has upregulated their expression. Western blotting and immunohistochemical analysis for various cardiac fibrosis related proteins as well as histopathological studies have shown that both drugs have potential anti-fibrotic effects. Among them, torasemide has superior efficacy in offering protection against adverse cardiac remodeling in the selected rat model of dilated cardiomyopathy. In conclusion, torasemide treatment has potential anti-fibrotic effect in the hearts of CHF rats, possibly via improving the gap junction proteins expression and thereby improving the cell-cell interaction in the heart. © 2016 BioFactors, 43(2):187-194, 2017. © 2016 International Union of Biochemistry and Molecular Biology.

[New aspects of the molecular effect of anti-arrhythmia agents].

PubMed

Honerjäger, P

1990-04-01

Excitation propagation is mediated by the brief opening of voltage-dependent Na-channels in the plasma membranes of cells of the conduction system and working myocardium. The refractory period is a function of the re-availability of the Na-channel for renewed opening. Most antiarrhythmic agents block cardiac Na-channels and, consequently, affect the desired refractory period prolongation. At the same time, however, dependent on the concentration and the substance, they slow conduction; an effect which can facilitate reentry excitation in the injured heart. The Na-channel blocking drugs, class I antiarrhythmic agents, are distinguished from the beta-receptor blockers, class II, repolarizing prolonging drugs, class III, and the cardiac Ca-channel blocking drugs (class IV) (Table 1). MOLECULAR STRUCTURE OF THE CARDIAC NA-CHANNEL: Voltage-dependent Na-channels which have been structurally elucidated to date are glycoprotein macromolecules of about 2000 amino acids with a molecular weight of about 260,000. Beginning at the amino terminal, four consecutive homologous domains can be differentiated which are composed of six transmembranous segments each. The terminal portion of the chain as well as the connecting segments between the domains appear intracellular. There are important relationships between the molecular structure and the function of the Na-channel (Figure 1). On comparison of the primary structures of neuronal and cardiac Na-channels, domains I to IV as well as the connecting segment between domains III and IV, are nearly identical. Homology in all of the remaining molecular regions, in contrast, is less than 70%. These segments as well as the differing structure of the four S5-S6 connecting chains may be responsible for the varying functional response of the cardiac Na-channels. MOLECULAR SITE OF ACTION OF ANTIARRHYTHMIC AGENTS AT THE CARDIAC NA-CHANNEL: Since most antiarrhythmic agents are weak bases with pK values between 7.5 and 9.5, in the physiologic range of pH, they are present in part in the protonated, positively-charged form, in part as uncharged free base. It is assumed that the Na-channel of nerve and skeletal muscle has one receptor for local anesthetics at which both the protonated and the uncharged molecular forms bind. The receptor is thought to be located on the inner wall of the ion pore about half of the distance between the intracellular and the extracellular channel opening. The uncharged form of the Na-channel blocker penetrates directly from the lipid phase of the surrounding cell membrane, the protonated form only from the intracellular space during the short opening of the channel at the beginning of the action potential. Through binding on the receptor, the Na-channel is blocked. Dissociation of the molecular forms takes place in the same manner. The peptide region on which antiarrhythmic drugs bind, however, has not been identified. By means of the patch-clamp technique, it has been shown that on extracellular application of the quaternary lidocaine derivative QX-314 there is a rapid and marked reduction of Na-flux in cardiac Purkinje fibers in contrast to the effects at neuronal and skeletal muscle Na-channels. Intracellular application similarly leads to blockade but only in the course of repetitive depolarizations indicating that the cardiac Na-channel may have a second binding site for local anesthetics at the extracellular side.(ABSTRACT TRUNCATED AT 400 WORDS)

Detailed comparative anatomy of the extrinsic cardiac nerve plexus and postnatal reorganization of the cardiac position and innervation in the great apes: orangutans, gorillas, and chimpanzees.

PubMed

Kawashima, Tomokazu; Sato, Fumi

2012-03-01

To speculate how the extrinsic cardiac nerve plexus (ECNP) evolves phyletically and ontogenetically within the primate lineage, we conducted a comparative anatomical study of the ECNP, including an imaging examination in the great apes using 20 sides from 11 bodies from three species and a range of postnatal stages from newborns to mature adults. Although the position of the middle cervical ganglion (MG) in the great apes tended to be relatively lower than that in humans, the morphology of the ECNP in adult great apes was almost consistent with that in adult humans but essentially different from that in the lesser apes or gibbons. Therefore, the well-argued anatomical question of when did the MG acquire communicating branches with the spinal cervical nerves and appear constantly in all sympathetic cardiac nerves during primate evolution is clearly considered to be after the great apes and gibbons split. Moreover, a horizontal four-chambered heart and a lifted cardiac apex with a relatively large volume in newborn great apes rapidly changed its position downward, as seen in humans during postnatal growth and was associated with a reduction in the hepatic volume by imaging diagnosis and gross anatomy. In addition, our observation using a range of postnatal stages exhibits that two sympathetic ganglia, the middle cervical and cervicothoracic ganglia, differed between the early and later postnatal stages. Copyright © 2011 Wiley Periodicals, Inc.

Fat embolism after fractures in Duchenne muscular dystrophy: an underdiagnosed complication? A systematic review.

PubMed

Feder, David; Koch, Miriam Eva; Palmieri, Beniamino; Fonseca, Fernando Luiz Affonso; Carvalho, Alzira Alves de Siqueira

2017-01-01

Duchenne muscular dystrophy is the most frequent lethal genetic disease. Several clinical trials have established both the beneficial effect of steroids in Duchenne muscular dystrophy and the well-known risk of side effects associated with their daily use. For many years it has been known that steroids associated with ambulation loss lead to obesity and also damage the bone structure resulting in the bone density reduction and increased incidence of bone fractures and fat embolism syndrome, an underdiagnosed complication after fractures. Fat embolism syndrome is characterized by consciousness disturbance, respiratory failure and skin rashes. The use of steroids in Duchenne muscular dystrophy may result in vertebral fractures, even without previous trauma. Approximately 25% of patients with Duchenne muscular dystrophy have a long bone fracture, and 1% to 22% of fractures have a chance to develop fat embolism syndrome. As the patients with Duchenne muscular dystrophy have progressive cardiac and respiratory muscle dysfunction, the fat embolism may be unnoticed clinically and may result in increased risk of death and major complications. Different treatments and prevention measures of fat embolism have been proposed; however, so far, there is no efficient therapy. The prevention, early diagnosis and adequate symptomatic treatment are of paramount importance. The fat embolism syndrome should always be considered in patients with Duchenne muscular dystrophy presenting with fractures, or an unexplained and sudden worsening of respiratory and cardiac symptoms.

Fat embolism after fractures in Duchenne muscular dystrophy: an underdiagnosed complication? A systematic review

PubMed Central

Feder, David; Koch, Miriam Eva; Palmieri, Beniamino; Fonseca, Fernando Luiz Affonso; Carvalho, Alzira Alves de Siqueira

2017-01-01

Duchenne muscular dystrophy is the most frequent lethal genetic disease. Several clinical trials have established both the beneficial effect of steroids in Duchenne muscular dystrophy and the well-known risk of side effects associated with their daily use. For many years it has been known that steroids associated with ambulation loss lead to obesity and also damage the bone structure resulting in the bone density reduction and increased incidence of bone fractures and fat embolism syndrome, an underdiagnosed complication after fractures. Fat embolism syndrome is characterized by consciousness disturbance, respiratory failure and skin rashes. The use of steroids in Duchenne muscular dystrophy may result in vertebral fractures, even without previous trauma. Approximately 25% of patients with Duchenne muscular dystrophy have a long bone fracture, and 1% to 22% of fractures have a chance to develop fat embolism syndrome. As the patients with Duchenne muscular dystrophy have progressive cardiac and respiratory muscle dysfunction, the fat embolism may be unnoticed clinically and may result in increased risk of death and major complications. Different treatments and prevention measures of fat embolism have been proposed; however, so far, there is no efficient therapy. The prevention, early diagnosis and adequate symptomatic treatment are of paramount importance. The fat embolism syndrome should always be considered in patients with Duchenne muscular dystrophy presenting with fractures, or an unexplained and sudden worsening of respiratory and cardiac symptoms. PMID:29066903

Early High-Dose Erythropoietin Therapy After Out-of-Hospital Cardiac Arrest: A Multicenter, Randomized Controlled Trial.

PubMed

Cariou, Alain; Deye, Nicolas; Vivien, Benoît; Richard, Olivier; Pichon, Nicolas; Bourg, Angèle; Huet, Loïc; Buleon, Clément; Frey, Jérôme; Asfar, Pierre; Legriel, Stéphane; Narcisse, Sophie; Mathonnet, Armelle; Cravoisy, Aurélie; Dequin, Pierre-François; Wiel, Eric; Razazi, Keyvan; Daubin, Cédric; Kimmoun, Antoine; Lamhaut, Lionel; Marx, Jean-Sébastien; de la Garanderie, Didier Payen; Ecollan, Patrick; Combes, Alain; Spaulding, Christian; Barat, Florence; Ben Boutieb, Myriam; Coste, Joël; Chiche, Jean-Daniel; Pène, Frédéric; Mira, Jean-Paul; Treluyer, Jean-Marc; Hermine, Olivier; Carli, Pierre

2016-07-05

Preliminary data suggested a clinical benefit in treating out-of-hospital cardiac arrest (OHCA) patients with a high dose of erythropoietin (Epo) analogs. The authors aimed to evaluate the efficacy of epoetin alfa treatment on the outcome of OHCA patients in a phase 3 trial. The authors performed a multicenter, single-blind, randomized controlled trial. Patients still comatose after a witnessed OHCA of presumed cardiac origin were eligible. In the intervention group, patients received 5 intravenous injections spaced 12 h apart during the first 48 h (40,000 units each, resulting in a maximal dose of 200,000 total units), started as soon as possible after resuscitation. In the control group, patients received standard care without Epo. The main endpoint was the proportion of patients in each group reaching level 1 on the Cerebral Performance Category (CPC) scale (survival with no or minor neurological sequelae) at day 60. Secondary endpoints included all-cause mortality rate, distribution of patients in CPC levels at different time points, and side effects. In total, 476 patients were included in the primary analysis. Baseline characteristics were similar in the 2 groups. At day 60, 32.4% of patients (76 of 234) in the intervention group reached a CPC 1 level, as compared with 32.1% of patients (78 of 242) in the control group (odds ratio: 1.01; 95% confidence interval: 0.68 to 1.48). The mortality rate and proportion of patients in each CPC level did not differ at any time points. Serious adverse events were more frequent in Epo-treated patients as compared with controls (22.6% vs. 14.9%; p = 0.03), particularly thrombotic complications (12.4% vs. 5.8%; p = 0.01). In patients resuscitated from an OHCA of presumed cardiac cause, early administration of erythropoietin plus standard therapy did not confer a benefit, and was associated with a higher complication rate. (High Dose of Erythropoietin Analogue After Cardiac Arrest [Epo-ACR-02]; NCT00999583). Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Critical congenital heart disease--utility of routine screening for chromosomal and other extracardiac malformations.

PubMed

Baker, Kimberly; Sanchez-de-Toledo, Joan; Munoz, Ricardo; Orr, Richard; Kiray, Shareen; Shiderly, Dana; Clemens, Michele; Wearden, Peter; Morell, Victor O; Chrysostomou, Constantinos

2012-01-01

Objective.  Infants with critical congenital heart disease (CHD) can have genetic and other extracardiac malformations, which add to the short- and long-term risk of morbidity and perhaps mortality. We sought to examine our center's practice of screening for extracardiac anomalies and to determine the yield of these tests among specific cardiac diagnostic categories. Design.  Retrospective review of infants admitted to the cardiac intensive care unit with a new diagnosis of CHD. Subjects were categorized into six groups: septal defects (SD), conotruncal defects (CTD), single-ventricle physiology (SV), left-sided obstructive lesions (LSO), right-sided obstructive lesions (RSO), and "other" (anomalous pulmonary venous return, Ebstein's anomaly). Screening modalities included genetic testing (karyotype and fluorescent in situ hybridization for 22q11.2 deletion), renal ultrasound (RUS), and head ultrasound (HUS). Results.  One hundred forty-one patients were identified. The incidence of cardiac anomalies was: CTD (36%), SD (18%), SV (18%), LSO (14%), RSO (3%), and "other" (8%). Overall 14% had an abnormal karyotype, 5% had a deletion for 22q11.2, 28% had an abnormal RUS and 22% had abnormal HUS. Patients in SD and SV had the highest incidence of abnormal karyotype (36% and 17%); 22q11.2 deletion was present only in CTD and LSO groups (9% and 7%, respectively); abnormal RUS and HUS were seen relatively uniformly in all categories. Premature infants had significantly higher incidence of renal 43% vs. 24%, and intracranial abnormalities 46% vs. 16%. Conclusion.  Infants with critical CHD and particularly premature infants have high incidence of genetic and other extracardiac anomalies. Universal screening for these abnormalities with ultrasonographic and genetic testing maybe warranted because early detection could impact short and long-term outcomes. © 2011 Wiley Periodicals, Inc.

Nanoparticles: Nanoscale Systems for Medical Applications

NASA Astrophysics Data System (ADS)

Wadkins, David Allen

The goal of this project was to develop a series of nano platforms for single cell analysis and drug delivery. Nanoparticles are a promising option to improve our medical therapies by controlling biodistribution and pharmacokinetics of therapeutics. Nanosystems also offer significant opportunity to improve current imaging modalities. The systems developed during this thesis work can be foundations for developing advanced therapies for obesity and improving our fundamental understandings of single cell behavior. The first of the two systems we attempt to create was a drug delivery system that could selectively target adipose tissue to deliver uncoupling agents and drive browning of adipose tissue and associated weight loss. Protonophores have a history of significant toxic side effects in cardiac and neuronal tissues a recently discovered protonophore, but BAM-15, has been shown to have reduced cytotoxicity. We hypothesized that the altered biodistribution of BAM-15 encapsulated in a nanoparticle could provide systemic weight loss with minimized side effects. The second system developed utilized quantum dots to create a fluorescent barcode that could be repeatedly identified using quantitative fluorescent emission readings. This platform would allow for the tracking of individual cells, allowing repeat interrogation across time and space in complex multicellular environments. Ultimately this work demonstrates the process and complexity involved in developing nanoparticulate systems meant to interact with incredibly complex intracellular environments.

Ion Fluxes in Giant Excised Cardiac Membrane Patches Detected and Quantified with Ion-selective Microelectrodes

PubMed Central

Kang, Tong Mook; Markin, Vladislav S.; Hilgemann, Donald W.

2003-01-01

We have used ion-selective electrodes (ISEs) to quantify ion fluxes across giant membrane patches by measuring and simulating ion gradients on both membrane sides. Experimental conditions are selected with low concentrations of the ions detected on the membrane side being monitored. For detection from the cytoplasmic (bath) side, the patch pipette is oscillated laterally in front of an ISE. For detection on the extracellular (pipette) side, ISEs are fabricated from flexible quartz capillary tubing (tip diameters, 2–3 microns), and an ISE is positioned carefully within the patch pipette with the tip at a controlled distance from the mouth of the patch pipette. Transport activity is then manipulated by solution changes on the cytoplasmic side. Ion fluxes can be quantified by simulating the ion gradients with appropriate diffusion models. For extracellular (intrapatch pipette) recordings, ion diffusion coefficients can be determined from the time courses of concentration changes. The sensitivity and utility of the methods are demonstrated with cardiac membrane patches by measuring (a) potassium fluxes via ion channels, valinomycin, and Na/K pumps; (b) calcium fluxes mediated by Na/Ca exchangers; (c) sodium fluxes mediated by gramicidin and Na/K pumps; and (d) proton fluxes mediated by an unknown electrogenic mechanism. The potassium flux-to-current ratio for the Na/K pump is approximately twice that determined for potassium channels and valinomycin, as expected for a 3Na/2K pump stoichiometery (i.e., 2K/charge moved). For valinomycin-mediated potassium currents and gramicidin-mediated sodium currents, the ion fluxes calculated from diffusion models are typically 10–15% smaller than expected from the membrane currents. As presently implemented, the ISE methods allow reliable detection of calcium and proton fluxes equivalent to monovalent cation currents <1 pA in magnitude, and they allow detection of sodium and potassium fluxes equivalent to <5 pA currents. The capability to monitor ion fluxes, independent of membrane currents, should facilitate studies of both electrogenic and electroneutral ion–coupled transporters in giant patches. PMID:12668735

Short-term evaluation of captopril in patients with chronic left sided valvular regurgitations.

PubMed

Jirasirirojanakorn, K; Mahanonda, N; Jootar, P; Chaithiraphan, S; Wansanit, K; Watanaprakarnchai, W

1998-01-01

To evaluate the clinical effects and the changes in cardiac performance of high- and low-dose captopril compared to placebo in patients with chronic symptomatic aortic regurgitation (AR), and/or mitral regurgitation (MR). We randomized patients into three groups, placebo (Group 1), incremental daily doses of 50 mg (Group 2), and 100 mg captopril (Group 3). We compared exercise capacity before and after four-week of treatment. Treatment was well tolerated with no serious side effects including blood chemistry. There were no significant effects of treatment on left ventricular dimensions nor calculated left ventricular ejection fraction (LVEF) between groups (LVEF change -0.6%, -2.6%, 2.4%, in group 1, 2 and 3 respectively; p > 0.05). No difference of exercise duration between treatment and placebo arms (change by 13%, 12.8%, 16.4%, respectively; p > 0.05). However, there were trends in the number of the patients who improved in left ventricular performance (absolute LVEF change > 5% unit = 15%, 16%, and 42% respectively; p > 0.05) and exercise performance (exercise time improvement > 75 sec = 50%, 47%, and 68% respectively; p > 0.05) in high dose captopril treatment group. There was no significant improvement of left ventricular performance and exercise capacity after four-weeks' treatment of low and high dose captopril. Further study with a larger sample size, and longer follow-up period may be required.

Noninvasive Imaging of Three-dimensional Cardiac Activation Sequence during Pacing and Ventricular Tachycardia

PubMed Central

Han, Chengzong; Pogwizd, Steven M.; Killingsworth, Cheryl R.; He, Bin

2011-01-01

Background Imaging cardiac excitation within ventricular myocardium is important in the treatment of cardiac arrhythmias and might help improve our understanding of arrhythmia mechanisms. Objective This study aims to rigorously assess the imaging performance of a three-dimensional (3-D) cardiac electrical imaging (3-DCEI) technique with the aid of 3-D intra-cardiac mapping from up to 216 intramural sites during paced rhythm and norepinephrine (NE) induced ventricular tachycardia (VT) in the rabbit heart. Methods Body surface potentials and intramural bipolar electrical recordings were simultaneously measured in a closed-chest condition in thirteen healthy rabbits. Single-site pacing and dual-site pacing were performed from ventricular walls and septum. VTs and premature ventricular complexes (PVCs) were induced by intravenous NE. Computer tomography images were obtained to construct geometry model. Results The non-invasively imaged activation sequence correlated well with invasively measured counterparts, with a correlation coefficient of 0.72±0.04, and a relative error of 0.30±0.02 averaged over 520 paced beats as well as 73 NE-induced PVCs and VT beats. All PVCs and VT beats initiated in the subendocardium by a nonreentrant mechanism. The averaged distance from imaged site of initial activation to pacing site or site of arrhythmias determined from intra-cardiac mapping was ~5mm. For dual-site pacing, the double origins were identified when they were located at contralateral sides of ventricles or at the lateral wall and the apex. Conclusion 3-DCEI can non-invasively delineate important features of focal or multi-focal ventricular excitation. It offers the potential to aid in localizing the origins and imaging activation sequence of ventricular arrhythmias, and to provide noninvasive assessment of the underlying arrhythmia mechanisms. PMID:21397046

Biologic variability in NT-proBNP and cardiac troponin-I in healthy dogs and dogs with mitral valve degeneration.

PubMed

Ruaux, Craig; Scollan, Katherine; Suchodolski, Jan S; Steiner, Jörg M; Sisson, D David

2015-09-01

The N-terminal fragment of the prohormone B-type natriuretic peptide (NT-proBNP) and cardiac troponin-I are candidate biomarkers for cardiac disease in dogs. The degree of biologic variation in these biomarkers has not previously been reported in healthy dogs or dogs with mitral regurgitation. The purpose of the study was to derive estimates of intrinsic biologic variability and reference change values for NT-proBNP and cardiac troponin-I in healthy dogs and dogs with mitral regurgitation grade IB and II according to the International Small Animal Cardiac Health Council (ISACHC) grading system. Plasma and sera were collected weekly for up to 7 weeks from 12 control dogs and 9 dogs with mitral regurgitation. NT-proBNP and troponin-I (C-TnI) concentrations were determined. Indices of biologic variation such as reciprocal index of individuality (r-IoI) and reference change values (RCV) were calculated in both the groups. Individuality was high in control dogs and dogs with grade IB and II mitral valve regurgitation for both C-TnI (r-IoI 1.6 and 2) and NT-proBNP (1.5 and 2.7), while the 2-sided RCV for NT-proBNP was significantly lower in dogs with mitral regurgitation (52.5% vs 99.4%, P<0.01.). High individuality of these cardiac biomarkers suggests that, following diagnosis, these assays are best interpreted by serial determination in individual canine patients rather than by comparison to a population-based reference interval. The smaller RCV values for dogs with mitral regurgitation suggest that smaller relative changes in NT-proBNP are clinically meaningful in these patients. © 2015 American Society for Veterinary Clinical Pathology.

Design and characterization of the first peptidomimetic molecule that prevents acidification-induced closure of cardiac gap junctions

PubMed Central

Verma, Vandana; Larsen, Bjarne Due; Coombs, Wanda; Lin, Xianming; Sarrou, Eliana; Taffet, Steven M.; Delmar, Mario

2010-01-01

Background Gap junctions are potential targets for pharmacological intervention. We have previously developed a series of peptide sequences that prevent closure of Cx43 channels, bind to cardiac Cx43 and prevent acidification-induced uncoupling of cardiac gap junctions. Objective We aimed to identify and validate the minimum core active structure in peptides containing an RR-N/Q-Y motif. Based on that information, we sought to generate a peptidomimetic molecule that acts on the chemical regulation of Cx43 channels. Methods Experiments were based on a combination of biochemical, spectroscopic and electrophysiological techniques, as well as molecular modeling of active pharmacophores with Cx43 activity. Results Molecular modeling analysis indicated that the functional elements of the side chains in the motif RRXY form a triangular structure. Experimental data revealed that compounds containing such a structure bind to Cx43 and prevent Cx43 chemical gating. These results provided us with the first platform for drug design targeted to the carboxyl terminal of Cx43. Using that platform, we designed and validated a peptidomimetic compound (ZP2519; molecular weight 619 Da) that prevented octanol-induced uncoupling of Cx43 channels, and pH gating of cardiac gap junctions. Conclusion Structure-based drug design can be applied to the development of pharmacophores that act directly on Cx43. Small molecules containing these pharmacophores can serve as tools to determine the role of gap junction regulation in the control of cardiac rhythm. Future studies will determine whether these compounds can function as pharmacological agents for the treatment of a selected subset of cardiac arrhythmias. PMID:20601149

The effect of perhexiline on myocardial protection during coronary artery surgery: a two-centre, randomized, double-blind, placebo-controlled trial

PubMed Central

Drury, Nigel E.; Howell, Neil J.; Calvert, Melanie J.; Weber, Ralf J.M.; Senanayake, Eshan L.; Lewis, Michael E.; Hyde, Jonathan A.J.; Green, David H.; Mascaro, Jorge G.; Wilson, Ian C.; Graham, Timothy R.; Rooney, Stephen J.; Viant, Mark R.; Freemantle, Nick; Frenneaux, Michael P.; Pagano, Domenico

2015-01-01

OBJECTIVES Perhexiline is thought to modulate metabolism by inhibiting mitochondrial carnitine palmitoyltransferase-1, reducing fatty acid uptake and increasing carbohydrate utilization. This study assessed whether preoperative perhexiline improves markers of myocardial protection in patients undergoing coronary artery bypass graft surgery and analysed its effect on the myocardial metabolome. METHODS In a prospective, randomized, double-blind, placebo-controlled trial, patients at two centres were randomized to receive either oral perhexiline or placebo for at least 5 days prior to surgery. The primary outcome was a low cardiac output episode in the first 6 h. All pre-specified analyses were conducted according to the intention-to-treat principle with a statistical power of 90% to detect a relative risk of 0.5 and a conventional one-sided α-value of 0.025. A subset of pre-ischaemic left ventricular biopsies was analysed using mass spectrometry-based metabolomics. RESULTS Over a 3-year period, 286 patients were randomized, received the intervention and were included in the analysis. The incidence rate of a low cardiac output episode in the perhexiline arm was 36.7% (51/139) vs 34.7% (51/147) in the control arm [odds ratio (OR) 0.92, 95% confidence interval (CI) 0.56–1.50, P = 0.74]. Perhexiline was associated with a reduction in the cardiac index at 6 h [difference in means 0.19, 95% CI 0.07–0.31, P = 0.001] and an increase in inotropic support in the first 12 h (OR 0.55, 95% CI 0.34–0.89, P = 0.015). There were no significant differences in myocardial injury with troponin-T or electrocardiogram, reoperation, renal dysfunction or length of stay. No difference in the preischaemic left ventricular metabolism was identified between groups on metabolomics analysis. CONCLUSIONS Preoperative perhexiline does not improve myocardial protection in patients undergoing coronary surgery and in fact reduced perioperative cardiac output, increasing the need for inotropic support. Perhexiline has no significant effect on the mass spectrometry-visible polar myocardial metabolome in vivo in humans, supporting the suggestion that it acts via a pathway that is independent of myocardial carnitine palmitoyltransferase inhibition and may explain the lack of clinical benefit observed following surgery. ClinicalTrials.Gov ID NCT00845364. PMID:24948413

The effect of perhexiline on myocardial protection during coronary artery surgery: a two-centre, randomized, double-blind, placebo-controlled trial.

PubMed

Drury, Nigel E; Howell, Neil J; Calvert, Melanie J; Weber, Ralf J M; Senanayake, Eshan L; Lewis, Michael E; Hyde, Jonathan A J; Green, David H; Mascaro, Jorge G; Wilson, Ian C; Graham, Timothy R; Rooney, Stephen J; Viant, Mark R; Freemantle, Nick; Frenneaux, Michael P; Pagano, Domenico

2015-03-01

Perhexiline is thought to modulate metabolism by inhibiting mitochondrial carnitine palmitoyltransferase-1, reducing fatty acid uptake and increasing carbohydrate utilization. This study assessed whether preoperative perhexiline improves markers of myocardial protection in patients undergoing coronary artery bypass graft surgery and analysed its effect on the myocardial metabolome. In a prospective, randomized, double-blind, placebo-controlled trial, patients at two centres were randomized to receive either oral perhexiline or placebo for at least 5 days prior to surgery. The primary outcome was a low cardiac output episode in the first 6 h. All pre-specified analyses were conducted according to the intention-to-treat principle with a statistical power of 90% to detect a relative risk of 0.5 and a conventional one-sided α-value of 0.025. A subset of pre-ischaemic left ventricular biopsies was analysed using mass spectrometry-based metabolomics. Over a 3-year period, 286 patients were randomized, received the intervention and were included in the analysis. The incidence rate of a low cardiac output episode in the perhexiline arm was 36.7% (51/139) vs 34.7% (51/147) in the control arm [odds ratio (OR) 0.92, 95% confidence interval (CI) 0.56-1.50, P = 0.74]. Perhexiline was associated with a reduction in the cardiac index at 6 h [difference in means 0.19, 95% CI 0.07-0.31, P = 0.001] and an increase in inotropic support in the first 12 h (OR 0.55, 95% CI 0.34-0.89, P = 0.015). There were no significant differences in myocardial injury with troponin-T or electrocardiogram, reoperation, renal dysfunction or length of stay. No difference in the preischaemic left ventricular metabolism was identified between groups on metabolomics analysis. Preoperative perhexiline does not improve myocardial protection in patients undergoing coronary surgery and in fact reduced perioperative cardiac output, increasing the need for inotropic support. Perhexiline has no significant effect on the mass spectrometry-visible polar myocardial metabolome in vivo in humans, supporting the suggestion that it acts via a pathway that is independent of myocardial carnitine palmitoyltransferase inhibition and may explain the lack of clinical benefit observed following surgery. NCT00845364. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.

DIOL Triterpenes Block Profibrotic Effects of Angiotensin II and Protect from Cardiac Hypertrophy

PubMed Central

Jurado-López, Raquel; Martínez-Martínez, Ernesto; Gómez-Hurtado, Nieves; Delgado, Carmen; Visitación Bartolomé, Maria; San Román, José Alberto; Cordova, Claudia; Lahera, Vicente; Nieto, Maria Luisa; Cachofeiro, Victoria

2012-01-01

Background The natural triterpenes, erythrodiol and uvaol, exert anti-inflammatory, vasorelaxing and anti-proliferative effects. Angiotensin II is a well-known profibrotic and proliferative agent that participates in the cardiac remodeling associated with different pathological situations through the stimulation and proliferation of cardiac fibroblasts. Therefore, the aim of the study was to investigate the preventive effects of the natural triterpenes erythrodiol and uvaol on the proliferation and collagen production induced by angiotensin II in cardiac myofibroblasts. Their actions on cardiac hypertrophy triggered by angiotensin II were also studied. Methodology/Principal Findings The effect of erythrodiol and uvaol on angiotensin II-induced proliferation was evaluated in cardiac myofibroblasts from adult rats in the presence or the absence of the inhibitors of PPAR-γ, GW9662 or JNK, SP600125. The effect on collagen levels induced by angiotensin II was evaluated in cardiac myofibroblasts and mouse heart. The presence of low doses of both triterpenes reduced the proliferation of cardiac myofibroblasts induced by angiotensin II. Pretreatment with GW9662 reversed the effect elicited by both triterpenes while SP600125 did not modify it. Both triterpenes at high doses produced an increase in annexing-V binding in the presence or absence of angiotensin II, which was reduced by either SP600125 or GW9662. Erythrodiol and uvaol decreased collagen I and galectin 3 levels induced by angiotensin II in cardiac myofribroblasts. Finally, cardiac hypertrophy, ventricular remodeling, fibrosis, and increases in myocyte area and brain natriuretic peptide levels observed in angiotensin II-infused mice were reduced in triterpene-treated animals. Conclusions/Significance Erythrodiol and uvaol reduce cardiac hypertrophy and left ventricle remodeling induced by angiotensin II in mice by diminishing fibrosis and myocyte area. They also modulate growth and survival of cardiac myofibroblasts. They inhibit the angiotensin II-induced proliferation in a PPAR-γ-dependent manner, while at high doses they activate pathways of programmed cell death that are dependent on JNK and PPAR-γ. PMID:22844495

Efficacy of imipenem/cilastatin in endocarditis.

PubMed

Dickinson, G; Rodriguez, K; Arcey, S; Alea, A; Greenman, R

1985-06-07

Imipenem, a potent new beta-lactam antibiotic, which is bactericidal against most pathogenic bacteria, and cilastatin, a dehydropeptidase inhibitor combined with imipenem to prevent the metabolism of imipenem in the kidney, were evaluated in the treatment of bacterial endocarditis. Seventeen patients, including 14 who used intravenous drugs, were treated with imipenem/cilastatin in a dose of 500 mg each infused over 30 minutes every six hours. The mean duration of treatment was 29 days with a range of 21 to 56 days. Causative bacteria were Staphylococcus aureus in 10 patients, S. aureus plus group B Streptococcus in one, viridans group Streptococcus in two, Neisseria subflava, Eikenella corrodens, and group G Streptococcus in one patient, and Staphylococcus epidermidis, Hemophilus aphrophilus, and Enterobacter aerogenes in one patient each. The minimal bactericidal concentration of imipenem against 16 of 18 isolates tested was 0.04 micrograms/ml, 1 microgram/ml against H. aphrophilus, and 0.4 micrograms/ml against E. aerogenes. The site of infection was the right side of the heart in 11 patients, the left side in five, and both sides in one. The mean number of days to defervescence was 9.7. All patients were cured, and none required cardiac surgery. Adverse effects were few and interrupted treatment occurred in only one patient who had acute dyspnea during an infusion on Day 26 of therapy. Imipenem/cilastatin appears to be a relatively safe and highly effective treatment of staphylococcal endocarditis in intravenous drug users; too few patients with endocarditis caused by other bacteria were treated to allow a firm statement about efficacy in non-staphylococcal endocarditis.

The effects of listening to preferred music on pain intensity after open heart surgery

PubMed Central

Jafari, Hedayat; Zeydi, Amir Emami; Khani, Soghra; Esmaeili, Ravanbakhsh; Soleimani, Aria

2012-01-01

Background: Pain is a common phenomenon after surgery. Cardiac surgeries are no exception and patients generally experience acute pain after these surgeries. Inadequate pain management after cardiac surgery predisposes patients to many complications. Therefore, the aim of this study was to determine the effects of listening to preferred music on pain intensity after open heart surgery. Materials and Methods: This study was a randomized clinical trial (RCT) conducted in open heart intensive care unit (ICU) of a university hospital in Sari, Iran. A total of 60 patients who were scheduled to undergo open heart surgery were randomly allocated in two groups. Patients in the intervention group (n = 30) listened to their preferred music by headphones for 30 minutes, whereas those in the control group (n = 30) did not listen to music. Using a Numerical Rating Scale (NRS), pain intensity was measured among the patients before the intervention, and immediately, 30 minutes and one hour after the intervention. Data was analyzed by Chi-square test, student's t-test and repeated measures analysis of variance (ANOVA). Findings: Mean pain intensity in the intervention group before, immediately after, 30 minutes and one hour after the intervention were 5.8, 3.1, 2.5 and 2.4, respectively. Corresponding numbers in the control group were 4.7, 4.7, 4.8 and 4.9, respectively. Repeated measures ANOVA showed music to significantly reduce pain intensity (p = 0.0001) Conclusions: Music can be effective as a non-pharmacological, inexpensive, non-invasive and side effect free method for pain management after open heart surgery. PMID:23493927

Cardiac Safety of Ozanimod, a Novel Sphingosine-1-Phosphate Receptor Modulator: Results of a Thorough QT/QTc Study.

PubMed

Tran, Jonathan Q; Hartung, Jeffrey P; Olson, Allan D; Mendzelevski, Boaz; Timony, Gregg A; Boehm, Marcus F; Peach, Robert J; Gujrathi, Sheila; Frohna, Paul A

2018-03-01

Ozanimod is a novel, selective, oral sphingosine-1-phosphate (1 and 5) receptor modulator in development for multiple sclerosis and inflammatory bowel disease. This randomized, double-blind, placebo-controlled, positive-controlled, parallel-group thorough QT study characterized the effects of ozanimod on cardiac repolarization in healthy subjects. Eligible subjects were randomized to 1 of 2 groups: ozanimod (escalated from 0.25 to 2 mg over 14 days) or placebo (for 14 days). A single dose of moxifloxacin 400 mg or placebo was administered on days 2 and 17. The primary end point was the time-matched, placebo-corrected, baseline-adjusted mean QTcF (ΔΔQTcF). A total of 113/124 (91.1%) subjects completed the study. The upper limits of the 2-sided 90% confidence intervals for ΔΔQTcF for both ozanimod 1 and 2 mg were below the 10-millisecond regulatory threshold. No QTcF >480 milliseconds or postdose change in QTcF of >60 milliseconds was observed. There was no evidence of a positive relationship between concentrations of ozanimod and its active metabolites and ΔΔQTcF. Although ozanimod blunted the observed diurnal increase in heart rate, excursions below predose heart rates were no greater than with placebo. Results demonstrate that ozanimod does not prolong the QTc interval or cause clinically significant bradycardia, supporting ozanimod's evolving favorable cardiac safety profile. © 2017 The Authors. Clinical Pharmacology in Drug Development Published by Wiley Periodicals, Inc. on behalf of The American College of Clinical Pharmacology.

High-throughput screening of tyrosine kinase inhibitor cardiotoxicity with human induced pluripotent stem cells.

PubMed

Sharma, Arun; Burridge, Paul W; McKeithan, Wesley L; Serrano, Ricardo; Shukla, Praveen; Sayed, Nazish; Churko, Jared M; Kitani, Tomoya; Wu, Haodi; Holmström, Alexandra; Matsa, Elena; Zhang, Yuan; Kumar, Anusha; Fan, Alice C; Del Álamo, Juan C; Wu, Sean M; Moslehi, Javid J; Mercola, Mark; Wu, Joseph C

2017-02-15

Tyrosine kinase inhibitors (TKIs), despite their efficacy as anticancer therapeutics, are associated with cardiovascular side effects ranging from induced arrhythmias to heart failure. We used human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), generated from 11 healthy individuals and 2 patients receiving cancer treatment, to screen U.S. Food and Drug Administration-approved TKIs for cardiotoxicities by measuring alterations in cardiomyocyte viability, contractility, electrophysiology, calcium handling, and signaling. With these data, we generated a "cardiac safety index" to reflect the cardiotoxicities of existing TKIs. TKIs with low cardiac safety indices exhibit cardiotoxicity in patients. We also derived endothelial cells (hiPSC-ECs) and cardiac fibroblasts (hiPSC-CFs) to examine cell type-specific cardiotoxicities. Using high-throughput screening, we determined that vascular endothelial growth factor receptor 2 (VEGFR2)/platelet-derived growth factor receptor (PDGFR)-inhibiting TKIs caused cardiotoxicity in hiPSC-CMs, hiPSC-ECs, and hiPSC-CFs. With phosphoprotein analysis, we determined that VEGFR2/PDGFR-inhibiting TKIs led to a compensatory increase in cardioprotective insulin and insulin-like growth factor (IGF) signaling in hiPSC-CMs. Up-regulating cardioprotective signaling with exogenous insulin or IGF1 improved hiPSC-CM viability during cotreatment with cardiotoxic VEGFR2/PDGFR-inhibiting TKIs. Thus, hiPSC-CMs can be used to screen for cardiovascular toxicities associated with anticancer TKIs, and the results correlate with clinical phenotypes. This approach provides unexpected insights, as illustrated by our finding that toxicity can be alleviated via cardioprotective insulin/IGF signaling. Copyright © 2017, American Association for the Advancement of Science.

Seizures after open heart surgery: comparison of ε-aminocaproic acid and tranexamic acid.

PubMed

Martin, Klaus; Knorr, Jürgen; Breuer, Tamás; Gertler, Ralph; Macguill, Martin; Lange, Rüdiger; Tassani, Peter; Wiesner, Gunther

2011-02-01

Although the lysine analogs tranexamic acid (TXA) and aminocaproic acid (EACA) are used widely for antifibrinolytic therapy in cardiac surgery, relatively little research has been performed on their safety profiles, especially in the setting of cardiac surgery. Two antifibrinolytic protocols using either TXA or aminocaproic acid were compared according to postoperative outcome. A retrospective analysis. A university-affiliated hospital. Six hundred four patients undergoing cardiac surgery. One cohort of 275 consecutive patients received TXA; a second cohort of 329 consecutive patients was treated with EACA. Except for antifibrinolytic therapy, the anesthetic and surgical teams and their protocols remained unchanged. Besides major outcome criteria, namely postoperative bleeding, the need for allogeneic transfusions, operative revision because of bleeding, postoperative renal dysfunction, neurologic events, heart failure, and in-hospital mortality, the authors specifically sought differences between the groups concerning seizures. The 2 cohorts were comparable over a range of perioperative factors. Postoperative seizures occurred significantly more frequently in TXA patients (7.6% v 3.3%, p = 0.019), whereas EACA patients had a higher incidence of postoperative renal dysfunction (20.0% v 30.1%, p = 0.005). There were no differences in all other measured major outcome factors. Both lysine analogs are associated with significant side effects, which must be taken into account when performing risk-benefit analyses of their use. Their use should be restricted to patients at high risk for bleeding; routine use on low-risk patients undergoing standard surgeries should face renewed critical reappraisal. Copyright © 2011 Elsevier Inc. All rights reserved.

Complicated infective endocarditis: a case series.

PubMed

Kim, Joo Seop; Kang, Min-Kyung; Cho, A Jin; Seo, Yu Bin; Kim, Kun Il

2017-05-08

Infective endocarditis is associated with not only cardiac complications but also neurologic, renal, musculoskeletal, and systemic complications related to the infection, such as embolization, metastatic infection, and mycotic aneurysm. We report three cases (the first patient is Chinese and the other two are Koreans) of complicated infective endocarditis; two of the cases were associated with a mycotic aneurysm, and one case was associated with a splenic abscess. One case of a patient with prosthetic valve endocarditis was complicated by intracerebral hemorrhage caused by mycotic aneurysm rupture. A second case of a patient with right-sided valve endocarditis associated with a central catheter was complicated by an abdominal aortic mycotic aneurysm. The third patient had a splenic infarction and abscess associated with infected cardiac thrombi. Complicated infective endocarditis is rare and is associated with cardiac, neurologic, renal, musculoskeletal, and systemic complications related to infection, such as embolization, metastatic infection, and mycotic aneurysm. Infective endocarditis caused by Staphylococcus aureus is more frequently associated with complications. Because the mortality rate increases when complications develop, aggressive antibiotic therapy and surgery, combined with specific treatments for the complications, are necessary.

Discovery and Optimization of 5-Amino-1,2,3-triazole-4-carboxamide Series against Trypanosoma cruzi.

PubMed

Brand, Stephen; Ko, Eun Jung; Viayna, Elisabet; Thompson, Stephen; Spinks, Daniel; Thomas, Michael; Sandberg, Lars; Francisco, Amanda F; Jayawardhana, Shiromani; Smith, Victoria C; Jansen, Chimed; De Rycker, Manu; Thomas, John; MacLean, Lorna; Osuna-Cabello, Maria; Riley, Jennifer; Scullion, Paul; Stojanovski, Laste; Simeons, Frederick R C; Epemolu, Ola; Shishikura, Yoko; Crouch, Sabrinia D; Bakshi, Tania S; Nixon, Christopher J; Reid, Iain H; Hill, Alan P; Underwood, Tim Z; Hindley, Sean J; Robinson, Sharon A; Kelly, John M; Fiandor, Jose M; Wyatt, Paul G; Marco, Maria; Miles, Timothy J; Read, Kevin D; Gilbert, Ian H

2017-09-14

Chagas' disease, caused by the protozoan parasite Trypanosoma cruzi, is the most common cause of cardiac-related deaths in endemic regions of Latin America. There is an urgent need for new safer treatments because current standard therapeutic options, benznidazole and nifurtimox, have significant side effects and are only effective in the acute phase of the infection with limited efficacy in the chronic phase. Phenotypic high content screening against the intracellular parasite in infected VERO cells was used to identify a novel hit series of 5-amino-1,2,3-triazole-4-carboxamides (ATC). Optimization of the ATC series gave improvements in potency, aqueous solubility, and metabolic stability, which combined to give significant improvements in oral exposure. Mitigation of a potential Ames and hERG liability ultimately led to two promising compounds, one of which demonstrated significant suppression of parasite burden in a mouse model of Chagas' disease.

Goal-directed fluid optimization based on stroke volume variation and cardiac index during one-lung ventilation in patients undergoing thoracoscopy lobectomy operations: a pilot study.

PubMed

Zhang, Jian; Chen, Chao Qin; Lei, Xiu Zhen; Feng, Zhi Ying; Zhu, Sheng Mei

2013-07-01

This pilot study was designed to utilize stroke volume variation and cardiac index to ensure fluid optimization during one-lung ventilation in patients undergoing thoracoscopic lobectomies. Eighty patients undergoing thoracoscopic lobectomy were randomized into either a goal-directed therapy group or a control group. In the goal-directed therapy group, the stroke volume variation was controlled at 10%±1%, and the cardiac index was controlled at a minimum of 2.5 L.min-1.m-2. In the control group, the MAP was maintained at between 65 mm Hg and 90 mm Hg, heart rate was maintained at between 60 BPM and 100 BPM, and urinary output was greater than 0.5 mL/kg-1/h-1. The hemodynamic variables, arterial blood gas analyses, total administered fluid volume and side effects were recorded. The PaO2/FiO2-ratio before the end of one-lung ventilation in the goal-directed therapy group was significantly higher than that of the control group, but there were no differences between the goal-directed therapy group and the control group for the PaO2/FiO2-ratio or other arterial blood gas analysis indices prior to anesthesia. The extubation time was significantly earlier in the goal-directed therapy group, but there was no difference in the length of hospital stay. Patients in the control group had greater urine volumes, and they were given greater colloid and overall fluid volumes. Nausea and vomiting were significantly reduced in the goal-directed therapy group. The results of this study demonstrated that an optimization protocol, based on stroke volume variation and cardiac index obtained with a FloTrac/Vigileo device, increased the PaO2/FiO2-ratio and reduced the overall fluid volume, intubation time and postoperative complications (nausea and vomiting) in thoracic surgery patients requiring one-lung ventilation.

Effects of catheter-based renal denervation on cardiac sympathetic activity and innervation in patients with resistant hypertension.

PubMed

Donazzan, Luca; Mahfoud, Felix; Ewen, Sebastian; Ukena, Christian; Cremers, Bodo; Kirsch, Carl-Martin; Hellwig, Dirk; Eweiwi, Tareq; Ezziddin, Samer; Esler, Murray; Böhm, Michael

2016-04-01

To investigate, whether renal denervation (RDN) has a direct effect on cardiac sympathetic activity and innervation density. RDN demonstrated its efficacy not only in reducing blood pressure (BP) in certain patients, but also in decreasing cardiac hypertrophy and arrhythmias. These pleiotropic effects occur partly independent from the observed BP reduction. Eleven patients with resistant hypertension (mean office systolic BP 180 ± 18 mmHg, mean antihypertensive medications 6.0 ± 1.5) underwent I-123-mIBG scintigraphy to exclude pheochromocytoma. We measured cardiac sympathetic innervation and activity before and 9 months after RDN. Cardiac sympathetic innervation was assessed by heart to mediastinum ratio (H/M) and sympathetic activity by wash out ratio (WOR). Effects on office BP, 24 h ambulatory BP monitoring, were documented. Office systolic BP and mean ambulatory systolic BP were significantly reduced from 180 to 141 mmHg (p = 0.006) and from 149 to 129 mmHg (p = 0.014), respectively. Cardiac innervation remained unchanged before and after RDN (H/M 2.5 ± 0.5 versus 2.6 ± 0.4, p = 0.285). Cardiac sympathetic activity was significantly reduced by 67 % (WOR decreased from 24.1 ± 12.7 to 7.9 ± 25.3 %, p = 0.047). Both, responders and non-responders experienced a reduction of cardiac sympathetic activity. RDN significantly reduced cardiac sympathetic activity thereby demonstrating a direct effect on the heart. These changes occurred independently from BP effects and provide a pathophysiological basis for studies, investigating the potential effect of RDN on arrhythmias and heart failure.

Automated external defibrillation training on the left or the right side – a randomized simulation study

PubMed Central

Stærk, Mathilde; Bødtker, Henrik; Lauridsen, Kasper G; Løfgren, Bo

2017-01-01

Background Correct placement of the left automated external defibrillator (AED) electrode is rarely achieved. AED electrode placement is predominantly illustrated and trained with the rescuer sitting on the right side of the patient. Placement of the AED electrodes from the left side of the patient may result in a better overview of and access to the left lateral side of the thorax. This study aimed to investigate if training in automated external defibrillation on the left side compared to the right side of a manikin improves left AED electrode placement. Methods Laypeople attending basic life support training were randomized to learn automated external defibrillation from the left or right side of a manikin. After course completion, participants used an AED and placed AED electrodes in a simulated cardiac arrest scenario. Results In total, 40 laypersons were randomized to AED training on the left (n=19 [missing data =1], 63% female, mean age: 47.3 years) and right (n=20, 75% female, mean age: 48.7 years) sides of a manikin. There was no difference in left AED electrode placement when trained on the left or right side: the mean (SD) distances to the recommended left AED electrode position were 5.9 (2.1) cm vs 6.9 (2.2) cm (p=0.15) and to the recommended right AED electrode position were 2.6 (1.5) cm vs 1.8 (0.8) cm (p=0.06), respectively. Conclusion Training in automated external defibrillation on the left side of a manikin does not improve left AED electrode placement compared to training on the right side. PMID:29066936

The Cytoplasmic Region of Inner Helix S6 Is an Important Determinant of Cardiac Ryanodine Receptor Channel Gating.

PubMed

Sun, Bo; Guo, Wenting; Tian, Xixi; Yao, Jinjing; Zhang, Lin; Wang, Ruiwu; Chen, S R Wayne

2016-12-09

The ryanodine receptor (RyR) channel pore is formed by four S6 inner helices, with its intracellular gate located at the S6 helix bundle crossing region. The cytoplasmic region of the extended S6 helix is held by the U motif of the central domain and is thought to control the opening and closing of the S6 helix bundle. However, the functional significance of the S6 cytoplasmic region in channel gating is unknown. Here we assessed the role of the S6 cytoplasmic region in the function of cardiac RyR (RyR2) via structure-guided site-directed mutagenesis. We mutated each residue in the S6 cytoplasmic region of the mouse RyR2 ( 4876 QQEQVKEDM 4884 ) and characterized their functional impact. We found that mutations Q4876A, V4880A, K4881A, and M4884A, located mainly on one side of the S6 helix that faces the U motif, enhanced basal channel activity and the sensitivity to Ca 2+ or caffeine activation, whereas mutations Q4877A, E4878A, Q4879A, and D4883A, located largely on the opposite side of S6, suppressed channel activity. Furthermore, V4880A, a cardiac arrhythmia-associated mutation, markedly enhanced the frequency of spontaneous openings and the sensitivity to cytosolic and luminal Ca 2+ activation of single RyR2 channels. V4880A also increased the propensity and reduced the threshold for arrhythmogenic spontaneous Ca 2+ release in HEK293 cells. Collectively, our data suggest that interactions between the cytoplasmic region of S6 and the U motif of RyR2 are important for stabilizing the closed state of the channel. Mutations in the S6/U motif domain interface likely destabilize the closed state of RyR2, resulting in enhanced basal channel activity and sensitivity to activation and increased propensity for spontaneous Ca 2+ release and cardiac arrhythmias. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

[Experimental therapy of cardiac remodeling with quercetin-containing drugs].

PubMed

Kuzmenko, M A; Pavlyuchenko, V B; Tumanovskaya, L V; Dosenko, V E; Moybenko, A A

2013-01-01

It was shown that continuous beta-adrenergic hyperstimulation resulted in cardiac function disturbances and fibrosis of cardiac tissue. Treatment with quercetin-containing drugs, particularly, water-soluble corvitin and tableted quertin exerted favourable effect on cardiac hemodynamics, normalized systolic and diastolic function in cardiac remodeling, induced by sustained beta-adrenergic stimulation. It was estimated that conducted experimental therapy limited cardiac fibrosis area almost three-fold, that could be associated with first and foremost improved cardiac distensibility, characteristics of diastolic and also pump function in cardiac remodeling.

Effects of Kaempferia parviflora Wall. Ex. Baker and sildenafil citrate on cGMP level, cardiac function, and intracellular Ca2+ regulation in rat hearts.

PubMed

Weerateerangkul, Punate; Palee, Siripong; Chinda, Kroekkiat; Chattipakorn, Siriporn C; Chattipakorn, Nipon

2012-09-01

Although Kaempferia parviflora extract (KPE) and its flavonoids have positive effects on the nitric oxide (NO) signaling pathway, its mechanisms on the heart are still unclear. Because our previous studies demonstrated that KPE decreased defibrillation efficacy in swine similar to that of sildenafil citrate, the phosphodiesterase-5 inhibitor, it is possible that KPE may affect the cardiac NO signaling pathway. In the present study, the effects of KPE and sildenafil citrate on cyclic guanosine monophosphate (cGMP) level, modulation of cardiac function, and Ca transients in ventricular myocytes were investigated. In a rat model, cardiac cGMP level, cardiac function, and Ca transients were measured before and after treatment with KPE and sildenafil citrate. KPE significantly increased the cGMP level and decreased cardiac function and Ca transient. These effects were similar to those found in the sildenafil citrate-treated group. Furthermore, the nonspecific NOS inhibitor could abolish the effects of KPE and sildenafil citrate on Ca transient. KPE has positive effect on NO signaling in the heart, resulting in an increased cGMP level, similar to that of sildenafil citrate. This effect was found to influence the physiology of normal heart via the attenuation of cardiac function and the reduction of Ca transient in ventricular myocytes.

Comparison of cardiac and lung doses for breast cancer patients with free breathing and deep inspiration breath hold technique in 3 dimensional conformal radiotherapy - a dosimetric study

NASA Astrophysics Data System (ADS)

Raj Mani, Karthick; Poudel, Suresh; Maria Das, K. J.

2017-12-01

Purpose: To investigate the cardio-pulmonary doses between Deep Inspiration Breath Hold (DIBH) and Free Breathing (FB) technique in left sided breast irradiation. Materials & Methods: DIBH CT and FB CT were acquired for 10 left sided breast patients who underwent whole breast irradiation with or without nodal irradiation. Three fields single isocenter technique were used for patients with node positive patients along with two tangential conformal fields whereas only two tangential fields were used in node negative patients. All the critical structures like lungs, heart, esophagus, thyroid, etc., were delineated in both DIBH and FB scan. Both DIBH and FB scans were fused with the Dicom origin as they were acquired with the same Dicom coordinates. Plans were created in the DIBH scan for a dose range between 50 Gy in 25 fractions. Critical structures doses were recorded from the Dose Volume Histogram for both the DIBH and FB data set for evaluation. Results: The average mean heart dose in DIBH vs FB was 13.18 Gy vs 6.97 Gy, (p = 0.0063) significantly with DIBH as compared to FB technique. The relative reduction in average mean heart dose was 47.12%. The relative V5 reduced by 14.70% (i.e. 34.42% vs 19.72%, p = 0.0080), V10 reduced by 13.83% (i.e. 27.79 % vs 13.96%, p = 0.0073). V20 reduced by 13.19% (i.e. 24.54 % vs 11.35%, p = 0.0069), V30 reduced by 12.38% (i.e. 22.27 % vs 9.89 %, p = 0.0073) significantly with DIBH as compared to FB. The average mean left lung dose reduced marginally by 1.43 Gy (13.73 Gy vs 12.30 Gy, p = 0.4599) but insignificantly with DIBH as compared to FB. Other left lung parameters (V5, V10, V20 and V30) shows marginal decreases in DIBH plans compare to FB plans. Conclusion: DIBH shows a substantial reduction of cardiac doses but slight and insignificant reduction of pulmonary doses as compared with FB technique. Using the simple DIBH technique, we can effectively reduce the cardiac morbidity and at the same time radiation induced lung pneumonitis is unlikely to increase.

The associations between psychological distress and healthcare use in patients with non-cardiac chest pain: does a history of cardiac disease matter?

PubMed

Mourad, Ghassan; Jaarsma, Tiny; Strömberg, Anna; Svensson, Erland; Johansson, Peter

2018-06-05

Psychological distress such as somatization, fear of body sensations, cardiac anxiety and depressive symptoms is common among patients with non-cardiac chest pain, and this may lead to increased healthcare use. However, the relationships between the psychological distress variables and healthcare use, and the differences in relation to history of cardiac disease in these patients has not been studied earlier. Therefore, our aim was to explore and model the associations between different variables of psychological distress (i.e. somatization, fear of body sensations, cardiac anxiety, and depressive symptoms) and healthcare use in patients with non-cardiac chest pain in relation to history of cardiac disease. In total, 552 patients with non-cardiac chest pain (mean age 64 years, 51% women) responded to the Patient Health Questionnaire-15, Body Sensations Questionnaire, Cardiac Anxiety Questionnaire, Patient Health Questionnaire-9 and one question regarding number of healthcare visits. The relationships between the psychological distress variables and healthcare visits were analysed using Structural Equation Modeling in two models representing patients with or without history of cardiac disease. A total of 34% of the patients had previous cardiac disease. These patients were older, more males, and reported more comorbidities, psychological distress and healthcare visits. In both models, no direct association between depressive symptoms and healthcare use was found. However, depressive symptoms had an indirect effect on healthcare use, which was mediated by somatization, fear of body sensations, and cardiac anxiety, and this effect was significantly stronger in patients with history of cardiac disease. Additionally, all the direct and indirect effects between depressive symptoms, somatization, fear of body sensations, cardiac anxiety, and healthcare use were significantly stronger in patients with history of cardiac disease. In patients with non-cardiac chest pain, in particular those with history of cardiac disease, psychological mechanisms play an important role for seeking healthcare. Development of interventions targeting psychological distress in these patients is warranted. Furthermore, there is also a need of more research to clarify as to whether such interventions should be tailored with regard to history of cardiac disease or not.

Protective effect of pulmonary hypertension against right-sided tamponade in pericardial effusion.

PubMed

Khan, M Usman; Khouzam, Rami N

2015-01-01

Patients with pericardial effusion are susceptible to cardiac tamponade. A compressing circumferential pericardial effusion typically results in an equalization of intracardiac and pericardial pressure during diastole and a progressive collapse of the right atrium and ventricle. Pulmonary hypertension that increases the afterload of the right ventricle may result in elevated pressures initially in the right ventricle and subsequently in the right atrium. This may lead to right ventricular hypertrophy and a pathologic structural and functional remodeling of both right heart chambers. Conversely, elevated pressures within the right heart chambers caused by longstanding pulmonary hypertension may resist and protect against tamponade of these chambers in the setting of a coexisting pericardial effusion. In such cases, a sudden reduction in pulmonary arterial pressures may result in tamponade of the right heart chambers.

[A case report of right-sided cardiac and pulmonary thromboembolism treated by emergent operation].

PubMed

Asaoka, M; Sasaki, M; Masumoto, H; Kajiyama, M; Seki, A

1996-05-01

A forty-four-year-old man with a clinical diagnosis of diabetes melitus and severe obesity (height 170 cm, weight 108 kg) was admitted to the hospital on 12th January 1995 because of acute myocardial infarction, and on 21st January, he was referred to our hospital with sudden onset of shock, bradycardia, loss of consciousness in spite of having recovered well from myocardial infarction. The echocardiography and pulmonary arteriography revealed a pulmonary embolism and a tumor in the right atrium. Administration of tissue plasminogen activator (TPA) was not sufficiently effective. An emergency operation (pulmonary arteriotomy, right atriotomy, milking of bilateral lungs) with cardiopulmonary bypass revealed a massive consecutive thrombus, which occupied the right atrium, right ventricle and bilateral pulmonary artery. The postoperative course was uneventful.

[Time to bury the adrenaline-myth!--Safe use of adrenaline anesthesia in hand surgery and orthopedics].

PubMed

Hagert, Elisabet; Lalonde, Donald

2015-02-03

The epinephrine myth originated in the 1940s, when acidic (pH 1) procaine-epinephrine was injected into fingers, causing finger necrosis. Today, level 1 evidence exists for the safe use of epinephrine in fingers. The ability to use lidocaine-epinephrine in hand surgery and orthopedics eliminates the need for a tourniquet, or "bloodless field". Surgery using Wide Awake, Lidocaine-epinephrine Anesthesia, No Tourniquet (WALANT) reduces patient discomfort, facilitates patient participation in surgery, improves safe outcomes following reconstructions and greatly reduces the cost of medical care. Furthermore, patients regarded as high-risk can be safely treated without risk of cardiac or pulmonary side effects. In this manuscript, the background of the epinephrine myth is described, as well as recommended use of WALANT in hand surgery and orthopedics.

Effect of experimental hyperthyroidism on protein turnover in skeletal and cardiac muscle.

PubMed

Carter, W J; Van Der Weijden Benjamin, W S; Faas, F H

1980-10-01

Since experimental hyperthyroidism reduces skeletal muscle mass while simultaneously increasing cardiac muscle mass, the effect of hyperthyroidism on muscle protein degradation was compared in skeletal and cardiac muscle. Pulse-labeling studies using (3H) leucine and (14C) carboxyl labeled aspartate and glutamate were carried out. Hyperthyroidism caused a 25%-29% increase in protein breakdown in both sarcoplasmic and myofibrillar fractions of skeletal muscle. Increased muscle protein degradation may be a major factor in the development of skeletal muscle wasting and weakness in hyperthyroidism. In contrast, protein breakdown appeared to be reduced 22% in the sarcoplasmic fraction of hyperthyroid heart muscle and was unchanged in the myofibrillar fraction. Possible reasons for the contrasting effects of hyperthyroidism on skeletal and cardiac muscle include increased sensitivity of the hyperthyroid heart to catecholamines, increased cardiac work caused by the hemodynamic effects of hyperthyroidism, and a different direct effect of thyroid hormone at the nuclear level in cardiac as opposed to skeletal muscle.

Natural product derivative BIO promotes recovery after myocardial infarction via unique modulation of the cardiac microenvironment

PubMed Central

Kim, Yong Sook; Jeong, Hye-yun; Kim, Ah Ra; Kim, Woong-Hee; Cho, Haaglim; Um, JungIn; Seo, Youngha; Kang, Wan Seok; Jin, Suk-Won; Kim, Min Chul; Kim, Yong-Chul; Jung, Da-Woon; Williams, Darren R.; Ahn, Youngkeun

2016-01-01

The cardiac microenvironment includes cardiomyocytes, fibroblasts and macrophages, which regulate remodeling after myocardial infarction (MI). Targeting this microenvironment is a novel therapeutic approach for MI. We found that the natural compound derivative, BIO ((2′Z,3′E)-6-Bromoindirubin-3′-oxime) modulated the cardiac microenvironment to exert a therapeutic effect on MI. Using a series of co-culture studies, BIO induced proliferation in cardiomyocytes and inhibited proliferation in cardiac fibroblasts. BIO produced multiple anti-fibrotic effects in cardiac fibroblasts. In macrophages, BIO inhibited the expression of pro-inflammatory factors. Significantly, BIO modulated the molecular crosstalk between cardiac fibroblasts and differentiating macrophages to induce polarization to the anti-inflammatory M2 phenotype. In the optically transparent zebrafish-based heart failure model, BIO induced cardiomyocyte proliferation and completely recovered survival rate. BIO is a known glycogen synthase kinase-3β inhibitor, but these effects could not be recapitulated using the classical inhibitor, lithium chloride; indicating novel therapeutic effects of BIO. We identified the mechanism of BIO as differential modulation of p27 protein expression and potent induction of anti-inflammatory interleukin-10. In a rat MI model, BIO reduced fibrosis and improved cardiac performance. Histological analysis revealed modulation of the cardiac microenvironment by BIO, with increased presence of anti-inflammatory M2 macrophages. Our results demonstrate that BIO produces unique effects in the cardiac microenvironment to promote recovery post-MI. PMID:27510556

Inhibition of G-Protein-Activated Inwardly Rectifying K+ Channels by the Selective Norepinephrine Reuptake Inhibitors Atomoxetine and Reboxetine

PubMed Central

Kobayashi, Toru; Washiyama, Kazuo; Ikeda, Kazutaka

2010-01-01

Atomoxetine and reboxetine are commonly used as selective norepinephrine reuptake inhibitors (NRIs) for the treatment of attention-deficit/hyperactivity disorder and depression, respectively. Furthermore, recent studies have suggested that NRIs may be useful for the treatment of several other psychiatric disorders. However, the molecular mechanisms underlying the various effects of NRIs have not yet been sufficiently clarified. G-protein-activated inwardly rectifying K+ (GIRK or Kir3) channels have an important function in regulating neuronal excitability and heart rate, and GIRK channel modulation has been suggested to be a potential treatment for several neuropsychiatric disorders and cardiac arrhythmias. In this study, we investigated the effects of atomoxetine and reboxetine on GIRK channels using the Xenopus oocyte expression assay. In oocytes injected with mRNA for GIRK1/GIRK2, GIRK2, or GIRK1/GIRK4 subunits, extracellular application of atomoxetine or reboxetine reversibly reduced GIRK currents. The inhibitory effects were concentration-dependent, but voltage-independent, and time-independent during each voltage pulse. However, Kir1.1 and Kir2.1 channels were insensitive to atomoxetine and reboxetine. Atomoxetine and reboxetine also inhibited GIRK currents induced by activation of cloned A1 adenosine receptors or by intracellularly applied GTPγS, a nonhydrolyzable GTP analogue. Furthermore, the GIRK currents induced by ethanol were concentration-dependently inhibited by extracellularly applied atomoxetine but not by intracellularly applied atomoxetine. The present results suggest that atomoxetine and reboxetine inhibit brain- and cardiac-type GIRK channels, revealing a novel characteristic of clinically used NRIs. GIRK channel inhibition may contribute to some of the therapeutic effects of NRIs and adverse side effects related to nervous system and heart function. PMID:20393461

Dronedarone: an amiodarone analogue.

PubMed

Doggrell, Sheila A; Hancox, Jules C

2004-04-01

Of the antiarrhythmic drugs in current use, amiodarone is one of the most effective and is associated with a comparatively low risk of drug-induced pro-arrhythmia, probably due to its multiple pharmacological actions on cardiac ion channels and receptors. However, amiodarone is associated with significant extra-cardiac side effects and this has driven development of amiodarone analogues. These analogues include short acting analogues (e.g., AT-2001) with similar acute effects to amiodarone, the thyroid receptor antagonist KB-130015 and dronedarone. Dronedarone, (SR-33589; Sanofi-Synthelabo), is a non-iodinated amiodarone derivative that inhibits Na +, K + and Ca 2+ currents. It is a potent inhibitor of the acetylcholine-activated K + current from atrial and sinoatrial nodal tissue, and inhibits the rapid delayed rectifier more potently than slow and inward rectifier K + currents and inhibits L-type calcium current. Dronedarone is an antagonist at alpha- and beta-adrenoceptors and unlike amiodarone, has little effect at thyroid receptors. Dronedarone is more potent than amiodarone in inhibiting arrhythmias and death in animal models of ischaemia- and reperfusion-induced arrhythmias. In the Dronedarone Atrial Fibrillation Study After Electrical Cardioversion (DAFNE) clinical trial, dronedarone 800 mg/day appeared to be effective and safe for the prevention of atrial fibrillation relapses after cardioversion. The Antiarrhythmic Trial with Dronedarone in Moderate-to-Severe Congestive Heart Failure Evaluating Morbidity Decrease (ANDROMEDA) trial was stopped due to a potential increased risk of death in the dronedarone group. Trials of dronedarone in the maintenance of sinus rhythm in patients with atrial fibrillation and a safety and tolerability study in patients with an implantable cardioverter defibrillator are ongoing. Further experimental and clinical studies are required before we have a definitive answer to whether dronedarone has advantages over amiodarone and other amiodarone analogues.

Cardiac Hypertrophy is Positively Regulated by MicroRNA-24 in Rats

PubMed Central

Gao, Juan; Zhu, Min; Liu, Rui-Feng; Zhang, Jian-Shu; Xu, Ming

2018-01-01

Background: MicroRNA-24 (miR-24) plays an important role in heart failure by reducing the efficiency of myocardial excitation-contraction coupling. Prolonged cardiac hypertrophy may lead to heart failure, but little is known about the role of miR-24 in cardiac hypertrophy. This study aimed to preliminarily investigate the function of miR-24 and its mechanisms in cardiac hypertrophy. Methods: Twelve Sprague-Dawley rats with a body weight of 50 ± 5 g were recruited and randomly divided into two groups: a transverse aortic constriction (TAC) group and a sham surgery group. Hypertrophy index was measured and calculated by echocardiography and hematoxylin and eosin staining. TargetScans algorithm-based prediction was used to search for the targets of miR-24, which was subsequently confirmed by a real-time polymerase chain reaction and luciferase assay. Immunofluorescence labeling was used to measure the cell surface area, and 3H-leucine incorporation was used to detect the synthesis of total protein in neonatal rat cardiac myocytes (NRCMs) with the overexpression of miR-24. In addition, flow cytometry was performed to observe the alteration in the cell cycle. Statistical analysis was carried out with GraphPad Prism v5.0 and SPSS 19.0. A two-sided P < 0.05 was considered as the threshold for significance. Results: The expression of miR-24 was abnormally increased in TAC rat cardiac tissue (t = −2.938, P < 0.05). TargetScans algorithm-based prediction demonstrated that CDKN1B (p27, Kip1), a cell cycle regulator, was a putative target of miR-24, and was confirmed by luciferase assay. The expression of p27 was decreased in TAC rat cardiac tissue (t = 2.896, P < 0.05). The overexpression of miR-24 in NRCMs led to the decreased expression of p27 (t = 4.400, P < 0.01), and decreased G0/G1 arrest in cell cycle and cardiomyocyte hypertrophy. Conclusion: MiR-24 promotes cardiac hypertrophy partly by affecting the cell cycle through down-regulation of p27 expression. PMID:29786048

Cardiac Hypertrophy is Positively Regulated by MicroRNA‑24 in Rats

PubMed

Gao, Juan; Zhu, Min; Liu, Rui-Feng; Zhang, Jian-Shu; Xu, Ming

2018-06-05

MicroRNA-24 (miR-24) plays an important role in heart failure by reducing the efficiency of myocardial excitation-contraction coupling. Prolonged cardiac hypertrophy may lead to heart failure, but little is known about the role of miR-24 in cardiac hypertrophy. This study aimed to preliminarily investigate the function of miR-24 and its mechanisms in cardiac hypertrophy. Twelve Sprague-Dawley rats with a body weight of 50 ± 5 g were recruited and randomly divided into two groups: a transverse aortic constriction (TAC) group and a sham surgery group. Hypertrophy index was measured and calculated by echocardiography and hematoxylin and eosin staining. TargetScans algorithm-based prediction was used to search for the targets of miR-24, which was subsequently confirmed by a real-time polymerase chain reaction and luciferase assay. Immunofluorescence labeling was used to measure the cell surface area, and 3 H-leucine incorporation was used to detect the synthesis of total protein in neonatal rat cardiac myocytes (NRCMs) with the overexpression of miR-24. In addition, flow cytometry was performed to observe the alteration in the cell cycle. Statistical analysis was carried out with GraphPad Prism v5.0 and SPSS 19.0. A two-sided P < 0.05 was considered as the threshold for significance. The expression of miR-24 was abnormally increased in TAC rat cardiac tissue (t = -2.938, P < 0.05). TargetScans algorithm-based prediction demonstrated that CDKN1B (p27, Kip1), a cell cycle regulator, was a putative target of miR-24, and was confirmed by luciferase assay. The expression of p27 was decreased in TAC rat cardiac tissue (t = 2.896, P < 0.05). The overexpression of miR-24 in NRCMs led to the decreased expression of p27 (t = 4.400, P < 0.01), and decreased G0/G1 arrest in cell cycle and cardiomyocyte hypertrophy. MiR-24 promotes cardiac hypertrophy partly by affecting the cell cycle through down-regulation of p27 expression.

Nitrite exerts antioxidant effects, inhibits the mTOR pathway and reverses hypertension-induced cardiac hypertrophy.

PubMed

Guimaraes, Danielle A; Dos Passos, Madla A; Rizzi, Elen; Pinheiro, Lucas C; Amaral, Jefferson H; Gerlach, Raquel F; Castro, Michele M; Tanus-Santos, Jose E

2018-05-20

Cardiac hypertrophy is a common consequence of chronic hypertension and leads to heart failure and premature death. The anion nitrite is now considered as a bioactive molecule able to exert beneficial cardiovascular effects. Previous results showed that nitrite attenuates hypertension-induced increases in reactive oxygen species (ROS) production in the vasculature. Whether antioxidant effects induced by nitrite block critical signaling pathways involved in cardiac hypertrophy induced by hypertension has not been determined yet. The Akt/mTOR signaling pathway is responsible to activate protein synthesis during cardiac remodeling and is activated by increased ROS production, which is commonly found in hypertension. Here, we investigated the effects of nitrite treatment on cardiac remodeling and activation of this hypertrophic signaling pathway in 2 kidney-1 clip (2K1C) hypertension. Sham and 2K1C rats were treated with oral nitrite at 1 or 15 mg/kg for four weeks. Nitrite treatment (15 mg/kg) reduced systolic blood pressure and decreased ROS production in the heart tissue from hypertensive rats. This nitrite dose also blunted hypertension-induced activation of mTOR pathway and cardiac hypertrophy. While the lower nitrite dose (1 mg/kg) did not affect blood pressure, it exerted antioxidant effects and tended to attenuate mTOR pathway activation and cardiac hypertrophy induced by hypertension. Our findings provide strong evidence that nitrite treatment decreases cardiac remodeling induced by hypertension as a result of its antioxidant effects and downregulation of mTOR signaling pathway. This study may help to establish nitrite as an effective therapy in hypertension-induced cardiac hypertrophic remodeling. Copyright © 2018 Elsevier Inc. All rights reserved.

Effect of comprehensive cardiac telerehabilitation on one-year cardiovascular rehospitalization rate, medical costs and quality of life: A cost-effectiveness analysis.

PubMed

Frederix, Ines; Hansen, Dominique; Coninx, Karin; Vandervoort, Pieter; Vandijck, Dominique; Hens, Niel; Van Craenenbroeck, Emeline; Van Driessche, Niels; Dendale, Paul

2016-05-01

Notwithstanding the cardiovascular disease epidemic, current budgetary constraints do not allow for budget expansion of conventional cardiac rehabilitation programmes. Consequently, there is an increasing need for cost-effectiveness studies of alternative strategies such as telerehabilitation. The present study evaluated the cost-effectiveness of a comprehensive cardiac telerehabilitation programme. This multi-centre randomized controlled trial comprised 140 cardiac rehabilitation patients, randomized (1:1) to a 24-week telerehabilitation programme in addition to conventional cardiac rehabilitation (intervention group) or to conventional cardiac rehabilitation alone (control group). The incremental cost-effectiveness ratio was calculated based on intervention and health care costs (incremental cost), and the differential incremental quality adjusted life years (QALYs) gained. The total average cost per patient was significantly lower in the intervention group (€2156 ± €126) than in the control group (€2720 ± €276) (p = 0.01) with an overall incremental cost of €-564.40. Dividing this incremental cost by the baseline adjusted differential incremental QALYs (0.026 QALYs) yielded an incremental cost-effectiveness ratio of €-21,707/QALY. The number of days lost due to cardiovascular rehospitalizations in the intervention group (0.33 ± 0.15) was significantly lower than in the control group (0.79 ± 0.20) (p = 0.037). This paper shows the addition of cardiac telerehabilitation to conventional centre-based cardiac rehabilitation to be more effective and efficient than centre-based cardiac rehabilitation alone. These results are useful for policy makers charged with deciding how limited health care resources should best be allocated in the era of exploding need. © The European Society of Cardiology 2015.

Cardiovascular effect of 7.5% sodium chloride-dextran infusion after thermal injury.

PubMed

Murphy, J T; Horton, J W; Purdue, G F; Hunt, J L

1999-10-01

Clinical study can help determine the safety and cardiovascular and systemic effects of an early infusion of 7.5% sodium chloride in 6% dextran-70 (hypertonic saline-dextran-70 [HSD]) given as an adjuvant to a standard resuscitation with lactated Ringer (RL) solution following severe thermal injury. Prospective clinical study. Intensive care unit of tertiary referral burn care center. Eighteen patients with thermal injury over more than 35% of the total body surface area (TBSA) (range, 36%-71%) were studied. Eight patients (mean +/- SEM, 48.2% +/- 2% TBSA) received a 4-mL/kg HSD infusion approximately 3.5 hours (range, 1.5-5.0 hours) after thermal injury in addition to routine RL resuscitation. Ten patients (46.0% +/- 6% TBSA) received RL resuscitation alone. Pulmonary artery catheters were employed to monitor cardiac function, while hemodynamic, metabolic, and biochemical measurements were taken for 24 hours. Serum troponin I levels, while detectable in all patients, were significantly lower after HSD compared with RL alone (mean +/- SEM, 0.45 +/- 0.32 vs 1.35 +/- 0.35 microg/L at 8 hours, 0.88 +/- 0.55 vs 2.21 +/- 0.35 microg/L at 12 hours). While cardiac output increased proportionately between 4 and 24 hours in both groups (from 5.79 +/- 0.8 to 9.45 +/- 1.1 L/min [mean +/- SEM] for HSD vs from 5.4 +/- 0.4 to 9.46 +/- 1.22 L/min for RL), filling pressure (central venous pressure and pulmonary capillary wedge pressure) remained low for 12 hours after HSD infusion (P = .048). Total fluid requirements at 8 hours (2.76 +/- 0.7 mL/kg per each 1% TBSA burned [mean +/- SEM] for HSD vs 2.67 +/- 0.24 mL/kg per each 1% TBSA burned for RL) and 24 hours (6.11 +/- 4.4 vs 6.76 +/- 0.75 mL/kg per each 1% TBSA burned) were similar. Blood pressure remained unchanged, and serum sodium levels did not exceed 150 +/- 2 mmol/L (mean +/- SD) in either group. The absence of deleterious hemodynamic or metabolic side effects following HSD infusion in patients with major thermal injury confirms the safety of this resuscitation strategy. Postburn cardiac dysfunction was demonstrated in all burn patients through the use of cardiospecific serum markers and pulmonary artery catheter monitoring. Early administration of HSD after a severe thermal injury may reduce burn-related cardiac dysfunction, but it had no effect on the volume of resuscitation or serum biochemistry values.

Spinal cord processing of cardiac nociception: are there sex differences between male and proestrous female rats?

PubMed

Little, Janine M; Qin, Chao; Farber, Jay P; Foreman, Robert D

2011-09-21

Sex differences in the characteristics of cardiac pain have been reported from clinical studies. For example, women experience chest pain less frequently than men. Women describe their chest pain as sharp and stabbing, while men have chest pain that is felt as a pressure or heaviness. Pain is also referred to the back more often in women than men. The mechanisms underlying sex differences in cardiac pain are unknown. One possible mechanism for the observed differences could be related to plasma estradiol. This study investigated the actions of estradiol on the activity of T(3) spinal neurons that process cardiosomatic information in male and female rats. Extracellular potentials of T(3) spinal neurons were recorded in response to mechanical somatic stimulation and noxious chemical cardiac stimulation in pentobarbital-anesthetized male and proestrous female rats. Fifty one percent and fifty percent of neurons responded to intrapericardial algogenic chemicals (0.2 ml) in male and female rats, respectively. Somatic fields were located by applying brush, pressure, and pinch to the upper body. Of those neurons receiving cardiac input, 54% in female and 55% in male rats also received somatic input. In both male and female rats, 81% of neurons responding to somatic stimuli had somatic fields located on the side of the upper body, while 19% of neurons had somatic fields located on the chest. These results indicate there are no significant differences in the responses of T(3) spinal neurons to cardiosomatic stimulation between male and proestrous female rats, despite differences in estradiol levels. Published by Elsevier B.V.

Renal ultrasound provides low utility in evaluating cardiac surgery associated acute kidney injury.

PubMed

Young, Allen; Crawford, Todd; Pierre, Alejandro Suarez; Trent Magruder, J; Fraser, Charles; Conte, John; Whitman, Glenn; Sciortino, Christopher

2017-09-02

Renal ultrasonography is part of the algorithm in assessing acute kidney injury (AKI). The purpose of this study was to assess the clinical utility of renal US in postoperative cardiac patients who develop AKI. We conducted a retrospective study of 90 postoperative cardiac surgery patients at a single institution from 1/19/2010 to 3/19/2016 who underwent renal US for AKI. We reviewed provider documentation to determine whether renal US changed management. We defined change as: administration of crystalloid or colloid, addition of inotropic or vasopressor, or procedural interventions on the renal system. Mean age of study patients was 68 ± 13 years. 48/90 patients (53.3%) had pre-existing chronic kidney disease of varying severity. 48 patients (53.3%) had normal renal US with incidental findings and 31 patients (34.4%) had US evidence of medical kidney disease. 10 patients (11.1%) had limited US results due to poor visualization and 1 patient (1.1%) had mild right-sided hydronephrosis. No patients were found to have obstructive uropathy or renal artery stenosis. Clinical management was altered in only 4/90 patients (4.4%), which included 3 patients that received a fluid bolus and 1 patient that received a fluid bolus and inotropes. No vascular or urologic procedures resulted from US findings. Although renal ultrasound is often utilized in the work-up of AKI, our study shows that renal US provides little benefit in managing postoperative cardiac patients. This diagnostic modality should be scrutinized rather than viewed as a universal measure in the cardiac surgery population.

Right ventricular involvement in cardiac sarcoidosis demonstrated with cardiac magnetic resonance

PubMed Central

van Geuns, Robert‐Jan; Ainslie, Gillian; Ector, Joris; Heidbuchel, Hein; Crijns, Harry J.G.M.

2017-01-01

Abstract Aims Cardiac involvement in sarcoidosis is reported in up to 30% of patients. Left ventricular involvement demonstrated by contrast‐enhanced cardiac magnetic resonance has been well validated. We sought to determine the prevalence and distribution of right ventricular late gadolinium enhancement in patients diagnosed with pulmonary sarcoidosis. Methods and results We prospectively evaluated 87 patients diagnosed with pulmonary sarcoidosis with contrast‐enhanced cardiac magnetic resonance for right ventricular involvement. Pulmonary artery pressures were non‐invasively evaluated with Doppler echocardiography. Patient characteristics were compared between the groups with and without right ventricular involvement, and right ventricular enhancement was correlated with pulmonary hypertension, ventricular mass, volume, and systolic function. Left ventricular late gadolinium enhancement was demonstrated in 30 patients (34%). Fourteen patients (16%) had right ventricular late gadolinium enhancement, with sole right ventricular enhancement in only two patients. The pattern of right ventricular enhancement consisted of right ventricular outflow tract enhancement in 1 patient, free wall enhancement in 8 patients, ventricular insertion point enhancement in 10 patients, and enhancement of the right side of the interventricular septum in 11 patients. Pulmonary arterial hypertension correlated with the presence of right ventricular enhancement (P < 0.001). Right ventricular enhancement correlated with systolic ventricular dysfunction (P < 0.001), hypertrophy (P = 0.001), and dilation (P < 0.001). Conclusions Right ventricular enhancement was present in 16% of patients diagnosed with pulmonary sarcoidosis and in 48% of patients with left ventricular enhancement. The presence of right ventricular enhancement correlated with pulmonary arterial hypertension, right ventricular systolic dysfunction, hypertrophy, and dilation. PMID:29154434

Improving the effectiveness of psychological interventions for depression and anxiety in the cardiac rehabilitation pathway using group-based metacognitive therapy (PATHWAY Group MCT): study protocol for a randomised controlled trial.

PubMed

Wells, Adrian; McNicol, Kirsten; Reeves, David; Salmon, Peter; Davies, Linda; Heagerty, Anthony; Doherty, Patrick; McPhillips, Rebecca; Anderson, Rebecca; Faija, Cintia; Capobianco, Lora; Morley, Helen; Gaffney, Hannah; Shields, Gemma; Fisher, Peter

2018-04-03

Anxiety and depression are prevalent among cardiac rehabilitation patients but pharmacological and psychological treatments have limited effectiveness in this group. Furthermore, psychological interventions have not been systematically integrated into cardiac rehabilitation services despite being a strategic priority for the UK National Health Service. A promising new treatment, metacognitive therapy, may be well-suited to the needs of cardiac rehabilitation patients and has the potential to improve outcomes. It is based on the metacognitive model, which proposes that a thinking style dominated by rumination, worry and threat monitoring maintains emotional distress. Metacognitive therapy is highly effective at reducing this thinking style and alleviating anxiety and depression in mental health settings. This trial aims to evaluate the effectiveness and cost-effectiveness of group-based metacognitive therapy for cardiac rehabilitation patients with elevated anxiety and/or depressive symptoms. The PATHWAY Group-MCT trial is a multicentre, two-arm, single-blind, randomised controlled trial comparing the clinical- and cost-effectiveness of group-based metacognitive therapy plus usual cardiac rehabilitation to usual cardiac rehabilitation alone. Cardiac rehabilitation patients (target sample n = 332) with elevated anxiety and/or depressive symptoms will be recruited across five UK National Health Service Trusts. Participants randomised to the intervention arm will receive six weekly sessions of group-based metacognitive therapy delivered by either cardiac rehabilitation professionals or research nurses. The intervention and control groups will both be offered the usual cardiac rehabilitation programme within their Trust. The primary outcome is severity of anxiety and depressive symptoms at 4-month follow-up measured by the Hospital Anxiety and Depression Scale total score. Secondary outcomes are severity of anxiety/depression at 12-month follow-up, health-related quality of life, severity of post-traumatic stress symptoms and strength of metacognitive beliefs at 4- and 12-month follow-up. Qualitative interviews will help to develop an account of barriers and enablers to the effectiveness of the intervention. This trial will evaluate the effectiveness and cost-effectiveness of group-based metacognitive therapy in alleviating anxiety and depression in cardiac rehabilitation patients. The therapy, if effective, offers the potential to improve psychological wellbeing and quality of life in this large group of patients. UK Clinical Trials Gateway, ISRCTN74643496 , Registered on 8 April 2015.

[Sports in Luxembourg. The role of heart healthy sports].

PubMed

Delagardelle, C

2015-01-01

30 years of organized ambulatory heart sport in Luxembourg Promoter of health sports. For more than 30 years both mortality and morbidity due to coronary artery disease (CAD) are significantly decreasing (> 70%) in the western world. This achievement is due to multiple interventions in the direct treatment of CAD and, especially, in fighting its risk factors: smoking, high blood pressure, hypercholesterolemia and physical inactivity. In 1984 the first ambulatory heart sport group (phase 3 of cardiac reeducation) was founded in Luxembourg City, followed in 1991 by a section in Esch/Alzette and in 2002 by a 3ème section in Ettelbrück. These phase 3 cardiac sport groups (= chronic phase) are organized by some committed patients working on a voluntary basis and performing a professional job. Paradoxically these phase 3 groups preceded the phases 1 and 2 (= "in hospital" and subacute) of cardiac rehabilitation. However, in a parallel way ambulatory phase 2 physical activity (PA) was started in the main hospitals in Luxembourg City (Centrum), Esch/Alzette (South) and Ettelbrück ( North). In 2002 a cornerstone study by Myers et al proved that physical fitness is the most determinant of survival both for healthy people and for cardiac patients: The better the fitness, quantified in METs, the better the prognosis and this fact is the basis for the application of sports therapy in cardiac and most other patients. An important epidemiological study published in 2012 by Lee et al in Lancet analyzed the effects of physical inactivity (PI) all over the world: 4 important diseases were studied: CAD, breast cancer, colon cancer and type 2 diabetes. The effects of PI are most pronounced in colon cancer followed by diabetes 2, breast cancer and then CAD. As a mean about 9% of all deaths -5.9 million in 57 million deaths/year worldwide- are caused by PI and for Luxembourg 12.9%. This cornerstone study can serve as rationale for physical therapy (PT) intervention in oncology, diabetes and CAD. It is noteworthy that the basic RF are more or less the same for the chronic diseases investigated in this study. Since the beginning of the new century PT has become an integral part of the strategies for cancer prevention and treatment. This option has been studied thoroughly first in breast cancer, later also in colon, prostate, and bronchial cancers etc. In primary prevention regular medium intensity training decreases the incidence of cancers by about 20-30%. For patients with proven cancers the application of PA as treatment option is more complicated compared to patients with cardiac problems since cancer patients often have to undergo surgery, then chemo- and/or irradiation therapy. All these interventions and their side effects have to be considered before applying PA. Above the physical alterations most cancer patients have to face anxiety and depression problems. PT improves the outcome between 15-25% and plays an important role in improving the psychological problems of the cancer patients. Since 10 years several oncologists in Luxembourg became interested in PA as a therapeutic option for their patients. They contacted the cardiologists and physiotherapists in charge of cardiac reeducation and progressively programs for PA in oncology were launched also in Luxembourg. Meanwhile several groups of cancer patients offer regular PT programs. In 2014 a stock concerning the different health sport activities in Luxembourg was taken by a young researcher of the Luxembourg Institute of health (LIH). 11 different associations are active; the most important and best organized are the cardiac sports groups, but there are also several oncologic, neurologic and orthopedic sports groups. A target for the coming years is to confer a robust infrastructure to all these associations following the model used by the cardiac groups. For the next year all these groups should be integrated into the Federation of Health Sports of the national Olympic Committee.

The effectiveness of and satisfaction with high-fidelity simulation to teach cardiac surgical resuscitation skills to nurses.

PubMed

McRae, Marion E; Chan, Alice; Hulett, Renee; Lee, Ai Jin; Coleman, Bernice

2017-06-01

There are few reports of the effectiveness or satisfaction with simulation to learn cardiac surgical resuscitation skills. To test the effect of simulation on the self-confidence of nurses to perform cardiac surgical resuscitation simulation and nurses' satisfaction with the simulation experience. A convenience sample of sixty nurses rated their self-confidence to perform cardiac surgical resuscitation skills before and after two simulations. Simulation performance was assessed. Subjects completed the Satisfaction with Simulation Experience scale and demographics. Self-confidence scores to perform all cardiac surgical skills as measured by paired t-tests were significantly increased after the simulation (d=-0.50 to 1.78). Self-confidence and cardiac surgical work experience were not correlated with time to performance. Total satisfaction scores were high (mean 80.2, SD 1.06) indicating satisfaction with the simulation. There was no correlation of the satisfaction scores with cardiac surgical work experience (τ=-0.05, ns). Self-confidence scores to perform cardiac surgical resuscitation procedures were higher after the simulation. Nurses were highly satisfied with the simulation experience. Copyright © 2016 Elsevier Ltd. All rights reserved.

Flavonoids and Chagas' Disease: The Story So Far!

PubMed

Nabavi, Seyed Fazel; Sureda, Antoni; Daglia, Maria; Izadi, Morteza; Rastrelli, Luca; Nabavi, Seyed Mohammad

2017-01-01

Chagas disease is one of the major health problems in Central and South America, which is caused by the parasitic protozoa, Trypanosoma cruzi. It is commonly transmitted by members of blood-sucking subfamily Triatominae. Chagas disease is associated with cardiac and gastrointestinal manifestations. Up to now, there are no effective vaccines for treatment of Chagas disease and benznidazole and nifurtimox are the only effective anti-Chagas drugs that cause different adverse and side effects. Therefore, much attention has been paid to natural products as novel therapeutic strategies for Chagas disease and its manifestations. Nowadays, some flavonoids could be considered as effective and safe bioactive natural products with potential anti-Chagas activity. Despite the increasing evidence, there is lack of review papers regarding the beneficial effects of flavonoids against Chagas disease and its manifestations. The aim of this paper is to review the available scientific data on the beneficial effects of flavonoids on Chagas disease and its manifestations published over the past two decades. Moreover, we provide an overview on etiology, transmission, epidemiology, clinical manifestations, and current treatment protocols of Chagas disease.

Which rivastigmine formula is better for heart in elderly patients with Alzheimer's disease: oral or patch?

PubMed

Isik, Ahmet Turan; Soysal, Pinar; Yay, Adnan

2014-12-01

Rivastigmine is commonly used for the treatment of Alzheimer's disease (AD). All cholinesterase inhibitors, including rivastigmine, may cause cardiac side effects. The aim of this study is to compare the electrocardiographic (ECG) and hypotensive effects of formulations of rivastigmine. Eighty-five newly diagnosed patients with AD who were treated with rivastigmine were retrospectively evaluated. The ECG records were reviewed at baseline and at administration of either 12 mg of oral rivastigmine or 10 cm(2) transdermal rivastigmine. When compared with the baseline, there were no changes in any of the ECG parameters in all of the patients (P > .05). Moreover, when compared with the mean change from baseline for each treatment group, there were no changes, except heart rate (P = .035). It was demonstrated that rivastigmine formulations were not associated with increased arrhythmogenic or hypotensive effects in elderly patients with AD and was not superior to each other. © The Author(s) 2014.

Cardiac myocyte-protective effect of microRNA-22 during ischemia and reperfusion through disrupting the caveolin-3/eNOS signaling

PubMed Central

Chen, Zhenfei; Qi, Yinliang; Gao, Chao

2015-01-01

MicroRNA-22 (miR-22) was previously reported to elicit cardiac myocyte hypertrophy and had an anti-apoptotic effect on neurons. However, its effects on cardiac myocyte apoptosis and cardiac function during ischemia and reperfusion (I/R) are not clear. In the present study, we demonstrate that pre-administration of miR-22 mimic reduced I/R-induced cardiac dysfunction significantly in a rat model. We found that miR-22 overexpression inhibited cardiac myocyte apoptosis, and reduced cardiac remodeling during I/R. Significant cardiac myocyte apoptosis was also observed in a cardiac myocyte model after hypoxia/reoxygenation (H/R), a representative process of I/R. Further experiments showed that eNOS activity and the following NO production were significantly decreased during I/R and H/R, while such decrease was inhibited by overexpression of miR-22. Mechanistically, overexpression of miR-22 had little effect on the total protein level of eNOS, but restored the level of p-eNOS (Ser1177) which was down-regulated during H/R. Further RT-PCR results demonstrated that Caveolin 3 (Cav3), an upstream negative regulator of eNOS, was upregulated during H/R, resulting in a decrease of p-eNOS. However, such upregulation of Cav3 transcript level was inhibited directly by miR-22 during H/R, leading to a restored p-eNOS level and followed NO production in cardiac myocytes. Together, the present study revealed that miR-22 down-regulated Cav3, leading to restored eNOS activity and NO production, which further inhibited cardiac myocyte apoptosis and promoted cardiac function after I/R. Of clinical interest, the present study may highlight miR-22 as a potential therapeutic agent for reducing I/R induced cardiac injury. PMID:26191152

Relationship between cardiac function and resting cerebral blood flow: MRI measurements in healthy elderly subjects.

PubMed

Henriksen, Otto M; Jensen, Lars T; Krabbe, Katja; Larsson, Henrik B W; Rostrup, Egill

2014-11-01

Although both impaired cardiac function and reduced cerebral blood flow are associated with ageing, current knowledge of the influence of cardiac function on resting cerebral blood flow (CBF) is limited. The aim of this study was to investigate the potential effects of cardiac function on CBF. CBF and cardiac output were measured in 31 healthy subjects 50-75 years old using magnetic resonance imaging techniques. Mean values of CBF, cardiac output and cardiac index were 43.6 ml per 100 g min(-1), 5.5 l min(-1) and 2.7 l min(-1) m(-2), respectively, in males, and 53.4 ml per 100 g min(-1), 4.3 l min(-1) and 2.4 l min(-1) m(-2), respectively, in females. No effects of cardiac output or cardiac index on CBF or structural signs of brain ageing were observed. However, fractional brain flow defined as the ratio of total brain flow to cardiac output was inversely correlated with cardiac index (r(2) = 0.22, P = 0.008) and furthermore lower in males than in females (8.6% versus 12.5%, P = 0.003). Fractional brain flow was also inversely correlated with cerebral white matter lesion grade, although this effect was not significant when adjusted for age. Frequency analysis of heart rate variability showed a gender-related inverse association of increased low-to-high-frequency power ratio with CBF and fractional brain flow. The findings do not support a direct effect of cardiac function on CBF, but demonstrates gender-related differences in cardiac output distribution. We propose fractional brain flow as a novel index that may be a useful marker of adequate brain perfusion in the context of ageing as well as cardiovascular disease. © 2013 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

Bioimpedance harmonic analysis as a tool to simultaneously assess circulation and nervous control.

PubMed

Mudraya, I S; Revenko, S V; Nesterov, A V; Gavrilov, I Yu; Kirpatovsky, V I

2011-07-01

Multicycle harmonic (Fourier) analysis of bioimpedance was employed to simultaneously assess circulation and neural activity in visceral (rat urinary bladder) and somatic (human finger) organs. The informative value of the first cardiac harmonic of the bladder impedance as an index of bladder circulation is demonstrated. The individual reactions of normal and obstructive bladders in response to infusion cystometry were recorded. The potency of multicycle harmonic analysis of bioimpedance to assess sympathetic and parasympathetic neural control in urinary bladder is discussed. In the human finger, bioimpedance harmonic analysis revealed three periodic components at the rate of the heart beat, respiration and Mayer wave (0.1 Hz), which were observed under normal conditions and during blood flow arrest in the hand. The revealed spectrum peaks were explained by the changes in systemic blood pressure and in regional vascular tone resulting from neural vasomotor control. During normal respiration and circulation, two side cardiac peaks were revealed in a bioimpedance amplitude spectrum, whose amplitude reflected the depth of amplitude respiratory modulation of the cardiac output. During normal breathing, the peaks corresponding to the second and third cardiac harmonics were split, reflecting frequency respiratory modulation of the heart rate. Multicycle harmonic analysis of bioimpedance is a novel potent tool to examine the interaction between the respiratory and cardiovascular system and to simultaneously assess regional circulation and neural influences in visceral and somatic organs.

Resuscitation Outcomes Consortium (ROC) PRIMED Cardiac Arrest Trial Methods Part 2: Rationale and Methodology for “Analyze Later” Protocol

PubMed Central

Stiell, Ian G.; Callaway, Clif; Davis, Dan; Terndrup, Tom; Powell, Judy; Cook, Andrea; Kudenchuk, Peter J.; Daya, Mohamud; Kerber, Richard; Idris, Ahamed; Morrison, Laurie J.; Aufderheide, Tom

2008-01-01

Objective The primary objective of the trial is to compare survival to hospital discharge with Modified Rankin Score (MRS) ≤3 between a strategy that prioritizes a specified period of CPR before rhythm analysis (Analyze Later) versus a strategy of minimal CPR followed by early rhythm analysis (Analyze Early) in patients with out-of-hospital cardiac arrest. Methods   Design Cluster randomized trial with cluster units defined by geographic region, or monitor/defibrillator machine. Population Adults treated by Emergency Medical Service (EMS) providers for non-traumatic out-of-hospital cardiac arrest not witnessed by EMS. Setting EMS systems participating in the Resuscitation Outcomes Consortium and agreeing to cluster randomization to the Analyze Later versus Analyze Early intervention in a crossover fashion. Sample Size Based on a two-sided significance level of 0.05, a maximum of 13,239 evaluable patients will allow statistical power of 0.996 to detect a hypothesized improvement in the probability of survival to discharge with MRS ≤ 3 rate from 5.41% after Analyze Early to 7.45% after Analyze Later (2.04% absolute increase in primary outcome). Conclusion If this trial demonstrates a significant improvement in survival with a strategy of Analyze Later, it is estimated that 4,000 premature deaths from cardiac arrest would be averted annually in North America alone. PMID:18487004

Transplanted hematopoietic stem cells demonstrate impaired sarcoglycan expression after engraftment into cardiac and skeletal muscle.

PubMed

Lapidos, Karen A; Chen, Yiyin E; Earley, Judy U; Heydemann, Ahlke; Huber, Jill M; Chien, Marcia; Ma, Averil; McNally, Elizabeth M

2004-12-01

Pluripotent bone marrow-derived side population (BM-SP) stem cells have been shown to repopulate the hematopoietic system and to contribute to skeletal and cardiac muscle regeneration after transplantation. We tested BM-SP cells for their ability to regenerate heart and skeletal muscle using a model of cardiomyopathy and muscular dystrophy that lacks delta-sarcoglycan. The absence of delta-sarcoglycan produces microinfarcts in heart and skeletal muscle that should recruit regenerative stem cells. Additionally, sarcoglycan expression after transplantation should mark successful stem cell maturation into cardiac and skeletal muscle lineages. BM-SP cells from normal male mice were transplanted into female delta-sarcoglycan-null mice. We detected engraftment of donor-derived stem cells into skeletal muscle, with the majority of donor-derived cells incorporated within myofibers. In the heart, donor-derived nuclei were detected inside cardiomyocytes. Skeletal muscle myofibers containing donor-derived nuclei generally failed to express sarcoglycan, with only 2 sarcoglycan-positive fibers detected in the quadriceps muscle from all 14 mice analyzed. Moreover, all cardiomyocytes with donor-derived nuclei were sarcoglycan-negative. The absence of sarcoglycan expression in cardiomyocytes and skeletal myofibers after transplantation indicates impaired differentiation and/or maturation of bone marrow-derived stem cells. The inability of BM-SP cells to express this protein severely limits their utility for cardiac and skeletal muscle regeneration.

Resuscitation Outcomes Consortium (ROC) PRIMED cardiac arrest trial methods part 2: rationale and methodology for "Analyze Later vs. Analyze Early" protocol.

PubMed

Stiell, Ian G; Callaway, Clif; Davis, Dan; Terndrup, Tom; Powell, Judy; Cook, Andrea; Kudenchuk, Peter J; Daya, Mohamud; Kerber, Richard; Idris, Ahamed; Morrison, Laurie J; Aufderheide, Tom

2008-08-01

The primary objective of the trial is to compare survival to hospital discharge with modified Rankin score (MRS) < or =3 between a strategy that prioritizes a specified period of CPR before rhythm analysis (Analyze Later) versus a strategy of minimal CPR followed by early rhythm analysis (Analyze Early) in patients with out-of-hospital cardiac arrest. Design-Cluster randomized trial with cluster units defined by geographic region, or monitor/defibrillator machine. Population-Adults treated by emergency medical service (EMS) providers for non-traumatic out-of-hospital cardiac arrest not witnessed by EMS. Setting-EMS systems participating in the Resuscitation Outcomes Consortium and agreeing to cluster randomization to the Analyze Later versus Analyze Early intervention in a crossover fashion. Sample size-Based on a two-sided significance level of 0.05, a maximum of 13,239 evaluable patients will allow statistical power of 0.996 to detect a hypothesized improvement in the probability of survival to discharge with MRS < or =3 rate from 5.41% after Analyze Early to 7.45% after Analyze Later (2.04% absolute increase in primary outcome). If this trial demonstrates a significant improvement in survival with a strategy of Analyze Later, it is estimated that 4000 premature deaths from cardiac arrest would be averted annually in North America alone.

Interventional cardiology for the criticalist.

PubMed

Scansen, Brian A

2011-04-01

To review indications, procedures, and prognosis for common cardiovascular emergencies requiring intervention in small animals. Pericardial effusion, symptomatic bradycardia, and heartworm-induced caval syndrome are examples of clinical scenarios commonly requiring intervention. Pericardial effusion in small animals occurs most frequently from cardiac neoplasia, idiopathic pericarditis, or congestive heart failure. Indications for temporary pacing include transient bradyarrhythmias, ingestions resulting in chronotropic incompetence, and emergency stabilization of critical bradyarrhythmias. Caval syndrome results from a large dirofilarial worm burden, pulmonary hypertension, and mechanical obstruction of right-sided cardiac output with resultant hemolysis and organ dysfunction. The diagnosis of pericardial effusion is suspected from signalment and physical findings and confirmed with cardiac ultrasound. Symptomatic bradycardias often present for syncope and definitive diagnosis derives from an ECG. Caval syndrome is diagnosed upon clinical, hematologic, and ultrasonographic evidence of severe heartworm infestation, cardiovascular compromise, and/or mechanical hemolysis. Pericardial effusion is alleviated by pericardiocentesis in the emergency setting, though may require further intervention for long-term palliation. Temporary transvenous pacing can be performed emergently to stabilize the symptomatic patient with a bradyarrhythmia. Dirofilariasis leading to caval syndrome requires urgent heartworm extraction. The prognosis for pericardial effusion is dependent upon the underlying etiology; the prognosis for cardiac pacing is favorable, and the prognosis for caval syndrome is grave if untreated and guarded to fair if heartworm extraction is performed. © Veterinary Emergency and Critical Care Society 2011.

A dosimetric study of cardiac dose sparing using the reverse semi-decubitus technique for left breast and internal mammary chain irradiation.

PubMed

Niglas, Mark; McCann, Claire; Keller, Brian M; Makhani, Nadiya; Presutti, Joseph; Vesprini, Danny; Rakovitch, Eileen; Elzibak, Alyaa; Mashouf, Shahram; Lee, Justin

2016-01-01

Breath-hold techniques can reduce cardiac dose in breast radiotherapy. The reverse semi-decubitus (RSD) technique is an alternative free-breathing method used at our centre. This study compares the dosimetry of free-breathing supine, RSD and moderate deep inspiration breath-hold (mDIBH) techniques. Twelve patients with left-sided breast cancer who were simulated using standard supine, RSD and mDIBH techniques were identified retrospectively. New plans using standard breast tangents and techniques for internal mammary chain (IMC) nodal coverage were assessed. Using standard tangents, mean heart dose, heart V25Gy and mean left anterior descending artery (LAD) dose were found to be significantly lower for RSD and mDIBH when compared to free-breathing supine (p ⩽ 0.03). Using wide-tangents, the maximum LAD point dose was also lower for RSD and mDIBH (p ⩽ 0.02). There were no statistically significant dosimetric differences found between the RSD and mDIBH simulation techniques for standard breast-tangent plans, though organ-at-risk doses were lower for mDIBH in wide-tangent plans. There was no improvement in cardiac dosimetry between RSD and free-breathing supine when using an electron field IMC plan. For patients unable to tolerate breath-hold, the RSD technique is an alternative approach that can reduce cardiac dose. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Graphical and statistical techniques for cardiac cycle time (phase) dependent changes in interbeat interval: problems with the Jennings et al. (1991) proposals.

PubMed

Barry, R J

1993-01-01

Two apparently new effects in human cardiac responding, "primary bradycardia" and "vagal inhibition", were first described by the Laceys. These effects have been considered by some researchers to reflect differential cardiac innervation, analogous to similar effects observed in animal preparations with direct vagal stimulation. However, it has been argued that such effects arise merely from the data-analytic techniques introduced by the Laceys, and hence are not genuine cardiac cycle effects. Jennings, van der Molen, Somsen and Ridderinkhoff (Psychophysiology, 28 (1991) 596-606) recently proposed a plotting technique and statistical procedure in an attempt to resolve this issue. The present paper demonstrates that the plotting technique fails to achieve their stated aim, since it identifies data from identical cardiac responses as showing cardiac-cycle effects. In addition, the statistical procedure is shown to be reducible to a trivial test of response occurrence. The implication of these demonstrations, in the context of other work, is that this area of investigation has reached a dead end.

To kiss or not to kiss? Impact of final kissing-balloon inflation on early and long-term results of percutaneous coronary intervention for bifurcation lesions.

PubMed

Biondi-Zoccai, Giuseppe; Sheiban, Imad; De Servi, Stefano; Tamburino, Corrado; Sangiorgi, Giuseppe; Romagnoli, Enrico

2014-11-01

Final kissing-balloon inflation is often recommended for percutaneous coronary intervention (PCI) of bifurcation lesions. However, randomized trials focusing on kissing inflation have not confirmed its beneficial impact. We compared outcomes of kissing inflation for PCI of bifurcation lesions, explicitly stratifying results according to stenting strategy. Patients undergoing bifurcation PCI were retrospectively enrolled. Subjects receiving final kissing inflation were compared with those not undergoing kissing inflation, after stratification for a single-stent technique. The primary end point was the long-term rate of major adverse cardiac events (MACE, i.e., death, myocardial infarction, or target lesion revascularization (TLR)). A total of 4314 patients were included: 1176 (27.3 %) treated with a single stent and kissing inflation, 1637 (37.9 %) with a single stent but no kissing, 1072 (24.8 %) with two stents and kissing, and 429 (9.9 %) with two stents but no kissing. At unadjusted analyses kissing was associated with fewer short-term MACE and deaths in the two-stent group, and with fewer long-term MACE, cardiac deaths, and side-branch TLR in the two-stent group (all P < 0.05). Conversely, kissing appeared detrimental after single stenting. However, after multivariable analyses, kissing no longer significantly affected the risk of adverse events, with the exception of the risk of side-branch TLR, which was lower in those receiving two stents and final kissing inflation (hazard ratio = 0.52, 95 % confidence interval 0.30–0.90, P = 0.020). Kissing inflation can be avoided in bifurcation lesions uneventfully treated with single-stent PCI. However, final kissing-balloon inflation appears beneficial in reducing the risk of side-branch repeat revascularization after using a two-stent strategy.

Cardiac Dose Reduction with Deep-Inspiratory Breath Hold Technique of Radiotherapy for Left-Sided Breast Cancer.

PubMed

Sripathi, Lalitha Kameshwari; Ahlawat, Parveen; Simson, David K; Khadanga, Chira Ranjan; Kamarsu, Lakshmipathi; Surana, Shital Kumar; Arasu, Kavi; Singh, Harpreet

2017-01-01

Different techniques of radiation therapy have been studied to reduce the cardiac dose in left breast cancer. In this prospective dosimetric study, the doses to heart as well as other organs at risk (OAR) were compared between free-breathing (FB) and deep inspiratory breath hold (DIBH) techniques in intensity modulated radiotherapy (IMRT) and opposed-tangent three-dimensional radiotherapy (3DCRT) plans. Fifteen patients with left-sided breast cancer underwent computed tomography simulation and images were obtained in both FB and DIBH. Radiotherapy plans were generated with 3DCRT and IMRT techniques in FB and DIBH images in each patient. Target coverage, conformity index, homogeneity index, and mean dose to heart (Heart D mean ), left lung, left anterior descending artery (LAD) and right breast were compared between the four plans using the Wilcoxon signed rank test. Target coverage was adequate with both 3DCRT and IMRT plans, but IMRT plans showed better conformity and homogeneity. A statistically significant dose reduction of all OARs was found with DIBH. 3DCRT DIBH decreased the Heart D mean by 53.5% (7.1 vs. 3.3 Gy) and mean dose to LAD by 28% compared to 3DCRT FB . IMRT further lowered mean LAD dose by 18%. Heart D mean was lower with 3DCRT DIBH over IMRT DIBH (3.3 vs. 10.2 Gy). Mean dose to the contralateral breast was also lower with 3DCRT over IMRT (0.32 vs. 3.35 Gy). Mean dose and the V 20 of ipsilateral lung were lower with 3DCRT DIBH over IMRT DIBH (13.78 vs. 18.9 Gy) and (25.16 vs. 32.95%), respectively. 3DCRT DIBH provided excellent dosimetric results in patients with left-sided breast cancer without the need for IMRT.

Cardiac Dose Reduction with Deep-Inspiratory Breath Hold Technique of Radiotherapy for Left-Sided Breast Cancer

PubMed Central

Sripathi, Lalitha Kameshwari; Ahlawat, Parveen; Simson, David K; Khadanga, Chira Ranjan; Kamarsu, Lakshmipathi; Surana, Shital Kumar; Arasu, Kavi; Singh, Harpreet

2017-01-01

Introduction: Different techniques of radiation therapy have been studied to reduce the cardiac dose in left breast cancer. Aim: In this prospective dosimetric study, the doses to heart as well as other organs at risk (OAR) were compared between free-breathing (FB) and deep inspiratory breath hold (DIBH) techniques in intensity modulated radiotherapy (IMRT) and opposed-tangent three-dimensional radiotherapy (3DCRT) plans. Materials and Methods: Fifteen patients with left-sided breast cancer underwent computed tomography simulation and images were obtained in both FB and DIBH. Radiotherapy plans were generated with 3DCRT and IMRT techniques in FB and DIBH images in each patient. Target coverage, conformity index, homogeneity index, and mean dose to heart (Heart Dmean), left lung, left anterior descending artery (LAD) and right breast were compared between the four plans using the Wilcoxon signed rank test. Results: Target coverage was adequate with both 3DCRT and IMRT plans, but IMRT plans showed better conformity and homogeneity. A statistically significant dose reduction of all OARs was found with DIBH. 3DCRTDIBH decreased the Heart Dmean by 53.5% (7.1 vs. 3.3 Gy) and mean dose to LAD by 28% compared to 3DCRTFB. IMRT further lowered mean LAD dose by 18%. Heart Dmean was lower with 3DCRTDIBH over IMRTDIBH (3.3 vs. 10.2 Gy). Mean dose to the contralateral breast was also lower with 3DCRT over IMRT (0.32 vs. 3.35 Gy). Mean dose and the V20 of ipsilateral lung were lower with 3DCRTDIBH over IMRTDIBH (13.78 vs. 18.9 Gy) and (25.16 vs. 32.95%), respectively. Conclusions: 3DCRTDIBH provided excellent dosimetric results in patients with left-sided breast cancer without the need for IMRT. PMID:28974856

Deep inspiration breath hold with electromagnetic confirmation of chest wall position for adjuvant therapy of left-sided breast cancer: Technique and accuracy.

PubMed

Kathpal, Madeera; Tinnel, Brent; Sun, Kelly; Ninneman, Stephanie; Malmer, Cynthia; Wendt, Stacie; Buff, Sheena; Valentich, David; Gossweiler, Marisa; Macdonald, Dusten

2016-01-01

With most patients now living long after their breast cancer diagnosis, minimizing long-term side effects of breast cancer treatment, such as reducing late cardiac and pulmonary side effects of radiation therapy (RT), is particularly important. It is now possible to use an electromagnetic tracking system to allow real-time tracking of chest wall (CW) position during the delivery of RT. Here, we report our experience using electromagnetic surface transponders as an added measure of CW position during deep inspiration breath hold (DIBH). We conducted a single-institution institutional review board-approved retrospective review of 15 female left-sided breast cancer patients treated between July 2012 and June 2013 with conventional whole breast radiation. We compared daily port films with treatment planning digitally reconstructed radiographs to establish daily setup accuracy, then used Calypso tracings to compare the position of the CW during the daily port film with the position of the CW during that day's treatment to determine the reproducibility of the breath hold position. Finally, we created competing treatment plans not using DIBH and used a paired t test to compare mean heart (MH) and left anterior descending (LAD) coronary artery dose between the 2 techniques. Mean total error (inter- and intrafraction) was dominated by interfraction error and was greatest in the longitudinal direction with a mean of 2.13 mm and 2 standard deviations of 8.2 mm. DIBH significantly reduced MH and LAD dose versus free breathing plans (MH, 1.26 Gy vs 2.84 Gy, P ≤ .001; LAD, 5.49 Gy vs 18.15 Gy, P ≤ .001). This study demonstrates that DIBH with electromagnetic confirmation of CW position is feasible, and allows potential improvement in the accurate delivery of adjuvant RT therapy for breast cancer. Published by Elsevier Inc.

Temperature effects on aerobic scope and cardiac performance of European perch (Perca fluviatilis).

PubMed

Jensen, Denise Lyager; Overgaard, Johannes; Wang, Tobias; Gesser, Hans; Malte, Hans

2017-08-01

Several recent studies have highlighted how impaired cardiac performance at high temperatures and in hypoxia may compromise the capacity for oxygen transport. Thus, at high temperatures impaired cardiac capacity is proposed to reduce oxygen transport to a degree that lowers aerobic scope and compromises thermal tolerance (the oxygen- and capacity-limited thermal tolerance (OCLTT) hypothesis). To investigate this hypothesis, we measured aerobic and cardiac performance of a eurythermal freshwater teleost, the European perch (Perca fluviatilis). Rates of oxygen consumption were measured during rest and activity at temperatures between 5°C and 27°C, and we evaluated cardiac function by in vivo measurements of heart rate and in vitro studies to determine contractility of myocardial strips. Aerobic scope increased progressively from 5°C to 21°C, after which it levelled off. Heart rate showed a similar response. We found little difference between resting and active heart rate at high temperature suggesting that increased cardiac scope during activity is primarily related to changes in stroke volume. To examine the effects of temperature on cardiac capacity, we measured isometric force development in electrically paced myocardial preparations during different combinations of temperature, pacing frequency, oxygenation and adrenergic stimulation. The force-frequency product increased markedly upon adrenergic stimulation at 21 and 27°C (with higher effects at 21°C) and the cardiac preparations were highly sensitive to hypoxia. These findings suggest that at (critically) high temperatures, cardiac output may diminish due to a decreased effect of adrenergic stimulation and that this effect may be further exacerbated if the heart becomes hypoxic. Hence cardiac limitations may contribute to the inability to increase aerobic scope at high temperatures in the European perch (Perca fluviatilis). Copyright © 2017 Elsevier Ltd. All rights reserved.

Consequences of cardiovascular adaptation to spaceflight: implications for the use of pharmacological countermeasures

NASA Technical Reports Server (NTRS)

Convertino, Victor A.

2005-01-01

There is little evidence obtained from space flight to support the notion that occurrence of cardiac dysrhythmias, impaired cardiac and vascular function, and manifestation of asymptomatic cardiovascular disease represent serious risks during space flight. Therefore, the development of orthostatic hypotension and instability immediately after return from spaceflight probably reflect the most significant operational risks associated with the cardiovascular system of astronauts. Significant reductions in stroke volume and lower reserve for increasing peripheral vascular resistance contribute to ineffective maintenance of systemic arterial blood pressure during standing after spaceflight despite compensatory elevations in heart rate. The primary mechanism underlying reduced stroke volume appears to be a reduction in preload associated with less circulating blood volume while inadequate peripheral vasoconstriction may be caused partly by hyporeactivity of receptors that control arterial smooth muscle function. A focus for development of future countermeasures for hemodynamic responses to central hypovolemia includes the potential application of pharmacological agents that specifically target and restore blood volume (e.g., fludrocortisone, electrolyte-containing beverages) and reserve for vasoconstriction (e.g., midodrine, vasopressin). Based on systematic evaluations, acute physical exercise designed to elicit maximal effort or inspiratory resistance have shown promise as successful countermeasures that provide protection against development of orthostatic hypotension and intolerance without potential risks and side effects associated with specific pharmacological interventions.

Whole-body strength training with Huber Motion Lab and traditional strength training in cardiac rehabilitation: A randomized controlled study.

PubMed

Guiraud, Thibaut; Labrunée, Marc; Besnier, Florent; Sénard, Jean-Michel; Pillard, Fabien; Rivière, Daniel; Richard, Lisa; Laroche, Davy; Sanguignol, Frédéric; Pathak, Atul; Gayda, Mathieu; Gremeaux, Vincent

2017-01-01

Isometric strengthening has been rarely studied in patients with coronary heart disease (CHD), mainly because of possible potential side effects and lack of appropriate and reliable devices. We aimed to compare 2 different modes of resistance training, an isometric mode with the Huber Motion Lab (HML) and traditional strength training (TST), in CHD patients undergoing a cardiac rehabilitation program. We randomly assigned 50 patients to HML or TST. Patients underwent complete blinded evaluation before and after the rehabilitation program, including testing for cardiopulmonary exercise, maximal isometric voluntary contraction, endothelial function and body composition. After 4 weeks of training (16 sessions), the groups did not differ in body composition, anthropometric characteristics, or endothelial function. With HML, peak power output (P=0.035), maximal heart rate (P<0.01) and gain of force measured in the chest press position (P<0.02) were greater after versus before training. Both protocols appeared to be well tolerated, safe and feasible for these CHD patients. A training protocol involving 6s phases of isometric contractions with 10s of passive recovery on an HML device could be safely implemented in rehabilitation programs for patients with CHD and improve functional outcomes. Copyright © 2016. Published by Elsevier Masson SAS.

Generation of a Homozygous Transgenic Rat Strain Stably Expressing a Calcium Sensor Protein for Direct Examination of Calcium Signaling.

PubMed

Szebényi, Kornélia; Füredi, András; Kolacsek, Orsolya; Pergel, Enikő; Bősze, Zsuzsanna; Bender, Balázs; Vajdovich, Péter; Tóvári, József; Homolya, László; Szakács, Gergely; Héja, László; Enyedi, Ágnes; Sarkadi, Balázs; Apáti, Ágota; Orbán, Tamás I

2015-08-03

In drug discovery, prediction of selectivity and toxicity require the evaluation of cellular calcium homeostasis. The rat is a preferred laboratory animal for pharmacology and toxicology studies, while currently no calcium indicator protein expressing rat model is available. We established a transgenic rat strain stably expressing the GCaMP2 fluorescent calcium sensor by a transposon-based methodology. Zygotes were co-injected with mRNA of transposase and a CAG-GCaMP2 expressing construct, and animals with one transgene copy were pre-selected by measuring fluorescence in blood cells. A homozygous rat strain was generated with high sensor protein expression in the heart, kidney, liver, and blood cells. No pathological alterations were found in these animals, and fluorescence measurements in cardiac tissue slices and primary cultures demonstrated the applicability of this system for studying calcium signaling. We show here that the GCaMP2 expressing rat cardiomyocytes allow the prediction of cardiotoxic drug side-effects, and provide evidence for the role of Na(+)/Ca(2+) exchanger and its beneficial pharmacological modulation in cardiac reperfusion. Our data indicate that drug-induced alterations and pathological processes can be followed by using this rat model, suggesting that transgenic rats expressing a calcium-sensitive protein provide a valuable system for pharmacological and toxicological studies.

Detection and monitoring of cardiotoxicity-what does modern cardiology offer?

PubMed

Jurcut, Ruxandra; Wildiers, Hans; Ganame, Javier; D'hooge, Jan; Paridaens, Robert; Voigt, Jens-Uwe

2008-05-01

With new anticancer therapies, many patients can have a long life expectancy. Treatment-related comorbidities become an issue for cancer survivors. Cardiac toxicity remains an important side effect of anticancer therapies. Myocardial dysfunction can become apparent early or long after end of therapy and may be irreversible. Detection of cardiac injury is crucial since it may facilitate early therapeutic measures. Traditionally, chemotherapy-induced cardiotoxicity has been detected by measuring changes in left ventricular ejection fraction. This parameter is, however, insensitive to subtle changes in myocardial function as they occur in early cardiotoxicity. This review will discuss conventional and modern cardiologic approaches of assessing myocardial function. It will focus on Doppler myocardial imaging, a method which allows to sensitively measure myocardial function parameters like myocardial velocity, deformation (strain), or deformation rate (strain rate) and which has been shown to reliably detect early abnormalities in both regional and global myocardial function in an early stage. Other newer echocardiographic function estimators are based on automated border detection algorithms and ultrasonic integrated backscatter analysis. A further technique to be discussed is dobutamine stress echocardiography. The use of new biomarkers like B-type natriuretic peptide and troponin and less often used imaging techniques like magnetic resonance imaging and computed tomography will also be mentioned.

Ultrasound image guidance of cardiac interventions

NASA Astrophysics Data System (ADS)

Peters, Terry M.; Pace, Danielle F.; Lang, Pencilla; Guiraudon, Gérard M.; Jones, Douglas L.; Linte, Cristian A.

2011-03-01

Surgical procedures often have the unfortunate side-effect of causing the patient significant trauma while accessing the target site. Indeed, in some cases the trauma inflicted on the patient during access to the target greatly exceeds that caused by performing the therapy. Heart disease has traditionally been treated surgically using open chest techniques with the patient being placed "on pump" - i.e. their circulation being maintained by a cardio-pulmonary bypass or "heart-lung" machine. Recently, techniques have been developed for performing minimally invasive interventions on the heart, obviating the formerly invasive procedures. These new approaches rely on pre-operative images, combined with real-time images acquired during the procedure. Our approach is to register intra-operative images to the patient, and use a navigation system that combines intra-operative ultrasound with virtual models of instrumentation that has been introduced into the chamber through the heart wall. This paper illustrates the problems associated with traditional ultrasound guidance, and reviews the state of the art in real-time 3D cardiac ultrasound technology. In addition, it discusses the implementation of an image-guided intervention platform that integrates real-time ultrasound with a virtual reality environment, bringing together the pre-operative anatomy derived from MRI or CT, representations of tracked instrumentation inside the heart chamber, and the intra-operatively acquired ultrasound images.

Dispersant use as a response to oil spills: toxicological effects on fish cardiac performance.

PubMed

Milinkovitch, Thomas; Thomas-Guyon, Hélène; Lefrançois, Christel; Imbert, Nathalie

2013-04-01

Dispersant use is a controversial technique used to respond to oil spills in nearshore areas. In order to assess the toxicity of this technique, this study evaluated the cardiac toxicological effects on juvenile golden grey mullets Liza aurata exposed for 48 h to either dispersant alone, chemically dispersed oil, mechanically dispersed oil, the water-soluble fraction of oil or a control condition. Following exposure, the positive inotropic effects of adrenaline were assessed in order to evaluate a potential impairment on the cardiac performance. The results revealed an impairment of the positive inotropic effects of adrenaline for all the contaminants (single dispersant, dispersed and undispersed oil, water-soluble fraction of oil). This suggests that: (1) cardiac performance is a valuable parameter to study the physiopathological effects of dispersed oil; (2) dispersant application is likely to impair cardiac performance.

Serum cortisol concentration with exploratory cut-off values do not predict the effects of hydrocortisone administration in children with low cardiac output after cardiac surgery.

PubMed

Verweij, E J; Hogenbirk, Karin; Roest, Arno A W; van Brempt, Ronald; Hazekamp, Mark G; de Jonge, Evert

2012-10-01

Low cardiac output syndrome is common after paediatric cardiac surgery. Previous studies suggested that hydrocortisone administration may improve haemodynamic stability in case of resistant low cardiac output syndrome in critically ill children. This study was set up to test the hypothesis that the effects of hydrocortisone on haemodynamics in children with low cardiac output syndrome depend on the presence of (relative) adrenal insufficiency. A retrospective study was done on paediatric patients who received hydrocortisone when diagnosed with resistant low cardiac output syndrome after paediatric cardiac surgery in the period from 1 November 2005 to 31 December 2008. We studied the difference in effects of treatment with hydrocortisone administration between patients with adrenal insufficiency defined as an exploratory cut-off value of total cortisol of <100 nmol/l and patients with a serum total cortisol of ≥ 100 nmol/l. A total of 62 of patients were enrolled, meeting the inclusion criteria for low cardiac output syndrome. Thirty-two patients were assigned to Group 1 (<100 nmol/l) and 30 were assigned to Group 2 (≥ 100 nmol/l). Haemodynamics improved after hydrocortisone administration, with an increase in blood pressure, a decrease in administered vasopressors and inotropic drugs, an increase in urine production and a decrease in plasma lactate concentrations. The effects of treatment with hydrocortisone in children with low cardiac output after cardiac surgery was similar in patients with a low baseline serum cortisol concentration and those with normal baseline cortisol levels. A cortisol value using an exploratory cut-off value of 100 nmol/l for adrenal insufficiency should not be used as a criterion to treat these patients with hydrocortisone.

Effect of autogenic training on cardiac autonomic nervous activity in high-risk fire service workers for posttraumatic stress disorder.

PubMed

Mitani, Satoko; Fujita, Masatoshi; Sakamoto, Satoko; Shirakawa, Taro

2006-05-01

We investigated the effect of autogenic training (AT) on cardiac autonomic nervous activity in fire services workers with the use of the questionnaire of the Japanese-language version of Impact of Event Scale-Revised (IES-R-J) and indexes of heart rate variability. We studied 22 male fire services workers who were divided into posttraumatic stress disorder (PTSD)-related stress group (n=10) and control group (n=12). They underwent AT twice or three times a week for 2 months. Posttraumatic stress disorder-related stress group showed a significantly higher cardiac sympathetic nervous activity and a significantly lower cardiac parasympathetic nervous activity than control group at baseline. Autogenic training significantly decreased cardiac sympathetic nervous activity and significantly increased cardiac parasympathetic nervous activity in both groups. These changes were accompanied by a significant decrease in the total points of IES-R-J. Autogenic training is effective for ameliorating the disturbance of cardiac autonomic nervous activity and psychological issues secondary to PTSD.

Caffeic acid phenethyl ester attenuates pathological cardiac hypertrophy by regulation of MEK/ERK signaling pathway in vivo and vitro.

PubMed

Ren, Jie; Zhang, Nan; Liao, Haihan; Chen, Si; Xu, Ling; Li, Jing; Yang, Zheng; Deng, Wei; Tang, Qizhu

2017-07-15

To explore the effects of caffeic acid phenethyl ester (CAPE) on cardiac hypertrophy induced by pressure overload. Male wild-type C57 mice, aged 8-10weeks, were used for aortic banding (AB) to induce cardiac hypertrophy. CAPE or (resveratrol) RS was administered from the 3rd day after AB surgery for 6weeks. Echocardiography and hemodynamic analysis were performed to estimate cardiac function. Mice hearts were collected for H&E and PSR staining. Western blot analysis and quantitative PCR were performed for to investigate molecular mechanism. We further confirmed our findings in H9c2 cardiac fibroblasts treated with PE or CAPE. CAPE protected against cardiac hypertrophy induced by pressure overload, as evidenced by inhibition of cardiac hypertrophy and improvement in mouse cardiac function. The effect of CAPE on cardiac hypertrophy was mediated via inhibition of the MEK/ERK and TGFβ-Smad signaling pathways. We also demonstrated that CAPE protected H9c2 cells from PE-induced hypertrophy in vitro via a similar molecular mechanism as seen in the mouse heart. Finally, CAPE seemed to be as effective as RS for treatment of pressure overload induced mouse cardiac hypertrophy. Our results suggest that CAPE may play an important role in the regulation of cardiac hypertrophy induced by pressure overload via negative regulation of the MEK/ERK and TGFβ/Smad signaling pathways. These results indicate that CAPE could potentially be used for treatment of cardiac hypertrophy. Copyright © 2017 Elsevier Inc. All rights reserved.

Fresh gasoline emissions, not paved road dust, alter cardiac repolarization in ApoE-/- mice.

PubMed

Campen, Matthew J; McDonald, Jacob D; Reed, Matthew D; Seagrave, Jeanclare

2006-01-01

Fresh vehicular emissions potentially represent a ubiquitous environmental concern for cardiovascular health. We compared electrocardiographic effects of fresh gasoline engine emissions with resuspended paved road dust in a mouse model of coronary insufficiency. Apolipoprotein E (ApoE)-/- mice on a high fat diet were exposed by whole-body inhalation to either gasoline emissions at 60 microg/m3 particulate matter (PM), an equivalent atmosphere with particles filtered out of the whole exhaust, or paved road dust at 0.5 and 3.5 mg /m3 for 6 h/d for 3 d. Radiotelemetry recordings of electrocardiogram (ECG) were analyzed for changes in T-wave morphology (QT interval, T-wave amplitude, and T-wave Area). Following exposures, lung lavage and blood samples were obtained to assay for markers of pulmonary and systemic inflammation. No exposure induced significant changes in heart rate and only the high concentration of road dust induced signs of pulmonary inflammation. T-wave area exhibited significant deviation from baseline values during exposure to gasoline exhaust particulates, but not to either concentration of road dust or gasoline emissions sans particulates. Gasoline-exposed mice demonstrated elevated plasma endothelin-1, but did not cause systemic inflammation. These data support the hypothesis that freshly-generated engine emissions, as opposed to resuspended paved road dust, may drive cardiac effects that have been observed at road-sides in the environment. The absence of ECG effects for both very high concentrations of road dust PM and equivalent concentrations of the vapor/gas phase of gasoline engine exhaust further indicate the specific risk conferred by fresh vehicular PM.

Cardiac DPP-4 inhibition by saxagliptin ameliorates isoproterenol-induced myocardial remodeling and cardiac diastolic dysfunction in rats.

PubMed

Ikeda, Junichi; Kimoto, Naoya; Kitayama, Tetsuya; Kunori, Shunji

2016-09-01

Saxagliptin, a potent and selective DPP-4 inhibitor, is characterized by its slow dissociation from DPP-4 and its long half-life and is expected to have a potent tissue membrane-bound DPP-4-inhibitory effect in various tissues. In the present study, we examined the effects of saxagliptin on in situ cardiac DPP-4 activity. We also examined the effects of saxagliptin on isoproterenol-induced the changes in the early stage such as, myocardial remodeling and cardiac diastolic dysfunction. Male SD rats treated with isoproterenol (1 mg/kg/day via osmotic pump) received vehicle or saxagliptin (17.5 mg/kg via drinking water) for 2 weeks. In situ cardiac DPP-4 activity was measured by a colorimetric assay. Cardiac gene expressions were examined and an echocardiographic analysis was performed. Saxagliptin treatment significantly inhibited in situ cardiac DPP-4 activity and suppressed isoproterenol-induced myocardial remodeling and the expression of related genes without altering the blood glucose levels. Saxagliptin also significantly ameliorated cardiac diastolic dysfunction in isoproterenol-treated rats. In conclusion, the inhibition of DPP-4 activity in cardiac tissue by saxagliptin was associated with suppression of myocardial remodeling and cardiac diastolic dysfunction independently of its glucose-lowering action in isoproterenol-treated rats. Cardiac DPP-4 activity may contribute to myocardial remodeling in the development of heart failure. Copyright © 2016 Kyowa Hakko Kirin Co.,Ltd. Production and hosting by Elsevier B.V. All rights reserved.

[Exercise guidelines for health-oriented recreational sports].

PubMed

Faude, Oliver; Zahner, Lukas; Donath, Lars

2015-05-01

Physical inactivity is one the biggest Public Health problems of the 21th century. Regular physical activity and sports can contribute to a reduction of overall mortality and morbidity and, thus, can have a considerable health impact for individuals as well as for the society as a whole. The beneficial health effects of exercise are convincingly evaluated yet and there is further evidence that physical activity can result in improvements in specific cardiorespiratory and metabolic diseases similar to pharmacological treatments. It is the aim of this review article to outline evidence-based guidelines for exercise to improve physical fitness and health in primary prevention in healthy adults. Based on the current scientific evidence a dose-response-relationship between physical activity and health markers as well as physical fitness is likely. Health-oriented exercise training should allow for an exercise-induced energy expenditure of at least 1000 kcal per week. This should be approached by an appropriate combination of exercises targeting on an improvement in cardiorespiratory and metabolic functioning as well as muscular fitness. It is recommended to supplement such a training regimen by appropriate amounts of functional and flexibility exercises. Usually, sports targeting on these particular fitness areas are recommended, for instance, typical endurance sports like cycling, jogging, (Nordic) walking or swimming for the cardiorespiratory and metabolic domains and strength training for muscular fitness. In recent years, scientific studies have evaluated potentially more attractive sports like football, dancing and Tai Chi and reported promising results. Such sports may contribute to an increased long-term compliance to health-oriented exercise programmes. Although regular physical activity is associated with considerable health benefits, risks and side effects should be taken into account. The most frequent side effects are injuries, and the most severe are fatal cardiac events. Preventive measures should be applied to reduce the risk of these side effects. Health-oriented exercise guidelines should incorporate individual preferences and training responses to support a permanent adaptation towards a sportive life style.

[Reintervention with percutaneous balloon angioplasty in patients with congenital heart disease with left-sided obstructions].

PubMed

Márquez-González, Horacio; López-Gallegos, Diana; Pérez-Velázquez, Nataly Alejandra; Yáñez-Gutiérrez, Lucelli

2017-01-01

Left-sided cardiac obstructions represent 15% of congenital heart disease (CHD). The treatment in adults is surgical; however, balloon dilation by interventional catheterization can alleviate the symptoms in pediatric patients to allow them to reach the target height. The aim was to determine the survival and the factors associated with reintervention in patients with CHD with left-sided obstruction treated with balloon angioplasty. A cohort study was conducted in patients aged 4 to 17 years with left-sided heart obstruction (valvular stenosis [VS], supravalvular aortic stenosis [SAS], coarctation of the aorta [CA]) successfully treated with balloon angioplasty. The follow-up was of 10 years and the outcome variable was the restenosis with reintervention criteria. Pediatric stage at the time of the procedure, nutritional status, residual gradient, and presence of genetic syndromes were considered prognostic variables. For statistical analysis, measures of central tendency and dispersion were used. Chi squared was employed in qualitative variables and Kruskal-Wallis in quantitative variables. We had a total of 110 patients: 40% had CA, 35% VS, and 25% SAS. 39% required reintervention: 80% in SAS, 35% in CA, and 14% in VS. The intervention balloon is a stopgap measure that allows patients with left-sided obstructions to reach the target height.

Doxorubicin Regulates Autophagy Signals via Accumulation of Cytosolic Ca2+ in Human Cardiac Progenitor Cells.

PubMed

Park, Ji Hye; Choi, Sung Hyun; Kim, Hyungtae; Ji, Seung Taek; Jang, Woong Bi; Kim, Jae Ho; Baek, Sang Hong; Kwon, Sang Mo

2016-10-09

Doxorubicin (DOXO) is widely used to treat solid tumors. However, its clinical use is limited by side effects including serious cardiotoxicity due to cardiomyocyte damage. Resident cardiac progenitor cells (hCPCs) act as key regulators of homeostasis in myocardial cells. However, little is known about the function of hCPCs in DOXO-induced cardiotoxicity. In this study, we found that DOXO-mediated hCPC toxicity is closely related to calcium-related autophagy signaling and was significantly attenuated by blocking mTOR signaling in human hCPCs. DOXO induced hCPC apoptosis with reduction of SMP30 (regucalcin) and autophagosome marker LC3, as well as remarkable induction of the autophagy-related markers, Beclin-1, APG7, and P62/SQSTM1 and induction of calcium-related molecules, CaM (Calmodulin) and CaMKII (Calmodulin kinase II). The results of an LC3 puncta assay further indicated that DOXO reduced autophagosome formation via accumulation of cytosolic Ca 2+ . Additionally, DOXO significantly induced mTOR expression in hCPCs, and inhibition of mTOR signaling by rapamycin, a specific inhibitor, rescued DOXO-mediated autophagosome depletion in hCPCs with significant reduction of DOXO-mediated cytosolic Ca 2+ accumulation in hCPCs, and restored SMP30 and mTOR expression. Thus, DOXO-mediated hCPC toxicity is linked to Ca 2+ -related autophagy signaling, and inhibition of mTOR signaling may provide a cardio-protective effect against DOXO-mediated hCPC toxicity.

Doxorubicin Regulates Autophagy Signals via Accumulation of Cytosolic Ca2+ in Human Cardiac Progenitor Cells

PubMed Central

Park, Ji Hye; Choi, Sung Hyun; Kim, Hyungtae; Ji, Seung Taek; Jang, Woong Bi; Kim, Jae Ho; Baek, Sang Hong; Kwon, Sang Mo

2016-01-01

Doxorubicin (DOXO) is widely used to treat solid tumors. However, its clinical use is limited by side effects including serious cardiotoxicity due to cardiomyocyte damage. Resident cardiac progenitor cells (hCPCs) act as key regulators of homeostasis in myocardial cells. However, little is known about the function of hCPCs in DOXO-induced cardiotoxicity. In this study, we found that DOXO-mediated hCPC toxicity is closely related to calcium-related autophagy signaling and was significantly attenuated by blocking mTOR signaling in human hCPCs. DOXO induced hCPC apoptosis with reduction of SMP30 (regucalcin) and autophagosome marker LC3, as well as remarkable induction of the autophagy-related markers, Beclin-1, APG7, and P62/SQSTM1 and induction of calcium-related molecules, CaM (Calmodulin) and CaMKII (Calmodulin kinase II). The results of an LC3 puncta assay further indicated that DOXO reduced autophagosome formation via accumulation of cytosolic Ca2+. Additionally, DOXO significantly induced mTOR expression in hCPCs, and inhibition of mTOR signaling by rapamycin, a specific inhibitor, rescued DOXO-mediated autophagosome depletion in hCPCs with significant reduction of DOXO-mediated cytosolic Ca2+ accumulation in hCPCs, and restored SMP30 and mTOR expression. Thus, DOXO-mediated hCPC toxicity is linked to Ca2+-related autophagy signaling, and inhibition of mTOR signaling may provide a cardio-protective effect against DOXO-mediated hCPC toxicity. PMID:27735842

An automatic alignment tool to improve repeatability of left ventricular function and dyssynchrony parameters in serial gated myocardial perfusion SPECT studies

PubMed Central

Zhou, Yanli; Faber, Tracy L.; Patel, Zenic; Folks, Russell D.; Cheung, Alice A.; Garcia, Ernest V.; Soman, Prem; Li, Dianfu; Cao, Kejiang; Chen, Ji

2013-01-01

Objective Left ventricular (LV) function and dyssynchrony parameters measured from serial gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) using blinded processing had a poorer repeatability than when manual side-by-side processing was used. The objective of this study was to validate whether an automatic alignment tool can reduce the variability of LV function and dyssynchrony parameters in serial gated SPECT MPI. Methods Thirty patients who had undergone serial gated SPECT MPI were prospectively enrolled in this study. Thirty minutes after the first acquisition, each patient was repositioned and a gated SPECT MPI image was reacquired. The two data sets were first processed blinded from each other by the same technologist in different weeks. These processed data were then realigned by the automatic tool, and manual side-by-side processing was carried out. All processing methods used standard iterative reconstruction and Butterworth filtering. The Emory Cardiac Toolbox was used to measure the LV function and dyssynchrony parameters. Results The automatic tool failed in one patient, who had a large, severe scar in the inferobasal wall. In the remaining 29 patients, the repeatability of the LV function and dyssynchrony parameters after automatic alignment was significantly improved from blinded processing and was comparable to manual side-by-side processing. Conclusion The automatic alignment tool can be an alternative method to manual side-by-side processing to improve the repeatability of LV function and dyssynchrony measurements by serial gated SPECT MPI. PMID:23211996

Metabonomics Indicates Inhibition of Fatty Acid Synthesis, β-Oxidation, and Tricarboxylic Acid Cycle in Triclocarban-Induced Cardiac Metabolic Alterations in Male Mice.

PubMed

Xie, Wenping; Zhang, Wenpeng; Ren, Juan; Li, Wentao; Zhou, Lili; Cui, Yuan; Chen, Huiming; Yu, Wenlian; Zhuang, Xiaomei; Zhang, Zhenqing; Shen, Guolin; Li, Haishan

2018-02-14

Triclocarban (TCC) has been identified as a new environmental pollutant that is potentially hazardous to human health; however, the effects of short-term TCC exposure on cardiac function are not known. The aim of this study was to use metabonomics and molecular biology techniques to systematically elucidate the molecular mechanisms of TCC-induced effects on cardiac function in mice. Our results show that TCC inhibited the uptake, synthesis, and oxidation of fatty acids, suppressed the tricarboxylic acid (TCA) cycle, and increased aerobic glycolysis levels in heart tissue after short-term TCC exposure. TCC also inhibited the nuclear peroxisome proliferator-activated receptor α (PPARα), confirming its inhibitory effects on fatty acid uptake and oxidation. Histopathology and other analyses further confirm that TCC altered mouse cardiac physiology and pathology, ultimately affecting normal cardiac metabolic function. We elucidate the molecular mechanisms of TCC-induced harmful effects on mouse cardiac metabolism and function from a new perspective, using metabonomics and bioinformatics analysis data.

Cardiac Effects of Lightning Strikes

PubMed Central

Khan, Sarosh; Ahmad, Mahmood; Fayed, Hossam; Bogle, Richard

2017-01-01

Lightning strikes are a common and leading cause of morbidity and mortality. Multiple organ systems can be involved, though the effects of the electrical current on the cardiovascular system are one of the main modes leading to cardiorespiratory arrest in these patients. Cardiac effects of lightning strikes can be transient or persistent, and include benign or life-threatening arrhythmias, inappropriate therapies from cardiac implantable electronic devices, cardiac ischaemia, myocardial contusion, pericardial disease, aortic injury, as well as cardiomyopathy with associated ventricular failure. Prolonged resuscitation can lead to favourable outcomes especially in young and previously healthy victims. PMID:29018518

Effects of therapeutic touch on anxiety, vital signs, and cardiac dysrhythmia in a sample of Iranian women undergoing cardiac catheterization: a quasi-experimental study.

PubMed

Zolfaghari, Mitra; Eybpoosh, Sana; Hazrati, Maryam

2012-12-01

To investigate the effects of Therapeutic Touch (TT) on anxiety, vital signs, and cardiac dysrhythmia in women undergoing cardiac catheterization. It was a quasi-experimental study. The participants had no history of hallucination, anxiety, or other psychological problems. Participants had to be conscious and have attained at least sixth-grade literacy level. Participants were randomly assigned into an intervention group (n = 23; received 10-15 minutes TT), a placebo group (n = 23; received 10-15 minutes simulated touch), and a control group (n = 23; did not receive any therapy). Data were collected using Spielberger's anxiety test, cardiac dysrhythmia checklist, and vital signs recording sheet. Statistical analyses were considered to be significant at α = .05 levels. Sixty-nine women ranging in age from 35 to 65 years participated. TT significantly decreased state anxiety p < 0.0001 but not trait anxiety (p = .88), decreased the incidence of all cardiac dysrhythmias p < 0.0001 except premature ventricular contraction (p = .01), and regulated vital signs p < 0.0001 in the intervention group versus placebo and control group. TT is an effective approach for managing state anxiety, regulating vital signs, and decreasing the incidence of cardiac dysrhythmia during stressful situations, such as cardiac catheterization, in Iranian cardiac patients.

A realist study of the mechanisms of cardiac rehabilitation.

PubMed

Clark, Alexander M; Whelan, Heather K; Barbour, Rosaline; MacIntyre, Paul D

2005-11-01

The aim of this paper is to report patients' experiences of cardiac rehabilitation and perceptions of the mechanisms and contexts influencing its long-term effectiveness. Cardiac rehabilitation programmes for the secondary prevention of coronary heart disease are common. The effects of these programmes, however, can be inconsistent and little is known of the personal and contextual factors that influence service effectiveness. Forty-seven participants with a formal diagnosis of coronary heart disease who had attended a programme of cardiac rehabilitation in Scotland 3 years previously were included in focus groups to discuss their perceptions and experiences (30 males and 17 females). The data were generated in 2002 and analysed using the realist approach of Pawson and Tilley (1997). Participants' accounts indicated that the didactic content of cardiac rehabilitation was not strongly linked to longer-term health behaviour change. The main positive effects of cardiac rehabilitation were related to the effect of participation on mediating social and body-focused mechanisms that were triggered when the rehabilitation setting was perceived to be safe. Social mechanisms identified included social comparisons, camaraderie, and social capital. Body-focused mechanisms included greater knowledge of personal physical boundaries and a greater trust in the heart-diseased body. Collectively, these mechanisms had a positive effect on confidence that was perceived as being imperative to maintain health behaviour change. More support is required to promote health behaviour change after the completion of cardiac rehabilitation. Use of community-based exercise services and conventional or web-based support groups for coronary heart disease patients should be encouraged, as these appear to extend the positive health effects of the mechanisms that promote behaviour change. At the completion of cardiac rehabilitation programmes, patients should be referred to safe and appropriate community-based exercise services. Further research is needed to examine the effects on health outcomes of mechanisms and contexts related to cardiac rehabilitation.

TU-F-17A-06: Motion Stability and Dosimetric Impact of Spirometer-Based DIBH-RT of Left-Sided Breast Cancer

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

McKenzie, E; Yang, W; Burnison, M

2014-06-15

Purpose: Patients undergoing radiotherapy (RT) for left-sided breast cancer have increased risk of coronary artery disease. Deep Inhalation Breath Hold assisted RT (DIBH-RT) is shown to increase the geometric separation of the target area and heart, reducing cardiac radiation dose. The purposes of this study are to use Cine MV portal images to determine the stability of spirometer-guided DIBH-RT and examine the dosimetric cardiopulmonary impact of this technique. Methods: Twenty consecutive patients with left-sided breast cancer were recruited to the IRB-approved study. Free-breathing (FB) and DIBH-CT's were acquired at simulation. Rigid registration of the FB-CT and DIBH-CT was performed usingmore » primarily breast tissue. Treatment plans were created for each FB-CT and DIBH-CT using identical paired tangent fields with field-in-field or electronic compensation techniques. Dosimetric evaluation included mean and maximum (Dmax) doses for the left anterior descending artery (LAD), mean heart dose, and left lung V20. Cine MV portal images were acquired for medial and lateral fields during treatment. Analysis of Cine images involved chest wall segmentation using an algorithm developed in-house. Intra- and inter-fractional chest wall motion were determined through affine registration to the first frame of each Cine. Results: Dose to each cardiac structure evaluated was significantly (p<0.001) reduced with the DIBH plans. Mean heart dose decreased from 2.9(0.9–6.6) to 1.6(0.6–5.3) Gy; mean LAD dose from 16.6(3–43.6) to 7.4(1.7–32.7) Gy; and LAD Dmax from 35.4 (6.1–53) to 18.4(2.5–51.2) Gy. No statistically significant reduction was found for the left lung V20. Average AP and SI median chest wall motion (intrafractional) was 0.1 (SD=0.9) and 0.5 (SD=1.1) mm, respectively. Average AP inter-fractional chest wall motion was 2.0 (SD=1.4) mm. Conclusion: Spirometer-based DIBH treatments of the left breast are reproducible both inter- and intra-fractionally, and provide a statistically and potentially clinically useful dosimetric advantage to cardiac structures.« less

Are There Deleterious Cardiac Effects of Acute and Chronic Endurance Exercise?

PubMed Central

Eijsvogels, Thijs M. H.; Fernandez, Antonio B.; Thompson, Paul D.

2015-01-01

Multiple epidemiological studies document that habitual physical activity reduces the risk of atherosclerotic cardiovascular disease (ASCVD), and most demonstrate progressively lower rates of ASCVD with progressively more physical activity. Few studies have included individuals performing high-intensity, lifelong endurance exercise, however, and recent reports suggest that prodigious amounts of exercise may increase markers for, and even the incidence of, cardiovascular disease. This review examines the evidence that extremes of endurance exercise may increase cardiovascular disease risk by reviewing the causes and incidence of exercise-related cardiac events, and the acute effects of exercise on cardiovascular function, the effect of exercise on cardiac biomarkers, including “myocardial” creatine kinase, cardiac troponins, and cardiac natriuretic peptides. This review also examines the effect of exercise on coronary atherosclerosis and calcification, the frequency of atrial fibrillation in aging athletes, and the possibility that exercise may be deleterious in individuals genetically predisposed to such cardiac abnormalities as long QT syndrome, right ventricular cardiomyopathy, and hypertrophic cardiomyopathy. This review is to our knowledge unique because it addresses all known potentially adverse cardiovascular effects of endurance exercise. The best evidence remains that physical activity and exercise training benefit the population, but it is possible that prolonged exercise and exercise training can adversely affect cardiac function in some individuals. This hypothesis warrants further examination. PMID:26607287

Differential cardiac effects in rats exposed to atmospheric smog generated from isoprene versus toluene

EPA Science Inventory

The results of this study demonstrate that atmospheric smog generated from both isoprene and toluene cause cardiac effects in rats. In addition, it appears that smog from toluene is more toxic in terms of cardiac arrhythmogenicity. Smog, which is a comple...

Anthracycline-induced cardiotoxicity in patients with paediatric bone sarcoma and soft tissue sarcoma.

PubMed

Bini, Ilaria; Asaftei, Sebastian D; Riggi, Chiara; Tirtei, Elisa; Manicone, Rosaria; Biasin, Eleonora; Basso, Maria Eleonora; Agnoletti, Gabriella; Fagioli, Franca

2017-11-01

Anthracycline cardiotoxicity is an important side-effect in long-term childhood cancer survivors. We evaluated the incidence of and factors associated with anthracycline cardiotoxicity in a population of patients diagnosed with bone or soft tissue sarcoma. Materials and methods We retrospectively enrolled patients diagnosed with bone or soft tissue sarcoma, from 1995 to 2011, treated with anthracycline chemotherapy at our Centre and with a follow-up echocardiography carried out ⩾3 years from cardiotoxic therapy completion. Cardiac toxicity was graded using Common Terminology Criteria for Adverse Events version 4.0. A total of 82 patients were eligible. The median age at treatment was 11.9 years (1.44-18). We evaluated the median cumulative anthracycline dose, age at treatment, sex, thoracic radiotherapy, hematopoietic stem cell transplantation, and high-dose cyclophosphamide treatment as possible risk factors for cardiotoxicity. The median cumulative anthracycline dose was 390.75 mg/m2 (80-580). Of the 82 patients, 12 (14.6%) developed cardiotoxicity with grade ⩾2 ejection fraction decline: four patients were asymptomatic and did not receive any treatment; six patients were treated with pharmacological heart failure therapy; one patient with severe cardiomyopathy underwent heart transplantation and did not need any further treatment; and one patient died while waiting for heart transplantation. The median time at cardiac toxicity, from the end of anthracycline frontline chemotherapy, was 4.2 years (0.05-9.6). Cumulative anthracycline dose ⩾300 mg/m2 (p 0.04) was the only risk factor for cardiotoxicity on statistical analyses. In our population, the cumulative incidence of cardiotoxicity is comparable to rates in the literature. This underlines the need for primary prevention and lifelong cardiac toxicity surveillance programmes in long-term childhood cancer survivors.

Outcomes of nonemergent percutaneous coronary intervention with and without on-site surgical backup: a meta-analysis.

PubMed

Singh, Param Puneet; Singh, Mukesh; Bedi, Updesh Singh; Adigopula, Sasikanth; Singh, Sarabjeet; Kodumuri, Vamsi; Molnar, Janos; Ahmed, Aziz; Arora, Rohit; Khosla, Sandeep

2011-01-01

Despite major advances in percutaneous coronary intervention (PCI) techniques, the current guidelines recommend against elective PCI at hospitals without on-site cardiac surgery backup. Nonetheless, an increasing number of hospitals without on-site cardiac surgery in the United States have developed programs for elective PCI. Studies evaluating outcome in this setting have yielded mixed results, leaving the question unanswered. Hence, a meta-analysis comparing outcomes of nonemergent PCI in hospitals with and without on-site surgical backup was performed. A systematic review of literature identified four studies involving 6817 patients. Three clinical end points were extracted from each study and included in-hospital death, myocardial infarction, and the need for emergency coronary artery bypass grafting. The studies were homogenous for each outcome studied. Therefore, the combined relative risks (RRs) across all the studies and the 95% confidence intervals (CIs) were computed using the Mantel-Haenszel fixed-effect model. A two-sided alpha error less than 0.05 was considered to be statistically significant. Compared with facilities with on-site surgical backup, the risk of in-hospital death (RR, 2.7; CI, 0.6-12.9; P = 0.18), nonfatal myocardial infarction (RR, 1.3; CI, 0.7- 2.2; P = 0.29), and need of emergent coronary artery bypass grafting (RR, 0.46; CI, 0.06- 3.1; P = 0.43) was similar in those lacking on-site surgical backup. The present meta-analysis suggests that there is no difference in the outcome with regard to risk of nonfatal myocardial infarction, need for emergency coronary artery bypass grafting, and the risk of death in patients undergoing elective PCI in hospitals with and without on-site cardiac surgery backup.

A Cardiopulmonary Bypass Based Blood Management Strategy in Adult Cardiac Surgery.

PubMed

Budak, Ali Baran; McCusker, Kevin; Gunaydin, Serdar

2017-10-24

Despite the recent introduction of a number of technical and pharmacologic blood conservation measures, bleeding and allogeneic transfusion remain persistent problems in open-heart surgical procedures. Efforts should be made to decrease or completely avoid transfusions to avoid these negative reactions. Our coronary artery bypass grafting database was reviewed retrospectively and a total of 243 patients who underwent cardiac surgery with cardiopulmonary bypass (CPB) were studied in a 12-month period (January-December 2016) after the implementation of the new program, and compared with 275 patients of the previous 12-month period.All the staff involved in the care of the patients were educated about the risks and benefits of blood transfusions and the new transfusion guidelines in a 45-min training. We revised our guidelines for transfusions based on the STS. A transfusion log was created. Reduction in IV fluid volume was targeted. CPB circuitry was redesigned to achieve significantly less prime volume. Results: The proportion of patients transfused with red blood cells was 56% (n =154) in the control group and reduced by 26.8% in the study group (29.2%; 71 patients; P < .01). Blood transfusion rate (1.7 ± 1/3.05 ± 1 units), postoperative hemorrhage (545 ± 50/ 775 ± 55 mL), respiratory support duration (12.4 ± 7/16.8 ± 8 h) and ICU stay (2.2±1.1/ 3.5±1.2 days) were significantly better in the blood conservation group.  Conclusion: These findings, in addition to risks and side effects of blood transfusion and the rising cost of safer blood products, justify blood conservation in adult cardiac operations.

Approach to cardio-oncologic patients with special focus on patients with cardiac implantable electronic devices planned for radiotherapy: results of the European Heart Rhythm Association survey.

PubMed

Lenarczyk, Radoslaw; Potpara, Tatjana S; Haugaa, Kristina H; Deharo, Jean-Claude; Hernandez-Madrid, Antonio; Del Carmen Exposito Pineda, Maria; Kiliszek, Marek; Dagres, Nikolaos

2017-09-01

The aim of this European Heart Rhythm Association (EHRA) survey was to evaluate clinical practice regarding cardio-oncologic patients, with special focus on patients with cardiac implantable electronic devices (CIEDs) planned for anticancer radiotherapy (RT), among members of the EHRA electrophysiology research network. Of the 36 responding centres, 89% managed patients who were diagnosed or treated oncologically, and this diagnosis affected 1-5% of cardiovascular patients in majority of centres (57%). The main side effects of anticancer therapy in patients treated by cardiologists were thromboembolic complications and left ventricular dysfunction (both reported as 'frequent' by 43% of the centres). The main agents associated with complications were anthracyclines, RT, and monoclonal antibodies. Echocardiography was the most common method of screening for cardiovascular complications (93%), and 10% of the centres did not routinely screen for treatment-induced cardiotoxicity. Opinions on the safe radiation dose, methods of device shielding, and risk calculation prior to RT in CIED patients differed among centres. Precaution measures in high-risk CIED patients were very heterogeneous among centres. Our survey has shown that the awareness of cardiac consequences of anticancer therapy is high, despite relatively low proportion of patients treated oncologically among all cardiovascular patients. There is a consensus of which screening methods should be used for cardiotoxicity of anticancer treatment, but the apprehension of screening necessity is low. Methods of risk assessment and safety measures in CIED patients undergoing RT are very heterogeneous among the European centres, underscoring the need for standardization of the approach to cardio-oncologic patients. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For Permissions, please email: journals.permissions@oup.com.

Nutraceuticals and Dietary Supplements to Improve Quality of Life and Outcomes in Heart Failure Patients.

PubMed

Cicero, Arrigo F G; Colletti, Alessandro

2017-01-01

Heart failure (HF) is a complex clinical syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the ventricle to fill or eject blood. It represents a major public health issue, with a prevalence of over 23 million worldwide. The lifetime risk of developing HF is one in five and the most important risk factors identified are ischemic heart disease, hypertension, smoking, obesity and diabetes. Preventive approaches are based on improvements of lifestyle, associated with pharmacological therapy. Several nutraceuticals have shown interesting clinical results in prevention of HF as well as in the treatment of the early stages of the disease, alone or in association with pharmacological therapy. The aim of this review is to resume the available clinical evidence on phytochemicals effect on HF prevention and/or treatment. A systematic search strategy was developed to identify trials in PubMed (January 1980 to April 2016). The terms 'nutraceuticals', 'dietary supplements', 'herbal drug' and 'heart failure' were incorporated into an electronic search strategy. Clinical trials reported that the intake of some nutraceuticals (hawthorn, coenzyme Q10, L-carnitine, Dribose, Carnosine, Vitamin D, Some probiotics, Omega-3 PUFAs, Beet nitrates) is associated with improvements in functional parameters such as ejection fraction, stroke volume and cardiac output in HF patients, with minimal side effects. These findings were sometimes reinforced by subsequent meta-analyses, which further concluded that benefits tended to be greater in earlier stage HF. The main mechanisms involved are antioxidant, antinflammatory, anti-ischemic and antiaggregant effects. Evidence suggests that the supplementation with nutraceuticals may be a useful option for effective management of HF, with the advantage of excellent clinical tolerance. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The CAROLE (CArdiac Related Oncologic Late Effects) Study

ClinicalTrials.gov

2018-03-29

Coronary Artery Disease; Cardiac Disease; Cardiac Toxicity; Radiation; Radiation Therapy; Atherosclerotic Heart Disease; Cardiotoxicity; Breast Cancer; Lung Cancer; Lymphoma; Cancer; Carcinoma, Intraductal, Noninfiltrating

In Vitro Effects of Pirfenidone on Cardiac Fibroblasts: Proliferation, Myofibroblast Differentiation, Migration and Cytokine Secretion

PubMed Central

Shi, Qiang; Liu, Xiaoyan; Bai, Yuanyuan; Cui, Chuanjue; Li, Jun; Li, Yishi; Hu, Shengshou; Wei, Yingjie

2011-01-01

Cardiac fibroblasts (CFs) are the primary cell type responsible for cardiac fibrosis during pathological myocardial remodeling. Several studies have illustrated that pirfenidone (5-methyl-1-phenyl-2-[1H]-pyridone) attenuates cardiac fibrosis in different animal models. However, the effects of pirfenidone on cardiac fibroblast behavior have not been examined. In this study, we investigated whether pirfenidone directly modulates cardiac fibroblast behavior that is important in myocardial remodeling such as proliferation, myofibroblast differentiation, migration and cytokine secretion. Fibroblasts were isolated from neonatal rat hearts and bioassays were performed to determine the effects of pirfenidone on fibroblast function. We demonstrated that treatment of CFs with pirfenidone resulted in decreased proliferation, and attenuated fibroblast α-smooth muscle actin expression and collagen contractility. Boyden chamber assay illustrated that pirfenidone inhibited fibroblast migration ability, probably by decreasing the ratio of matrix metalloproteinase-9 to tissue inhibitor of metalloproteinase-1. Furthermore, pirfenidone attenuated the synthesis and secretion of transforming growth factor-β1 but elevated that of interleukin-10. These direct and pleiotropic effects of pirfenidone on cardiac fibroblasts point to its potential use in the treatment of adverse myocardial remodeling. PMID:22132230

Balloon pulmonary angioplasty relieves haemodynamic stress towards untreated-side pulmonary vasculature and improves its resistance in patients with chronic thromboembolic pulmonary hypertension.

PubMed

Hosokawa, Kazuya; Abe, Kohtaro; Horimoto, Koshin; Yamasaki, Yuzo; Nagao, Michinobu; Tsutsui, Hiroyuki

2018-04-20

Chronic thromboembolic pulmonary hypertension (CTEPH) is characterised by organised thrombotic obliteration of major vessels and small-vessel arteriopathy in the non-thrombosed vessels. The aim of this study was to investigate the impact of balloon pulmonary angioplasty (BPA) on the non-BPA-side pulmonary vasculature in patients with CTEPH. This study explored the outcomes of 20 unilateral BPA sessions in 13 CTEPH patients. We measured the pulmonary vascular resistance (PVR), pulmonary artery (PA) flow in the BPA-side and non-BPA-side lungs, respectively, using phase contrast MRI and cardiac catheterisation. The interval from BPA to the follow-up evaluation was 92.8±52.0 days. A single session of BPA decreased mean PA pressure from 37.4±6.2 to 30.9±6.5 mmHg (p<0.001). In the BPA side, BPA increased the PA flow from 1.58±0.65 to 1.95±0.62 L/min (p=0.001) and decreased the PVR from 27.3±27.4 to 14.4±9.0 Wood units (p=0.004). In contrast, it decreased both the non-BPA-side PA flow from 2.25±0.64 to 1.90±0.23 L/min (p=0.008) and the non-BPA-side PVR from 14.8±6.6 to 12.8±3.9 Wood units (p=0.01). BPA could relieve haemodynamic stress towards the non-BPA-side vasculature and decrease its PVR in patients with CTEPH, suggesting that it can suppress or regress the progression of the small-vessel arteriopathy in non-BPA-side vasculature, presumably due to haemodynamic unloading.

Preoperative education interventions to reduce anxiety and improve recovery among cardiac surgery patients: a review of randomised controlled trials.

PubMed

Guo, Ping

2015-01-01

To update evidence of the effectiveness of preoperative education among cardiac surgery patients. Patients awaiting cardiac surgery may experience high levels of anxiety and depression, which can adversely affect their existing disease and surgery and result in prolonged recovery. There is evidence that preoperative education interventions can lead to improved patient experiences and positive postoperative outcomes among a mix of general surgical patients. However, a previous review suggested limited evidence to support the positive impact of preoperative education on patients' recovery from cardiac surgery. Comprehensive review of the literature. The Cochrane Central Register of Controlled Trials from the Cochrane Library, MEDLINE, CINAHL, PsycINFO, EMBASE and Web of Science were searched for English-language articles published between 2000-2011. Original articles were included reporting randomised controlled trials of cardiac preoperative education interventions. Six trials were identified and have produced conflicting findings. Some trials have demonstrated the effects of preoperative education on improving physical and psychosocial recovery of cardiac patients, while others found no evidence that patients' anxiety is reduced or of any effect on pain or hospital stay. Evidence of the effectiveness of preoperative education interventions among cardiac surgery patients remains inconclusive. Further research is needed to evaluate cardiac preoperative education interventions for sustained effect and in non-Western countries. A nurse-coordinated multidisciplinary preoperative education approach may offer a way forward to provide a more effective and efficient service. Staff training in developing and delivering such interventions is a priority. © 2014 John Wiley & Sons Ltd.

Traumatic Tricuspid Insufficiency Requiring Valve Repair in an Acute Setting.

PubMed

Enomoto, Yoshinori; Sudo, Yoshio; Sueta, Tomonori

2015-01-01

Tricuspid insufficiency due to penetrating cardiac trauma is rare. Patients with tricuspid insufficiency due to trauma can tolerate this abnormality for months or even years. We report a case of a 66-year-old female with penetrating cardiac trauma on the right side of her heart that required tricuspid valve repair in an acute setting. She sustained cut and stab wounds on her bilateral forearms and in the neck and epigastric region. She had cardiac tamponade and developed pulseless electrical activity, which required emergency surgery. The right ventricle and superior vena cava were dissected approximately 5 cm and 2 cm, respectively. After these wounds had been repaired, the patient's inability to wean from cardiopulmonary bypass suggested rightsided heart failure; transesophageal echocardiography revealed tricuspid insufficiency. Right atriotomy was performed, and a detailed examination revealed that the tricuspid valve septal leaflet was split in two. There was also an atrial septal injury that created a connection with the left atrium; these injuries were not detected from the right ventricular wound. After repair, weaning from cardiopulmonary bypass with mild tricuspid insufficiency was achieved, and she recovered uneventfully. This case emphasized the importance of thoroughly investigating intracardiac injury and transesophageal echocardiography.

Effects of nitric oxide synthesis inhibitor or fluoxetine treatment on depression-like state and cardiovascular changes induced by chronic variable stress in rats.

PubMed

Almeida, Jeferson; Duarte, Josiane O; Oliveira, Leandro A; Crestani, Carlos C

2015-01-01

Comorbidity between mood disorders and cardiovascular disease has been described extensively. However, available antidepressants can have cardiovascular side effects. Treatment with selective inhibitors of neuronal nitric oxide synthase (nNOS) induces antidepressant effects, but whether the antidepressant-like effects of these drugs are followed by cardiovascular changes has not been previously investigated. Here, we tested in male rats exposed to chronic variable stress (CVS) the hypothesis that nNOS blockers are advantageous compared with conventional antidepressants in terms of cardiovascular side effects. We compared the effects of chronic treatment with the preferential nNOS inhibitor 7-nitroindazole (7-NI) with those evoked by the conventional antidepressant fluoxetine on alterations that are considered as markers of depression (immobility in the forced swimming test, FST, decreased body weight gain and increased plasma corticosterone concentration) and cardiovascular changes caused by CVS. Rats were exposed to a 14-day CVS protocol, while being concurrently treated daily with either 7-NI (30 mg/kg) or fluoxetine (10 mg/kg). Fluoxetine and 7-NI prevented the increase in immobility in the FST induced by CVS and reduced plasma corticosterone concentration in stressed rats. Both these treatments also prevented the CVS-evoked reduction of the depressor response to vasodilator agents and baroreflex changes. Fluoxetine and 7-NI-induced cardiovascular changes independent of stress exposure, including cardiac autonomic imbalance, increased intrinsic heart rate and vascular sympathetic modulation, a reduction of the pressor response to vasoconstrictor agents, and impairment of baroreflex activity. Altogether, these findings provide evidence that fluoxetine and 7-NI have similar effects on the depression-like state induced by CVS and on cardiovascular function.

Subaortic membrane in an adult patient with coronary artery disease.

PubMed

Okutan, Huseyin; Kutsal, Ali

2005-01-01

A case of subaortic membrane with coronary artery disease in a 48-year-old man is described. He was referred to our hospital for cardiac murmur, which was discovered on routine clinical examination. He had no significant past medical history apart from dizziness while exercising. Subaortic membrane was totally excised; left internal thoracic artery was anastomosed to left anterior descending artery by end-to-side technique. The postoperative 2-year course of the patient was uneventful.

Left atrial extension of hepatoblastoma via left superior pulmonary vein.

PubMed

Atalay, Atakan; Gocen, Uğur; Yaliniz, Hafize

2014-10-01

Hepatoblastoma is the most common malignant liver tumour in early childhood. The metastatic extension of hepatoblastoma into the left atrium via the pulmonary vein is rare. Reported lesions almost always involve a right-sided approach. Here we report the case of a 3-year-old girl with a recurrent hepatoblastoma at multiple sites, including the left atrium, brain, and lung. The patient was treated surgically for the prevention of further embolic complications and cardiac failure.

Protective effect of creatine against inhibition by methylglyoxal of mitochondrial respiration of cardiac cells.

PubMed Central

Roy, Soumya Sinha; Biswas, Swati; Ray, Manju; Ray, Subhankar

2003-01-01

Previous publications from our laboratory have shown that methylglyoxal inhibits mitochondrial respiration of malignant and cardiac cells, but it has no effect on mitochondrial respiration of other normal cells [Biswas, Ray, Misra, Dutta and Ray (1997) Biochem. J. 323, 343-348; Ray, Biswas and Ray (1997) Mol. Cell. Biochem. 171, 95-103]. However, this inhibitory effect of methylglyoxal is not significant in cardiac tissue slices. Moreover, post-mitochondrial supernatant (PMS) of cardiac cells could almost completely protect the mitochondrial respiration against the inhibitory effect of methylglyoxal. A systematic search indicated that creatine present in cardiac cells is responsible for this protective effect. Glutathione has also some protective effect. However, creatine phosphate, creatinine, urea, glutathione disulphide and beta-mercaptoethanol have no protective effect. The inhibitory and protective effects of methylglyoxal and creatine respectively on cardiac mitochondrial respiration were studied with various concentrations of both methylglyoxal and creatine. Interestingly, neither creatine nor glutathione have any protective effect on the inhibition by methylglyoxal on the mitochondrial respiration of Ehrlich ascites carcinoma cells. The creatine and glutathione contents of several PMS, which were tested for the possible protective effect, were measured. The activities of two important enzymes, namely glyoxalase I and creatine kinase, which act upon glutathione plus methylglyoxal and creatine respectively, were also measured in different PMS. Whether mitochondrial creatine kinase had any role in the protective effect of creatine had also been investigated using 1-fluoro-2,4-dinitrobenzene, an inhibitor of creatine kinase. The differential effect of creatine on mitochondria of cardiac and malignant cells has been discussed with reference to the therapeutic potential of methylglyoxal. PMID:12605598

Requirement for Pathogenic IL-23 Signaling Is Restricted to Initiation of Autoimmune Myocarditis

PubMed Central

Wu, Lei; Diny, Nicola L.; Ong, SuFey; Barin, Jobert G.; Hou, Xuezhou; Rose, Noel R.; Talor, Monica V.; Čiháková, Daniela

2016-01-01

Using a mouse model of experimental autoimmune myocarditis (EAM), we showed for the first time that IL-23 stimulation of CD4+ T cells is required only briefly at the initiation of GM-CFS-dependent cardiac autoimmunity. IL-23 signal, acting as a switch, turns on pathogenicity of CD4+ T cells, and becomes dispensable once autoreactivity is established. Il23a−/− mice failed to mount an efficient Th17 response to immunization, and were protected from myocarditis. However, remarkably, transient IL-23 stimulation ex vivo fully restored pathogenicity in otherwise nonpathogenic CD4+ T cells raised from Il23a−/− donors. Thus, IL-23 may no longer be necessary to uphold inflammation in established autoimmune diseases. In addition, we demonstrated that IL-23 induced GM-CSF mediates the pathogenicity of CD4+ T cells in EAM. The neutralization of GM-CSF abrogated cardiac inflammation. However, sustained IL-23 signaling is required to maintain IL-17A production in CD4+ T cells. Despite inducing inflammation in Il23a−/− recipients comparable to WT, autoreactive CD4+ T cells downregulated IL-17A production without persistent IL-23 signaling. This divergence on the controls of GM-CSF-dependent pathogenicity on one side and IL-17A production on the other side may contribute to the discrepant efficacies of anti-IL-23 therapy in different autoimmune diseases. PMID:26660726

The use of echocardiography in Wolff-Parkinson-White syndrome.

PubMed

Cai, Qiangjun; Shuraih, Mossaab; Nagueh, Sherif F

2012-04-01

Endocardial mapping and radiofrequency catheter ablation are well established modalities for the diagnosis and treatment of patients with Wolff-Parkinson-White (WPW) syndrome associated with tachyarrhythmias. However, the electrophysiologic techniques are invasive, require radiation exposure, and lack spatial resolution of cardiac structures. A variety of echocardiographic techniques have been investigated as a non-invasive alternative for accessory pathway localization. Conventional M-mode echocardiography can detect the fine premature wall motion abnormalities associated with WPW syndrome. However, it is unable to identify the exact site of accessory pathway with sufficient accuracy. 2D, 2D-guided M-mode, and 2D phase analysis techniques are limited by image quality and endocardial border definition. Various modalities of tissue Doppler echocardiography significantly increase the accuracy of left-sided accessory pathway localization to 80-90% even in patients with poor acoustic window. However, right-sided pathways remain a diagnostic challenge. Strain echocardiography by speckle tracking has recently been evaluated and appears promising. Different cardiac abnormalities have been detected by echocardiography in WPW patients. Patients with WPW syndrome and tachyarrhythmias have impaired systolic and diastolic function which improves after radiofrequency ablation. Echocardiography is useful in identifying patient with accessory pathway-associated left ventricular dyssynchrony and dysfunction who may benefit from ablation therapy. Transesophageal and intracardiac echocardiography have been used to guide ablation procedure. Ablation-related complications detected by routine echocardiography are infrequent, rarely clinically relevant, and of limited value.

Calcitriol attenuates cardiac remodeling and dysfunction in a murine model of polycystic ovary syndrome.

PubMed

Gao, Ling; Cao, Jia-Tian; Liang, Yan; Zhao, Yi-Chao; Lin, Xian-Hua; Li, Xiao-Cui; Tan, Ya-Jing; Li, Jing-Yi; Zhou, Cheng-Liang; Xu, Hai-Yan; Sheng, Jian-Zhong; Huang, He-Feng

2016-05-01

Polycystic ovary syndrome (PCOS) is a complex reproductive and metabolic disorder affecting 10 % of reproductive-aged women, and is well associated with an increased prevalence of cardiovascular risk factors. However, there are few data concerning the direct association of PCOS with cardiac pathologies. The present study aims to investigate the changes in cardiac structure, function, and cardiomyocyte survival in a PCOS model, and explore the possible effect of calcitriol administration on these changes. PCOS was induced in C57BL/6J female mice by chronic dihydrotestosterone administration, as evidenced by irregular estrous cycles, obesity and dyslipidemia. PCOS mice progressively developed cardiac abnormalities including cardiac hypertrophy, interstitial fibrosis, myocardial apoptosis, and cardiac dysfunction. Conversely, concomitant administration of calcitriol significantly attenuated cardiac remodeling and cardiomyocyte apoptosis, and improved cardiac function. Molecular analysis revealed that the beneficial effect of calcitriol was associated with normalized autophagy function by increasing phosphorylation levels of AMP-activated protein kinase and inhibiting phosphorylation levels of mammalian target of rapamycin complex. Our findings provide the first evidence for the presence of cardiac remodeling in a PCOS model, and vitamin D supplementation may be a potential therapeutic strategy for the prevention and treatment of PCOS-related cardiac remodeling.

Partial anomalous pulmonary venous connection with suspected pulmonary hypertension in a cat.

PubMed

Nicolson, Geoff; Daley, Michael; Makara, Mariano; Beijerink, Niek

2015-12-01

Partial anomalous pulmonary venous connection has previously been reported in the dog, but never in a cat. A 14-month-old Devon Rex cat was presented for echocardiography to evaluate a heart murmur noticed during a routine examination. The pertinent finding was right-sided cardiomegaly in the absence of an atrial septal defect or tricuspid regurgitation; pulmonary hypertension was suspected. A thoracic computed tomographic angiography study identified a partial anomalous pulmonary venous connection with the lobar veins of the left caudal, right middle, right caudal and accessory lung lobes draining into the caudal vena cava. The resultant volume overload is an easily overlooked differential diagnosis for right-sided cardiac enlargement. This is the first such report of this anomaly in a cat. Copyright © 2015 Elsevier B.V. All rights reserved.

The cost-effectiveness of cardiac computed tomography for patients with stable chest pain.

PubMed

Agus, A M; McKavanagh, P; Lusk, L; Verghis, R M; Walls, G M; Ball, P A; Trinick, T R; Harbinson, M T; Donnelly, P M

2016-03-01

To assess the cost-effectiveness of cardiac CT compared with exercise stress testing (EST) in improving the health-related quality of life of patients with stable chest pain. A cost-utility analysis alongside a single-centre randomised controlled trial carried out in Northern Ireland. Patients with stable chest pain were randomised to undergo either cardiac CT assessment or EST (standard care). The main outcome measure was cost per quality adjusted life year (QALY) gained at 1 year. Of the 500 patients recruited, 250 were randomised to cardiac CT and 250 were randomised to EST. Cardiac CT was the dominant strategy as it was both less costly (incremental total costs -£50.45; 95% CI -£672.26 to £571.36) and more effective (incremental QALYs 0.02; 95% CI -0.02 to 0.05) than EST. At a willingness-to-pay threshold of £20 000 per QALY the probability of cardiac CT being cost-effective was 83%. Subgroup analyses indicated that cardiac CT appears to be most cost-effective in patients with a likelihood of coronary artery disease (CAD) of <30%, followed by 30%-60% and then >60%. Cardiac CT is cost-effective compared with EST and cost-effectiveness was observed to vary with likelihood of CAD. This finding could have major implications for how patients with chest pain in the UK are assessed, however it would need to be validated in other healthcare systems. (ISRCTN52480460); results. 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/

Effect of Different Formulations of Magnesium Chloride Used As Anesthetic Agents on the Performance of the Isolated Heart of Octopus vulgaris.

PubMed

Pugliese, Chiara; Mazza, Rosa; Andrews, Paul L R; Cerra, Maria C; Fiorito, Graziano; Gattuso, Alfonsina

2016-01-01

Magnesium chloride (MgCl 2 ) is commonly used as a general anesthetic in cephalopods, but its physiological effects including those at cardiac level are not well-characterized. We used an in vitro isolated perfused systemic heart preparation from the common octopus, Octopus vulgaris , to investigate: (a) if in vivo exposure to MgCl 2 formulations had an effect on cardiac function in vitro and, if so, could this impact recovery and (b) direct effects of MgCl 2 formulations on cardiac function. In vitro hearts removed from animals exposed in vivo to 3.5% MgCl 2 in sea water (20 min) or to a mixture of MgCl 2 + ethanol (1.12/1%; 20 min) showed cardiac function (heart rate, stroke volume, cardiac output) comparable to hearts removed from animals killed under hypothermia. However, 3.5% MgCl 2 (1:1, sea water: distilled water, 20 min) produced a significant impairment of the Frank-Starling response as did 45 min exposure to the MgCl 2 + ethanol mixture. Perfusion of the isolated heart with MgCl 2 ± ethanol formulations produced a concentration-related bradycardia (and arrest), a decreased stroke volume and cardiac output indicating a direct effect on the heart. The cardiac effects of MgCl 2 are discussed in relation to the involvement of magnesium, sodium, chloride, and calcium ions, exposure time and osmolality of the formulations and the implications for the use of various formulations of MgCl 2 as anesthetics in octopus. Overall, provided that the in vivo exposure to 3.5% MgCl 2 in sea water or to a mixture of MgCl 2 + ethanol is limited to ~20 min, residual effects on cardiac function are unlikely to impact post-anesthetic recovery.

Targeted Gene Silencing of Tumor Necrosis Factor Attenuates the Negative Inotropic Effects of Lipopolysaccharide in Isolated Contracting Cardiac Myocytes

PubMed Central

Ramabadran, R. S.; Chancey, Amanda; Vallejo, Jesus G.; Barger, Philip M.; Sivasubramanian, Natarajan; Mann, Douglas L.

2008-01-01

Bacterial endotoxin (lipopolysaccharide) depresses cardiovascular function; however, the mediators and signaling pathways that are responsible for the negative inotropic effects of lipopolysaccharide are not fully known. We used RNA interference to determine the relative role of tumor necrosis factor with respect to mediating the negative inotropic effects of lipopolysaccharide in isolated cardiac myocytes. Cardiac myocyte cultures were treated with lipopolysaccharide in the presence or absence of small interfering RNAs (siRNA) for tumor necrosis factor. We examined the effects of tumor necrosis factor siRNA on lipopolysaccharide-induced tumor necrosis factor messenger RNA (mRNA) and protein biosynthesis, as well as the negative inotropic effects of lipopolysaccharide in isolated contracting cardiac myocytes. Treatment of adult cardiac myocyte cultures with tumor necrosis factor siRNA significantly attenuated lipopolysaccharide-induced tumor necrosis factor mRNA and protein biosynthesis, whereas transfection with a double-stranded RNA that does not target mammalian mRNA had no effect. Pretreatment with tumor necrosis factor siRNA significantly attenuated, but did not abrogate, the lipopolysaccharide-induced decrease in sarcomere shortening in isolated contracting cardiac myocytes. In contrast, tumor necrosis factor siRNA had a comparatively smaller effect on improving sarcomere shortening once the negative inotropic effects of lipopolysaccharide were fully established. These results suggest that tumor necrosis factor plays an important upstream role in lipopolysaccharide-induced negative inotropic effects in isolated contracting cardiac myocytes and that other molecular mechanisms are responsible for the decrease in sarcomere shortening after sustained lipopolysaccharide signaling. PMID:18427645

LC-REHAB: randomised trial assessing the effect of a new patient education method--learning and coping strategies--in cardiac rehabilitation.

PubMed

Lynggaard, Vibeke; May, Ole; Beauchamp, Alison; Nielsen, Claus Vinther; Wittrup, Inge

2014-12-13

Due to improved treatments and ageing population, many countries now report increasing prevalence in rates of ischemic heart disease and heart failure. Cardiac rehabilitation has potential to reduce morbidity and mortality, but not all patients complete. In light of favourable effects of cardiac rehabilitation it is important to develop patient education methods which can enhance adherence to this effective program. The LC-REHAB study aims to compare the effect of a new patient education strategy in cardiac rehabilitation called 'learning and coping' to that of standard care. Further, this paper aims to describe the theoretical basis and details of this intervention. Open parallel randomised controlled trial conducted in three hospital units in Denmark among patients recently discharged with ischemic heart disease or heart failure. Patients are allocated to either the intervention group with learning and coping strategies incorporated into standard care in cardiac rehabilitation or the control group who receive the usual cardiac rehabilitation program. Learning and coping consists of two individual clarifying interviews, participation of experienced patients as educators together with health professionals and theory based, situated and inductive teaching. Usual care in cardiac rehabilitation is characterised by a structured deductive teaching style with use of identical pre-written slides in all hospital units. In both groups, cardiac rehabilitation consists of training three times a week and education once a week over eight weeks. The primary outcomes are adherence to cardiac rehabilitation, morbidity and mortality, while secondary outcomes are quality of life (SF-12, Health education impact questionnaire and Major Depression Inventory) and lifestyle and risk factors (Body Mass Index, waist circumference, blood pressure, exercise work capacity, lipid profile and DXA-scan). Data collection occurs four times; at baseline, at immediate completion of cardiac rehabilitation, and at three months and three years after the finished program. It is expected that learning and coping incorporated in cardiac rehabilitation will improve adherence in cardiac rehabilitation and may decrease morbidity and mortality. By describing learning and coping strategies the study aims to provide knowledge that can contribute to an increased transparency in patient education in cardiac rehabilitation. Identifier NCT01668394.

Cardiac mTOR rescues the detrimental effects of diet-induced obesity in the heart after ischemia-reperfusion.

PubMed

Aoyagi, Toshinori; Higa, Jason K; Aoyagi, Hiroko; Yorichika, Naaiko; Shimada, Briana K; Matsui, Takashi

2015-06-15

Diet-induced obesity deteriorates the recovery of cardiac function after ischemia-reperfusion (I/R) injury. While mechanistic target of rapamycin (mTOR) is a key mediator of energy metabolism, the effects of cardiac mTOR in ischemic injury under metabolic syndrome remains undefined. Using cardiac-specific transgenic mice overexpressing mTOR (mTOR-Tg mice), we studied the effect of mTOR on cardiac function in both ex vivo and in vivo models of I/R injury in high-fat diet (HFD)-induced obese mice. mTOR-Tg and wild-type (WT) mice were fed a HFD (60% fat by calories) for 12 wk. Glucose intolerance and insulin resistance induced by the HFD were comparable between WT HFD-fed and mTOR-Tg HFD-fed mice. Functional recovery after I/R in the ex vivo Langendorff perfusion model was significantly lower in HFD-fed mice than normal chow diet-fed mice. mTOR-Tg mice demonstrated better cardiac function recovery and had less of the necrotic markers creatine kinase and lactate dehydrogenase in both feeding conditions. Additionally, mTOR overexpression suppressed expression of proinflammatory cytokines, including IL-6 and TNF-α, in both feeding conditions after I/R injury. In vivo I/R models showed that at 1 wk after I/R, HFD-fed mice exhibited worse cardiac function and larger myocardial scarring along myofibers compared with normal chow diet-fed mice. In both feeding conditions, mTOR overexpression preserved cardiac function and prevented myocardial scarring. These findings suggest that cardiac mTOR overexpression is sufficient to prevent the detrimental effects of diet-induced obesity on the heart after I/R, by reducing cardiac dysfunction and myocardial scarring. Copyright © 2015 the American Physiological Society.

Digoxin Induces Cardiac Hypertrophy Without Negative Effects on Cardiac Function and Physical Performance in Trained Normotensive Rats.

PubMed

Neves, Claodete Hasselstrom; Tibana, Ramires Alsamir; Prestes, Jonato; Voltarelli, Fabricio Azevedo; Aguiar, Andreo Fernando; Ferreira Mota, Gustavo Augusto; de Sousa, Sergio Luiz Borges; Leopoldo, Andre Soares; Leopoldo, Ana Paula Lima; Mueller, Andre; Aguiar, Danilo Henrique; Navalta, James Wilfred; Sugizaki, Mario Mateus

2017-04-01

Cardiotonic drugs and exercise training promote cardiac inotropic effects, which may affect training-induced cardiac adaptations. This study investigated the effects of long-term administration of digoxin on heart structure and function, and physical performance of rats submitted to high-intensity interval training (HIIT). Male Wistar rats, 60 days old, were divided into control (C), digoxin (DIGO), trained (T), and trained with digoxin (TDIGO). Digoxin was administered by gavage (30 µg/kg/day) for 75 days. The HIIT program consisted of treadmill running 60 min/day (8 min at 80% of the maximum speed (MS) and 2 min at 20% of the MS), 5 days per week during 60 days. The main cardiac parameters were evaluated by echocardiograph and cardiomyocyte area was determined by histology. There were no group x time effects of digoxin, HIIT or interactions (digoxin and HIIT) on functional echocardiographic parameters (heart rate; ejection fraction) or in the maximum exercise test. There was a group x time interaction, as evidenced by observed cardiac hypertrophy in the TDIGO group evaluated by ratio of left ventricle weight to body weight (p<0.002) and cardiomyocyte area (p<0.000002). Long-term administration of digoxin promoted cardiac hypertrophy without affecting cardiac function and physical performance in rats submitted to HIIT. © Georg Thieme Verlag KG Stuttgart · New York.

Comparison of different techniques for in microgravity-a simple mathematic estimation of cardiopulmonary resuscitation quality for space environment.

PubMed

Braunecker, S; Douglas, B; Hinkelbein, J

2015-07-01

Since astronauts are selected carefully, are usually young, and are intensively observed before and during training, relevant medical problems are rare. Nevertheless, there is a certain risk for a cardiac arrest in space requiring cardiopulmonary resuscitation (CPR). Up to now, there are 5 known techniques to perform CPR in microgravity. The aim of the present study was to analyze different techniques for CPR during microgravity about quality of CPR. To identify relevant publications on CPR quality in microgravity, a systematic analysis with defined searching criteria was performed in the PubMed database (http://www.pubmed.com). For analysis, the keywords ("reanimation" or "CPR" or "resuscitation") and ("space" or "microgravity" or "weightlessness") and the specific names of the techniques ("Standard-technique" or "Straddling-manoeuvre" or "Reverse-bear-hug-technique" or "Evetts-Russomano-technique" or "Hand-stand-technique") were used. To compare quality and effectiveness of different techniques, we used the compression product (CP), a mathematical estimation for cardiac output. Using the predefined keywords for literature search, 4 different publications were identified (parabolic flight or under simulated conditions on earth) dealing with CPR efforts in microgravity and giving specific numbers. No study was performed under real-space conditions. Regarding compression depth, the handstand (HS) technique as well as the reverse bear hug (RBH) technique met parameters of the guidelines for CPR in 1G environments best (HS ratio, 0.91 ± 0.07; RBH ratio, 0.82 ± 0.13). Concerning compression rate, 4 of 5 techniques reached the required compression rate (ratio: HS, 1.08 ± 0.11; Evetts-Russomano [ER], 1.01 ± 0.06; standard side straddle, 1.00 ± 0.03; and straddling maneuver, 1.03 ± 0.12). The RBH method did not meet the required criteria (0.89 ± 0.09). The HS method showed the highest cardiac output (69.3% above the required CP), followed by the ER technique (33.0% above the required CP). Concerning CPR quality, the HS seems to be most effective to treat a cardiac arrest. In some environmental conditions where this technique cannot be used, the ER technique is a good alternative because CPR quality is only slightly lower. Copyright © 2015 Elsevier Inc. All rights reserved.

[Surgical therapy of life-threatening tachycardic cardiac arrhythmias in children].

PubMed

Frank, G; Schmid, C; Baumgart, D; Lowes, D; Klein, H; Kallfelz, H C

1989-05-01

Surgical techniques for tachyarrhythmias refractory to medical treatment are used with increasing frequency. Among 211 patients undergoing antiarrhythmic surgery 10 children (2 to 14 years old) were operated by electrophysiologically directed procedures. 7 patients suffered from WPW syndrome, 2 from focal atrial tachycardias and 1 from recurrent ventricular tachycardia following the repair of Fallot's tetralogy. In all cases preoperative electrophysiologic study and intraoperative mapping preceded operative ablation. Surgical treatment consisted of interruption of the bundle of Kent (3 right-sided, 2 left-sided, 3 septal), ablation of the atrial focus (1 right-sided, 1 left-sided) and right ventricular outflow tract incision. In 7 operations cryo-techniques were added. 2 children with WPW syndrome had two interventions because of tachycardia recurrences due to multiple accessory pathways. In 1 case a VVI-pacemaker was implanted postoperatively due to complete atrioventricular block. Another 2 children with prolonged postoperative bradycardia received a pacemaker prophylactically. Only the child with previous tetralogy of Fallot is still under antiarrhythmic medication while all other children are free of tachycardiac episodes. Our data confirm the efficacy of surgical treatment of tachyarrhythmias in children thereby abolishing the need for life-long antiarrhythmic medication.

Model-based estimation with boundary side information or boundary regularization [cardiac emission CT].

PubMed

Chiao, P C; Rogers, W L; Fessler, J A; Clinthorne, N H; Hero, A O

1994-01-01

The authors have previously developed a model-based strategy for joint estimation of myocardial perfusion and boundaries using ECT (emission computed tomography). They have also reported difficulties with boundary estimation in low contrast and low count rate situations. Here they propose using boundary side information (obtainable from high resolution MRI and CT images) or boundary regularization to improve both perfusion and boundary estimation in these situations. To fuse boundary side information into the emission measurements, the authors formulate a joint log-likelihood function to include auxiliary boundary measurements as well as ECT projection measurements. In addition, they introduce registration parameters to align auxiliary boundary measurements with ECT measurements and jointly estimate these parameters with other parameters of interest from the composite measurements. In simulated PET O-15 water myocardial perfusion studies using a simplified model, the authors show that the joint estimation improves perfusion estimation performance and gives boundary alignment accuracy of <0.5 mm even at 0.2 million counts. They implement boundary regularization through formulating a penalized log-likelihood function. They also demonstrate in simulations that simultaneous regularization of the epicardial boundary and myocardial thickness gives comparable perfusion estimation accuracy with the use of boundary side information.

Total Cavopulmonary Connection for Functionally Single Ventricle without Cardiopulmonary Bypass Support.

PubMed

Bangash, Sohail Khan; Pathan, Iqbal Hussain; Zaki, Saad Bader

2016-10-01

A heart with two atriums but one ventricle, an anatomy with a unique physiology, is responsible for many creative surgical and interventional approaches in history. Different surgical techniques have been used to address this strange physiology of parallel circulation. All these attempts met with failure till the concept of Fontan circulation was described. Currently, controversy exists between multistage vs. single stage total cavopulmonary connections. Total cavopulmonary connection is the only definitive procedure performed to provide palliation for patients with complex congenital heart defects which cannot support a biventricular circulation. We report a case with tricuspid atresia with transposition of great arteries and pulmonary stenosis with persistant left-sided superior vena cava and functionally single ventricle. Patient successfully underwent single stage extra-cardiac total cavopulmonary connection. In this case, bilateral Glenn with extra-cardiac inferior vena cava to main pulmonary artery shunt was performed off-pump.

Right ventricular involvement in cardiac sarcoidosis demonstrated with cardiac magnetic resonance.

PubMed

Smedema, Jan-Peter; van Geuns, Robert-Jan; Ainslie, Gillian; Ector, Joris; Heidbuchel, Hein; Crijns, Harry J G M

2017-11-01

Cardiac involvement in sarcoidosis is reported in up to 30% of patients. Left ventricular involvement demonstrated by contrast-enhanced cardiac magnetic resonance has been well validated. We sought to determine the prevalence and distribution of right ventricular late gadolinium enhancement in patients diagnosed with pulmonary sarcoidosis. We prospectively evaluated 87 patients diagnosed with pulmonary sarcoidosis with contrast-enhanced cardiac magnetic resonance for right ventricular involvement. Pulmonary artery pressures were non-invasively evaluated with Doppler echocardiography. Patient characteristics were compared between the groups with and without right ventricular involvement, and right ventricular enhancement was correlated with pulmonary hypertension, ventricular mass, volume, and systolic function. Left ventricular late gadolinium enhancement was demonstrated in 30 patients (34%). Fourteen patients (16%) had right ventricular late gadolinium enhancement, with sole right ventricular enhancement in only two patients. The pattern of right ventricular enhancement consisted of right ventricular outflow tract enhancement in 1 patient, free wall enhancement in 8 patients, ventricular insertion point enhancement in 10 patients, and enhancement of the right side of the interventricular septum in 11 patients. Pulmonary arterial hypertension correlated with the presence of right ventricular enhancement (P < 0.001). Right ventricular enhancement correlated with systolic ventricular dysfunction (P < 0.001), hypertrophy (P = 0.001), and dilation (P < 0.001). Right ventricular enhancement was present in 16% of patients diagnosed with pulmonary sarcoidosis and in 48% of patients with left ventricular enhancement. The presence of right ventricular enhancement correlated with pulmonary arterial hypertension, right ventricular systolic dysfunction, hypertrophy, and dilation. © 2017 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

The other side of cardiac Ca2+ signaling: transcriptional control

PubMed Central

Domínguez-Rodríguez, Alejandro; Ruiz-Hurtado, Gema; Benitah, Jean-Pierre; Gómez, Ana M.

2012-01-01

Ca2+ is probably the most versatile signal transduction element used by all cell types. In the heart, it is essential to activate cellular contraction in each heartbeat. Nevertheless Ca2+ is not only a key element in excitation-contraction coupling (EC coupling), but it is also a pivotal second messenger in cardiac signal transduction, being able to control processes such as excitability, metabolism, and transcriptional regulation. Regarding the latter, Ca2+ activates Ca2+-dependent transcription factors by a process called excitation-transcription coupling (ET coupling). ET coupling is an integrated process by which the common signaling pathways that regulate EC coupling activate transcription factors. Although ET coupling has been extensively studied in neurons and other cell types, less is known in cardiac muscle. Some hints have been found in studies on the development of cardiac hypertrophy, where two Ca2+-dependent enzymes are key actors: Ca2+/Calmodulin kinase II (CaMKII) and phosphatase calcineurin, both of which are activated by the complex Ca2+/Calmodulin. The question now is how ET coupling occurs in cardiomyocytes, where intracellular Ca2+ is continuously oscillating. In this focused review, we will draw attention to location of Ca2+ signaling: intranuclear ([Ca2+]n) or cytoplasmic ([Ca2+]c), and the specific ionic channels involved in the activation of cardiac ET coupling. Specifically, we will highlight the role of the 1,4,5 inositol triphosphate receptors (IP3Rs) in the elevation of [Ca2+]n levels, which are important to locally activate CaMKII, and the role of transient receptor potential channels canonical (TRPCs) in [Ca2+]c, needed to activate calcineurin (Cn). PMID:23226134

SPECT Analysis of Cardiac Perfusion Changes After Whole-Breast/Chest Wall Radiation Therapy With or Without Active Breathing Coordinator: Results of a Randomized Phase 3 Trial

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

Zellars, Richard, E-mail: zellari@jhmi.edu; Bravo, Paco E.; Tryggestad, Erik

2014-03-15

Purpose: Cardiac muscle perfusion, as determined by single-photon emission computed tomography (SPECT), decreases after breast and/or chest wall (BCW) irradiation. The active breathing coordinator (ABC) enables radiation delivery when the BCW is farther from the heart, thereby decreasing cardiac exposure. We hypothesized that ABC would prevent radiation-induced cardiac toxicity and conducted a randomized controlled trial evaluating myocardial perfusion changes after radiation for left-sided breast cancer with or without ABC. Methods and Materials: Stages I to III left breast cancer patients requiring adjuvant radiation therapy (XRT) were randomized to ABC or No-ABC. Myocardial perfusion was evaluated by SPECT scans (before andmore » 6 months after BCW radiation) using 2 methods: (1) fully automated quantitative polar mapping; and (2) semiquantitative visual assessment. The left ventricle was divided into 20 segments for the polar map and 17 segments for the visual method. Segments were grouped by anatomical rings (apical, mid, basal) or by coronary artery distribution. For the visual method, 2 nuclear medicine physicians, blinded to treatment groups, scored each segment's perfusion. Scores were analyzed with nonparametric tests and linear regression. Results: Between 2006 and 2010, 57 patients were enrolled and 43 were available for analysis. The cohorts were well matched. The apical and left anterior descending coronary artery segments had significant decreases in perfusion on SPECT scans in both ABC and No-ABC cohorts. In unadjusted and adjusted analyses, controlling for pretreatment perfusion score, age, and chemotherapy, ABC was not significantly associated with prevention of perfusion deficits. Conclusions: In this randomized controlled trial, ABC does not appear to prevent radiation-induced cardiac perfusion deficits.« less

Basic study on a lower-energy defibrillation method using computer simulation and cultured myocardial cell models.

PubMed

Yaguchi, A; Nagase, K; Ishikawa, M; Iwasaka, T; Odagaki, M; Hosaka, H

2006-01-01

Computer simulation and myocardial cell models were used to evaluate a low-energy defibrillation technique. A generated spiral wave, considered to be a mechanism of fibrillation, and fibrillation were investigated using two myocardial sheet models: a two-dimensional computer simulation model and a two-dimensional experimental model. A new defibrillation technique that has few side effects, which are induced by the current passing into the patient's body, on cardiac muscle is desired. The purpose of the present study is to conduct a basic investigation into an efficient defibrillation method. In order to evaluate the defibrillation method, the propagation of excitation in the myocardial sheet is measured during the normal state and during fibrillation, respectively. The advantages of the low-energy defibrillation technique are then discussed based on the stimulation timing.

[Neurologic manifestations associated with antiphospholipid antibodies. Or what remains of neurolupus?].

PubMed

Hachulla, E; Leys, D; Deleume, J F; Pruvo, J P; Devulder, B

1995-01-01

Antiphospholipid antibody is associated with a clinical syndrome of vascular thrombosis, thrombocytopenia, recurrent fetal loss and livedo reticularis, whether or not a clinical diagnosis of systemic lupus erythematosus (SLE) coexists. Central nervous system involvement in SLE is multifactorial, thrombotic events, antineuronal antibodies, hypertension, infection, side effects of drugs etc. Antiphospholipid antibodies may play a role in focal neurological manifestations in SLE. In the absence of SLE, different neurological symptoms are well associated with antiphospholipid antibodies including stroke, seizures, dementia, migraine, ocular ischemia, chorea, transverse myelopathy, cerebral phlebitis. Other association are more controversal like Guillain Barré syndrome, motor neuron disease, communicating hydrocephalus. In all patients with antiphospholipid antibodies with neurological involvement, cerebral MRI may be performed with an echocardiographic study because a possible association with Libman and Sacks endocarditis, valve dysfunction or cardiac thrombus source of cerebral ischemia.

Effect of siRNA silencing of inducible co-stimulatory molecule on myocardial cell hypertrophy after cardiac infarction in rats.

PubMed

Wang, W M; Liu, Z; Chen, G

2016-05-20

As the most common cardiac disease, myocardial infarction is followed by hypertrophy of cardiac myocytes and reconstruction of ventricular structure. The up-regulation of a series of factors including metalloproteinases, inflammatory factors, and growth factors after primary infarction lead to the hypertrophy, apoptosis, necrosis, and fibroblast proliferation in cardiac muscle tissues. Recent studies have reported on the potency of small interfering RNA (siRNA) in treating cardiac diseases. We thus investigated the efficacy of inducible co-stimulatory molecule (ICOS)-specific siRNA silencing in myocardial hypertrophy in a cardiac infarction rat model. This cardiac infarction model was prepared by ligating the left anterior descending coronary artery. ICOS-siRNA treatment was administered in parallel with non-sense siRNA. After 18 days, the cross-sectional area of cardiac muscle tissues and the left ventricle weight index were measured, along with ICOS mRNA and protein expression levels, and pathological staining. Compared to those in the control groups, in myocardial infarcted rats, the application of ICOS-siRNA effectively decreased the left ventricle weight index, as well as the surface area of cardiac myocytes. Both mRNA and protein levels of ICOS were also significantly decreased. HE staining was consistent with these results. In conclusion, ICOS-targeted siRNA can effectively silence gene expression of ICOS, and provided satisfactory treatment efficacy for myocardial cell hypertrophy after infarction.

An evaluation of three methods of in-hospital cardiac arrest educational debriefing: The cardiopulmonary resuscitation debriefing study.

PubMed

Couper, Keith; Kimani, Peter K; Davies, Robin P; Baker, Annalie; Davies, Michelle; Husselbee, Natalie; Melody, Teresa; Griffiths, Frances; Perkins, Gavin D

2016-08-01

The use of cardiac arrest educational debriefing has been associated with improvements in cardiopulmonary resuscitation (CPR) quality and patient outcome. The practical challenges associated with delivering some debriefing approaches may not be generalisable to the UK health setting. The aim of this study was to evaluate the deliverability and effectiveness of three cardiac arrest debriefing approaches that were tailored to UK working practice. We undertook a before/after study at three hospital sites. During the post-intervention period of the study, three cardiac arrest educational debriefing models were implemented at study hospitals (one model per hospital). To evaluate the effectiveness of the interventions, CPR quality and patient outcome data were collected from consecutive adult cardiac arrest events attended by the hospital cardiac arrest team. The primary outcome was chest compression depth. Between November 2011 and July 2014, 1198 cardiac arrest events were eligible for study inclusion (782 pre-intervention; 416 post-intervention). The quality of CPR was high at baseline. During the post-intervention period, cardiac arrest debriefing interventions were delivered to 191 clinicians on 344 occasions. Debriefing interventions were deliverable in practice, but were not associated with a clinically important improvement in CPR quality. The interventions had no effect on patient outcome. The delivery of these cardiac arrest educational debriefing strategies was feasible, but did not have a large effect on CPR quality. This may be attributable to the high-quality of CPR being delivered in study hospitals at baseline. ISRCTN39758339. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Use of beta-adrenoceptor blocking drugs in hyperthyroidism.

PubMed

Feely, J; Peden, N

1984-05-01

There is an increasing use and variety of beta-adrenoceptor blocking agents (beta-blockers) available for the treatment of hyperthyroidism. Recent comparative studies suggest that atenolol (200mg daily), metoprolol (200mg daily); acebutolol (400mg daily), oxprenolol ( 160mg daily), nadolol ( 80mg daily) and timolol (20mg daily) produce a beneficial clinical response equal to that seen with propranolol ( 160mg daily). Most beta-blockers reduce resting heart rate by approximately 25 to 30 beats/min, although a lesser reduction is seen with those possessing intrinsic sympathomimetic activity such as oxprenolol and pindolol. While earlier studies employing large doses of intravenous propranolol concluded that beta-blockade reduced myocardial contractility, more recent non-invasive studies suggest that the predominant cardiac effect is on heart rate. In patients with cardiac failure, beta-blockers may, however, produce a profound fall in cardiac output. Nevertheless, in combination with digoxin they may be useful in controlling the atrial fibrillation of thyrocardiac disease. beta-Blockers improve nervousness and tremor (although to a lesser extent with cardioselective agents) and severe myopathy, and they also reduce the frequency of paralysis in patients with thyrotoxic periodic paralysis. There is often subjective improvement in sweating but usually no major effect on eye signs. Recent studies show a 10% reduction in oxygen consumption/basal metabolic rate with long term oral use of selective or nonselective beta-blockers. In addition, many agents (propranolol, metoprolol, nadolol and sotalol but not acebutolol, atenolol or oxprenolol) reduce circulating tri-iodothyronine (T3) concentration by between 10 and 40%, although the clinical significance of this effect (if any) is not established. beta-Blockers may also have endocrinological effects on gastrin, cyclic AMP, catecholamines and other hormone levels. Given in adequate dosage, propranolol has been shown to control thyrotoxic hypercalcaemia. Minor side effects (nausea, headaches, tiredness, etc.) are quite common but overall beta-blockers are well tolerated by the thyrotoxic patient. The major use of these drugs is in symptomatic control while awaiting definitive diagnosis or treatment. As an adjunct to antithyroid drugs or radioactive iodine, beta-blockers will produce a satisfactory clinical response in the weeks to months before these forms of therapy produce a euthyroid state. beta-Blockers are more convenient than antithyroid drugs in the control of patients receiving therapeutic radioiodine, in that continuous therapy and assessment of biochemical response is possible.(ABSTRACT TRUNCATED AT 400 WORDS)

Cardiac Modulation of Startle: Effects on Eye Blink and Higher Cognitive Processing

ERIC Educational Resources Information Center

Schulz, Andre; Reichert, Carolin F.; Richter, Steffen; Lass-Hennemann, Johanna; Blumenthal, Terry D.; Schachinger, Hartmut

2009-01-01

Cardiac cycle time has been shown to affect pre-attentive brainstem startle processes, such as the magnitude of acoustically evoked reflexive startle eye blinks. These effects were attributed to baro-afferent feedback mechanisms. However, it remains unclear whether cardiac cycle time plays a role in higher startle-related cognitive processes, as…

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.

Effects of testosterone and nandrolone on cardiac function: a randomized, placebo-controlled study.

PubMed

Chung, T; Kelleher, S; Liu, P Y; Conway, A J; Kritharides, L; Handelsman, D J

2007-02-01

Androgens have striking effects on skeletal muscle, but the effects on human cardiac muscle function are not well defined, neither has the role of metabolic activation (aromatization, 5alpha reduction) of testosterone on cardiac muscle been directly studied. To assess the effects of testosterone and nandrolone, a non-amplifiable and non-aromatizable pure androgen, on cardiac muscle function in healthy young men. Double-blind, randomized, placebo-controlled, three-arm parallel group clinical trial. Ambulatory care research centre. Healthy young men randomized into three groups of 10 men. Weekly intramuscular injections of testosterone (200 mg mixed esters), nandrolone (200 mg nandrolone decanoate) or matching (2 ml arachis oil vehicle) placebo for 4 weeks. Comprehensive measures of cardiac muscle function involving transthoracic cardiac echocardiography measuring myocardial tissue velocity, peak systolic strain and strain rates, and bioimpedance measurement of cardiac output and systematic vascular resistance. Left ventricular (LV) function (LV ejection fraction, LV modified TEI index), right ventricular (RV) function (ejection area, tricuspid annular systolic planar motion, RV modified TEI index) as well as cardiac afterload (mean arterial pressure, systemic vascular resistance) and overall cardiac contractility (stroke volume, cardiac output) were within age- and gender-specific reference ranges and were not significantly (P < 0.05) altered by either androgen or placebo over 4 weeks of treatment. Minor changes remaining within normal range were observed solely within the testosterone group for: increased LV end-systolic diameter (30 +/- 7 vs. 33 +/- 5 mm, P = 0.04) and RV end-systolic area (12.8 +/- 1.3 vs. 14.6 +/- 3.3 cm(2), P = 0.04), reduced LV diastolic septal velocity (Em, 9.5 +/- 2.6 vs. 8.7 +/- 2.0 cm/s, P = 0.006), increased LV filling pressure (E/Em ratio, 7.1 +/- 1.6 vs. 8.3 +/- 1.8, P = 0.02) and shortened PR interval on the electrocardiogram (167 +/- 13 vs. 154 +/- 12, P = 0.03). Four weeks of treatment with testosterone or nandrolone had no beneficial or adverse effects compared with placebo on cardiac function in healthy young men.

Sympathetic Nervous System Modulation of Inflammation and Remodeling in the Hypertensive Heart

PubMed Central

Levick, Scott P.; Murray, David B.; Janicki, Joseph S.; Brower, Gregory L.

2010-01-01

Chronic activation of the sympathetic nervous system (SNS) is a key component of cardiac hypertrophy and fibrosis. However, previous studies have provided evidence to also implicate inflammatory cells, including mast cells, in the development of cardiac fibrosis. The current study investigated the potential interaction of cardiac mast cells with the SNS. Eight week old male SHR were sympathectomized to establish the effect of the SNS on cardiac mast cell density, myocardial remodeling and cytokine production in the hypertensive heart. Age-matched WKY served as controls. Cardiac fibrosis and hypertension were significantly attenuated and left ventricular mass normalized while cardiac mast cell density was markedly increased in sympathectomized SHR. Sympathectomy normalized myocardial levels of IFN-γ, IL-6 and IL-10, but had no effect on IL-4. The effect of norepinephrine and substance P on isolated cardiac mast cell activation was investigated as potential mechanisms of interaction between the two. Only substance P elicited mast cell degranulation. Substance P was also shown to induce the production of angiotensin II by a mixed population of isolated cardiac inflammatory cells, including mast cells, lymphocytes and macrophages. These results demonstrate the ability of neuropeptides to regulate inflammatory cell function, providing a potential mechanism by which the SNS and afferent nerves may interact with inflammatory cells in the hypertensive heart. PMID:20048196

Effect of HeartMate left ventricular assist device on cardiac autonomic nervous activity.

PubMed

Kim, S Y; Montoya, A; Zbilut, J P; Mawulawde, K; Sullivan, H J; Lonchyna, V A; Terrell, M R; Pifarré, R

1996-02-01

Clinical performance of a left ventricular assist device is assessed via hemodynamic parameters and end-organ function. This study examined effect of a left ventricular assist device on human neurophysiology. This study evaluated the time course change of cardiac autonomic activity of 3 patients during support with a left ventricular assist device before cardiac transplantation. Cardiac autonomic activity was determined by power spectral analysis of short-term heart rate variability. The heart rate variability before cardiac transplantation was compared with that on the day before left ventricular assist device implantation. The standard deviation of the mean of the R-R intervals of the electrocardiogram, an index of vagal activity, increased to 27 +/- 7 ms from 8 +/- 0.6 ms. The modulus of power spectral components increased. Low frequency (sympathetic activity) and high frequency power (vagal activity) increased by a mean of 9 and 22 times of each baseline value (low frequency power, 5.2 +/- 3.0 ms2; high frequency power, 2.1 +/- 0.7 ms2). The low over high frequency power ratio decreased substantially, indicating an improvement of cardiac sympatho-vagal balance. The study results suggest that left ventricular assist device support before cardiac transplantation may exert a favorable effect on cardiac autonomic control in patients with severe heart failure.

Intracardiac thrombi in extracardiac disorders: an autopsy study.

PubMed

Vaideeswar, Pradeep; Divate, Smita; Harke, Megha

2012-01-01

Intracardiac thrombi (ICT), more commonly encountered at autopsy, are well documented with underlying cardiovascular disease. Occurrence of ICT in systemic diseases without an intrinsic cardiac disorder is rare. The aim of this autopsy study was to highlight such an occurrence. From 1996 to 2010, cases with ICT unrelated to primary cardiac disorders were selected at autopsy and analyzed. Clinical and investigational data were obtained from the medical records. The location, morphology, size, and histological appearance of the thrombi were noted. The thrombi were then classified on the basis of their location, nature, and histology (fresh and/or organized); this was correlated with the clinical setting. Among a total of 11,724 autopsies performed in 15 years, 276 patients (2.4%) had ICT. Of these, 45 patients (0.4%) had ICT that were unrelated to primary cardiac diseases. There were 25 men and 20 women with a mean age of 46.1 years. Antemortem diagnosis was not made in any of these patients. Eight patients each (35.6%) showed isolated left-sided and multichambered involvement, while the rest of the hearts (64.4%) had thrombi in the right-sided chamber(s). The recognizable risk factors were underlying cancers (24.4%), prolonged immobilization (20%), systemic lupus erythematosus (6.7%), pregnancy (4.4%), nephropathy (4.4%), primary antiphospholipid antibody syndrome (2.2%), and ulcerative colitis (2.2%). However, 16 patients (35.7%) had no obvious predisposing factor, although investigations for prothrombotic markers had not been done. Diabetes mellitus, chronic alcoholism, and deep vein thrombosis of the lower limbs had been clinically documented in some of them. The cause of death in most patients (73.3%) had been related to pulmonary and/or systemic thromboembolism. This autopsy study emphasizes the great need for a higher index of suspicion of in situ thrombosis in the heart in hypercoagulable states so as to curtail the morbidity and mortality of the primary disease process. Copyright © 2012 Elsevier Inc. All rights reserved.

Acupuncture Effects on Cardiac Functions Measured by Cardiac Magnetic Resonance Imaging in a Feline Model

PubMed Central

Lin, Jen-Hsou; Shih, Chen-Haw; Kaphle, Krishna; Wu, Leang-Shin; Tseng, Weng-Yih; Chiu, Jen-Hwey; Lee, Tzu-chi

2010-01-01

The usefulness of acupuncture (AP) as a complementary and/or alternative therapy in animals is well established but more research is needed on its clinical efficacy relative to conventional therapy, and on the underlying mechanisms of the effects of AP. Cardiac magnetic resonance imaging (CMRI), an important tool in monitoring cardiovascular diseases, provides a reliable method to monitor the effects of AP on the cardiovascular system. This controlled experiment monitored the effect electro-acupuncture (EA) at bilateral acupoint Neiguan (PC6) on recovery time after ketamine/xylazine cocktail anesthesia in healthy cats. The CMRI data established the basic feline cardiac function index (CFI), including cardiac output and major vessel velocity. To evaluate the effect of EA on the functions of the autonomic nervous and cardiovascular systems, heart rate, respiration rate, electrocardiogram and pulse rate were also measured. Ketamine/xylazine cocktail anesthesia caused a transient hypertension in the cats; EA inhibited this anesthetic-induced hypertension and shortened the post-anesthesia recovery time. Our data support existing knowledge on the cardiovascular benefits of EA at PC6, and also provide strong evidence for the combination of anesthesia and EA to shorten post-anesthesia recovery time and counter the negative effects of anesthetics on cardiac physiology. PMID:18955311

Structural and functional screening in human induced-pluripotent stem cell-derived cardiomyocytes accurately identifies cardiotoxicity of multiple drug types

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

Doherty, Kimberly R., E-mail: kimberly.doherty@quintiles.com; Talbert, Dominique R.; Trusk, Patricia B.

Safety pharmacology studies that evaluate new drug entities for potential cardiac liability remain a critical component of drug development. Current studies have shown that in vitro tests utilizing human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CM) may be beneficial for preclinical risk evaluation. We recently demonstrated that an in vitro multi-parameter test panel assessing overall cardiac health and function could accurately reflect the associated clinical cardiotoxicity of 4 FDA-approved targeted oncology agents using hiPS-CM. The present studies expand upon this initial observation to assess whether this in vitro screen could detect cardiotoxicity across multiple drug classes with known clinical cardiac risks.more » Thus, 24 drugs were examined for their effect on both structural (viability, reactive oxygen species generation, lipid formation, troponin secretion) and functional (beating activity) endpoints in hiPS-CM. Using this screen, the cardiac-safe drugs showed no effects on any of the tests in our panel. However, 16 of 18 compounds with known clinical cardiac risk showed drug-induced changes in hiPS-CM by at least one method. Moreover, when taking into account the Cmax values, these 16 compounds could be further classified depending on whether the effects were structural, functional, or both. Overall, the most sensitive test assessed cardiac beating using the xCELLigence platform (88.9%) while the structural endpoints provided additional insight into the mechanism of cardiotoxicity for several drugs. These studies show that a multi-parameter approach examining both cardiac cell health and function in hiPS-CM provides a comprehensive and robust assessment that can aid in the determination of potential cardiac liability. - Highlights: • 24 drugs were tested for cardiac liability using an in vitro multi-parameter screen. • Changes in beating activity were the most sensitive in predicting cardiac risk. • Structural effects add in-depth insight towards mechanism of cardiac toxicity. • Testing functional and structural endpoints enhances early cardiac risk assessment.« less

Effect of a puzzle on the process of students' learning about cardiac physiology.

PubMed

Cardozo, Lais Tono; Miranda, Aline Soares; Moura, Maria José Costa Sampaio; Marcondes, Fernanda Klein

2016-09-01

The aim of the present study was to evaluate the effects of using a puzzle to learn about cardiac physiology. Students were divided into control and game groups. In class 1, the control group had a 2-h theoretical class about cardiac physiology, including a detailed description of the phases of the cardiac cycle, whereas the game group had a 50-min theoretical class without the description of the cardiac cycle. In class 2, the control group did an assessment exercise before an activity with the cardiac puzzle and the game group answered questions after the above-mentioned activity. While solving the puzzle, the students had to describe the cardiac cycle by relating the concepts of heart morphology and physiology. To evaluate short-term learning, the number of wrong answers and grades in the assessment exercise were compared between the control and game groups. To evaluate medium-term learning, we compared the grades obtained by students of the control and game groups in questions about cardiac physiology that formed part of the academic exam. In the assessment exercise, the game group presented a lower number of errors and higher score compared with the control group. In the academic exam, applied after both groups had used the puzzle, there was no difference in the scores obtained by the control and game groups in questions about cardiac physiology. These results showed a positive effect of the puzzle on students' learning about cardiac physiology compared with those not using the puzzle. Copyright © 2016 The American Physiological Society.

ASCI 2010 contrast media guideline for cardiac imaging: a report of the Asian Society of Cardiovascular Imaging cardiac computed tomography and cardiac magnetic resonance imaging guideline working group.

PubMed

Jinzaki, Masahiro; Kitagawa, Kakuya; Tsai, I-Chen; Chan, Carmen; Yu, Wei; Yong, Hwan Seok; Choi, Byoung Wook

2010-12-01

The use of contrast media for cardiac imaging becomes increasing as the widespread of cardiac CT and cardiac MR. A radiologist needs to carefully consider the indication and the injection protocol of contrast media to be used as well as the possibility of adverse effect. There are several guidelines for contrast media in western countries. However, these are focusing the adverse effect of contrast media. The Asian Society of Cardiovascular Imaging, the only society dedicated to cardiovascular imaging in Asia, formed a Working Group and created a guideline, which summarizes the integrated knowledge of contrast media for cardiac imaging. In cardiac imaging, coronary artery evaluation is feasible by non-contrast MR angiography, which can be an alternative examination in high risk patients for the use of iodine contrast media. Furthermore, the body habitus of Asian patients is usually smaller than that of their western counterparts. This necessitates modifications in the injection protocol and in the formula for calculation of estimated glomerular filtration rate. This guideline provided fundamental information for the use of contrast media for Asian patients in cardiac imaging.

Aerobic exercise conditioning: a nonpharmacological antiarrhythmic intervention.

PubMed

Billman, George E

2002-02-01

Sudden, unexpected cardiac death due to ventricular fibrillation is the leading cause of death in most industrially developed countries. Yet, despite the enormity of this problem, the development of safe and effective antiarrhythmic therapies has proven to be an elusive goal. In fact, many initially promising antiarrhythmic medications were subsequently found to increase rather than to decrease cardiac mortality. It is now known that cardiac disease alters cardiac autonomic balance and that the patients with the greatest changes in this cardiac neural regulation (i.e., decreased parasympathetic coupled with increased sympathetic activity) are also the patients at the greatest risk for sudden death. A growing body of experimental and epidemiological data demonstrates that aerobic exercise conditioning can dramatically reduce cardiac mortality, even in patients with preexisting cardiac disease. Conversely, the lack of exercise is strongly associated with an increased incidence of many chronic debilitating diseases, including coronary heart disease. Because it is well established that aerobic exercise conditioning can alter autonomic balance (increasing parasympathetic tone and decreasing sympathetic activity), a prudently designed exercise program could prove to be an effective and nonpharmacological way to enhance cardiac electrical stability, thereby protecting against sudden cardiac death.

ASCI 2010 contrast media guideline for cardiac imaging: a report of the Asian Society of Cardiovascular Imaging cardiac computed tomography and cardiac magnetic resonance imaging guideline working group

PubMed Central

Kitagawa, Kakuya; Tsai, I-Chen; Chan, Carmen; Yu, Wei; Yong, Hwan Seok; Choi, Byoung Wook

2010-01-01

The use of contrast media for cardiac imaging becomes increasing as the widespread of cardiac CT and cardiac MR. A radiologist needs to carefully consider the indication and the injection protocol of contrast media to be used as well as the possibility of adverse effect. There are several guidelines for contrast media in western countries. However, these are focusing the adverse effect of contrast media. The Asian Society of Cardiovascular Imaging, the only society dedicated to cardiovascular imaging in Asia, formed a Working Group and created a guideline, which summarizes the integrated knowledge of contrast media for cardiac imaging. In cardiac imaging, coronary artery evaluation is feasible by non-contrast MR angiography, which can be an alternative examination in high risk patients for the use of iodine contrast media. Furthermore, the body habitus of Asian patients is usually smaller than that of their western counterparts. This necessitates modifications in the injection protocol and in the formula for calculation of estimated glomerular filtration rate. This guideline provided fundamental information for the use of contrast media for Asian patients in cardiac imaging. PMID:20931289

The modified Yi qi decoction protects cardiac ischemia-reperfusion induced injury in rats.

PubMed

Yu, Xiao; Zhao, Xiao-Dong; Bao, Rong-Qi; Yu, Jia-Yu; Zhang, Guo-Xing; Chen, Jing-Wei

2017-06-21

To investigate the effects and involved mechanisms of the modified Yi Qi decoction (MYQ) in cardiac ischemia-reperfusion (IR) induced injury. Male Sprague-Dawley rats were subjected to a 30-min coronary arterial occlusion followed by reperfusion, low or high dose decoction of MYQ was administrated orally for 1 week or 1 month. Both in 1 week and 1 month IR rat groups, cardiac function indexes were significantly impaired compared with sham group rats, accompanied with higher ratio of infarct size to risk size, decreased expressions of sodium calcium exchanger (NCX1) and sarcoplasmic reticulum Ca 2+ -ATPase (Serca2a), and different expressions of autophagic proteins, Beclin-1 and LC3. Treatment with MYQ (low or high dose) for 1 week showed no marked beneficial effects on cardiac function and cardiac injury (ratio of infarct size to risk size), although expressions of anti-apoptotic protein, Bcl-2, NCX1 and Serca2a were increased. Treatment with MYQ (low or high dose) for 1 month showed significantly improved effects on cardiac function and cardiac injury (ratio of infarct size to risk size), accompanied with increase of Bcl-2, NCX1 and Serca2a expressions, and decrease of Bax (a pro-apoptotic protein) and Beclin-1 expressions. The results show that MYQ have potential therapeutic effects on IR-induced cardiac injury, which may be through regulation of apoptotic proteins, cytosolic Ca 2+ handling proteins and autophagic proteins signal pathways.

Selective management of embolized intracardiac missiles.

PubMed

Gandhi, S K; Marts, B C; Mistry, B M; Brown, J W; Durham, R M; Mazuski, J E

1996-07-01

Intracardiac projectiles are occasionally found in stable patients who have sustained penetrating trauma. These missiles may arise from embolization from a peripheral injury site. We describe 3 patients with embolized intracardiac projectiles. The diagnosis was suggested by the presence of a foreign body within the cardiac silhouette on chest roentgenograms and was confirmed using fluoroscopy, echocardiography, or computed tomography. The management of embolized intracardiac missiles should be individualized to each patient. All of our patients had fixed intracavitary right-sided missiles and were successfully managed expectantly.

The Effect of Previous Coronary Artery Revascularization on the Adverse Cardiac Events Ninety days After Total Joint Arthroplasty.

PubMed

Feng, Bin; Lin, Jin; Jin, Jin; Qian, Wenwei; Cao, Shiliang; Weng, Xisheng

2018-01-01

Although coronary artery revascularization therapies are effective for treating coronary artery disease (CAD), these patients may be more susceptible to adverse cardiac events during later non-cardiac surgeries. The purpose of this study is to evaluate post-operative 90-day complications of total joint arthroplasty (TJA) in CAD patients with a history of CAD and to study the risk factors for cardiac complications. We performed a retrospective analysis of TJA patients between 2005 and 2015 at our institute by summarizing the history of CAD, cardiac revascularization, and cardiac complications within 90 days after the operation. Multivariate logistic regression was performed to identify the factors that predicted cardiac complications within 90 days after the operation. A total of 4414 patients were included; of these, 64 underwent cardiac revascularization and 201 CAD patients underwent medical therapy other than revascularization. All the revascularization had history of myocardial infarction (MI). The rate of cardiac complications within 90 days for the CAD with revascularization was 18.7%, 18.4% for the CAD without revascularization, and 2.0% for the non-CAD group. A history of CAD and revascularization, bilateral TJA, general anesthesia, body mass index ≥30 kg/m 2 , and history of MI were associated with a higher risk of cardiac complications. Patients who underwent TJA within 2 years after cardiac revascularization had a significantly higher cardiac complication rate, and the risk decreased with time. There is an increased risk of cardiac complications within 90 days after the operation among TJA patients with a history of CAD. Revascularization cannot significantly reduce the risk of cardiac complications after TJA for CAD patients. However, the risk decreased as the interval between revascularization and TJA increased. Copyright © 2017 Elsevier Inc. All rights reserved.

Mild hypothermia as a treatment for central nervous system injuries: Positive or negative effects

PubMed Central

Darwazeh, Rami; Yan, Yi

2013-01-01

Besides local neuronal damage caused by the primary insult, central nervous system injuries may secondarily cause a progressive cascade of related events including brain edema, ischemia, oxida-tive stress, excitotoxicity, and dysregulation of calcium homeostasis. Hypothermia is a beneficial strategy in a variety of acute central nervous system injuries. Mild hypothermia can treat high intra-cranial pressure following traumatic brain injuries in adults. It is a new treatment that increases sur-vival and quality of life for patients suffering from ischemic insults such as cardiac arrest, stroke, and neurogenic fever following brain trauma. Therapeutic hypothermia decreases free radical produc-tion, inflammation, excitotoxicity and intracranial pressure, and improves cerebral metabolism after traumatic brain injury and cerebral ischemia, thus protecting against central nervous system dam-age. Although a series of pathological and physiological changes as well as potential side effects are observed during hypothermia treatment, it remains a potential therapeutic strategy for central nervous system injuries and deserves further study. PMID:25206579

Mild hypothermia as a treatment for central nervous system injuries: Positive or negative effects.

PubMed

Darwazeh, Rami; Yan, Yi

2013-10-05

Besides local neuronal damage caused by the primary insult, central nervous system injuries may secondarily cause a progressive cascade of related events including brain edema, ischemia, oxida-tive stress, excitotoxicity, and dysregulation of calcium homeostasis. Hypothermia is a beneficial strategy in a variety of acute central nervous system injuries. Mild hypothermia can treat high intra-cranial pressure following traumatic brain injuries in adults. It is a new treatment that increases sur-vival and quality of life for patients suffering from ischemic insults such as cardiac arrest, stroke, and neurogenic fever following brain trauma. Therapeutic hypothermia decreases free radical produc-tion, inflammation, excitotoxicity and intracranial pressure, and improves cerebral metabolism after traumatic brain injury and cerebral ischemia, thus protecting against central nervous system dam-age. Although a series of pathological and physiological changes as well as potential side effects are observed during hypothermia treatment, it remains a potential therapeutic strategy for central nervous system injuries and deserves further study.

Analyzing Thorough QT Study 1 & 2 in the Telemetric and Holter ECG Warehouse (THEW) using Hannover ECG System HES : A validation study.

PubMed

Khawaja, A; Petrovic, R; Safer, A; Baas, T; Dössel, O; Fischer, R

2010-01-01

Following the ICH E14 clinical evaluation guideline [1], the measurement of QT/QTc interval prolongation has become the standard surrogate biomarker for cardiac drug safety assessment and the faith of a drug development. In Thorough QT (TQT) study, a so-called positive control is employed to assess the ability of this study to detect the endpoint of interest, i.e. the QT prolongation by about five milliseconds. In other words the lower bound of the one-sided 95% confidence interval (CI) must be above 0 [ms]. Fully automated detection of ECG fiducial points and measurement of the corresponding intervals including QT intervals and RR intervals vary between different computerized algorithms. In this work we demonstrate the ability and reliability of Hannover ECG System (HES(®)) to assess drug effects by detecting QT/QTc prolongation effects that meet the threshold of regulatory concern as mentioned by using THEW database studies namely TQT studies one and two.

[Medical cannabis: the opportunity versus the temptation].

PubMed

Naftali, Timna

2011-12-01

The cannabis plant has been known to humanity for centuries as a remedy for pain, diarrhea, and inflammation. Current research has shown cannabis to be a useful remedy for many diseases, including multiple sclerosis, dystonia, and chronic pain. Cannabinoids are used to improve food intake in anorexia of AIDS patients and to prevent vomiting due to cancer chemotherapy. In inflammatory conditions cannabinoids improve pain in rheumatoid arthritis and pain and diarrhea in Crohn's disease. Cannabinoids reduce the size of brain infarct and cardiac reperfusion injury. However, cannabinoid treatment is not free of side effects including euphoria, psychosis, anxiety, paranoia, dependence and abuse. Since the cannabinoid system is involved in many physiological and pathological processes, the therapeutic potential is great. We must not be blind to the opportunity offered to us by medical cannabis just because it is an illicit drug, nor should we be temped by the quick response of patients to the central effect of cannabis. More research is warranted to explore the full potential of cannabis as medicine.

Endocannabinoids in Liver Disease

PubMed Central

Tam, Joseph; Liu, Jie; Mukhopadhyay, Bani; Cinar, Resat; Godlewski, Grzegorz; Kunos, George

2010-01-01

Endocannabinoids are lipid mediators of the same cannabinoid (CB) receptors that mediate the effects of marijuana. The endocannabinoid system (ECS) consists of CB receptors, endocannabinoids, and the enzymes involved in their biosynthesis and degradation, and is present both in brain and peripheral tissues, including the liver. The hepatic ECS is activated in various liver diseases, which contributes to the underlying pathologies. In cirrhosis of various etiologies, activation of vascular and cardiac CB1 receptors by macrophage- and platelet-derived endocannabinoids contribute to the vasodilated state and cardiomyopathy, which can be reversed by CB1 blockade. In mouse models of liver fibrosis, activation of CB1 receptors on hepatic stellate cells is fibrogenic, and CB1 blockade slows the progression of fibrosis. Fatty liver induced by high-fat diets or chronic alcohol feeding depend on activation of peripheral, including hepatic CB1 receptors, which also contribute to insulin resistance and dyslipidemias. Although the documented therapeutic potential of CB1 blockade is limited by neuropsychiatric side effects, these may be mitigated by using novel, peripherally restricted CB1 antagonists. PMID:21254182

Cardiovascular toxicity and sorafenib: a case report.

PubMed

García-Lledó, Javier; Cortejoso, Lucía; Tenorio Núñez, María; Giménez-Manzorro, Alvaro; Matilla-Peña, Ana; Salcedo-Plaza, Magdalena; Sanjurjo-Sáez, María

2014-01-01

We report a case of a 55-year-old male with chronic hepatitis C virus infection and compensated liver disease treated with sorafenib for advanced hepatocarcinoma (Barcelona Clinic Liver Cancer stage C). At follow-up, the patient developed hypertension, which was well controlled with beta-blocker medication, and an aortic dilation detected by abdominal computerized tomography and echocardiography. There are some reports of the side effects of sorafenib on the cardiovascular system. The patient had no cardiac or aortic pathology before the start of this palliative chemotherapy. There is an article that describes the development of an aortic aneurysm in a patient with uncontrolled hypertension, who received treatment with sorafenib for renal carcinoma. However, our patient had a good control of blood pressure. The adverse vascular effects of Sorafenib may be due to the inhibition of the proliferation of vascular endothelial muscle cells. We believe that this case illustrates a probable relationship between sorafenib and aortic dilatation according to the Karch and Lasagna causality algorithm.

PEG-coated gold nanoparticles attenuate β-adrenergic receptor-mediated cardiac hypertrophy.

PubMed

Qiao, Yuhui; Zhu, Baoling; Tian, Aiju; Li, Zijian

2017-01-01

Gold nanoparticles (AuNPs) are widely used as a drug delivery vehicle, which can accumulate in the heart through blood circulation. Therefore, it is very important to understand the effect of AuNPs on the heart, especially under pathological conditions. In this study, we found that PEG-coated AuNPs attenuate β-adrenergic receptor (β-AR)-mediated acute cardiac hypertrophy and inflammation. However, both isoproterenol, a non-selective β-AR agonist, and AuNPs did not induce cardiac function change or cardiac fibrosis. AuNPs exerted an anti-cardiac hypertrophy effect by decreasing β 1 -AR expression and its downstream ERK1/2 hypertrophic pathway. Our results indicated that AuNPs might be safe and have the potential to be used as multi-functional materials (drug carrier systems and anti-cardiac hypertrophy agents).

Naringenin exhibits the protective effect on cardiac hypertrophy via EETs-PPARs activation in streptozocin-induced diabetic mice.

PubMed

Zhang, Jie; Qiu, Hongmei; Huang, Jiajun; Ding, Shumei; Huang, Bo; Wu, Qin; Jiang, Qingsong

2018-07-07

Cardiac hypertrophy is one of the key structural changes in diabetic cardiomyopathy. Naringenin, a dihydroflavonoid extracted from citrus plants with multiple pharmacological activities, yet the underlying effects on diabetic cardiac hypertrophy remain unclear. This study aimed to evaluate the potential effects of naringenin on cardiac hypertrophy in diabetic mice. Long-term high-fat feeding combined with streptozotocin resulted in cardiac hypertrophy after a diabetic model has been established for 4 weeks in mice, which were improved by naringenin supplementation (25 or 75 mg/kg/day, i. g.) for another 4 weeks. The protein and mRNA expressions of PPARs were down-regulated, the protein express of CYP2J3 and level of 14, 15-EET were decreased following diabetic cardiac hypertrophy. Naringenin administration up-regulated PPARs expression, elevated CYP2J3 protein and 14,15-EET content. In conclusion, naringenin can improve cardiac hypertrophy in diabetic mice, which may be related to up-regulate the expression of CYP2J3, elevate the level of EETs, and activate the expression of PPARs. Copyright © 2018 Elsevier Inc. All rights reserved.