A Decline in Intraoperative Renal Near-Infrared Spectroscopy Is Associated With Adverse Outcomes in Children Following Cardiac Surgery.

PubMed

Gist, Katja M; Kaufman, Jonathan; da Cruz, Eduardo M; Friesen, Robert H; Crumback, Sheri L; Linders, Megan; Edelstein, Charles; Altmann, Christopher; Palmer, Claire; Jalal, Diana; Faubel, Sarah

2016-04-01

Renal near-infrared spectroscopy is known to be predictive of acute kidney injury in children following cardiac surgery using a series of complex equations and area under the curve. This study was performed to determine if a greater than or equal to 20% reduction in renal near-infrared spectroscopy for 20 consecutive minutes intraoperatively or within the first 24 postoperative hours is associated with 1) acute kidney injury, 2) increased acute kidney injury biomarkers, or 3) other adverse clinical outcomes in children following cardiac surgery. Prospective single center observational study. Pediatric cardiac ICU. Children less than or equal to age 4 years who underwent cardiac surgery with the use of cardiopulmonary bypass during the study period (June 2011-July 2012). None. A reduction in near-infrared spectroscopy was not associated with acute kidney injury. Nine of 12 patients (75%) with a reduction in renal near-infrared spectroscopy did not develop acute kidney injury. The remaining three patients had mild acute kidney injury (pediatric Risk, Injury, Failure, Loss, End stage-Risk). A reduction in renal near-infrared spectroscopy was associated with the following adverse clinical outcomes: 1) a longer duration of mechanical ventilation (p = 0.05), 2) longer intensive care length of stay (p = 0.05), and 3) longer hospital length of stay (p < 0.01). A decline in renal near-infrared spectroscopy in combination with an increase in serum interleukin-6 and serum interleukin-8 was associated with a longer intensive care length of stay, and the addition of urine interleukin-18 to this was associated with a longer hospital length of stay. In this cohort, the rate of acute kidney injury was much lower than anticipated thereby limiting the evaluation of a reduction in renal near-infrared spectroscopy as a predictor of acute kidney injury. A greater than or equal to 20% reduction in renal near-infrared spectroscopy was significantly associated with adverse outcomes in

Association of Low-Grade Albuminuria with Adverse Cardiac Mechanics: Findings from the HyperGEN Study

PubMed Central

Katz, Daniel H.; Selvaraj, Senthil; Aguilar, Frank G.; Martinez, Eva E.; Beussink, Lauren; Kim, Kwang-Youn A.; Peng, Jie; Sha, Jin; Irvin, Marguerite R.; Eckfeldt, John H.; Turner, Stephen T.; Freedman, Barry I.; Arnett, Donna K.; Shah, Sanjiv J.

2013-01-01

Introduction Albuminuria is a marker of endothelial dysfunction and has been associated with adverse cardiovascular outcomes. The reasons for this association are unclear, but may be due to the relationship between endothelial dysfunction and intrinsic myocardial dysfunction. Methods and Results In the HyperGEN study, a population- and family-based study of hypertension, we examined the relationship between urine albumin-to-creatinine ratio (UACR) and cardiac mechanics (N=1894, all of whom had normal left ventricular ejection fraction and wall motion). We performed speckle-tracking echocardiographic analysis to quantify global longitudinal, circumferential, and radial strain (GLS, GCS, and GRS, respectively), and early diastolic (e′) tissue velocities. We used E/e′ ratio as a marker of increased LV filling pressures. We used multivariable-adjusted linear mixed effect models to determine independent associations between UACR and cardiac mechanics. The mean age was 50±14 years, 59% were female, and 46% were African-American. Comorbidities were increasingly prevalent among higher UACR quartiles. Albuminuria was associated with GLS, GCS, GRS, e′ velocity, and E/e′ ratio on unadjusted analyses. After adjustment for covariates, UACR was independently associated with lower absolute GLS (multivariable-adjusted mean GLS [95% CI] for UACR Quartile 1 = 15.3 [15.0–15.5]% vs. UACR Q4 = 14.6 [14.3–14.9]%, P for trend <0.001) and increased E/e′ ratio (Q1 = 25.3 [23.5–27.1] vs. Q4 = 29.0 [27.0–31.0], P= 0.003). The association between UACR and GLS was present even in participants with UACR < 30 mg/g (P<0.001 after multivariable adjustment). Conclusions Albuminuria, even at low levels, is associated with adverse cardiac mechanics and higher E/e′ ratio. PMID:24077169

Differential cardiac effects in rats exposed to atmospheric ...

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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 complex mixture of particulate matter and gaseous irritants (ozone, sulfur dioxide, reactive aldehydes), as well as components which react with sunlight to form secondary pollutants, has recently been linked to increased risk of adverse cardiac responses. The components, and therefore health effects, of atmospheric smog are determined by the fuel used to generate them. In this study we examined the difference between isoprene- and toluene-generated smog in causing cardiac effects in rats and hypothesized that both atmospheres would cause cardiac electrical and functional changes in rats. Male Wistar-Kyoto rats were exposed to either atmospheric smog generated by the USEPA’s mobile reaction chamber using either isoprene or toluene, or filtered air for four hours. One day later, rats were anesthetized and left ventricular functional responses to dobutamine were measured using a Millar probe and arrhythmia sensitivity to aconitine. Baseline left ventricular pressure (LVP) was lower in toluene-exposed animals but not isoprene when compared to air. Increases in LVP with increasing doses of dobutamine were impaired only in toluene-exposed rats. Both isoprene and toluene impaired the rate of ventri

Exposure to medium and high ambient levels of ozone causes adverse systemic inflammatory and cardiac autonomic effects

PubMed Central

Wong, Hofer; Donde, Aneesh; Frelinger, Jessica; Dalton, Sarah; Ching, Wendy; Power, Karron; Balmes, John R.

2015-01-01

Epidemiological evidence suggests that exposure to ozone increases cardiovascular morbidity. However, the specific biological mechanisms mediating ozone-associated cardiovascular effects are unknown. To determine whether short-term exposure to ambient levels of ozone causes changes in biomarkers of cardiovascular disease including heart rate variability (HRV), systemic inflammation, and coagulability, 26 subjects were exposed to 0, 100, and 200 ppb ozone in random order for 4 h with intermittent exercise. HRV was measured and blood samples were obtained immediately before (0 h), immediately after (4 h), and 20 h after (24 h) each exposure. Bronchoscopy with bronchoalveolar lavage (BAL) was performed 20 h after exposure. Regression modeling was used to examine dose-response trends between the endpoints and ozone exposure. Inhalation of ozone induced dose-dependent adverse changes in the frequency domains of HRV across exposures consistent with increased sympathetic tone [increase of (parameter estimate ± SE) 0.4 ± 0.2 and 0.3 ± 0.1 in low- to high-frequency domain HRV ratio per 100 ppb increase in ozone at 4 h and 24 h, respectively (P = 0.02 and P = 0.01)] and a dose-dependent increase in serum C-reactive protein (CRP) across exposures at 24 h [increase of 0.61 ± 0.24 mg/l in CRP per 100 ppb increase in ozone (P = 0.01)]. Changes in HRV and CRP did not correlate with ozone-induced local lung inflammatory responses (BAL granulocytes, IL-6, or IL-8), but changes in HRV and CRP were associated with each other after adjustment for age and ozone level. Inhalation of ozone causes adverse systemic inflammatory and cardiac autonomic effects that may contribute to the cardiovascular mortality associated with short-term exposure. PMID:25862833

Presence of Late Gadolinium Enhancement by Cardiac Magnetic Resonance Among Patients With Suspected Cardiac Sarcoidosis Is Associated With Adverse Cardiovascular Prognosis: A Systematic Review and Meta-Analysis.

PubMed

Hulten, Edward; Agarwal, Vikram; Cahill, Michael; Cole, Geoff; Vita, Tomas; Parrish, Scott; Bittencourt, Marcio Sommer; Murthy, Venkatesh L; Kwong, Raymond; Di Carli, Marcelo F; Blankstein, Ron

2016-09-01

Individuals with cardiac sarcoidosis have an increased risk of ventricular arrhythmia and death. Several small cohort studies have evaluated the ability of late gadolinium enhancement (LGE) by cardiac magnetic resonance imaging (MRI) to predict adverse cardiovascular events. However, studies have yielded inconsistent results, and some analyses were underpowered. Therefore, we sought to systematically review and perform meta-analysis of the prognostic value of cardiac MRI for patients with known or suspected cardiac sarcoidosis. We systematically searched for cohort studies of patients with known sarcoidosis with suspected cardiac involvement who underwent cardiac MRI with LGE with at least 12 months of either prospective or retrospective follow-up data regarding post-MRI adverse cardiovascular outcomes. We identified 7 studies of 694 subjects (mean age 53; 42% men).One hundred and ninety-nine patients (29%) were LGE positive. All-cause mortality occurred in 19 LGE-positive versus 17 LGE-negative subjects (annualized incidence, 3.1% versus 0.6%). The pooled relative risk was 3.38 (95% confidence interval, 1.07-10.7; P=0.04). Cardiovascular mortality occurred in 10 LGE-positive versus 2 LGE-negative subjects (annualized incidence, 1.9% versus 0.3%; relative risk 10.7 [95% confidence interval, 1.34-86.3]; P=0.03). Ventricular arrhythmia occurred in 41 LGE-positive versus 0 LGE-negative subjects (annualized incidence, 5.9% versus 0%; relative risk 19.5 [95% confidence interval, 2.68-143]; P=0.003). A combined end point of death or ventricular arrhythmia occurred in 64 LGE-positive versus 18 LGE-negative subjects (annualized incidence, 8.8% versus 0.6%; relative risk 6.20 [95% confidence interval, 2.47-15.6]; P<0.001). There was no significant heterogeneity for any outcomes. LGE is associated with future cardiovascular death and ventricular arrhythmia among patients referred to MRI for known or suspected cardiac sarcoidosis. © 2016 American Heart Association, Inc.

Facility-level association of preoperative stress testing and postoperative adverse cardiac events.

PubMed

Valle, Javier A; Graham, Laura; Thiruvoipati, Thejasvi; Grunwald, Gary; Armstrong, Ehrin J; Maddox, Thomas M; Hawn, Mary T; Bradley, Steven M

2018-06-22

Despite limited indications, preoperative stress testing is often used prior to non-cardiac surgery. Patient-level analyses of stress testing and outcomes are limited by case mix and selection bias. Therefore, we sought to describe facility-level rates of preoperative stress testing for non-cardiac surgery, and to determine the association between facility-level preoperative stress testing and postoperative major adverse cardiac events (MACE). We identified patients undergoing non-cardiac surgery within 2 years of percutaneous coronary intervention in the Veterans Affairs (VA) Health Care System, from 2004 to 2011, facility-level rates of preoperative stress testing and postoperative MACE (death, myocardial infarction (MI) or revascularisation within 30 days). We determined risk-standardised facility-level rates of stress testing and postoperative MACE, and the relationship between facility-level preoperative stress testing and postoperative MACE. Among 29 937 patients undergoing non-cardiac surgery at 131 VA facilities, the median facility rate of preoperative stress testing was 13.2% (IQR 9.7%-15.9%; range 6.0%-21.5%), and 30-day postoperative MACE was 4.0% (IQR 2.4%-5.4%). After risk standardisation, the median facility-level rate of stress testing was 12.7% (IQR 8.4%-17.4%) and postoperative MACE was 3.8% (IQR 2.3%-5.6%). There was no correlation between risk-standardised stress testing and composite MACE at the facility level (r=0.022, p=0.81), or with individual outcomes of death, MI or revascularisation. In a national cohort of veterans undergoing non-cardiac surgery, we observed substantial variation in facility-level rates of preoperative stress testing. Facilities with higher rates of preoperative stress testing were not associated with better postoperative outcomes. These findings suggest an opportunity to reduce variation in preoperative stress testing without sacrificing patient outcomes. © Article author(s) (or their employer(s) unless otherwise

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.

Increased titres of anti-human heat shock protein 60 predict an adverse one year prognosis in patients with acute cardiac chest pain

PubMed Central

Birnie, D H; Vickers, L E; Hillis, W S; Norrie, J; Cobbe, S M

2005-01-01

Objective: To assess whether antibodies to human heat shock protein 60 (anti-huhsp60) or to mycobacterial heat shock protein 65 (anti-mhsp65) predict an adverse one year prognosis in patients admitted with acute cardiac chest pain. Design: Prospective observational study. Setting: Teaching hospital. Patients: 588 consecutive emergency admissions of patients with acute chest pain of suspected cardiac origin. Main outcome measures: Anti-huhsp60 and anti-mhsp65 titres were assayed on samples drawn on the morning after admission. The end points after discharge were coronary heart disease death, non-fatal myocardial infarction, coronary artery bypass grafting, percutaneous transluminal coronary angioplasty, angiogram, or readmission with further cardiac ischaemic chest pain. Results: During follow up after discharge (mean of 304 days, range 1–788 days), 277 patients had at least one of the study outcomes. Patients with increased titres of anti-huhsp60 had an adverse prognosis (hazard ratio 1.56 (95% confidence interval 1.09 to 2.23) comparing highest versus lowest quartiles, p  =  0.015). Anti-mhsp65 titres were not predictive. Conclusions: Patients admitted with acute cardiac chest pain and increased titres of anti-huhsp60 had an adverse one year prognosis. PMID:16103543

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.

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

Effects of Hypertension and Exercise on Cardiac Proteome Remodelling

PubMed Central

Petriz, Bernardo A.; Franco, Octavio L.

2014-01-01

Left ventricle hypertrophy is a common outcome of pressure overload stimulus closely associated with hypertension. This process is triggered by adverse molecular signalling, gene expression, and proteome alteration. Proteomic research has revealed that several molecular targets are associated with pathologic cardiac hypertrophy, including angiotensin II, endothelin-1 and isoproterenol. Several metabolic, contractile, and stress-related proteins are shown to be altered in cardiac hypertrophy derived by hypertension. On the other hand, exercise is a nonpharmacologic agent used for hypertension treatment, where cardiac hypertrophy induced by exercise training is characterized by improvement in cardiac function and resistance against ischemic insult. Despite the scarcity of proteomic research performed with exercise, healthy and pathologic heart proteomes are shown to be modulated in a completely different way. Hence, the altered proteome induced by exercise is mostly associated with cardioprotective aspects such as contractile and metabolic improvement and physiologic cardiac hypertrophy. The present review, therefore, describes relevant studies involving the molecular characteristics and alterations from hypertensive-induced and exercise-induced hypertrophy, as well as the main proteomic research performed in this field. Furthermore, proteomic research into the effect of hypertension on other target-demerged organs is examined. PMID:24877123

Admission hyperglycemia predicts inhospital mortality and major adverse cardiac events after primary percutaneous coronary intervention in patients without diabetes mellitus.

PubMed

Ekmekci, Ahmet; Cicek, Gokhan; Uluganyan, Mahmut; Gungor, Baris; Osman, Faizel; Ozcan, Kazim Serhan; Bozbay, Mehmet; Ertas, Gokhan; Zencirci, Aycan; Sayar, Nurten; Eren, Mehmet

2014-02-01

Admission hyperglycemia is associated with high inhospital and long-term adverse events in patients that undergo primary percutaneous coronary intervention (PCI). We aimed to evaluate whether hyperglycemia predicts inhospital mortality. We prospectively analyzed 503 consecutive patients. The patients were divided into tertiles according to the admission glucose levels. Tertile I: glucose <118 mg/dL (n = 166), tertile II: glucose 118 to 145 mg/dL (n = 168), and tertile III: glucose >145 mg/dL (n = 169). Inhospital mortality was 0 in tertile I, 2 in tertile II, and 9 in tertile III (P < .02). Cardiogenic shock occurred more frequently in tertile III compared to tertiles I and II (10% vs 4.1% and 0.6%, respectively, P = .01). Multivariate logistic regression analysis revealed that patients in tertile III had significantly higher risk of inhospital major adverse cardiac events compared to patients in tertile I (odds ratio: 9.55, P < .02). Admission hyperglycemia predicts inhospital adverse cardiac events in mortality and acute ST-segment elevation myocardial infarction in patients that underwent primary PCI.

A Review on the Effect of Traditional Chinese Medicine Against Anthracycline-Induced Cardiac Toxicity

PubMed Central

Yang, Xinyu; Liu, Nian; Li, Xinye; Yang, Yihan; Wang, Xiaofeng; Li, Linling; Jiang, Le; Gao, Yonghong; Tang, Hebin; Tang, Yong; Xing, Yanwei; Shang, Hongcai

2018-01-01

Anthracyclines are effective agents generally used to treat solid-tumor and hematologic malignancies. The use of anthracyclines for over 40 years has improved cancer survival statistics. Nevertheless, the clinical utility of anthracyclines is limited by its dose-dependent cardiotoxicity that adversely affects 10–30% of patients. Anthracycline-induced cardiotoxicity may be classified as acute/subacute or chronic/late toxicity and leads to devastating adverse effects resulting in poor quality of life, morbidity, and premature mortality. Traditional Chinese medicine has a history of over 2,000 years, involving both unique theories and substantial experience. Several studies have investigated the potential of natural products to decrease the cardiotoxic effects of chemotherapeutic agents on healthy cells, without negatively affecting their antineoplastic activity. This article discusses the mechanism of anthracycline-induced cardiotoxicity, and summarizes traditional Chinese medicine treatment for anthracycline-induced heart failure (HF), cardiac arrhythmia, cardiomyopathy, and myocardial ischemia in recent years, in order to provide a reference for the clinical prevention and treatment of cardiac toxicity. PMID:29867456

Adverse Effects and Surgical Complications in Pediatric Patients Undergoing Vagal Nerve Stimulation for Drug-Resistant Epilepsy.

PubMed

Trezza, A; Landi, A; Grioni, D; Pirillo, D; Fiori, L; Giussani, C; Sganzerla, E P

2017-01-01

Vagal nerve stimulation (VNS) is an effective treatment for drug-resistant epilepsy that is not suitable for resective surgery, both in adults and in children. Few reports describe the adverse effects and complications of VNS. The aim of our study was to present a series of 33 pediatric patients who underwent VNS for drug-resistant epilepsy and to discuss the adverse effects and complications through a review of the literature.The adverse effects of VNS are usually transient and are dependent on stimulation of the vagus and its efferent fibers; surgical complications of the procedure may be challenging and patients sometimes require further surgery; generally these complications affect VNS efficacy; in addition, hardware complications also have to be taken into account.In our experience and according to the literature, adverse effects and surgical and hardware complications are uncommon and can usually be managed definitely. Careful selection of patients, particularly from a respiratory and cardiac point of view, has to be done before surgery to limit the incidence of some adverse effects.

Reduced aspirin responsiveness as assessed by impedance aggregometry is not associated with adverse outcome after cardiac surgery in a small low-risk cohort.

PubMed

Bolliger, Daniel; Filipovic, Miodrag; Matt, Peter; Tanaka, Kenichi A; Gregor, Michael; Zenklusen, Urs; Seeberger, Manfred D; Lurati Buse, Giovanna

2016-01-01

Reduced aspirin responsiveness (i.e. persistent high platelet reactivity in platelet function testing) might be associated with increased risk of myocardial ischemia and cardiac mortality in patients with coronary disease. However, the impact in patients undergoing coronary artery bypass grafting (CABG) is unclear. The aim of this prospective cohort study was to evaluate the predictive value of reduced aspirin responsiveness on cardiac and thromboembolic events in patients undergoing elective isolated CABG surgery with aspirin intake until at least two days before surgery. We included 304 patients in this prospective single-center cohort study. Impedance platelet aggregometry (Multiplate®) was performed directly before and on the first day after surgery. Reduced aspirin responsiveness was defined as area under the curve in ASPItest (AUCASPI) ≥300 U. The primary outcome was a composite of all-cause mortality and/or major adverse cardiac or thromboembolic events within 1 year. Reduced aspirin responsiveness was found in 13 and 24% of patients pre and postoperatively, respectively. There was no difference in the outcomes between patients with normal and reduced aspirin responsiveness in the preoperative measurement (log-rank test, p = 0.540). Multivariate analysis including logistic EuroSCORE I and postoperative troponin T levels did not show any association of reduced aspirin responsiveness with adverse outcome (hazard ratio, 0.576; (95% CI 0.128-2.585; p = 0.471). Similarly, postoperative reduced aspirin responsiveness was not associated with adverse events. To conclude, reduced aspirin responsiveness as evaluated by Multiplate® platelet function analyzer was not associated with increased incidence of major adverse cardiac and thromboembolic events and mortality after CABG surgery.

Association of hypothyroidism with adverse events in patients with heart failure receiving cardiac resynchronization therapy.

PubMed

Sharma, Ajay K; Vegh, Eszter; Orencole, Mary; Miller, Alexandra; Blendea, Dan; Moore, Stephanie; Lewis, Gregory D; Singh, Jagmeet P; Parks, Kimberly A; Heist, E Kevin

2015-05-01

Hypothyroidism is associated with an adverse prognosis in cardiac patients in general and in particular in patients with heart failure (HF). The aim of this study was to evaluate the impact of hypothyroidism on patients with HF receiving cardiac resynchronization therapy (CRT). Additionally, the impact of level of control of hypothyroidism on risk of adverse events after CRT implantation was also evaluated. We included consecutive patients in whom a CRT device was implanted from April 2004 to April 2010 at our institution with sufficient follow-up data available for analysis; 511 patients were included (age 68.5±12.4 years, women 20.4%); 84 patients with a clinical history of hypothyroidism, on treatment with thyroid hormone repletion or serum thyroid-stimulating hormone level≥5.00 μU/ml, were included in the hypothyroid group. The patients were followed for up to 3 years after implant for a composite end point of hospitalization for HF, left ventricular assist device placement, or heart transplant and cardiac death; 215 composite end point events were noted in this period. In a multivariate model, hypothyroidism (hazard ratio [HR] 1.46, 95% confidence interval [CI] 1.027 to 2.085, p=0.035), female gender (HR 0.64, 95% CI 0.428 to 0.963, p=0.032), and creatinine (HR 1.26, 95% CI 1.145 to 1.382, p<0.001) were significantly associated with occurrence of the composite end point; 53.6% of patients with hypothyroidism at baseline developed the composite end point compared with 39.8% of those with euthyroidism (p=0.02). In conclusion, hypothyroidism is associated with a worse prognosis after CRT implantation. Copyright © 2015 Elsevier Inc. All rights reserved.

A Systematic Review of Early Warning Systems' Effects on Nurses' Clinical Performance and Adverse Events Among Deteriorating Ward Patients.

PubMed

Lee, Ju-Ry; Kim, Eun-Mi; Kim, Sun-Aee; Oh, Eui Geum

2018-04-25

Early warning systems (EWSs) are an integral part of processes that aim to improve the early identification and management of deteriorating patients in general wards. However, the widespread implementation of these systems has not generated robust data regarding nurses' clinical performance and patients' adverse events. This review aimed to determine the ability of EWSs to improve nurses' clinical performance and prevent adverse events among deteriorating ward patients. The PubMed, CINAHL, EMBASE, and Cochrane Library databases were searched for relevant publications (January 1, 1997, to April 12, 2017). In addition, a grey literature search evaluated several guideline Web sites. The main outcome measures were nurses' clinical performance (vital sign monitoring and rapid response team notification) and patients' adverse events (in-hospital mortality, cardiac arrest, and unplanned intensive care unit [ICU] admission). The search identified 888 reports, although only five studies fulfilled the inclusion criteria. The findings of these studies revealed that EWSs implementation had a positive effect on nurses' clinical performance, based on their frequency of documenting vital signs that were related to the patient's clinical deterioration. In addition, postimplementation reductions were identified for cardiac arrest, unplanned ICU admission, and unexpected death. It seems that EWSs can improve nurses' clinical performance and prevent adverse events (e.g., in-hospital mortality, unplanned ICU admission, and cardiac arrest) among deteriorating ward patients. However, additional high-quality evidence is needed to more comprehensively evaluate the effects of EWSs on these outcomes.

Maternal adverse effects of different antenatal magnesium sulphate regimens for improving maternal and infant outcomes: a systematic review

PubMed Central

2013-01-01

Background Antenatal magnesium sulphate, widely used in obstetrics to improve maternal and infant outcomes, may be associated with adverse effects for the mother sufficient for treatment cessation. This systematic review aimed to quantify maternal adverse effects attributed to treatment, assess how adverse effects vary according to different regimens, and explore women’s experiences with this treatment. Methods Bibliographic databases were searched from their inceptions to July 2012 for studies of any design that reported on maternal adverse effects associated with antenatal magnesium sulphate given to improve maternal or infant outcomes. Primary outcomes were life-threatening adverse effects of treatment (death, cardiac arrest, respiratory arrest). For randomised controlled trials, data were meta-analysed, and risk ratios (RR) pooled using fixed-effects or random-effects models. For non-randomised studies, data were tabulated by design, and presented as RR, odds ratios or percentages, and summarised narratively. Results A total of 143 publications were included (21 randomised trials, 15 non-randomised comparative studies, 32 case series and 75 reports of individual cases), of mixed methodological quality. Compared with placebo or no treatment, magnesium sulphate was not associated with an increased risk of maternal death, cardiac arrest or respiratory arrest. Magnesium sulphate significantly increased the risk of 'any adverse effects’ overall (RR 4.62, 95% CI 2.42-8.83; 4 trials, 13,322 women), and treatment cessation due to adverse effects (RR 2.77; 95% CI 2.32-3.30; 5 trials, 13,666 women). Few subgroup differences were observed (between indications for use and treatment regimens). In one trial, a lower dose regimen (2 g/3 hours) compared with a higher dose regimen (5 g/4 hours) significantly reduced treatment cessation (RR 0.05; 95% CI 0.01-0.39, 126 women). Adverse effect estimates from studies of other designs largely supported data from randomised

Preoperative and intraoperative predictors of cardiac adverse events after general, vascular, and urological surgery.

PubMed

Kheterpal, Sachin; O'Reilly, Michael; Englesbe, Michael J; Rosenberg, Andrew L; Shanks, Amy M; Zhang, Lingling; Rothman, Edward D; Campbell, Darrell A; Tremper, Kevin K

2009-01-01

The authors sought to determine the incidence and risk factors for perioperative cardiac adverse events (CAEs) after noncardiac surgery using detailed preoperative and intraoperative hemodynamic data. The authors conducted a prospective observational study at a single university hospital from 2002 to 2006. All American College of Surgeons-National Surgical Quality Improvement Program patients undergoing general, vascular, and urological surgery were included. The CAE outcome definition included cardiac arrest, non-ST elevation myocardial infarction, Q-wave myocardial infarction, and new clinically significant cardiac dysrhythmia within the first 30 postoperative days. Four years of data demonstrated that of 7,740 noncardiac operations, 83 patients (1.1%) experienced a CAE within 30 days. Nine independent predictors were identified (P < or = 0.05): age > or = 68, body mass index > or = 30, emergent surgery, previous coronary intervention or cardiac surgery, active congestive heart failure, cerebrovascular disease, hypertension, operative duration > or = 3.8 h, and the administration of 1 or more units of packed red blood cells intraoperatively. The c-statistic of this model was 0.81 +/- 0.02. Univariate analysis demonstrated that high-risk patients experiencing a CAE were more likely to experience an episode of mean arterial pressure < 50 mmHg (6% vs. 24%, P = 0.02), experience an episode of 40% decrease in mean arterial pressure (26% vs. 53%, P = 0.01), and an episode of heart rate > 100 (22% vs. 34%, P = 0.05). In comparison with current risk stratification indices, the inclusion of intraoperative elements improves the ability to predict a perioperative CAE after noncardiac surgery.

Reduction of Serious Adverse Events Demanding Study Exclusion in Model Development: Extracorporeal Life Support Resuscitation of Ventricular Fibrillation Cardiac Arrest in Rats.

PubMed

Warenits, Alexandra-Maria; Sterz, Fritz; Schober, Andreas; Ettl, Florian; Magnet, Ingrid Anna Maria; Högler, Sandra; Teubenbacher, Ursula; Grassmann, Daniel; Wagner, Michael; Janata, Andreas; Weihs, Wolfgang

2016-12-01

Extracorporeal life support is a promising concept for selected patients in refractory cardiogenic shock and for advanced life support of persistent ventricular fibrillation cardiac arrest. Animal models of ventricular fibrillation cardiac arrest could help to investigate new treatment strategies for successful resuscitation. Associated procedural pitfalls in establishing a rat model of extracorporeal life support resuscitation need to be replaced, refined, reduced, and reported.Anesthetized male Sprague-Dawley rats (350-600 g) (n = 126) underwent cardiac arrest induced with a pacing catheter placed into the right ventricle via a jugular cannula. Rats were resuscitated with extracorporeal life support, mechanical ventilation, defibrillation, and medication. Catheter and cannula explantation was performed if restoration of spontaneous circulation was achieved. All observed serious adverse events (SAEs) occurring in each of the experimental phases were analyzed.Restoration of spontaneous circulation could be achieved in 68 of 126 rats (54%); SAEs were observed in 76 (60%) experiments. Experimental procedures related SAEs were 62 (82%) and avoidable human errors were 14 (18%). The most common serious adverse events were caused by insertion or explantation of the venous bypass cannula and resulted in lethal bleeding, cannula dislocation, or air embolism.Establishing an extracorporeal life support model in rats has confronted us with technical challenges. Even advancements in small animal critical care management over the years delivered by an experienced team and technical modifications were not able to totally avoid such serious adverse events. Replacement, refinement, and reduction reports of serious adverse events demanding study exclusions to avoid animal resources are missing and are presented hereby.

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

Cumulative Burden of Myocardial Dysfunction in Cardiac Amyloidosis Assessed Using Four-Chamber Cardiac Strain.

PubMed

Kado, Yuichiro; Obokata, Masaru; Nagata, Yasufumi; Ishizu, Tomoko; Addetia, Karima; Aonuma, Kazutaka; Kurabayashi, Masahiko; Lang, Roberto M; Takeuchi, Masaaki; Otsuji, Yutaka

2016-11-01

The aim of this study was to test the hypothesis that prognosis in patients with cardiac amyloidosis is closely coupled with amyloid burden in all four cardiac chambers. The goal was to evaluate longitudinal strain (LS) in each cardiac chamber and to determine whether LS in specific cardiac chambers is preferentially associated with prognosis over conventional two-dimensional echocardiographic parameters in patients with cardiac amyloidosis. Patients with two phenotypes of left ventricular (LV) hypertrophy (cardiac amyloidosis in 55 patients and nonobstructive hypertrophic cardiomyopathy in 40 patients) and 55 healthy subjects were retrospectively enrolled for the simultaneous assessment of LS of all four cardiac chambers in the apical four-chamber view. Patients with cardiac amyloidosis were followed up to record major adverse cardiovascular events, including cardiac death, heart transplantation, nonfatal myocardial infarction, ventricular tachyarrhythmia, and exacerbation of heart failure requiring hospitalization. LS in each chamber was significantly depressed in patients with both LV hypertrophy phenotypes compared with healthy subjects. Right atrial LS was significantly lower in patients with cardiac amyloidosis than those with nonobstructive hypertrophic cardiomyopathy after adjusting for LV ejection fraction and LV mass index. During a median follow-up period of 10 months, major adverse cardiovascular events developed in 22 patients with cardiac amyloidosis. Four-chamber LS were significantly associated with major adverse cardiovascular events, with incremental value over traditional echocardiographic parameters. Cardiac amyloidosis involves all cardiac chambers, and thus, chamber-specific strain analysis may be useful to assess the total cumulative burden of cardiac dysfunction. Copyright © 2016 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

A critical pathway for patients with acute chest pain and low risk for short-term adverse cardiac events: role of outpatient stress testing.

PubMed

Meyer, Mary C; Mooney, Robert P; Sekera, Anna K

2006-05-01

We evaluate the safety and feasibility of a critical care pathway protocol in which patients with acute chest pain who are low risk for coronary artery disease and short-term adverse cardiac outcomes receive outpatient stress testing within 72 hours of an emergency department (ED) visit. We performed an observational study of an ED-based chest pain critical pathway in an urban, community hospital in 979 consecutive patients. Patients enrolled in the protocol were observed in the ED before receiving 72-hour outpatient stress testing. The pathway was primarily analyzed for rates of death or myocardial infarction in the 6 months after ED discharge and outpatient stress testing. Secondary outcome measures included need for coronary intervention at initial stress testing and within 6 months after discharge, subsequent ED visits for chest pain, and subsequent hospitalization. Of 871 stress-tested patients aged 40 years or older, who had low risk for coronary artery disease and short-term adverse cardiac events, and had 6-month follow-up, 18 (2%) required coronary intervention, 1 (0.1%) had a myocardial infarction within 1 month, 2 (0.2%) had a myocardial infarction within 6 months, 6 (0.7%) had normal stress test results after discharge but required cardiac catheterization within 6 months, and 5 (0.6%) returned to the ED within 6 months for ongoing chest pain. Hospital admission rates decreased significantly from 31.2% to 26.1% after initiation of the protocol (P<.001). For patients with chest pain and low risk for short-term cardiac events, outpatient stress testing is feasible, safe, and associated with decreased hospital admission rates. With an evidence-based protocol, physicians efficiently identify patients at low risk for clinically significant coronary artery disease and short-term adverse cardiac outcomes.

Association of apical rocking with long-term major adverse cardiac events in patients undergoing cardiac resynchronization therapy.

PubMed

Ghani, Abdul; Delnoy, Peter Paul H M; Ottervanger, Jan Paul; Ramdat Misier, Anand R; Smit, Jaap Jan J; Adiyaman, Ahmet; Elvan, Arif

2016-02-01

Correctly identifying patients who will benefit from cardiac resynchronization therapy (CRT) is still challenging. 'Apical rocking' is observed in asynchronously contracting ventricles and is associated with echocardiographic response to CRT. The association of apical rocking and long-term clinical outcome is however unknown at present. We assessed the predictive value of left ventricular (LV) apical rocking on a long-term clinical outcome in patients treated with CRT. Consecutive heart failure patients treated with primary indication for CRT-D between 2005 and 2009 were included in a prospective registry. Echocardiography was performed prior to CRT to assess apical rocking, defined as motion of the LV apical myocardium perpendicular to the LV long axis. Major adverse cardiac event (MACE) was defined as combined end point of cardiac death and/or heart failure hospitalization and/or appropriate therapy (ATP and/or ICD shocks). All echocardiograms were assessed by independent cardiologists, blinded for clinical data. Multivariable analyses were performed to adjust for potential confounders. Two hundred and ninety-five patients with echocardiography prior to implantation were included in the final analyses. Apical rocking was present in 45% of the study patients. Apical rocking was significantly more common in younger patients, females, patients with sinus rhythm, non-ischaemic cardiomyopathy, and in patients with LBBB and wider QRS duration. During a mean clinical follow-up of 5.2 ± 1.6 years, 92 (31%) patients reached the end point of the study (MACE). Patients with MACE had shorter QRS duration, had more ischaemic cardiomyopathy, and were more often on Amiodarone. In univariate analyses, MACE was associated with shorter QRS duration, ischaemic aetiology, and the absence of apical rocking. After multivariable analyses, apical rocking was associated with less MACE (hazards ratio, HR 0.44, 95% confidence interval, CI 0.25-0.77). Apical rocking is an independent

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

+/- 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.

European guidelines on managing adverse effects of medication for ADHD

PubMed Central

Banaschewski, T.; Buitelaar, J.; Coghill, D.; Danckaerts, M.; Dittmann, R. W.; Döpfner, M.; Hamilton, R.; Hollis, C.; Holtmann, M.; Hulpke-Wette, M.; Lecendreux, M.; Rosenthal, E.; Rothenberger, A.; Santosh, P.; Sergeant, J.; Simonoff, E.; Sonuga-Barke, E.; Wong, I. C. K.; Zuddas, A.; Steinhausen, H.-C.; Taylor, E.

2010-01-01

The safety of ADHD medications is not fully known. Concerns have arisen about both a lack of contemporary-standard information about medications first licensed several decades ago, and signals of possible harm arising from more recently developed medications. These relate to both relatively minor adverse effects and extremely serious issues such as sudden cardiac death and suicidality. A guidelines group of the European Network for Hyperkinetic Disorders (EUNETHYDIS) has therefore reviewed the literature, recruited renowned clinical subspecialists and consulted as a group to examine these concerns. Some of the effects examined appeared to be minimal in impact or difficult to distinguish from risk to untreated populations. However, several areas require further study to allow a more precise understanding of these risks. PMID:21042924

PM101: a cyclodextrin-based intravenous formulation of amiodarone devoid of adverse hemodynamic effects.

PubMed

Cushing, Daniel J; Kowey, Peter R; Cooper, Warren D; Massey, Bill W; Gralinski, Michael R; Lipicky, Raymond J

2009-04-01

Intravenous amiodarone (Amiodarone i.v.) is widely used to treat cardiac arrhythmias. The most frequent clinical adverse event associated with Amiodarone i.v. administration is systemic hypotension which has been attributed to the cosolvents used in the formulation, polysorbate 80 and benzyl alcohol. To minimize hypotension Amiodarone i.v. is diluted in 5% dextrose in water prior to administration and slowly infused. PM101 is a novel intravenous formulation that uses sulfobutylether-7-beta-cyclodextrin to solubilize amiodarone, and thus should be devoid of the untoward hemodynamic effects associated with polysorbate 80 and benzyl alcohol. Beagle dogs (n=7/group) were anesthetized with morphine and alpha-chloralose and instrumented to assess aortic blood pressure, cardiac output, cardiac contractility, and heart rate. Animals were treated with the U.S. approved human-equivalent loading dose (2.14 mg/kg) of Amiodarone i.v., PM101, and their respective vehicle controls. Administration of Amiodarone i.v. rapidly and significantly decreased mean aortic pressure, cardiac output, and cardiac contractility. A significant increase in heart rate was also observed as was a transient, but not significant, decrease in systemic vascular resistance. A similar pattern of rapid and significant hemodynamic changes was produced by the Amiodarone i.v. Vehicle (polysorbate 80/benzyl alcohol) alone. In marked contrast, PM101 and its vehicle produced no significant hemodynamic effects. This study provides a useful model for the continued search for a safe and effective intravenous amiodarone formulation devoid of the hypotensive risk associated with the current commercial formulation.

[Adverse effects of oxcarbazepine].

PubMed

Fang, Shu; Gong, Zhi-Cheng

2015-04-01

Oxcarbazepine is a new antiepileptic drug. The results of clinical trials suggest that oxcarbazepine is well tolerated and has less drug interactions. It is being used more and more widely in clinical practice, but its adverse effects should not be ignored. The most common adverse effects of oxcarbazepine are usually related to the central nervous system and digestive system, including fatigue, drowsiness, diplopia, dizziness, nausea and vomit. The common skin adverse reaction is rash. Long-term use of oxcarbazepine may also cause hyponatremia. This article reviews the literature from China and overseas about the adverse effets of oxcarbazepine over the last 10 years in order to find information about rational clinical use of oxcarbazepine.

Adverse events in cardiac surgery, a mixed methods retrospective study in an Italian teaching hospital.

PubMed

Bellandi, Tommaso; Tartaglia, Riccardo; Forni, Silvia; D'Arienzo, Sara; Tulli, Giorgio

2017-08-01

Adverse events (AEs) are a major concern in surgery, but the evidence in cardiac surgery is limited, especially on the contributory factors. According to the data of the National Outcomes Program, a unit was selected to conduct a mixed methods investigation into the incidence, type, and cause of AE, given its mortality rate that was double the national average on coronary artery bypass grafting, valve reparation, and replacement. A retrospective investigation on the performance of a cardiac surgery, combining the routinely collected data on process and outcome measures with a 2-stage structured review of 280 medical records performed by 3 expert clinicians, with the support of a methodologist. At least one risk had been verified in 137 of 280 cases (48.9%, 95% CI, 43.1-54.8). The total number of AE was 42, with an incidence of 15% (95% CI, 10.8-20.2) and a preventability of 80.9% (95% CI, 69.1-92.8). In 11.9% of AE, the consequence is death, disability in 40.5%, and extended hospital stay in 69% of the cases. Adverse events are associated with problems in care management at the ward (89/137, 64.9%, 95% CI, 56.9-72.9), followed by surgical complications (46/137, 33.6%, 95% CI, 25.7-41.5) and infection/sepsis (32/137, 23.4%, 95% CI, 16.3-30.4). An active error was made by the health care workers in 31 of 42 cases with AE, either during the decision making or during the execution of an action. A total of 36 AEs were due to deficiencies attributed to organizational factors and 31 were linked to poor teamwork. The mixed methods approach demonstrated how a deep understanding of AE and poor performance may emerge thanks to the combination of routinely available data and experts' evaluations. The main limitation of this study is its focus on the cardiac surgery rather than on the entire process of care. The evaluation could have been integrated with on-site observations and the analysis of reported incidents. © 2017 John Wiley & Sons, Ltd.

Adverse cardiovascular, cerebrovascular, and peripheral vascular effects of marijuana inhalation: what cardiologists need to know.

PubMed

Thomas, Grace; Kloner, Robert A; Rezkalla, Shereif

2014-01-01

Marijuana is the most widely used illicit drug, with approximately 200 million users worldwide. Once illegal throughout the United States, cannabis is now legal for medicinal purposes in several states and for recreational use in 3 states. The current wave of decriminalization may lead to more widespread use, and it is important that cardiologists be made aware of the potential for marijuana-associated adverse cardiovascular effects that may begin to occur in the population at a greater frequency. In this report, the investigators focus on the known cardiovascular, cerebrovascular, and peripheral effects of marijuana inhalation. Temporal associations between marijuana use and serious adverse events, including myocardial infarction, sudden cardiac death, cardiomyopathy, stroke, transient ischemic attack, and cannabis arteritis have been described. In conclusion, the potential for increased use of marijuana in the changing legal landscape suggests the need for the community to intensify research regarding the safety of marijuana use and for cardiologists to maintain an awareness of the potential for adverse effects. Copyright © 2014 Elsevier Inc. All rights reserved.

Incidence and management of life-threatening adverse events during cardiac catheterization for congenital heart disease.

PubMed

Lin, C Huie; Hegde, Sanjeet; Marshall, Audrey C; Porras, Diego; Gauvreau, Kimberlee; Balzer, David T; Beekman, Robert H; Torres, Alejandro; Vincent, Julie A; Moore, John W; Holzer, Ralf; Armsby, Laurie; Bergersen, Lisa

2014-01-01

Continued advancements in congenital cardiac catheterization and interventions have resulted in increased patient and procedural complexity. Anticipation of life-threatening events and required rescue measures is a critical component to preprocedural preparation. We sought to determine the incidence and nature of life-threatening adverse events in congenital and pediatric cardiac catheterization, risk factors, and resources necessary to anticipate and manage events. Data from 8905 cases performed at the 8 participating institutions of the Congenital Cardiac Catheterization Project on Outcomes were captured between 2007 and 2010 [median 1,095/site (range 133-3,802)]. The incidence of all life-threatening events was 2.1 % [95 % confidence interval (CI) 1.8-2.4 %], whereas mortality was 0.28 % (95 % CI 0.18-0.41 %). Fifty-seven life-threatening events required cardiopulmonary resuscitation, whereas 9 % required extracorporeal membrane oxygenation. Use of a risk adjustment model showed that age <1 year [odd ratio (OR) 1.9, 95 % CI 1.4-2.7, p < 0.001], hemodynamic vulnerability (OR 1.6, 95 % CI 1.1-2.3, p < 0.01), and procedure risk (category 3: OR 2.3, 95 % CI 1.3-4.1; category 4: OR 4.2, 95 % CI 2.4-7.4) were predictors of life-threatening events. Using this model, standardized life-threatening event ratios were calculated, thus showing that one institution had a life-threatening event rate greater than expected. Congenital cardiac catheterization and intervention can be performed safely with a low rate of life-threatening events and mortality; preprocedural evaluation of risk may optimize preparation of emergency rescue and bailout procedures. Risk predictors (age < 1, hemodynamic vulnerability, and procedure risk category) can enhance preprocedural patient risk stratification and planning.

The Knowledge-Integrated Network Biomarkers Discovery for Major Adverse Cardiac Events

PubMed Central

Jin, Guangxu; Zhou, Xiaobo; Wang, Honghui; Zhao, Hong; Cui, Kemi; Zhang, Xiang-Sun; Chen, Luonan; Hazen, Stanley L.; Li, King; Wong, Stephen T. C.

2010-01-01

The mass spectrometry (MS) technology in clinical proteomics is very promising for discovery of new biomarkers for diseases management. To overcome the obstacles of data noises in MS analysis, we proposed a new approach of knowledge-integrated biomarker discovery using data from Major Adverse Cardiac Events (MACE) patients. We first built up a cardiovascular-related network based on protein information coming from protein annotations in Uniprot, protein–protein interaction (PPI), and signal transduction database. Distinct from the previous machine learning methods in MS data processing, we then used statistical methods to discover biomarkers in cardiovascular-related network. Through the tradeoff between known protein information and data noises in mass spectrometry data, we finally could firmly identify those high-confident biomarkers. Most importantly, aided by protein–protein interaction network, that is, cardiovascular-related network, we proposed a new type of biomarkers, that is, network biomarkers, composed of a set of proteins and the interactions among them. The candidate network biomarkers can classify the two groups of patients more accurately than current single ones without consideration of biological molecular interaction. PMID:18665624

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

A Public-Private Consortium Advances Cardiac Safety Evaluation: Achievements of the HESI Cardiac Safety Technical Committee

EPA Science Inventory

The evaluation of cardiovascular side-effects is a critical element in the development of all new drugs and chemicals. Cardiac safety issues have been and continue to be a major cause of attrition and withdrawal due to Adverse Drug Reactions (ADRs) in pharmaceutical drug developm...

Intraoperative adverse events can be compensated by technical performance in neonates and infants after cardiac surgery: a prospective study.

PubMed

Nathan, Meena; Karamichalis, John M; Liu, Hua; del Nido, Pedro; Pigula, Frank; Thiagarajan, Ravi; Bacha, Emile A

2011-11-01

Our objective was to define the relationship between surgical technical performance score, intraoperative adverse events, and major postoperative adverse events in complex pediatric cardiac repairs. Infants younger than 6 months were prospectively followed up until discharge from the hospital. Technical performance scores were graded as optimal, adequate, or inadequate based on discharge echocardiograms and need for reintervention after initial surgery. Case complexity was determined by Risk Adjustment in Congenital Heart Surgery (RACHS-1) category, and preoperative illness severity was assessed by Pediatric Risk of Mortality (PRISM) III score. Intraoperative adverse events were prospectively monitored. Outcomes were analyzed using nonparametric methods and a logistic regression model. A total of 166 patients (RACHS 4-6 [49%]), neonates [50%]) were observed. Sixty-one (37%) had at least 1 intraoperative adverse event, and 47 (28.3%) had at least 1 major postoperative adverse event. There was no correlation between intraoperative adverse events and RACHS, preoperative PRISM III, technical performance score, or postoperative adverse events on multivariate analysis. For the entire cohort, better technical performance score resulted in lower postoperative adverse events, lower postoperative PRISM, and lower length of stay and ventilation time (P < .001). Patients requiring intraoperative revisions fared as well as patients without, provided the technical score was at least adequate. In neonatal and infant open heart repairs, technical performance score is one of the main predictors of postoperative morbidity. Outcomes are not affected by intraoperative adverse events, including surgical revisions, provided technical performance score is at least adequate. Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Subclinical and Overt Adverse Cardiac Effects with Ozone Inhalation in Rats: Potentially Dire Implications of Low Exposures

EPA Science Inventory

Ozone is a ubiquitous smog-associated photochemical oxidant with deleterious health effects. While most of the adverse effects described to date involve the respiratory system (i.e, decrements in lung function, airway injury and inflammation, exacerbation of asthma, and compromis...

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

Sequential cyclophosphamide-bortezomib-dexamethasone unmasks the harmful cardiac effect of dexamethasone in primary light-chain cardiac amyloidosis.

PubMed

Le Bras, Fabien; Molinier-Frenkel, Valerie; Guellich, Aziz; Dupuis, Jehan; Belhadj, Karim; Guendouz, Soulef; Ayad, Karima; Colombat, Magali; Benhaiem, Nicole; Tissot, Claire Marie; Hulin, Anne; Jaccard, Arnaud; Damy, Thibaud

2017-05-01

Chemotherapy combining cyclophosphamide, bortezomib and dexamethasone is widely used in light-chain amyloidosis. The benefit is limited in patients with cardiac amyloidosis mainly because of adverse cardiac events. Retrospective analysis of our cohort showed that 39 patients died with 42% during the first month. A new escalation-sequential regimen was set to improve the outcomes. Nine newly-diagnosed patients were prospectively treated with close monitoring of serum N-terminal pro-brain natriuretic peptide, troponin-T and free light chains. The results show that corticoids may destabilise the heart through fluid retention. Thus, a sequential protocol may be a promising approach to treat these patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

Tolerability of sirolimus: a decade of experience at a single cardiac transplant center.

PubMed

Thibodeau, Jennifer T; Mishkin, Joseph D; Patel, Parag C; Kaiser, Patricia A; Ayers, Colby R; Mammen, Pradeep P A; Markham, David W; Ring, William Steves; Peltz, Matthias; Drazner, Mark H

2013-01-01

Sirolimus is used in cardiac transplant recipients to prevent rejection, progression of cardiac allograft vasculopathy, and renal dysfunction. However, sirolimus has many potential side effects and its tolerability when used outside of clinical trials is not well established. We describe a decade of experience with sirolimus in cardiac transplant recipients at our institution. We retrospectively reviewed records of all adult cardiac transplant recipients living between September 1999 and February 2010 (n = 329) and identified 67 patients (20%) who received sirolimus. The indications for sirolimus were cardiac allograft vasculopathy (67%), renal dysfunction (25%), rejection (4%), and intolerability of tacrolimus (3%). One-third of patients discontinued sirolimus at a median (25th, 75th percentiles) of 0.9 (0.2, 1.6) yr of duration. Over 70% of subjects experienced an adverse event attributed to sirolimus. Adverse events were associated with higher average sirolimus levels (9.1 ng/mL vs. 7.1 ng/mL, p = 0.004). We conclude that sirolimus is frequently used in cardiac transplant recipients (20%) and commonly causes side effects, often necessitating discontinuation. Higher average sirolimus levels were associated with adverse events, suggesting that tolerability may improve if levels are maintained within the lower end of the current therapeutic range; however, the improvement in tolerability would need to be balanced with the potential for decreased efficacy. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Prehospital cardiac arrest and the adverse effect of male gender, but not age, on outcome.

PubMed

Vukmir, Rade B

2003-09-01

To analyze the incidence and outcome of prehospital cardiac arrest as it correlated to gender and age as a secondary end point in an interventional clinical trial. This prospective, randomized, double-blinded clinical intervention trial enrolled 874 prehospital cardiopulmonary arrest patients encountered by prehospital urban, suburban, and rural regional emergency medical service (EMS) areas. This trial evaluated outcome and profiled demographic predictors of cardiac arrest patients refractory to defibrillation with intravenous access who underwent standard advanced cardiac life support (ACLS) intervention and empiric early administration of bicarbonate. Survival was measured to the emergency department (ED), and data analysis used chi-square with Pearson correlation. The overall survival rate was 14.2%. There was no age correlate to survival, with an average age of 67.4 for both groups. Male patients had a 2.4-fold increased incidence (70.7 vs. 29.3%, p = 0.001) of arrest, which was associated with a 60% increase in mortality (19.6% vs. 11.8, p = 0.004) compared with women. The risk of unfavorable outcome was increased for men (OR 1.826, 95% CI 1.182-2.821; RR 1.097, 95% CI 1.025-1.180) on univariate analysis. There appeared to be no intergroup differences found with other historical variables, such as the presence of myocardial infarction (MI), hypertension (HTN), diabetes mellitus (DM), congestive heart failure (CHF), and chronic obstructive pulmonary disease (COPD), which were analyzed. However, HTN was found more commonly (2.2 times) in men (69.1 vs. 30.9%) than in women but did not correlate with survival. Male gender, but not age, is associated with both an increased incidence and a worsened outcome in prehospital cardiac arrest.

Omega-3 Fatty Acid Supplementation Appears to Attenuate Particulate Air Pollution-induced Cardiac Effects and Lipid Changes in Healthy Middle-aged Adults.

EPA Science Inventory

Context: Air pollution exposure has been associated with adverse cardiovascular effects. A recent epidemiologic study reported that omega-3 fatty acid (fish oil) supplementation blunted the cardiac responses to air pollution exposure. Objective: To evaluate in a randomized contro...

Modeling Major Adverse Outcomes of Pediatric and Adult Patients With Congenital Heart Disease Undergoing Cardiac Catheterization: Observations From the NCDR IMPACT Registry (National Cardiovascular Data Registry Improving Pediatric and Adult Congenital Treatment).

PubMed

Jayaram, Natalie; Spertus, John A; Kennedy, Kevin F; Vincent, Robert; Martin, Gerard R; Curtis, Jeptha P; Nykanen, David; Moore, Phillip M; Bergersen, Lisa

2017-11-21

Risk standardization for adverse events after congenital cardiac catheterization is needed to equitably compare patient outcomes among different hospitals as a foundation for quality improvement. The goal of this project was to develop a risk-standardization methodology to adjust for patient characteristics when comparing major adverse outcomes in the NCDR's (National Cardiovascular Data Registry) IMPACT Registry (Improving Pediatric and Adult Congenital Treatment). Between January 2011 and March 2014, 39 725 consecutive patients within IMPACT undergoing cardiac catheterization were identified. Given the heterogeneity of interventional procedures for congenital heart disease, new procedure-type risk categories were derived with empirical data and expert opinion, as were markers of hemodynamic vulnerability. A multivariable hierarchical logistic regression model to identify patient and procedural characteristics predictive of a major adverse event or death after cardiac catheterization was derived in 70% of the cohort and validated in the remaining 30%. The rate of major adverse event or death was 7.1% and 7.2% in the derivation and validation cohorts, respectively. Six procedure-type risk categories and 6 independent indicators of hemodynamic vulnerability were identified. The final risk adjustment model included procedure-type risk category, number of hemodynamic vulnerability indicators, renal insufficiency, single-ventricle physiology, and coagulation disorder. The model had good discrimination, with a C-statistic of 0.76 and 0.75 in the derivation and validation cohorts, respectively. Model calibration in the validation cohort was excellent, with a slope of 0.97 (standard error, 0.04; P value [for difference from 1] =0.53) and an intercept of 0.007 (standard error, 0.12; P value [for difference from 0] =0.95). The creation of a validated risk-standardization model for adverse outcomes after congenital cardiac catheterization can support reporting of risk

Effects of red-cell storage duration on patients undergoing cardiac surgery.

PubMed

Steiner, Marie E; Ness, Paul M; Assmann, Susan F; Triulzi, Darrell J; Sloan, Steven R; Delaney, Meghan; Granger, Suzanne; Bennett-Guerrero, Elliott; Blajchman, Morris A; Scavo, Vincent; Carson, Jeffrey L; Levy, Jerrold H; Whitman, Glenn; D'Andrea, Pamela; Pulkrabek, Shelley; Ortel, Thomas L; Bornikova, Larissa; Raife, Thomas; Puca, Kathleen E; Kaufman, Richard M; Nuttall, Gregory A; Young, Pampee P; Youssef, Samuel; Engelman, Richard; Greilich, Philip E; Miles, Ronald; Josephson, Cassandra D; Bracey, Arthur; Cooke, Rhonda; McCullough, Jeffrey; Hunsaker, Robert; Uhl, Lynne; McFarland, Janice G; Park, Yara; Cushing, Melissa M; Klodell, Charles T; Karanam, Ravindra; Roberts, Pamela R; Dyke, Cornelius; Hod, Eldad A; Stowell, Christopher P

2015-04-09

Some observational studies have reported that transfusion of red-cell units that have been stored for more than 2 to 3 weeks is associated with serious, even fatal, adverse events. Patients undergoing cardiac surgery may be especially vulnerable to the adverse effects of transfusion. We conducted a randomized trial at multiple sites from 2010 to 2014. Participants 12 years of age or older who were undergoing complex cardiac surgery and were likely to undergo transfusion of red cells were randomly assigned to receive leukocyte-reduced red cells stored for 10 days or less (shorter-term storage group) or for 21 days or more (longer-term storage group) for all intraoperative and postoperative transfusions. The primary outcome was the change in Multiple Organ Dysfunction Score (MODS; range, 0 to 24, with higher scores indicating more severe organ dysfunction) from the preoperative score to the highest composite score through day 7 or the time of death or discharge. The median storage time of red-cell units provided to the 1098 participants who received red-cell transfusion was 7 days in the shorter-term storage group and 28 days in the longer-term storage group. The mean change in MODS was an increase of 8.5 and 8.7 points, respectively (95% confidence interval for the difference, -0.6 to 0.3; P=0.44). The 7-day mortality was 2.8% in the shorter-term storage group and 2.0% in the longer-term storage group (P=0.43); 28-day mortality was 4.4% and 5.3%, respectively (P=0.57). Adverse events did not differ significantly between groups except that hyperbilirubinemia was more common in the longer-term storage group. The duration of red-cell storage was not associated with significant differences in the change in MODS. We did not find that the transfusion of red cells stored for 10 days or less was superior to the transfusion of red cells stored for 21 days or more among patients 12 years of age or older who were undergoing complex cardiac surgery. (Funded by the National

Evaluation of the acute cardiac and central nervous system effects of the fluorocarbon trifluoromethane in baboons

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

Branch, C.A.; Goldberg, D.A.; Ewing, J.R.

1994-12-31

The gaseous fluorocarbon trifluoromethane has recently been investigated for its potential as an in vivo gaseous indicator for nuclear magnetic resonance studies of brain perfusion. Trifluoromethane may also have significant value as a replacement for chlorofluorocarbon fire retardants. Because of possible species-specific cardiotoxic and anesthetic properties, the toxicological evaluation of trifluoromethane in primates (Papio anubis) is necessary prior to its evaluation in humans. We report the acute cardiac and central nervous system effects of trifluoromethane in eight anesthetized baboons. A dose-response effect was established for respiratory rate, electroencephalogram, and cardiac sinus rate, which exhibited a stepwise decrease from 10% trifluoromethane.more » No spontaneous arrhythmias were noted, and arterial blood pressure remained unchanged at any inspired level. Intravenous epinephrine infusions (1 {mu}g/kg) induced transient cardiac arrhythmia in 1 animal only at 70% FC-23 (v/v) trifluoromethane. Trifluoromethane appears to induce mild dose-related physiological changes at inspired levels of 30% or more, indicative of an anesthetic effect. These data suggest that trifluoromethane may be safe to use in humans, without significant adverse acute effects, at an inspired level of 30%. 23 refs., 3 figs., 3 tabs.« less

Defining the Intrinsic Cardiac Risks of Operations to Improve Preoperative Cardiac Risk Assessments.

PubMed

Liu, Jason B; Liu, Yaoming; Cohen, Mark E; Ko, Clifford Y; Sweitzer, Bobbie J

2018-02-01

Current preoperative cardiac risk stratification practices group operations into broad categories, which might inadequately consider the intrinsic cardiac risks of individual operations. We sought to define the intrinsic cardiac risks of individual operations and to demonstrate how grouping operations might lead to imprecise estimates of perioperative cardiac risk. Elective operations (based on Common Procedural Terminology codes) performed from January 1, 2010 to December 31, 2015 at hospitals participating in the American College of Surgeons National Surgical Quality Improvement Program were studied. A composite measure of perioperative adverse cardiac events was defined as either cardiac arrest requiring cardiopulmonary resuscitation or acute myocardial infarction. Operations' intrinsic cardiac risks were derived from mixed-effects models while controlling for patient mix. Resultant risks were sorted into low-, intermediate-, and high-risk categories, and the most commonly performed operations within each category were identified. Intrinsic operative risks were also examined using a representative grouping of operations to portray within-group variation. Sixty-six low, 30 intermediate, and 106 high intrinsic cardiac risk operations were identified. Excisional breast biopsy had the lowest intrinsic cardiac risk (overall rate, 0.01%; odds ratio, 0.11; 95% CI, 0.02 to 0.25) relative to the average, whereas aorto-bifemoral bypass grafting had the highest (overall rate, 4.1%; odds ratio, 6.61; 95% CI, 5.54 to 7.90). There was wide variation in the intrinsic cardiac risks of operations within the representative grouping (median odds ratio, 1.40; interquartile range, 0.88 to 2.17). A continuum of intrinsic cardiac risk exists among operations. Grouping operations into broad categories inadequately accounts for the intrinsic cardiac risk of individual operations.

Myocardial Dysfunction and Shock after Cardiac Arrest

PubMed Central

Jentzer, Jacob C.; Chonde, Meshe D.; Dezfulian, Cameron

2015-01-01

Postarrest myocardial dysfunction includes the development of low cardiac output or ventricular systolic or diastolic dysfunction after cardiac arrest. Impaired left ventricular systolic function is reported in nearly two-thirds of patients resuscitated after cardiac arrest. Hypotension and shock requiring vasopressor support are similarly common after cardiac arrest. Whereas shock requiring vasopressor support is consistently associated with an adverse outcome after cardiac arrest, the association between myocardial dysfunction and outcomes is less clear. Myocardial dysfunction and shock after cardiac arrest develop as the result of preexisting cardiac pathology with multiple superimposed insults from resuscitation. The pathophysiology involves cardiovascular ischemia/reperfusion injury and cardiovascular toxicity from excessive levels of inflammatory cytokine activation and catecholamines, among other contributing factors. Similar mechanisms occur in myocardial dysfunction after cardiopulmonary bypass, in sepsis, and in stress-induced cardiomyopathy. Hemodynamic stabilization after resuscitation from cardiac arrest involves restoration of preload, vasopressors to support arterial pressure, and inotropic support if needed to reverse the effects of myocardial dysfunction and improve systemic perfusion. Further research is needed to define the role of postarrest myocardial dysfunction on cardiac arrest outcomes and identify therapeutic strategies. PMID:26421284

Myocardial Dysfunction and Shock after Cardiac Arrest.

PubMed

Jentzer, Jacob C; Chonde, Meshe D; Dezfulian, Cameron

2015-01-01

Postarrest myocardial dysfunction includes the development of low cardiac output or ventricular systolic or diastolic dysfunction after cardiac arrest. Impaired left ventricular systolic function is reported in nearly two-thirds of patients resuscitated after cardiac arrest. Hypotension and shock requiring vasopressor support are similarly common after cardiac arrest. Whereas shock requiring vasopressor support is consistently associated with an adverse outcome after cardiac arrest, the association between myocardial dysfunction and outcomes is less clear. Myocardial dysfunction and shock after cardiac arrest develop as the result of preexisting cardiac pathology with multiple superimposed insults from resuscitation. The pathophysiology involves cardiovascular ischemia/reperfusion injury and cardiovascular toxicity from excessive levels of inflammatory cytokine activation and catecholamines, among other contributing factors. Similar mechanisms occur in myocardial dysfunction after cardiopulmonary bypass, in sepsis, and in stress-induced cardiomyopathy. Hemodynamic stabilization after resuscitation from cardiac arrest involves restoration of preload, vasopressors to support arterial pressure, and inotropic support if needed to reverse the effects of myocardial dysfunction and improve systemic perfusion. Further research is needed to define the role of postarrest myocardial dysfunction on cardiac arrest outcomes and identify therapeutic strategies.

Association Between Hyperuricemia and Major Adverse Cardiac Events in Patients with Acute Myocardial Infarction.

PubMed

Ranjith, Naresh; Myeni, Nomcebo N; Sartorius, Ben; Mayise, Chamsanqua

2017-02-01

To investigate the association between hyperuricemia and major adverse cardiac events (MACE) in patients with acute myocardial infarction (AMI). Consecutive patients admitted with AMI to the Coronary Care Unit at R. K. Khan Hospital (Durban, South Africa) between the years 2006 and 2014 were included. Demographic data, including clinical and biochemical information stored in an electronic database, were obtained from all patients. A total of 2683 patients were studied, of whom 65% were males. The mean age of the participants was 57.1 ± 11.5 years, with 79% presenting with ST elevation myocardial infarction. Sixty-one percent were smokers, 59% had diabetes mellitus, 52% had hypertension, and 58% presented with a family history of premature coronary artery disease. Twenty-six percent (n = 690) had hyperuricemia, were older (59 ± 12.1 vs. 56.5 ± 11.2 years) and more likely to present with hypertension (P < 0.001), lower ejection fraction (P < 0.001), and higher median creatinine levels (P < 0.001). A significantly greater proportion of patients with hyperuricemia experienced MACE (45% vs. 30%, P < 0.001). In both sexes, considerable heterogeneity for risk factors and clinical events was noted in individuals with hyperuricemia. Multivariable analyses for risk factors associated with mortality suggest that hyperuricemia conferred a significantly increased risk of mortality after adjustment [odds ratio (OR) 1.7 (95% confidence interval 1.0-2.8); P = 0.042]. A significant increasing risk trend for MACE was observed for increasing tertiles of serum uric acid concentrations above normal (P < 0.001), particularly for cardiac failure (P < 0.001) and death (P = 0.006). Hyperuricemia is significantly associated with hypertension, renal dysfunction, MACE, and independently confers a higher risk of mortality in patients with AMI. Significant heterogeneity was found by gender for risk factors and clinical events in individuals

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

Stress Perfusion Cardiac Magnetic Resonance Imaging Effectively Risk Stratifies Diabetic Patients With Suspected Myocardial Ischemia.

PubMed

Heydari, Bobak; Juan, Yu-Hsiang; Liu, Hui; Abbasi, Siddique; Shah, Ravi; Blankstein, Ron; Steigner, Michael; Jerosch-Herold, Michael; Kwong, Raymond Y

2016-04-01

Diabetics remain at high risk of cardiovascular disease and mortality despite advancements in medical therapy. Noninvasive cardiac risk profiling is often more difficult in diabetics owing to the prevalence of silent ischemia with unrecognized myocardial infarction, reduced exercise capacity, nondiagnostic electrocardiographic changes, and balanced ischemia from diffuse epicardial coronary atherosclerosis and microvascular dysfunction. A consecutive cohort of 173 patients with diabetes mellitus (mean age, 61.7±11.9 years; 37% women) with suspected myocardial ischemia underwent stress perfusion cardiac magnetic resonance imaging. Patients were evaluated for adverse cardiac events after cardiac magnetic resonance imaging with mean follow-up time of 2.9±2.5 years. Mean hemoglobin A1c for the population was 7.9±1.8%. Primary end point was a composite of cardiac death and nonfatal myocardial infarction. Diabetics with no inducible ischemia (n=94) experienced an annualized event rate of 1.4% compared with 8.2% (P=0.0003) in those with inducible ischemia (n=79). Diabetics without late gadolinium enhancement or inducible ischemia had a low annual cardiac event rate (0.5% per year). The presence of inducible ischemia was the strongest unadjusted predictor (hazard ratio, 4.86; P<0.01) for cardiac death and nonfatal myocardial infarction. This association remained robust in adjusted stepwise multivariable Cox regression analysis (hazard ratio, 4.28; P=0.02). In addition, categorical net reclassification index using 5-year risk cutoffs of 5% and 10% resulted in reclassification of 43.4% of the diabetic cohort with net reclassification index of 0.38 (95% confidence interval, 0.20-0.56; P<0.0001). Stress perfusion cardiac magnetic resonance imaging provided independent prognostic utility and effectively reclassified risk in patients with diabetes mellitus referred for ischemic assessment. Further evaluation is required to determine whether a noninvasive imaging strategy with

Adverse Effects Associated With Newer Diabetes Therapies.

PubMed

Akiyode, Oluwaranti F; Adesoye, Adebola A

2017-04-01

The increasing number of newer type 2 diabetes therapies has allowed providers an increased armamentarium for the optimal management of patients with diabetes. In fact, these newer agents have unique benefits in the management of type 2 diabetes. However, they are also associated with certain adverse effects. This review article aims to describe the notable adverse effects of these newer antidiabetic therapies including the glucagon-like peptide 1 receptor agonists, dipeptidyl peptidase-4 inhibitors, and the sodium-glucose cotransporter 2 inhibitors. The adverse effects reviewed herein include pancreatitis, medullary thyroid carcinoma, heart failure, gastrointestinal disturbances, renal impairment, and genitourinary infections. More clinical data are necessary to solidify the association of some of these adverse effects with the newer diabetes agents. However, it is important for health care practitioners to be well informed and prepared to properly monitor patients for these adverse effects.

Beneficial effects of leptin treatment in a setting of cardiac dysfunction induced by transverse aortic constriction in mouse.

PubMed

Gómez-Hurtado, Nieves; Domínguez-Rodríguez, Alejandro; Mateo, Philippe; Fernández-Velasco, María; Val-Blasco, Almudena; Aizpún, Rafael; Sabourin, Jessica; Gómez, Ana María; Benitah, Jean-Pierre; Delgado, Carmen

2017-07-01

Leptin, is a 16 kDa pleiotropic peptide not only primarily secreted by adipocytes, but also produced by other tissues, including the heart. Controversy exists regarding the adverse and beneficial effects of leptin on the heart We analysed the effect of a non-hypertensive dose of leptin on cardiac function, [Ca 2+ ] i handling and cellular electrophysiology, which participate in the genesis of pump failure and related arrhythmias, both in control mice and in mice subjected to chronic pressure-overload by transverse aorta constriction. We find that leptin activates mechanisms that contribute to cardiac dysfunction under physiological conditions. However, after the establishment of pressure overload, an increase in leptin levels has protective cardiac effects with respect to rescuing the cellular heart failure phenotype. These beneficial effects of leptin involve restoration of action potential duration via normalization of transient outward potassium current and sarcoplasmic reticulum Ca 2+ content via rescue of control sarcoplasmic/endoplasmic reticulum Ca 2+ ATPase levels and ryanodine receptor function modulation, leading to normalization of Ca 2+ handling parameters. Leptin, is a 16 kDa pleiotropic peptide not only primary secreted by adipocytes, but also produced by other tissues, including the heart. Evidence indicates that leptin may have either adverse or beneficial effects on the heart. To obtain further insights, in the present study, we analysed the effect of leptin treatment on cardiac function, [Ca 2+ ] i handling and cellular electrophysiology, which participate in the genesis of pump failure and related arrhythmias, both in control mice and in mice subjected to chronic pressure-overload by transverse aorta constriction (TAC). Three weeks after surgery, animals received either leptin (0.36 mg kg -1  day -1 ) or vehicle via osmotic minipumps for 3 weeks. Echocardiographic measurements showed that, although leptin treatment was deleterious on

Adverse event detection using the FDA post-marketing drug safety surveillance system: Cardiotoxicity associated with loperamide abuse and misuse.

PubMed

Swank, Kimberley A; Wu, Eileen; Kortepeter, Cindy; McAninch, Jana; Levin, Robert L

The purpose of this investigation was to identify and characterize post-marketing reports of cardiotoxicity, including torsades de pointes (TdP), associated with loperamide use. We searched the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database for post-marketing reports of serious cardiac adverse events associated with loperamide use from December 28, 1976 (U.S. drug approval date), through December 14, 2015. We also conducted a Pubmed and Google Scholar search to identify additional published reports of cardiotoxicity associated with loperamide in the medical literature through February 11, 2016. Forty-eight cases of serious cardiac adverse events associated with loperamide use composed the case series. The most frequently reported cardiac adverse events were syncope (n = 24), cardiac arrest (n = 13), QT-interval prolongation (n = 13), ventricular tachycardia (n = 10), and TdP (n = 7). There were 10 cases that resulted in death. Of the 48 cases, the most commonly reported reasons for use can be characterized as drug abuse (n = 22) and diarrhea treatment (n = 17). More than one-half of the 48 cases were reported after 2010. Of the 22 drug abuse cases, the median daily dose was 250 mg (range 70 mg to 1600 mg) and events occurred as early as 6 hours after a dose and as long as 18 months after initiation of loperamide. Thirteen of the 22 cases reported using loperamide for euphoric or analgesic effects, and 9 reported use to prevent opioid withdrawal symptoms. The FAERS case reports provide evidence to suggest that high doses of loperamide are associated with TdP and other serious cardiac adverse events. The majority of cases in this series occurred in the setting of drug abuse for the purpose of preventing opioid withdrawal or to produce euphoric effects. It is important for both clinicians and patients to be aware of this potential risk, because prompt therapy and discontinuation of the offending agent are often essential to

A Low-Normal Free Triiodothyronine Level Is Associated with Adverse Prognosis in Euthyroid Patients with Heart Failure Receiving Cardiac Resynchronization Therapy.

PubMed

Chen, Yu-Yang; Shu, Xiao-Rong; Su, Zi-Zhuo; Lin, Rong-Jie; Zhang, Hai-Feng; Yuan, Wo-Liang; Wang, Jing-Feng; Xie, Shuang-Lun

2017-12-12

Thyroid dysfunction is prevalent in patients with heart failure (HF) and hypothyroidism is related to the adverse prognosis of HF subjects receiving cardiac resynchronization therapy (CRT). We aim to investigate whether low-normal free triiodothyronine (fT3) level is related to CRT response and the prognosis of euthyroid patients with HF after CRT implantation.One hundred and thirteen euthyroid patients who received CRT therapy without previous thyroid disease and any treatment affecting thyroid hormones were enrolled. All of patients were evaluated for cardiac function and thyroid hormones (serum levels of fT3, free thyroxine [fT4] and thyroid-stimulating hormone [TSH]). The end points were overall mortality and hospitalization for HF worsening. During a follow-up period of 39 ± 3 weeks, 36 patients (31.9%) died and 45 patients (39.8%) had hospitalization for HF exacerbation. A higher rate of NYHA III/IV class and a lower fT3 level were both observed in death group and HF event group. Multivariate Cox regression analyses disclosed that a lower-normal fT3 level (HR = 0.648, P = 0.009) and CRT response (HR = 0.441, P = 0.001) were both independent predictors of overall mortality. In addition, they were also both related to HF re-hospitalization event (P < 0.01 for both). Patients with fT3 < 3.00 pmol/L had a significantly higher overall mortality than those with fT3 ≥ 3.00 pmol/L (P = 0.027). Meanwhile, a higher HF hospitalization event rate was also found in patients with fT3 < 3.00 pmol/L (P < 0.001).A lower-normal fT3 level is correlated with a worse cardiac function an adverse prognosis in euthyroid patients with HF after CRT implantation.

Cardiac and Metabolic Effects of Dietary Selenomethionine Exposure in Adult Zebrafish.

PubMed

Pettem, Connor M; Weber, Lynn P; Janz, David M

2017-10-01

Selenium (Se) is an essential micronutrient involved in important metabolic functions for all vertebrate species. As Se is reported to have a narrow margin between essentiality and toxicity, there is growing concern surrounding the adverse effects of elevated Se exposure caused by anthropogenic activities. Recent studies have reported that elevated dietary exposure of fish to selenomethionine (Se-Met) can alter aerobic metabolic capacity, energetics and swimming performance. This study aims to further investigate mechanisms of sublethal Se-Met toxicity, particularly potential underlying cardiovascular implications of chronic exposure to environmentally relevant concentrations of dietary Se-Met in adult zebrafish (Danio rerio). Adult zebrafish were fed either control food (1.1 μg Se/g dry mass [d.m.]) or Se-Met spiked food (10.3 or 28.8 μg Se/g d.m.) for 90 d at 5% body weight per day. Following exposure, ultrahigh resolution B-mode and Doppler ultrasound was used to characterize cardiac function. Chronic dietary exposure to elevated Se-Met significantly reduced ventricular contractile rate, stroke volume, and cardiac output. Exposure to Se-Met significantly decreased mRNA expression of methionine adenosyltransferase 1 alpha and glutathione-S-transferase pi class in liver, and a key cardiac remodelling enzyme, matrix metalloproteinase 2, in adult zebrafish heart. Se-Met significantly increased echodensity at the junction between atrium and ventricle, and these results combined with increased matrix metalloproteinase 2 expression are consistent with cardiac remodelling and fibrosis. The results of this study suggest that chronic exposure to dietary Se-Met can negatively impact cardiac function, and such physiological consequences could reduce the aerobic capacity and survivability of fish. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Pay attention to cardiac remodeling in cancer cachexia.

PubMed

Zheng, Yawen; Chen, Han; Li, Xiaoqing; Sun, Yuping

2016-07-01

Cancer cachexia is a complex and multifaceted disease state characterized by fatigue, weakness, and loss of skeletal muscle and adipose tissue. Recently, the profound negative effects of cancer cachexia on cardiac tissue draw much attention, which is likely to contribute to mortality in tumor-bearing animals. The mechanism of cardiac remodeling is not so clear and involved with a series of molecular alterations. In cancer cachexia model, progressive loss of left ventricular mass and decrease in myocardial function is observed and cardiac autonomic functions are altered. Levels of several emerging cardiovascular neurohormones are found elevating in patients with cancer, but it is still controversial whether the changes could reflect the heart injury accurately. The remedy for cardiac remodeling has been explored. It is showed that exercise can modulate signaling pathways activated by wasting cytokines and impact on the resulting outcomes on heart adaptation. Some drugs, such as bisoprolol, spironolactone, perindopril, tandospirone, and simvastatin, can mitigate adverse effects of the tumor on the heart and prolong survival.

Effects of stanozolol on apoptosis mechanisms and oxidative stress in rat cardiac tissue.

PubMed

Kara, Mehtap; Ozcagli, Eren; Kotil, Tuğba; Alpertunga, Buket

2018-06-01

Stanozolol is a widely used 17α-alkylated anabolic androgenic steroid (AAS) derivative. Despite stanozolol's adverse effects, its effect on oxidative stress parameters and mitochondrial apoptosis pathway is not clearly defined. In our study, thirty four male Sprague-Dawley rats were divided into 5 groups as control (C), vehicle control (VC), steroid (ST), vehicle control-exercise (VCE), and steroid-exercise (STE). Animals were subcutaneously administered stanozolol 5 mg/kg in steroid groups and propylene glycol 1 ml/kg in the vehicle-control groups. On the 28th day-after sacrification, oxidative stress (MDA, GSH, PC, SOD, CAT) and apoptosis parameters (TUNEL, Cytochrome-c) in cardiac tissue were evaluated. Also, blood vessel morphology of cardiac tissue was evaluated with Verhoeff-van Giesen staining. It has been demonstrated that stanozolol administration triggers apoptosis by using TUNEL assay and cytochrome-c immunohistochemical staining intensity, while this effect is significantly reduced in the presence of exercise. In conclusion, the present study demonstrated that stanozolol administration induces apoptosis with increasing PC and CAT levels, while GSH, MDA and SOD parameters do not reveal any significant change. Exercise has a protective role in stanozolol induced oxidative stress and apoptosis. According to Verhoeff-van Giesen staining results for blood vessel morphology assessment, it has been seen that exercise has a protective role on cardiac blood vessels. This mechanism needs further investigations with long term exposure studies for clarifying possible pathways. Copyright © 2018 Elsevier Inc. All rights reserved.

Risk prediction models for major adverse cardiac event (MACE) following percutaneous coronary intervention (PCI): A review

NASA Astrophysics Data System (ADS)

Manan, Norhafizah A.; Abidin, Basir

2015-02-01

Five percent of patients who went through Percutaneous Coronary Intervention (PCI) experienced Major Adverse Cardiac Events (MACE) after PCI procedure. Risk prediction of MACE following a PCI procedure therefore is helpful. This work describes a review of such prediction models currently in use. Literature search was done on PubMed and SCOPUS database. Thirty literatures were found but only 4 studies were chosen based on the data used, design, and outcome of the study. Particular emphasis was given and commented on the study design, population, sample size, modeling method, predictors, outcomes, discrimination and calibration of the model. All the models had acceptable discrimination ability (C-statistics >0.7) and good calibration (Hosmer-Lameshow P-value >0.05). Most common model used was multivariate logistic regression and most popular predictor was age.

Cardiac misconceptions in healthcare workers.

PubMed

Angus, Neil; Patience, Fiona; Maclean, Elizabeth; Corrigall, Helen; Bradbury, Ian; Thompson, David R; Atherton, Iain; Leslie, Stephen J

2012-12-01

Cardiac misconceptions are common and may have a detrimental effect on patients. Such misconceptions may be introduced or reinforced by vague and inconsistent advice from healthcare staff and can adversely affect health outcomes. To assess whether level of cardiac misconceptions significantly differs between groups of healthcare staff based on occupation. The 22-item York cardiac beliefs questionnaire (YCBQ) was administered to a convenience sample of healthcare staff (n = 263) in direct contact with cardiac patients. Data was also collected on the occupation of healthcare staff and years worked. Medical staff had the lowest mean score (17.5, CI 15.6-19.4), indicating fewest misconceptions, and unqualified healthcare workers had the highest mean score (32.1, CI 28.4-35.7). Analysis by ANOVA indicated differences between staff groups to be statistically significant (F = 17.66, p < 0.001). Length of time worked was found to be significantly associated with cardiac misconception score (Pearson's r = - 0.243, p < 0.001). Further analysis demonstrated that significant differences between mean group scores remained when years worked was defined as a covariate, F = 15.68, p < 0.001). There is significant variability in cardiac misconceptions in different groups of healthcare staff. Education to correct cardiac misconceptions should be particularly targeted at unqualified healthcare staff. The importance of maintaining appropriate ratios of qualified to unqualified healthcare staff in the care of cardiac patients is supported by this study.

The adverse health effects of chronic cannabis use.

PubMed

Hall, Wayne; Degenhardt, Louisa

2014-01-01

This paper summarizes the most probable of the adverse health effects of regular cannabis use sustained over years, as indicated by epidemiological studies that have established an association between cannabis use and adverse outcomes; ruled out reverse causation; and controlled for plausible alternative explanations. We have also focused on adverse outcomes for which there is good evidence of biological plausibility. The focus is on those adverse health effects of greatest potential public health significance--those that are most likely to occur and to affect a substantial proportion of regular cannabis users. These most probable adverse effects of regular use include a dependence syndrome, impaired respiratory function, cardiovascular disease, adverse effects on adolescent psychosocial development and mental health, and residual cognitive impairment. Copyright © 2013 John Wiley & Sons, Ltd.

36 CFR 800.6 - Resolution of adverse effects.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Resolution of adverse effects... PROTECTION OF HISTORIC PROPERTIES The section 106 Process § 800.6 Resolution of adverse effects. (a) Continue... the undertaking that could avoid, minimize, or mitigate adverse effects on historic properties. (1...

Adverse effects of cannabis.

PubMed

2011-01-01

Cannabis, Cannabis sativa L., is used to produce a resin that contains high levels of cannabinoids, particularly delta9-tetrahydrocannabinol (THC), which are psychoactive substances. Although cannabis use is illegal in France and in many other countries, it is widely used for its relaxing or euphoric effects, especially by adolescents and young adults. What are the adverse effects of cannabis on health? During consumption? And in the long term? Does cannabis predispose users to the development of psychotic disorders? To answer these questions, we reviewed the available evidence using the standard Prescrire methodology. The long-term adverse effects of cannabis are difficult to evaluate. Since and associated substances, with or without the user's knowledge. Tobacco and alcohol consumption, and particular lifestyles and behaviours are often associated with cannabis use. Some traits predispose individuals to the use of psychoactive substances in general. The effects of cannabis are dosedependent.The most frequently report-ed adverse effects are mental slowness, impaired reaction times, and sometimes accentuation of anxiety. Serious psychological disorders have been reported with high levels of intoxication. The relationship between poor school performance and early, regular, and frequent cannabis use seems to be a vicious circle, in which each sustains the other. Many studies have focused on the long-term effects of cannabis on memory, but their results have been inconclusive. There do not * About fifteen longitudinal cohort studies that examined the influence of cannabis on depressive thoughts or suicidal ideation have yielded conflicting results and are inconclusive. Several longitudinal cohort studies have shown a statistical association between psychotic illness and self-reported cannabis use. However, the results are difficult to interpret due to methodological problems, particularly the unknown reliability of self-reported data. It has not been possible to

Strategies for blood conservation in pediatric cardiac surgery

PubMed Central

Singh, Sarvesh Pal

2016-01-01

Cardiac surgery accounts for the majority of blood transfusions in a hospital. Blood transfusion has been associated with complications and major adverse events after cardiac surgery. Compared to adults it is more difficult to avoid blood transfusion in children after cardiac surgery. This article takes into account the challenges and emphasizes on the various strategies that could be implemented, to conserve blood during pediatric cardiac surgery. PMID:27716703

Acupuncture therapy related cardiac injury.

PubMed

Li, Xue-feng; Wang, Xian

2013-12-01

Cardiac injury is the most serious adverse event in acupuncture therapy. The causes include needling chest points near the heart, the cardiac enlargement and pericardial effusion that will enlarge the projected area on the body surface and make the proper depth of needling shorter, and the incorrect needling method of the points. Therefore, acupuncture practitioners must be familiar with the points of the heart projected area on the chest and the correct needling methods in order to reduce the risk of acupuncture therapy related cardiac injury.

Nitrates for the prevention of cardiac morbidity and mortality in patients undergoing non-cardiac surgery.

PubMed

Zhao, Na; Xu, Jin; Singh, Balwinder; Yu, Xuerong; Wu, Taixiang; Huang, Yuguang

2016-08-04

resolved differences by discussion and, when necessary, sought help and suggestions from a third review author. We used a random-effects model for data analysis. We included 27 randomized controlled trials (RCTs) (8244 participants analysed). Investigators reported 12 different comparisons of three different nitrates (nitroglycerin, isosorbide dinitrate and nicorandil) versus no treatment, placebo or other pharmacological interventions. All participants were older than 15 years of age. More than half of the trials used general anaesthesia. Surgical procedures in most trials were at low to moderate risk for perioperative cardiac complications. Only two comparisons including three studies reported the primary outcome - all-cause mortality up to 30 days post operation. Researchers reported other morbidity outcomes and adverse events in a variable and heterogeneous way, resulting in limited available data for inclusion in the meta-analysis. We determined that the overall methodological quality of included studies was fair to low, in accordance with risk of bias in most domains.In summary, we found no difference in the primary outcome - all-cause mortality up to 30 days post operation - when nitroglycerin was compared with no treatment (one study, 60 participants, 0/30 vs 1/30; (risk ratio (RR) 0.33, 95% confidence interval (CI) 0.01 to 7.87, very low-quality evidence based on GRADE criteria) or with placebo (two studies, 89 participants, 1/45 vs 0/44; RR 2.81, 95% CI 0.12 to 63.83, very low-quality evidence). Regarding our secondary outcomes, we noted no statistically significant differences in angina pectoris, acute myocardial infarction, acute heart failure, cardiac arrhythmia or cardiac arrest in any comparisons. In comparisons versus nitroglycerin, although more events of cardiac ischaemia were observed in participants receiving no treatment or placebo, we found no statistically significant differences in any comparisons, except the comparison of nicorandil versus placebo

36 CFR 800.5 - Assessment of adverse effects.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Assessment of adverse effects... PROTECTION OF HISTORIC PROPERTIES The section 106 Process § 800.5 Assessment of adverse effects. (a) Apply criteria of adverse effect. In consultation with the SHPO/THPO and any Indian tribe or Native Hawaiian...

A systematic evaluation of the potential effects of trichloroethylene exposure on cardiac development.

PubMed

Makris, Susan L; Scott, Cheryl Siegel; Fox, John; Knudsen, Thomas B; Hotchkiss, Andrew K; Arzuaga, Xabier; Euling, Susan Y; Powers, Christina M; Jinot, Jennifer; Hogan, Karen A; Abbott, Barbara D; Hunter, E Sidney; Narotsky, Michael G

2016-10-01

The 2011 EPA trichloroethylene (TCE) IRIS assessment, used developmental cardiac defects from a controversial drinking water study in rats (Johnson et al. [51]), along with several other studies/endpoints to derive reference values. An updated literature search of TCE-related developmental cardiac defects was conducted. Study quality, strengths, and limitations were assessed. A putative adverse outcome pathway (AOP) construct was developed to explore key events for the most commonly observed cardiac dysmorphologies, particularly those involved with epithelial-mesenchymal transition (EMT) of endothelial origin (EndMT); several candidate pathways were identified. A hypothesis-driven weight-of-evidence analysis of epidemiological, toxicological, in vitro, in ovo, and mechanistic/AOP data concluded that TCE has the potential to cause cardiac defects in humans when exposure occurs at sufficient doses during a sensitive window of fetal development. The study by Johnson et al. [51] was reaffirmed as suitable for hazard characterization and reference value derivation, though acknowledging study limitations and uncertainties. Published by Elsevier Inc.

Long-Term Overexpression of Hsp70 Does Not Protect against Cardiac Dysfunction and Adverse Remodeling in a MURC Transgenic Mouse Model with Chronic Heart Failure and Atrial Fibrillation

PubMed Central

Bernardo, Bianca C.; Sapra, Geeta; Patterson, Natalie L.; Cemerlang, Nelly; Kiriazis, Helen; Ueyama, Tomomi; Febbraio, Mark A.; McMullen, Julie R.

2015-01-01

Previous animal studies had shown that increasing heat shock protein 70 (Hsp70) using a transgenic, gene therapy or pharmacological approach provided cardiac protection in models of acute cardiac stress. Furthermore, clinical studies had reported associations between Hsp70 levels and protection against atrial fibrillation (AF). AF is the most common cardiac arrhythmia presenting in cardiology clinics and is associated with increased rates of heart failure and stroke. Improved therapies for AF and heart failure are urgently required. Despite promising observations in animal studies which targeted Hsp70, we recently reported that increasing Hsp70 was unable to attenuate cardiac dysfunction and pathology in a mouse model which develops heart failure and intermittent AF. Given our somewhat unexpected finding and the extensive literature suggesting Hsp70 provides cardiac protection, it was considered important to assess whether Hsp70 could provide protection in another mouse model of heart failure and AF. The aim of the current study was to determine whether increasing Hsp70 could attenuate adverse cardiac remodeling, cardiac dysfunction and episodes of arrhythmia in a mouse model of heart failure and AF due to overexpression of Muscle-Restricted Coiled-Coil (MURC). Cardiac function and pathology were assessed in mice at approximately 12 months of age. We report here, that chronic overexpression of Hsp70 was unable to provide protection against cardiac dysfunction, conduction abnormalities, fibrosis or characteristic molecular markers of the failing heart. In summary, elevated Hsp70 may provide protection in acute cardiac stress settings, but appears insufficient to protect the heart under chronic cardiac disease conditions. PMID:26660322

Long-Term Overexpression of Hsp70 Does Not Protect against Cardiac Dysfunction and Adverse Remodeling in a MURC Transgenic Mouse Model with Chronic Heart Failure and Atrial Fibrillation.

PubMed

Bernardo, Bianca C; Sapra, Geeta; Patterson, Natalie L; Cemerlang, Nelly; Kiriazis, Helen; Ueyama, Tomomi; Febbraio, Mark A; McMullen, Julie R

2015-01-01

Previous animal studies had shown that increasing heat shock protein 70 (Hsp70) using a transgenic, gene therapy or pharmacological approach provided cardiac protection in models of acute cardiac stress. Furthermore, clinical studies had reported associations between Hsp70 levels and protection against atrial fibrillation (AF). AF is the most common cardiac arrhythmia presenting in cardiology clinics and is associated with increased rates of heart failure and stroke. Improved therapies for AF and heart failure are urgently required. Despite promising observations in animal studies which targeted Hsp70, we recently reported that increasing Hsp70 was unable to attenuate cardiac dysfunction and pathology in a mouse model which develops heart failure and intermittent AF. Given our somewhat unexpected finding and the extensive literature suggesting Hsp70 provides cardiac protection, it was considered important to assess whether Hsp70 could provide protection in another mouse model of heart failure and AF. The aim of the current study was to determine whether increasing Hsp70 could attenuate adverse cardiac remodeling, cardiac dysfunction and episodes of arrhythmia in a mouse model of heart failure and AF due to overexpression of Muscle-Restricted Coiled-Coil (MURC). Cardiac function and pathology were assessed in mice at approximately 12 months of age. We report here, that chronic overexpression of Hsp70 was unable to provide protection against cardiac dysfunction, conduction abnormalities, fibrosis or characteristic molecular markers of the failing heart. In summary, elevated Hsp70 may provide protection in acute cardiac stress settings, but appears insufficient to protect the heart under chronic cardiac disease conditions.

A Review of Radiation Protection Solutions for the Staff in the Cardiac Catheterisation Laboratory.

PubMed

Badawy, Mohamed Khaldoun; Deb, Pradip; Chan, Robert; Farouque, Omar

2016-10-01

Adverse health effects of radiation exposure to staff in cardiac catheterisation laboratories have been well documented in the literature. Examples include increased risk of cataracts as well as possible malignancies. These risks can be partly mitigated by reducing scatter radiation exposure to staff during diagnostic and interventional cardiac procedures. There are currently commercially available radiation protection tools, including radioprotective caps, gloves, eyewear, thyroid collars, aprons, mounted shields, table skirts and patient drapes to protect staff from excessive radiation exposure. Furthermore, real-time dose feedback could lead to procedural changes that reduce operator dose. The objective of this review is to examine the efficacy of these tools and provide practical recommendations to reduce occupational radiation exposure with the aim of minimising long-term adverse health outcomes. 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.

Vidarabine, an Anti-Herpes Virus Agent, Protects Against the Development of Heart Failure With Relatively Mild Side-Effects on Cardiac Function in a Canine Model of Pacing-Induced Dilated Cardiomyopathy.

PubMed

Nakamura, Takashi; Fujita, Takayuki; Kishimura, Megumi; Suita, Kenji; Hidaka, Yuko; Cai, Wenqian; Umemura, Masanari; Yokoyama, Utako; Uechi, Masami; Ishikawa, Yoshihiro

2016-11-25

In heart failure patients, chronic hyperactivation of sympathetic signaling is known to exacerbate cardiac dysfunction. In this study, the cardioprotective effect of vidarabine, an anti-herpes virus agent, which we identified as a cardiac adenylyl cyclase inhibitor, in dogs with pacing-induced dilated cardiomyopathy (DCM) was evaluated. In addition, the adverse effects of vidarabine on basal cardiac function was compared to those of the β-blocker, carvedilol.Methods and Results:Vidarabine and carvedilol attenuated the development of pacing-induced systolic dysfunction significantly and with equal effectiveness. Both agents also inhibited the development of cardiac apoptosis and fibrosis and reduced the Na + -Ca 2+ exchanger-1 protein level in the heart. Importantly, carvedilol significantly enlarged the left ventricle and atrium; vidarabine, in contrast, did not. Vidarabine-treated dogs maintained cardiac response to β-AR stimulation better than carvedilol-treated dogs did. Vidarabine may protect against pacing-induced DCM with less suppression of basal cardiac function than carvedilol in a dog model. (Circ J 2016; 80: 2496-2505).

The Adverse Cardiac Effects of Di(2-ethylhexyl) phthalate and Bisphenol A

PubMed Central

Posnack, Nikki Gillum

2014-01-01

The ubiquitous nature of plastics has raised concerns pertaining to continuous exposure to plastic polymers and human health risks. Of particular concern is the use of endocrine-disrupting chemicals (EDCs) in plastic production, including Di(2-ethylhexyl) phthalate (DEHP) and Bisphenol A (BPA). Widespread and continuous exposure to DEHP and BPA occurs through dietary intake, inhalation, dermal and intravenous exposure via consumer products and medical devices. This article reviews the literature examining the relationship between DEHP and BPA exposure and cardiac toxicity. In vitro and in vivo experimental reports are outlined, as well as epidemiological studies which examine the association between these chemicals and cardiovascular outcomes. Gaps in our current knowledge are also discussed, along with future investigative endeavors that may help resolve whether DEHP and/or BPA exposure has a negative impact on cardiovascular physiology. PMID:24811950

Rare and very rare adverse effects of clozapine

PubMed Central

De Fazio, Pasquale; Gaetano, Raffaele; Caroleo, Mariarita; Cerminara, Gregorio; Maida, Francesca; Bruno, Antonio; Muscatello, Maria Rosaria; Moreno, Maria Jose Jaén; Russo, Emilio; Segura-García, Cristina

2015-01-01

Clozapine (CLZ) is the drug of choice for the treatment of resistant schizophrenia; however, its suitable use is limited by the complex adverse effects’ profile. The best-described adverse effects in the literature are represented by agranulocytosis, myocarditis, sedation, weight gain, hypotension, and drooling; nevertheless, there are other known adverse effects that psychiatrists should readily recognize and manage. This review covers the “rare” and “very rare” known adverse effects of CLZ, which have been accurately described in literature. An extensive search on the basis of predefined criteria was made using CLZ and its combination with adverse effects as keywords in electronic databases. Data show the association between the use of CLZ and uncommon adverse effects, including ischemic colitis, paralytic ileus, hematemesis, gastroesophageal reflux disease, priapism, urinary incontinence, pityriasis rosea, intertriginous erythema, pulmonary thromboembolism, pseudo-pheochromocytoma, periorbital edema, and parotitis, which are influenced by other variables including age, early diagnosis, and previous/current pharmacological therapies. Some of these adverse effects, although unpredictable, are often manageable if promptly recognized and treated. Others are serious and potentially life-threatening. However, an adequate knowledge of the drug, clinical vigilance, and rapid intervention can drastically reduce the morbidity and mortality related to CLZ treatment. PMID:26273202

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.

Adverse health effects of non-medical cannabis use.

PubMed

Hall, Wayne; Degenhardt, Louisa

2009-10-17

For over two decades, cannabis, commonly known as marijuana, has been the most widely used illicit drug by young people in high-income countries, and has recently become popular on a global scale. Epidemiological research during the past 10 years suggests that regular use of cannabis during adolescence and into adulthood can have adverse effects. Epidemiological, clinical, and laboratory studies have established an association between cannabis use and adverse outcomes. We focus on adverse health effects of greatest potential public health interest-that is, those that are most likely to occur and to affect a large number of cannabis users. The most probable adverse effects include a dependence syndrome, increased risk of motor vehicle crashes, impaired respiratory function, cardiovascular disease, and adverse effects of regular use on adolescent psychosocial development and mental health.

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

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.

Adverse effects of neuromuscular blockers and their antagonists.

PubMed

Naguib, M; Magboul, M M

1998-02-01

Among all the drugs used for general anaesthesia, neuromuscular blockers appear to play a prominent role in the incidence of severe adverse reactions. It now seems likely that most serious adverse drug reactions occurring during anaesthesia are immunological in type. The frequency of life-threatening anaphylactic or anaphylactoid reactions occurring during anaesthesia has been estimated to be between 1 in 1000 and 1 in 25,000 anaesthetic procedures, with the neuromuscular blockers being involved in 80% of cases. The mortality from such serious reactions is reported to be in the range of 3.4 to 6%. The highly immunogenic drug, suxamethonium chloride (succinylcholine), was found to be the most hazardous agent. Drug-specific immunoglobulin E antibodies to suxamethonium chloride and other neuromuscular blockers have been demonstrated. This sensitivity to neuromuscular blockers seems to be a long-lasting phenomenon. During anaesthesia, the clinical features of an allergic reaction are often masked. Tachycardia and circulatory collapse may be the only signs of an allergic reaction, and they are easily misdiagnosed. Bronchospasm is reported to be present in about 40% of cases. Successful management of these patients includes stabilisation during the acute reaction and avoidance of future reactions. The latter is based on the identification of the causative drug and potentially cross-reacting compounds. The use of suxamethonium chloride is associated with many other adverse effects, such as fasciculations, myalgia, potassium release, changes in the heart rate, increases in intragastric and intraocular pressures, and malignant hyperthermia. Because of the dangers of hyperkalaemic cardiac arrest after suxamethonium chloride administration in children with unrecognised muscular dystrophy, there have now been moves to limit the use of this drug in children. Although neuromuscular blockers are designed to specifically block nicotinic cholinergic receptors at the neuromuscular

Adverse effects of neuromuscular blockers and their antagonists.

PubMed

Naguib, M; Magboul, M M

1998-06-01

Among all the drugs used for general anesthesia, neuromuscular blockers appear to play a prominent role in the incidence of severe adverse reactions. It now seems likely that most serious adverse drug reactions occurring during anesthesia are immunological in type. The frequency of life-threatening anaphylactic or anaphylactoid reactions occurring during anesthesia has been estimated to be between 1 in 1000 and 1 in 25,000 anesthetic procedures, with the neuromuscular blockers being involved in 80% of cases. The mortality from such serious reactions is reported to be in the range of 3.4 to 6%. The highly immunogenic drug, suxamethonium chloride (succinylcholine), was found to be the most hazardous agent. Drug-specific immunoglobulin E antibodies to suxamethonium chloride and other neuromuscular blockers have been demonstrated. This sensitivity to neuromuscular blockers seems to be a long-lasting phenomenon. During anesthesia, the clinical features of an allergic reaction are often masked. Tachycardia and circulatory collapse may be the only signs of an allergic reaction, and they are easily misdiagnosed. Bronchospasm is reported to be present in about 40% of cases. Successful management of these patients includes stabilisation during the acute reaction and avoidance of future reactions. The latter is based on the identification of the causative drug and potentially cross-reacting compounds. The use of suxamethonium chloride is associated with many other adverse effects, such as fasciculations, myalgia, potassium release, changes in the heart rate, increases in intragastric and intraocular pressures, and malignant hyperthermia. Because of the dangers of hyperkalemic cardiac arrest suxamethonium chloride administration in children with unrecognised muscular dystrophy, there have now been moves to limit the use of this drug in children. Although neuromuscular blockers are designed to specifically block nicotinic cholinergic receptors at the neuromuscular junction

Effects of milrinone on left ventricular cardiac function during cooling in an intact animal model.

PubMed

Tveita, Torkjel; Sieck, Gary C

2012-08-01

Due to adverse effects of β-receptor agonists reported when applied during hypothermia, left ventricular (LV) cardiac effects of milrinone, a PDE3 inhibitor which mode of action is deprived the sarcolemmal β-receptor-G protein-PKA system, was tested during cooling to 15 °C. Sprague Dawley rats were instrumented to measure left ventricular (LV) pressure-volume changes using a Millar pressure-volume conductance catheter. Core temperature was reduced from 37 to 15 °C (60 min) using internal and external heat exchangers. Milrinone, or saline placebo, was given as continuous i.v. infusions for 30 min at 37 °C and during cooling. In normothermic controls continuous milrinone infusion for 90 min elevated cardiac output (CO) and stroke volume (SV) significantly. Significant differences in cardiac functional variables between the milrinone group and the saline control group during cooling to 15 °C were found: Compared to saline treated animals throughout cooling from 33 to 15 °CSV was significantly elevated in milrinone animals, the index of LV isovolumic relaxation, Tau, was significantly better preserved, and both HR and CO were significantly higher from 33 to 24 °C. Likewise, during cooling between 33 and 28 °C also LVdP/dt(max) was significantly higher in the milrinone group. Milrinone preserved LV systolic and diastolic function at a significantly higher level than in saline controls during cooling to 15 °C. In essential contrast to our previous results when using β-receptor agonists during hypothermia, the present experiment demonstrates the positive inotropic effects of milrinone on LV cardiac function during cooling to 15 °C. Copyright © 2012 Elsevier Inc. All rights reserved.

Association of comorbidity burden with abnormal cardiac mechanics: findings from the HyperGEN study.

PubMed

Selvaraj, Senthil; Aguilar, Frank G; Martinez, Eva E; Beussink, Lauren; Kim, Kwang-Youn A; Peng, Jie; Rasmussen-Torvik, Laura; Sha, Jin; Irvin, Marguerite R; Gu, C Charles; Lewis, Cora E; Hunt, Steven C; Arnett, Donna K; Shah, Sanjiv J

2014-04-29

Comorbidities are common in heart failure (HF), and the number of comorbidities has been associated with poor outcomes in HF patients. However, little is known about the effect of multiple comorbidities on cardiac mechanics, which could impact the pathogenesis of HF. We sought to determine the relationship between comorbidity burden and adverse cardiac mechanics. We performed speckle-tracking analysis on echocardiograms from the HyperGEN study (n=2150). Global longitudinal, circumferential, and radial strain, and early diastolic (e') tissue velocities were measured. We evaluated the association between comorbidity number and cardiac mechanics using linear mixed effects models to account for relatedness among subjects. The mean age was 51 ± 14 years, 58% were female, and 47% were African American. Dyslipidemia and hypertension were the most common comorbidities (61% and 58%, respectively). After adjusting for left ventricular (LV) mass index, ejection fraction, and several potential confounders, the number of comorbidities remained associated with all indices of cardiac mechanics except global circumferential strain (eg, β=-0.32 [95% CI -0.44, -0.20] per 1-unit increase in number of comorbidities for global longitudinal strain; β=-0.16 [95% CI -0.20, -0.11] for e' velocity; P ≤ 0.0001 for both comparisons). Results were similar after excluding participants with abnormal LV geometry (P<0.05 for all comparisons). Higher comorbidity burden is associated with worse cardiac mechanics, even in the presence of normal LV geometry. The deleterious effect of multiple comorbidities on cardiac mechanics may explain both the high comorbidity burden and adverse outcomes in patients who ultimately develop HF.

Oil Exposure Impairs In Situ Cardiac Function in Response to β-Adrenergic Stimulation in Cobia (Rachycentron canadum).

PubMed

Cox, Georgina K; Crossley, Dane A; Stieglitz, John D; Heuer, Rachael M; Benetti, Daniel D; Grosell, Martin

2017-12-19

Aqueous crude oil spills expose fish to varying concentrations of dissolved polycyclic aromatic hydrocarbons (PAHs), which can have lethal and sublethal effects. The heart is particularly vulnerable in early life stages, as PAH toxicity causes developmental cardiac abnormalities and impaired cardiovascular function. However, cardiac responses of juvenile and adult fish to acute oil exposure remain poorly understood. We sought to assess cardiac function in a pelagic fish species, the cobia (Rachycentron canadum), following acute (24 h) exposure to two ecologically relevant levels of dissolved PAHs. Cardiac power output (CPO) was used to quantify cardiovascular performance using an in situ heart preparation. Cardiovascular performance was varied using multiple concentrations of the β-adrenoceptor agonist isoproterenol (ISO) and by varying afterload pressures. Oil exposure adversely affected CPO with control fish achieving maximum CPO's (4 mW g -1 Mv) greater than that of oil-exposed fish (1 mW g -1 Mv) at ISO concentrations of 1 × 10 -6 M. However, the highest concentration of ISO (1 × 10 -5 M) rescued cardiac function. This indicates an interactive effect between oil-exposure and β-adrenergic stimulation and suggests if animals achieve very large increases in β-adrenergic stimulation it could play a compensatory role that may mitigate some adverse effects of oil-exposure in vivo.

Comparison of Levalbuterol and Racemic Albuterol Based on Cardiac Adverse Effects in Children

PubMed Central

Bio, Laura L.; Willey, Vincent J.; Poon, Cathy Y.

2011-01-01

OBJECTIVE To compare the cardiac effects of levalbuterol with those of racemic albuterol based on changes in heart rate (HR) in pediatric patients. METHODS The medical records of hospitalized children ages 1 month to 12 years, who received either levalbuterol or racemic albuterol via nebulizer for 3 consecutive doses between January 2006 and December 2008 were reviewed. The documented HR was collected prior to and after each administered dose of bronchodilator. The primary outcome was the largest percentage of change in HR between groups. Secondary outcomes of comparisons of the number of patients who had more than a 10% change in HR and incidence of tachycardia were included. RESULTS A total of 50 patients, 25 in each group, was included in the study. All patients in the racemic albuterol group received 2.5 mg per dose, while most of the patients in the levalbuterol group received 0.63 mg per dose (19 patients, 76%). Only 6 levalbuterol patients received a dose of 1.25 mg. Nineteen of 25 patients (76%) in the levalbuterol group were tachycardic prior to the first recorded dose compared to 15 patients (60%) in the racemic albuterol group (p = 0.36). The median of the largest percentage of change in HR was 4.1% (interquartile range [IQR], 1.8–8.7) in the levalbuterol group compared to 5% (IQR, 1.9–7.8) in the racemic albuterol group (p = 0.763). Four patients in the levalbuterol group experienced an HR increase of more than 10% compared to 5 patients in the racemic albuterol group (p = 1.0). CONCLUSION Levalbuterol and racemic albuterol bronchodilator therapies produced similar effects on HR. No clinically significant differences were detected in HR changes between the two treatment groups, despite administration of a larger equipotent albuterol dose in the racemic albuterol group than in the levalbuterol group. PMID:22479161

The Effects of Frailty in Patients Undergoing Elective Cardiac Surgery.

PubMed

Ad, Niv; Holmes, Sari D; Halpin, Linda; Shuman, Deborah J; Miller, Casey E; Lamont, Deborah

2016-04-01

The Society of Thoracic Surgeons (STS) recommends using gait speed as a marker of frailty to identify cardiac surgery patients at risk for adverse outcomes. However, a single marker of frailty may not provide consistently reliable risk information. We evaluated the impact of frailty and gait speed on patient outcomes after elective cardiac surgery. This was a prospective study of 167 older (≥65 years) coronary artery bypass grafting (CABG) and/or valve surgery patients. Patients were assessed using Cardiovascular Health Study (CHS) Frailty Index criteria: weight loss, exhaustion, physical activity, gait speed, and grip strength. Frailty was identified in 39 patients (23%) using CHS criteria. Frail patients had longer median intensive care unit stays (54 vs. 28 h, p = 0.003), longer median length of stay (8 vs. 5 days, p < 0.001), and greater likelihood of STS-defined complications (54% vs. 32%, p = 0.011) and discharge to an intermediate-care facility (45% vs. 12%, p < 0.001) but were not different from nonfrail patients on major outcome, operative mortality, or readmissions. After multivariate adjustment, frail and nonfrail patients were similar on perioperative outcomes. Absolute gait speed and slow gait speed using a cutoff were not related to incidence of STS-defined complications or major outcome in multivariate analyses. However, higher body mass index was correlated with slower gait speed (rs  = 0.30, p < 0.001). The CHS index did not identify "frail" patients at increased risk for adverse outcomes. No relationship was found between gait speed and outcome. There is a need for alternative multidimensional measures to assess frailty in cardiac surgical patients. doi: 10.1111/jocs.12699 (J Card Surg 2016;31:187-194). © 2016 Wiley Periodicals, Inc.

40 CFR 350.21 - Adverse health effects.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 29 2012-07-01 2012-07-01 false Adverse health effects. 350.21 Section... RIGHT-TO-KNOW INFORMATION: AND TRADE SECRET DISCLOSURES TO HEALTH PROFESSIONALS Trade Secrecy Claims § 350.21 Adverse health effects. The Governor or State emergency response commission shall identify the...

40 CFR 350.21 - Adverse health effects.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 29 2013-07-01 2013-07-01 false Adverse health effects. 350.21 Section... RIGHT-TO-KNOW INFORMATION: AND TRADE SECRET DISCLOSURES TO HEALTH PROFESSIONALS Trade Secrecy Claims § 350.21 Adverse health effects. The Governor or State emergency response commission shall identify the...

40 CFR 350.21 - Adverse health effects.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 28 2011-07-01 2011-07-01 false Adverse health effects. 350.21 Section... RIGHT-TO-KNOW INFORMATION: AND TRADE SECRET DISCLOSURES TO HEALTH PROFESSIONALS Trade Secrecy Claims § 350.21 Adverse health effects. The Governor or State emergency response commission shall identify the...

40 CFR 350.21 - Adverse health effects.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 27 2010-07-01 2010-07-01 false Adverse health effects. 350.21 Section... RIGHT-TO-KNOW INFORMATION: AND TRADE SECRET DISCLOSURES TO HEALTH PROFESSIONALS Trade Secrecy Claims § 350.21 Adverse health effects. The Governor or State emergency response commission shall identify the...

40 CFR 350.21 - Adverse health effects.

Code of Federal Regulations, 2014 CFR

2014-07-01

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

PubMed

Aversano, Thomas; Lemmon, Cynthia C; Liu, Li

2012-05-10

Performance of percutaneous coronary intervention (PCI) is usually restricted to hospitals with cardiac surgery on site. We conducted a noninferiority trial to compare the outcomes of PCI performed at hospitals without and those with on-site cardiac surgery. We randomly assigned participants to undergo PCI at a hospital with or without on-site cardiac surgery. Patients requiring primary PCI were excluded. The trial had two primary end points: 6-week mortality and 9-month incidence of major adverse cardiac events (the composite of death, Q-wave myocardial infarction, or target-vessel revascularization). Noninferiority margins for the risk difference were 0.4 percentage points for mortality at 6 weeks and 1.8 percentage points for major adverse cardiac events at 9 months. A total of 18,867 patients were randomly assigned in a 3:1 ratio to undergo PCI at a hospital without on-site cardiac surgery (14,149 patients) or with on-site cardiac surgery (4718 patients). The 6-week mortality rate was 0.9% at hospitals without on-site surgery versus 1.0% at those with on-site surgery (difference, -0.04 percentage points; 95% confidence interval [CI], -0.31 to 0.23; P=0.004 for noninferiority). The 9-month rates of major adverse cardiac events were 12.1% and 11.2% at hospitals without and those with on-site surgery, respectively (difference, 0.92 percentage points; 95% CI, 0.04 to 1.80; P=0.05 for noninferiority). The rate of target-vessel revascularization was higher in hospitals without on-site surgery (6.5% vs. 5.4%, P=0.01). We found that PCI performed at hospitals without on-site cardiac surgery was noninferior to PCI performed at hospitals with on-site cardiac surgery with respect to mortality at 6 weeks and major adverse cardiac events at 9 months. (Funded by the Cardiovascular Patient Outcomes Research Team [C-PORT] participating sites; ClinicalTrials.gov number, NCT00549796.).

A rare adverse effect of metronidazole: nervous system symptoms.

PubMed

Kafadar, Ihsan; Moustafa, Fatma; Yalçın, Koray; Klç, Betül Aydn

2013-06-01

Metronidazole, as a 5-nitroimidazole compound, is effective on anaerobic bacteria and protozoon diseases. Mostly, metronidazole is a tolerable drug but rarely presents serious adverse effects on the nervous system. In case of these adverse effects, treatment must be stopped.In this report, a 3-year-old child hospitalized because of diarrhea is presented. During the metronidazole treatment, loss of sight, vertigo, ataxia, and headache occurred as the adverse effects. By this report, we want to express the rare adverse effects of drugs in the differential diagnoses of nervous system diseases.

Depression and Cardiac Disease: Epidemiology, Mechanisms, and Diagnosis

PubMed Central

Huffman, Jeff C.; Celano, Christopher M.; Beach, Scott R.; Motiwala, Shweta R.; Januzzi, James L.

2013-01-01

In patients with cardiovascular disease (CVD), depression is common, persistent, and associated with worse health-related quality of life, recurrent cardiac events, and mortality. Both physiological and behavioral factors—including endothelial dysfunction, platelet abnormalities, inflammation, autonomic nervous system dysfunction, and reduced engagement in health-promoting activities—may link depression with adverse cardiac outcomes. Because of the potential impact of depression on quality of life and cardiac outcomes, the American Heart Association has recommended routine depression screening of all cardiac patients with the 2- and 9-item Patient Health Questionnaires. However, despite the availability of these easy-to-use screening tools and effective treatments, depression is underrecognized and undertreated in patients with CVD. In this paper, we review the literature on epidemiology, phenomenology, comorbid conditions, and risk factors for depression in cardiac disease. We outline the associations between depression and cardiac outcomes, as well as the mechanisms that may mediate these links. Finally, we discuss the evidence for and against routine depression screening in patients with CVD and make specific recommendations for when and how to assess for depression in this high-risk population. PMID:23653854

Pregnancy as a cardiac stress model

PubMed Central

Chung, Eunhee; Leinwand, Leslie A.

2014-01-01

Cardiac hypertrophy occurs during pregnancy as a consequence of both volume overload and hormonal changes. Both pregnancy- and exercise-induced cardiac hypertrophy are generally thought to be similar and physiological. Despite the fact that there are shared transcriptional responses in both forms of cardiac adaptation, pregnancy results in a distinct signature of gene expression in the heart. In some cases, however, pregnancy can induce adverse cardiac events in previously healthy women without any known cardiovascular disease. Peripartum cardiomyopathy is the leading cause of non-obstetric mortality during pregnancy. To understand how pregnancy can cause heart disease, it is first important to understand cardiac adaptation during normal pregnancy. This review provides an overview of the cardiac consequences of pregnancy, including haemodynamic, functional, structural, and morphological adaptations, as well as molecular phenotypes. In addition, this review describes the signalling pathways responsible for pregnancy-induced cardiac hypertrophy and angiogenesis. We also compare and contrast cardiac adaptation in response to disease, exercise, and pregnancy. The comparisons of these settings of cardiac hypertrophy provide insight into pregnancy-associated cardiac adaptation. PMID:24448313

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

Perinatal outcomes associated with abnormal cardiac remodeling in women with treated chronic hypertension.

PubMed

Ambia, Anne M; Morgan, Jamie L; Wells, C Edward; Roberts, Scott W; Sanghavi, Monika; Nelson, David B; Cunningham, F Gary

2018-05-01

Adverse maternal outcomes associated with chronic hypertension include accelerated hypertension and resultant target organ damage. One example is long-standing hypertension leading to maternal cardiac dysfunction. Our group has previously identified that features of such injury manifest as cardiac remodeling with left ventricular hypertrophy. Moreover, these features of cardiac remodeling identified in women with chronic hypertension during pregnancy were associated with adverse perinatal outcomes. Recent definitions of maternal cardiac remodeling using echocardiography have been expanded to include measurements of wall thickness. We hypothesized that these new features characterizing cardiac remodeling in women with chronic hypertension may also be associated with adverse perinatal outcomes. There were 3 aims in this study of women with treated chronic hypertension during pregnancy: to (1) apply the updated definitions of maternal cardiac remodeling; (2) elucidate whether these features of cardiac remodeling were associated with adverse perinatal outcomes; and (3) determine which, if any, of the newly defined cardiac remodeling strata were most damaging when compared to women with normal cardiac geometry. This was a retrospective study of women with treated chronic hypertension during pregnancy delivered from January 2009 through January 2016. Cardiac remodeling was categorized by left ventricular mass index and relative wall thickness into 4 groups determined using the 2015 American Society of Echocardiography guidelines: normal geometry, concentric remodeling, eccentric hypertrophy, and concentric hypertrophy. Perinatal outcomes were analyzed according to each category of cardiac remodeling compared with outcomes in women with normal geometry. A total of 314 women with treated chronic hypertension underwent echocardiography at a mean gestational age of 17.9 weeks. There were no differences between maternal age (P = .896), habitus (P = .36), or duration of

Adverse effects of ketoconazole in dogs--a retrospective study.

PubMed

Mayer, Ursula K; Glos, Katharina; Schmid, Matthias; Power, Helen T; Bettenay, Sonya V; Mueller, Ralf S

2008-08-01

Although ketoconazole has been used extensively in dogs for the treatment of various fungal infections, information about adverse effects is mainly anecdotal. Common adverse effects in humans include dose-dependant anorexia, nausea and vomiting, allergic rashes and pruritus. Drug-induced hepatitis is very rare, but potentially fatal. The aim of this study was to evaluate the type and frequency of adverse effects associated with ketoconazole therapy in dogs treated for skin diseases and any possible influence of dosage, duration of therapy, signalment or concurrent medication. The medical records of 632 dogs treated with ketoconazole (2.6-33.4 mg/kg) were reviewed. Adverse effects occurred in 14.6% (92 dogs) and included vomiting (7.1%), anorexia (4.9%), lethargy (1.9%), diarrhea (1.1%), pruritus (0.6%), erythema (0.3%) and other adverse effects (2.5%). Of the dogs with other adverse effects, four of 16 (25%) were ataxic and three of these received concurrent ivermectin. Adverse effects were significantly more often recorded in dogs concurrently treated with ciclosporin (P = 0.034) or ivermectin (P = 0.007). Increased liver enzyme levels were reported rarely, and icterus was not seen in any of the dogs. However, monitoring liver enzymes during therapy is recommended, although this might not necessarily prevent severe idiosyncratic hepatotoxicity.

Clinical outcomes and adverse effect monitoring in allergic rhinitis.

PubMed

Juniper, Elizabeth F; Ståhl, Elisabeth; Doty, Richard L; Simons, F Estelle R; Allen, David B; Howarth, Peter H

2005-03-01

reduced or absent CNS sedative effects. Therefore, the CNS effects are entirely avoidable, and the first-generation H 1 -antihistamines should no longer be used in the management of allergic rhinitis. The considerably rarer but potentially very serious cardiac arrhythmogenic effects of H 1 -antihistamines are appreciated to be molecule-specific rather than class-specific. The in vitro screening of new compounds to eliminate the further development of those with cardiotoxicity ideally will lead to this adverse effect being historic. The incorporation of electrocardiogram recording in clinical trials provides direct information relating to prolongation of QT interval corrected for heart rate. Although administered at low doses, intranasal steroids still have the potential for systemic absorption and adverse consequences. However, it is appreciated that meaningful differences exist in the bioavailability of different steroid molecules, and although a small but statistically significant effect on growth in children has been identified with the long-term use of intranasal beclomethasone when administered twice daily for 1 year, this is not evident with all intranasal steroids. In addition, twice-daily intranasal steroid administration may have more effect--from the endocrinologic perspective--than once-daily administration in the morning, which coincides better with the natural diurnal variation in cortisol. Thus, once-daily intranasal steroid administration is preferable, and when used in studies in children, measurement of height change during the study period is an important outcome variable together with other indices of systemic steroid bioavailability (eg, tests of hypothalamic-pituitary-adrenal axis function). These considerations have even greater relevance if children are concurrently also receiving inhaled steroids for asthma, because the total steroid load will be greater.

Prenatal exposure to methyldopa leading to hypertensive crisis and cardiac failure in a neonate.

PubMed

Su, Jennifer A; Tang, William; Rivero, Niurka; Bar-Cohen, Yaniv

2014-05-01

A 2-week-old infant with normal intracardiac anatomy presented to the emergency department in a hypertensive crisis with acute cardiac failure. Despite extensive evaluation, no underlying disease was found. The patient's hypertension and cardiac dysfunction resolved after 1 week of supportive care in the PICU, and she was discharged within 2 weeks of presentation. The patient's history revealed transplacental exposure to the α-adrenergic agonist methyldopa for 10 weeks before delivery. Her age at presentation and the self-limited nature of cardiac sequelae with complete resolution of cardiac dysfunction suggest withdrawal effects from this exposure. Whereas the rebound hypertensive effects of α-adrenergic agonists are well established in the adult population, this report shows an unusual adverse outcome of in utero exposure to methyldopa. Copyright © 2014 by the American Academy of Pediatrics.

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

Comparison of the cardiac electrophysiology and general toxicology of two formulations of intravenous amiodarone in dogs.

PubMed

Cushing, Daniel J; Cooper, Warren D; Gralinski, Michael R; Lipicky, Raymond J; Kudenchuk, Peter J; Kowey, Peter R

2009-09-01

Intravenous amiodarone (AIV) must be administered slowly after dilution to avoid hypotension, which is due to the cosolvents polysorbate 80 and benzyl alcohol used in its formulation. PM101 is a formulation of amiodarone devoid of these cosolvents, which enables bolus administration. We evaluated any potential toxicity or exaggerated adverse cardiac electrophysiologic effects of PM101 compared with AIV and control. Beagle dogs were treated with the human-equivalent amiodarone loading dose (2.14 mg/kg) with PM101 (bolus push) or AIV (10 min infusion in the toxicology study and bolus push in the electrophysiology study) followed by maintenance infusion (0.014 mg kg(-1) min(-1) through 6 h followed by 0.007 mg kg(-1) min(-1) through 14 days) or a control. General toxicology was assessed in conscious dogs over 14 days. Cardiac electrophysiology was assessed in a separate cohort of anesthetized dogs during the first 20 min of dosing. In the toxicology study, dosing in all animals in the AIV group was terminated within 17 min of initiation due to a severe hypersensitivity reaction. There were no acute adverse clinical signs in the PM101 or control groups. There were no significant effects on body weight or ECG parameters, and no adverse histomorphologic changes were seen in dogs that received PM101 or AIV. No significant exaggerated cardiac electrophysiologic effects of the approved doses PM101 or AIV were observed. PM101 may represent a formulation of intravenous amiodarone that could be administered rapidly without dilution in the setting of life-threatening cardiac arrhythmias.

High-intensity interval training versus moderate-intensity continuous training within cardiac rehabilitation: a systematic review and meta-analysis.

PubMed

Hannan, Amanda L; Hing, Wayne; Simas, Vini; Climstein, Mike; Coombes, Jeff S; Jayasinghe, Rohan; Byrnes, Joshua; Furness, James

2018-01-01

Aerobic capacity has been shown to be inversely proportionate to cardiovascular mortality and morbidity and there is growing evidence that high-intensity interval training (HIIT) appears to be more effective than moderate-intensity continuous training (MICT) in improving cardiorespiratory fitness within the cardiac population. Previously published systematic reviews in cardiovascular disease have neither investigated the effect that the number of weeks of intervention has on cardiorespiratory fitness changes, nor have adverse events been collated. We aimed to undertake a systematic review and meta-analysis of randomized controlled trials (RCTs) within the cardiac population that investigated cardiorespiratory fitness changes resulting from HIIT versus MICT and to collate adverse events. A critical narrative synthesis and meta-analysis was conducted after systematically searching relevant databases up to July 2017. We searched for RCTs that compared cardiorespiratory fitness changes resulting from HIIT versus MICT interventions within the cardiac population. Seventeen studies, involving 953 participants (465 for HIIT and 488 for MICT) were included in the analysis. HIIT was significantly superior to MICT in improving cardiorespiratory fitness overall (SMD 0.34 mL/kg/min; 95% confidence interval [CI; 0.2-0.48]; p <0.00001; I 2 =28%). There were no deaths or cardiac events requiring hospitalization reported in any study during training. Overall, there were more adverse events reported as a result of the MICT (n=14) intervention than the HIIT intervention (n=9). However, some adverse events (n=5) were not classified by intervention group. HIIT is superior to MICT in improving cardiorespiratory fitness in participants of cardiac rehabilitation (CR). Improvements in cardiorespiratory fitness are significant for CR programs of >6-week duration. Programs of 7-12 weeks' duration resulted in the largest improvements in cardiorespiratory fitness for patients with coronary

High-intensity interval training versus moderate-intensity continuous training within cardiac rehabilitation: a systematic review and meta-analysis

PubMed Central

Hannan, Amanda L; Hing, Wayne; Simas, Vini; Climstein, Mike; Coombes, Jeff S; Jayasinghe, Rohan; Byrnes, Joshua; Furness, James

2018-01-01

Background Aerobic capacity has been shown to be inversely proportionate to cardiovascular mortality and morbidity and there is growing evidence that high-intensity interval training (HIIT) appears to be more effective than moderate-intensity continuous training (MICT) in improving cardiorespiratory fitness within the cardiac population. Previously published systematic reviews in cardiovascular disease have neither investigated the effect that the number of weeks of intervention has on cardiorespiratory fitness changes, nor have adverse events been collated. Objective We aimed to undertake a systematic review and meta-analysis of randomized controlled trials (RCTs) within the cardiac population that investigated cardiorespiratory fitness changes resulting from HIIT versus MICT and to collate adverse events. Methods A critical narrative synthesis and meta-analysis was conducted after systematically searching relevant databases up to July 2017. We searched for RCTs that compared cardiorespiratory fitness changes resulting from HIIT versus MICT interventions within the cardiac population. Results Seventeen studies, involving 953 participants (465 for HIIT and 488 for MICT) were included in the analysis. HIIT was significantly superior to MICT in improving cardiorespiratory fitness overall (SMD 0.34 mL/kg/min; 95% confidence interval [CI; 0.2–0.48]; p<0.00001; I2=28%). There were no deaths or cardiac events requiring hospitalization reported in any study during training. Overall, there were more adverse events reported as a result of the MICT (n=14) intervention than the HIIT intervention (n=9). However, some adverse events (n=5) were not classified by intervention group. Conclusion HIIT is superior to MICT in improving cardiorespiratory fitness in participants of cardiac rehabilitation (CR). Improvements in cardiorespiratory fitness are significant for CR programs of >6-week duration. Programs of 7–12 weeks’ duration resulted in the largest improvements in

Echocardiography in cardiac arrest: An emergency medicine review.

PubMed

Long, Brit; Alerhand, Stephen; Maliel, Kurian; Koyfman, Alex

2018-03-01

Cardiac arrest management primarily focuses on optimal chest compressions and early defibrillation for shockable cardiac rhythms. Non-shockable rhythms such as pulseless electrical activity (PEA) and asystole present challenges in management. Point-of-care ultrasound (POCUS) in cardiac arrest is promising. This review provides a focused assessment of POCUS in cardiac arrest, with an overview of transthoracic (TTE) and transesophageal echocardiogram (TEE), uses in arrest, and literature support. Cardiac arrest can be distinguished between shockable and non-shockable rhythms, with management varying based on the rhythm. POCUS provides a diagnostic and prognostic tool in the emergency department (ED), which may improve accuracy in clinical decision-making. Several protocols incorporate POCUS based on different cardiac views. TTE includes parasternal long axis, parasternal short axis, apical 4-chamber, and subxiphoid views, which may be used in cardiac arrest for diagnosis of underlying cause and potential prognostication. TEE is conducted by inserting the probe into the esophagus of intubated patients, with several studies evaluating its use in cardiac arrest. It is associated with few adverse effects, while allowing continued compressions (and evaluation of those compressions) and not interrupting resuscitation efforts. POCUS is a valuable diagnostic and prognostic tool in cardiac arrest, with recent literature supporting its diagnostic ability. TTE can guide resuscitation efforts dependent on the rhythm, though TTE should not interrupt other resuscitation measures. TEE can be useful during arrest, but further studies based in the ED are needed. Published by Elsevier Inc.

Geraniol alleviates diabetic cardiac complications: Effect on cardiac ischemia and oxidative stress.

PubMed

El-Bassossy, Hany M; Ghaleb, Hanna; Elberry, Ahmed A; Balamash, Khadijah S; Ghareib, Salah A; Azhar, Ahmad; Banjar, Zainy

2017-04-01

The present study was planned to assess the possible protective effect of geraniol on cardiovascular complications in an animal model with diabetes. Diabetes was induced in rats by a single streptozotocin injection. In the treated group, geraniol (150mgkg -1 day -1 ) was administered orally starting from the 15th day after induction of diabetes, and ending after 7 weeks; diabetic control rats were given vehicle for the same period. At the end of the study, cardiac contractility was assessed by using a Millar microtip catheter in anesthetised rats, and cardiac conductivity determined by a surface ECG. Serum levels of glucose, cholesterol, triglyceride and adiponectin as well as urine 8-isoprostane were determined. In addition, cardiac superoxide dismutase (SOD) and catalase activity were measured. Geraniol administration significantly alleviated the attenuated cardiac systolic function associated with diabetes as indicated by inhibiting the decrease in the rate of rise (dP/dt max ) in ventricular pressure and the increase in systolic duration observed in diabetic rats. In addition, geraniol alleviated impaired diastolic function as shown by inhibiting the decrease in the rate of fall (dP/dt min ) in ventricular pressure and increased isovolumic relaxation constant (Tau) observed in diabetic rats. ECG recordings showed that geraniol prevented any increase in QTc and T-peak-T-end intervals, and markers of LV ischemia and arrhythmogenesis, seen in diabetic animals. Geraniol suppressed the exaggerated oxidative stress as evidenced by preventing the increase in 8-isoprotane. In diabetic heart tissue, geraniol prevented the inhibition in catalase activity but did not affect the heart SOD. Geraniol partially reduced hyperglycemia, prevented the hypercholesterolemia, but did not affect the serum level of adiponectin in diabetic animals. Results obtained in this study suggest that geraniol provides a potent protective effect against cardiac dysfunction induced by diabetes

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.

The two sides of adversity: the effect of distant versus recent adversity on updating emotional content in working memory.

PubMed

Levens, Sara M; Armstrong, Laura Marie; Orejuela-Dávila, Ana I; Alverio, Tabitha

2017-09-01

Previous research suggests that adversity can have both adaptive and maladaptive effects, yet the emotional and working memory processes that contribute to more or less adaptive outcomes are unclear. The present study sought to investigate how updating emotional content differs in adolescents who have experienced past, recent, or no adversity. Participants who had experienced distant adversity (N = 53), no adversity (N = 58), or recent adversity only (N = 20) performed an emotion n-back task with emotional facial expressions. Results revealed that the distant adversity group exhibited significantly faster reaction times (RTs) than the no adversity and recent adversity only groups. In contrast, the recent adversity only group exhibited significantly slower RTs and more errors than the distant adversity and no adversity groups. These results suggest an emotion and executive control pathway by which both the benefits and negative effects of adversity may be conferred. Results also highlight the importance of time in assessing the impact of adversity.

Adverse cardiac events in children with Williams syndrome undergoing cardiovascular surgery: An analysis of the Society of Thoracic Surgeons Congenital Heart Surgery Database.

PubMed

Hornik, Christoph P; Collins, Ronnie Thomas; Jaquiss, Robert D B; Jacobs, Jeffrey P; Jacobs, Marshall L; Pasquali, Sara K; Wallace, Amelia S; Hill, Kevin D

2015-06-01

Patients with Williams syndrome (WS) undergoing cardiac surgery are at risk for major adverse cardiac events (MACE). Prevalence and risk factors for such events have not been well described. We sought to define frequency and risk of MACE in patients with WS using a multicenter clinical registry. We identified cardiac operations performed in patients with WS using the Society of Thoracic Surgeons Congenital Heart Surgery Database (2000-2012). Operations were divided into 4 groups: isolated supravalvular aortic stenosis, complex left ventricular outflow tract (LVOT), isolated right ventricular outflow tract (RVOT), and combined LVOT/RVOT procedures. The proportion of patients with MACE (in-hospital mortality, cardiac arrest, or postoperative mechanical circulatory support) was described and the association with preoperative factors was examined. Of 447 index operations (87 centers), median (interquartile range) age and weight at surgery were 2.4 years (0.6-7.4 years) and 10.6 kg (6.5-21.5 kg), respectively. Mortality occurred in 20 patients (5%). MACE occurred in 41 patients (9%), most commonly after combined LVOT/RVOT (18 out of 87; 21%) and complex LVOT (12 out of 131; 9%) procedures, but not after isolated RVOT procedures. Odds of MACE decreased with age (odds ratio [OR], 0.99; 95% confidence interval [CI], 0.98-0.99), weight (OR, 0.97; 95% CI, 0.93-0.99), but increased in the presence of any preoperative risk factor (OR, 2.08; 95% CI, 1.06-4.00), and in procedures involving coronary artery repair (OR, 5.37; 95% CI, 2.05-14.06). In this multicenter analysis, MACE occurred in 9% of patients with WS undergoing cardiac surgery. Demographic and operative characteristics were associated with risk. Further study is needed to elucidate mechanisms of MACE in this high-risk population. Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Adverse effects of methotrexate in three psoriatic arthritis patients.

PubMed

Maejima, Hideki; Watarai, Akira; Nakano, Toshiaki; Katayama, Chieko; Nishiyama, Hiromi; Katsuoka, Kensei

2014-04-01

Methotrexate, a folic acid analogue with anti-proliferative and anti-inflammatory effects, is commonly used to treat patients with severe destructive psoriatic arthritis and has considerable efficacy. Combined anti-tumor necrosis factor and MTX therapy result in less treatment discontinuation due to adverse events. Despite its efficacy, MTX may result in adverse effects including hepatic, pulmonary, and renal toxicity as well as lymphoproliferative disorders and predisposition to infection. We herein report rare adverse effects of MTX treatment, specifically asymptomatic pulmonary tuberculosis, renal cell carcinoma, and lateral uveitis, in three psoriatic arthritis patients treated with MTX. MTX is an important drug for the treatment for psoriatic arthritis patient, but an awareness of the possible adverse effects is needed.

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.

[Vasopressin intravenous infusion causes dose dependent adverse cardiovascular effects in anesthetized dogs.

PubMed

Martins, Luiz Cláudio; Sabha, Maricene; Paganelli, Maria Ondina; Coelho, Otávio Rizzi; Ferreira-Melo, Silvia Elaine; Moreira, Marcos Mello; Cavalho, Adriana Camargo de; Araujo, Sebastião; Moreno Junior, Heitor

2010-01-15

BACKGROUND: Arginine vasopressin (AVP) has been broadly used in the management of vasodilatory shock. However, there are many concerns regarding its clinical use, especially in high doses, as it can be associated with adverse cardiovascular events. OBJECTIVE: To investigate the cardiovascular effects of AVP in continuous IV infusion on hemodynamic parameters in dogs. METHODS: Sixteen healthy mongrel dogs, anesthetized with pentobarbital were intravascularly catheterized, and randomly assigned to: control (saline-placebo; n=8) and AVP (n=8) groups. The study group was infused with AVP for three consecutive 10-minute periods at logarithmically increasing doses (0.01; 0.1 and 1.0U/kg/min), at them 20-min intervals. Heart rate (HR) and intravascular pressures were continuously recorded. Cardiac output was measured by the thermodilution method. RESULTS: No significant hemodynamic effects were observed during 0.01U/kg/min of AVP infusion, but at higher doses (0.1 and 1.0U/kg/min) a progressive increase in mean arterial pressure (MAP) and systemic vascular resistance index (SVRI) were observed, with a significant decrease in HR and the cardiac index (CI). A significant increase in the pulmonary vascular resistance index (PVRI) was also observed with the 1.0U/kg/min dose, mainly due to the decrease in the CI. CONCLUSION: AVP, when administered at doses between 0.1 and 1.0U/kg/min, induced significant increases in MAP and SVRI, with negative inotropic and chronotropic effects in healthy animals. Although these doses are ten to thousand times greater than those routinely used for the management of vasodilatory shock, our data confirm that AVP might be used carefully and under strict hemodynamic monitoring in clinical practice, especially if doses higher than 0.01 U/kg/min are needed. Martins, LC et al.

Adverse Effects of Electronic Cigarette Use: A Concept Mapping Approach

PubMed Central

Nasim, Aashir; Rosas, Scott

2016-01-01

Abstract Introduction: Electronic cigarette (ECIG) use has grown rapidly in popularity within a short period of time. As ECIG products continue to evolve and more individuals begin using ECIGs, it is important to understand the potential adverse effects that are associated with ECIG use. The purpose of this study was to examine and describe the acute adverse effects associated with ECIG use. Methods: This study used an integrated, mixed-method participatory approach called concept mapping (CM). Experienced ECIG users ( n = 85) provided statements that answered the focus prompt “A specific negative or unpleasant effect (ie, physical or psychological) that I have experienced either during or immediately after using an electronic cigarette device is…” in an online program. Participants sorted these statements into piles of common themes and rated each statement. Using multidimensional scaling and hierarchical cluster analysis, a concept map of the adverse effects statements was created. Results: Participants generated 79 statements that completed the focus prompt and were retained by researchers. Analysis generated a map containing five clusters that characterized perceived adverse effects of ECIG use: Stigma, Worry/Guilt, Addiction Signs, Physical Effects, and Device/Vapor Problems. Conclusions: ECIG use is associated with adverse effects that should be monitored as ECIGs continue to grow in popularity. If ECIGs are to be regulated, policies should be created that minimize the likelihood of user identified adverse effects. Implications: This article provides a list of adverse effects reported by experienced ECIG users. This article organizes these effects into a conceptual model that may be useful for better understanding the adverse outcomes associated with ECIG use. These identified adverse effects may be useful for health professionals and policy makers. Health professionals should be aware of potential negative health effects that may be associated with

Adverse Effects of GLP-1 Receptor Agonists

PubMed Central

Filippatos, Theodosios D.; Panagiotopoulou, Thalia V.; Elisaf, Moses S.

2014-01-01

Glucagon-like peptide-1 (GLP-1) receptor agonists are a class of injective anti-diabetic drugs that improve glycemic control and many other atherosclerosis-related parameters in patients with type 2 diabetes (T2D). However, the use of this relatively new class of drugs may be associated with certain adverse effects. Concerns have been expressed regarding the effects of these drugs on pancreatic and thyroid tissue, since animal studies and analyses of drug databases indicate an association of GLP-1 receptor agonists with pancreatitis, pancreatic cancer, and thyroid cancer. However, several meta-analyses failed to confirm a cause-effect relation between GLP-1 receptor agonists and the development of these adverse effects. One benefit of GLP-1 receptor agonists is that they do not cause hypoglycemia when combined with metformin or thiazolidinediones, but the dose of concomitant sulphonylurea or insulin may have to be decreased to reduce the risk of hypoglycemic episodes. On the other hand, several case reports have linked the use of these drugs, mainly exenatide, with the occurrence of acute kidney injury, primarily through hemodynamic derangement due to nausea, vomiting, and diarrhea. The most common symptoms associated with the use of GLP-1 receptor agonists are gastrointestinal symptoms, mainly nausea. Other common adverse effects include injection site reactions, headache, and nasopharyngitis, but these effects do not usually result in discontinuation of the drug. Current evidence shows that GLP-1 receptor agonists have no negative effects on the cardiovascular risk of patients with T2D. Thus, GLP-1 receptor agonists appear to have a favorable safety profile, but ongoing trials will further assess their cardiovascular effects. The aim of this review is to analyze critically the available data regarding adverse events of GLP-1 receptor agonists in different anatomic systems published in Pubmed and Scopus. Whenever possible, certain differences between GLP-1

Dual Endothelin-A/Endothelin-B Receptor Blockade and Cardiac Remodeling in Heart Failure With Preserved Ejection Fraction

PubMed Central

Valero-Munoz, Maria; Li, Shanpeng; Wilson, Richard M.; Boldbaatar, Batbold; Iglarz, Marc; Sam, Flora

2017-01-01

Background Despite the increasing prevalence of heart failure with preserved ejection fraction (HFpEF) in humans, there remains no evidence-based therapies for HFpEF. Endothelin-1 (ET-1) antagonists are a possibility because elevated ET-1 levels are associated with adverse cardiovascular effects, such as arterial and pulmonary vasoconstriction, impaired left ventricular (LV) relaxation, and stimulation of LV hypertrophy. LV hypertrophy is a common phenotype in HFpEF, particularly when associated with hypertension. Methods and Results In the present study, we found that ET-1 levels were significantly elevated in patients with chronic stable HFpEF. We then sought to investigate the effects of chronic macitentan, a dual ET-A/ET-B receptor antagonist, on cardiac structure and function in a murine model of HFpEF induced by chronic aldosterone infusion. Macitentan caused LV hypertrophy regression independent of blood pressure changes in HFpEF. Although macitentan did not modulate diastolic dysfunction in HFpEF, it significantly reduced wall thickness and relative wall thickness after 2 weeks of therapy. In vitro studies showed that macitentan decreased the aldosterone-induced cardiomyocyte hypertrophy. These changes were mediated by a reduction in the expression of cardiac myocyte enhancer factor 2a. Moreover, macitentan improved adverse cardiac remodeling, by reducing the stiffer cardiac collagen I and titin n2b expression in the left ventricle of mice with HFpEF. Conclusions These findings indicate that dual ET-A/ET-B receptor inhibition improves HFpEF by abrogating adverse cardiac remodeling via antihypertrophic mechanisms and by reducing stiffness. Additional studies are needed to explore the role of dual ET-1 receptor antagonists in patients with HFpEF. PMID:27810862

Dual Endothelin-A/Endothelin-B Receptor Blockade and Cardiac Remodeling in Heart Failure With Preserved Ejection Fraction.

PubMed

Valero-Munoz, Maria; Li, Shanpeng; Wilson, Richard M; Boldbaatar, Batbold; Iglarz, Marc; Sam, Flora

2016-11-01

Despite the increasing prevalence of heart failure with preserved ejection fraction (HFpEF) in humans, there remains no evidence-based therapies for HFpEF. Endothelin-1 (ET-1) antagonists are a possibility because elevated ET-1 levels are associated with adverse cardiovascular effects, such as arterial and pulmonary vasoconstriction, impaired left ventricular (LV) relaxation, and stimulation of LV hypertrophy. LV hypertrophy is a common phenotype in HFpEF, particularly when associated with hypertension. In the present study, we found that ET-1 levels were significantly elevated in patients with chronic stable HFpEF. We then sought to investigate the effects of chronic macitentan, a dual ET-A/ET-B receptor antagonist, on cardiac structure and function in a murine model of HFpEF induced by chronic aldosterone infusion. Macitentan caused LV hypertrophy regression independent of blood pressure changes in HFpEF. Although macitentan did not modulate diastolic dysfunction in HFpEF, it significantly reduced wall thickness and relative wall thickness after 2 weeks of therapy. In vitro studies showed that macitentan decreased the aldosterone-induced cardiomyocyte hypertrophy. These changes were mediated by a reduction in the expression of cardiac myocyte enhancer factor 2a. Moreover, macitentan improved adverse cardiac remodeling, by reducing the stiffer cardiac collagen I and titin n2b expression in the left ventricle of mice with HFpEF. These findings indicate that dual ET-A/ET-B receptor inhibition improves HFpEF by abrogating adverse cardiac remodeling via antihypertrophic mechanisms and by reducing stiffness. Additional studies are needed to explore the role of dual ET-1 receptor antagonists in patients with HFpEF. © 2016 American Heart Association, Inc.

GPR30 decreases cardiac chymase/angiotensin II by inhibiting local mast cell number

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

Zhao, Zhuo; Department of Cardiology, Jinan Central Hospital, Affiliated with Shandong University, 105 Jiefang Road, Jinan, 250013; Wang, Hao

2015-03-27

Chronic activation of the novel estrogen receptor GPR30 by its agonist G1 mitigates the adverse effects of estrogen (E2) loss on cardiac structure and function. Using the ovariectomized (OVX) mRen2.Lewis rat, an E2-sensitive model of diastolic dysfunction, we found that E2 status is inversely correlated with local cardiac angiotensin II (Ang II) levels, likely via Ang I/chymase-mediated production. Since chymase is released from cardiac mast cells during stress (e.g., volume/pressure overload, inflammation), we hypothesized that GPR30-related cardioprotection after E2 loss might occur through its opposing actions on cardiac mast cell proliferation and chymase production. Using real-time quantitative PCR, immunohistochemistry, andmore » immunoblot analysis, we found mast cell number, chymase expression, and cardiac Ang II levels were significantly increased in the hearts of OVX-compared to ovary-intact mRen2.Lewis rats and the GPR30 agonist G1 (50 mg/kg/day, s.c.) administered for 2 weeks limited the adverse effects of estrogen loss. In vitro studies revealed that GPR30 receptors are expressed in the RBL-2H3 mast cell line and G1 inhibits serum-induced cell proliferation in a dose-dependent manner, as determined by cell counting, BrdU incorporation assay, and Ki-67 staining. Using specific antagonists to estrogen receptors, blockage of GPR30, but not ERα or ERβ, attenuated the inhibitory effects of estrogen on BrdU incorporation in RBL-2H3 cells. Further study of the mechanism underlying the effect on cell proliferation showed that G1 inhibits cyclin-dependent kinase 1 (CDK1) mRNA and protein expression in RBL-2H3 cells in a dose-dependent manner. - Highlights: • GPR30 activation limits mast cell number in hearts from OVX mRen2.Lewis rats. • GPR30 activation decreases cardiac chymase/angiotensin II after estrogen loss. • GPR30 activation inhibits RBL-2H3 mast cell proliferation and CDK1 expression.« less

Potential Adverse Cardiovascular Effects From Excessive Endurance Exercise

PubMed Central

O'Keefe, James H.; Patil, Harshal R.; Lavie, Carl J.; Magalski, Anthony; Vogel, Robert A.; McCullough, Peter A.

2012-01-01

A routine of regular exercise is highly effective for prevention and treatment of many common chronic diseases and improves cardiovascular (CV) health and longevity. However, long-term excessive endurance exercise may induce pathologic structural remodeling of the heart and large arteries. Emerging data suggest that chronic training for and competing in extreme endurance events such as marathons, ultramarathons, ironman distance triathlons, and very long distance bicycle races, can cause transient acute volume overload of the atria and right ventricle, with transient reductions in right ventricular ejection fraction and elevations of cardiac biomarkers, all of which return to normal within 1 week. Over months to years of repetitive injury, this process, in some individuals, may lead to patchy myocardial fibrosis, particularly in the atria, interventricular septum, and right ventricle, creating a substrate for atrial and ventricular arrhythmias. Additionally, long-term excessive sustained exercise may be associated with coronary artery calcification, diastolic dysfunction, and large-artery wall stiffening. However, this concept is still hypothetical and there is some inconsistency in the reported findings. Furthermore, lifelong vigorous exercisers generally have low mortality rates and excellent functional capacity. Notwithstanding, the hypothesis that long-term excessive endurance exercise may induce adverse CV remodeling warrants further investigation to identify at-risk individuals and formulate physical fitness regimens for conferring optimal CV health and longevity. PMID:22677079

Diabetes mellitus is associated with adverse structural and functional cardiac remodelling in chronic heart failure with reduced ejection fraction.

PubMed

Walker, Andrew Mn; Patel, Peysh A; Rajwani, Adil; Groves, David; Denby, Christine; Kearney, Lorraine; Sapsford, Robert J; Witte, Klaus K; Kearney, Mark T; Cubbon, Richard M

2016-09-01

Diabetes mellitus is associated with an increased risk of death and hospitalisation in patients with chronic heart failure. Better understanding of potential underlying mechanisms may aid the development of diabetes mellitus-specific chronic heart failure therapeutic strategies. Prospective observational cohort study of 628 patients with chronic heart failure associated with left ventricular systolic dysfunction receiving contemporary evidence-based therapy. Indices of cardiac structure and function, along with symptoms and biochemical parameters, were compared in patients with and without diabetes mellitus at study recruitment and 1 year later. Patients with diabetes mellitus (24.2%) experienced higher rates of all-cause [hazard ratio, 2.3 (95% confidence interval, 1.8-3.0)] and chronic heart failure-specific mortality and hospitalisation despite comparable pharmacological and device-based therapies. At study recruitment, patients with diabetes mellitus were more symptomatic, required greater diuretic doses and more frequently had radiologic evidence of pulmonary oedema, despite higher left ventricular ejection fraction. They also exhibited echocardiographic evidence of increased left ventricular wall thickness and pulmonary arterial pressure. Diabetes mellitus was associated with reduced indices of heart rate variability and increased heart rate turbulence. During follow-up, patients with diabetes mellitus experienced less beneficial left ventricular remodelling and greater deterioration in renal function. Diabetes mellitus is associated with features of adverse structural and functional cardiac remodelling in patients with chronic heart failure. © The Author(s) 2016.

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.

Social inhibition modulates the effect of negative emotions on cardiac prognosis following percutaneous coronary intervention in the drug-eluting stent era.

PubMed

Denollet, Johan; Pedersen, Susanne S; Ong, Andrew T L; Erdman, Ruud A M; Serruys, Patrick W; van Domburg, Ron T

2006-01-01

Negative emotions have an adverse effect on cardiac prognosis. We investigated whether social inhibition (inhibited self-expression in social interaction) modulates the effect of negative emotions on clinical outcome following percutaneous coronary intervention (PCI). Eight hundred and seventy-five consecutive patients from the RESEARCH registry (Erasmus Medical Centre, Rotterdam) completed depression, anxiety, negativity (negative emotions in general), and social inhibition scales 6 months following PCI. The endpoint was major adverse cardiac event (MACE-death, myocardial infarction, coronary artery bypass graft (CABG), or PCI) at 9 months following assessment. There were 100 MACE; patients who were high in both negativity and inhibition were at increased risk of MACE (38/254=15%) when compared with high negativity/low inhibition patients (13/136=10%; P=0.018). Depression (P=0.23) or anxiety (P=0.63) did not explain away this moderating effect of inhibition. High negativity/high inhibition (HR=1.92, 95%CI 1.22-3.01, P=0.005) and previous CABG (HR=1.90, 95%CI 1.04-3.47, P=0.038) were independent predictors of MACE. Patients with high negativity but low inhibition were not at increased risk (P=0.76). High negativity/high inhibition also independently predicted death/MI (n=20) as a more specific endpoint (HR=5.85, P=0.001). The interaction effect of social inhibition and negative emotions, rather than negative emotions per se, predicted poor clinical outcome following PCI. Social inhibition should not be overlooked as a modulating factor.

Williams Syndrome and Anesthesia for Non-cardiac Surgery: High Risk Can Be Mitigated with Appropriate Planning.

PubMed

Brown, Morgan L; Nasr, Viviane G; Toohey, Rebecca; DiNardo, James A

2018-03-23

Patients with Williams syndrome are considered at high risk for anesthesia-related adverse events. At our institution, all William syndrome patients undergoing cardiac surgical, cardiac catheterization/interventional procedures, and cardiac imaging studies are cared for by cardiac anesthesiologists. All William syndrome patients undergoing non-cardiac surgical, interventional, or imaging studies are cared for by main operating room pediatric anesthesiologists with consultative input from a cardiac anesthesiologist. We reviewed our experience with 75 patients undergoing 202 separate anesthetics for 95 non-cardiac procedures and 107 cardiac procedures from 2012 to 2016. The mean age was 7.5 ± 7.0 years and the mean weight was 22.3 ± 17.0 kg. One hundred and eighty-seven patients had a general anesthetic (92.6%). Medications used included etomidate in 26.2%, propofol in 37.6%, isoflurane in 47.5%, and sevoflurane in 68.3%. Vasopressors and inotropes were required including calcium (22.8%), dopamine (10.4%), norepinephrine (17.3%), phenylephrine (35.1%), vasopressin (0.5%), and ephedrine (5.4%). The median length of stay after anesthesia was 2.8 days (range 0-32). No adverse events occurred in 89.6% of anesthetics. There were two cases of cardiac arrest, one of which required extracorporeal life support for resuscitation. Of the non-cardiac surgical procedures, 95.7% did not have a cardiovascular adverse event. Patients with Williams syndrome are at high risk for anesthesia, especially when undergoing cardiac procedures. The risk can be mitigated with appropriate planning and adherence to the hemodynamic goals for non-cardiac surgical procedures.

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

Adverse Effects of Common Drugs: Dietary Supplements.

PubMed

Felix, Todd Matthew; Karpa, Kelly Dowhower; Lewis, Peter R

2015-09-01

Dietary supplement-induced adverse effects often resolve quickly after discontinuation of the offending product, especially in younger patients. The potential for unwanted outcomes can be amplified in elderly patients or those taking multiple prescription drugs, especially where interactions exist with drugs metabolized by cytochrome P450 enzymes. Attributing injury or illness to a specific supplement can be challenging, especially in light of multi-ingredient products, product variability, and variability in reporting, as well as the vast underreporting of adverse drug reactions. Clinicians prescribing a new drug or evaluating a patient with a new symptom complex should inquire about use of herbal and dietary supplements as part of a comprehensive evaluation. Clinicians should report suspected supplement-related adverse effects to the local or state health department, as well as the Food and Drug Administration's MedWatch program (available at https://www.safetyreporting.hhs.gov). Clinicians should consider discussing suspected adverse effects involving drugs, herbal products, or dietary supplements with their community- and hospital-based pharmacists, and explore patient management options with medical or clinical toxicology subspecialists. Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.

Modelling the adverse effects associated with ecstasy use.

PubMed

Fisk, John E; Murphy, Philip N; Montgomery, Catharine; Hadjiefthyvoulou, Florentia

2011-04-01

Ecstasy, the street name for 3,4-meththylenedioxymethamphetamine, has been associated with a range of psychiatric symptoms and impaired psychological health in both problem and recreational users. The purpose of the present paper is to determine how these impairments are related to the history of polydrug use, and the conditions under which individuals ingest ecstasy. Associations between the variables of interest were investigated utilizing negative binomial regression. Liverpool and Preston in the North West of England. A convenience sample of 159 recreational ecstasy/polydrug users (80 males, 79 females). The sample was composed primarily of undergraduates. The dependent variable was the number of reported ecstasy-related adverse effects. Independent variables included quantitative aspects of ecstasy and other drug use, and the various beliefs and behaviours associated with ecstasy use. The number of adverse effects was associated positively with life-time exposure to ecstasy and negatively with period of abstinence from the drug. Adverse effects were more common among those who consumed ecstasy and alcohol concurrently, but were unrelated to other aspects of polydrug use. They were unaffected by whether the user took precautions when using the drug, and only weakly related to prior beliefs concerning the effects of ecstasy. Greater life-time exposure to ecstasy and consuming the drug concurrently with alcohol increase the likelihood of experiencing adverse effects, including paranoia, poor general health, irritability, confusion and moodiness. Adverse effects decrease with the period of abstinence from the drug. © 2010 The Authors, Addiction © 2010 Society for the Study of Addiction.

Adverse effects of public health interventions: a conceptual framework.

PubMed

Lorenc, Theo; Oliver, Kathryn

2014-03-01

Public health interventions may have a range of adverse effects. However, there is limited guidance as to how evaluations should address the possibility of adverse effects. This discussion paper briefly presents a framework for thinking about the potential harms of public health interventions, focusing on the following categories: direct harms; psychological harms; equity harms; group and social harms; and opportunity harms. We conclude that the possibility of adverse effects needs to be taken into account by those implementing and evaluating interventions, and requires a broad perspective on the potential impacts of public health strategies.

Effects of sildenafil on cardiac repolarization.

PubMed

Chiang, Chern-En; Luk, Hsiang-Ning; Wang, Tsui-Min; Ding, Philip Yu-An

2002-08-01

Sudden death has occasionally been reported in patients taking sildenafil. The objective of this study was to investigate the effect of sildenafil on cardiac repolarization. We used conventional microelectrode recording technique in isolated guinea pig papillary muscles and canine Purkinje fibers, whole-cell patch clamp techniques in guinea pig ventricular myocytes, and in vivo ECG measurements in guinea pigs. Action potential duration at 90% repolarization (APD(90)) was not affected by sildenafil in the therapeutic ranges (< or =1 microM), but shortened by higher concentration (> or =10 microM) in both guinea pig papillary muscles and canine Purkinje fibers. D-Sotalol prolonged APD(90) in the same preparations with concentrations > or =1 microM in a reverse frequency-dependent manner. Co-administration of sildenafil (10 and 30 microM) abolished the APD-prolonging effects of D-sotalol (30 microM) and amiodarone (100 microM). Sildenafil, with concentrations up to 30 microM, had no significant effect on both the rapid (I(Kr)) and the slow (I(Ks)) components of the delayed rectifier potassium currents in guinea pig ventricular myocytes. Sildenafil dose-dependently blocked L-type Ca(2+) current (I(Ca,L)), but had no effect on persistent Na(+) current in guinea pig ventricular myocytes. ECG recordings in intact guinea pigs revealed significant shortening of QTc interval by sildenafil (10 and 30 mg/kg orally). The QT-prolonging effects by D,L-sotalol (50 mg/kg) and amiodarone (100 mg/kg) were abolished by sildenafil (30 mg/kg). Sildenafil does not prolong cardiac repolarization. Instead, in supra-therapeutic concentrations, it accelerates cardiac repolarization, presumably through its blocking effect on I(Ca,L).

Effects of extracorporeal cardiopulmonary resuscitation on neurological and cardiac outcome after ischaemic refractory cardiac arrest.

PubMed

Cesana, Francesca; Avalli, Leonello; Garatti, Laura; Coppo, Anna; Righetti, Stefano; Calchera, Ivan; Scanziani, Elisabetta; Cozzolino, Paolo; Malafronte, Cristina; Mauro, Andrea; Soffici, Federica; Sulmina, Endrit; Bozzon, Veronica; Maggioni, Elena; Foti, Giuseppe; Achilli, Felice

2017-10-01

Extracorporeal cardiopulmonary resuscitation is increasingly recognised as a rescue therapy for refractory cardiac arrest, nevertheless data are scanty about its effects on neurologic and cardiac outcome. The aim of this study is to compare clinical outcome in patients with cardiac arrest of ischaemic origin (i.e. critical coronary plaque during angiography) and return of spontaneous circulation during conventional cardiopulmonary resuscitation vs refractory cardiac arrest patients needing extracorporeal cardiopulmonary resuscitation. Moreover, we tried to identify predictors of survival after successful cardiopulmonary resuscitation. We enrolled 148 patients with ischaemic cardiac arrest admitted to our hospital from 2011-2015. We compared clinical characteristics, cardiac arrest features, neurological and echocardiographic data obtained after return of spontaneous circulation (within 24 h, 15 days and six months). Patients in the extracorporeal cardiopulmonary resuscitation group ( n=63, 43%) were younger (59±9 vs 63±8 year-old, p=0.02) with lower incidence of atherosclerosis risk factors than those with conventional cardiopulmonary resuscitation. In the extracorporeal cardiopulmonary resuscitation group, left ventricular ejection fraction was lower than conventional cardiopulmonary resuscitation at early echocardiography (19±16% vs 37±11 p<0.01). Survivors in both groups showed similar left ventricular ejection fraction 15 days and 4-6 months after cardiac arrest (46±8% vs 49±10, 47±11% vs 45±13%, p not significant for both), despite a major extent and duration of cardiac ischaemia in extracorporeal cardiopulmonary resuscitation patients. At multivariate analysis, the total cardiac arrest time was the only independent predictor of survival. Extracorporeal cardiopulmonary resuscitation patients are younger and have less comorbidities than conventional cardiopulmonary resuscitation, but they have worse survival and lower early left ventricular ejection

Reoperative Cardiac Surgery: Part I - Preoperative Planning.

PubMed

Tribble, Curt

2018-02-26

While reoperative cardiac surgery has become safer in recent years, it is still more difficult and dangerous than a primary operation. In a recent review of the Cleveland Clinic's experience, 7% of the patients undergoing cardiac reoperations had major intraoperative adverse events (IAEs). In that report, if an IAE occurred, there was a 5% mortality and a 19% incidence of myocardial infarction (MI), stroke, or death [Roselli 2011]. Those are sobering statistics, particularly when reported by one of the busiest cardiac surgical services in the world. The take-home message is that reoperative cardiac surgery is riskier than primary cardiac operations and that there are strategies that should be employed at each juncture to lower the risks of a reoperation.However, many of these strategies and recommendations have been more implicit than explicit. In fact, surprisingly little has been written about reoperative cardiac surgery. Thus, it seems appropriate to collect some of the lessons, adages, tricks, and tools that might make reoperations a click safer.

Adverse Effects of Plasma Transfusion

PubMed Central

Pandey, Suchitra; Vyas, Girish N.

2012-01-01

Plasma utilization has increased over the last two decades, and there is a growing concern that many plasma transfusions are inappropriate. Plasma transfusion is not without risk, and certain complications are more likely with plasma than other blood components. Clinical and laboratory investigations of the patients suffering reactions following infusion of fresh frozen plasma (FFP) define the etiology and pathogenesis of the panoply of adverse effects. We review here the pathogenesis, diagnosis, and management of the risks associated with plasma transfusion. Risks commonly associated with FFP include: (1) transfusion related acute lung injury; (2) transfusion associated circulatory overload, and (3) allergic/anaphylactic reactions. Other less common risks include (1) transmission of infections, (2) febrile non-hemolytic transfusion reactions, (3) RBC allo-immunization, and (4) hemolytic transfusion reactions. The affect of pathogen inactivation/reduction methods on these risks are also discussed. Fortunately, a majority of the adverse effects are not lethal and are adequately treated in clinical practice. PMID:22578374

Childhood Adversity and Pain Sensitization.

PubMed

You, Dokyoung Sophia; Meagher, Mary W

Childhood adversity is a vulnerability factor for chronic pain. However, the underlying pain mechanisms influenced by childhood adversity remain unknown. The aim of the current study was to evaluate the impact of childhood adversity on dynamic pain sensitivity in young adults. After screening for childhood adverse events and health status, healthy individuals reporting low (below median; n = 75) or high levels of adversity (the top 5%; n = 51) were invited for pain testing. Both groups underwent heat pain threshold and temporal summation of second pain (TSSP) testing after reporting depressive symptoms. TSSP refers to a progressive increase in pain intensity with repetition of identical noxious stimuli and is attributed to central sensitization. Changes in pain ratings over time (slope) were computed for TSSP sensitization and decay of subsequent aftersensations. The high-adversity group showed greater TSSP sensitization (meanslope, 0.75; SDpositive slope, 1.78), and a trend toward a slower decay (meanslope, -11.9; SD, 3.4), whereas the low-adversity group showed minimal sensitization (meanslope, 0.07; SDnear-zero slope, 1.77), F(1,123) = 5.84, p = .017 and faster decay (meanslope, -13.1; SD, 3.4), F(1,123) = 3.79, p = .054. This group difference remained significant even after adjusting for adult depressive symptoms (p = .033). No group difference was found in heat pain threshold (p = .85). Lastly, the high-adversity group showed blunted cardiac and skin conductance responses. These findings suggest that enhancement of central sensitization may provide a mechanism underlying the pain hypersensitivity and chronicity linked to childhood adversity.

Meta-analysis of randomized trials of effect of milrinone on mortality in cardiac surgery: an update.

PubMed

Majure, David T; Greco, Teresa; Greco, Massimiliano; Ponschab, Martin; Biondi-Zoccai, Giuseppe; Zangrillo, Alberto; Landoni, Giovanni

2013-04-01

The long-term use of milrinone is associated with increased mortality in chronic heart failure. A recent meta-analysis suggested that it might increase mortality in patients undergoing cardiac surgery. The authors conducted an updated meta-analysis of randomized trials in patients undergoing cardiac surgery to determine if milrinone impacted survival. A meta-analysis. Hospitals. One thousand thirty-seven patients from 20 randomized trials. None. Biomed, Central, PubMed, EMBASE, the Cochrane central register of clinical trials, and conference proceedings were searched for randomized trials that compared milrinone versus placebo or any other control in adult and pediatric patients undergoing cardiac surgery. Authors of trials that did not include mortality data were contacted. Only trials for which mortality data were available were included. Overall analysis showed no difference in mortality between patients receiving milrinone versus control (12/554 [2.2%] in the milrinone group v 10/483 [2.1%] in the control arm; relative risk [RR] = 1.15; 95% confidence interval [CI], 0.55-2.43; p = 0.7) or in analysis restricted to adults (11/364 [3%] in the milrinone group v 9/371 [2.4%] in the control arm; RR = 1.17; 95% CI, 0.54-2.53; p = 0.7). Sensitivity analyses in trials with a low risk of bias showed a trend toward an increase in mortality with milrinone (8/153 [5.2%] in the milrinone arm v 2/152 [1.3%] in the control arm; RR = 2.71; 95% CI, 0.82-9; p for effect = 0.10). Despite theoretic concerns for increased mortality with intravenous milrinone in patients undergoing cardiac surgery, the authors were unable to confirm an adverse effect on survival. However, sensitivity analysis of high-quality trials showed a trend toward increased mortality with milrinone. Copyright © 2013 Elsevier Inc. All rights reserved.

Novel cardiac protective effects of urea: from shark to rat

PubMed Central

Wang, Xintao; Wu, Lingyun; Aouffen, M'hamed; Mateescu, Mircea-Alexandru; Nadeau, Réginald; Wang, Rui

1999-01-01

This study was carried out to investigate novel cardioprotective effects of urea and the underlying mechanisms. The cardiac functions under oxidative stress were evaluated using Langendorff perfused isolated heart.Isolated dogfish shark hearts tolerated the oxidative stress generated by electrolysis (10 mA, 1 min) of the perfusion solution (n=4), and also showed normal cardiac functions during post-ischaemia reperfusion (n=4). The high concentration of urea (350 mM) in the heart perfusate was indispensable for maintaining the normal cardiac functions of the shark heart.Urea at 3–300 mM (n=4 for each group) protected the isolated rat heart against both electrolysis-induced heart damage and post-ischaemia reperfusion-induced cardiac injury.A concentration-dependent scavenging effect of urea (3–300 mM, n=4 for each group) against electrolysis-induced reactive oxygen species was also demonstrated in vitro.Urea derivatives as hydroxyurea, dimethylurea, and thiourea had antioxidant cardioprotective effect against the electrolysis-induced cardiac dysfunction of rat heart, but were not as effective as urea in suppressing the post-ischaemia reperfusion injury.Our results suggest that urea and its derivatives are potential antioxidant cardioprotective agents against oxidative stress-induced myocardium damage including the post-ischaemia reperfusion-induced injury. PMID:10602326

Acute gouty arthritis complicated with acute ST elevation myocardial infarction is independently associated with short- and long-term adverse non-fatal cardiac events.

PubMed

Liu, Kuan-Liang; Lee, Hsin-Fu; Chou, Shing-Hsien; Lin, Yen-Chen; Lin, Chia-Pin; Wang, Chun-Li; Chang, Chi-Jen; Hsu, Lung-An

2014-01-01

Large epidemiologic studies have associated gouty arthritis with the risk of coronary heart disease. However, there has been a lack of information regarding the outcomes for patients who have gout attacks during hospitalization for acute myocardial infarction. We reviewed the data of 444 consecutive patients who were admitted to our hospital between 2005 and 2008 due to acute ST elevation myocardial infarction (STEMI). The clinical outcomes were compared between patients with gout attack and those without. Of the 444, 48 patients with acute STEMI developed acute gouty arthritis during hospitalization. The multivariate analysis identified prior history of gout and estimated glomerular filtration rate as independent risk factors of gout attack for patients with acute STEMI (odds ratio (OR) 21.02, 95 % CI 2.96-149.26, p = 0.002; OR 0.92, 95 % CI 0.86-0.99, p = 0.035, respectively). The in-hospital mortality and duration of hospital stay did not differ significantly between the gouty group and the non-gouty group (controls). During a mean follow-up of 49 ± 28 months, all-cause mortality and stroke were similar for both groups. Multivariate Cox regression showed that gout attack was independently associated with short- and long-term adverse non-fatal cardiac events (hazard ratio (HR) 1.88, 95 % CI 1.09-3.24, p = 0.024; HR 1.82, 95 % CI 1.09-3.03, p = 0.022, respectively). Gout attack among patients hospitalized due to acute STEMI was independently associated with short-term and long-term rates of adverse non-fatal cardiac events.

Troponin Limit of Detection Plus Cardiac Risk Stratification Scores to Rule Out Acute Myocardial Infarction and 30-Day Major Adverse Cardiac Events in ED Patients.

PubMed

Datlow, Mitchell D; Gray, Kelly M; Watts, Adriel; Diercks, Deborah B; Mumma, Bryn E

2017-12-01

When screening for acute myocardial infarction (AMI), troponin levels below the 99th percentile, including those below the limit of detection (LOD), are considered normal. We hypothesized that a low-risk HEART score (0-3) or ACS Pretest Probability Assessment <2% plus a single troponin below the LOD would rule out both AMI and 30-day major adverse cardiac events (MACE). We studied all patients who presented to a single academic emergency department and received a troponin I (Siemens Ultra Troponin I) from September 1, 2013, to November 13, 2013 (n=888). Demographic and clinical data were abstracted from the electronic medical record. Primary outcome was a final encounter diagnosis of myocardial infarction. Secondary outcome was 30-day MACE, defined as composite of myocardial infarction, revascularization, or death from a cardiac or uncertain etiology. Sensitivities of low-risk HEART score and ACS Pretest Probability <2% alone were 98% (95% confidence interval [CI], 89%-100%) and 96% (95% CI, 86%-100%) for AMI and 94% (95% CI, 86%-98%) and 95% (95% CI, 88%-99%), respectively, for 30-day MACE. When combined with troponin below the LOD, sensitivity for AMI was 100% (95% CI, 93%-100%; difference 2%; 95% CI, -2% to 6%) for low-risk HEART Score and 100% (95% CI, 93%-100%; difference 4%; 95% CI, -1.5% to 10%) for ACS Pretest Probability <2%. When combined with troponin below the LOD, sensitivity for 30-day MACE was 100% (95% CI, 95%-100%; difference 6%; 95% CI, 1%-12%) for low-risk HEART Score and 100% (95% CI, 95%-100%; difference 5%; 95% CI, 0.2%-10%) for ACS Pretest Probability <2%. Addition of a single troponin below the LOD to these scores improves sensitivity for 30-day MACE.

Adverse Cardiovascular Effects with Acute Particulate Matter and Ozone Exposures: Interstrain Variation in Mice

PubMed Central

Hamade, Ali K.; Rabold, Richard; Tankersley, Clarke G.

2008-01-01

Objectives Increased ambient particulate matter (PM) levels are associated with cardiovascular morbidity and mortality, as shown by numerous epidemiology studies. Few studies have investigated the role of copollutants, such as ozone, in this association. Furthermore, the mechanisms by which PM affects cardiac function remain uncertain. We hypothesized that PM and O3 induce adverse cardiovascular effects in mice and that these effects are strain dependent. Study design After implanting radiotelemeters to measure heart rate (HR) and HR variability (HRV) parameters, we exposed C57Bl/6J (B6), C3H/HeJ (HeJ), and C3H/HeOuJ (OuJ) inbred mouse strains to three different daily exposures of filtered air (FA), carbon black particles (CB), or O3 and CB sequentially [O3CB; for CB, 536 ± 24 μg/m3; for O3, 584 ± 35 ppb (mean ± SE)]. Results We observed significant changes in HR and HRV in all strains due to O3CB exposure, but not due to sequential FA and CB exposure (FACB). The data suggest that primarily acute HR and HRV effects occur during O3CB exposure, especially in HeJ and OuJ mice. For example, HeJ and OuJ mice demonstrated dramatic increases in HRV parameters associated with marked brady-cardia during O3CB exposure. In contrast, depressed HR responses occurred in B6 mice without detectable changes in HRV parameters. Conclusions These findings demonstrate that important interstrain differences exist with respect to PM- and O3-induced cardiac effects. This interstrain variation suggests that genetic factors may modulate HR regulation in response to and recuperation from acute copollutant exposures. PMID:18709144

Adverse cardiac events after orthotopic liver transplantation: a cross-sectional study in 389 consecutive patients.

PubMed

Nicolau-Raducu, Ramona; Gitman, Marina; Ganier, Donald; Loss, George E; Cohen, Ari J; Patel, Hamang; Girgrah, Nigel; Sekar, Krish; Nossaman, Bobby

2015-01-01

Current American College of Cardiology/American Heart Association guidelines caution that preoperative noninvasive cardiac tests may have poor predictive value for detecting coronary artery disease in liver transplant candidates. The purpose of our study was to evaluate the role of clinical predictor variables for early and late cardiac morbidity and mortality and the predictive values of noninvasive cardiac tests for perioperative cardiac events in a high-risk liver transplant population. In all, 389 adult recipients were retrospectively analyzed for a median follow-up time of 3.4 years (range = 2.3-4.4 years). Overall survival was 83%. During the first year after transplantation, cardiovascular morbidity and mortality rates were 15.2% and 2.8%. In patients who survived the first year, cardiovascular morbidity and mortality rates were 3.9% and 2%, with cardiovascular etiology as the third leading cause of death. Dobutamine stress echocardiography (DSE) and single-photon emission computed tomography had respective sensitivities of 9% and 57%, specificities of 98% and 75%, positive predictive values of 33% and 28%, and negative predictive values of 89% and 91% for predicting early cardiac events. A rate blood pressure product less than 12,000 with DSE was associated with an increased risk for postoperative atrial fibrillation. Correspondence analysis identified a statistical association between nonalcoholic steatohepatitis/cryptogenic cirrhosis and postoperative myocardial ischemia. Logistic regression identified 3 risk factors for postoperative acute coronary syndrome: age, history of coronary artery disease, and pretransplant requirement for vasopressors. Multivariable analysis showed statistical associations of the Model for End-Stage Liver Disease score and the development of acute kidney injury as risk factors for overall cardiac-related mortality. These findings may help in identifying high-risk patients and may lead to the development of better cardiac

Prevention of liver cancer cachexia-induced cardiac wasting and heart failure.

PubMed

Springer, Jochen; Tschirner, Anika; Haghikia, Arash; von Haehling, Stephan; Lal, Hind; Grzesiak, Aleksandra; Kaschina, Elena; Palus, Sandra; Pötsch, Mareike; von Websky, Karoline; Hocher, Berthold; Latouche, Celine; Jaisser, Frederic; Morawietz, Lars; Coats, Andrew J S; Beadle, John; Argiles, Josep M; Thum, Thomas; Földes, Gabor; Doehner, Wolfram; Hilfiker-Kleiner, Denise; Force, Thomas; Anker, Stefan D

2014-04-01

Symptoms of cancer cachexia (CC) include fatigue, shortness of breath, and impaired exercise capacity, which are also hallmark symptoms of heart failure (HF). Herein, we evaluate the effects of drugs commonly used to treat HF (bisoprolol, imidapril, spironolactone) on development of cardiac wasting, HF, and death in the rat hepatoma CC model (AH-130). Tumour-bearing rats showed a progressive loss of body weight and left-ventricular (LV) mass that was associated with a progressive deterioration in cardiac function. Strikingly, bisoprolol and spironolactone significantly reduced wasting of LV mass, attenuated cardiac dysfunction, and improved survival. In contrast, imidapril had no beneficial effect. Several key anabolic and catabolic pathways were dysregulated in the cachectic hearts and, in addition, we found enhanced fibrosis that was corrected by treatment with spironolactone. Finally, we found cardiac wasting and fibrotic remodelling in patients who died as a result of CC. In living cancer patients, with and without cachexia, serum levels of brain natriuretic peptide and aldosterone were elevated. Systemic effects of tumours lead not only to CC but also to cardiac wasting, associated with LV-dysfunction, fibrotic remodelling, and increased mortality. These adverse effects of the tumour on the heart and on survival can be mitigated by treatment with either the β-blocker bisoprolol or the aldosterone antagonist spironolactone. We suggest that clinical trials employing these agents be considered to attempt to limit this devastating complication of cancer.

Prevention of liver cancer cachexia-induced cardiac wasting and heart failure

PubMed Central

Springer, Jochen; Tschirner, Anika; Haghikia, Arash; von Haehling, Stephan; Lal, Hind; Grzesiak, Aleksandra; Kaschina, Elena; Palus, Sandra; Pötsch, Mareike; von Websky, Karoline; Hocher, Berthold; Latouche, Celine; Jaisser, Frederic; Morawietz, Lars; Coats, Andrew J.S.; Beadle, John; Argiles, Josep M.; Thum, Thomas; Földes, Gabor; Doehner, Wolfram; Hilfiker-Kleiner, Denise; Force, Thomas; Anker, Stefan D.

2014-01-01

Aims Symptoms of cancer cachexia (CC) include fatigue, shortness of breath, and impaired exercise capacity, which are also hallmark symptoms of heart failure (HF). Herein, we evaluate the effects of drugs commonly used to treat HF (bisoprolol, imidapril, spironolactone) on development of cardiac wasting, HF, and death in the rat hepatoma CC model (AH-130). Methods and results Tumour-bearing rats showed a progressive loss of body weight and left-ventricular (LV) mass that was associated with a progressive deterioration in cardiac function. Strikingly, bisoprolol and spironolactone significantly reduced wasting of LV mass, attenuated cardiac dysfunction, and improved survival. In contrast, imidapril had no beneficial effect. Several key anabolic and catabolic pathways were dysregulated in the cachectic hearts and, in addition, we found enhanced fibrosis that was corrected by treatment with spironolactone. Finally, we found cardiac wasting and fibrotic remodelling in patients who died as a result of CC. In living cancer patients, with and without cachexia, serum levels of brain natriuretic peptide and aldosterone were elevated. Conclusion Systemic effects of tumours lead not only to CC but also to cardiac wasting, associated with LV-dysfunction, fibrotic remodelling, and increased mortality. These adverse effects of the tumour on the heart and on survival can be mitigated by treatment with either the β-blocker bisoprolol or the aldosterone antagonist spironolactone. We suggest that clinical trials employing these agents be considered to attempt to limit this devastating complication of cancer. PMID:23990596

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.

Effectiveness of adverse effects search filters: drugs versus medical devices.

PubMed

Farrah, Kelly; Mierzwinski-Urban, Monika; Cimon, Karen

2016-07-01

The study tested the performance of adverse effects search filters when searching for safety information on medical devices, procedures, and diagnostic tests in MEDLINE and Embase. The sensitivity of 3 filters was determined using a sample of 631 references from 131 rapid reviews related to the safety of health technologies. The references were divided into 2 sets by type of intervention: drugs and nondrug health technologies. Keyword and indexing analysis were performed on references from the nondrug testing set that 1 or more of the filters did not retrieve. For all 3 filters, sensitivity was lower for nondrug health technologies (ranging from 53%-87%) than for drugs (88%-93%) in both databases. When tested on the nondrug health technologies set, sensitivity was lower in Embase (ranging from 53%-81%) than in MEDLINE (67%-87%) for all filters. Of the nondrug records that 1 or more of the filters missed, 39% of the missed MEDLINE records and 18% of the missed Embase records did not contain any indexing terms related to adverse events. Analyzing the titles and abstracts of nondrug records that were missed by any 1 filter, the most commonly used keywords related to adverse effects were: risk, complications, mortality, contamination, hemorrhage, and failure. In this study, adverse effects filters were less effective at finding information about the safety of medical devices, procedures, and tests compared to information about the safety of drugs.

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.

Identification and Characterization of Adverse Effects in 21st Century Toxicology

EPA Science Inventory

The ILSI Health and Environmental Sciences Institute Project Committee on Distinguishing Adverse from Non-Adverse / Adaptive Effects held a workshop in May 2011 to discuss approaches to identifying adverse effects in the context of the 2007 NRC committee report titled “Toxicity T...

Effect of various electrolytes upon cardiac and skeletal musculature

PubMed Central

Selye, H.; Bajusz, E.

1959-01-01

In rats kept on a low-potassium diet that contains only maintenance levels of magnesium, cardiac necroses and muscular cramps were readily induced by the oral administration of sodium perchlorate or disodium hydrogen phosphate. The precipitation of these cardiac and skeletal muscle changes by sodium chlorate was prevented by the prophylactic administration of either potassium or magnesium chlorides. The protective effect of these chlorides against the cardiotoxic and convulsive effects of disodium hydrogen phosphate has already been demonstrated by our earlier experiments. Sodium sulphate produced cardiac necroses in rats maintained on the same diet, and both potassium and magnesium chlorides had a prophylactic action. Unlike sodium perchlorate, however, sodium sulphate produced no muscular cramps under these conditions. Equimolecular amounts of sodium given in the form of sodium chloride (instead of sodium perchlorate, sodium sulphate, or disodium hydrogen phosphate) did not cause cardiac necroses or muscular cramps in rats maintained on the potassium-deficient diet. As the same three sodium salts, namely the perchlorate, the sulphate, and the hydrogen phosphate, produced cardiac necroses in rats sensitized by either a potassium-deficient diet or by certain corticoids, it seems that the anion must play a decisive rôle, since equivalent amounts of NaCl are ineffective. PMID:13651583

Long term effects of early adversity on cognitive function.

PubMed

Richards, M; Wadsworth, M E J

2004-10-01

To investigate long term effects of early adverse circumstances on cognitive function. Associations between early material home circumstances, parental divorce, maternal management and understanding, and cognitive function in childhood, adolescence, and adulthood were analysed using multiple linear regression, controlling for sex, parental SES, and birth order in 1339 males and females from the MRC National Survey of Health and Development. Early adverse circumstances were strongly associated with lower cognitive ability in childhood and adolescence, and were detectable on measures of verbal ability, memory, and speed and concentration in midlife. However, these long term effects were mostly explained by the effects of adversity on childhood or adolescent cognitive ability or by differences in educational attainment and adult social class. An exception was the effect of poor material home conditions on visual search speed at 53 years, which was maintained after controlling for adolescent ability, as well as further control for educational attainment, adult social class, physical growth, cigarette smoking, and affective state. There was no evidence of more rapid decline in memory and psychomotor function across middle age in those exposed to early adversity. The effect of early adversity on cognitive function tracks across the life course at least as far as middle age, although there was little evidence from this study of effect amplification over this interval. Nevertheless, in view of the persistence of child poverty in the industrialised world, these findings give cause for concern.

Are adverse effects incorporated in economic models? An initial review of current practice.

PubMed

Craig, D; McDaid, C; Fonseca, T; Stock, C; Duffy, S; Woolacott, N

2009-12-01

To identify methodological research on the incorporation of adverse effects in economic models and to review current practice. Major electronic databases (Cochrane Methodology Register, Health Economic Evaluations Database, NHS Economic Evaluation Database, EconLit, EMBASE, Health Management Information Consortium, IDEAS, MEDLINE and Science Citation Index) were searched from inception to September 2007. Health technology assessment (HTA) reports commissioned by the National Institute for Health Research (NIHR) HTA programme and published between 2004 and 2007 were also reviewed. The reviews of methodological research on the inclusion of adverse effects in decision models and of current practice were carried out according to standard methods. Data were summarised in a narrative synthesis. Of the 719 potentially relevant references in the methodological research review, five met the inclusion criteria; however, they contained little information of direct relevance to the incorporation of adverse effects in models. Of the 194 HTA monographs published from 2004 to 2007, 80 were reviewed, covering a range of research and therapeutic areas. In total, 85% of the reports included adverse effects in the clinical effectiveness review and 54% of the decision models included adverse effects in the model; 49% included adverse effects in the clinical review and model. The link between adverse effects in the clinical review and model was generally weak; only 3/80 (< 4%) used the results of a meta-analysis from the systematic review of clinical effectiveness and none used only data from the review without further manipulation. Of the models including adverse effects, 67% used a clinical adverse effects parameter, 79% used a cost of adverse effects parameter, 86% used one of these and 60% used both. Most models (83%) used utilities, but only two (2.5%) used solely utilities to incorporate adverse effects and were explicit that the utility captured relevant adverse effects; 53% of

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.

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

Biophysics and Molecular Biology of Cardiac Ion Channels for the Safety Pharmacologist.

PubMed

Pugsley, Michael K; Curtis, Michael J; Hayes, Eric S

2015-01-01

Cardiac safety pharmacology is a continuously evolving discipline that uses the basic principles of pharmacology in a regulatory-driven process to generate data to inform risk/benefit assessment of a new chemical entity (NCE). The aim of cardiac safety pharmacology is to characterise the pharmacodynamic/pharmacokinetic (PK/PD) relationship of a drug's adverse effects on the heart using continuously evolving methodology. Unlike Toxicology, safety pharmacology includes within its remit a regulatory requirement to predict the risk of rare cardiotoxic (potentially lethal) events such as torsades de pointes (TdP), which is statistically associated with drug-induced changes in the QT interval of the ECG due to blockade of I Kr or K v11.1 current encoded by hERG. This gives safety pharmacology its unique character. The key issues for the safety pharmacology assessment of a drug on the heart are detection of an adverse effect liability, projection of the data into safety margin calculation and clinical safety monitoring. This chapter will briefly review the current cardiac safety pharmacology paradigm outlined in the ICH S7A and ICH S7B guidance documents and the non-clinical models and methods used in the evaluation of new chemical entities in order to define the integrated risk assessment for submission to regulatory authorities. An overview of how the present cardiac paradigm was developed will be discussed, explaining how it was based upon marketing authorisation withdrawal of many non-cardiovascular compounds due to unanticipated proarrhythmic effects. The role of related biomarkers (of cardiac repolarisation, e.g. prolongation of the QT interval of the ECG) will be considered. We will also provide an overview of the 'non-hERG-centric' concepts utilised in the evolving comprehensive in vitro proarrhythmia assay (CIPA) that details conduct of the proposed ion channel battery test, use of human stem cells and application of in silico models to early cardiac safety

Adverse Impact of Diet-Induced Hypercholesterolemia on Cardiovascular Tissue Homeostasis in a Rabbit Model: Time-Dependent Changes in Cardiac Parameters

PubMed Central

Kertész, Attila; Bombicz, Mariann; Priksz, Daniel; Balla, Jozsef; Balla, Gyorgy; Gesztelyi, Rudolf; Varga, Balazs; Haines, David D.; Tosaki, Arpad; Juhasz, Bela

2013-01-01

The present study evaluates a hypothesis that diet-related hypercholesterolemia increases oxidative stress-related burden to cardiovascular tissue, resulting in progressively increased mortality, along with deterioration of electrophysiological and enzymatic function in rabbit myocardium. New Zealand white rabbits were divided into four groups, defined as follows: GROUP I, cholesterol-free rabbit chow for 12 weeks; GROUP II, cholesterol-free chow, 40 weeks; GROUP III, chow supplemented with 2% cholesterol, 12 weeks; GROUP IV, chow supplemented with 2% cholesterol, 40 weeks. At the 12 and 40 weeks time points, animals in each of the aforementioned cohorts were subjected to echocardiographic measurements, followed by sacrifice. Significant deterioration in major outcome variables measured in the present study were observed only in animals maintained for 40 weeks on 2% cholesterol-supplemented chow, with much lesser adverse effects noted in animals fed high cholesterol diets for only 12 weeks. It was observed that rabbits receiving high cholesterol diets for 40 weeks exhibited significantly increased mortality, worsened ejection fraction and general deterioration of cardiac functions, along with increased atherosclerotic plaque formation and infarct size. Additionally, myocardium of GROUP IV animals was observed to contain lower levels of heme oxygenase-1 (HO-1) and cytochrome c oxidase III (COX III) protein relative to the controls. PMID:24048247

The chemokine decoy receptor D6 prevents excessive inflammation and adverse ventricular remodeling after myocardial infarction.

PubMed

Cochain, Clément; Auvynet, Constance; Poupel, Lucie; Vilar, José; Dumeau, Edouard; Richart, Adèle; Récalde, Alice; Zouggari, Yasmine; Yin, Kiave Yune Ho Wang; Bruneval, Patrick; Renault, Gilles; Marchiol, Carmen; Bonnin, Philippe; Lévy, Bernard; Bonecchi, Raffaella; Locati, Massimo; Combadière, Christophe; Silvestre, Jean-Sébastien

2012-09-01

Leukocyte infiltration in ischemic areas is a hallmark of myocardial infarction, and overwhelming infiltration of innate immune cells has been shown to promote adverse remodeling and cardiac rupture. Recruitment of inflammatory cells in the ischemic heart depends highly on the family of CC-chemokines and their receptors. Here, we hypothesized that the chemokine decoy receptor D6, which specifically binds and scavenges inflammatory CC-chemokines, might limit inflammation and adverse cardiac remodeling after infarction. D6 was expressed in human and murine infarcted myocardium. In a murine model of myocardial infarction, D6 deficiency led to increased chemokine (C-C motif) ligand 2 and chemokine (C-C motif) ligand 3 levels in the ischemic heart. D6-deficient (D6(-/-)) infarcts displayed increased infiltration of pathogenic neutrophils and Ly6Chi monocytes, associated with strong matrix metalloproteinase-9 and matrix metalloproteinase-2 activities in the ischemic heart. D6(-/-) mice were cardiac rupture prone after myocardial infarction, and functional analysis revealed that D6(-/-) hearts had features of adverse remodeling with left ventricle dilation and reduced ejection fraction. Bone marrow chimera experiments showed that leukocyte-borne D6 had no role in this setting, and that leukocyte-specific chemokine (C-C motif) receptor 2 deficiency rescued the adverse phenotype observed in D6(-/-) mice. We show for the first time that the chemokine decoy receptor D6 limits CC-chemokine-dependent pathogenic inflammation and is required for adequate cardiac remodeling after myocardial infarction.

Effectiveness of nurse-led cardiac clinics in adult patients with a diagnosis of coronary heart disease.

PubMed

Page, Tamara; Lockwood, Craig; Conroy-Hiller, Tiffany

2005-02-01

Background  Coronary heart disease is the major cause of illness and death in Western countries and this is likely to increase as the average age of the population rises. Consumers with established coronary heart disease are at the highest risk of experiencing further coronary events. Lifestyle measures can contribute significantly to a reduction in cardiovascular mortality in established coronary heart disease. Improved management of cardiac risk factors by providing education and referrals as required has been suggested as one way of maintaining quality care in patients with established coronary heart disease. There is a need to ascertain whether or not nurse-led clinics would be an effective adjunct for patients with coronary heart disease to supplement general practitioner advice and care. Objectives  The objective of this review was to present the best available evidence related to nurse-led cardiac clinics. Inclusion criteria  This review considered any randomised controlled trials that evaluated cardiac nurse-led clinics. In the absence of randomised controlled trials, other research designs such as non-randomised controlled trials and before and after studies were considered for inclusion. Participants were adults (18 years and older) with new or existing coronary heart disease. The interventions of interest to the review included education, assessment, consultation, referral and administrative structures. Outcomes measured included adverse event rates, readmissions, admissions, clinical and cost effectiveness, consumer satisfaction and compliance with therapy. Results  Based on the search terms used, 80 papers were initially identified and reviewed for inclusion; full reports of 24 of these papers were retrieved. There were no papers included that addressed cost effectiveness or adverse events; and none addressed the outcome of referrals. A critical appraisal of the 24 remaining papers identified a total of six randomised controlled trials that

Adverse effects of aromatherapy: a systematic review of case reports and case series.

PubMed

Posadzki, Paul; Alotaibi, Amani; Ernst, Edzard

2012-01-01

This systematic review was aimed at critically evaluating the evidence regarding the adverse effects associated with aromatherapy. Five electronic databases were searched to identify all relevant case reports and case series. Forty two primary reports met our inclusion criteria. In total, 71 patients experienced adverse effects of aromatherapy. Adverse effects ranged from mild to severe and included one fatality. The most common adverse effect was dermatitis. Lavender, peppermint, tea tree oil and ylang-ylang were the most common essential oils responsible for adverse effects. Aromatherapy has the potential to cause adverse effects some of which are serious. Their frequency remains unknown. Lack of sufficiently convincing evidence regarding the effectiveness of aromatherapy combined with its potential to cause adverse effects questions the usefulness of this modality in any condition.

[Adverse ocular effects of vaccinations].

PubMed

Ness, T; Hengel, H

2016-07-01

Vaccinations are very effective measures for prevention of infections but are also associated with a long list of possible side effects. Adverse ocular effects following vaccination have been rarely reported or considered to be related to vaccinations. Conjunctivitis is a frequent sequel of various vaccinations. Oculorespiratory syndrome and serum sickness syndrome are considered to be related to influenza vaccinations. The risk of reactivation or initiation of autoimmune diseases (e. g. uveitis) cannot be excluded but has not yet been proven. Overall the benefit of vaccination outweighs the possible but very low risk of ocular side effects.

Feasibility and cardiac safety of inhaled xenon in combination with therapeutic hypothermia following out-of-hospital cardiac arrest.

PubMed

Arola, Olli J; Laitio, Ruut M; Roine, Risto O; Grönlund, Juha; Saraste, Antti; Pietilä, Mikko; Airaksinen, Juhani; Perttilä, Juha; Scheinin, Harry; Olkkola, Klaus T; Maze, Mervyn; Laitio, Timo T

2013-09-01

Preclinical studies reveal the neuroprotective properties of xenon, especially when combined with hypothermia. The purpose of this study was to investigate the feasibility and cardiac safety of inhaled xenon treatment combined with therapeutic hypothermia in out-of-hospital cardiac arrest patients. An open controlled and randomized single-centre clinical drug trial (clinicaltrials.gov NCT00879892). A multipurpose ICU in university hospital. Thirty-six adult out-of-hospital cardiac arrest patients (18-80 years old) with ventricular fibrillation or pulseless ventricular tachycardia as initial cardiac rhythm. Patients were randomly assigned to receive either mild therapeutic hypothermia treatment with target temperature of 33°C (mild therapeutic hypothermia group, n=18) alone or in combination with xenon by inhalation, to achieve a target concentration of at least 40% (Xenon+mild therapeutic hypothermia group, n=18) for 24 hours. Thirty-three patients were evaluable (mild therapeutic hypothermia group, n=17; Xenon+mild therapeutic hypothermia group, n=16). Patients were treated and monitored according to the Utstein protocol. The release of troponin-T was determined at arrival to hospital and at 24, 48, and 72 hours after out-of-hospital cardiac arrest. The median end-tidal xenon concentration was 47% and duration of the xenon inhalation was 25.5 hours. The frequency of serious adverse events, including inhospital mortality, status epilepticus, and acute kidney injury, was similar in both groups and there were no unexpected serious adverse reactions to xenon during hospital stay. In addition, xenon did not induce significant conduction, repolarization, or rhythm abnormalities. Median dose of norepinephrine during hypothermia was lower in xenon-treated patients (mild therapeutic hypothermia group=5.30 mg vs Xenon+mild therapeutic hypothermia group=2.95 mg, p=0.06). Heart rate was significantly lower in Xenon+mild therapeutic hypothermia patients during hypothermia

Potential adverse cardiac remodelling in highly trained athletes: still unknown clinical significance.

PubMed

Gabrielli, Luigi; Sitges, Marta; Chiong, Mario; Jalil, Jorge; Ocaranza, María; Llevaneras, Silvana; Herrera, Sebastian; Fernandez, Rodrigo; Saavedra, Rodrigo; Yañez, Fernando; Vergara, Luis; Diaz, Alexis; Lavandero, Sergio; Castro, Pablo

2018-06-12

Moderate endurance exercise has long been considered an essential element to maintain cardiovascular health, and sedentary behaviour in the general population has been related to a significant increase in all-causes of mortality, cardiovascular disease mortality and cardiovascular disease incidence. However, a growing group of people performs an intense exercise that leads to multiple heart adaptive changes that are collectively called "athlete's heart". In this review, we discussed the evidence of cardiac remodelling process secondary to repetitive and strenuous exercise in some predisposed athletes that produces intense and probably deleterious changes in cardiac morphology and function with no clear clinical significance in long-term follow-up. Moreover, we also discussed the individual biological response to exercise assessed by myocardial damage, inflammation, oxidative stress, fibrosis and ventricular hypertrophy biomarkers showing different intensities with equivalent exertion.

Heart repair by reprogramming non-myocytes with cardiac transcription factors

PubMed Central

Song, Kunhua; Nam, Young-Jae; Luo, Xiang; Qi, Xiaoxia; Tan, Wei; Huang, Guo N.; Acharya, Asha; Smith, Christopher L.; Tallquist, Michelle D.; Neilson, Eric G.; Hill, Joseph A.; Bassel-Duby, Rhonda; Olson, Eric N.

2012-01-01

The adult mammalian heart possesses little regenerative potential following injury. Fibrosis due to activation of cardiac fibroblasts impedes cardiac regeneration and contributes to loss of contractile function, pathological remodeling and susceptibility to arrhythmias. Cardiac fibroblasts account for a majority of cells in the heart and represent a potential cellular source for restoration of cardiac function following injury through phenotypic reprogramming to a myocardial cell fate. Here we show that four transcription factors, GATA4, Hand2, MEF2C and Tbx5 can cooperatively reprogram adult mouse tail-tip and cardiac fibroblasts into beating cardiac-like myocytes in vitro. Forced expression of these factors in dividing non-cardiomyocytes in mice reprograms these cells into functional cardiac-like myocytes, improves cardiac function and reduces adverse ventricular remodeling following myocardial infarction. Our results suggest a strategy for cardiac repair through reprogramming fibroblasts resident in the heart with cardiogenic transcription factors or other molecules. PMID:22660318

Prevalence and detection of neuropsychiatric adverse effects during hepatitis C treatment.

PubMed

Masip, Montserrat; Tuneu, Laura; Pagès, Neus; Torras, Xavier; Gallego, Adolfo; Guardiola, Josep Maria; Faus, María José; Mangues, Maria Antònia

2015-12-01

Current treatment combinations for chronic hepatitis C virus infection still include pegylated interferon and ribavirin despite the new therapeutic options available. Interferon-based treatments are associated with a high incidence of adverse effects. Central nervous system events are among the most frequent adverse drug reactions and their influence on treatment adherence and effectiveness is controversial. The aim of the study was to evaluate neuropsychiatric adverse effects of interferon-based treatment for chronic hepatitis C in standard multidisciplinary clinical practice. Risk factors for these adverse effects and their impact on adherence and sustained viral response were also evaluated. Setting Ambulatory care pharmacy in coordination with the liver unit and the infectious diseases unit at a 650-bed tertiary university hospital. We included all consecutive patients with chronic hepatitis C who completed treatment with pegylated interferon and ribavirin between 2005 and 2013. All patients underwent a multidisciplinary follow-up during treatment. Neuropsychiatric adverse effects were evaluated in relation to severity, management and outcome. The presence of anxiety and depression was evaluated by means of specific tests. A total of 717 treatments in 679 patients were included. During treatment, we detected 1679 neuropsychiatric adverse effects in 618 patients (86.2 %), generating 1737 clinical interventions. Fifty-seven (3.3 %) neuropsychiatric adverse effects were severe and 2 (0.1 %) were life-threatening (suicidal attempts). Most neuropsychiatric adverse effects (1555 events, 92.6 %) resolved without sequelae. Psychiatric medication was required in 289 patients (40.3 %). Sustained viral response was achieved in 400 cases (55.8 %) and was associated with adherence (OR = 1.942, 95 % CI = 1.235-3.052, p = 0.004). A multivariate analysis did not show any relationship between neuropsychiatric adverse effects and treatment adherence or sustained viral response

Glycated hemoglobin level is an independent predictor of major adverse cardiac events after nonfatal acute myocardial infarction in nondiabetic patients: A retrospective observational study.

PubMed

Chen, Chin-Lan; Yen, David H-T; Lin, Chin-Sheng; Tsai, Shih-Hung; Chen, Sy-Jou; Sheu, Wayne H-H; Hsu, Chin-Wang

2017-05-01

The effect of glycemic control on the prognosis of nondiabetic patients after acute myocardial infarction (AMI) remains uncertain. We investigated whether glycated hemoglobin (HbA1c) is associated with adverse outcomes after AMI in nondiabetic patients. In this observational study, we enrolled nondiabetic patients with AMI in the emergency department of 2 medical centers from January 2011 to September 2014. All patients received primary percutaneous coronary intervention and were divided into 4 groups according to the interquartile range of average HbA1c level (Group I, ≤5.6%; Group II, 5.6%-5.8%; Group III, 5.8%-6.0%; and Group IV, >6.0%). Multivariate logistic analysis was performed to estimate the correlation of HbA1c with major adverse cardiac events (MACEs) after AMI. In total, 267 eligible patients were enrolled; 48 patients (18%) developed MACEs within a median follow-up of 178 days. Univariate analysis showed HbA1c > 6.0%, with a higher risk of MACEs in Group IV than in Group I (odds ratio [OR]: 2.733; 95% confidence interval [CI]: 1.123-6.651 vs OR: 1.511; 95% CI: 0.595-3.835). Multivariate analysis revealed an approximately 3.8 times higher risk of MACEs in Group IV than in Group I (OR: 3.769; 95% CI: 1.30-10.86). The HbA1 level is a significant predictor of MACEs after AMI in nondiabetic patients.

Contrast-induced encephalopathy following cardiac catheterization.

PubMed

Spina, Roberto; Simon, Neil; Markus, Romesh; Muller, David Wm; Kathir, Krishna

2017-08-01

To describe the epidemiology, pathophysiology, clinical presentation, and management of contrast-induced encephalopathy (CIE) following cardiac catheterization. CIE is an acute, reversible neurological disturbance directly attributable to the intra-arterial administration of iodinated contrast medium. The PubMed database was searched and all cases in the literature were retrieved and reviewed. 52 reports of CIE following cardiac catheterization were found. Encephalopathy, motor and sensory disturbances, vision disturbance, opthalmoplegia, aphasia, and seizures have been reported. Transient cortical blindness is the most commonly reported neurological syndrome, occurring in approximately 50% of cases. The putative mechanism involves disruption of the blood brain barrier and direct neuronal injury. Contrast-induced transient vasoconstriction has also been implicated. Symptoms typically appear within minutes to hours of contrast administration and resolve entirely within 24-48 hr. Risk factors may include hypertension, diabetes mellitus, renal impairment, the administration of large volumes of iodinated contrast, percutaneous coronary intervention or selective angiography of internal mammary grafts, and previous adverse reaction to iodinated contrast. Characteristic findings on cerebral imaging include cortical and sub-cortical contrast enhancement on computed tomography (CT). Imaging findings in CIE may mimic subarachnoid hemorrhage or cerebral ischemia; the Hounsfield scale on CT and the apparent diffusion coefficient on magnetic resonance imaging (MRI) are useful imaging tools in distinguishing these entities. In some cases, brain imaging is normal. Prognosis is excellent with supportive management alone. CIE tends to recur, although re-challenge with iodinated contrast without adverse effects has been documented. CIE is an important clinical entity to consider in the differential diagnosis of stroke following cardiac catheterization. Given that prognosis is

Novel Sternal Protection Device for Cardiac Surgery Via Median Sternotomy Incision.

PubMed

Marasco, Silvana F; McGiffin, David C; Zimmet, Adam D; Solis, Pablo C; Bingham, Judy M; Moshinsky, Randall A

Sternal bleeding during cardiac surgery is currently controlled using bone wax or other chemical substances that may result in adverse effects and affect wound healing and recovery. The purpose of this study was to identify a safe, cost-effective, and easy-to-use technique to reduce sternal bleeding and sternal trauma during cardiac surgery. After sternotomy, a sternal protection device was placed over each hemisternal section before insertion of the retractor and remained in situ until the end of surgery. Sternal bleeding and ease of use were assessed and recorded during surgery. Sternal trauma was assessed and recorded within 5 minutes of removal of the device, and overall satisfaction (Global Impression) and any intraoperative adverse events or device malfunction were reported at surgery completion. Patients were followed up 24 hours and 4 weeks after surgery. Twelve patients completed the study. Adverse events reported were not considered related to the device. No sternal trauma was identified in any patient. In 9 of 11 patients, sternal bleeding was reduced after insertion of the device. The device was generally considered easy to use, although some difficulty was encountered when used with the Internal Mammary Artery retractor. Our data suggest that the device is safe and able to reduce sternal bleeding during surgery using sternal retractors. We recommend further studies in a larger population of patients with a control group to evaluate the device's ability to reduce the morbidity associated with sternal bleeding and sternal trauma.

Radiation effect on implanted pacemakers

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

Pourhamidi, A.H.

1983-10-01

It was previously thought that diagnostic or therapeutic ionizing radiation did not have an adverse effect on the function of cardiac pacemakers. Recently, however, some authors have reported damaging effect of therapeutic radiation on cardiac pulse generators. An analysis of a recently-extracted pacemaker documented the effect of radiation on the pacemaker pulse generator.

Medications and Adverse Voice Effects.

PubMed

Nemr, Kátia; Di Carlos Silva, Ariana; Rodrigues, Danilo de Albuquerque; Zenari, Marcia Simões

2017-08-16

To identify the medications used by patients with dysphonia, describe the voice symptoms reported on initial speech-language pathology (SLP) examination, evaluate the possible direct and indirect effects of medications on voice production, and determine the association between direct and indirect adverse voice effects and self-reported voice symptoms, hydration and smoking habits, comorbidities, vocal assessment, and type and degree of dysphonia. This is a retrospective cross-sectional study. Fifty-five patients were evaluated and the vocal signs and symptoms indicated in the Dysphonia Risk Protocol were considered, as well as data on hydration, smoking and medication use. We analyzed the associations between type of side effect and self-reported vocal signs/symptoms, hydration, smoking, comorbidities, type of dysphonia, and auditory-perceptual and acoustic parameters. Sixty percent were women, the mean age was 51.8 years, 29 symptoms were reported on the screening, and 73 active ingredients were identified with 8.2% directly and 91.8% indirectly affecting vocal function. There were associations between the use of drugs with direct adverse voice effects, self-reported symptoms, general degree of vocal deviation, and pitch deviation. The symptoms of dry throat and shortness of breath were associated with the direct vocal side effect of the medicine, as well as the general degree of vocal deviation and the greater pitch deviation. Shortness of breath when speaking was also associated with the greatest degree of vocal deviation. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Industrial wind turbines and adverse health effects.

PubMed

Jeffery, Roy D; Krogh, Carmen M E; Horner, Brett

2014-01-01

Some people living in the environs of industrial wind turbines (IWTs) report experiencing adverse health and socioeconomic effects. This review considers the hypothesis that annoyance from audible IWTs is the cause of these adverse health effects. We searched PubMed and Google Scholar for articles published since 2000 that included the terms "wind turbine health," "wind turbine infrasound," "wind turbine annoyance," "noise annoyance" or "low frequency noise" in the title or abstract. Industrial wind turbines produce sound that is perceived to be more annoying than other sources of sound. Reported effects from exposure to IWTs are consistent with well-known stress effects from persistent unwanted sound. If placed too close to residents, IWTs can negatively affect the physical, mental and social well-being of people. There is sufficient evidence to support the conclusion that noise from audible IWTs is a potential cause of health effects. Inaudible low-frequency noise and infrasound from IWTs cannot be ruled out as plausible causes of health effects.

The effect of matrix stiffness of injectable hydrogels on the preservation of cardiac function after a heart attack.

PubMed

Plotkin, Marian; Vaibavi, Srirangam Ramanujam; Rufaihah, Abdul Jalil; Nithya, Venkateswaran; Wang, Jing; Shachaf, Yonatan; Kofidis, Theo; Seliktar, Dror

2014-02-01

This study compares the effect of four injectable hydrogels with different mechanical properties on the post-myocardial infarction left ventricle (LV) remodeling process. The bioactive hydrogels were synthesized from Tetronic-fibrinogen (TF) and PEG-fibrinogen (PF) conjugates; each hydrogel was supplemented with two levels of additional cross-linker to increase the matrix stiffness as measured by the shear storage modulus (G'). Infarcts created by ligating the left anterior descending coronary artery in a rodent model were treated with the hydrogels, and all four treatment groups showed an increase in wall thickness, arterial density, and viable cardiac tissue in the peri-infarct areas of the LV. Echocardiography and hemodynamics data of the PF/TF treated groups showed significant improvement of heart function associated with the attenuated effects of the remodeling process. Multi-factorial regression analysis indicated that the group with the highest modulus exhibited the best rescue of heart function and highest neovascularization. The results of this study demonstrate that multiple properties of an injectable bioactive biomaterial, and notably the matrix stiffness, provide the multifaceted stimulation necessary to preserve cardiac function and prevent adverse remodeling following a heart attack. Copyright © 2013 Elsevier Ltd. All rights reserved.

Examining the role of TRPA1 in air pollution-induced cardiac arrhythmias and autonomic imbalance

EPA Science Inventory

Here we describe how air pollution causes cardiac arrhythmogenesis through sensory irritation in the airways. Time-series studies show the risk of adverse cardiac events increases significantly in the hours to days after expos...

Prognostic role of cardiac power index in ambulatory patients with advanced heart failure.

PubMed

Grodin, Justin L; Mullens, Wilfried; Dupont, Matthias; Wu, Yuping; Taylor, David O; Starling, Randall C; Tang, W H Wilson

2015-07-01

Cardiac pump function is often quantified by left ventricular ejection fraction by various imaging modalities. As the heart is commonly conceptualized as a hydraulic pump, cardiac power describes the hydraulic function of the heart. We aim to describe the prognostic value of resting cardiac power index (CPI) in ambulatory patients with advanced heart failure. We calculated CPI in 495 sequential ambulatory patients with advanced heart failure who underwent invasive haemodynamic assessment with longitudinal follow-up of adverse outcomes (all-cause mortality, cardiac transplantation, or ventricular assist device placement). The median CPI was 0.44 W/m(2) (interquartile range 0.37, 0.52). Over a median of 3.3 years, there were 117 deaths, 104 transplants, and 20 ventricular assist device placements in our cohort. Diminished CPI (<0.44 W/m(2) ) was associated with increased adverse outcomes [hazard ratio (HR) 2.4, 95% confidence interval (CI) 1.8-3.1, P < 0.0001). The prognostic value of CPI remained significant after adjustment for age, gender, pulmonary capillary wedge pressure, cardiac index, pulmonary vascular resistance, left ventricular ejection fraction, and creatinine [HR 1.5, 95% CI 1.03-2.3, P = 0.04). Furthermore, CPI can risk stratify independently of peak oxygen consumption (HR 2.2, 95% CI 1.4-3.4, P = 0.0003). Resting cardiac power index provides independent and incremental prediction in adverse outcomes beyond traditional haemodynamic and cardio-renal risk factors. © 2015 The Authors. European Journal of Heart Failure © 2015 European Society of Cardiology.

Late Administration of a Palladium Lipoic Acid Complex (POLY-MVA) Modifies Cardiac Mitochondria but Not Functional or Structural Manifestations of Radiation-Induced Heart Disease in a Rat Model

PubMed Central

Sridharan, Vijayalakshmi; Seawright, John W.; Antonawich, Francis J.; Garnett, Merrill; Cao, Maohua; Singh, Preeti; Boerma, Marjan

2017-01-01

Exposure of the heart to ionizing radiation can cause adverse myocardial remodeling. In small animal models, local heart irradiation causes persistent alterations in cardiac mitochondrial function and swelling. POLY-MVA is a dietary supplement that contains a palladium lipoic acid complex that targets mitochondrial complex I and has been demonstrated to have greater redox potential than lipoic acid alone. POLY-MVA improves mitochondrial function and anti-oxidant enzyme activity in the aged rat heart. In this study, we tested whether POLY-MVA can mitigate cardiac effects of ionizing radiation. Adult male rats were exposed to local heart X rays with a daily dose of 9 Gy for 5 consecutive days. Eighteen weeks after irradiation, POLY-MVA was administered orally at 1 ml/kg bodyweight per day during weekdays, for 6 weeks. Alterations in cardiac function as measured with echocardiography coincided with enhanced mitochondrial swelling, a reduction in mitochondrial expression of complex II, manifestations of adverse remodeling such as a reduction in myocardial microvessel density and an increase in collagen deposition and mast cell numbers. POLY-MVA enhanced left ventricular expression of superoxide dismutase 2, but only in sham-irradiated animals. In irradiated animals, POLY-MVA caused a reduction in markers of inflammatory infiltration, CD2 and CD68. Moreover, POLY-MVA mitigated the effects of radiation on mitochondria. Nonetheless, POLY-MVA did not mitigate adverse cardiac remodeling, suggesting that this tissue remodeling may not be alleviated by altering cardiac mitochondria alone. However, we cannot exclude the possibility that an earlier onset of POLY-MVA administration may have more profound effects on radiation-induced cardiac remodeling. PMID:28231026

Cardiac effects of electrically induced intrathoracic autonomic reflexes.

PubMed

Armour, J A

1988-06-01

Electrical stimulation of the afferent components in one cardiopulmonary nerve (the left vagosympathetic complex at a level immediately caudal to the origin of the left recurrent laryngeal nerve) in acutely decentralized thoracic autonomic ganglionic preparations altered cardiac chronotropism and inotropism in 17 of 44 dogs. Since these neural preparations were acutely decentralized, the effects were mediated presumably via intrathoracic autonomic reflexes. The lack of consistency of these reflexly generated cardiac responses presumably were due in part to anatomical variation of afferent axons in the afferent nerve stimulated. As stimulation of the afferent components in the same neural structure caudal to the heart (where cardiopulmonary afferent axons are not present) failed to elicit cardiac responses in any dog, it is presumed that when cardiac responses were elicited by the more cranially located stimulations, these were due to activation of afferent axons arising from the heart and (or) lungs. When cardiac responses were elicited, intramyocardial pressures in the right ventricular conus as well as the ventral and lateral walls of the left ventricle were augmented. Either bradycardia or tachycardia was elicited. Following hexamethonium administration no responses were produced, demonstrating that nicotonic cholinergic synaptic mechanisms were involved in these intrathoracic cardiopulmonary-cardiac reflexes. In six of the animals, when atropine was administered before hexamethonium, reflexly generated responses were attenuated. The same thing occurred when morphine was administered in four animals. In contrast, in four animals following administration of phentolamine, the reflexly generated changes were enhanced.(ABSTRACT TRUNCATED AT 250 WORDS)

40 CFR 174.71 - Submission of information regarding adverse effects.

Code of Federal Regulations, 2011 CFR

2011-07-01

... any information regarding adverse effects on human health or the environment alleged to have been... information. (b) Adverse effects on human health or the environment for purposes of plant-incorporated... (CONTINUED) PESTICIDE PROGRAMS PROCEDURES AND REQUIREMENTS FOR PLANT-INCORPORATED PROTECTANTS Monitoring and...

40 CFR 174.71 - Submission of information regarding adverse effects.

Code of Federal Regulations, 2014 CFR

2014-07-01

... any information regarding adverse effects on human health or the environment alleged to have been... information. (b) Adverse effects on human health or the environment for purposes of plant-incorporated... (CONTINUED) PESTICIDE PROGRAMS PROCEDURES AND REQUIREMENTS FOR PLANT-INCORPORATED PROTECTANTS Monitoring and...

40 CFR 174.71 - Submission of information regarding adverse effects.

Code of Federal Regulations, 2012 CFR

2012-07-01

... any information regarding adverse effects on human health or the environment alleged to have been... information. (b) Adverse effects on human health or the environment for purposes of plant-incorporated... (CONTINUED) PESTICIDE PROGRAMS PROCEDURES AND REQUIREMENTS FOR PLANT-INCORPORATED PROTECTANTS Monitoring and...

40 CFR 174.71 - Submission of information regarding adverse effects.

Code of Federal Regulations, 2010 CFR

2010-07-01

... any information regarding adverse effects on human health or the environment alleged to have been... information. (b) Adverse effects on human health or the environment for purposes of plant-incorporated... (CONTINUED) PESTICIDE PROGRAMS PROCEDURES AND REQUIREMENTS FOR PLANT-INCORPORATED PROTECTANTS Monitoring and...

40 CFR 174.71 - Submission of information regarding adverse effects.

Code of Federal Regulations, 2013 CFR

2013-07-01

... any information regarding adverse effects on human health or the environment alleged to have been... information. (b) Adverse effects on human health or the environment for purposes of plant-incorporated... (CONTINUED) PESTICIDE PROGRAMS PROCEDURES AND REQUIREMENTS FOR PLANT-INCORPORATED PROTECTANTS Monitoring and...

Effects of levosimendan on mortality in patients undergoing cardiac surgery: A systematic review and meta-analysis.

PubMed

Chen, Peili; Wu, Xiaoqiang; Wang, Zhiwei; Li, Zhenya; Tian, Xiangyong; Wang, Junpeng; Yan, Tianzhong

2018-06-01

We sought to determine the impact of levosimendan on mortality following cardiac surgery based on large-scale randomized controlled trials (RCTs). We searched PubMed, Web of Science, Cochrane databases, and ClinicalTrials.gov for RCTs published up to December 2017, on levosimendan for patients undergoing cardiac surgery. A total of 25 RCTs enrolling 2960 patients met the inclusion criteria; data from 15 placebo-controlled randomized trials were included for meta-analysis. Pooled analysis showed that the all-cause mortality rate was 6.4% (71 of 1106) in the levosimendan group and 8.4% (93 of 1108) in the placebo group (odds ratio [OR], 0.76; 95% confidence interval [CI], 0.55-1.04; P = 0.09). There were no significant differences between the two groups in the rates of myocardial infarction (OR: 0.91; 95% CI, 0.68-1.21; P = 0.52), serious adverse events (OR: 0.84; 95% CI, 0.66-1.07; P = 0.17), hypotension (OR: 1.69; 95% CI, 0.94-3.03; P = 0.08), and low cardiac output syndrome (OR: 0.47; 95% CI, 0.22-1.02; P = 0.05). Levosimendan did not result in a reduction in mortality in adult cardiac surgery patients. Well designed, adequately powered, multicenter trials are necessary to determine the role of levosimendan in adult cardiac surgery. © 2018 The Authors. Journal of Cardiac Surgery Published by Wiley Periodicals Inc.

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

Serum from Diesel Exhaust-Exposed Rats with Cardiac Dysfunction Alters Aortic Endothelial Cell Function In Vitro: Circulating Mediators as Causative Factors?

EPA Science Inventory

Although circulating inflammatory mediators are strongly associated with adverse cardiovascular outcomes triggered by inhaled air pollution, direct cause-effect linkage has not been established. Given that endothelial toxicity often precedes and precipitates cardiac dysfunction, ...

Inhibitor of lysyl oxidase improves cardiac function and the collagen/MMP profile in response to volume overload.

PubMed

El Hajj, Elia C; El Hajj, Milad C; Ninh, Van K; Gardner, Jason D

2018-05-18

The cardiac extracellular matrix is a complex architectural network that serves many functions including providing structural and biochemical support to surrounding cells, and regulating intercellular signaling pathways. Cardiac function is directly affected by extracellular matrix (ECM) composition, and alterations of the ECM contribute to progression of heart failure. Initially, collagen deposition is an adaptive response that aims to preserve tissue integrity and maintain normal ventricular function. However, the synergistic effects of the pro-inflammatory and pro-fibrotic responses induce a vicious cycle which causes excess activation of myofibroblasts, significantly increasing collagen deposition and accumulation in the matrix. Further, excess synthesis and activation of the enzyme lysyl oxidase (LOX) during disease increases collagen cross-linking, which significantly increases collagen resistance to degradation by matrix metalloproteinases (MMPs). In this study, the aortocaval fistula model of volume overload (VO) was used to determine whether LOX inhibition could prevent adverse changes in the ECM and subsequent cardiac dysfunction. The major findings from this study are that LOX inhibition: (a) prevented VO-induced increases in LV wall stress, (b) partially attenuated VO-induced ventricular hypertrophy, (c) completely blocked the increases in fibrotic proteins, including collagens, MMPs, and their tissue inhibitors (TIMPs), and (d) prevented the VO-induced decline in cardiac function. It remains unclear whether a direct interaction between LOX and MMPs exists; however our studies suggest a potential link between the two since LOX inhibition completely attenuated the VO-induced increases in MMPs. Overall, our studies demonstrate key cardioprotective effects of LOX inhibition against adverse cardiac remodeling due to chronic VO.

Analysis of bedside entertainment services' effect on post cardiac surgery physical activity: a prospective, randomised clinical trial.

PubMed

Papaspyros, Sotiris; Uppal, Shitansu; Khan, Shakeeb A; Paul, Sanjoy; O'Regan, David J

2008-11-01

A rising number of acute hospitals in the UK have been providing patients with bedside entertainment services (BES) since 1995. However, their effect on postoperative patient mobility has not been explored. The aim of this prospective randomised clinical trial was to compare the level of postoperative physical activity and length of in-hospital stay of patients undergoing cardiac surgery depending on whether they had access to BES or not. One hundred patients requiring elective cardiac surgery were randomised to receive access to BES (52 patients) or not (48 patients). Pedometers were used to quantify postoperative physical activity for 5 days. To assess the significance of the effect of intervention (TV off or on) on the pedometer counts over time a mixed effect Poisson regression model is used, with the time varying aspect as random component. The potential influence of gender difference and age on pedometer counts were assessed by incorporating these two factors as covariates in the Poisson model. On average, patients with no access to BES walked more than those with BES access. This difference ranged between 192 and 609 steps in favour of the first group for each individual postoperative day. Patients with no access to BES were 84% more likely (risk ratio: 1.84, 95% CI: 1.29-2.63) to walk higher number of steps than patients with access to BES. On average, participants with access to BES were likely to stay longer in hospital (median of 7 days with interquartile range 6-7 days), than participants with no access to BES (median of 6 days with interquartile range 5-7 days), however the difference did not reach statistical significance. We have demonstrated that the bedside entertainment systems may have an adverse effect on post cardiac surgery patient ambulation and may contribute to an increase in hospital stay.

Capturing the cardiac effects of racial discrimination: Do the effects "keep going"?

PubMed

Hoggard, Lori S; Hill, LaBarron K; Gray, DeLeon L; Sellers, Robert M

2015-08-01

Racial discrimination negatively impacts cardiac functioning, but few studies examine the more distal cardiac effects of racial discrimination experiences. The present study examined the momentary and prolonged impact of lab-based intergroup and intragroup racial discrimination on heart rate variability (HRV) and heart rate (HR) in a sample (N = 42) of African American (AA) women across two days. On day one, the women were exposed to simulated racial discrimination from either a European American (EA) or AA confederate in the lab. On day two, the women returned to the lab for additional physiological recording and debriefing. Women insulted by the EA confederate exhibited lower HRV on day one and marginally lower HRV on day two. These women also exhibited marginally higher HR on day two. The HRV and HR effects on day two were not mediated by differences in perseveration about the stressor. The findings indicate that racial discrimination - particularly intergroup racial discrimination - may have both momentary and prolonged effects on cardiac activity in AAs. Copyright © 2015 Elsevier B.V. All rights reserved.

Epicardial adipose tissue density and volume are related to subclinical atherosclerosis, inflammation and major adverse cardiac events in asymptomatic subjects.

PubMed

Goeller, Markus; Achenbach, Stephan; Marwan, Mohamed; Doris, Mhairi K; Cadet, Sebastien; Commandeur, Frederic; Chen, Xi; Slomka, Piotr J; Gransar, Heidi; Cao, J Jane; Wong, Nathan D; Albrecht, Moritz H; Rozanski, Alan; Tamarappoo, Balaji K; Berman, Daniel S; Dey, Damini

We investigated whether epicardial adipose tissue (EAT) volume and density are related to early atherosclerosis, plaque inflammation and major adverse cardiac events (MACE, cardiac death and myocardial infarction) in asymptomatic subjects. EAT volume and density were quantified from non-contrast cardiac CT in 456 asymptomatic individuals (age 60.3 ± 8.3; 68% with CCS>0) from the prospective EISNER trial. EAT volume and density were examined in relation to coronary calcium score (CCS), inflammatory biomarkers and MACE. EAT volume was higher and EAT density lower in subjects with coronary calcium compared to subjects without [89 vs 74 cm 3 , p < 0.001] [-76.9 vs -75.7 HU,p = 0.024]. EAT volume was lowest in individuals with no coronary calcium and was significant higher in subjects with early atherosclerosis (CCS 1-99) [74 vs 87 cm 3 ,p = 0.016] and in subjects with more advanced atherosclerosis (CCS≥100) [89 cm 3 ,p = 0.002]). EAT volume was independently related to serum levels of PAI-1, and MCP-1 and inversely related to adiponectin and HDL-cholesterol (p < 0.05). EAT density was inversely related to PAI-1 and LDL-cholesterol and positively associated to adiponectin, sICAM-1 and HDL-cholesterol (p < 0.05). EAT density was more significantly associated with MACE [(HR 0.8, 95%CI:0.7-0.98), p = 0.029] than EAT volume or CCS. EAT volume was higher and density lower in subjects with coronary calcium compared to subjects with CCS = 0, with similar EAT volume in CCS<100 and CCS≥100. Lower EAT density and increased EAT volume were associated with coronary calcification, serum levels of plaque inflammatory markers and MACE, suggesting that dysfunctional EAT may be linked to early plaque formation and inflammation. Copyright © 2018 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.

Relationship of Kidney Injury Biomarkers with Long-Term Cardiovascular Outcomes after Cardiac Surgery.

PubMed

Parikh, Chirag R; Puthumana, Jeremy; Shlipak, Michael G; Koyner, Jay L; Thiessen-Philbrook, Heather; McArthur, Eric; Kerr, Kathleen; Kavsak, Peter; Whitlock, Richard P; Garg, Amit X; Coca, Steven G

2017-12-01

Clinical AKI, measured by serum creatinine elevation, is associated with long-term risks of adverse cardiovascular (CV) events and mortality in patients after cardiac surgery. To evaluate the relative contributions of urine kidney injury biomarkers and plasma cardiac injury biomarkers in adverse events, we conducted a multicenter prospective cohort study of 968 adults undergoing cardiac surgery. On postoperative days 1-3, we measured five urine biomarkers of kidney injury (IL-18, NGAL, KIM-1, L-FABP, and albumin) and five plasma biomarkers of cardiac injury (NT-proBNP, H-FABP, hs-cTnT, cTnI, and CK-MB). The primary outcome was a composite of long-term CV events or death, which was assessed via national health care databases. During a median 3.8 years of follow-up, 219 (22.6%) patients experienced the primary outcome (136 CV events and 83 additional deaths). Compared with patients without postsurgical AKI, patients who experienced AKI Network stage 2 or 3 had an adjusted hazard ratio for the primary composite outcome of 3.52 (95% confidence interval, 2.17 to 5.71). However, none of the five urinary kidney injury biomarkers were significantly associated with the primary outcome. In contrast, four out of five postoperative cardiac injury biomarkers (NT-proBNP, H-FABP, hs-cTnT, and cTnI) strongly associated with the primary outcome. Mediation analyses demonstrated that cardiac biomarkers explained 49% (95% confidence interval, 1% to 97%) of the association between AKI and the primary outcome. These results suggest that clinical AKI at the time of cardiac surgery is indicative of concurrent CV stress rather than an independent renal pathway for long-term adverse CV outcomes. Copyright © 2017 by the American Society of Nephrology.

Parkin regulation of CHOP modulates susceptibility to cardiac endoplasmic reticulum stress.

PubMed

Han, Kim; Hassanzadeh, Shahin; Singh, Komudi; Menazza, Sara; Nguyen, Tiffany T; Stevens, Mark V; Nguyen, An; San, Hong; Anderson, Stasia A; Lin, Yongshun; Zou, Jizhong; Murphy, Elizabeth; Sack, Michael N

2017-05-18

The regulatory control of cardiac endoplasmic reticulum (ER) stress is incompletely characterized. As ER stress signaling upregulates the E3-ubiquitin ligase Parkin, we investigated the role of Parkin in cardiac ER stress. Parkin knockout mice exposed to aortic constriction-induced cardiac pressure-overload or in response to systemic tunicamycin (TM) developed adverse ventricular remodeling with excessive levels of the ER regulatory C/EBP homologous protein CHOP. CHOP was identified as a Parkin substrate and its turnover was Parkin-dose and proteasome-dependent. Parkin depletion in cardiac HL-1 cells increased CHOP levels and enhanced susceptibility to TM-induced cell death. Parkin reconstitution rescued this phenotype and the contribution of excess CHOP to this ER stress injury was confirmed by reduction in TM-induced cell death when CHOP was depleted in Parkin knockdown cardiomyocytes. Isogenic Parkin mutant iPSC-derived cardiomyocytes showed exaggerated ER stress induced CHOP and apoptotic signatures and myocardium from subjects with dilated cardiomyopathy showed excessive Parkin and CHOP induction. This study identifies that Parkin functions to blunt excessive CHOP to prevent maladaptive ER stress-induced cell death and adverse cardiac ventricular remodeling. Additionally, Parkin is identified as a novel post-translational regulatory moderator of CHOP stability and uncovers an additional stress-modifying function of this E3-ubiquitin ligase.

Interventions to decrease the risk of adverse cardiac events for post-surgery or chemotherapy patients taking serotonin (5-HT3) receptor antagonists: protocol for a systematic review and network meta-analysis.

PubMed

Tricco, Andrea C; Soobiah, Charlene; Antony, Jesmin; Hemmelgarn, Brenda; Moher, David; Hutton, Brian; Straus, Sharon E

2013-06-28

Patients undergoing surgery or chemotherapy often experience nausea and vomiting. To increase their quality of life and treatment satisfaction, antiemetic medication, such as serotonin receptor antagonists, is often prescribed for patients experiencing these symptoms. However, early warning signs suggest that serotonin receptor antagonists can cause harm, including arrhythmia. Our objective is to identify the most effective interventions that mitigate the risk of adverse cardiac events associated with serotonin receptor antagonists in patients undergoing surgery and chemotherapy through a systematic review and network meta-analysis. We will search electronic databases (for example, MEDLINE, Embase) from inception onwards, as well as dissertations and governmental reports, to identify interventions (for example, telemetry, electrocardiography, electrolyte monitoring) that decrease the cardiac risk associated with serotonin receptor antagonists among surgery and chemotherapy patients. Eligible comparators include placebo or supportive care; eligible study designs are experimental studies (randomized controlled trials (RCTs), quasi-RCTs, non-RCTs), non-experimental studies (interrupted time series, controlled before-and-after studies), and cohort studies. Outcomes of interest include arrhythmia, sudden cardiac death, QT prolongation, PR prolongation, and all-cause mortality. We will include unpublished studies and studies published in languages other than English.Draft inclusion and exclusion criteria will be established and pilot tested amongst the team. Subsequently, two team members will screen the results in duplicate and resolve conflicts through discussion. The same process will be followed to screen full-text articles, data abstraction, and appraise quality or risk of bias. To determine validity of results, experimental and quasi-experimental studies will be assessed using the Cochrane Effective Practice and Organisation of Care (EPOC) Risk of Bias tool, while

Effects of preoperative aspirin on cardiocerebral and renal complications in non-emergent cardiac surgery patients: a sub-group and cohort study.

PubMed

Cao, Longhui; Silvestry, Scott; Zhao, Ning; Diehl, James; Sun, Jianzhong

2012-01-01

Postoperative cardiocerebral and renal complications are a major threat for patients undergoing cardiac surgery. This study was aimed to examine the effect of preoperative aspirin use on patients undergoing cardiac surgery. An observational cohort study was performed on consecutive patients (n = 1879) receiving cardiac surgery at this institution. The patients excluded from the study were those with preoperative anticoagulants, unknown aspirin use, or underwent emergent cardiac surgery. Outcome events included were 30-day mortality, renal failure, readmission and a composite outcome--major adverse cardiocerebral events (MACE) that include permanent or transient stroke, coma, perioperative myocardial infarction (MI), heart block and cardiac arrest. Of all patients, 1145 patients met the inclusion criteria and were divided into two groups: those taking (n = 858) or not taking (n = 287) aspirin within 5 days preceding surgery. Patients with aspirin presented significantly more with history of hypertension, diabetes, peripheral arterial disease, previous MI, angina and older age. With propensity scores adjusted and multivariate logistic regression, however, this study showed that preoperative aspirin therapy (vs. no aspirin) significantly reduced the risk of MACE (8.4% vs. 12.5%, odds ratio [OR] 0.585, 95% CI 0.355-0.964, P = 0.035), postoperative renal failure (2.6% vs. 5.2%, OR 0.438, CI 0.203-0.945, P = 0.035) and dialysis required (0.8% vs. 3.1%, OR 0.230, CI 0.071-0.742, P = 0.014), but did not significantly reduce 30-day mortality (4.1% vs. 5.8%, OR 0.744, CI 0.376-1.472, P = 0.396) nor it increased readmissions in the patients undergoing cardiac surgery. Preoperative aspirin therapy is associated with a significant decrease in the risk of MACE and renal failure and did not increase readmissions in patients undergoing non-emergent cardiac surgery.

Reduction in dynamin-2 is implicated in ischaemic cardiac arrhythmias

PubMed Central

Shi, Dan; Xie, Duanyang; Zhang, Hong; Zhao, Hong; Huang, Jian; Li, Changming; Liu, Yi; Lv, Fei; The, Erlinda; Liu, Yuan; Yuan, Tianyou; Wang, Shiyi; Chen, Jinjin; Pan, Lei; Yu, Zuoren; Liang, Dandan; Zhu, Weidong; Zhang, Yuzhen; Li, Li; Peng, Luying; Li, Jun; Chen, Yi-Han

2014-01-01

Ischaemic cardiac arrhythmias cause a large proportion of sudden cardiac deaths worldwide. The ischaemic arrhythmogenesis is primarily because of the dysfunction and adverse remodelling of sarcolemma ion channels. However, the potential regulators of sarcolemma ion channel turnover and function in ischaemic cardiac arrhythmias remains unknown. Our previous studies indicate that dynamin-2 (DNM2), a cardiac membrane-remodelling GTPase, modulates ion channels membrane trafficking in the cardiomyocytes. Here, we have found that DNM2 plays an important role in acute ischaemic arrhythmias. In rat ventricular tissues and primary cardiomyocytes subjected to acute ischaemic stress, the DNM2 protein and transcription levels were markedly down-regulated. This DNM2 reduction was coupled with severe ventricular arrhythmias. Moreover, we identified that the down-regulation of DNM2 within cardiomyocytes increases the action potential amplitude and prolongs the re-polarization duration by depressing the retrograde trafficking of Nav1.5 and Kir2.1 channels. These effects are likely to account for the DNM2 defect-induced arrhythmogenic potentials. These results suggest that DNM2, with its multi-ion channel targeting properties, could be a promising target for novel antiarrhythmic therapies. PMID:25092467

Biomass fuel smoke exposure was associated with adverse cardiac remodeling and left ventricular dysfunction in Peru.

PubMed

Burroughs Peña, M S; Velazquez, E J; Rivera, J D; Alenezi, F; Wong, C; Grigsby, M; Davila-Roman, V G; Gilman, R H; Miranda, J J; Checkley, W

2017-07-01

While household air pollution from biomass fuel combustion has been linked to cardiovascular disease, the effects on cardiac structure and function have not been well described. We sought to determine the association between biomass fuel smoke exposure and cardiac structure and function by transthoracic echocardiography. We identified a random sample of urban and rural residents living in the high-altitude region of Puno, Peru. Daily biomass fuel use was self-reported. Participants underwent transthoracic echocardiography. Multivariable linear regression was used to examine the relationship of biomass fuel use with echocardiographic measures of cardiac structure and function, adjusting for age, sex, height, body mass index, diabetes, physical activity, and tobacco use. One hundred and eighty-seven participants (80 biomass fuel users and 107 non-users) were included in this analysis (mean age 59 years, 58% women). After adjustment, daily exposure to biomass fuel smoke was associated with increased left ventricular internal diastolic diameter (P=.004), left atrial diameter (P=.03), left atrial area (four-chamber) (P=.004) and (two-chamber) (P=.03), septal E' (P=.006), and lateral E' (P=.04). Exposure to biomass fuel smoke was also associated with worse global longitudinal strain in the two-chamber view (P=.01). Daily biomass fuel use was associated with increased left ventricular size and decreased left ventricular systolic function by global longitudinal strain. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Ibogaine-associated cardiac arrest and death: case report and review of the literature.

PubMed

Meisner, Jessica A; Wilcox, Susan R; Richards, Jeremy B

2016-04-01

A naturally occurring hallucinogenic plant alkaloid, ibogaine has been used as an adjuvant for opiate withdrawal for the past 50 years. In the setting of an escalating nationwide opiate epidemic, use of substances such as ibogaine may also increase. Therefore, familiarity with the mechanisms and potential adverse effects of ibogaine is important for clinicians. We present the case report of a man whose use of ibogaine resulted in cardiac arrest and death, complemented by a review of the literature regarding ibogaine's clinical effects. A 40-year-old man who used ibogaine for symptoms of heroin withdrawal suffered acute cardiac arrest leading to cerebral edema and brain death. His presentation was consistent with ibogaine-induced cardiotoxicity and ibogaine-induced cardiac arrest, and a review of the literature regarding the history, mechanisms, risks and clinical outcomes associated with ibogaine is presented. The case presented underscores the significant potential clinical risks of ibogaine. It is important the healthcare community be aware of the possible effects of ibogaine such that clinicians can provide informed counseling to their patients regarding the risks of attempting detoxification with ibogaine.

Defective branched chain amino acid catabolism contributes to cardiac dysfunction and remodeling following myocardial infarction.

PubMed

Wang, Wei; Zhang, Fuyang; Xia, Yunlong; Zhao, Shihao; Yan, Wenjun; Wang, Helin; Lee, Yan; Li, Congye; Zhang, Ling; Lian, Kun; Gao, Erhe; Cheng, Hexiang; Tao, Ling

2016-11-01

Cardiac metabolic remodeling is a central event during heart failure (HF) development following myocardial infarction (MI). It is well known that myocardial glucose and fatty acid dysmetabolism contribute to post-MI cardiac dysfunction and remodeling. However, the role of amino acid metabolism in post-MI HF remains elusive. Branched chain amino acids (BCAAs) are an important group of essential amino acids and function as crucial nutrient signaling in mammalian animals. The present study aimed to determine the role of cardiac BCAA metabolism in post-MI HF progression. Utilizing coronary artery ligation-induced murine MI models, we found that myocardial BCAA catabolism was significantly impaired in response to permanent MI, therefore leading to an obvious elevation of myocardial BCAA abundance. In MI-operated mice, oral BCAA administration further increased cardiac BCAA levels, activated the mammalian target of rapamycin (mTOR) signaling, and exacerbated cardiac dysfunction and remodeling. These data demonstrate that BCAAs act as a direct contributor to post-MI cardiac pathologies. Furthermore, these BCAA-mediated deleterious effects were improved by rapamycin cotreatment, revealing an indispensable role of mTOR in BCAA-mediated adverse effects on cardiac function/structure post-MI. Of note, pharmacological inhibition of branched chain ketoacid dehydrogenase kinase (BDK), a negative regulator of myocardial BCAA catabolism, significantly improved cardiac BCAA catabolic disorders, reduced myocardial BCAA levels, and ameliorated post-MI cardiac dysfunction and remodeling. In conclusion, our data provide the evidence that impaired cardiac BCAA catabolism directly contributes to post-MI cardiac dysfunction and remodeling. Moreover, improving cardiac BCAA catabolic defects may be a promising therapeutic strategy against post-MI HF. Copyright © 2016 the American Physiological Society.

Cognition- and Dementia-Related Adverse Effects With Sacubitril-Valsartan: Analysis of the FDA Adverse Event Report System Database.

PubMed

Perlman, Amichai; Hirsh Raccah, Bruria; Matok, Ilan; Muszkat, Mordechai

2018-05-07

Because neprilysin is involved in the degradation of amyloid-beta, there is concern that the angiotensin-neprilysin inhibitor sacubitril-valsartan could increase the risk for dementia. We analyzed adverse event cases submitted to the Food and Drug Administration Adverse Event Report System from July 2015 to March 2017. Cognition- and dementia-related adverse event cases were defined with the use of broad and narrow structured medical queries. During the period evaluated, 9,004 adverse event reports (out of a total of 2,249,479) involved the use of sacubitril-valsartan. Based on the broad definition, sacubitril-valsartan was associated with cognition- and dementia-related adverse events in 459 reports (5.1%), but this was lower than the proportion of these reports among other medications (6.6%, reporting odds ratio [ROR] 0.72, 95% confidence interval [CI] 0.65-0.79). Restricting the comparison to cases with age >60 years and with the use of a comparator group with heart failure resulted in no association between sacubitril-valsartan and dementia-related adverse events, with the use of both the broad and the narrow definitions (ROR 0.87, 95% CI 0.76-1.02, and ROR 1.06, 95% CI 0.4-3.16, respectively). Sacubitril-valsartan is not associated with a disproportionately high rate of short-term dementia-related adverse effect reports. Long-term studies assessing cognitive outcomes are required to better establish the medication's cognition effects. Copyright © 2018 Elsevier Inc. All rights reserved.

Blood glucose management in the patient undergoing cardiac surgery: A review

PubMed Central

Reddy, Pingle; Duggar, Brian; Butterworth, John

2014-01-01

Both diabetes mellitus and hyperglycemia per se are associated with negative outcomes after cardiac surgery. In this article, we review these associations, the possible mechanisms that lead to adverse outcomes, and the epidemiology of diabetes focusing on those patients requiring cardiac surgery. We also examine outpatient and perioperative management of diabetes with the same focus. Finally, we discuss our own efforts to improve glycemic management of patients undergoing cardiac surgery at our institution, including keys to success, results of implementation, and patient safety concerns. PMID:25429332

Interferon Regulatory Factor 7 Functions as a Novel Negative Regulator of Pathological Cardiac Hypertrophy

PubMed Central

Jiang, Ding-Sheng; Liu, Yu; Zhou, Heng; Zhang, Yan; Zhang, Xiao-Dong; Zhang, Xiao-Fei; Chen, Ke; Gao, Lu; Peng, Juan; Gong, Hui; Chen, Yingjie; Yang, Qinglin; Liu, Peter P.; Fan, Guo-Chang; Zou, Yunzeng; Li, Hongliang

2017-01-01

Cardiac hypertrophy is a complex pathological process that involves multiple factors including inflammation and apoptosis. Interferon regulatory factor 7 (IRF7) is a multifunctional regulator that participates in immune regulation, cell differentiation, apoptosis, and oncogenesis. However, the role of IRF7 in cardiac hypertrophy remains unclear. We performed aortic banding in cardiac-specific IRF7 transgenic mice, IRF7 knockout mice, and the wild-type littermates of these mice. Our results demonstrated that IRF7 was downregulated in aortic banding–induced animal hearts and cardiomyocytes that had been treated with angiotensin II or phenylephrine for 48 hours. Accordingly, heart-specific overexpression of IRF7 significantly attenuated pressure overload–induced cardiac hypertrophy, fibrosis, and dysfunction, whereas loss of IRF7 led to opposite effects. Moreover, IRF7 protected against angiotensin II–induced cardiomyocyte hypertrophy in vitro. Mechanistically, we identified that IRF7-dependent cardioprotection was mediated through IRF7 binding to inhibitor of κB kinase-β, and subsequent nuclear factor-κB inactivation. In fact, blocking nuclear factor-κB signaling with cardiac-specific inhibitors of κBαS32A/S36A super-repressor transgene counteracted the adverse effect of IRF7 deficiency. Conversely, activation of nuclear factor-κB signaling via a cardiac-specific conditional inhibitor of κB kinase-βS177E/S181E (constitutively active) transgene negated the antihypertrophic effect of IRF7 overexpression. Our data demonstrate that IRF7 acts as a novel negative regulator of pathological cardiac hypertrophy by inhibiting nuclear factor-κB signaling and may constitute a potential therapeutic target for pathological cardiac hypertrophy. PMID:24396025

Rationally engineered Troponin C modulates in vivo cardiac function and performance in health and disease.

PubMed

Shettigar, Vikram; Zhang, Bo; Little, Sean C; Salhi, Hussam E; Hansen, Brian J; Li, Ning; Zhang, Jianchao; Roof, Steve R; Ho, Hsiang-Ting; Brunello, Lucia; Lerch, Jessica K; Weisleder, Noah; Fedorov, Vadim V; Accornero, Federica; Rafael-Fortney, Jill A; Gyorke, Sandor; Janssen, Paul M L; Biesiadecki, Brandon J; Ziolo, Mark T; Davis, Jonathan P

2016-02-24

Treatment for heart disease, the leading cause of death in the world, has progressed little for several decades. Here we develop a protein engineering approach to directly tune in vivo cardiac contractility by tailoring the ability of the heart to respond to the Ca(2+) signal. Promisingly, our smartly formulated Ca(2+)-sensitizing TnC (L48Q) enhances heart function without any adverse effects that are commonly observed with positive inotropes. In a myocardial infarction (MI) model of heart failure, expression of TnC L48Q before the MI preserves cardiac function and performance. Moreover, expression of TnC L48Q after the MI therapeutically enhances cardiac function and performance, without compromising survival. We demonstrate engineering TnC can specifically and precisely modulate cardiac contractility that when combined with gene therapy can be employed as a therapeutic strategy for heart disease.

Rationally engineered Troponin C modulates in vivo cardiac function and performance in health and disease

PubMed Central

Shettigar, Vikram; Zhang, Bo; Little, Sean C.; Salhi, Hussam E.; Hansen, Brian J.; Li, Ning; Zhang, Jianchao; Roof, Steve R.; Ho, Hsiang-Ting; Brunello, Lucia; Lerch, Jessica K.; Weisleder, Noah; Fedorov, Vadim V.; Accornero, Federica; Rafael-Fortney, Jill A.; Gyorke, Sandor; Janssen, Paul M. L.; Biesiadecki, Brandon J.; Ziolo, Mark T.; Davis, Jonathan P.

2016-01-01

Treatment for heart disease, the leading cause of death in the world, has progressed little for several decades. Here we develop a protein engineering approach to directly tune in vivo cardiac contractility by tailoring the ability of the heart to respond to the Ca2+ signal. Promisingly, our smartly formulated Ca2+-sensitizing TnC (L48Q) enhances heart function without any adverse effects that are commonly observed with positive inotropes. In a myocardial infarction (MI) model of heart failure, expression of TnC L48Q before the MI preserves cardiac function and performance. Moreover, expression of TnC L48Q after the MI therapeutically enhances cardiac function and performance, without compromising survival. We demonstrate engineering TnC can specifically and precisely modulate cardiac contractility that when combined with gene therapy can be employed as a therapeutic strategy for heart disease. PMID:26908229

Diet compounds, glycemic index and obesity-related cardiac effects.

PubMed

Diniz, Yeda S; Burneiko, Regina M; Seiva, Fabio R F; Almeida, Flávia Q A; Galhardi, Cristiano Machado; Filho, José Luiz V B Novelli; Mani, Fernanda; Novelli, Ethel L B

2008-02-20

Diet compounds may influence obesity-related cardiac oxidative stress and metabolic sifting. Carbohydrate-rich diet may be disadvantageous from fat-rich diet to cardiac tissue and glycemic index rather than lipid profile may predict the obesity-related cardiac effects. Male Wistar rats were divided into three groups (n=8/group): (C) receiving standard chow (3.0 kcal/g); (CRD) receiving carbohydrate-rich diet (4.0 kcal/g), and (FRD) receiving fat-rich diet (4.0 kcal/g). Rats were sacrificed after the oral glucose tolerance test (OGTT) at 60 days of dietary treatments. Lipid profile and oxidative stress parameters were determined in serum. Myocardial samples were used to determine oxidative stress, metabolic enzymes, glycogen and triacylglycerol. FRD rats showed higher final body weight and body mass index than CRD and C. Serum cholesterol and low-density lipoprotein were higher in FRD than in CRD, while triacylglycerol and oxidized low-density lipoprotein cholesterol were higher in CRD than in FRD. CRD rats had the highest myocardial lipid hydroperoxide and diminished superoxide dismutase and catalase activities. Myocardial glycogen was lower and triacylglycerol was higher in CRD than in C and FRD rats. Although FRD rats had depressed myocardial-reducing power, no significant changes were observed in myocardial energy metabolism. Myocardial beta-hydroxyacyl coenzyme-A dehydrogenase and citrate synthase, as well as the enhanced lactate dehydrogenase/citrate synthase ratio indicated that fatty acid degradation was decreased in CRD rats. Glycemic index was positively correlated with obesity-related cardiac effects. Isoenergetic carbohydrate-rich and fat-rich diets induced different degree of obesity and differently affected lipid profile. Carbohydrate-rich diet was deleterious relative to fat-rich diet in the heart enhancing lipoperoxidation and shifting the metabolic pathway for energy production. Glycemic index rather than dyslipidemic profile may predict the obesity

Novel Sternal Protection Device for Cardiac Surgery Via Median Sternotomy Incision

PubMed Central

Marasco, Silvana F.; McGiffin, David C.; Zimmet, Adam D.; Solis, Pablo C.; Bingham, Judy M.; Moshinsky, Randall A.

2017-01-01

Objective Sternal bleeding during cardiac surgery is currently controlled using bone wax or other chemical substances that may result in adverse effects and affect wound healing and recovery. The purpose of this study was to identify a safe, cost-effective, and easy-to-use technique to reduce sternal bleeding and sternal trauma during cardiac surgery. Methods After sternotomy, a sternal protection device was placed over each hemisternal section before insertion of the retractor and remained in situ until the end of surgery. Sternal bleeding and ease of use were assessed and recorded during surgery. Sternal trauma was assessed and recorded within 5 minutes of removal of the device, and overall satisfaction (Global Impression) and any intraoperative adverse events or device malfunction were reported at surgery completion. Patients were followed up 24 hours and 4 weeks after surgery. Results Twelve patients completed the study. Adverse events reported were not considered related to the device. No sternal trauma was identified in any patient. In 9 of 11 patients, sternal bleeding was reduced after insertion of the device. The device was generally considered easy to use, although some difficulty was encountered when used with the Internal Mammary Artery retractor. Conclusions Our data suggest that the device is safe and able to reduce sternal bleeding during surgery using sternal retractors. We recommend further studies in a larger population of patients with a control group to evaluate the device's ability to reduce the morbidity associated with sternal bleeding and sternal trauma. PMID:29023352

An epigenome-wide association analysis of cardiac autonomic responses among a population of welders.

PubMed

Zhang, Jinming; Liu, Zhonghua; Umukoro, Peter E; Cavallari, Jennifer M; Fang, Shona C; Weisskopf, Marc G; Lin, Xihong; Mittleman, Murray A; Christiani, David C

2017-02-01

DNA methylation is one of the potential epigenetic mechanisms associated with various adverse cardiovascular effects; however, its association with cardiac autonomic dysfunction, in particular, is unknown. In the current study, we aimed to identify epigenetic variants associated with alterations in cardiac autonomic responses. Cardiac autonomic responses were measured with two novel markers: acceleration capacity (AC) and deceleration capacity (DC). We examined DNA methylation levels at more than 472,506 CpG probes through the Illumina Infinium HumanMethylation450 BeadChip assay. We conducted separate linear mixed models to examine associations of DNA methylation levels at each CpG with AC and DC. One CpG (cg26829071) located in the GPR133 gene was negatively associated with DC values after multiple testing corrections through false discovery rate. Our study suggests the potential functional importance of methylation in cardiac autonomic responses. Findings from the current study need to be replicated in future studies in a larger population.

Alcohol and cannabis: Comparing their adverse health effects and regulatory regimes.

PubMed

Hall, Wayne

2017-04-01

The claim that the adverse health effects of cannabis are much less serious than those of alcohol has been central to the case for cannabis legalisation. Regulators in US states that have legalised cannabis have adopted regulatory models based on alcohol. This paper critically examines the claim about adverse health effects and the wisdom of regulating cannabis like alcohol. First, it compares what we know about the adverse health effects of alcohol and cannabis. Second, it discusses the uncertainties about the long term health effects of sustained daily cannabis use. Third, it speculates about how the adverse health effects of cannabis may change after legalisation. Fourth, it questions the assumption that alcohol provides the best regulatory model for a legal cannabis market. Fifth, it outlines the major challenges in regulating cannabis under the liberal alcohol-like regulatory regimes now being introduced. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

Cardiac ion channels

PubMed Central

Priest, Birgit T; McDermott, Jeff S

2015-01-01

Ion channels are critical for all aspects of cardiac function, including rhythmicity and contractility. Consequently, ion channels are key targets for therapeutics aimed at cardiac pathophysiologies such as atrial fibrillation or angina. At the same time, off-target interactions of drugs with cardiac ion channels can be the cause of unwanted side effects. This manuscript aims to review the physiology and pharmacology of key cardiac ion channels. The intent is to highlight recent developments for therapeutic development, as well as elucidate potential mechanisms for drug-induced cardiac side effects, rather than present an in-depth review of each channel subtype. PMID:26556552

Novel therapeutic effects of sesamin on diabetes-induced cardiac dysfunction.

PubMed

Thuy, Tran Duong; Phan, Nam Nhut; Wang, Chih-Yang; Yu, Han-Gang; Wang, Shu-Yin; Huang, Pung-Ling; Do, Yi-Yin; Lin, Yen-Chang

2017-05-01

Diabetes is a risk factor that increases the occurrence and severity of cardiovascular events. Cardiovascular complications are the leading cause of mortality of 75% of patients with diabetes >40 years old. Sesamin, the bioactive compound extracted from Sesamum indicum, is a natural compound that has diverse beneficial effects on hypoglycemia and reducing cholesterol. The aim of this study is to investigate sesamin effects to diabetes-inducing cardiac hypertrophy. In the present study bioinformatics analysis demonstrated cardiac hypertrophy signaling may be the most important pathway for upregulating genes in sesamin-treated groups. To verify the bioinformatics prediction, sesamin was used as the main bioactive compound to attenuate the impact of diabetes induced by streptozotocin (STZ) on cardiac function in a rat model. The results revealed that oral administration of sesamin for 4 weeks (100 and 200 mg/kg body weight) marginally improved blood glucose levels, body weight and significantly ameliorated the effects on heart rate and blood pressure in rats with type 1 diabetes relative to control rats. The QT interval of sesamin was also reduced relative to the control group. The findings indicated that sesamin has potential cardioprotective effects in the STZ-induced diabetes model. This suggested that this can be used as a novel treatment for patients with diabetes with cardiac dysfunction complication.

Novel therapeutic effects of sesamin on diabetes-induced cardiac dysfunction

PubMed Central

Thuy, Tran Duong; Phan, Nam Nhut; Wang, Chih-Yang; Yu, Han-Gang; Wang, Shu-Yin; Huang, Pung-Ling; Do, Yi-Yin; Lin, Yen-Chang

2017-01-01

Diabetes is a risk factor that increases the occurrence and severity of cardiovascular events. Cardiovascular complications are the leading cause of mortality of 75% of patients with diabetes >40 years old. Sesamin, the bioactive compound extracted from Sesamum indicum, is a natural compound that has diverse beneficial effects on hypoglycemia and reducing cholesterol. The aim of this study is to investigate sesamin effects to diabetes-inducing cardiac hypertrophy. In the present study bioinformatics analysis demonstrated cardiac hypertrophy signaling may be the most important pathway for upregulating genes in sesamin-treated groups. To verify the bioinformatics prediction, sesamin was used as the main bioactive compound to attenuate the impact of diabetes induced by streptozotocin (STZ) on cardiac function in a rat model. The results revealed that oral administration of sesamin for 4 weeks (100 and 200 mg/kg body weight) marginally improved blood glucose levels, body weight and significantly ameliorated the effects on heart rate and blood pressure in rats with type 1 diabetes relative to control rats. The QT interval of sesamin was also reduced relative to the control group. The findings indicated that sesamin has potential cardioprotective effects in the STZ-induced diabetes model. This suggested that this can be used as a novel treatment for patients with diabetes with cardiac dysfunction complication. PMID:28358428

Differential effects of aprotinin and tranexamic acid on outcomes and cytokine profiles in neonates undergoing cardiac surgery.

PubMed

Graham, Eric M; Atz, Andrew M; Gillis, Jenna; Desantis, Stacia M; Haney, A Lauren; Deardorff, Rachael L; Uber, Walter E; Reeves, Scott T; McGowan, Francis X; Bradley, Scott M; Spinale, Francis G

2012-05-01

Factors contributing to postoperative complications include blood loss and a heightened inflammatory response. The objective of this study was to test the hypothesis that aprotinin would decrease perioperative blood product use, reduce biomarkers of inflammation, and result in improved clinical outcome parameters in neonates undergoing cardiac operations. This was a secondary retrospective analysis of a clinical trial whereby neonates undergoing cardiac surgery received either aprotinin (n = 34; before May 2008) or tranexamic acid (n = 42; after May 2008). Perioperative blood product use, clinical course, and measurements of cytokines were compared. Use of perioperative red blood cells, cryoprecipitate, and platelets was reduced in neonates receiving aprotinin compared with tranexamic acid (P < .05). Recombinant activated factor VII use (2/34 [6%] vs 18/42 [43%]; P < .001), delayed sternal closure (12/34 [35%] vs 26/42 [62%]; P = .02), and inotropic requirements at 24 and 36 hours (P < .05) were also reduced in the aprotinin group. Median duration of mechanical ventilation was reduced compared with tranexamic acid: 2.9 days (interquartile range: 1.7-5.1 days) versus 4.2 days (2.9-5.2 days), P = .04. Production of tumor necrosis factor and interleukin-2 activation were attenuated in the aprotinin group at 24 hours postoperatively. No differential effects on renal function were seen between agents. Aprotinin, compared with tranexamic acid, was associated with reduced perioperative blood product use, improved early indices of postoperative recovery, and attenuated indices of cytokine activation, without early adverse effects. These findings suggest that aprotinin may have unique effects in the context of neonatal cardiac surgery and challenge contentions that antifibrinolytics are equivalent with respect to early postoperative outcomes. Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Differential effects of aprotinin and tranexamic acid on outcomes and cytokine profiles in neonates undergoing cardiac surgery

PubMed Central

Graham, Eric M.; Atz, Andrew M.; Gillis, Jenna; DeSantis, Stacia M.; Haney, A. Lauren; Deardorff, Rachael L.; Uber, Walter E.; Reeves, Scott T.; McGowan, Francis X.; Bradley, Scott M.; Spinale, Francis G.

2011-01-01

Objective Factors contributing to postoperative complications include blood loss and a heightened inflammatory response. The objective of this study was to test the hypothesis that aprotinin would decrease perioperative blood product use, reduce biomarkers of inflammation, and result in improved clinical outcome parameters in neonates undergoing cardiac operations. Methods This was a secondary retrospective analysis of a clinical trial whereby neonates undergoing cardiac surgery received either aprotinin (n = 34; before May 2008) or tranexamic acid (n = 42; after May 2008). Perioperative blood product use, clinical course, and measurements of cytokines were compared. Results Use of perioperative red blood cells, cryoprecipitate, and platelets was reduced in neonates receiving aprotinin compared with tranexamic acid (P < .05). Recombinant activated factor VII use (2/34 [6%] vs 18/42 [43%]; P < .001), delayed sternal closure (12/34 [35%] vs 26/42 [62%]; P = .02), and inotropic requirements at 24 and 36 hours (P < .05) were also reduced in the aprotinin group. Median duration of mechanical ventilation was reduced compared with tranexamic acid: 2.9 days (interquartile range: 1.7–5.1 days) versus 4.2 days (2.9–5.2days), P = .04. Production of tumor necrosis factor and interleukin-2 activation were attenuated in the aprotinin group at 24 hours postoperatively. No differential effects on renal function were seen between agents. Conclusions Aprotinin, compared with tranexamic acid, was associated with reduced perioperative blood product use, improved early indices of postoperative recovery, and attenuated indices of cytokine activation, without early adverse effects. These findings suggest that aprotinin may have unique effects in the context of neonatal cardiac surgery and challenge contentions that antifibrinolytics are equivalent with respect to early postoperative outcomes. PMID:22075061

Search strategies to identify information on adverse effects: a systematic review

PubMed Central

Golder, Su; Loke, Yoon

2009-01-01

Objectives: The review evaluated studies of electronic database search strategies designed to retrieve adverse effects data for systematic reviews. Methods: Studies of adverse effects were located in ten databases as well as by checking references, hand-searching, searching citations, and contacting experts. Two reviewers screened the retrieved records for potentially relevant papers. Results: Five thousand three hundred thirteen citations were retrieved, yielding 19 studies designed to develop or evaluate adverse effect filters, of which 3 met the inclusion criteria. All 3 studies identified highly sensitive search strategies capable of retrieving over 95% of relevant records. However, 1 study did not evaluate precision, while the level of precision in the other 2 studies ranged from 0.8% to 2.8%. Methodological issues in these papers included the relatively small number of records, absence of a validation set of records for testing, and limited evaluation of precision. Conclusions: The results indicate the difficulty of achieving highly sensitive searches for information on adverse effects with a reasonable level of precision. Researchers who intend to locate studies on adverse effects should allow for the amount of resources and time required to conduct a highly sensitive search. PMID:19404498

The effect of heart motion on parameter bias in dynamic cardiac SPECT

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

Ross, S.G.; Gullberg, G.T.; Huesman, R.H.

1996-12-31

Dynamic cardiac SPECT can be used to estimate kinetic rate parameters which describe the wash-in and wash-out of tracer activity between the blood and the myocardial tissue. These kinetic parameters can in turn be correlated to myocardial perfusion. There are, however, many physical aspects associated with dynamic SPECT which can introduce errors into the estimates. This paper describes a study which investigates the effect of heart motion on kinetic parameter estimates. Dynamic SPECT simulations are performed using a beating version of the MCAT phantom. The results demonstrate that cardiac motion has a significant effect on the blood, tissue, and backgroundmore » content of regions of interest. This in turn affects estimates of wash-in, while it has very little effect on estimates of wash-out. The effect of cardiac motion on parameter estimates appears not to be as great as effects introduced by photon noise and geometric collimator response. It is also shown that cardiac motion results in little extravascular contamination of the left ventricle blood region of interest.« less

"Freshman's week": characteristics associated with participation and experiencing adverse effects.

PubMed

Erevik, E K; Pallesen, S; Vedaa, Ø; Andreassen, C S; Torsheim, T

2018-05-29

"Freshman's week" (FW) is a Norwegian initiation ritual to higher education. Previous research has suggested that FW-participation is associated with better social adjustment to the student setting, as well as heavy alcohol use both during and after the event. In this study, we aimed to identify characteristics associated with participation in FW and characteristics associated with experiencing adverse effects of alcohol use during FW. Students in the city of Bergen, Norway participated in a survey during fall 2015, shortly after FW. The current sample consisted of the first-year students (N = 4, 401, estimated response rate: 49%). The sample's mean age was 24 years (range: 17-73 years), 65% were females, and the majority were born in Norway (93%). Logistic regressions were conducted to identify characteristics associated with participation in FW and experiencing adverse effects. A total of 64% of the first-year students reported participation in FW, and 27% of these reported experiencing at least one adverse alcohol-related effect during FW. Participation in FW was positively associated with being single (OR = 1.29), extroversion (OR = 1.18), and alcohol use (OR = 1.28), and inversely associated with age (OR = 0.70), and having children (OR = 0.36). Several characteristics (e.g., alcohol use (OR = 1.84), extroversion (OR = 0.60), symptoms of depression (OR = 1.60)) were associated with an increased risk of experiencing adverse effects of alcohol use during participation. The current results suggest that initiatives for increasing the participation rate in FW, reducing alcohol use during FW, and decreasing the occurrence of adverse alcohol effects during FW are warranted. Aiming to reduce the focus on alcohol use during FW, and seeking to make FW more available and enjoyable for students with other priorities, students who do not match the stereotype of the typical first-year student, and less sociable students, might both

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/

Surveillance of adverse effects during a vaccination campaign against meningitis C.

PubMed

Laribière, Anne; Miremont-Salamé, Ghada; Reyre, Hadrien; Abouelfath, Abdelilah; Liège, Ludovic; Moore, Nicholas; Haramburu, Françoise

2005-12-01

To describe adverse events occurring after mass vaccination with conjugate and nonconjugate vaccines and to assess the incidence of serious adverse effects. A mass immunisation campaign against meningococcal C disease was conducted in two French administrative areas, Landes and Pyrénées atlantiques, for 2 months (from October to December 2002). Adverse events were reported by families and physicians by means of a specific reporting form returned to the pharmacovigilance centre 15 days after vaccination. The target population was 260,630 individuals aged between 2 months and 24 years. About 179,000 children and young adults were vaccinated. A total of 92,711 report forms were received by the pharmacovigilance centre, and 12,695 subjects presented at least one adverse event. The most frequently involved systems/disorders were application site disorders (48.4%), whole-body general disorders (21.8%), central and peripheral nervous system disorders (14.6%), and gastrointestinal system disorders (4.7%). Most of these adverse events were transient and not serious. There were 13 serious adverse events: one each of syncope, fever, headache with fever, neuralgia, serum sickness, arthritis, purpura, facial paralysis, multiple sclerosis, lipoma, and meningism, and two cases of bronchospasm. No significant difference was found in rates of adverse event reports between both vaccines. The estimated incidence of serious adverse effect reports was 7 per 100,000. This campaign was the second immunisation campaign undertaken in France involving both physicians and families as reporters. Although unlabeled adverse effects were identified during this campaign, they were mostly nonserious and have been known to occur with other vaccines.

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.

Obesity and Diabetes Mellitus Adversely Affect Outcomes after Cardiac Surgery in Children's Hospitals.

PubMed

Shamszad, Pirouz; Rossano, Joseph W; Marino, Bradley S; Lowry, Adam W; Knudson, Jarrod D

2016-09-01

To assess how obesity or diabetes mellitus impacts outcomes in patients undergoing cardiac surgery in pediatric hospitals. A multi-institutional, matched case-control study of the Pediatric Health Information System database was performed. Tertiary children's hospitals in the United States. All cardiac surgical cases in patients with obesity or diabetes mellitus between 2004 and 2012 were included. Cases were matched to controls by age, sex, race, and Risk Adjustment for Congenital Heart Surgery score. Mortality, surgical complications, and hospital utilization. Differences in outcome measures were assessed by chi-square and Mann-Whitney tests. P value < .05 was significant. Six hundred twenty-nine cardiac surgical cases (median age 17 years [IQR 12-32]) with obesity or diabetes mellitus were matched to 629 controls. Cases demonstrated lower median household income than those in the control group ($38,031 [IQR $31,900-$48,844] vs. ($41,896 [IQR $32,854-$56,020], P < .001). Mortality was similar between cases and controls (22% vs. 1.9%, P =.692). Surgical complications occurred similarly between cases and controls (13.5% vs. 12.4%, P = .535). Cases had longer intensive care unit length of stay than controls (3 vs. 2 days, P = .001), resulting in longer overall hospital length of stay (5 vs. 4 days, P < .001). Cases also had a higher odds of undergoing mechanical ventilation for >96 hours (OR 2.0, 95% CI 1.1-3.7) and higher rate of total parenteral nutrition use (7.2% vs. 4.5%, P = .040). Median hospital charges were higher in cases (clinical: $6,696 vs. $5,872; laboratory: $14,168 vs. $12,251; pharmacy: $12,971 vs. $10,426; imaging: $6,259 vs. $5,660; P ≤ .030 for all). The presence of obesity or diabetes mellitus was associated with increased postoperative morbidity, hospital utilization, and cost in patients undergoing cardiac surgery in pediatric hospitals. © 2016 Wiley Periodicals, Inc.

Adverse Left Ventricular Remodeling and Age Assessed with Cardiac MR Imaging: The Multi-Ethnic Study of Atherosclerosis

PubMed Central

McClelland, Robyn L.; Gomes, Antoinette S.; Hundley, W. Gregory; Cheng, Susan; Wu, Colin O.; Carr, J. Jeffrey; Shea, Steven; Bluemke, David A.; Lima, Joao A. C.

2016-01-01

Purpose To evaluate age-related left ventricular (LV) remodeling during longitudinal observation of a large cohort of asymptomatic individuals who were free of clinical cardiovascular disease at baseline. Materials and Methods The applicable institutional review boards approved this study, and all participants gave informed consent. Cardiac magnetic resonance (MR) imaging was used to identify longitudinal changes in LV structure and function in 2935 participants who underwent baseline and follow-up cardiac MR imaging in the Multi-Ethnic Study of Atherosclerosis. Participants were free of clinical cardiovascular disease at baseline. Participants who experienced an incident coronary heart disease event were excluded. Data were analyzed with multivariable mixed-effects regression models in which the outcome was cardiac MR imaging measurement, and the covariates included follow-up time and cardiac risk factors. Results Participants were aged 54–94 years at follow-up, and 53% of the participants were women. Median time between baseline and follow-up cardiac MR imaging was 9.4 years. Over this period, LV mass increased in men and decreased slightly in women (8.0 and −1.6 g per decade, respectively; P < .001). In both men and women, LV end-diastolic volume decreased (−9.8 and −13.3 mL per decade, respectively; P < .001), stroke volume decreased (−8.8 and −8.6 mL per decade, respectively; P < .001), and mass-to-volume ratio increased (0.14 and 0.11 g/mL per decade, respectively; P < .001). Change in LV mass was positively associated with systolic blood pressure and body mass index and negatively associated with treated hypertension and high-density lipoprotein cholesterol level. In men, the longitudinal LV mass increase was in contrast to a cross-sectional pattern of LV mass decrease. Conclusion As patients age, the LV responds differently in its mass and volume between men and women, although both men and women experience increased concentric LV remodeling

Adverse mood effects of combined oral contraceptives in relation to personality traits.

PubMed

Borgström, Anna; Odlind, Viveca; Ekselius, Lisa; Sundström-Poromaa, Inger

2008-12-01

Mood symptoms, such as depressed mood, anxiety and increased irritability, remain one of the major reasons for discontinuation of combined oral contraceptive (COC) pills. The aim of this study was to compare personality traits in women with ongoing or previous use of COCs and different experiences from these compounds with respect to adverse mood symptoms. Thirty women currently on COCs with no reports of adverse mood symptoms, 28 women currently on COCs and experiencing mood-related side effects, 27 women who had discontinued COC use for reasons other than adverse mood symptoms and 33 women who had discontinued COC use due to adverse mood effects were included. All participants were asked to fill out the Swedish universities Scales of Personality (SSP) to assess different personality traits. The women who were experiencing mood-related side effects on their current COC use exhibited higher scores on the somatic anxiety and stress susceptibility traits as compared to the women who did not experience any mood-related side effects from their current COCs. Women who had discontinued COC treatment because of adverse mood effects had higher scores of detachment and mistrust compared to women who had discontinued COC for reasons unrelated to mood effects. Higher scores on specific personality traits such as somatic anxiety and stress susceptibility are found in women with ongoing experience of adverse mood symptoms from COC. Higher scores of mistrust and detachment are more common among women who have discontinued COC treatment due to adverse mood effects.

Diesel Exhaust Inhalation Increases Cardiac Output, Bradyarrhythmias, and Parasympathetic Tone in Aged Heart Failure-Prone Rats

EPA Science Inventory

Acute air pollutant inhalation is linked to adverse cardiac events and death, and hospitalizations for heart failure. Diesel exhaust (DE) is a major air pollutant suspected to exacerbate preexisting cardiac conditions, in part, through autonomic and electrophysiologic disturbance...

Clinical and cost-effectiveness of home-based cardiac rehabilitation compared to conventional, centre-based cardiac rehabilitation: Results of the FIT@Home study.

PubMed

Kraal, Jos J; Van den Akker-Van Marle, M Elske; Abu-Hanna, Ameen; Stut, Wim; Peek, Niels; Kemps, Hareld Mc

2017-08-01

Aim Although cardiac rehabilitation improves physical fitness after a cardiac event, many eligible patients do not participate in cardiac rehabilitation and the beneficial effects of cardiac rehabilitation are often not maintained over time. Home-based training with telemonitoring guidance could improve participation rates and enhance long-term effectiveness. Methods and results We randomised 90 low-to-moderate cardiac risk patients entering cardiac rehabilitation to three months of either home-based training with telemonitoring guidance or centre-based training. Although training adherence was similar between groups, satisfaction was higher in the home-based group ( p = 0.02). Physical fitness improved at discharge ( p < 0.01) and at one-year follow-up ( p < 0.01) in both groups, without differences between groups (home-based p = 0.31 and centre-based p = 0.87). Physical activity levels did not change during the one-year study period (centre-based p = 0.38, home-based p = 0.80). Healthcare costs were statistically non-significantly lower in the home-based group (€437 per patient, 95% confidence interval -562 to 1436, p = 0.39). From a societal perspective, a statistically non-significant difference of €3160 per patient in favour of the home-based group was found (95% confidence interval -460 to 6780, p = 0.09) and the probability that it was more cost-effective varied between 97% and 75% (willingness-to-pay of €0 and €100,000 per quality-adjusted life-years, respectively). Conclusion We found no differences between home-based training with telemonitoring guidance and centre-based training on physical fitness, physical activity level or health-related quality of life. However, home-based training was associated with a higher patient satisfaction and appears to be more cost-effective than centre-based training. We conclude that home-based training with telemonitoring guidance can be used as an alternative to centre

Oral adverse effects due to the use of Nevirapine.

PubMed

Moura, Mariela Dutra Gontijo; Senna, Maria Inês Barreiros; Madureira, Davidson Fróis; Fonseca, Linaena Merícy Silva; Mesquita, Ricardo Alves

2008-01-01

The aim of this article is to present the clinical characteristics and management of an oral adverse effect stemming from the use of the antiretroviral medication Nevirapine (NVP). NVP is a non-nucleoside reverse transcriptase inhibitor used in the treatment of Human Immunodeficiency Virus (HIV) infection. A 29-year-old black man, HIV-infected since 1996, began highly active antiretroviral therapy (HAART) with zidovudine, lamivudine, and indinavir. From 1996 to 2002 several medications were changed due to their adverse effects: indinavir (renal colic and fever), nelfinavir (cutaneous rash), and efavirenz (nausea and temporary memory loss). When the patient presented to our service he was taking NVP, zidovudine, and lamivudine. A whitish plaque in the lips and bilateral buccal mucosa, burning, taste disturbance, and xerostomia were observed. The discontinuation of HAART led to the complete resolution of signs and symptoms. The patient has received follow-up treatment for three years and five months without local or systemic effects observed. Unfortunately, the clinical features of the oral adverse effect from NVP are not well known. This paper contributed to the identification of possible reactions in the oral cavity due to antiretroviral medication. Although HAART is very important in the treatment of HIV, its side effects are responsible for patients' non-adherence to medications. While more studies are needed to better understand the mechanism of action after suspending HAART, the complete resolution of the signs and symptoms was observed. Therefore, physicians and dentists alike must understand how to identify and prevent these adverse effects in order to further improve HIV patient treatments.

Effects of Obstructive Sleep Apnea and Obesity on Cardiac Remodeling: The Wisconsin Sleep Cohort Study.

PubMed

Korcarz, Claudia E; Peppard, Paul E; Young, Terry B; Chapman, Carrie B; Hla, K Mae; Barnet, Jodi H; Hagen, Erika; Stein, James H

2016-06-01

To characterize the prospective associations of obstructive sleep apnea (OSA) with future echocardiographic measures of adverse cardiac remodeling. This was a prospective long-term observational study. Participants had overnight polysomnography followed by transthoracic echocardiography a mean (standard deviation) of 18.0 (3.7) y later. OSA was characterized by the apnea-hypopnea index (AHI, events/hour). Echocardiography was used to assess left ventricular (LV) systolic and diastolic function and mass, left atrial volume and pressure, cardiac output, systemic vascular resistance, and right ventricular (RV) systolic function, size, and hemodynamics. Multivariate regression models estimated associations between log10(AHI+1) and future echocardiographic findings. A secondary analysis looked at oxygen desaturation indices and future echocardiographic findings. At entry, the 601 participants were mean (standard deviation) 47 (8) y old (47% female). After adjustment for age, sex, and body mass index, baseline log10(AHI+1) was associated significantly with future reduced LV ejection fraction and tricuspid annular plane systolic excursion (TAPSE) ≤ 15 mm. After further adjustment for cardiovascular risk factors, participants with higher baseline log10(AHI+1) had lower future LV ejection fraction (β = -1.35 [standard error = 0.6]/log10(AHI+1), P = 0.03) and higher odds of TAPSE ≤ 15 mm (odds ratio = 6.3/log10(AHI+1), 95% confidence interval = 1.3-30.5, P = 0.02). SaO2 desaturation indices were associated independently with LV mass, LV wall thickness, and RV area (all P < 0.03). OSA is associated independently with decreasing LV systolic function and with reduced RV function. Echocardiographic measures of adverse cardiac remodeling are strongly associated with OSA but are confounded by obesity. Hypoxia may be a stimulus for hypertrophy in individuals with OSA. © 2016 Associated Professional Sleep Societies, LLC.

TRPA1 mediates changes in heart rate variability and cardiac ...

EPA Pesticide Factsheets

Short-term exposure to ambient air pollution is linked with adverse cardiovascular effects. While previous research focused primarily on particulate matter-induced responses, gaseous air pollutants also contribute to cause short-term cardiovascular effects. Mechanisms underlying such effects have not been adequately described; however, the immediate nature of the response suggests involvement of irritant neural activation and downstream autonomic dysfunction. Thus, this study examines the role of TRPA1, an irritant sensory receptor found in the airways, in the cardiac response of mice to acrolein and ozone. Conscious unrestrained wild-type C57BL/6 (WT) and TRPA1 knockout (KO) mice implanted with radiotelemeters were exposed once to 3ppm acrolein, 0.3ppm ozone, or filtered air. Heart rate (HR) and electrocardiogram (ECG) were recorded continuously before, during and after exposure. Analysis of ECG morphology, incidence of arrhythmia and heart rate variability (HRV) were performed. Cardiac mechanical function was assessed using a Langendorff perfusion preparation 24h post-exposure. Acrolein exposure increased HRV independent of HR, as well as incidence of arrhythmia. Acrolein also increased left ventricular developed pressure in WT mice at 24h post-exposure. Ozone did not produce any changes in cardiac function. Neither gas produced ECG effects, changes in HRV, arrhythmogenesis, or mechanical function in KO mice. These data demonstrate that a single exposure to ac

Enhancing Cardiac Triacylglycerol Metabolism Improves Recovery From Ischemic Stress

PubMed Central

Liu, Li; Goldberg, Ira J.

2015-01-01

Elevated cardiac triacylglycerol (TAG) content is traditionally equated with cardiolipotoxicity and suggested to be a culprit in cardiac dysfunction. However, previous work demonstrated that myosin heavy-chain–mediated cardiac-specific overexpression of diacylglycerol transferase 1 (MHC-DGAT1), the primary enzyme for TAG synthesis, preserved cardiac function in two lipotoxic mouse models despite maintaining high TAG content. Therefore, we examined whether increased cardiomyocyte TAG levels due to DGAT1 overexpression led to changes in cardiac TAG turnover rates under normoxia and ischemia-reperfusion conditions. MHC-DGAT1 mice had elevated TAG content and synthesis rates, which did not alter cardiac function, substrate oxidation, or myocardial energetics. MHC-DGAT1 hearts had ischemia-induced lipolysis; however, when a physiologic mixture of long-chain fatty acids was provided, enhanced TAG turnover rates were associated with improved functional recovery from low-flow ischemia. Conversely, exogenous supply of palmitate during reperfusion suppressed elevated TAG turnover rates and impaired recovery from ischemia in MHC-DGAT1 hearts. Collectively, this study shows that elevated TAG content, accompanied by enhanced turnover, does not adversely affect cardiac function and, in fact, provides cardioprotection from ischemic stress. In addition, the results highlight the importance of exogenous supply of fatty acids when assessing cardiac lipid metabolism and its relationship with cardiac function. PMID:25858561

North American ginseng (Panax quinquefolius) suppresses β-adrenergic-dependent signalling, hypertrophy, and cardiac dysfunction.

PubMed

Tang, Xilan; Gan, Xiaohong Tracey; Rajapurohitam, Venkatesh; Huang, Cathy Xiaoling; Xue, Jenny; Lui, Edmund M K; Karmazyn, Morris

2016-12-01

There is increasing evidence for a beneficial effect of ginseng on cardiac pathology. Here, we determined whether North American ginseng can modulate the deleterious effects of the β-adrenoceptor agonist isoproterenol on cardiac hypertrophy and function using in vitro and in vivo approaches. Isoproterenol was administered for 2 weeks at either 25 mg/kg per day or 50 mg/kg per day (ISO25 or ISO50) via a subcutaneously implanted osmotic mini-pump to either control rats or those receiving ginseng (0.9 g/L in the drinking water ad libitum). Isoproterenol produced time- and dose-dependent left ventricular dysfunction, although these effects were attenuated by ginseng. Improved cardiac functions were associated with reduced heart masses, as well as prevention in the upregulation of the hypertrophy-related fetal gene expression. Lung masses were similarly attenuated, suggesting reduced pulmonary congestion. In in vitro studies, ginseng (10 μg/mL) completely suppressed the hypertrophic response to 1 μmol/L isoproterenol in terms of myocyte surface area, as well as reduction in the upregulation of fetal gene expression. These effects were associated with attenuation in both protein kinase A and cAMP response element-binding protein phosphorylation. Ginseng attenuates adverse cardiac adrenergic responses and, therefore, may be an effective therapy to reduce hypertrophy and heart failure associated with excessive catecholamine production.

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).

Changes in paced signals may predict in-hospital cardiac arrest.

PubMed

Attin, Mina; Rosero, Spencer Z; Ding, Jimmy; Nolan, Scot; Tucker, Rebecca

2018-01-01

An increasing number of patients with chronic illnesses have implanted cardiac rhythm devices such as pacemakers and implantable cardioverter-defibrillators (ICDs). This study was conducted to identify potentially useful predictors of in-hospital cardiac arrest (I-HCA) within paced electrocardiogram (ECG) signals from cardiovascular patients with implanted medical devices. In this retrospective study of 17 subjects, full-disclosure ECG traces prior to the time of documented I-HCA were analyzed to determine R-R intervals and QRS durations (QRSd). Ventricular paced QRSd prolongation was observed prior to I-HCA in 10/16 (63%) subjects. QRSd was significantly greater immediately preceding cardiac arrest than during each of the 8 hours prior to cardiac arrest (P < 0.05). Heart rate changes (measured using standard deviation) within 15 minutes of cardiac arrest were significantly greater in subjects with pulseless electrical activity (PEA)/asystolic arrest compared to those with cardiac arrests due to ventricular tachycardia/ventricular fibrillation (VT/VF) (10.13 vs 3.31; P  =  0.024). Significant differences over the 8 hours preceding cardiac arrest in heart rate (74 vs 86 beats/min; P  =  0.002) and QRS duration (172 ms vs 137 ms; P < 0.001) were observed between subjects with initial rhythms of VT/VF and those with initial rhythms of PEA/asystole. Patterns of diagnostic ECG features can be extracted from the telemetry data of patients with implanted medical devices prior to adverse events including I-HCA. The detection of these significant changes might have an immediate prognostic impact on the timely treatment of some patients at risk of adverse events. © 2017 Wiley Periodicals, Inc.

Increased Cardiac Myocyte Progenitors in Failing Human Hearts

PubMed Central

Kubo, Hajime; Jaleel, Naser; Kumarapeli, Asangi; Berretta, Remus M.; Bratinov, George; Shan, Xiaoyin; Wang, Hongmei; Houser, Steven R.; Margulies, Kenneth B.

2009-01-01

Background Increasing evidence, derived mainly from animal models, supports the existence of endogenous cardiac renewal and repair mechanisms in adult mammalian hearts that could contribute to normal homeostasis and the responses to pathological insults. Methods and Results Translating these results, we isolated small c-kit+ cells from 36 of 37 human hearts using primary cell isolation techniques and magnetic cell sorting techniques. The abundance of these cardiac progenitor cells was increased nearly 4-fold in patients with heart failure requiring transplantation compared with nonfailing controls. Polychromatic flow cytometry of primary cell isolates (<30 μm) without antecedent c-kit enrichment confirmed the increased abundance of c-kit+ cells in failing hearts and demonstrated frequent coexpression of CD45 in these cells. Immunocytochemical characterization of freshly isolated, c-kit–enriched human cardiac progenitor cells confirmed frequent coexpression of c-kit and CD45. Primary cardiac progenitor cells formed new human cardiac myocytes at a relatively high frequency after coculture with neonatal rat ventricular myocytes. These contracting new cardiac myocytes exhibited an immature phenotype and frequent electric coupling with the rat myocytes that induced their myogenic differentiation. Conclusions Despite the increased abundance and cardiac myogenic capacity of cardiac progenitor cells in failing human hearts, the need to replace these organs via transplantation implies that adverse features of the local myocardial environment overwhelm endogenous cardiac repair capacity. Developing strategies to improve the success of endogenous cardiac regenerative processes may permit therapeutic myocardial repair without cell delivery per se. PMID:18645055

Effects of Trichothecenes on Cardiac Cell Electrical Function

DTIC Science & Technology

1985-12-16

toxic effects . These studies demonstrated unequivocal reversible effects of certain mycotoxins on heart cell electrical activity. Preliminary studies...muscle cells shown in Figure 8 illustrate the typical effects of trichothecene mycotoxins in canine ventricular cells. T-2 tetraol, for 3xample...false tendon cells and V ventricular muscle cells (shown in Figure 8) illustrate the typical effects of trichothecene mycotoxins in canine cardiac

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.

Adverse Effects of Electroconvulsive Therapy.

PubMed

Andrade, Chittaranjan; Arumugham, Shyam Sundar; Thirthalli, Jagadisha

2016-09-01

Electroconvulsive therapy (ECT) is an effective treatment commonly used for depression and other major psychiatric disorders. We discuss potential adverse effects (AEs) associated with ECT and strategies for their prevention and management. Common acute AEs include headache, nausea, myalgia, and confusion; these are self-limiting and are managed symptomatically. Serious but uncommon AEs include cardiovascular, pulmonary, and cerebrovascular events; these may be minimized with screening for risk factors and by physiologic monitoring. Although most cognitive AEs of ECT are short-lasting, troublesome retrograde amnesia may rarely persist. Modifications of and improvements in treatment techniques minimize cognitive and other AEs. Copyright © 2016 Elsevier Inc. All rights reserved.

Energy Drink Consumption: Beneficial and Adverse Health Effects.

PubMed

Alsunni, Ahmed Abdulrahman

2015-10-01

Consumption of energy drinks has been increasing dramatically in the last two decades, particularly amongst adolescents and young adults. Energy drinks are aggressively marketed with the claim that these products give an energy boost to improve physical and cognitive performance. However, studies supporting these claims are limited. In fact, several adverse health effects have been related to energy drink; this has raised the question of whether these beverages are safe. This review was carried out to identify and discuss the published articles that examined the beneficial and adverse health effects related to energy drink. It is concluded that although energy drink may have beneficial effects on physical performance, these products also have possible detrimental health consequences. Marketing of energy drinks should be limited or forbidden until independent research confirms their safety, particularly among adolescents.

Diesel Exhaust-Induced Cardiac Dysfunction Is Mediated by Sympathetic Dominance in Heart Failure-Prone Rats

EPA Science Inventory

Short-term exposure to vehicular emissions is associated with adverse cardiac events. Diesel exhaust (DE) may provoke cardiac events through defective co-ordination of the two main autonomic nervous system (ANS) branches. We exposed heart failure-prone rats once to DE (500 g/m3 ...

Probable Nootropicinduced Psychiatric Adverse Effects: A Series of Four Cases

PubMed Central

Ajaltouni, Jean

2015-01-01

The misuse of nootropics—any substance that may alter, improve, or augment cognitive performance, mainly through the stimulation or inhibition of certain neurotransmitters—may potentially be dangerous and deleterious to the human brain, and certain individuals with a history of mental or substance use disorders might be particularly vulnerable to their adverse effects. We describe four cases of probable nootropic-induced psychiatric adverse effects to illustrate this theory. To the best of our knowledge this has not been previously reported in the formal medical literature. We briefly describe the most common classes of nootropics, including their postulated or proven methods of actions, their desired effects, and their adverse side effects, and provide a brief discussion of the cases. Our objective is to raise awareness among physicians in general and psychiatrists and addiction specialists in particular of the potentially dangerous phenomenon of unsupervised nootropic use among young adults who may be especially vulnerable to nootropics’ negative effects. PMID:27222762

Adverse effects of anticancer agents that target the VEGF pathway.

PubMed

Chen, Helen X; Cleck, Jessica N

2009-08-01

Antiangiogenesis agents that target the VEGF/VEGF receptor pathway have become an important part of standard therapy in multiple cancer indications. With expanded clinical experience with this class of agents has come the increasing recognition of the diverse adverse effects related to disturbance of VEGF-dependent physiological functions and homeostasis in the cardiovascular and renal systems, as well as wound healing and tissue repair. Although most adverse effects of VEGF inhibitors are modest and manageable, some are associated with serious and life-threatening consequences, particularly in high-risk patients and in certain clinical settings. This Review examines the toxicity profiles of anti-VEGF antibodies and small-molecule inhibitors. The potential mechanisms of the adverse effects, risk factors, and the implications for selection of patients and management are discussed.

Adverse effects of dietary fructose.

PubMed

Gaby, Alan R

2005-12-01

The consumption of fructose, primarily from high-fructose corn syrup (HFCS), has increased considerably in the United States during the past several decades. Intake of HFCS may now exceed that of the other major caloric sweetener, sucrose. Some nutritionists believe fructose is a safer form of sugar than sucrose, particularly for people with diabetes mellitus, because it does not adversely affect blood-glucose regulation, at least in the short-term. However, fructose has potentially harmful effects on other aspects of metabolism. In particular, fructose is a potent reducing sugar that promotes the formation of toxic advanced glycation end-products, which appear to play a role in the aging process; in the pathogenesis of the vascular, renal, and ocular complications of diabetes; and in the development of atherosclerosis. Fructose has also been implicated as the main cause of symptoms in some patients with chronic diarrhea or other functional bowel disturbances. In addition, excessive fructose consumption may be responsible in part for the increasing prevalence of obesity, diabetes mellitus, and non-alcoholic fatty liver disease. Although the long-term effects of fructose consumption have not been adequately studied in humans, the available evidence suggests it may be more harmful than is generally recognized. The extent to which a person might be adversely affected by dietary fructose depends both on the amount consumed and on individual tolerance. With a few exceptions, the relatively small amounts of fructose that occur naturally in fruits and vegetables are unlikely to have deleterious effects, and this review is not meant to discourage the consumption of these healthful foods.

Recombinant human deoxyribonuclease improves atelectasis in mechanically ventilated children with cardiac disease.

PubMed

Prodhan, Parthak; Greenberg, B; Bhutta, Adnan T; Hyde, Carrie; Vankatesan, Ajay; Imamura, Michiaki; Jaquiss, Robert Db; Dyamenahalli, Umesh

2009-01-01

To investigate whether a mucolytic agent, recombinant human deoxyribonuclease (rhDNase), improves atelectasis in children with cardiac illness requiring mechanical ventilation. A retrospective cohort study on consecutive patients receiving short-term (< or =14 days) rhDNase therapy for atelectasis in the cardiac intensive care unit from January 2005 through February 2007 was carried out. Data relating to patient characteristics, gas exchange, ventilatory parameters, and chest radiographs were collected and analyzed. The effectiveness of rhDNase therapy in the presence of neutrophils and/or bacteria in the pre-rhDNase therapy tracheal aspirates was also investigated. rhDNase was effective in significantly improving established atelectasis without any major changes in gas exchange and ventilatory parameters. Therapeutic effect of rhDNase is most effective in ameliorating atelectasis in the lungs within 10 doses. rhDNase was more effective in improving chest radiographic atelectasis score in patients who had > moderate amounts of polymophonuclear neutrophils (P value = 0.0008), or bacteria (P value = 0.007) or both (P value = 0.004) present in their pre-rhDNase therapy trachea aspirate. No adverse effects were seen with rhDNase administration in the study cohort. rhDNase can be safely and effectively used to improve atelectasis in mechanically ventilated children with cardiac disease especially in the presence of bacteria and/or moderate amounts of polymophonuclear neutrophils in the pre-rhDNase therapy tracheal aspirate.

Recombinant Human Deoxyribonuclease Improves Atelectasis in Mechanically Ventilated Children with Cardiac Disease

PubMed Central

Prodhan, P; Greenberg, B; Bhutta, AT; Hyde, C; Vankatesan, A; Imamura, M; Jaquiss, RDB; Dyamenahalli, U

2010-01-01

Objective To investigate if a mucolytic agent, recombinant human deoxyribonuclease (rhDNase), improves atelectasis in children with cardiac illness requiring mechanical ventilation. Design A retrospective cohort study on consecutive patients receiving short-term (≤ 14 days) rhDNase therapy for atelectasis in the cardiac intensive care unit from January 2005 through February 2007 was carried out. Data relating to patient characteristics, gas exchange, ventilatory parameters and chest radiographs was collected and analyzed. The effectiveness of rhDNase therapy in the presence of neutrophils and/ or bacteria in the pre-rhDNase therapy tracheal aspirates was also investigated. Results rhDNase was effective in significantly improving established atelectasis without any major changes in gas exchange and ventilatory parameters. Therapeutic effect of rhDNase is most effective in ameliorating atelectasis in the lungs within 10 doses. rhDNase was more effective in improving chest radiographic atelectasis score in patients who had > moderate amounts PMN (p value= 0.0008), or bacteria (p value=0.007) or both (p value =0.004) present in their pre-rhDNase therapy trachea aspirate. No adverse effects were seen with rhDNase administration in the study cohort. Conclusions rhDNase can be safely and effectively used to improve atelectasis in mechanically ventilated children with cardiac disease especially in the presence of bacteria and/ or moderate amounts of PMN in the pre-rhDNase therapy tracheal aspirate. PMID:19489944

Minimizing AED adverse effects: improving quality of life in the interictal state in epilepsy care.

PubMed

St Louis, Erik K; Louis, Erik K

2009-06-01

The goals of epilepsy therapy are to achieve seizure freedom while minimizing adverse effects of treatment. However, producing seizure-freedom is often overemphasized, at the expense of inducing adverse effects of treatment. All antiepileptic drugs (AEDs) have the potential to cause dose-related, "neurotoxic" adverse effects (i.e., drowsiness, fatigue, dizziness, blurry vision, and incoordination). Such adverse effects are common, especially when initiating AED therapy and with polytherapy. Dose-related adverse effects may be obviated in most patients by dose reduction of monotherapy, reduction or elimination of polytherapy, or substituting for a better tolerated AED. Additionally, all older and several newer AEDs have idiosyncratic adverse effects which usually require withdrawal in an affected patient, including serious rash (i.e., Stevens-Johnson Syndrome, toxic epidermal necrolysis), hematologic dyscrasias, hepatotoxicity, teratogenesis in women of child bearing potential, bone density loss, neuropathy, and severe gingival hyperplasia. Unfortunately, occurrence of idiosyncratic AED adverse effects cannot be predicted or, in most cases, prevented in susceptible patients. This article reviews a practical approach for the definition and identification of adverse effects of epilepsy therapies, and reviews the literature demonstrating that adverse effects result in detrimental quality of life in epilepsy patients. Strategies for minimizing AED adverse effects by reduction or elimination of AED polytherapy, appropriately employing drug-sparing therapies, and optimally administering AEDs are outlined, including tenets of AED selection, titration, therapeutic AED laboratory monitoring, and avoidance of chronic idiosyncratic adverse effects.

Cardiac effects of 3-iodothyronamine: a new aminergic system modulating cardiac function.

PubMed

Chiellini, Grazia; Frascarelli, Sabina; Ghelardoni, Sandra; Carnicelli, Vittoria; Tobias, Sandra C; DeBarber, Andrea; Brogioni, Simona; Ronca-Testoni, Simonetta; Cerbai, Elisabetta; Grandy, David K; Scanlan, Thomas S; Zucchi, Riccardo

2007-05-01

3-Iodothyronamine T1AM is a novel endogenous thyroid hormone derivative that activates the G protein-coupled receptor known as trace anime-associated receptor 1 (TAAR1). In the isolated working rat heart and in rat cardiomyocytes, T1AM produced a reversible, dose-dependent negative inotropic effect (e.g., 27+/-5, 51+/-3, and 65+/-2% decrease in cardiac output at 19, 25, and 38 microM concentration, respectively). An independent negative chronotropic effect was also observed. The hemodynamic effects of T1AM were remarkably increased in the presence of the tyrosine kinase inhibitor genistein, whereas they were attenuated in the presence of the tyrosine phosphatase inhibitor vanadate. No effect was produced by inhibitors of protein kinase A, protein kinase C, calcium-calmodulin kinase II, phosphatidylinositol-3-kinase, or MAP kinases. Tissue cAMP levels were unchanged. In rat ventricular tissue, Western blot experiments with antiphosphotyrosine antibodies showed reduced phosphorylation of microsomal and cytosolic proteins after perfusion with synthetic T1AM; reverse transcriptase-polymerase chain reaction experiments revealed the presence of transcripts for at least 5 TAAR subtypes; specific and saturable binding of [125I]T1AM was observed, with a dissociation constant in the low micromolar range (5 microM); and endogenous T1AM was detectable by tandem mass spectrometry. In conclusion, our findings provide evidence for the existence of a novel aminergic system modulating cardiac function.

Effect of a single intraoperative high-dose ATG-Fresenius on delayed graft function in donation after cardiac-death donor renal allograft recipients: a randomized study.

PubMed

van den Hoogen, Martijn W F; Kho, Marcia M L; Abrahams, Alferso C; van Zuilen, Arjan D; Sanders, Jan-Stephan; van Dijk, Marja; Hilbrands, Luuk B; Weimar, Willem; Hoitsma, Andries J

2013-04-01

Reducing the incidence of delayed graft function after transplant with donation after cardiac death donor renal allografts would facilitate managing recipients during their first weeks after a transplant. To reduce this incidence, in most studies, induction therapy with depleting anti-T-lymphocyte antibodies is coupled with a reduction of the dosage of the calcineurin inhibitor. The separate effect of anti-T-cell therapy on the incidence and duration of delayed graft function is therefore difficult to assess. We performed a randomized study to evaluate the effect of a single intraoperative high-dose of anti-T-lymphocyte immunoglobulin (ATG)-Fresenius (9 mg/kg body weight) on the incidence of delayed graft function. Eligible adult recipients of a first donation after cardiac death donor renal allograft were randomly assigned to ATG-Fresenius or no induction therapy. Maintenance immunosuppression consisted of tacrolimus, in an unadjusted dose, mycophenolate mofetil, and steroids. The study was prematurely terminated because of a lower-than-anticipated inclusion rate. Baseline characteristics were comparable in the ATG-Fresenius group (n=28) and the control group (n=24). Twenty-two patients in the ATG-Fresenius group (79%) had delayed graft function, compared with 13 in the control group (54%; P = .06). Allograft and patient survival were comparable in both groups. Serious adverse events occurred more frequently in the ATG-Fresenius group than they did in the control group (57% vs 29%; P < .05). Intraoperative administration of a single high-dose of ATG-Fresenius in donation after cardiac death donor renal allograft recipients, followed by triple immunosuppression with an unadjusted tacrolimus dose, seems ineffective to reduce the incidence of delayed graft function. Moreover, this was associated with a higher rate of serious adverse events (EudraCT-number, 2007-000210-36.).

Effects of percutaneous renal sympathetic denervation on cardiac function and exercise tolerance in patients with chronic heart failure.

PubMed

Gao, Jun-Qing; Xie, Yun; Yang, Wei; Zheng, Jian-Pu; Liu, Zong-Jun

2017-01-01

Sympathetic hyperactivity, a vital factor in the genesis and development of heart failure (HF), has been reported to be effectively reduced by percutaneous renal denervation (RDN), which may play an important role in HF treatment. To determine the effects of percutaneous RDN on cardiac function in patients with chronic HF (CHF). Fourteen patients (mean age 69.6 years; ejection fraction [EF] <45%) with CHF received bilateral RDN. Adverse cardiac events, blood pressure (BP), and biochemical parameters were assessed before and six months after percutaneous operation. Patients also underwent echocardiographic assessment of cardiac function and 6-min walk test before and at six months after percutaneous operation. The distance achieved by the 14 patients in the 6-min walk test increased significantly from 152.9±38.0 m before RDN to 334.3±94.4 m at six months after RDN (p<0.001), while EF increased from 36.0±4.1% to 43.8±7.9% (p=0.003) on echocardiography. No RDN-related complications were observed during the follow-up period. In 6-month follow-up, systolic BP decreased from 138.6±22.1 mmHg to 123.2±10.5 mmHg (p=0.026) and diastolic BP from 81.1±11.3 mmHg to 72.9±7.5 mmHg (p=0.032). Creatinine levels did not change significantly (1.3±0.65 mg/dl to 1.2±0.5 mg/dl, p=0.8856). RDN is potentially an effective technique for the treatment of severe HF that can significantly increase EF and improve exercise tolerance. Copyright © 2016 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

Comparison of search strategies in systematic reviews of adverse effects to other systematic reviews.

PubMed

Golder, Su; Loke, Yoon K; Zorzela, Liliane

2014-06-01

Research indicates that the methods used to identify data for systematic reviews of adverse effects may need to differ from other systematic reviews. To compare search methods in systematic reviews of adverse effects with other reviews. The search methodologies in 849 systematic reviews of adverse effects were compared with other reviews. Poor reporting of search strategies is apparent in both systematic reviews of adverse effects and other types of systematic reviews. Systematic reviews of adverse effects are less likely to restrict their searches to MEDLINE or include only randomised controlled trials (RCTs). The use of other databases is largely dependent on the topic area and the year the review was conducted, with more databases searched in more recent reviews. Adverse effects search terms are used by 72% of reviews and despite recommendations only two reviews report using floating subheadings. The poor reporting of search strategies in systematic reviews is universal, as is the dominance of searching MEDLINE. However, reviews of adverse effects are more likely to include a range of study designs (not just RCTs) and search beyond MEDLINE. © 2014 Crown Copyright.

[Liver transplant with donated graft after controlled cardiac death. Current situation].

PubMed

Abradelo De Usera, Manuel; Jiménez Romero, Carlos; Loinaz Segurola, Carmelo; Moreno González, Enrique

2013-11-01

An increasing pressure on the liver transplant waiting list, forces us to explore new sources, in order to expand the donor pool. One of the most interesting and with a promising potential, is donation after cardiac death (DCD). Initially, this activity has developed in Spain by means of the Maastricht type II donation in the uncontrolled setting. For different reasons, donation after controlled cardiac death has been reconsidered in our country. The most outstanding circumstance involved in DCD donation is a potential ischemic stress, that could cause severe liver graft cell damage, resulting in an adverse effect on liver transplant results, in terms of complications and outcomes. The complex and particular issues related to DCD Donation will be discussed in this review. Copyright © 2012 AEC. Published by Elsevier Espana. All rights reserved.

Validity and reliability of a novel immunosuppressive adverse effects scoring system in renal transplant recipients.

PubMed

Meaney, Calvin J; Arabi, Ziad; Venuto, Rocco C; Consiglio, Joseph D; Wilding, Gregory E; Tornatore, Kathleen M

2014-06-12

After renal transplantation, many patients experience adverse effects from maintenance immunosuppressive drugs. When these adverse effects occur, patient adherence with immunosuppression may be reduced and impact allograft survival. If these adverse effects could be prospectively monitored in an objective manner and possibly prevented, adherence to immunosuppressive regimens could be optimized and allograft survival improved. Prospective, standardized clinical approaches to assess immunosuppressive adverse effects by health care providers are limited. Therefore, we developed and evaluated the application, reliability and validity of a novel adverse effects scoring system in renal transplant recipients receiving calcineurin inhibitor (cyclosporine or tacrolimus) and mycophenolic acid based immunosuppressive therapy. The scoring system included 18 non-renal adverse effects organized into gastrointestinal, central nervous system and aesthetic domains developed by a multidisciplinary physician group. Nephrologists employed this standardized adverse effect evaluation in stable renal transplant patients using physical exam, review of systems, recent laboratory results, and medication adherence assessment during a clinic visit. Stable renal transplant recipients in two clinical studies were evaluated and received immunosuppressive regimens comprised of either cyclosporine or tacrolimus with mycophenolic acid. Face, content, and construct validity were assessed to document these adverse effect evaluations. Inter-rater reliability was determined using the Kappa statistic and intra-class correlation. A total of 58 renal transplant recipients were assessed using the adverse effects scoring system confirming face validity. Nephrologists (subject matter experts) rated the 18 adverse effects as: 3.1 ± 0.75 out of 4 (maximum) regarding clinical importance to verify content validity. The adverse effects scoring system distinguished 1.75-fold increased gastrointestinal adverse

Ibogaine-associated cardiac arrest and death: case report and review of the literature

PubMed Central

Meisner, Jessica A.; Wilcox, Susan R.; Richards, Jeremy B.

2016-01-01

A naturally occurring hallucinogenic plant alkaloid, ibogaine has been used as an adjuvant for opiate withdrawal for the past 50 years. In the setting of an escalating nationwide opiate epidemic, use of substances such as ibogaine may also increase. Therefore, familiarity with the mechanisms and potential adverse effects of ibogaine is important for clinicians. We present the case report of a man whose use of ibogaine resulted in cardiac arrest and death, complemented by a review of the literature regarding ibogaine’s clinical effects. A 40-year-old man who used ibogaine for symptoms of heroin withdrawal suffered acute cardiac arrest leading to cerebral edema and brain death. His presentation was consistent with ibogaine-induced cardiotoxicity and ibogaine-induced cardiac arrest, and a review of the literature regarding the history, mechanisms, risks and clinical outcomes associated with ibogaine is presented. The case presented underscores the significant potential clinical risks of ibogaine. It is important the healthcare community be aware of the possible effects of ibogaine such that clinicians can provide informed counseling to their patients regarding the risks of attempting detoxification with ibogaine. PMID:27141291

Long-term mucocutaneous adverse effects of imatinib in Indian chronic myeloid leukemia patients.

PubMed

Vinay, Keshavamurthy; Yanamandra, Uday; Dogra, Sunil; Handa, Sanjeev; Suri, Vikas; Kumari, Savita; Khadwal, Alka; Prakash, Gaurav; Lad, Deepesh; Varma, Subhash; Malhotra, Pankaj

2018-03-01

Short-term mucocutaneous adverse effects are well documented with imatinib. However, studies on long-term adverse effects and in the ethnic population are lacking. To study the long-term mucocutaneous adverse effects of imatinib and factors predicting these adverse effects. In this cross-sectional study, consenting adult chronic myeloid leukemia patients on imatinib for more than 250 days were recruited. The details of imatinib treatment were retrieved from hematology clinic records. Four hundred and thirty-eight patients who were on imatinib for a mean duration of 1820 days were recruited. A mean number of 1.42 ± 0.98 cutaneous adverse effects were seen per patient. Melasma-like pigmentation, periorbital edema, oral lichenoid reaction, cutaneous hypopigmentation, and vesicobullous eruptions were seen in 236 (53.9%), 81 (18.5%), 70 (16%), 42 (9.6%), and 12 (2.7%) patients, respectively. Drug-induced cutaneous eruptions (9.1%) and cutaneous hypopigmentation (9.6%) were seen less frequently. Cutaneous hyperpigmentation was more likely seen in younger patients (P = 0.001) and females (P < 0.001). On multivariate analysis, female gender was a significant risk factor for developing cutaneous hyperpigmentation and periorbital edema. Cutaneous hyperpigmentation and periorbital edema are common long-term adverse effects of imatinib in Indian patients. Female gender is a significant risk factor for the development of both these adverse effects. © 2017 The International Society of Dermatology.

Identification of genes regulated during mechanical load-induced cardiac hypertrophy

NASA Technical Reports Server (NTRS)

Johnatty, S. E.; Dyck, J. R.; Michael, L. H.; Olson, E. N.; Abdellatif, M.; Schneider, M. (Principal Investigator)

2000-01-01

Cardiac hypertrophy is associated with both adaptive and adverse changes in gene expression. To identify genes regulated by pressure overload, we performed suppressive subtractive hybridization between cDNA from the hearts of aortic-banded (7-day) and sham-operated mice. In parallel, we performed a subtraction between an adult and a neonatal heart, for the purpose of comparing different forms of cardiac hypertrophy. Sequencing more than 100 clones led to the identification of an array of functionally known (70%) and unknown genes (30%) that are upregulated during cardiac growth. At least nine of those genes were preferentially expressed in both the neonatal and pressure over-load hearts alike. Using Northern blot analysis to investigate whether some of the identified genes were upregulated in the load-independent calcineurin-induced cardiac hypertrophy mouse model, revealed its incomplete similarity with the former models of cardiac growth. Copyright 2000 Academic Press.

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

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.

Retrieval of the Leadless Cardiac Pacemaker: A Multicenter Experience.

PubMed

Reddy, Vivek Y; Miller, Marc A; Knops, Reinoud E; Neuzil, Petr; Defaye, Pascal; Jung, Werner; Doshi, Rahul; Castellani, Mark; Strickberger, Adam; Mead, R Hardwin; Doppalapudi, Harish; Lakkireddy, Dhanunjaya; Bennett, Matthew; Sperzel, Johannes

2016-12-01

Leadless cardiac pacemakers have emerged as a safe and effective alternative to conventional transvenous single-chamber ventricular pacemakers. Herein, we report a multicenter experience on the feasibility and safety of acute retrieval (<6 weeks) and chronic retrieval (>6 weeks) of the leadless cardiac pacemaker in humans. This study included patients enrolled in 3 multicenter trials, who received a leadless cardiac pacemaker implant and who subsequently underwent a device removal attempt. The overall leadless pacemaker retrieval success rate was 94%: for patients whose leadless cardiac pacemaker had been implanted for <6 weeks (acute retrieval cohort), complete retrieval was achieved in 100% (n=5/5); for those implanted for ≥ 6 weeks (chronic retrieval cohort), retrieval was achieved in 91% (n=10/11) of patients. The mean duration of time from implant to retrieval attempt was 346 days (range, 88-1188 days) in the chronic retrieval cohort, and nearly two thirds (n=7; 63%) had been implanted for >6 months before the retrieval attempt. There were no procedure-related adverse events at 30 days post retrieval procedure. This multicenter experience demonstrated the feasibility and safety of retrieving a chronically implanted single-chamber (right ventricle) active fixation leadless pacemaker. URL: https://www.clinicaltrials.gov. Unique identifiers: NCT02051972, NCT02030418, and NCT01700244. © 2016 American Heart Association, Inc.

10 CFR 1017.10 - Adverse effect test.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 4 2011-01-01 2011-01-01 false Adverse effect test. 1017.10 Section 1017.10 Energy DEPARTMENT OF ENERGY (GENERAL PROVISIONS) IDENTIFICATION AND PROTECTION OF UNCLASSIFIED CONTROLLED NUCLEAR INFORMATION Initially Determining What Information Is Unclassified Controlled Nuclear Information § 1017.10...

10 CFR 1017.10 - Adverse effect test.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 4 2012-01-01 2012-01-01 false Adverse effect test. 1017.10 Section 1017.10 Energy DEPARTMENT OF ENERGY (GENERAL PROVISIONS) IDENTIFICATION AND PROTECTION OF UNCLASSIFIED CONTROLLED NUCLEAR INFORMATION Initially Determining What Information Is Unclassified Controlled Nuclear Information § 1017.10...

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.

The Effects of Climate Change on Cardiac Health.

PubMed

De Blois, Jonathan; Kjellstrom, Tord; Agewall, Stefan; Ezekowitz, Justin A; Armstrong, Paul W; Atar, Dan

2015-01-01

The earth's climate is changing and increasing ambient heat levels are emerging in large areas of the world. An important cause of this change is the anthropogenic emission of greenhouse gases. Climate changes have a variety of negative effects on health, including cardiac health. People with pre-existing medical conditions such as cardiovascular disease (including heart failure), people carrying out physically demanding work and the elderly are particularly vulnerable. This review evaluates the evidence base for the cardiac health consequences of climate conditions, with particular reference to increasing heat exposure, and it also explores the potential further implications. © 2015 S. Karger AG, Basel.

Endocrine and Metabolic Adverse Effects of Psychotropic Medications in Children and Adolescents

ERIC Educational Resources Information Center

Correll, Christoph U.; Carlson, Harold E.

2006-01-01

Objective: Despite increasing use of psychotropic medications in children and adolescents, data regarding their efficacy and safety are limited. Endocrine and metabolic adverse effects are among the most concerning adverse effects of commonly used psychotropic medications. Method: Selective review of endocrine and metabolic effects of psychotropic…

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.

Cardiac effects of mitoxanthrone therapy in patients with multiple sclerosis.

PubMed

Pastuszak, Żanna; Tomczykiewicz, Kazimierz; Piusińska-Macoch, Renata; Stępień, Adam

2016-01-01

Mitoxanthrone (MTX) is a synthetic anthracycline antibiotic that has been used for several years in the treatment of patients with primary progressive, secondary progressive, and relapsing remitting multiple sclerosis (MS) who do not respond to other drugs. MTX has antineoplastic, immunomodulatory, and antibacterial properties. The most common adverse effects of MTX include nausea and vomiting, hair loss, increased risk of urinary and respiratory tract infections, and amenorrhea. Less frequent problems include leukopenia, thrombocytopenia, anaemia, and an increase in hepatic enzyme and bilirubin levels. Other severe sequelae of MTX treatment are drug cardiotoxicity and a potential to induce leukaemia. Drug toxicity results from its affinity to iron ions. The resulting complex strongly induces formation of free oxygen radicals and increases lipid peroxidation. Asymptomatic reduction in left ventricular ejection fraction (LVEF) by two-dimensional (2D) echocardiography, cardiomyopathy, and congestive heart failure have been observed in patients with MS at a rate of about 2.6-5%. Few studies evaluated cardiotoxicity of MTX in MS patients. Most previous studies were performed in small groups of cancer patients and cardiac evaluation was limited to physical examination. To evaluate the effect of MTX treatment on LVEF by 2D echocardiography. We studied 72 MS patients aged 25-63 years who were treated with MTX in 2002-2014. The diagnosis of MS was made using the 2001 McDonald criteria updated in 2005. The study group included primary progressive MS in 40 (56%) patients, secondary progressive MS in 5 (7%) patients, and relapsing remitting MS in 27 (37%) patients. MTX was administered at 12 mg/m2 of body surface area every 3 months (up to the total dose of 140 mg/m2). MTX treatment was initiated in patients with no signs of heart failure on physical examination, normal electrocardiogram (ECG), normal LVEF by 2D echocardiography, and normal laboratory test findings including

Adverse effects of antioxidative vitamins.

PubMed

Rutkowski, Maciej; Grzegorczyk, Krzysztof

2012-06-01

High doses of synthetic antioxidative vitamins: A, E, C and β-carotene are often used on long-term basis in numerous preventive and therapeutic medical applications. Instead of expected health effects, the use of those vitamins may however lead to cases of hypervitaminosis and even to intoxication. The article points out main principles of safety which are to be observed during supplementation with antioxidative vitamins. Toxic effects resulting from erroneous administration of high doses of those substances on organs and systems of the organism are also discussed. Attention is drawn to interactions of antioxidative vitamins with concomitantly used drugs, as well as intensification of adverse effects caused by various exogenous chemical factors. Moreover, the article presents the evaluation of supplementation with these vitamins, which was performed in large studies.

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.

Risk-adjusted sequential probability ratio tests: applications to Bristol, Shipman and adult cardiac surgery.

PubMed

Spiegelhalter, David; Grigg, Olivia; Kinsman, Robin; Treasure, Tom

2003-02-01

To investigate the use of the risk-adjusted sequential probability ratio test in monitoring the cumulative occurrence of adverse clinical outcomes. Retrospective analysis of three longitudinal datasets. Patients aged 65 years and over under the care of Harold Shipman between 1979 and 1997, patients under 1 year of age undergoing paediatric heart surgery in Bristol Royal Infirmary between 1984 and 1995, adult patients receiving cardiac surgery from a team of cardiac surgeons in London,UK. Annual and 30-day mortality rates. Using reasonable boundaries, the procedure could have indicated an 'alarm' in Bristol after publication of the 1991 Cardiac Surgical Register, and in 1985 or 1997 for Harold Shipman depending on the data source and the comparator. The cardiac surgeons showed no significant deviation from expected performance. The risk-adjusted sequential probability test is simple to implement, can be applied in a variety of contexts, and might have been useful to detect specific instances of past divergent performance. The use of this and related techniques deserves further attention in the context of prospectively monitoring adverse clinical outcomes.

Association of chronic kidney disease with abnormal cardiac mechanics and adverse outcomes in patients with heart failure and preserved ejection fraction.

PubMed

Unger, Erin D; Dubin, Ruth F; Deo, Rajat; Daruwalla, Vistasp; Friedman, Julie L; Medina, Crystal; Beussink, Lauren; Freed, Benjamin H; Shah, Sanjiv J

2016-01-01

Chronic kidney disease (CKD) is associated with worse outcomes in heart failure with preserved ejection fraction (HFpEF). Whether this association is due the effect of CKD on intrinsic abnormalities in cardiac function is unknown. We hypothesized that CKD is independently associated with worse cardiac mechanics in HFpEF. We prospectively studied 299 patients enrolled in the Northwestern University HFpEF Program. Using the creatinine-based CKD-Epi equation to calculate estimated glomerular filtration rate (eGFR), study participants were analysed by CKD status (using eGFR <60 mL/min/1.73 m(2) to denote CKD). Indices of cardiac mechanics (longitudinal strain parameters) were measured using speckle-tracking echocardiography. Using multivariable-adjusted linear and Cox regression analyses, we determined the association between CKD and echocardiographic parameters and clinical outcomes (cardiovascular hospitalization or death). Of 299 study participants, 48% had CKD. CKD (dichotomous variable) and reduced eGFR (continuous variable) were both associated with worse cardiac mechanics indices including left atrial (LA) reservoir strain, LV longitudinal strain, and right ventricular free wall strain even after adjusting for potential confounders, including co-morbidities, EF, and volume status. For example, for each 1-SD decrease in eGFR, LA reservoir strain was 3.52% units lower (P < 0.0001) after multivariable adjustment. Reduced eGFR was also associated with worse outcomes [adjusted hazard ratio (HR) 1.28, 95% confidence interval (CI) 1.01-1.61 per 1-SD decrease in eGFR; P = 0.039]. The association was attenuated after adjustment for indices of cardiac mechanics (P = 0.064). In HFpEF, CKD is independently associated with worse cardiac mechanics, which may explain why HFpEF patients with CKD have worse outcomes. NCT01030991. © 2015 The Authors European Journal of Heart Failure © 2015 European Society of Cardiology.

Adverse hematological effects of hexavalent chromium: an overview

PubMed Central

2016-01-01

Workers of tanneries, welding industries, factories manufacturing chromate containing paints are exposed to hexavalent chromium that increases the risk of developing serious adverse health effects. This review elucidates the mode of action of hexavalent chromium on blood and its adverse effects. Both leukocyte and erythrocyte counts of blood sharply decreased in Swiss mice after two weeks of intraperitoneal treatment with Cr (VI), with the erythrocytes transforming into echinocytes. The hexavalent chromium in the blood is readily reduced to trivalent form and the reductive capacity of erythrocytes is much greater than that of plasma. Excess Cr (VI), not reduced in plasma, may enter erythrocytes and lymphocytes and in rodents it induces microcytic anemia. The toxic effects of chromium (VI) include mitochondrial injury and DNA damage of blood cells that leads to carcinogenicity. Excess Cr (VI) increases cytosolic Ca2+ activity and ATP depletion thereby inducing eryptosis. Se, vitamin C, and quercetin are assumed to have some protective effect against hexavalent chromium induced hematological disorders. PMID:28652847

Adverse hematological effects of hexavalent chromium: an overview.

PubMed

Ray, Rina Rani

2016-06-01

Workers of tanneries, welding industries, factories manufacturing chromate containing paints are exposed to hexavalent chromium that increases the risk of developing serious adverse health effects. This review elucidates the mode of action of hexavalent chromium on blood and its adverse effects. Both leukocyte and erythrocyte counts of blood sharply decreased in Swiss mice after two weeks of intraperitoneal treatment with Cr (VI), with the erythrocytes transforming into echinocytes. The hexavalent chromium in the blood is readily reduced to trivalent form and the reductive capacity of erythrocytes is much greater than that of plasma. Excess Cr (VI), not reduced in plasma, may enter erythrocytes and lymphocytes and in rodents it induces microcytic anemia. The toxic effects of chromium (VI) include mitochondrial injury and DNA damage of blood cells that leads to carcinogenicity. Excess Cr (VI) increases cytosolic Ca 2+ activity and ATP depletion thereby inducing eryptosis. Se, vitamin C, and quercetin are assumed to have some protective effect against hexavalent chromium induced hematological disorders.

The effects of malnutrition on cardiac function in African children.

PubMed

Silverman, Jonathan A; Chimalizeni, Yamikani; Hawes, Stephen E; Wolf, Elizabeth R; Batra, Maneesh; Khofi, Harriet; Molyneux, Elizabeth M

2016-02-01

Cardiac dysfunction may contribute to high mortality in severely malnourished children. Our objective was to assess the effect of malnutrition on cardiac function in hospitalised African children. Prospective cross-sectional study. Public referral hospital in Blantyre, Malawi. We enrolled 272 stable, hospitalised children ages 6-59 months, with and without WHO-defined severe acute malnutrition. Cardiac index, heart rate, mean arterial pressure, stroke volume index and systemic vascular resistance index were measured by the ultrasound cardiac output monitor (USCOM, New South Wales, Australia). We used linear regression with generalised estimating equations controlling for age, sex and anaemia. Our primary outcome, cardiac index, was similar between those with and without severe malnutrition: difference=0.22 L/min/m(2) (95% CI -0.08 to 0.51). No difference was found in heart rate or stroke volume index. However, mean arterial pressure and systemic vascular resistance index were lower in children with severe malnutrition: difference=-8.6 mm Hg (95% CI -12.7 to -4.6) and difference=-200 dyne s/cm(5)/m(2) (95% CI -320 to -80), respectively. In this largest study to date, we found no significant difference in cardiac function between hospitalised children with and without severe acute malnutrition. Further study is needed to determine if cardiac function is diminished in unstable malnourished children. 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/

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.

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.

Streptococcus pneumoniae Translocates into the Myocardium and Forms Unique Microlesions That Disrupt Cardiac Function

PubMed Central

Brown, Armand O.; Mann, Beth; Gao, Geli; Hankins, Jane S.; Humann, Jessica; Giardina, Jonathan; Faverio, Paola; Restrepo, Marcos I.; Halade, Ganesh V.; Mortensen, Eric M.; Lindsey, Merry L.; Hanes, Martha; Happel, Kyle I.; Nelson, Steve; Bagby, Gregory J.; Lorent, Jose A.; Cardinal, Pablo; Granados, Rosario; Esteban, Andres; LeSaux, Claude J.; Tuomanen, Elaine I.; Orihuela, Carlos J.

2014-01-01

Hospitalization of the elderly for invasive pneumococcal disease is frequently accompanied by the occurrence of an adverse cardiac event; these are primarily new or worsened heart failure and cardiac arrhythmia. Herein, we describe previously unrecognized microscopic lesions (microlesions) formed within the myocardium of mice, rhesus macaques, and humans during bacteremic Streptococcus pneumoniae infection. In mice, invasive pneumococcal disease (IPD) severity correlated with levels of serum troponin, a marker for cardiac damage, the development of aberrant cardiac electrophysiology, and the number and size of cardiac microlesions. Microlesions were prominent in the ventricles, vacuolar in appearance with extracellular pneumococci, and remarkable due to the absence of infiltrating immune cells. The pore-forming toxin pneumolysin was required for microlesion formation but Interleukin-1β was not detected at the microlesion site ruling out pneumolysin-mediated pyroptosis as a cause of cell death. Antibiotic treatment resulted in maturing of the lesions over one week with robust immune cell infiltration and collagen deposition suggestive of long-term cardiac scarring. Bacterial translocation into the heart tissue required the pneumococcal adhesin CbpA and the host ligands Laminin receptor (LR) and Platelet-activating factor receptor. Immunization of mice with a fusion construct of CbpA or the LR binding domain of CbpA with the pneumolysin toxoid L460D protected against microlesion formation. We conclude that microlesion formation may contribute to the acute and long-term adverse cardiac events seen in humans with IPD. PMID:25232870

Automated cardiopulmonary resuscitation using a load-distributing band external cardiac support device for in-hospital cardiac arrest: a single centre experience of AutoPulse-CPR.

PubMed

Spiro, J R; White, S; Quinn, N; Gubran, C J; Ludman, P F; Townend, J N; Doshi, S N

2015-02-01

Poor quality cardiopulmonary resuscitation (CPR) predicts adverse outcome. During invasive cardiac procedures automated-CPR (A-CPR) may help maintain effective resuscitation. The use of A-CPR following in-hospital cardiac arrest (IHCA) remains poorly described. Firstly, we aimed to assess the efficiency of healthcare staff using A-CPR in a cardiac arrest scenario at baseline, following re-training and over time (Scenario-based training). Secondly, we studied our clinical experience of A-CPR at our institution over a 2-year period, with particular emphasis on the details of invasive cardiac procedures performed, problems encountered, resuscitation rates and in-hospital outcome (AutoPulse-CPR Registry). Scenario-based training: Forty healthcare professionals were assessed. At baseline, time-to-position device was slow (mean 59 (±24) s (range 15-96s)), with the majority (57%) unable to mode-switch. Following re-training time-to-position reduced (28 (±9) s, p<0.01 vs baseline) with 95% able to mode-switch. This improvement was maintained over time. AutoPulse-CPR Registry: 285 patients suffered IHCA, 25 received A-CPR. Survival to hospital discharge following conventional CPR was 28/260 (11%) and 7/25 (28%) following A-CPR. A-CPR supported invasive procedures in 9 patients, 2 of whom had A-CPR dependant circulation during transfer to the catheter lab. A-CPR may provide excellent haemodynamic support and facilitate simultaneous invasive cardiac procedures. A significant learning curve exists when integrating A-CPR into clinical practice. Further studies are required to better define the role and effectiveness of A-CPR following IHCA. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

The hemodynamic effects of intravenous paracetamol (acetaminophen) vs normal saline in cardiac surgery patients: A single center placebo controlled randomized study

PubMed Central

Churilov, Leonid

2018-01-01

The hemodynamic effects of intravenous (IV) paracetamol in patients undergoing cardiac surgery are unknown. We performed a prospective single center placebo controlled randomized study with parallel group design in adult patients undergoing elective cardiac surgery. Participants received paracetamol (1 gram) IV or placebo (an equal volume of 0.9% saline) preoperatively followed by two postoperative doses 6 hours apart. The primary endpoint was the absolute change in systolic (SBP) 30 minutes after the preoperative infusion, analysed using an ANCOVA model. Secondary endpoints included absolute changes in mean arterial pressure (MAP) and diastolic blood pressure (DPB), and other key hemodynamic variables after each infusion. All other endpoints were analysed using random-effect generalized least squares regression modelling with individual patients treated as random effects. Fifty participants were randomly assigned to receive paracetamol (n = 25) or placebo (n = 25). Post preoperative infusion, paracetamol decreased SBP by a mean (SD) of 13 (18) mmHg, p = 0.02, compared to a mean (SD) of 1 (11) mmHg with saline. Paracetamol decreased MAP and DBP by a mean (SD) of 9 (12) mmHg and 8 (9) mmHg (p = 0.01 and 0.02), respectively, compared to a mean (SD) of 1 (8) mmHg and 0 (6) mmHg with placebo. Postoperatively, there were no significant differences in pressure or flow based hemodynamic parameters in both groups. This study provides high quality evidence that the administration of IV paracetamol in patients undergoing cardiac surgery causes a transient decrease in preoperative blood pressure when administered before surgery but no adverse hemodynamic effects when administered in the postoperative setting. PMID:29659631

The hemodynamic effects of intravenous paracetamol (acetaminophen) vs normal saline in cardiac surgery patients: A single center placebo controlled randomized study.

PubMed

Chiam, Elizabeth; Bellomo, Rinaldo; Churilov, Leonid; Weinberg, Laurence

2018-01-01

The hemodynamic effects of intravenous (IV) paracetamol in patients undergoing cardiac surgery are unknown. We performed a prospective single center placebo controlled randomized study with parallel group design in adult patients undergoing elective cardiac surgery. Participants received paracetamol (1 gram) IV or placebo (an equal volume of 0.9% saline) preoperatively followed by two postoperative doses 6 hours apart. The primary endpoint was the absolute change in systolic (SBP) 30 minutes after the preoperative infusion, analysed using an ANCOVA model. Secondary endpoints included absolute changes in mean arterial pressure (MAP) and diastolic blood pressure (DPB), and other key hemodynamic variables after each infusion. All other endpoints were analysed using random-effect generalized least squares regression modelling with individual patients treated as random effects. Fifty participants were randomly assigned to receive paracetamol (n = 25) or placebo (n = 25). Post preoperative infusion, paracetamol decreased SBP by a mean (SD) of 13 (18) mmHg, p = 0.02, compared to a mean (SD) of 1 (11) mmHg with saline. Paracetamol decreased MAP and DBP by a mean (SD) of 9 (12) mmHg and 8 (9) mmHg (p = 0.01 and 0.02), respectively, compared to a mean (SD) of 1 (8) mmHg and 0 (6) mmHg with placebo. Postoperatively, there were no significant differences in pressure or flow based hemodynamic parameters in both groups. This study provides high quality evidence that the administration of IV paracetamol in patients undergoing cardiac surgery causes a transient decrease in preoperative blood pressure when administered before surgery but no adverse hemodynamic effects when administered in the postoperative setting.

[Adverse Effect Predictions Based on Computational Toxicology Techniques and Large-scale Databases].

PubMed

Uesawa, Yoshihiro

2018-01-01

　Understanding the features of chemical structures related to the adverse effects of drugs is useful for identifying potential adverse effects of new drugs. This can be based on the limited information available from post-marketing surveillance, assessment of the potential toxicities of metabolites and illegal drugs with unclear characteristics, screening of lead compounds at the drug discovery stage, and identification of leads for the discovery of new pharmacological mechanisms. This present paper describes techniques used in computational toxicology to investigate the content of large-scale spontaneous report databases of adverse effects, and it is illustrated with examples. Furthermore, volcano plotting, a new visualization method for clarifying the relationships between drugs and adverse effects via comprehensive analyses, will be introduced. These analyses may produce a great amount of data that can be applied to drug repositioning.

Left ventricular global longitudinal strain predicts major adverse cardiac events and all-cause mortality in heart transplant patients.

PubMed

Clemmensen, Tor Skibsted; Eiskjær, Hans; Løgstrup, Brian Bridal; Ilkjær, Lars Bo; Poulsen, Steen Hvitfeldt

2017-05-01

Left ventricular global longitudinal strain (LVGLS) is a robust longitudinal myocardial deformation marker that is strongly affected by cardiac allograft vasculopathy (CAV), microvascular dysfunction, and acute cellular rejection (ACR). We evaluated graft deformation for risk stratification in long-term heart transplant (HTx) patients. The study included 196 patients who underwent HTx between 2011 and 2013. Patients underwent comprehensive echocardiography and coronary angiography. Previous rejection burden was assessed, and ACR grades were calculated. Patients were prospectively followed until February 24, 2016. Major adverse cardiac events (MACE), including coronary event, heart failure, treated rejection, and cardiovascular death, and all-cause mortality were recorded. During follow-up, 57 patients experienced MACE. Median follow-up was 1,035 (interquartile range [IQR] 856-1,124) days. Median time to first event was 534 (IQR 276-763) days. LVGLS was a strong predictor of MACE (hazard ratio [HR] 4.9, 95% confidence interval [CI] 2.7-8.9, p < 0.0001) in patients with and without CAV. LVGLS was a strong predictor of all-cause mortality (HR 4.9, 95% CI 2.2-10.8, p < 0.0001). Left ventricular ejection fraction (LVEF) also predicted MACE, but only in patients with CAV. No relationship between LVEF and all-cause mortality was seen. We obtained a strong MACE (HR 6.3, 95% CI 2.8-14.1, p < 0.0001) and all-cause mortality (HR 6.6, 95% CI 2.3-19.2, p < 0.0001) predictive model by combining LVGLS and restrictive left ventricular filling pattern (LVFP), which remained strong after adjustment for CAV, ACR score, hemoglobin, creatinine, and time since transplantation. Measurement of LVGLS strongly predicts MACE and mortality in long-term HTx patients. Predictive ability was seen in patients with and without CAV. A combined model of left ventricular systolic deformation by LVGLS and diastolic graft performance by LVFP was a stronger model for prediction of MACE and all

The Role of Diacylglycerol Acyltransferase (DGAT) 1 and 2 in Cardiac Metabolism and Function.

PubMed

Roe, Nathan D; Handzlik, Michal K; Li, Tao; Tian, Rong

2018-03-21

It is increasingly recognized that synthesis and turnover of cardiac triglyceride (TG) play a pivotal role in the regulation of lipid metabolism and function of the heart. The last step in TG synthesis is catalyzed by diacylglycerol:acyltransferase (DGAT) which esterifies the diacylglycerol with a fatty acid. Mammalian heart has two DGAT isoforms, DGAT1 and DGAT2, yet their roles in cardiac metabolism and function remain poorly defined. Here, we show that inactivation of DGAT1 or DGAT2 in adult mouse heart results in a moderate suppression of TG synthesis and turnover. Partial inhibition of DGAT activity increases cardiac fatty acid oxidation without affecting PPARα signaling, myocardial energetics or contractile function. Moreover, coinhibition of DGAT1/2 in the heart abrogates TG turnover and protects the heart against high fat diet-induced lipid accumulation with no adverse effects on basal or dobutamine-stimulated cardiac function. Thus, the two DGAT isoforms in the heart have partially redundant function, and pharmacological inhibition of one DGAT isoform is well tolerated in adult hearts.

Adverse Effects of Iodine-derived Intravenous Radiopaque Contrast Media.

PubMed

Matthews, Eric P

2015-01-01

Although the advent of nonionic low-osmolar contrast agents has reduced the probability of a reaction to radiopaque contrast media derived from tri-iodinated benzoic acid, reactions still occur. Radiologic technologists must understand and know how to manage adverse effects of contrast media. Prompt attention to patients who exhibit the early signs of an adverse reaction can help to ensure the reaction does not progress to become severe or life-threatening.

Dual chamber stent prevents organ malperfusion in a model of donation after cardiac death.

PubMed

Tillman, Bryan W; Chun, Youngjae; Cho, Sung Kwon; Chen, Yanfei; Liang, Nathan; Maul, Timothy; Demetris, Anthony; Gu, Xinzhu; Wagner, William R; Tevar, Amit D

2016-10-01

The paradigm for donation after cardiac death subjects donor organs to ischemic injury. A dual-chamber organ perfusion stent would maintain organ perfusion without affecting natural cardiac death. A center lumen allows uninterrupted cardiac blood flow, while an external chamber delivers oxygenated blood to the visceral vessels. A prototype organ perfusion stent was constructed from commercial stents. In a porcine model, the organ perfusion stent was deployed, followed by a simulated agonal period. Oxygenated blood perfused the external stent chamber. Organ perfusion was compared between controls (n = 3) and organ perfusion stent (n = 6). Finally, a custom, nitinol, dual chamber organ perfusion stent was fabricated using a retrievable "petal and stem" design. Endovascular organ perfusion stent deployment achieved visceral isolation without adverse impact on cardiac parameters. Visceral oxygen delivery was 4.8-fold greater compared with controls. During the agonal period, organs in organ perfusion stent-treated animals appeared well perfused in contrast with the malperfused controls. A custom nitinol and polyurethane organ perfusion stent was recaptured easily with simple sheath advancement. An organ perfusion stent maintained organ perfusion during the agonal phase in a porcine model of donation after cardiac death organ donation without adversely affecting cardiac function. Ultimately, the custom retrievable design of this study may help resolve the critical shortage of donor organs for transplant. Copyright © 2016 Elsevier Inc. All rights reserved.

Early Effects of Prolonged Cardiac Arrest and Ischemic Postconditioning during Cardiopulmonary Resuscitation on Cardiac and Brain Mitochondrial Function in Pigs.

PubMed

Matsuura, Timothy R; Bartos, Jason A; Tsangaris, Adamantios; Shekar, Kadambari Chandra; Olson, Matthew D; Riess, Matthias L; Bienengraeber, Martin; Aufderheide, Tom P; Neumar, Robert W; Rees, Jennifer N; McKnite, Scott H; Dikalova, Anna E; Dikalov, Sergey I; Douglas, Hunter F; Yannopoulos, Demetris

2017-07-01

Out-of-hospital cardiac arrest (CA) is a prevalent medical crisis resulting in severe injury to the heart and brain and an overall survival of less than 10%. Mitochondrial dysfunction is predicted to be a key determinant of poor outcomes following prolonged CA. However, the onset and severity of mitochondrial dysfunction during CA and cardiopulmonary resuscitation (CPR) is not fully understood. Ischemic postconditioning (IPC), controlled pauses during the initiation of CPR, has been shown to improve cardiac function and neurologically favorable outcomes after 15min of CA. We tested the hypothesis that mitochondrial dysfunction develops during prolonged CA and can be rescued with IPC during CPR (IPC-CPR). A total of 63 swine were randomized to no ischemia (Naïve), 19min of ventricular fibrillation (VF) CA without CPR (Untreated VF), or 15min of CA with 4min of reperfusion with either standard CPR (S-CPR) or IPC-CPR. Mitochondria were isolated from the heart and brain to quantify respiration, rate of ATP synthesis, and calcium retention capacity (CRC). Reactive oxygen species (ROS) production was quantified from fresh frozen heart and brain tissue. Compared to Naïve, Untreated VF induced cardiac and brain ROS overproduction concurrent with decreased mitochondrial respiratory coupling and CRC, as well as decreased cardiac ATP synthesis. Compared to Untreated VF, S-CPR attenuated brain ROS overproduction but had no other effect on mitochondrial function in the heart or brain. Compared to Untreated VF, IPC-CPR improved cardiac mitochondrial respiratory coupling and rate of ATP synthesis, and decreased ROS overproduction in the heart and brain. Fifteen minutes of VF CA results in diminished mitochondrial respiration, ATP synthesis, CRC, and increased ROS production in the heart and brain. IPC-CPR attenuates cardiac mitochondrial dysfunction caused by prolonged VF CA after only 4min of reperfusion, suggesting that IPC-CPR is an effective intervention to reduce cardiac

A comparison of the effect of aprotinin and ε-aminocaproic acid on renal function in children undergoing cardiac surgery.

PubMed

Leyvi, Galina; Nelson, Olivia; Yedlin, Adam; Pasamba, Michelle; Belamarich, Peter F; Nair, Singh; Cohen, Hillel W

2011-06-01

To assess the incidence of renal injury among pediatric patients who received aprotinin while undergoing cardiac surgery compared with those who received ε-aminocaproic acid (EACA). A retrospective observational study. A single academic center. Pediatric cardiac patients who had cardiopulmonary bypass and received aprotinin or EACA. Patients undergoing pediatric cardiac surgery received aprotinin from 2005 to 2007 and EACA from 2008 to 2009. The primary outcome was acute kidney injury (AKI) defined as serum Cr elevation at discharge more than 1.5 times the baseline value. Secondary outcomes included bleeding, blood transfusion, and the volume of chest tube drainage in the first 24 hours postoperatively. One hundred seventy-eight patients met inclusion criteria; 120 patients received aprotinin, and 58 patients received EACA. These 2 groups did not differ significantly in age, weight, or duration of cardiac bypass. Logistic regression analysis, adjusted for confounding variables (ie, baseline Cr, sex, age, CPB time, inotropic support and vasopressors), showed a higher odds of suffering AKI at discharge with the usage of aprotinin (odds ratio = 4.7; 95% confidence interval, 1.1-19.5; p = 0.03). The volume of the first 24 hours of chest tube drainage was not significantly different between groups, as well as packed red blood cells and cryoprecipitate units. However, fresh frozen plasma and platelets showed statistically significant differences with more transfusion in the EACA group. In this retrospective study, the authors observed a higher odds of AKI for aprotinin usage compared with EACA, suggesting that the known concern for adults with adverse kidney effects with aprotinin is also appropriate for pediatric patients. Copyright © 2011 Elsevier Inc. All rights reserved.

Effects of Radiation Exposure From Cardiac Imaging: How Good Are the Data?

PubMed Central

Einstein, Andrew J.

2012-01-01

Concerns about medical exposure to ionizing radiation have become heightened in recent years due to rapid growth in procedure volumes and the high radiation doses incurred from some procedures. This article summarizes the evidence base undergirding concerns about radiation exposure in cardiac imaging. After classifying radiation effects, explaining terminology used to quantify the radiation received by patients, and describing typical doses from cardiac imaging procedures, I address the major epidemiological studies having bearing on radiation effects at doses comparable to those received by patients undergoing cardiac imaging. These include studies of atomic bomb survivors, nuclear industry workers, and children exposed in utero to x-rays, all of which have evidenced increased cancer risks at low doses. Additional higher dose epidemiological studies of cohorts exposed to radiation in the context of medical treatment are described and found to be generally compatible with these cardiac-dose-level studies, albeit with exceptions. Using risk projection models developed by the US National Academies that incorporate these data and reflect several evidence-based assumptions, cancer risk from cardiac imaging can be estimated and compared to benefits from imaging. Several ongoing epidemiological studies will provide better understanding of radiation-associated cancer risks. PMID:22300689

Taxifolin protects against cardiac hypertrophy and fibrosis during biomechanical stress of pressure overload

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

Guo, Haipeng; Zhang, Xin; Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan

Cardiac hypertrophy is a key pathophysiological component to biomechanical stress, which has been considered to be an independent and predictive risk factor for adverse cardiovascular events. Taxifolin (TAX) is a typical plant flavonoid, which has long been used clinically for treatment of cardiovascular and cerebrovascular diseases. However, very little is known about whether TAX can influence the development of cardiac hypertrophy. In vitro studies, we found that TAX concentration-dependently inhibited angiotensin II (Ang II) induced hypertrophy and protein synthesis in cardiac myocytes. Then we established a mouse model by transverse aortic constriction (TAC) to further confirm our findings. It wasmore » demonstrated that TAX prevented pressure overload induced cardiac hypertrophy in mice, as assessed by ventricular mass/body weight, echocardiographic parameters, myocyte cross-sectional area, and the expression of ANP, BNP and β-MHC. The excess production of reactive oxygen species (ROS) played critical role in the development of cardiac hypertrophy. TAX arrested oxidative stress and decreased the expression of 4-HNE induced by pressure overload. Moreover, TAX negatively modulated TAC-induced phosphorylation of ERK1/2 and JNK1/2. Further studies showed that TAX significantly attenuated left ventricular fibrosis and collagen synthesis through abrogating the phosphorylation of Smad2 and Smad2/3 nuclear translocation. These results demonstrated that TAX could inhibit cardiac hypertrophy and attenuate ventricular fibrosis after pressure overload. These beneficial effects were at least through the inhibition of the excess production of ROS, ERK1/2, JNK1/2 and Smad signaling pathways. Therefore, TAX might be a potential candidate for the treatment of cardiac hypertrophy and fibrosis. - Highlights: • We focus on the protective effect of taxifolin on cardiac remodeling. • Taxifolin inhibited cardiac hypertrophy and attenuated ventricular fibrosis. • Taxifolin

Clinical and genetic predictors of major cardiac events in patients with Anderson-Fabry Disease.

PubMed

Patel, Vimal; O'Mahony, Constantinos; Hughes, Derralynn; Rahman, Mohammad Shafiqur; Coats, Caroline; Murphy, Elaine; Lachmann, Robin; Mehta, Atul; Elliott, Perry M

2015-06-01

Anderson-Fabry Disease (AFD) is an X linked lysosomal storage disorder caused by mutations in the α-galactosidase A gene. Some mutations are associated with prominent and, in many cases, exclusive cardiac involvement. The primary aims of this study were to determine the incidence of major cardiac events in AFD and to identify clinical and genetic predictors of adverse outcomes. We studied 207 patients with AFD (47% male, mean age 44 years, mean follow-up 7.1 years). Fifty-eight (28%) individuals carried mutations that have been previously associated with a cardiac predominant phenotype. Twenty-one (10%) developed severe heart failure (New York Heart Association functional class (NYHA) ≥3), 13 (6%) developed atrial fibrillation (AF), 13 (6%) received devices for the treatment of bradycardia; there were a total of 7 (3%) cardiac deaths. The incidence of the primary endpoint (a composite of new onset AF, NYHA ≥ 3 symptoms, device insertion for bradycardia and cardiac death) was 2.64 per 100 person-years (CI 1.78 to 3.77). Age (HR 1.04, CI 1.01 to 1.08, p=0.004), Mainz Severity Score Index score (HR 1.05, CI 1.01 to 1.09, p=0.012) and QRS duration (HR 1.03, CI 1.00 to 1.05, p=0.020) were significant independent predictors of the primary endpoint. The presence of a cardiac genetic variant did not predict the primary end point. AFD is associated with a high burden of cardiac morbidity and mortality. Adverse cardiac outcomes are associated with age, global disease severity and advanced cardiac disease but not the presence of cardiac genetic variants. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Inhalation of diesel exhaust does not exacerbate cardiac hypertrophy or heart failure in two mouse models of cardiac hypertrophy

PubMed Central

2013-01-01

Background Strong associations have been observed between exposure to fine ambient particulate matter (PM2.5) and adverse cardiovascular outcomes. In particular, exposure to traffic related PM2.5 has been associated with increases in left ventricular hypertrophy, a strong risk factor for cardiovascular mortality. As much of traffic related PM2.5 is derived from diesel exhaust (DE), we investigated the effects of chronic DE exposure on cardiac hypertrophy and heart failure in the adult mouse by exposing mice to DE combined with either of two mouse models of cardiac hypertrophy: angiotensin II infusion or pressure overload induced by transverse aortic banding. Methods Wild type male C57BL/6 J mice were either infused with angiotensin II (800 ng/kg/min) via osmotic minipump implanted subcutaneously for 1 month, or underwent transverse aortic banding (27 gauge needle 1 week for observing acute reactions, 26 gauge needle 3 months or 6 months for observing chronic reactions). Vehicle (saline) infusion or sham surgery was used as a control. Shortly after surgery, mice were transferred to our exposure facility and randomly assigned to either diesel exhaust (300 or 400 μg/m3) or filtered air exposures. After reaching the end of designated time points, echocardiography was performed to measure heart structure and function. Gravimetric analysis was used to measure the ventricular weight to body weight ratio. We also measured heart rate by telemetry using implanted ambulatory ECG monitors. Results Both angiotensin II and transverse aortic banding promoted cardiac hypertrophy compared to vehicle or sham controls. Transverse aortic banding for six months also promoted heart failure in addition to cardiac hypertrophy. In all cases, DE failed to exacerbate the development of hypertrophy or heart failure when compared to filtered air controls. Prolonged DE exposure also led to a decrease in average heart rate. Conclusions Up to 6-months of DE exposure had no effect on

Evidence for a neural dual-process account for adverse effects of cognitive control.

PubMed

Zink, Nicolas; Stock, Ann-Kathrin; Colzato, Lorenza; Beste, Christian

2018-06-09

Advantageous effects of cognitive control are well-known, but cognitive control may also have adverse effects, for example when it suppresses the implicit processing of stimulus-response (S-R) bindings that could benefit task performance. Yet, the neurophysiological and functional neuroanatomical structures associated with adverse effects of cognitive control are poorly understood. We used an extreme group approach to compare individuals who exhibit adverse effects of cognitive control to individuals who do not by combining event-related potentials (ERPs), source localization, time-frequency analysis and network analysis methods. While neurophysiological correlates of cognitive control (i.e. N2, N450, theta power and theta-mediated neuronal network efficiency) and task-set updating (P3) both reflect control demands and implicit information processing, differences in the degree of adverse cognitive control effects are associated with two independent neural mechanisms: Individuals, who show adverse behavioral effects of cognitive control, show reduced small-world properties and thus reduced efficiency in theta-modulated networks when they fail to effectively process implicit information. In contrast to this, individuals who do not display adverse control effects show enhanced task-set updating mechanism when effectively processing implicit information, which is reflected by the P3 ERP component and associated with the temporo-parietal junction (TPJ, BA 40) and medial frontal gyrus (MFG; BA 8). These findings suggest that implicit S-R contingencies, which benefit response selection without cognitive control, are always 'picked up', but may fail to be integrated with task representations to guide response selection. This provides evidence for a neurophysiological and functional neuroanatomical "dual-process" account of adverse cognitive control effects.

Effect of preoperative angina pectoris on cardiac outcomes in patients with previous myocardial infarction undergoing major noncardiac surgery (data from ACS-NSQIP).

PubMed

Pandey, Ambarish; Sood, Akshay; Sammon, Jesse D; Abdollah, Firas; Gupta, Ena; Golwala, Harsh; Bardia, Amit; Kibel, Adam S; Menon, Mani; Trinh, Quoc-Dien

2015-04-15

The impact of preoperative stable angina pectoris on postoperative cardiovascular outcomes in patients with previous myocardial infarction (MI) who underwent major noncardiac surgery is not well studied. We studied patients with previous MI who underwent elective major noncardiac surgeries within the American College of Surgeons-National Surgical Quality Improvement Program (2005 to 2011). Primary outcome was occurrence of an adverse cardiac event (MI and/or cardiac arrest). Multivariable logistic regression models evaluated the impact of stable angina on outcomes. Of 1,568 patients (median age 70 years; 35% women) with previous MI who underwent major noncardiac surgery, 5.5% had postoperative MI and/or cardiac arrest. Patients with history of preoperative angina had significantly greater incidence of primary outcome compared to those without anginal symptoms (8.4% vs 5%, p = 0.035). In secondary outcomes, reintervention rates (22.5% vs 11%, p <0.001) and length of stay (median 6-days vs 5-days; p <0.001) were also higher in patients with preoperative angina. In multivariable analyses, preoperative angina was a significant predictor for postoperative MI (odds ratio 2.49 [1.20 to 5.58]) and reintervention (odds ratio 2.40 [1.44 to 3.82]). In conclusion, our study indicates that preoperative angina is an independent predictor for adverse outcomes in patients with previous MI who underwent major noncardiac surgery, and cautions against overreliance on predictive tools, for example, the Revised Cardiac Risk Index, in these patients, which does not treat stable angina and previous MI as independent risk factors during risk prognostication. Copyright © 2015 Elsevier Inc. All rights reserved.

Pretreatment Predictors of Adverse Radiation Effects After Radiosurgery for Arteriovenous Malformation

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

Hayhurst, Caroline; Monsalves, Eric; Prooijen, Monique van

Purpose: To identify vascular and dosimetric predictors of symptomatic T2 signal change and adverse radiation effects after radiosurgery for arteriovenous malformation, in order to define and validate preexisting risk models. Methods and Materials: A total of 125 patients with arteriovenous malformations (AVM) were treated at our institution between 2005 and 2009. Eighty-five patients have at least 12 months of clinical and radiological follow-up. Any new-onset headaches, new or worsening seizures, or neurological deficit were considered adverse events. Follow-up magnetic resonance images were assessed for new onset T2 signal change and the volume calculated. Pretreatment characteristics and dosimetric variables were analyzedmore » to identify predictors of adverse radiation effects. Results: There were 19 children and 66 adults in the study cohort, with a mean age of 34 (range 6-74). Twenty-three (27%) patients suffered adverse radiation effects (ARE), 9 patients with permanent neurological deficit (10.6%). Of these, 5 developed fixed visual field deficits. Target volume and 12 Gy volume were the most significant predictors of adverse radiation effects on univariate analysis (p < 0.001). Location and cortical eloquence were not significantly associated with the development of adverse events (p = 0.12). No additional vascular parameters were identified as predictive of ARE. There was a significant target volume threshold of 4 cm{sup 3}, above which the rate of ARE increased dramatically. Multivariate analysis target volume and the absence of prior hemorrhage are the only significant predictors of ARE. The volume of T2 signal change correlates to ARE, but only target volume is predictive of a higher volume of T2 signal change. Conclusions: Target volume and the absence of prior hemorrhage is the most accurate predictor of adverse radiation effects and complications after radiosurgery for AVMs. A high percentage of permanent visual field defects in this series

The dose effect of ephedrine on the onset time of vecuronium.

PubMed

Kim, Kyo S; Cheong, Mi A; Jeon, Jeong W; Lee, Jeong H; Shim, Jae C

2003-04-01

A small dose of ephedrine decreases the onset time of rocuronium and cisatracurium; however, ephedrine might be associated with adverse hemodynamic effects. The appropriate dose of ephedrine has not been determined. We, therefore, studied 120 patients anesthetized with fentanyl 2 microg/kg and propofol 2-2.5 mg/kg who were randomly divided to receive either ephedrine (30, 70, or 110 microg/kg) or saline. During propofol anesthesia, the neuromuscular block was monitored by mechanomyography by using submaximal current of train-of-four stimulation every 10 s. To determine cardiac output, a transcutaneous Doppler probe was placed externally at the suprasternal notch. Tracheal intubation was performed by a blinded investigator at 2 min after vecuronium. Neuromuscular block, intubating conditions, and hemodynamic effects were measured during the induction of anesthesia. Both ephedrine 70 and 110 microg/kg improved intubating conditions at 2 min after vecuronium; however, 110 microg/kg was associated with adverse hemodynamic effects. We conclude that ephedrine 70 microg/kg given before the induction of anesthesia improved intubating conditions at 2 min after vecuronium, probably by increased cardiac output without significant adverse hemodynamic effects. Ephedrine 70 microg/kg given before the induction of anesthesia improved tracheal intubating conditions at 2 min after vecuronium by increased cardiac output without significant adverse hemodynamic effects.

TRPA1 mediates changes in heart rate variability and cardiac mechanical function in mice exposed to acrolein

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

Kurhanewicz, Nicole

Short-term exposure to ambient air pollution is linked with adverse cardiovascular effects. While previous research focused primarily on particulate matter-induced responses, gaseous air pollutants also contribute to cause short-term cardiovascular effects. Mechanisms underlying such effects have not been adequately described, however the immediate nature of the response suggests involvement of irritant neural activation and downstream autonomic dysfunction. Thus, this study examines the role of TRPA1, an irritant sensory receptor found in the airways, in the cardiac response of mice to acrolein and ozone. Conscious unrestrained wild-type C57BL/6 (WT) and TRPA1 knockout (KO) mice implanted with radiotelemeters were exposed once tomore » 3 ppm acrolein, 0.3 ppm ozone, or filtered air. Heart rate (HR) and electrocardiogram (ECG) were recorded continuously before, during and after exposure. Analysis of ECG morphology, incidence of arrhythmia and heart rate variability (HRV) were performed. Cardiac mechanical function was assessed using a Langendorff perfusion preparation 24 h post-exposure. Acrolein exposure increased HRV independent of HR, as well as incidence of arrhythmia. Acrolein also increased left ventricular developed pressure in WT mice at 24 h post-exposure. Ozone did not produce any changes in cardiac function. Neither gas produced ECG effects, changes in HRV, arrhythmogenesis, or mechanical function in KO mice. These data demonstrate that a single exposure to acrolein causes cardiac dysfunction through TRPA1 activation and autonomic imbalance characterized by a shift toward parasympathetic modulation. Furthermore, it is clear from the lack of ozone effects that although gaseous irritants are capable of eliciting immediate cardiac changes, gas concentration and properties play important roles. - Highlights: • Acute acrolein exposure causes autonomic imbalance and altered CV function in mice. • TRPA1 mediates acrolein-induced autonomic nervous system

Value of improved lipid control in patients at high risk for adverse cardiac events.

PubMed

Jena, Anupam B; Blumenthal, Daniel M; Stevens, Warren; Chou, Jacquelyn W; Ton, Thanh G N; Goldman, Dana P

2016-06-01

Lipid-lowering therapy (LLT) is suboptimally used in patients with hyperlipidemia in the 2 highest statin benefit groups (SBGs), as categorized by the American College of Cardiology and the American Heart Association. This study estimated the social value of reducing low-density lipoprotein cholesterol (LDL-C) levels by 50% for patients in SBGs 1 and 2 who have been treated with standard LLT but have not reached LDL-C goal, as well as the potential value of PCSK9 inhibitors for patients in these groups. Simulation model. We used National Health and Nutrition Examination Surveys (NHANES) and US Census data to project the population of SBGs 1 and 2 in the time period 2015 to 2035. We used insurance claims data to estimate incidence rates of major adverse cardiac events (MACEs), and NHANES with National Vital Statistics data to estimate cardiovascular disease mortality rates. Using established associations between LDL-C and MACE risk, we estimated the value of reducing LDL-C levels by 50%. We incorporated results from a meta-analysis to estimate the value of PSCK9 inhibitors. Among those treated with LLT with LDL-C > 70 mg/dL in SBGs 1 and 2, the cumulative value of reducing LDL-C levels by 50% would be $2.9 trillion from 2015 to 2035, resulting primarily from 1.6 million deaths averted. The cumulative value of PCSK9 inhibitors would range from $3.4 trillion to $5.1 trillion (1.9-2.8 million deaths averted), or $12,000 to $17,000 per patient-year of treatment. Lowering LDL-C in high-risk patients with hyperlipidemia has enormous potential social value. For patients in these high-risk groups, PCSK9 inhibitors may have considerable net value depending on the final prices payers ultimately select.

The long noncoding RNA Wisper controls cardiac fibrosis and remodeling

PubMed Central

Micheletti, Rudi; Plaisance, Isabelle; Abraham, Brian J.; Sarre, Alexandre; Ting, Ching-Chia; Alexanian, Michael; Maric, Daniel; Maison, Damien; Nemir, Mohamed; Young, Richard A.; Schroen, Blanche; González, Arantxa; Ounzain, Samir; Pedrazzini, Thierry

2017-01-01

Long noncoding RNAs (lncRNAs) are emerging as powerful regulators of cardiac development and disease. However, our understanding of the importance of these molecules in cardiac fibrosis is limited. Using an integrated genomic screen, we identified Wisper (Wisp2 super-enhancer–associated RNA) as a cardiac fibroblast–enriched lncRNA that regulates cardiac fibrosis after injury. Wisper expression was correlated with cardiac fibrosis both in a murine model of myocardial infarction (MI) and in heart tissue from human patients suffering from aortic stenosis. Loss-of-function approaches in vitro using modified antisense oligonucleotides (ASOs) demonstrated that Wisper is a specific regulator of cardiac fibroblast proliferation, migration, and survival. Accordingly, ASO-mediated silencing of Wisper in vivo attenuated MI-induced fibrosis and cardiac dysfunction. Functionally, Wisper regulates cardiac fibroblast gene expression programs critical for cell identity, extracellular matrix deposition, proliferation, and survival. In addition, its association with TIA1-related protein allows it to control the expression of a profibrotic form of lysyl hydroxylase 2, implicated in collagen cross-linking and stabilization of the matrix. Together, our findings identify Wisper as a cardiac fibroblast–enriched super-enhancer–associated lncRNA that represents an attractive therapeutic target to reduce the pathological development of cardiac fibrosis in response to MI and prevent adverse remodeling in the damaged heart. PMID:28637928

Alpha-2 adrenergic agonists for the prevention of cardiac complications among adults undergoing surgery.

PubMed

Duncan, Dallas; Sankar, Ashwin; Beattie, W Scott; Wijeysundera, Duminda N

2018-03-06

The surgical stress response plays an important role on the pathogenesis of perioperative cardiac complications. Alpha-2 adrenergic agonists attenuate this response and may help prevent postoperative cardiac complications. To determine the efficacy and safety of α-2 adrenergic agonists for reducing mortality and cardiac complications in adults undergoing cardiac surgery and non-cardiac surgery. We searched CENTRAL (2017, Issue 4), MEDLINE (1950 to April Week 4, 2017), Embase (1980 to May 2017), the Science Citation Index, clinical trial registries, and reference lists of included articles. We included randomized controlled trials that compared α-2 adrenergic agonists (i.e. clonidine, dexmedetomidine or mivazerol) against placebo or non-α-2 adrenergic agonists. Included trials had to evaluate the efficacy and safety of α-2 adrenergic agonists for preventing perioperative mortality or cardiac complications (or both), or measure one or more relevant outcomes (i.e. death, myocardial infarction, heart failure, acute stroke, supraventricular tachyarrhythmia and myocardial ischaemia). Two authors independently assessed trial quality, extracted data and independently performed computer entry of abstracted data. We contacted study authors for additional information. Adverse event data were gathered from the trials. We evaluated included studies using the Cochrane 'Risk of bias' tool, and the quality of the evidence underlying pooled treatment effects using GRADE methodology. Given the clinical heterogeneity between cardiac and non-cardiac surgery, we analysed these subgroups separately. We expressed treatment effects as pooled risk ratios (RR) with 95% confidence intervals (CI). We included 47 trials with 17,039 participants. Of these studies, 24 trials only included participants undergoing cardiac surgery, 23 only included participants undergoing non-cardiac surgery and eight only included participants undergoing vascular surgery. The α-2 adrenergic agonist studied

Contribution of new technologies to characterization and prediction of adverse effects.

PubMed

Rouquié, David; Heneweer, Marjoke; Botham, Jane; Ketelslegers, Hans; Markell, Lauren; Pfister, Thomas; Steiling, Winfried; Strauss, Volker; Hennes, Christa

2015-02-01

Identification of the potential hazards of chemicals has traditionally relied on studies in laboratory animals where changes in clinical pathology and histopathology compared to untreated controls defined an adverse effect. In the past decades, increased consistency in the definition of adversity with chemically-induced effects in laboratory animals, as well as in the assessment of human relevance has been reached. More recently, a paradigm shift in toxicity testing has been proposed, mainly driven by concerns over animal welfare but also thanks to the development of new methods. Currently, in vitro approaches, toxicogenomic technologies and computational tools, are available to provide mechanistic insight in toxicological Mode of Action (MOA) of the adverse effects observed in laboratory animals. The vision described as Tox21c (Toxicity Testing in the 21st century) aims at predicting in vivo toxicity using a bottom-up-approach, starting with understanding of MOA based on in vitro data to ultimately predict adverse effects in humans. At present, a practical application of the Tox21c vision is still far away. While moving towards toxicity prediction based on in vitro data, a stepwise reduction of in vivo testing is foreseen by combining in vitro with in vivo tests. Furthermore, newly developed methods will also be increasingly applied, in conjunction with established methods in order to gain trust in these new methods. This confidence is based on a critical scientific prerequisite: the establishment of a causal link between data obtained with new technologies and adverse effects manifested in repeated-dose in vivo toxicity studies. It is proposed to apply the principles described in the WHO/IPCS framework of MOA to obtain this link. Finally, an international database of known MOAs obtained in laboratory animals using data-rich chemicals will facilitate regulatory acceptance and could further help in the validation of the toxicity pathway and adverse outcome pathway

Heterogeneous effects of tissue inhibitors of matrix metalloproteinases on cardiac fibroblasts.

PubMed

Lovelock, Joshua D; Baker, Andrew H; Gao, Feng; Dong, Jing-Fei; Bergeron, Angela L; McPheat, Willie; Sivasubramanian, Natarajan; Mann, Douglas L

2005-02-01

The balance between matrix metalloproteinases (MMPs) and their natural inhibitors, the tissue inhibitors of metalloproteinases (TIMPs), plays a critical role in cardiac remodeling. Although a number of studies have characterized the pathophysiological role of MMPs in the heart, very little is known with respect to the role of TIMPs in the heart. To delineate the role of TIMPs in the heart we examined the effects of adenovirus-mediated overexpression of TIMP-1, -2, -3, and -4 in cardiac fibroblasts. Infection of cardiac fibroblasts with adenoviral constructs containing human recombinant TIMP (AdTIMP-1, -2, -3, and -4) provoked a significant (P < 0.0001) 1.3-fold in increase in bromodeoxyuridine (BrdU) incorporation. Similarly, treatment of cardiac fibroblasts with AdTIMP-1-, -2-, -3-, and -4-conditioned medium led to a 1.2-fold increase in BrdU incorporation (P < 0.0001) that was abolished by pretreatment with anti-TIMP-1, -2, -3, and -4 antibodies. The effects of TIMPs were not mimicked by treating the cells with RS-130830, a broad-based MMP inhibitor, suggesting that the effects of TIMPs were independent of their ability to inhibit MMPs. Infection with AdTIMP-1, -2, -3, and -4 led to a significant increase in alpha-smooth muscle actin staining, consistent with TIMP-induced phenotypic differentiation into myofibroblasts. Finally, infection with AdTIMP-2 resulted in a significant increase in collagen synthesis, whereas infection with AdTIMP-3 resulted in a significant increase in fibroblast apoptosis. TIMPs exert overlapping as well as diverse effects on isolated cardiac fibroblasts. The observation that TIMPs stimulate fibroblast proliferation as well as phenotypic differentiation into myofibroblasts suggests that TIMPs may play an important role in tissue repair in the heart that extends beyond their traditional role as MMP inhibitors.

CKD and Sudden Cardiac Death: Epidemiology, Mechanisms, and Therapeutic Approaches

PubMed Central

Whitman, Isaac R.; Feldman, Harold I.

2012-01-01

Multiple studies demonstrate a strong independent association between CKD and cardiovascular events including death, heart failure, and myocardial infarction. This review focuses on recent clinical studies that expand this spectrum of adverse cardiovascular events to include ventricular arrhythmias and sudden cardiac death. In addition, experimental models suggest structural remodeling of the heart and electrophysiologic changes in this population. These processes may explain the increased arrhythmic risk in kidney disease and aid in identifying patients who are at higher risk for sudden cardiac death. Finally, we review here the data to support the use of pharmacologic and device-based therapies for both the primary and secondary prevention of sudden cardiac death. PMID:23100219

Adversity in Preschool-Aged Children: Effects on Salivary Interleukin-1β

PubMed Central

Tyrka, Audrey R.; Parade, Stephanie H.; Valentine, Thomas R.; Eslinger, Nicole M.; Seifer, Ronald

2016-01-01

Exposure to early life adversity is linked to impaired affective, cognitive, and behavioral functioning and increases risk for various psychiatric and medical conditions. Stress-induced increases in pro-inflammatory cytokines may be a biological mechanism of these effects. Few studies have examined cytokine levels in children experiencing early life adversity, and very little research has investigated cytokines or other markers of inflammation in saliva. In the present study, we examined salivary IL-1β and C-reactive protein (CRP) levels in relation to stress exposure in 40 children aged 3 to 5 years who were enrolled in a larger study of early life adversity. Childhood maltreatment status was assessed via review of child welfare records, and contextual stress exposure, traumatic life event history, and symptoms of psychopathology were assessed via caregiver interviews at a home visit. In a subsequent visit, salivary IL-1β and CRP were obtained before and after participation in four emotion-eliciting tasks. Number of past month contextual stressors, lifetime contextual stressors, and traumatic life events each demonstrated a significant main effect on IL-1β. Baseline IL-1β was positively associated with each of the significant main-effect adversities. Post-challenge IL-1β displayed positive associations with each adversity variable, but were not significant. CRP was not significantly associated with any of the adversity variables. Given evidence suggesting involvement of IL-1β in the neuropathology of psychiatric conditions, these results may have important implications for developmental outcomes. PMID:25997772

Adverse Effects of Collagenase in the Treatment of Dupuytren Disease: A Systematic Review.

PubMed

Sanjuan-Cerveró, Rafael; Carrera-Hueso, Francisco J; Vazquez-Ferreiro, Pedro; Gomez-Herrero, Diego

2017-04-01

Collagenase clostridium histolyticum (CCH) has proven to be both safe and effective in the treatment of Dupuytren disease (DD). The medium-term outcomes are similar to those achieved with surgery, and most adverse effects are self-limiting and considered to be mild or moderate. Our objective was to conduct a systematic review of the adverse effects of CCH in DD since the release of the drug to evaluate the incidence, severity, classification, and definitions of these effects. We analyzed the literature in terms of modifications to the original treatment protocol and grouped adverse effects according to their pathophysiological origin. We included 28 clinical studies and five case reports or case series analyzing 4456 patients with a mean age of 63.6 years. Mean follow-up was 7.07 months (range 3-24); the mean number of patients per study was 148 (range 5-1082). The studies did not classify the adverse effects they reported into groups. The most common effects were peripheral edema (54.4%), bruising (42.9%), and upper limb pain (28.3%). Significant biases were observed for use of terminology, demarcation of sites of involvement, severity criteria, and assessment methods. A simpler and clearer consensus-based classification system would enable better evaluation and comparison of the adverse effects of CCH in the treatment of DD. Consideration of inflammatory phenomena as part of the drug's mechanism of action would significantly reduce overall rates of adverse effects.

Recording Adverse Events Following Joint Arthroplasty: Financial Implications and Validation of an Adverse Event Assessment Form.

PubMed

Lee, Matthew J; Mohamed, Khalid M S; Kelly, John C; Galbraith, John G; Street, John; Lenehan, Brian J

2017-09-01

In Ireland, funding of joint arthroplasty procedures has moved to a pay-by-results national tariff system. Typically, adverse clinical events are recorded via retrospective chart-abstraction methods by administrative staff. Missed or undocumented events not only affect the quality of patient care but also may unrealistically skew budgetary decisions that impact fiscal viability of the service. Accurate recording confers clinical benefits and financial transparency. The aim of this study was to compare a prospectively implemented adverse events form with the current national retrospective chart-abstraction method in terms of pay-by-results financial implications. An adverse events form adapted from a similar validated model was used to prospectively record complications in 51 patients undergoing total hip or knee arthroplasties. Results were compared with the same cohort using an existing data abstraction method. Both data sets were coded in accordance with current standards for case funding. Overall, 114 events were recorded during the study through prospective charting of adverse events, compared with 15 events documented by customary method (a significant discrepancy). Wound drainage (15.8%) was the most common complication, followed by anemia (7.9%), lower respiratory tract infections (7.9%), and cardiac events (7%). A total of €61,956 ($67,778) in missed funding was calculated as a result. This pilot study demonstrates the ability to improve capture of adverse events through use of a well-designed assessment form. Proper perioperative data handling is a critical aspect of financial subsidies, enabling optimal allocation of funds. Copyright © 2017 Elsevier Inc. All rights reserved.

Cardiac and renal function in patients with type 2 diabetes who have chronic kidney disease: potential effects of bardoxolone methyl.

PubMed

McCullough, Peter A; Ali, Sajid

2012-01-01

The intracellular and tissue balance of oxidant and antioxidant forces is a potential therapeutic target for a variety of agents in the treatment of complications due to chronic disease including diabetes mellitus and hypertension. There are a myriad of processes controlled at the level of genes, transcription factors, and protein messages that work to control the normal use of oxidative reactions within cells. Loss of control of these processes may lead to reversible dysfunction in many cell lines including the podocyte, renal tubular cells, and cardiac myocytes. Bardoxolone methyl is a novel nuclear regulator factor (Nrf-2) activator which works to tip the balance of effects towards antioxidation and as an observation made serendipitously, improves renal filtration function in humans after approximately 12 weeks of therapy. The improvement in estimated glomerular filtration can be up to 30% in those with stage 3 and 4 chronic kidney disease. However, experimental evidence suggests there may be a consequence of relative hyperfiltration in diseased kidneys as well as potential adverse effects on skeletal and cardiac myocytes. Only large, prospective randomized trials with carefully collected and adjudicated clinical outcomes will inform the research community on the therapeutic risks and benefits of this important new agent.

Cardiac and renal function in patients with type 2 diabetes who have chronic kidney disease: potential effects of bardoxolone methyl

PubMed Central

McCullough, Peter A; Ali, Sajid

2012-01-01

The intracellular and tissue balance of oxidant and antioxidant forces is a potential therapeutic target for a variety of agents in the treatment of complications due to chronic disease including diabetes mellitus and hypertension. There are a myriad of processes controlled at the level of genes, transcription factors, and protein messages that work to control the normal use of oxidative reactions within cells. Loss of control of these processes may lead to reversible dysfunction in many cell lines including the podocyte, renal tubular cells, and cardiac myocytes. Bardoxolone methyl is a novel nuclear regulator factor (Nrf-2) activator which works to tip the balance of effects towards antioxidation and as an observation made serendipitously, improves renal filtration function in humans after approximately 12 weeks of therapy. The improvement in estimated glomerular filtration can be up to 30% in those with stage 3 and 4 chronic kidney disease. However, experimental evidence suggests there may be a consequence of relative hyperfiltration in diseased kidneys as well as potential adverse effects on skeletal and cardiac myocytes. Only large, prospective randomized trials with carefully collected and adjudicated clinical outcomes will inform the research community on the therapeutic risks and benefits of this important new agent. PMID:22787387

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…

Adverse effects of antiretroviral therapy for HIV infection.

PubMed

Montessori, Valentina; Press, Natasha; Harris, Marianne; Akagi, Linda; Montaner, Julio S G

2004-01-20

Long-term remission of HIV-1 disease can be readily achieved by combinations of antiretroviral agents. The suppression of plasma viral loads to less than the limit of quantification of the most sensitive commercially available assays (i.e., less than 50 copies/mL) and the coincident improvement in CD4 T cell counts is associated with resolution of established opportunistic infections and a decrease in the risk of new opportunistic infections. However, prolonged treatment with combination regimens can be difficult to sustain because of problems with adherence and toxic effects. All antiretroviral drugs can have both short-term and long-term adverse events. The risk of specific side effects varies from drug to drug, from drug class to drug class, and from patient to patient. A better understanding of the adverse effects of antiretroviral agents is of interest not only for HIV specialists as they try to optimize therapy, but also for other physicians who care for HIV-positive patients.

Adverse effects of antiretroviral therapy for HIV infection

PubMed Central

Montessori, Valentina; Press, Natasha; Harris, Marianne; Akagi, Linda; Montaner, Julio S.G.

2004-01-01

LONG-TERM REMISSION OF HIV-1 DISEASE CAN BE READILY ACHIEVED by combinations of antiretroviral agents. The suppression of plasma viral loads to less than the limit of quantification of the most sensitive commercially available assays (i.e., less than 50 copies/mL) and the coincident improvement in CD4 T cell counts is associated with resolution of established opportunistic infections and a decrease in the risk of new opportunistic infections. However, prolonged treatment with combination regimens can be difficult to sustain because of problems with adherence and toxic effects. All antiretroviral drugs can have both short-term and long-term adverse events. The risk of specific side effects varies from drug to drug, from drug class to drug class, and from patient to patient. A better understanding of the adverse effects of antiretroviral agents is of interest not only for HIV specialists as they try to optimize therapy, but also for other physicians who care for HIV-positive patients. PMID:14734438

Adverse CNS-effects of beta-adrenoceptor blockers.

PubMed

Gleiter, C H; Deckert, J

1996-11-01

In 1962 propranolol, the first beta adrenoceptor antagonist (beta blocker), was brought on to the market. There is now a host of different beta blockers available, and these compounds are among the most commonly prescribed groups of drugs. The efficacy of beta blockers has been proven predominantly for the treatment of cardiovascular diseases. Beta blockers are also used for certain types of CNS disorders, such as anxiety disorders, essential tremor and migraine. While low toxicity means that they have a favorable risk-benefit ratio, given the high intensity of use, it is essential to have a comprehensive knowledge of adverse events. Adverse events of beta blockers that can be related to the CNS are quite often neglected, even in textbooks of clinical pharmacology or review articles, and thus often misdiagnosed. The following article, therefore, after summarizing the use of beta blockers for CNS indications, critically reviews the literature on centrally mediated adverse events. General pharmacological features of beta blockers and their molecular basis of action will briefly be addressed to the extent that they are or may become relevant for central nervous pharmacotherapy and side-effects.

The interrelationship between preoperative anemia and N-terminal pro-B-type natriuretic peptide: the effect on predicting postoperative cardiac outcome in vascular surgery patients.

PubMed

Goei, Dustin; Flu, Willem-Jan; Hoeks, Sanne E; Galal, Wael; Dunkelgrun, Martin; Boersma, Eric; Kuijper, Ruud; van Kuijk, Jan-Peter; Winkel, Tamara A; Schouten, Olaf; Bax, Jeroen J; Poldermans, Don

2009-11-01

N-terminal pro-B-type natriuretic peptide (NT-proBNP) predicts adverse cardiac outcome in patients undergoing vascular surgery. However, several conditions might influence this prognostic value, including anemia. In this study, we evaluated whether anemia confounds the prognostic value of NT-proBNP for predicting cardiac events in patients undergoing vascular surgery. A detailed cardiac history, resting echocardiography, and hemoglobin and NT-proBNP levels were obtained in 666 patients before vascular surgery. Anemia was defined as serum hemoglobin <13 g/dL for men and <12 g/dL for women. Troponin T measurements and 12-lead electrocardiograms were performed on postoperative days 1, 3, 7, and 30 and whenever clinically indicated. The primary end point of the study was the composite of 30-day postoperative cardiovascular death, nonfatal myocardial infarction, and troponin T release. Receiver operating characteristic curve analysis was used to assess the optimal cutoff value of NT-proBNP for the prediction of the composite end point. Multivariable regression analysis was used to assess the additional value of NT-proBNP for the prediction of postoperative cardiac events in nonanemic and anemic patients. Anemia was present in 206 patients (31%) before surgery. Hemoglobin level was inversely related with the NT-proBNP levels (beta coefficient = -2.242; P = 0.025). The optimal predictive cutoff value of NT-proBNP for predicting the composite cardiovascular outcome was 350 pg/mL. After adjustment for clinical cardiac risk factors, both anemia (odds ratio [OR] 1.53; 95% confidence interval [CI]: 1.07-2.99) and increased levels of NT-proBNP (OR 4.09; 95% CI: 2.19-7.64) remained independent predictors for postoperative cardiac events. However, increased levels of NT-proBNP were not predictive for the risk of adverse cardiac events in the subgroup of anemic patients (OR 2.16; 95% CI: 0.90-5.21). Both anemia and NT-proBNP are independently associated with an increased risk for

Circadian clock and cardiac vulnerability: A time stamp on multi-scale neuroautonomic regulation

NASA Astrophysics Data System (ADS)

Ivanov, Plamen Ch.

2005-03-01

Cardiovascular vulnerability displays a 24-hour pattern with a peak between 9AM and 11AM. This daily pattern in cardiac risk is traditionally attributed to external factors including activity levels and sleep-wake cycles. However,influences from the endogenous circadian pacemaker independent from behaviors may also affect cardiac control. We investigate heartbeat dynamics in healthy subjects recorded throughout a 10-day protocol wherein the sleep/wake and behavior cycles are desynchronized from the endogenous circadian cycle,enabling assessment of circadian factors while controlling for behavior-related factors. We demonstrate that the scaling exponent characterizing temporal correlations in heartbeat dynamics over multiple time scales does exhibit a significant circadian rhythm with a sharp peak at the circadian phase corresponding to the period 9-11AM, and that this rhythm is independent from scheduled behaviors and mean heart rate. Our findings of strong circadian rhythms in the multi-scale heartbeat dynamics of healthy young subjects indicate that the underlying mechanism of cardiac regulation is strongly influenced by the endogenous circadian pacemaker. A similar circadian effect in vulnerable individuals with underlying cardiovascular disease would contribute to the morning peak of adverse cardiac events observed in epidemiological studies.

Potential adverse effects of omega-3 Fatty acids in dogs and cats.

PubMed

Lenox, C E; Bauer, J E

2013-01-01

Fish oil omega-3 fatty acids, mainly eicosapentaenoic acid and docosahexaenoic acid, are used in the management of several diseases in companion animal medicine, many of which are inflammatory in nature. This review describes metabolic differences among omega-3 fatty acids and outlines potential adverse effects that may occur with their supplementation in dogs and cats with a special focus on omega-3 fatty acids from fish oil. Important potential adverse effects of omega-3 fatty acid supplementation include altered platelet function, gastrointestinal adverse effects, detrimental effects on wound healing, lipid peroxidation, potential for nutrient excess and toxin exposure, weight gain, altered immune function, effects on glycemic control and insulin sensitivity, and nutrient-drug interactions. Copyright © 2013 by the American College of Veterinary Internal Medicine.

Cardiac arrhythmia induced by interferon beta-1a.

PubMed

Kastalli, Sarrah; El Aïdli, Sihem; Mourali, Sami; Zaïem, Ahmed; Daghfous, Riadh; Lakhal, Mohamed

2012-04-01

Cardiac adverse effects have never been reported with interferon (INF) beta. We report a case of left bundle branch block in a 35-year-old woman treated with INF beta-1a for multiple sclerosis. Five years after INF therapy, she presented loss of consciousness, retrosternal pains, short breath and lowered tolerance of effort. ECG and Holter 24-h ECG monitoring revealed permanent complete left bundle branch block. Nine months after stopping INF, no abnormalities were found at ECG and echocardiogram examination. © 2011 The Authors Fundamental and Clinical Pharmacology © 2011 Société Française de Pharmacologie et de Thérapeutique.

Countermeasures for space radiation induced adverse biologic effects

NASA Astrophysics Data System (ADS)

Kennedy, A. R.; Wan, X. S.

2011-11-01

Radiation exposure in space is expected to increase the risk of cancer and other adverse biological effects in astronauts. The types of space radiation of particular concern for astronaut health are protons and heavy ions known as high atomic number and high energy (HZE) particles. Recent studies have indicated that carcinogenesis induced by protons and HZE particles may be modifiable. We have been evaluating the effects of proton and HZE particle radiation in cultured human cells and animals for nearly a decade. Our results indicate that exposure to proton and HZE particle radiation increases oxidative stress, cytotoxicity, cataract development and malignant transformation in in vivo and/or in vitro experimental systems. We have also shown that these adverse biological effects can be prevented, at least partially, by treatment with antioxidants and some dietary supplements that are readily available and have favorable safety profiles. Some of the antioxidants and dietary supplements are effective in preventing radiation induced malignant transformation in vitro even when applied several days after the radiation exposure. Our recent progress is reviewed and discussed in the context of the relevant literature.

Lycopersicon esculentum (Tomato) Prevents Adverse Effects of Lead on Blood Constituents

PubMed Central

SALAWU, Emmanuel O

2010-01-01

Background: Lead is known for its adverse effects on various organs and systems. In this study, the ability of lead to adversely affect blood parameters was investigated, and Lycopersicon esculentum, or commonly known as tomato (a source of antioxidants), was administered orally in the form of tomato paste (TP) to reduce the adverse effects of lead. Methods: The study involved 56 Wistar rats divided equally into 4 groups of 14 rats each: Control, LAG, TPG, and LA+TPG. Control and TPG rats were given distilled water ad libitum, while LAG and LA+TPG rats were given 1% lead (II) acetate (LA) per day. TPG and LA+TPG rats were additionally treated with 1.5 ml of TP per day. All treatments lasted for 10 weeks, after which the rats were weighed and sacrificed, and haematological and biochemical parameters were measured. The independent samples t test was used to analyse the results. Results: Lead caused significant reductions in the following parameters: weight; packed cell volume; red blood cell and white blood cell counts; the percentages of lymphocytes and monocytes; total serum protein, albumin, and globulin levels; and plasma superoxide dismutase and catalase activities. In contrast, lead caused a significant increase in the percentage of neutrophils and the plasma malondialdehyde concentration. TP, however, significantly prevented the adverse effects of LA. Conclusion: The oral administration of TP prevents the adverse effects of lead on blood constituents. PMID:22135544

The psychological effects of a videotape educational intervention on cardiac catheterization patients.

PubMed

Chair, Sek Ying; Chau, Mei Yi; Sit, Janet Wing Hung; Wong, Eliza Mei Ling; Chan, Aileen Wai Kiu

2012-02-01

Coronary artery disease (CAD) is one of the leading causes of death and morbidity worldwide, and cardiac catheterization plays an essential role in its diagnostic evaluation. This quasi-experimental study examined the effectiveness of an educational intervention with the use of videotape and pamphlet among the Chinese patient undergoing the cardiac catheterization, and explored the relationship between anxiety, uncertainty, and other psychological variables. One hundred and thirty two Chinese patients of diagnosed or suspected CAD preparing for the first-time catheterization were recruited. Anxiety level (the Chinese State Anxiety Inventory) and uncertainty (the Chinese version of Mishel Uncertainty in Illness Scale) were measured before the intervention and within 2 hours before receiving cardiac catheterization; while patients' satisfaction and perceived knowledge gain were measured at 20-24 hours after it. The mean age of the participants was 61.3 and 64.8% of them were male. The findings indicated that the use of videotape to prepare patients for the cardiac catheterization is effective in reducing the level of anxiety (p < 0.001) and the uncertainty (p < 0.001), as the patients experienced higher satisfaction and knowledge level after the educational intervention. Therefore, videotape education is suggested for cardiac catheterization care on top of the usual pamphlet education.

Effectiveness of implantable cardioverter-defibrillators in survivors of inhospital cardiac arrest.

PubMed

Chan, Paul S; Krumholz, Harlan M; Spertus, John A; Curtis, Lesley H; Li, Yan; Hammill, Bradley G; Nallamothu, Brahmajee K

2015-06-01

Although implantable cardioverter-defibrillators (ICDs) reduce mortality in patients with out-of-hospital cardiac arrest, their effectiveness in survivors of "inhospital" cardiac arrest-a population with different arrest etiologies and higher illness acuity than out-of-hospital cardiac arrest-is unknown. We therefore sought to conduct a comparative effectiveness study of ICD therapy in survivors of inhospital cardiac arrest. We linked data from a national inpatient cardiac arrest registry with Medicare files and identified 1,200 adults from 267 hospitals between 2000 and 2008 who were discharged after surviving an inhospital cardiac arrest due to ventricular fibrillation or pulseless ventricular tachycardia and who otherwise met traditional inclusion and exclusion criteria for secondary prevention ICD trials. The association between ICD treatment and long-term mortality was evaluated using an optimal match (≤4 controls for each ICD patient) propensity-score analysis. Of 1,200 survivors, 343 (28.6%) received an ICD during the index hospitalization. Overall, 3-year mortality was 44.2%, with higher unadjusted mortality in the non-ICD versus the ICD group (46.9% vs 37.3%; log-rank; P < .001). After successfully matching 343 patients treated with ICDs with 823 untreated patients by propensity score, ICD treatment was associated with a 24% lower mortality rate (adjusted hazard ratio [HR] 0.76; 95% CI 0.60-0.97; P = .025). This lower mortality was mediated by lower rates of out-of-hospital deaths among ICD-treated patients (22.1% vs 30.8%; adjusted HR 0.71 [0.52-0.96]; P = .019), whereas deaths occurring during a readmission were similar (15.2% vs 16.1%; adjusted HR 0.89 [95% CI 0.60-1.32]; P = .56). Implantable cardioverter-defibrillator therapy in survivors of inhospital cardiac arrest due to a pulseless ventricular rhythm is used uncommonly but associated with lower long-term mortality. Given that fewer than 3 in 10 eligible survivors are treated with ICDs after

CARDIAC MOLECULAR EFFECTS INDUCED BY AIR POLLUTION PARTICLES

EPA Science Inventory

Abstract Submitted to the American Thoracic Society 98th International Conference, May 17 - 22, 2002, Atlanta, GA

CARDIAC MOLECULAR EFFECTS INDUCED BY AIR POLLUTION PARTICLES
K. Dreher1, R. Jaskot1, J. Richards1, and T. Knuckles2. 1U. S. Environmental Protection Agency,...

Adverse effects of orthodontic treatment: A clinical perspective

PubMed Central

Talic, Nabeel F.

2011-01-01

Orthodontic treatment is associated with a number of adverse effects, such as root resorption, pain, pulpal changes, periodontal disease, and temporomandibular dysfunction (TMD). Orthodontists should be aware of these effects and associated risk factors. Risk factors linked to root resorption include the duration of treatment, length, and shape of the root, trauma history, habits, and genetic predisposition. PMID:24151415

Adverse effects of concentrated green tea extracts.

PubMed

Schönthal, Axel H

2011-06-01

A myriad of health claims are being made in favor of the consumption of green tea. However, mostly due to the easy availability and greater than ever popularity of highly concentrated green tea extracts, sometimes combined with an attitude of more-is-better, certain health risks of green tea consumption have begun to emerge. Among such risks are the possibility of liver damage, the potential to interact with prescription drugs to alter their therapeutic efficacy, and the chance to cause harm when combined with other highly popular herbal remedies. This review will summarize documented examples of adverse effects of green tea in humans, and will discuss risks of copious consumption of highly concentrated green tea extracts as indicated by studies in animals. While there is no intention to minimize any of the scientifically established benefits of the use of green tea, the purpose of this review is to focus primarily on the potential for adverse effects and raise awareness of the rare, yet under-appreciated risks. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Biphasic Effect of Nitric Oxide on the Cardiac Voltage-dependent Anion Channel

PubMed Central

Cheng, Qunli; Sedlic, Filip; Pravdic, Danijel; Bosnjak, Zeljko J.; Kwok, Wai-Meng

2010-01-01

Nitric oxide (NO˙) effects on the cardiac mitochondrial voltage-dependent anion channel (VDAC) are unknown. The effects of exogenous NO˙ on VDAC purified from rat hearts were investigated in this study. When incorporated into lipid bilayers, VDAC was inhibited directly by an NO˙ donor, PAPA NONOate, in a concentration-dependent biphasic manner. This was prevented by an NO˙ scavenger, PTIO. The effect paralleled that of NO˙ in delaying the opening of the mitochondrial permeability transition (PT) pore. These biphasic effects on the cardiac VDAC and the PT pore reveal a tandem impact of NO˙ on the two mitochondrial entities. PMID:21156174

Teamwork, Communication, Formula-One Racing and the Outcomes of Cardiac Surgery

PubMed Central

Merry, Alan F.; Weller, Jennifer; Mitchell, Simon J.

2014-01-01

Abstract: Most cardiac units achieve excellent results today, but the risk of cardiac surgery is still relatively high, and avoidable harm is common. The story of the Green Lane Cardiothoracic Unit provides an exemplar of excellence, but also illustrates the challenges associated with changes over time and with increases in the size of a unit and the complexity of practice today. The ultimate aim of cardiac surgery should be the best outcomes for (often very sick) patients rather than an undue focus on the prevention of error or adverse events. Measurement is fundamental to improving quality in health care, and the framework of structure, process, and outcome is helpful in considering how best to achieve this. A combination of outcomes (including some indicators of important morbidity) with key measures of process is advocated. There is substantial evidence that failures in teamwork and communication contribute to inefficiency and avoidable harm in cardiac surgery. Minor events are as important as major ones. Six approaches to improving teamwork (and hence outcomes) in cardiac surgery are suggested. These are: 1) subspecialize and replace tribes with teams; 2) sort out the leadership while flattening the gradients of authority; 3) introduce explicit training in effective communication; 4) use checklists, briefings, and debriefings and engage in the process; 5) promote a culture of respect alongside a commitment to excellence and a focus on patients; 6) focus on the performance of the team, not on individuals. PMID:24779113

Teamwork, communication, formula-one racing and the outcomes of cardiac surgery.

PubMed

Merry, Alan F; Weller, Jennifer; Mitchell, Simon J

2014-03-01

Most cardiac units achieve excellent results today, but the risk of cardiac surgery is still relatively high, and avoidable harm is common. The story of the Green Lane Cardiothoracic Unit provides an exemplar of excellence, but also illustrates the challenges associated with changes over time and with increases in the size of a unit and the complexity of practice today. The ultimate aim of cardiac surgery should be the best outcomes for (often very sick) patients rather than an undue focus on the prevention of error or adverse events. Measurement is fundamental to improving quality in health care, and the framework of structure, process, and outcome is helpful in considering how best to achieve this. A combination of outcomes (including some indicators of important morbidity) with key measures of process is advocated. There is substantial evidence that failures in teamwork and communication contribute to inefficiency and avoidable harm in cardiac surgery. Minor events are as important as major ones. Six approaches to improving teamwork (and hence outcomes) in cardiac surgery are suggested. These are: 1) subspecialize and replace tribes with teams; 2) sort out the leadership while flattening the gradients of authority; 3) introduce explicit training in effective communication; 4) use checklists, briefings, and debriefings and engage in the process; 5) promote a culture of respect alongside a commitment to excellence and a focus on patients; 6) focus on the performance of the team, not on individuals.

PERTINENT DRY NEEDLING CONSIDERATIONS FOR MINIMIZING ADVERSE EFFECTS – PART ONE

PubMed Central

Halle, Rob J.

2016-01-01

ABSTRACT Background Dry needling is an evidence-based treatment technique that is accepted and used by physical therapists in the United States. This treatment approach focuses on releasing or inactivating muscular trigger points to decrease pain, reduce muscle tension, and assist patients with an accelerated return to active rehabilitation. Issue While commonly used, the technique has some patient risk and value of the treatment should be based on benefit compared to the potential risk. Adverse effects (AEs) with dry needling can be mild or severe, with overall incidence rates varying from zero to rates of approximately 10 percent. While mild AEs are the rule, any procedure that involves a needle insertion has the potential for an AE, with select regions and the underlying anatomy increasing the risk. Known significant AEs from small diameter needle insertion include pneumothorax, cardiac tamponade, hematoma, infection, central nervous system injury, and other complications. Purpose/Objective Underlying anatomy across individuals has variability, requiring an in-depth knowledge of anatomy prior to any needle placement. This commentary is an overview of pertinent anatomy in the region of the thorax, with a ‘part two’ that addresses the abdomen, pelvis, back, vasovagal response, informed consent and other pertinent issues. The purpose of the commentary is to minimize the risk of a dry needling AE. Conclusions/Implications Dry needling is an effective adjunct treatment procedure that is within the recognized scope of physical therapy practice. Physical therapy education and training provides practitioners with the anatomy, basic sciences, and clinical foundation to use this intervention safely and effectively. A safe and evidenced-based implementation of the procedure is based on a thorough understanding of the underlying anatomy and the potential risks, with risks coordinated with patients via informed consent. Levels of Evidence Level 5 PMID:27525188

A randomized controlled trial of levosimendan to reduce mortality in high-risk cardiac surgery patients (CHEETAH): Rationale and design.

PubMed

Zangrillo, Alberto; Alvaro, Gabriele; Pisano, Antonio; Guarracino, Fabio; Lobreglio, Rosetta; Bradic, Nikola; Lembo, Rosalba; Gianni, Stefano; Calabrò, Maria Grazia; Likhvantsev, Valery; Grigoryev, Evgeny; Buscaglia, Giuseppe; Pala, Giovanni; Auci, Elisabetta; Amantea, Bruno; Monaco, Fabrizio; De Vuono, Giovanni; Corcione, Antonio; Galdieri, Nicola; Cariello, Claudia; Bove, Tiziana; Fominskiy, Evgeny; Auriemma, Stefano; Baiocchi, Massimo; Bianchi, Alessandro; Frontini, Mario; Paternoster, Gianluca; Sangalli, Fabio; Wang, Chew-Yin; Zucchetti, Maria Chiara; Biondi-Zoccai, Giuseppe; Gemma, Marco; Lipinski, Michael J; Lomivorotov, Vladimir V; Landoni, Giovanni

2016-07-01

Patients undergoing cardiac surgery are at risk of perioperative low cardiac output syndrome due to postoperative myocardial dysfunction. Myocardial dysfunction in patients undergoing cardiac surgery is a potential indication for the use of levosimendan, a calcium sensitizer with 3 beneficial cardiovascular effects (inotropic, vasodilatory, and anti-inflammatory), which appears effective in improving clinically relevant outcomes. Double-blind, placebo-controlled, multicenter randomized trial. Tertiary care hospitals. Cardiac surgery patients (n = 1,000) with postoperative myocardial dysfunction (defined as patients with intraaortic balloon pump and/or high-dose standard inotropic support) will be randomized to receive a continuous infusion of either levosimendan (0.05-0.2 μg/[kg min]) or placebo for 24-48 hours. The primary end point will be 30-day mortality. Secondary end points will be mortality at 1 year, time on mechanical ventilation, acute kidney injury, decision to stop the study drug due to adverse events or to start open-label levosimendan, and length of intensive care unit and hospital stay. We will test the hypothesis that levosimendan reduces 30-day mortality in cardiac surgery patients with postoperative myocardial dysfunction. This trial is planned to determine whether levosimendan could improve survival in patients with postoperative low cardiac output syndrome. The results of this double-blind, placebo-controlled randomized trial may provide important insights into the management of low cardiac output in cardiac surgery. Copyright © 2016 Elsevier Inc. All rights reserved.

Nurse practitioners in postoperative cardiac surgery: are they effective?

PubMed

Goldie, Catherine L; Prodan-Bhalla, Natasha; Mackay, Martha

2012-01-01

High demand for acute care nurse practitioners (ACNPs) in Canadian postoperative cardiac surgery settings has outpaced methodologically rigorous research to support the role. To compare the effectiveness of ACNP-led care to hospitalist-led care in a postoperative cardiac surgery unit in a Canadian, university-affiliated, tertiary care hospital. Patients scheduled for urgent or elective coronary artery bypass and/or valvular surgery were randomly assigned to either ACNP-led (n=22) or hospitalist-led (n=81) postoperative care. Both ACNPs and hospitalists worked in collaboration with a cardiac surgeon. Outcome variables included length of hospital stay, hospital readmission rate, postoperative complications, adherence to follow-up appointments, attendance at cardiac rehabilitation and both patient and health care team satisfaction. Baseline demographic characteristics were similar between groups except more patients in the ACNP-led group had had surgery on an urgent basis (p < or = 0.01), and had undergone more complicated surgical procedures (p < or =0.01). After discharge, more patients in the hospitalist-led group had visited their family doctor within a week (p < or =0.02) and measures of satisfaction relating to teaching, answering questions, listening and pain management were higher in the ACNP-led group. Although challenges in recruitment yielded a lower than anticipated sample size, this study contributes to our knowledge of the ACNP role in postoperative cardiac surgery. Our findings provide support for the ACNP role in this setting as patients who received care from an ACNP had similar outcomes to hospitalist-led care and reported greater satisfaction in some measures of care.

[L-carnitine treatment and fish odor syndrome: an unwaited adverse effect].

PubMed

Rocher, F; Caruba, C; Broly, F; Lebrun, C

2011-01-01

Levocarnitine treatment is usually well tolerated, with essentially dose-dependent diarrhea as the main induced adverse effect. We report a case of fish odor syndrome during levocarnitine treatment which resolved after levocarnitine discontinuation. This adverse effect seems to be correlated with excedent carnitine intake and might be expressed when the elimination pathway becomes saturated or in a situation of deficiency enzymatic metabolism. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Causes of in-hospital cardiac arrest and influence on outcome.

PubMed

Wallmuller, Christian; Meron, Giora; Kurkciyan, Istepan; Schober, Andreas; Stratil, Peter; Sterz, Fritz

2012-10-01

To evaluate the relationship between cause and outcome of in-hospital cardiac arrest. Retrospective analysis of resuscitation data, causes of cardiac arrest and outcome with a follow-up to 6 months of a cardiac arrest registry in an emergency department of a tertiary care hospital, covering a 17.5-year period. Of 1041 patients, 653 were male (63%), the median age was 64 years (IQR 53-73), 51% suffered cardiac arrest in the emergency department. The first recorded rhythm showed PEA in 432 (41%), ventricular fibrillation in 404 (39%) and asystole in 205 (20%) patients. Cardiac arrest of cardiac origin occurred in 63% of all patients, with 35% of them due to acute myocardial infarction. Non-cardiac causes were mostly due to pulmonary causes (15% of all patients). Aortic dissection/rupture, exsanguination, intoxication and adverse drug reactions, metabolic, cerebral, sepsis and accidental hypothermia each ranged between 1 and 4% of the cohort. Of all patients, 376 (36%) were discharged in good neurologic condition. Overall, patients with cardiac causes had a significantly better outcome than those with non-cardiac causes (44% vs. 23%, p<0.01). Patients with pulmonary causes survived in 24%. The other subgroups showed widely divergent survival results (3-65%). Patients who had suffered cardiac arrest in the emergency department had a better outcome then patients of the regular ward or radiology department. In hospital cardiac arrest is caused mainly by cardiac and pulmonary causes, outcome depends on the cause, with a big variability. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Analysis of Complaints from Patients During Mechanical Ventilation After Cardiac Surgery: A Retrospective Study.

PubMed

Wang, Yi; Li, Hua; Zou, Honglin; Li, Yaxiong

2015-08-01

This study analyzed major complaints from patients during mechanical ventilation after cardiac surgery and identified the most common complaints to reduce adverse psychologic responses. Retrospective. A single tertiary university hospital. Patients with heart disease who were on mechanical ventilation after cardiac surgery (N = 800). The major complaints of the patients during mechanical ventilation after cardiac surgery were analyzed. Patients' comfort was evaluated using a visual analog scale, and the factors affecting comfort were analyzed. The average visual analog scale score in all patients was 5.8±2.0, and most patients presented moderate discomfort. The factors affecting comfort included dry mouth, thirst, tracheal intubation, aspiration of sputum, communication barriers, limited mobility, fear/anxiety, patient-ventilator dyssynchrony, and poor environmental conditions. Of these factors, 8 were independent predictors of the visual analog scale score. Patients considered mechanical ventilation to be the worst part of their hospitalization. The study identified 8 independent factors causing discomfort in patients during mechanical ventilation after cardiac surgery. Clinicians should take appropriate measures and implement nursing interventions to reduce suffering, physical and psychologic trauma, and adverse psychologic responses and to promote recovery. Copyright © 2015 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.

Coronary revascularization and adverse events in joint arthroplasty.

PubMed

Tabatabaee, Reza Mostafavi; Rasouli, Mohammad R; Rezapoor, Maryam; Maltenfort, Mitchell G; Ong, Alvin C; Parvizi, Javad

2015-09-01

There is a paucity of literature about outcome of total joint arthroplasty in patients with the history of angioplasty and/or stent or coronary artery bypass graft (CABG). The present study aimed to evaluate perioperative complications and mortality in these patients. We used the Nationwide Inpatient Sample data from 2002-2011. Using the Ninth Revision of the International Classification of Disease, Clinical Modification codes for disorders and procedures, we identified patients with a history of coronary revascularization (angioplasty and/or stent or CABG) and compared the inhospital adverse events in these patients with patients without a history of coronary revascularization. Cardiac complications occurred in 1.06% patients with a history of CABG; 0.95% of patients with a coronary angioplasty and/or stent and 0.82% of the control patients. In the multivariate analysis, neither the history of CABG (P = 0.07) nor the history of angioplasty and/or stenting (P = 0.86) was associated with a higher risk of cardiac complications. However, myocardial infarction occurred in a significantly higher proportion of patients with the history of CABG (0.66%, odds ratio, 1.24, P = 0.001) and coronary angioplasty and/or stenting (0.67%, odds ratio, 1.96, P < 0.001) compared with that in the controls (0.27%). History of coronary revascularization did not increase the risk of respiratory, renal, and wound complications, surgical site infection, and mortality. Based on the findings of this study, it appears that there is no increased risk of inhospital mortality and complications (except for myocardial infarction) in patients with a history of coronary artery revascularization undergoing total joint arthroplasty. We also found perioperative cardiac arrhythmia, particularly atrial fibrillation, to be an independent predictor of inhospital adverse events. Copyright © 2015 Elsevier Inc. All rights reserved.

Hemodynamic effects of calcium antagonists in cardiac patients.

PubMed

Pozenel, H

1982-01-01

Hemodynamic studies were carried out after cardiac catheterization with a floatation catheter in the pulmonary artery and cannulation of the brachial artery for the calculation of cardiac output by means of the Fick principle. Continuous pressure recordings were carried out at rest and under submaximal treadmill exercise in the supine body position in 5 homogeneous groups of 12 patients, all with disorders due to coronary disease. In a control test, hemodynamic investigations were carried out at rest before medication, under stress and after recovery. Similar tests were performed after intravenous administration of either isotonic saline as placebo, tiapamil (1.1 and 1.6 mg/kg) or verapamil (0.07 and 0.14 mg/kg). It was shown that there was a marked dose-related reduction in peripheral vascular resistance with a maximum effect occurring at 2-5 min after the intravenous administration of tiapamil (1.1 and 1.6 mg/kg) reaching 23 and 39%, respectively, or verapamil (0.07 and 0.14 mg/kg) attaining 28 and 39%, respectively, at rest and, to a similar extent, under stress conditions. In patients with sinus rhythm, the mean arterial pressure was reduced. Cardiac outputs and stroke volumes were increased at rest as well as under stress. There was no evidence of a depressant action of the drug on hemodynamic variables. An interplay of simultaneous changes in preload and afterload seems to be responsible for the effects obtained. The doses used were those commonly employed in the termination of supraventricular tachyarrhythmias. However, a potential depressant effect of tiapamil in patients with markedly reduced ventricular function is not excluded by this study.

Heart rate complexity: A novel approach to assessing cardiac stress reactivity.

PubMed

Brindle, Ryan C; Ginty, Annie T; Phillips, Anna C; Fisher, James P; McIntyre, David; Carroll, Douglas

2016-04-01

Correlation dimension (D2), a measure of heart rate (HR) complexity, has been shown to decrease in response to acute mental stress and relate to adverse cardiovascular health. However, the relationship between stress-induced changes in D2 and HR has yet to be established. The present studies aimed to assess this relationship systematically while controlling for changes in respiration and autonomic activity. In Study 1 (N = 25) D2 decreased during stress and predicted HR reactivity even after adjusting for changes in respiration rate, and cardiac vagal tone. This result was replicated in Study 2 (N = 162) and extended by including a measure of cardiac sympathetic activity; correlation dimension remained an independent predictor of HR reactivity in a hierarchical linear model containing measures of cardiac parasympathetic and sympathetic activity and their interaction. These results suggest that correlation dimension may provide additional information regarding cardiac stress reactivity above that provided by traditional measures of cardiac autonomic function. © 2015 Society for Psychophysiological Research.

Real-World Adverse Effects of Capecitabine Toxicity in an Elderly Population.

PubMed

van Beek, Michiel W H; Roukens, Monique; Jacobs, Wilco C H; Timmer-Bonte, Johanna N H; Kramers, Cees

2018-06-22

Few studies have assessed the safety and effectiveness of the numerous available chemotherapeutic therapies for geriatric oncology patients. Most safety studies are conducted in large trials, and there is some uncertainty surrounding whether the results would be the same in typical daily use. This retrospective study aims to assess the adverse effects of real-world capecitabine use in elderly patients. We reviewed the records of patients treated with capecitabine in an oncology department of a University Clinic in Nijmegen, The Netherlands. We scored adverse effects such as hand-foot syndrome and diarrhea, and dosage adjustments and the reasons for them. In total, 132 patients were included, 69 of whom were aged 70 years or below (mean age: 57 years), while 63 were aged older than 70 years (mean age: 74 years). Patients aged over 70 years experienced more serious adverse effects than younger patients. Grade 2 or 3 hand-foot syndrome toxicity was experienced by 20.2% of patients aged younger than 70 years and by 34.9% of patients older than 70 years (p = 0.059). Grade 2, 3, or 4 diarrhea was experienced by 17.4% of the patients aged younger than 70 years but by 31.7% of the patients aged older than 70 years (p = 0.044). Dosage was adjusted for 27/69 patients in the younger group and 52/63 patients in the older group (p = 0.001). The difference in observed adverse effects cannot be the sole explanation for the high incidence of observed dose adjustments. A prospective follow-up study of elderly patients using capecitabine outside clinical trials is needed to evaluate the optimum balance between adverse effects and efficacy.

Ketamine for Pain Management-Side Effects & Potential Adverse Events.

PubMed

Allen, Cheryl A; Ivester, Julius R

2017-12-01

An old anesthetic agent, ketamine is finding new use in lower doses for analgesic purposes. There are concerns stemming from its potential side effects-specifically psychomimetic effects. These side effects are directly related to dose amount. The doses used for analgesic purposes are much lower than those used for anesthesia purposes. A literature review was performed to ascertain potential side effects and/or adverse events when using ketamine for analgesia purposes. The search included CINAHL, PubMed, and Ovid using the search terms "ketamine," "ketamine infusion," "pain," "adverse events," "practice guideline," and "randomized controlled trial." Searches were limited to full-text, peer-reviewed articles and systematic reviews. Initially 1,068 articles were retrieved. The search was then narrowed by using the Boolean connector AND with various search term combinations. After adjusting for duplication, article titles and abstracts were reviewed, leaving 25 articles for an in-depth analysis. Specific exclusion criteria were then applied. The literature supports the use of ketamine for analgesic purposes, and ketamine offers a nonopioid option for the management of some pain conditions. Because ketamine is still classified as an anesthetic agent, health care institutions should develop their own set of policies and protocols for the administration of ketamine. By using forethought and understanding of the properties of ketamine, appropriate care may be planned to mitigate potential side effects and adverse events so that patients are appropriately cared for and their pain effectively managed. Copyright © 2017 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

The Psycho-cardiac Coupling, Myocardial Remodeling, and Neuroendocrine Factor Levels: The Psychosomatics of Major Depressive Disorder.

PubMed

Syeda, Javeria N; Rutkofsky, Ian H; Muhammad, Adnan S; Balla Abdalla, Tarig H; Saghir, Zahid

2018-04-11

The association of major depressive disorder (MDD) with myocardial infarction (MI) and vice versa is not unknown. Depression, along with many other systemic factors like atherosclerosis, obesity, diabetes and vascular dysfunction, contributes to the development of adverse cardiac events in the future and, has always been a topic of interest in the fields of cardiology and psychosomatics. We wrote this review article to elaborate this relationship in detail. This article suggests that the individuals with type D personality who already had cardiovascular disease had undergone more serious myocardial damage. In addition, we elucidated the effects of depression on sympathetic activity and remodeling of myocardium after MI. The alterations in the neuroendocrine factors, which included the changes in levels of Serotonin (5-HT), Norepinephrine and Corticosterone, also geared towards the changes associated with depression-induced myocardial injury. However, we need more studies in the near future to further dig into this association process. Therefore, we recommend more research to explore the relationship of psychological factors and adverse cardiac outcomes.

Beneficial effects of hypnosis and adverse effects of empathic attention during percutaneous tumor treatment: when being nice does not suffice.

PubMed

Lang, Elvira V; Berbaum, Kevin S; Pauker, Stephen G; Faintuch, Salomao; Salazar, Gloria M; Lutgendorf, Susan; Laser, Eleanor; Logan, Henrietta; Spiegel, David

2008-06-01

To determine how hypnosis and empathic attention during percutaneous tumor treatments affect pain, anxiety, drug use, and adverse events. For their tumor embolization or radiofrequency ablation, 201 patients were randomized to receive standard care, empathic attention with defined behaviors displayed by an additional provider, or self-hypnotic relaxation including the defined empathic attention behaviors. All had local anesthesia and access to intravenous medication. Main outcome measures were pain and anxiety assessed every 15 minutes by patient self-report, medication use (with 50 mug fentanyl or 1 mg midazolam counted as one unit), and adverse events, defined as occurrences requiring extra medical attention, including systolic blood pressure fluctuations (> or =50 mm Hg change to >180 mm Hg or <105 mm Hg), vasovagal episodes, cardiac events, and respiratory impairment. Patients treated with hypnosis experienced significantly less pain and anxiety than those in the standard care and empathy groups at several time intervals and received significantly fewer median drug units (mean, 2.0; interquartile range [IQR], 1-4) than patients in the standard (mean, 3.0; IQR, 1.5-5.0; P = .0147) and empathy groups (mean, 3.50; IQR, 2.0-5.9; P = .0026). Thirty-one of 65 patients (48%) in the empathy group had adverse events, which was significantly more than in the hypnosis group (eight of 66; 12%; P = .0001) and standard care group (18 of 70; 26%; P = .0118). Procedural hypnosis including empathic attention reduces pain, anxiety, and medication use. Conversely, empathic approaches without hypnosis that provide an external focus of attention and do not enhance patients' self-coping can result in more adverse events. These findings should have major implications in the education of procedural personnel.

Cardiac Safety of Methylphenidate Versus Amphetamine Salts in the Treatment of ADHD

PubMed Central

Winterstein, Almut Gertrud; Gerhard, Tobias; Shuster, Jonathan; Saidi, Arwa

2013-01-01

OBJECTIVES Safety concerns about central nervous system stimulants for the treatment of attention-deficit/hyperactivity disorder (ADHD) include adverse cardiac effects. This study aimed to compare the risk for cardiac events in users of methylphenidate and amphetamine salts. METHODS A retrospective cohort design using claims data from the Florida Medicaid fee-for-service program representing a total of 2 131 953 children and adolescents was used. The analysis included all beneficiaries who were between 3 and 20 years of age, enrolled between July 1994 and June 2004, had at least 1 physician diagnosis of ADHD and were newly started on methylphenidate or amphetamine salts. Each month of follow-up was classified according to stimulant use into current use or former use. We defined cardiac events as first emergency department (ED) visit for cardiac disease or symptoms. Risk between current users of methylphenidate versus amphetamine salts and former users of drugs in these categories was compared by using a time-dependent Cox proportional hazard model that adjusted for differences in gender; race; age; year of the index date; disability; congenital anomalies; history of circulatory disease; history of hospital admission; and use of antidepressants, antipsychotics, and bronchodilators. RESULTS A total of 456 youth visited the ED for cardiac reasons during 52 783 years of follow-up. After adjustment for differences in covariates, the risk for cardiac ED visits was similar among current users of methylphenidate or amphetamines. Periods of former use had a similar risk between youth with an exposure history to methylphenidate or amphetamine. CONCLUSION Exposure to methylphenidate and amphetamines salts showed similar risk for cardiac ED visits. Additional population-based studies that address manifestation of serious heart disease, especially after long-term use, dosage comparisons, and interactions with preexisting cardiac risk factors are needed to inform psychiatric

Incremental value of normal adenosine perfusion cardiac magnetic resonance: Long-term outcome.

PubMed

Sozzi, Fabiola B; Iacuzio, Laura; Civaia, Filippo; Canetta, Ciro; Berthier, Frederic; Rusek, Stephane; Rossi, Philippe; Lombardi, Federico; Dreyfus, Gilles; Dor, Vincent

2015-06-01

The purpose of the study was to determine the long-term prognostic value of normal adenosine stress cardiac magnetic resonance imaging (CMR) in patients referred for evaluation of myocardial ischemia. We reviewed 300 consecutive patients (age 65 ± 11 years, 74% male) with suspected or known coronary disease and normal wall motion who had undergone adenosine stress CMR negative for ischemia and scar. Most patients were at intermediate risk of coronary artery disease. The end points studied were all causes of mortality and major adverse cardiac events, including cardiac death, myocardial infarction, revascularization, and hospitalization for unstable angina. During a mean follow-up of 5.5 years (mean = 5.4 ± 1.1), 16 patients died because of various causes (cardiac death in 5 patients). Three patients had a nonfatal myocardial infarction, 7 patients were hospitalized for revascularization, and 11 were medically treated for unstable angina. The annual cardiac event rate was 1.3% (0.78% in the first 3 years and 1.9% between the fourth and sixth years). The predictors of major adverse cardiac events in a multivariate analysis model were as follows: advanced age (hazard ratio [HR] 1.15, 95% confidence interval [95% CI] 1.02-1.30), diabetes (HR 17.5, 95% CI 2.2-140), and the habit of smoking (HR 5.9, 95% CI 1.0-35.5). For all causes of mortality, the only predictor was diabetes (HR 11.4, 95% CI 1.76-74.2). Patients with normal stress CMR had an excellent outcome during the 3 years after the study. The cardiac event rate was higher between the fourth and sixth years. Over a 5.5-year period, a low event rate and excellent prognosis occurred in patients with normal adenosine stress CMR. Low- to intermediate-risk patients with a normal CMR are at low risk for subsequent cardiac events. Copyright © 2015 Elsevier Inc. All rights reserved.

Subclinical myocardial necrosis and cardiovascular risk in stable patients undergoing elective cardiac evaluation.

PubMed

Tang, W H Wilson; Wu, Yuping; Nicholls, Stephen J; Brennan, Danielle M; Pepoy, Michael; Mann, Shirley; Pratt, Alan; Van Lente, Frederick; Hazen, Stanley L

2010-03-01

The presence of subclinical myocardial necrosis as a prodrome to longer-term adverse cardiac event risk has been debated. The debate has focused predominantly within patients with acute coronary syndrome, and on issues of troponin assay variability and accuracy of detection, rather than on the clinical significance of the presence of subclinical myocardial necrosis (ie, "troponin leak") within stable cardiac patients. Herein, we examine the relationship between different degrees of subclinical myocardial necrosis and long-term adverse clinical outcomes within a stable cardiac patient population with essentially normal renal function. Sequential consenting patients (N=3828; median creatinine clearance, 100 mL/min/1.73m(2)) undergoing elective diagnostic coronary angiography with cardiac troponin I (cTnI) levels below the diagnostic cut-off for defining myocardial infarction (<0.03 ng/mL) were evaluated. The relationship of subclinical myocardial necrosis with incident major adverse cardiovascular events (defined as any death, myocardial infarction, or stroke) over 3-year follow-up was examined. "Probable" (cTnI 0.001-0.008 ng/mL) and "definite" (cTnI 0.009-0.029 ng/mL) subclinical myocardial necrosis were observed frequently within the cohort (34% and 18%, respectively). A linear relationship was observed between the magnitude of subclinical myocardial necrosis and risk of 3-year incident major adverse cardiovascular events, particularly in those with cTnI 0.009 ng/mL or higher (hazard ratio, 3.00; 95% confidence interval, 2.4-3.8), even after adjustment for traditional risk factors, C-reactive protein, and creatinine clearance. The presence of subclinical myocardial necrosis was associated with elevations in acute phase proteins (C-reactive protein, ceruloplasmin; P<0.01 each) and reduction in systemic antioxidant enzyme activities (arylesterase; P<0.01) but showed no significant associations with multiple specific measures of oxidant stress, and showed borderline

The effects of center of rotation errors on cardiac SPECT imaging

NASA Astrophysics Data System (ADS)

Bai, Chuanyong; Shao, Ling; Ye, Jinghan; Durbin, M.

2003-10-01

In SPECT imaging, center of rotation (COR) errors lead to the misalignment of projection data and can potentially degrade the quality of the reconstructed images. In this work, we study the effects of COR errors on cardiac SPECT imaging using simulation, point source, cardiac phantom, and patient studies. For simulation studies, we generate projection data using a uniform MCAT phantom first without modeling any physical effects (NPH), then with the modeling of detector response effect (DR) alone. We then corrupt the projection data with simulated sinusoid and step COR errors. For other studies, we introduce sinusoid COR errors to projection data acquired on SPECT systems. An OSEM algorithm is used for image reconstruction without detector response correction, but with nonuniform attenuation correction when needed. The simulation studies show that, when COR errors increase from 0 to 0.96 cm: 1) sinusoid COR errors in axial direction lead to intensity decrease in the inferoapical region; 2) step COR errors in axial direction lead to intensity decrease in the distal anterior region. The intensity decrease is more severe in images reconstructed from projection data with NPH than with DR; and 3) the effects of COR errors in transaxial direction seem to be insignificant. In other studies, COR errors slightly degrade point source resolution; COR errors of 0.64 cm or above introduce visible but insignificant nonuniformity in the images of uniform cardiac phantom; COR errors up to 0.96 cm in transaxial direction affect the lesion-to-background contrast (LBC) insignificantly in the images of cardiac phantom with defects, and COR errors up to 0.64 cm in axial direction only slightly decrease the LBC. For the patient studies with COR errors up to 0.96 cm, images have the same diagnostic/prognostic values as those without COR errors. This work suggests that COR errors of up to 0.64 cm are not likely to change the clinical applications of cardiac SPECT imaging when using

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.

Effects of radiation exposure from cardiac imaging: how good are the data?

PubMed

Einstein, Andrew J

2012-02-07

Concerns about medical exposure to ionizing radiation have become heightened in recent years as a result of rapid growth in procedure volumes and the high radiation doses incurred from some procedures. This paper summarizes the evidence base undergirding concerns about radiation exposure in cardiac imaging. After classifying radiation effects, explaining terminology used to quantify the radiation received by patients, and describing typical doses from cardiac imaging procedures, this paper will address the major epidemiological studies having bearing on radiation effects at doses comparable to those received by patients undergoing cardiac imaging. These include studies of atomic bomb survivors, nuclear industry workers, and children exposed in utero to x-rays, all of which have evidenced increased cancer risks at low doses. Additional higher-dose epidemiological studies of cohorts exposed to radiation in the context of medical treatment are described and found to be generally compatible with these cardiac dose-level studies, albeit with exceptions. Using risk projection models developed by the U.S. National Academies that incorporate these data and reflect several evidence-based assumptions, cancer risk from cardiac imaging can be estimated and compared with the benefits from imaging. Several ongoing epidemiological studies will provide better understanding of radiation-associated cancer risks. Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Cardiac biomarker changes in camels (Camelus dromedarius) secondary to road transportation.

PubMed

Tharwat, Mohamed; Al-Sobayil, Fahd; Buczinski, Sébastien

2013-03-01

Little is known about cardiac biomarkers in camels despite their extensive use as draft animals. This study was designed to establish reference ranges for the cardiac biomarkers cardiac troponin I (cTnI) and creatine kinase myocardial b fraction (CK-MB) in healthy camels and to investigate their changes in response to road transportation. Twenty-five healthy camels transported for a 5 h round-trip journey. None of the camels had evidence of cardiac abnormalities on cardiac auscultation, echocardiography or electrocardiography. Three blood samples were obtained from each camel: 24 h before transportation (T0), within 2 h after unloading (T1) and 24 h after transportation (T2). The mean cTnI concentration in the camels was 0.032 ± 0.023 ng/mL. All the camels had resting cTnI concentrations of <0.08 ng/mL. At T1, the cTnI concentration was significantly higher (P < 0.001) in all 25 camels compared to values at T0. The CK-MB concentration in the camels was 0.19 ± 0.05 ng/mL. All the camels had resting CK-MB concentrations of <0.33 ng/mL. At T1, the CK-MB concentration was higher in 3/25 camels compared to values at both T0 and T2. Concerning the hematobiochemical variables, significant increases were detected at T1 in total white blood cells, total protein, globulin, magnesium and phosphorus. Cardiac troponin I, CK-MB and all the hematobiochemical parameters had returned to their pre-transport values at T2. 5 h road transportation might have transient adverse effects on the cardiac muscle of healthy camels. Copyright © 2013 Elsevier B.V. All rights reserved.

Antioxidant treatment improves neonatal survival and prevents impaired cardiac function at adulthood following neonatal glucocorticoid therapy

PubMed Central

Niu, Youguo; Herrera, Emilio A; Evans, Rhys D; Giussani, Dino A

2013-01-01

Glucocorticoids are widely used to treat chronic lung disease in premature infants but their longer-term adverse effects on the cardiovascular system raise concerns. We reported that neonatal dexamethasone treatment in rats induced in the short term molecular indices of cardiac oxidative stress and cardiovascular tissue remodelling at weaning, and that neonatal combined antioxidant and dexamethasone treatment was protective at this time. In this study, we investigated whether such effects of neonatal dexamethasone have adverse consequences for NO bioavailability and cardiovascular function at adulthood, and whether neonatal combined antioxidant and dexamethasone treatment is protective in the adult. Newborn rat pups received daily i.p. injections of a human-relevant tapering dose of dexamethasone (D; n= 8; 0.5, 0.3, 0.1 μg g−1) or D with vitamins C and E (DCE; n= 8; 200 and 100 mg kg−1, respectively) on postnatal days 1–3 (P1–3); vitamins were continued from P4 to P6. Controls received equal volumes of vehicle from P1 to P6 (C; n= 8). A fourth group received vitamins alone (CCE; n= 8). At P100, plasma NO metabolites (NOx) was measured and isolated hearts were assessed under both Working and Langendorff preparations. Relative to controls, neonatal dexamethasone therapy increased mortality by 18% (P < 0.05). Surviving D pups at adulthood had lower plasma NOx concentrations (10.6 ± 0.8 vs. 28.0 ± 1.5 μm), an increased relative left ventricular (LV) mass (70 ± 2 vs. 63 ± 1%), enhanced LV end-diastolic pressure (14 ± 2 vs. 8 ± 1 mmHg) and these hearts failed to adapt output with increased preload (Δcardiac output: 2.9 ± 2.0 vs. 10.6 ± 1.2 ml min−1) or afterload (Δcardiac output: −5.3 ± 2.0 vs.1.4 ± 1.2 ml min−1); all P < 0.05. Combined neonatal dexamethasone with antioxidant vitamins improved postnatal survival, restored plasma NOx and protected against cardiac dysfunction at adulthood. In conclusion, neonatal dexamethasone therapy promotes

Incremental prognostic value of coronary computed tomography angiography over coronary calcium scoring for major adverse cardiac events in elderly asymptomatic individuals

PubMed Central

Han, Donghee; Hartaigh, Bríain Ó; Gransar, Heidi; Lee, Ji Hyun; Rizvi, Asim; Baskaran, Lohendran; Schulman-Marcus, Joshua; Dunning, Allison; Achenbach, Stephan; Al-Mallah, Mouaz H; Berman, Daniel S; Budoff, Matthew J; Cademartiri, Filippo; Maffei, Erica; Callister, Tracy Q; Chinnaiyan, Kavitha; Chow, Benjamin J W; DeLago, Augustin; Hadamitzky, Martin; Hausleiter, Joerg; Kaufmann, Philipp A; Raff, Gilbert; Shaw, Leslee J; Villines, Todd C; Kim, Yong-Jin; Leipsic, Jonathon; Feuchtner, Gudrun; Cury, Ricardo C; Pontone, Gianluca; Andreini, Daniele; Marques, Hugo; Rubinshtein, Ronen; Hindoyan, Niree; Jones, Erica C; Gomez, Millie; Lin, Fay Y; Chang, Hyuk-Jae; Min, James K

2018-01-01

Abstract Aims Coronary computed tomography angiography (CCTA) and coronary artery calcium score (CACS) have prognostic value for coronary artery disease (CAD) events beyond traditional risk assessment. Age is a risk factor with very high weight and little is known regarding the incremental value of CCTA over CAC for predicting cardiac events in older adults. Methods and results Of 27 125 individuals undergoing CCTA, a total of 3145 asymptomatic adults were identified. This study sample was categorized according to tertiles of age (cut-off points: 52 and 62 years). CAD severity was classified as 0, 1–49, and ≥50% maximal stenosis in CCTA, and further categorized according to number of vessels ≥50% stenosis. The Framingham 10-year risk score (FRS) and CACS were employed as major covariates. Major adverse cardiovascular events (MACE) were defined as a composite of all-cause death or non-fatal MI. During a median follow-up of 26 months (interquartile range: 18–41 months), 59 (1.9%) MACE occurred. For patients in the top age tertile, CCTA improved discrimination beyond a model included FRS and CACS (C-statistic: 0.75 vs. 0.70, P-value = 0.015). Likewise, the addition of CCTA improved category-free net reclassification (cNRI) of MACE in patients within the highest age tertile (e.g. cNRI = 0.75; proportion of events/non-events reclassified were 50 and 25%, respectively; P-value <0.05, all). CCTA displayed no incremental benefit beyond FRS and CACS for prediction of MACE in the lower age tertiles. Conclusion CCTA provides added prognostic value beyond cardiac risk factors and CACS for the prediction of MACE in asymptomatic older adults. PMID:28977374

The effect of malaria and anti-malarial drugs on skeletal and cardiac muscles.

PubMed

Marrelli, Mauro Toledo; Brotto, Marco

2016-11-02

Malaria remains one of the most important infectious diseases in the world, being a significant public health problem associated with poverty and it is one of the main obstacles to the economy of an endemic country. Among the several complications, the effects of malaria seem to target the skeletal muscle system, leading to symptoms, such as muscle aches, muscle contractures, muscle fatigue, muscle pain, and muscle weakness. Malaria cause also parasitic coronary artery occlusion. This article reviews the current knowledge regarding the effect of malaria disease and the anti-malarial drugs on skeletal and cardiac muscles. Research articles and case report publications that addressed aspects that are important for understanding the involvement of malaria parasites and anti-malarial therapies affecting skeletal and cardiac muscles were analysed and their findings summarized. Sequestration of red blood cells, increased levels of serum creatine kinase and reduced muscle content of essential contractile proteins are some of the potential biomarkers of the damage levels of skeletal and cardiac muscles. These biomarkers might be useful for prevention of complications and determining the effectiveness of interventions designed to protect cardiac and skeletal muscles from malaria-induced damage.

Adverse effects associated with photodynamic therapy (PDT) of port-wine stain (PWS) birthmarks.

PubMed

Yuan, Kai-Hua; Gao, Jian-Hua; Huang, Zheng

2012-12-01

Several Chinese studies suggest that Hemoporfin-mediated photodynamic therapy (PDT) is an alternative treatment for port-wine stain (PWS) birthmarks. To evaluate treatment responses and adverse effects associated with Hemoporfin PDT for the treatment of PWS and their management. The medical records of 700 patients who underwent PDT treatment in our center were retrospectively examined. Treatment-related reactions and adverse effects were reviewed. Different types of PWS lesions and different individuals showed different immediate responses (e.g. swelling, color change, pain). To certain extents these reactions were a useful indicator of the treatment endpoint. Edema and scabbing were the most common post-treatment responses. Short-term (e.g. blister, eczematous dermatitis, cutaneous photosensitivity) and long-term (e.g. pigmentation change, scar formation) adverse effects were generally caused by the phototoxicity associated with the combination of photosensitizer and light exposure. Although PDT is a safe treatment alternative for PWS birthmarks, treatment parameters must be selected for each individual patient and cutaneous changes must be monitored during light irradiation to minimize the risk of adverse effects. Over estimation of required light dosage or failure to recognize cutaneous changes associated with adverse effects can increase the risk of a poor outcome. Copyright © 2012 Elsevier B.V. All rights reserved.

Right bundle branch block as a risk factor for subsequent cardiac events.

DOT National Transportation Integrated Search

1990-08-01

The identification of risk factors for adverse cardiac events is valuable to the certification of airmen. This study examines the importance of right bundle branch block (RBBB) as a risk factor for myocardial infarction (MI), atherosclerotic heart di...

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

Treatment of Functional Abdominal Pain With Antidepressants: Benefits, Adverse Effects, and the Gastroenterologist's Role.

PubMed

Zar-Kessler, Claire A M; Belkind-Gerson, Jaime; Bender, Suzanne; Kuo, Braden M

2017-07-01

Pediatric functional abdominal pain is often treated with tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs). The aim is investigating antidepressant use for treatment efficacy, correlation of response to psychiatric factors, and impact of adverse effects in regard to physicians' prescribing patterns. Retrospective review (2005-2013) children (5-21 years old) with functional abdominal pain treated with SSRI or TCA. Of the 531 cases with functional abdominal pain, 192 initiated SSRIs or TCAs while followed by gastroenterology. Charts reviewed for symptoms, adverse effects, and response: decreased pain or increased daily functioning. Sixty-three of 84 (75%) SSRI patients improved, 56 of 92 (61%) TCA patients improved (P = 0.03). Logistic regression controlling for psychiatric factors: SSRI remained significant over TCA (P = 0.04). Thirty-two of 67 (48%) patients with constipation received TCAs and 26 of 45 (58%) patients with diarrhea received SSRIs (P = 0.64). Three SSRI patients reported gastrointestinal effects, all diarrheal-type symptoms, and 2 TCA patients reported gastrointestinal effects, both constipation, in all it led to discontinuation. Thirteen (29%) of diarrheal-type patients reported adverse effects causing discontinuation as compared to 7 (8%) in the constipation group (P = .01). Twenty-one (25%) SSRI patients reported adverse effects with 5 (6%) mood disturbances. Twenty (22%) TCA patients reported adverse effects, 13 (14%) with mood disturbances (P = .07). Overall, 12 (14%) SSRI patients discontinued medication due to adverse effects, whereas 16 (17%) TCA patients (P = 0.24) did. Patients had significantly greater response to SSRIs than TCAs, remaining significant after controlling for psychiatric factors. Little significance is given to patient's associated gastrointestinal symptoms, frequently resulting in adverse effects and termination of medication.

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...

Liposome encapsulated berberine treatment attenuates cardiac dysfunction after myocardial infarction.

PubMed

Allijn, Iris E; Czarny, Bertrand M S; Wang, Xiaoyuan; Chong, Suet Yen; Weiler, Marek; da Silva, Acarilia Eduardo; Metselaar, Josbert M; Lam, Carolyn Su Ping; Pastorin, Giorgia; de Kleijn, Dominique P V; Storm, Gert; Wang, Jiong-Wei; Schiffelers, Raymond M

2017-02-10

Inflammation is a known mediator of adverse ventricular remodeling after myocardial infarction (MI) that may lead to reduction of ejection fraction and subsequent heart failure. Berberine is a isoquinoline quarternary alkaloid from plants that has been associated with anti-inflammatory, anti-oxidative, and cardioprotective properties. Its poor solubility in aqueous buffers and its short half-life in the circulation upon injection, however, have been hampering the extensive usage of this natural product. We hypothesized that encapsulation of berberine into long circulating liposomes could improve its therapeutic availability and efficacy by protecting cardiac function against MI in vivo. Berberine-loaded liposomes were prepared by ethanol injection and characterized. They contained 0.3mg/mL of the drug and were 0.11μm in diameter. Subsequently they were tested for IL-6 secretion inhibition in RAW 264.7 macrophages and for cardiac function protection against adverse remodeling after MI in C57BL/6J mice. In vitro, free berberine significantly inhibited IL-6 secretion (IC 50 =10.4μM), whereas encapsulated berberine did not as it was not released from the formulation in the time frame of the in vitro study. In vivo, berberine-loaded liposomes significantly preserved the cardiac ejection fraction at day 28 after MI by 64% as compared to control liposomes and free berberine. In conclusion, liposomal encapsulation enhanced the solubility of berberine in buffer and preserves ejection fraction after MI. This shows that delivery of berberine-loaded liposomes significantly improves its therapeutic availability and identifies berberine-loaded liposomes as potential treatment of adverse remodeling after MI. Copyright © 2017 Elsevier B.V. All rights reserved.

Cardiac complications in beta-thalassemia: From mice to men.

PubMed

Kumfu, Sirinart; Fucharoen, Suthat; Chattipakorn, Siriporn C; Chattipakorn, Nipon

2017-06-01

Beta-thalassemia is an inherited hemoglobin disorder caused by reduced or absent synthesis of the beta globin chains of hemoglobin. This results in variable outcomes ranging from clinically asymptomatic to severe anemia, which then typically requires regular blood transfusion. These regular blood transfusions can result in an iron overload condition. The iron overload condition can lead to iron accumulation in various organs, especially in the heart, leading to iron overload cardiomyopathy, which is the major cause of mortality in patients with thalassemia. In the past decades, there is no doubt that the use of β-thalassemic mice as a study model to investigate the pathophysiology of iron overload cardiomyopathy and the role of various pharmacological interventions, has shed some light in understanding this serious complication and in improving the associated cardiac dysfunction. In this review, the effects that iron overload has on the hearts of β-thalassemic mice under conditions of iron overload as well as the efficacy of pharmacological interventions to combat these adverse effects on the heart are reviewed and discussed. The in-depth understanding of biomolecular alterations in the heart of these iron overload thalassemic mice will help give guidance for more effective therapeutic approaches in the near future. Impact statement Iron overload cardiomyopathy is a major cause of morbidity and mortality in patients with thalassemia. Since investigation of iron overload cardiomyopathy in thalassemia patients has many limitations, a search for an animal model for this condition has been ongoing for decades. In the past decades, there is no doubt that the use of β-thalassemic mice as a study model to investigate the pathophysiology of iron overload cardiomyopathy and the role of various pharmacological interventions, has shed some light in understanding this serious complication and in improving the associated cardiac dysfunction. In this review, the effects of

Cardiac complications in beta-thalassemia: From mice to men

PubMed Central

Kumfu, Sirinart; Fucharoen, Suthat; Chattipakorn, Siriporn C.

2017-01-01

Beta-thalassemia is an inherited hemoglobin disorder caused by reduced or absent synthesis of the beta globin chains of hemoglobin. This results in variable outcomes ranging from clinically asymptomatic to severe anemia, which then typically requires regular blood transfusion. These regular blood transfusions can result in an iron overload condition. The iron overload condition can lead to iron accumulation in various organs, especially in the heart, leading to iron overload cardiomyopathy, which is the major cause of mortality in patients with thalassemia. In the past decades, there is no doubt that the use of β-thalassemic mice as a study model to investigate the pathophysiology of iron overload cardiomyopathy and the role of various pharmacological interventions, has shed some light in understanding this serious complication and in improving the associated cardiac dysfunction. In this review, the effects that iron overload has on the hearts of β-thalassemic mice under conditions of iron overload as well as the efficacy of pharmacological interventions to combat these adverse effects on the heart are reviewed and discussed. The in-depth understanding of biomolecular alterations in the heart of these iron overload thalassemic mice will help give guidance for more effective therapeutic approaches in the near future. Impact statement Iron overload cardiomyopathy is a major cause of morbidity and mortality in patients with thalassemia. Since investigation of iron overload cardiomyopathy in thalassemia patients has many limitations, a search for an animal model for this condition has been ongoing for decades. In the past decades, there is no doubt that the use of β-thalassemic mice as a study model to investigate the pathophysiology of iron overload cardiomyopathy and the role of various pharmacological interventions, has shed some light in understanding this serious complication and in improving the associated cardiac dysfunction. In this review, the effects of

Geranylgeranylacetone blocks doxorubicin-induced cardiac toxicity and reduces cancer cell growth and invasion through RHO pathway inhibition.

PubMed

Sysa-Shah, Polina; Xu, Yi; Guo, Xin; Pin, Scott; Bedja, Djahida; Bartock, Rachel; Tsao, Allison; Hsieh, Angela; Wolin, Michael S; Moens, An; Raman, Venu; Orita, Hajime; Gabrielson, Kathleen L

2014-07-01

Doxorubicin is a widely used chemotherapy for solid tumors and hematologic malignancies, but its use is limited due to cardiotoxicity. Geranylgeranylacetone (GGA), an antiulcer agent used in Japan for 30 years, has no significant adverse effects, and unexpectedly reduces ovarian cancer progression in mice. Because GGA reduces oxidative stress in brain and heart, we hypothesized that GGA would prevent oxidative stress of doxorubicin cardiac toxicity and improve doxorubicin's chemotherapeutic effects. Nude mice implanted with MDA-MB-231 breast cancer cells were studied after chronic treatment with doxorubicin, doxorubicin/GGA, GGA, or saline. Transthoracic echocardiography was used to monitor systolic heart function and xenografts evaluated. Mice were euthanized and cardiac tissue evaluated for reactive oxygen species generation, TUNEL assay, and RHO/ROCK pathway analysis. Tumor metastases were evaluated in lung sections. In vitro studies using Boyden chambers were performed to evaluate GGA effects on RHO pathway activator lysophosphatidic acid (LPA)-induced motility and invasion. We found that GGA reduced doxorubicin cardiac toxicity, preserved cardiac function, prevented TUNEL-positive cardiac cell death, and reduced doxorubicin-induced oxidant production in a nitric oxide synthase-dependent and independent manner. GGA also reduced heart doxorubicin-induced ROCK1 cleavage. Remarkably, in xenograft-implanted mice, combined GGA/doxorubicin treatment decreased tumor growth more effectively than doxorubicin treatment alone. As evidence of antitumor effect, GGA inhibited LPA-induced motility and invasion by MDA-MB-231 cells. These anti-invasive effects of GGA were suppressed by geranylgeraniol suggesting GGA inhibits RHO pathway through blocking geranylation. Thus, GGA protects the heart from doxorubicin chemotherapy-induced injury and improves anticancer efficacy of doxorubicin in breast cancer. ©2014 American Association for Cancer Research.

Positive affect moderates the effect of negative affect on cardiovascular disease-related hospitalizations and all-cause mortality after cardiac rehabilitation.

PubMed

Meyer, Fiorenza Angela; von Känel, Roland; Saner, Hugo; Schmid, Jean-Paul; Stauber, Stefanie

2015-10-01

Little is known as to whether negative emotions adversely impact the prognosis of patients who undergo cardiac rehabilitation. We prospectively investigated the predictive value of state negative affect (NA) assessed at discharge from cardiac rehabilitation for prognosis and the moderating role of positive affect (PA) on the effect of NA on outcomes. A total of 564 cardiac patients (62.49 ± 11.51) completed a comprehensive three-month outpatient cardiac rehabilitation program, filling in the Global Mood Scale (GMS) at discharge. The combined endpoint was cardiovascular disease (CVD)-related hospitalizations plus all-cause mortality at follow-up. Cox regression models estimated the predictive value of NA, as well as the moderating influence of PA on outcomes. Survival models were adjusted for sociodemographic factors, traditional cardiovascular risk factors, and severity of disease. During a mean follow-up period of 3.4 years, 71 patients were hospitalized for a CVD-related event and 15 patients died. NA score (range 0-20) was a significant and independent predictor (hazard ratio (HR) 1.091, 95% confidence interval (CI) 1.012-1.175; p = 0.023) with a three-point higher level in NA increasing the relative risk by 9.1%. Furthermore, PA interacted significantly with NA (p < 0.001). The relative risk of poor prognosis with NA was increased in patients with low PA (p = 0.012) but remained unchanged in combination with high PA (p = 0.12). The combination of NA with low PA was particularly predictive of poor prognosis. Whether reduction of NA and increase of PA, particularly in those with high NA, improves outcome needs to be tested. © The European Society of Cardiology 2014.

Disproportionality analysis of buprenorphine transdermal system and cardiac arrhythmia using FDA and WHO postmarketing reporting system data.

PubMed

Sessler, Nelson E; Walker, Ekaterina; Chickballapur, Harsha; Kacholakalayil, James; Coplan, Paul M

2017-01-01

Positive-controlled clinical studies have shown a dose dependent effect of buprenorphine transdermal system on QTc interval prolongation. This study provides assessment of the buprenorphine transdermal system and cardiac arrhythmia using US FDA and WHO postmarketing reporting databases. Disproportionality analysis of spontaneously reported adverse events to assess whether the reporting rate of cardiac arrhythmia events was disproportionately elevated relative to expected rates of reporting in both FDA and WHO databases. Cardiac arrhythmia events were identified using the standardized Medical Dictionary for Regulatory Activities query for torsade de pointes and/or QT prolongation (TdP/QTP). The threshold for a signal of disproportionate adverse event reporting was defined as the lower 90% confidence limit ≥ 2 of the Empiric Bayes geometric mean in FDA database and as the lower 95% confidence limit of the Informational Component >0 in WHO database. There were 124 (<1%) and 77 (2%) cardiac arrhythmia event cases associated with buprenorphine transdermal as compared to 3206 (12%) and 2913 (14%) involving methadone in the FDA and WHO databases, respectively. In the FDA database methadone was associated with a signal of disproportionate reporting for TdP/QTP (EB05 3.26); however, buprenorphine transdermal was not (EB05 0.33). In the WHO database methadone was associated with a signal of disproportionate reporting for TdP/QTP (IC025 2.66); however, buprenorphine transdermal was not (IC025 -0.88). Similar trends were observed in sensitivity analyses by age, gender, and specific terms related to ventricular arrhythmia. The signal identified in the transdermal buprenorphine thorough QTc study, which led to a dose limitation in its US label, does not translate into a signal of increased risk for cardiac arrhythmia in real world use, as assessed by this method of analyzing post-market surveillance data.

FEMALE SEX AND DISCONTINUATION OF ISONIAZID DUE TO ADVERSE EFFECTS DURING THE TREATMENT OF LATENT TUBERCULOSIS

PubMed Central

Pettit, April C.; Bethel, James; Hirsch-Moverman, Yael; Colson, Paul W.; Sterling, Timothy R.

2013-01-01

SUMMARY Objectives To determine the rate of and risk factors for discontinuation of isoniazid due to adverse effects during the treatment of latent tuberculosis infection in a large, multi-site study. Methods The Tuberculosis Epidemiologic Studies Consortium (TBESC) conducted a prospective study from March 2007–September 2008 among adults initiating isoniazid for treatment of LTBI at 12 sites in the US and Canada. The relative risk for isoniazid discontinuation due to adverse effects was determined using negative binomial regression. Adjusted models were constructed using forward stepwise regression. Results Of 1,306 persons initiating isoniazid, 617 (47.2%, 95% CI 44.5–50.0%) completed treatment and 196 (15.0%, 95% CI 13.1–17.1%) discontinued due to adverse effects. In multivariable analysis, female sex (RR 1.67, 95% CI 1.32–2.10, p<0.001) and current alcohol use (RR 1.41, 95% CI 1.13–1.77, p=0.003) were independently associated with isoniazid discontinuation due to adverse effects. Conclusions The rate of discontinuation of isoniazid due to adverse effects was substantially higher than reported earlier. Women were at increased risk of discontinuing isoniazid due to adverse effects; close monitoring of women for adverse effects may be warranted. Current alcohol use was also associated with isoniazid discontinuation; counseling patients to abstain from alcohol could decrease discontinuation due to adverse effects. PMID:23845828

N-Terminal Pro-B-type Natriuretic Peptide Is Useful to Predict Cardiac Complications Following Lung Resection Surgery

PubMed Central

Lee, Chang Young; Bae, Mi Kyung; Lee, Jin Gu; Kim, Kwan-Wook; Park, In Kyu

2011-01-01

Background Cardiovascular complications are major causes of morbidity and mortality following non-cardiac thoracic operations. Recent studies have demonstrated that elevation of N-Terminal Pro-B-type natriuretic peptide (NT-proBNP) levels can predict cardiac complications following non-cardiac major surgery as well as cardiac surgery. However, there is little information on the correlation between lung resection surgery and NT-proBNP levels. We evaluated the role of NT-proBNP as a potential marker for the risk stratification of cardiac complications following lung resection surgery. Material and Methods Prospectively collected data of 98 patients, who underwent elective lung resection from August 2007 to February 2008, were analyzed. Postoperative adverse cardiac events were categorized as myocardial injury, ECG evidence of ischemia or arrhythmia, heart failure, or cardiac death. Results Postoperative cardiac complications were documented in 9 patients (9/98, 9.2%): Atrial fibrillation in 3, ECG-evidenced ischemia in 2 and heart failure in 4. Preoperative median NT-proBNP levels was significantly higher in patients who developed postoperative cardiac complications than in the rest (200.2 ng/L versus 45.0 ng/L, p=0.009). NT-proBNP levels predicted adverse cardiac events with an area under the receiver operating characteristic curve of 0.76 [95% confidence interval (CI) 0.545~0.988, p=0.01]. A preoperative NT-proBNP value of 160 ng/L was found to be the best cut-off value for detecting postoperative cardiac complication with a positive predictive value of 0.857 and a negative predictive value of 0.978. Other factors related to cardiac complications by univariate analysis were a higher American Society of Anesthesiologists grade, a higher NYHA functional class and a history of hypertension. In multivariate analysis, however, high preoperative NT-proBNP level (>160 ng/L) only remained significant. Conclusion An elevated preoperative NT-proBNP level is identified as an

Thrombosis and systemic and cardiac oxidative stress and DNA damage induced by pulmonary exposure to diesel exhaust particles and the effect of nootkatone thereon.

PubMed

Nemmar, Abderrahim; Al-Salam, Suhail; Beegam, Sumaya; Yuvaraju, Priya; Ali, Badreldin H

2018-05-01

Adverse cardiovascular effects of particulate air pollution persist even at lower concentrations than those of the current air quality limit. Therefore, identification of safe and effective measures against particle-induced cardiovascular toxicity is needed. Nootkatone is a sesquiterpenoid in grapefruit with diverse bioactivities including anti-inflammatory and antioxidant effects. However, its protective effect on the cardiovascular injury induced by diesel exhaust particles (DEPs) has not been studied before. We assessed the possible protective effect of nootkatone (90 mg/kg) administered by gavage 1 h before intratracheal instillation of DEPs (30 μg/mouse). Twenty-four hours after the intratracheal administration of DEPs, various thrombotic and cardiac parameters were assessed. Nootkatone inhibited the prothrombotic effect induced by DEPs in pial arterioles and venules in vivo and platelet aggregation in whole blood in vitro. Also, nootkatone prevented the shortening of activated partial thromboplastin time and prothrombin time induced by DEPs. Nootkatone inhibited the increase of plasma concentration of fibrinogen, plasminogen activator inhibitor-1, interleukin-6, and lipid peroxidation induced by DEPs. Immunohistochemically, hearts showed an analogous increase in glutathione and nuclear factor erythroid-derived 2-like 2 expression by cardiac myocytes and endothelial cells after DEP exposure, and these effects were enhanced in mice treated with nootkatone + DEPs. Likewise, heme oxygenase-1 was increased in mice treated with nootkatone + DEPs compared with those treated with DEPs or nootkatone + saline. The DNA damage caused by DEPs was prevented by nootkatoone pretreatment. In conclusion, nootkatoone alleviates DEP-induced thrombogenicity and systemic and cardiac oxidative stress and DNA damage, at least partly, through nuclear factor erythroid-derived 2-like 2 and heme oxygenase-1 activation. NEW & NOTEWORTHY Nootkatoone, a sesquiterpenoid found in grapefruit

Cardiac rehabilitation increases physical capacity but not mental health after heart valve surgery: a randomised clinical trial.

PubMed

Sibilitz, Kirstine L; Berg, Selina K; Rasmussen, Trine B; Risom, Signe Stelling; Thygesen, Lau C; Tang, Lars; Hansen, Tina B; Johansen, Pernille Palm; Gluud, Christian; Lindschou, Jane; Schmid, Jean Paul; Hassager, Christian; Køber, Lars; Taylor, Rod S; Zwisler, Ann-Dorthe

2016-12-15

The evidence for cardiac rehabilitation after valve surgery remains sparse. Current recommendations are therefore based on patients with ischaemic heart disease. The aim of this randomised clinical trial was to assess the effects of cardiac rehabilitation versus usual care after heart valve surgery. The trial was an investigator-initiated, randomised superiority trial (The CopenHeart VR trial, VR; valve replacement or repair). We randomised 147 patients after heart valve surgery 1:1 to 12 weeks of cardiac rehabilitation consisting of physical exercise and monthly psycho-educational consultations (intervention) versus usual care without structured physical exercise or psycho-educational consultations (control). Primary outcome was physical capacity measured by VO 2 peak and secondary outcome was self-reported mental health measured by Short Form-36. 76% were men, mean age 62 years, with aortic (62%), mitral (36%) or tricuspid/pulmonary valve surgery (2%). Cardiac rehabilitation compared with control had a beneficial effect on VO 2 peak at 4 months (24.8 mL/kg/min vs 22.5 mL/kg/min, p=0.045) but did not affect Short Form-36 Mental Component Scale at 6 months (53.7 vs 55.2 points, p=0.40) or the exploratory physical and mental outcomes. Cardiac rehabilitation increased the occurrence of self-reported non-serious adverse events (11/72 vs 3/75, p=0.02). Cardiac rehabilitation after heart valve surgery significantly improves VO 2 peak at 4 months but has no effect on mental health and other measures of exercise capacity and self-reported outcomes. Further research is needed to justify cardiac rehabilitation in this patient group. NCT01558765, 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/.

Efficacy and Adverse Effects of Atropine in Childhood Myopia: A Meta-analysis.

PubMed

Gong, Qianwen; Janowski, Miroslaw; Luo, Mi; Wei, Hong; Chen, Bingjie; Yang, Guoyuan; Liu, Longqian

2017-06-01

Some uncertainty about the clinical value and dosing of atropine for the treatment of myopia in children remains. To evaluate the efficacy vs the adverse effects of various doses of atropine in the therapy for myopia in children. Data were obtained from PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials, from inception to April 30, 2016. The reference lists of published reviews and clinicaltrials.gov were searched for additional relevant studies. Key search terms included myopia, refractive errors, and atropine. Only studies published in English were included. Randomized clinical trials and cohort studies that enrolled patients younger than 18 years with myopia who received atropine in at least 1 treatment arm and that reported the annual rate of myopia progression and/or any adverse effects of atropine therapy were included in the analysis. Two reviewers independently abstracted the data. Heterogeneity was statistically quantified by Q, H, and I2 statistics, and a meta-analysis was performed using the random-effects model. The Cochrane Collaboration 6 aspects of bias and the Newcastle-Ottawa Scale were used to assess the risk for bias. The primary outcome was a difference in efficacy and the presence of adverse effects at different doses of atropine vs control conditions. The secondary outcomes included the differences in adverse effects between Asian and white patients. Nineteen unique studies involving 3137 unique children were included in the analysis. The weighted mean differences between the atropine and control groups in myopia progression were 0.50 diopters (D) per year (95% CI, 0.24-0.76 D per year) for low-dose atropine, 0.57 D per year (95% CI, 0.43-0.71 D per year) for moderate-dose atropine, and 0.62 D per year (95% CI, 0.45-0.79 D per year) for high-dose atropine (P < .001), which translated to a high effect size (Cohen d, 0.97, 1.76, and 1.94, respectively). All doses of atropine, therefore, were equally beneficial with

Isometric exercise: cardiovascular responses in normal and cardiac populations.

PubMed

Hanson, P; Nagle, F

1987-05-01

Isometric exercise produces a characteristic pressor increase in blood pressure which may be important in maintaining perfusion of muscle during sustained contraction. This response is mediated by combined central and peripheral afferent input to medullary cardiovascular centers. In normal individuals the increase in blood pressure is mediated by a rise in cardiac output with little or no change in systemic vascular resistance. However, the pressor response is also maintained during pharmacologic blockade or surgical denervation by increasing systemic vascular resistance. Left ventricular function is normally maintained or improves in normal subjects and cardiac patients with mild impairment of left ventricular contractility. Patients with poor left ventricular function may show deterioration during isometric exercise, although this pattern of response is difficult to predict from resting studies. Recent studies have shown that patients with uncomplicated myocardial infarction can perform submaximum isometric exercise such as carrying weights in the range of 30 to 50 lb without difficulty or adverse responses. In addition, many patients who show ischemic ST depression or angina during dynamic exercise may have a reduced ischemic response during isometric or combined isometric and dynamic exercise. Isometric exercises are frequently encountered in activities of daily living and many occupational tasks. Cardiac patients should be gradually exposed to submaximum isometric training in supervised cardiac rehabilitation programs. Specific job tasks that require isometric or combined isometric and dynamic activities may be evaluated by work simulation studies. This approach to cardiac rehabilitation may facilitate patients who wish to return to a job requiring frequent isometric muscle contraction. Finally, there is a need for additional research on the long-term effects of isometric exercise training on left ventricular hypertrophy and performance. The vigorous training

Enhanced cardiac perception is associated with increased susceptibility to framing effects.

PubMed

Sütterlin, Stefan; Schulz, Stefan M; Stumpf, Theresa; Pauli, Paul; Vögele, Claus

2013-07-01

Previous studies suggest in line with dual process models that interoceptive skills affect controlled decisions via automatic or implicit processing. The "framing effect" is considered to capture implicit effects of task-irrelevant emotional stimuli on decision-making. We hypothesized that cardiac awareness, as a measure of interoceptive skills, is positively associated with susceptibility to the framing effect. Forty volunteers performed a risky-choice framing task in which the effect of loss versus gain frames on decisions based on identical information was assessed. The results show a positive association between cardiac awareness and the framing effect, accounting for 24% of the variance in the framing effect. These findings demonstrate that good interoceptive skills are linked to poorer performance in risky choices based on ambivalent information when implicit bias is induced by task-irrelevant emotional information. These findings support a dual process perspective on decision-making and suggest that interoceptive skills mediate effects of implicit bias on decisions. Copyright © 2013 Cognitive Science Society, Inc.

Enabling social listening for cardiac safety monitoring: Proceedings from a drug information association-cardiac safety research consortium cosponsored think tank.

PubMed

Seifert, Harry A; Malik, Raleigh E; Bhattacharya, Mondira; Campbell, Kevin R; Okun, Sally; Pierce, Carrie; Terkowitz, Jeffrey; Turner, J Rick; Krucoff, Mitchell W; Powell, Gregory E

2017-12-01

This white paper provides a summary of the presentations and discussions from a think tank on "Enabling Social Listening for Cardiac Safety Monitoring" trials that was cosponsored by the Drug Information Association and the Cardiac Safety Research Consortium, and held at the White Oak headquarters of the US Food and Drug Administration on June 3, 2016. The meeting's goals were to explore current methods of collecting and evaluating social listening data and to consider their applicability to cardiac safety surveillance. Social listening is defined as the act of monitoring public postings on the Internet. It has several theoretical advantages for drug and device safety. First, these include the ability to detect adverse events that are "missed" by traditional sources and the ability to detect adverse events sooner than would be allowed by traditional sources, both by affording near-real-time access to data from culturally and geographically diverse sources. Social listening can also potentially introduce a novel patient voice into the conversation about drug safety, which could uniquely augment understanding of real-world medication use obtained from more traditional methodologies. Finally, it can allow for access to information about drug misuse and diversion. To date, the latter 2 of these have been realized. Although regulators from the Food and Drug Administration and the United Kingdom's Medicines and Healthcare Products Regulatory Agency participated in the think tank along with representatives from industry, academia, and patient groups, this article should not be construed to constitute regulatory guidance. Copyright © 2017 Elsevier Inc. All rights reserved.

Complementary and alternative medicine usage among cardiac patients: a descriptive study.

PubMed

Bahall, Mandreker

2015-03-31

The use of complementary and alternative medicine (CAM) persists, despite the availability of conventional medicine (CM), modernisation, globalisation, technological advancement, and limited scientific evidence supporting CAM. People with cardiovascular diseases often use CAM, despite possible major adverse effects and lack of evidence supporting CAM claims. This study explored CAM use among cardiac patients, the types of CAM used, reasons and factors that influence its use, and the association between patient demographics and CAM use. This cross-sectional quantitative study was conducted using quota sampling to survey 329 public clinic adult cardiac patients within the South-West Regional Health Authority (SWRHA) of Trinidad and Tobago. From 1 July 2012 to 31August 2012, each participant completed questionnaires, after consenting to participate. Data analysis included χ(2) tests and binary logistic regression. One hundred eighty-five (56.2%; standard error [SE] = 2.74%) patients used CAM. Herbal medicine was the most common CAM (85.9%; SE = 2.56%), followed by spiritual therapy/mind-body systems (61.6%; SE = 3.58%), physical therapy/body manipulation (13.5%; SE = 2.51%), alternative systems (8.1%; SE = 2.01%), and other methods (3.8%; SE = 1. 41%). The patients believed that CAM promotes health and wellness (79.5%; SE = 2.97%), assists in fighting illness (78.9%; SE = 3.00%), addresses the limitations of CM (69.2%; SE = 3.56%), alleviates symptoms (21.6%; SE = 6.51%), costs less than CM (21.6 %, SE = 3.03), and has fewer adverse/damaging effects than CM (29.7, SE =3.36), or they were disappointed with CM (12.4%, SE = 2.42). Ethnicity and religion were associated with CAM usage, but only ethnicity was a useful predictor of CAM use. Complementary and alternative medicine use was high among cardiac patients (56.2%, SE = 2.74%), and associated with ethnicity and religion. Friends, family, and perceived mode of

An Autonomic Link Between Inhaled Diesel Exhaust and Impaired Cardiac Performance: Insight From Treadmill and Doubutamine Challenges in Heart Failure-Prone Rats

EPA Science Inventory

Background: Short-term exposure to vehicular emissions is associated with adverse cardiac events. Diesel exhaust (DE) is an ubiquitous air pollutant believed to provoke cardiac events partly through imbalance of the sympathetic and parasympathetic branches of the autonomic nervo...

Fully automated ultrasensitive digital immunoassay for cardiac troponin I based on single molecule array technology.

PubMed

Jarolim, Petr; Patel, Purvish P; Conrad, Michael J; Chang, Lei; Melenovsky, Vojtech; Wilson, David H

2015-10-01

The association between increases in cardiac troponin and adverse cardiac outcomes is well established. There is a growing interest in exploring routine cardiac troponin monitoring as a potential early indicator of adverse heart health trends. Prognostic use of cardiac troponin measurements requires an assay with very high sensitivity and outstanding analytical performance. We report development and preliminary validation of an investigational assay meeting these requirements and demonstrate its applicability to cohorts of healthy individuals and patients with heart failure. On the basis of single molecule array technology, we developed a 45-min immunoassay for cardiac troponin I (cTnI) for use on a novel, fully automated digital analyzer. We characterized its analytical performance and measured cTnI in healthy individuals and heart failure patients in a preliminary study of assay analytical efficacy. The assay exhibited a limit of detection of 0.01 ng/L, a limit of quantification of 0.08 ng/L, and a total CV of 10% at 2.0 ng/L. cTnI concentrations were well above the assay limit of detection for all samples tested, including samples from healthy individuals. cTnI was significantly higher in heart failure patients, and exhibited increasing median and interquartile concentrations with increasing New York Heart Association classification of heart failure severity. The robust 2-log increase in sensitivity relative to contemporary high-sensitivity cardiac troponin immunoassays, combined with full automation, make this assay suitable for exploring cTnI concentrations in cohorts of healthy individuals and for the potential prognostic application of serial cardiac troponin measurements in both apparently healthy and diseased individuals. © 2015 American Association for Clinical Chemistry.

Prediction of significant conduction disease through noninvasive assessment of cardiac calcification.

PubMed

Mainigi, Sumeet K; Chebrolu, Lakshmi Hima Bindu; Romero-Corral, Abel; Mehta, Vinay; Machado, Rodolfo Rozindo; Konecny, Tomas; Pressman, Gregg S

2012-10-01

Cardiac calcification is associated with coronary artery disease, arrhythmias, conduction disease, and adverse cardiac events. Recently, we have described an echocardiographic-based global cardiac calcification scoring system. The objective of this study was to evaluate the severity of cardiac calcification in patients with permanent pacemakers as based on this scoring system. Patients with a pacemaker implanted within the 2-year study period with a previous echocardiogram were identified and underwent blinded global cardiac calcium scoring. These patients were compared to matched control patients without a pacemaker who also underwent calcium scoring. The study group consisted of 49 patients with pacemaker implantation who were compared to 100 matched control patients. The mean calcium score in the pacemaker group was 3.3 ± 2.9 versus 1.8 ± 2.0 (P = 0.006) in the control group. Univariate and multivariate analysis revealed glomerular filtration rate and calcium scoring to be significant predictors of the presence of a pacemaker. Echocardiographic-based calcium scoring correlates with the presence of severe conduction disease requiring a pacemaker. © 2012, Wiley Periodicals, Inc.

Adverse Effects of Nutraceuticals and Dietary Supplements.

PubMed

Ronis, Martin J J; Pedersen, Kim B; Watt, James

2018-01-06

Over 70% of Americans take some form of dietary supplement every day, and the supplement industry is currently big business, with a gross of over $28 billion. However, unlike either foods or drugs, supplements do not need to be registered or approved by the US Food and Drug Administration (FDA) prior to production or sales. Under the Dietary Supplement Health and Education Act of 1994, the FDA is restricted to adverse report monitoring postmarketing. Despite widespread consumption, there is limited evidence of health benefits related to nutraceutical or supplement use in well-nourished adults. In contrast, a small number of these products have the potential to produce significant toxicity. In addition, patients often do not disclose supplement use to their physicians. Therefore, the risk of adverse drug-supplement interactions is significant. An overview of the major supplement and nutraceutical classes is presented here, together with known toxic effects and the potential for drug interactions.

Warnings of adverse side effects can backfire over time.

PubMed

Steinhart, Yael; Carmon, Ziv; Trope, Yaacov

2013-09-01

Warnings that a promoted product can have adverse side effects (e.g., smoking cigarettes can cause cancer) should dampen the product's allure. We predicted that with temporal distance (e.g., when an ad relates to future consumption or was viewed some time earlier), this common type of warning can have a worrisome alternative consequence: It can ironically boost the product's appeal. Building on construal-level theory, we argue that this is because temporal distance evokes high-level construal, which deemphasizes side effects and emphasizes message trustworthiness. In four studies, we demonstrated this phenomenon. For example, participants could buy cigarettes or artificial sweeteners after viewing an ad promoting the product. Immediately afterward, the quantity that participants bought predictably decreased if the ad they saw included a warning about adverse side effects. With temporal distance (product to be delivered 3 months later, or 2 weeks after the ad was viewed), however, participants who had seen an ad noting the benefits of the product but warning of risky side effects bought more than those who had seen an ad noting only benefits.

Heat, heat waves, and out-of-hospital cardiac arrest.

PubMed

Kang, Si-Hyuck; Oh, Il-Young; Heo, Jongbae; Lee, Hyewon; Kim, Jungeun; Lim, Woo-Hyun; Cho, Youngjin; Choi, Eue-Keun; Yi, Seung-Muk; Sang, Do Shin; Kim, Ho; Youn, Tae-Jin; Chae, In-Ho; Oh, Seil

2016-10-15

Cardiac arrest is one of the common presentations of cardiovascular disorders and a leading cause of death. There are limited data on the relationship between out-of-hospital cardiac arrest (OHCA) and ambient temperatures, specifically extreme heat. This study investigated how heat and heat waves affect the occurrence of OHCA. Seven major cities in Korea with more than 1 million residents were included in this study. A heat wave was defined as a daily mean temperature above the 98th percentile of the yearly distribution for at least two consecutive days. A total of 50,318 OHCAs of presumed cardiac origin were identified from the nationwide emergency medical service database between 2006 and 2013. Ambient temperature and OHCA had a J-shaped relationship with a trough at 28°C. Heat waves were shown to be associated with a 14-% increase in the risk of OHCA. Adverse effects were apparent from the beginning of each heat wave period and slightly increased during its continuation. Excess OHCA events during heat waves occurred between 3PM and 5PM. Subgroup analysis showed that those 65years or older were significantly more susceptible to heat waves. Ambient temperature and OHCA had a J-shaped relationship. The risk of OHCA was significantly increased with heat waves. Excess OHCA events primarily occurred during the afternoon when the temperature was high. We found that the elderly were more susceptible to the deleterious effects of heat waves. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Adverse effects of nickel in transosseous wires and surgical implants: literature review.

PubMed

Nwashindi, A; Dim, E M

2014-01-01

Transosseous wires used in the management of fractures are stainless steel alloys which contain nickel 14.5%, chromium 17.6%, iron 62.5% and molybdenum 2.8%. Gradual disintegration of the transosseous wires release nickel into the blood leading to increase nickel concentration in the blood. Nickel has been found to have some adverse systemic effects on the body. The aim of this paper is to discuss the sources of Nickel in the body as well as the systemic adverse effects of Nickel as a degradation product of stainless steel surgical implants. A study of pertinent literature on nickel as a content of stainless steel alloy used in implant surgery was done, taking note also of other sources of nickel in the body, the toxicokinetics of nickel and the related adverse effects of this metal and its compound in humans. As outcome,the sources of human exposure to nickel,distribution and metabolism of nickel in the body, host responseto stainless steel wires and the adverse effects of nickel in the body are presented. It may be necessary to discourage the use of wires or implants containing nickel in the management of fractures.The need for removal of these implants after they have served their purposes is emphasized.

Protective effects of isorhynchophylline on cardiac arrhythmias in rats and guinea pigs.

PubMed

Gan, Runtao; Dong, Guo; Yu, Jiangbo; Wang, Xu; Fu, Songbin; Yang, Shusen

2011-09-01

As one important constituent extracted from a traditional Chinese medicine, Uncaria Rhynchophylla Miq Jacks, isorhynchophylline has been used to treat hypertension, epilepsy, headache, and other illnesses. Whether isorhynchophylline protects hearts against cardiac arrhythmias is still incompletely investigated. This study was therefore aimed to examine the preventive effects of isorhynchophylline on heart arrhythmias in guinea pigs and rats and then explore their electrophysiological mechanisms. In vivo, ouabain and calcium chloride were used to establish experimental arrhythmic models in guinea pigs and rats. In vitro, the whole-cell patch-lamp technique was used to study the effect of isorhynchophylline on action potential duration and calcium channels in acutely isolated guinea pig and rat cardiomyocytes. The dose of ouabain required to induce cardiac arrhythmias was much larger in guinea pigs administered with isorhynchophylline. Additionally, the onset time of cardiac arrhythmias induced by calcium chloride was prolonged, and the duration was shortened in rats pretreated with isorhynchophylline. The further study showed that isorhynchophylline could significantly decrease action potential duration and inhibit calcium currents in isolated guinea pig and rat cardiomyocytes in a dose-dependent manner. In summary, isorhynchophylline played a remarkably preventive role in cardiac arrhythmias through the inhibition of calcium currents in rats and guinea pigs. © Georg Thieme Verlag KG Stuttgart · New York.

Sedation and Anesthesia in Pediatric and Congenital Cardiac Catheterization: A Prospective Multicenter Experience.

PubMed

Lin, C Huie; Desai, Sanyukta; Nicolas, Ramzi; Gauvreau, Kimberlee; Foerster, Susan; Sharma, Anshuman; Armsby, Laurie; Marshall, Audrey C; Odegard, Kirsten; DiNardo, James; Vincent, Julie; El-Said, Howaida; Spaeth, James; Goldstein, Bryan; Holzer, Ralf; Kreutzer, Jackie; Balzer, David; Bergersen, Lisa

2015-10-01

Sedation/anesthesia is critical to cardiac catheterization in the pediatric/congenital heart patient. We sought to identify current sedation/anesthesia practices, the serious adverse event rate related to airway, sedation, or anesthesia, and the rate of intra-procedural conversion from procedural sedation to the use of assisted ventilation or an artificial airway. Data from 13,611 patients who underwent catheterization at eight institutions were prospectively collected from 2007 to 2010. Ninety-four (0.69 %) serious sedation/airway-related adverse events occurred; events were more likely to occur in smaller patients (<4 kg, OR 4.4, 95 % CI 2.3-8.2, p < 0.001), patients with non-cardiac comorbidities (OR 1.7, 95 % CI 1.1-26, p < 0.01), and patients with low mixed venous oxygen saturation (OR 2.3, 95 % CI 1.4-3.6, p < 0.001). Nine thousand three hundred and seventy-nine (69 %) patients were initially managed with general endotracheal anesthesia, LMA, or tracheostomy, whereas 4232 (31 %) were managed with procedural sedation without an artificial airway, of which 75 (1.77 %) patients were converted to assisted ventilation/general anesthesia. Young age (<12 months, OR 5.2, 95 % CI 2.3-11.4, p < 0.001), higher-risk procedure (category 4, OR 10.1, 95 % CI 6.5-15.6, p < 0.001), and continuous pressor/inotrope requirement (OR 11.0, 95 % CI 8.6-14.0, p < 0.001) were independently associated with conversion. Cardiac catheterization in pediatric/congenital patients was associated with a low rate of serious sedation/airway-related adverse events. Smaller patients with non-cardiac comorbidities or low mixed venous oxygen saturation may be at higher risk. Patients under 1 year of age, undergoing high-risk procedures, or requiring continuous pressor/inotrope support may be at higher risk of requiring conversion from procedural sedation to assisted ventilation/general anesthesia.

Effect of treatment for Chlamydia pneumoniae and Helicobacter pylori on markers of inflammation and cardiac events in patients with acute coronary syndromes: South Thames Trial of Antibiotics in Myocardial Infarction and Unstable Angina (STAMINA).

PubMed

Stone, Adam F M; Mendall, Michael A; Kaski, Juan-Carlos; Edger, Tracey M; Risley, Paul; Poloniecki, Jan; Camm, A John; Northfield, Timothy C

2002-09-03

Infection with Helicobacter pylori and Chlamydia pneumoniae is associated with coronary heart disease. We conducted an intervention study using antibiotics against these bacteria in patients with acute coronary syndromes to determine whether antibiotics reduce inflammatory markers and adverse cardiac events. Patients (n=325) admitted with acute myocardial infarction or unstable angina (acute coronary syndromes) were randomized to receive a 1-week course of 1 of 3 treatment regimens: (1) placebo; (2) amoxicillin (500 mg twice daily), metronidazole (400 mg twice daily), and omeprazole (20 mg twice daily); or (3) azithromycin (500 mg once daily), metronidazole (400 mg twice daily), and omeprazole (20 mg twice daily). Serum fibrinogen, white cell count, and high-sensitivity C-reactive protein were measured at study entry and at 1, 3, and 12 months during follow-up. Cardiac death and readmission with acute coronary syndrome were considered clinical end points. Patients were followed for 1 year. C-reactive protein levels were reduced (P=0.03) in unstable angina patients receiving amoxicillin, and fibrinogen was reduced in both patient groups receiving antibiotics (P=0.06). There were 17 cardiac deaths and 71 readmissions with acute coronary syndrome. No difference in frequency or timing of end points was observed between the 2 antibiotic groups. At 12 weeks, there was a 36% reduction in all end points in patients receiving antibiotics compared with placebo (P=0.02). This reduction persisted during the 1-year follow-up. Neither C pneumoniae nor H pylori antibody status was significantly related to response to treatment. Antibiotic treatment significantly reduced adverse cardiac events in patients with acute coronary syndromes, but the effect was independent of H pylori or C pneumoniae seropositivity.

Protease-Activated Receptor 1 Inhibition by SCH79797 Attenuates Left Ventricular Remodeling and Profibrotic Activities of Cardiac Fibroblasts

PubMed Central

Sonin, Dmitry L.; Wakatsuki, Tetsuro; Routhu, Kasi V.; Harmann, Leanne M.; Petersen, Matthew; Meyer, Jennifer; Strande, Jennifer L.

2013-01-01

Purpose Fibroblast activity promotes adverse left ventricular (LV) remodeling that underlies the development of ischemic cardiomyopathy. Transforming growth factor-β (TGF-β) is a potent stimulus for fibrosis, and the extracellular signal-regulated kinases(ERK) 1/2 pathway also contributes to the fibrotic response. The thrombin receptor, protease-activated receptor 1 (PAR1), has been shown to play an important role in the excessive fibrosis in different tissues. The aim of this study was to investigate the influence of a PAR1 inhibitor, SCH79797, on cardiac fibrosis, tissue stiffness and postinfarction remodeling, and effects of PAR1 inhibition on thrombin-induced TGF-β and (ERK) 1/2 activities in cardiac fibroblasts. Methods We used a rat model of myocardial ischemia–reperfusion injury, isolated cardiac fibroblasts, and 3-dimensional (3D) cardiac tissue models fabricated to ascertain the contribution of PAR1 activation on cardiac fibrosis and LV remodeling. Results The PAR1 inhibitor attenuated LV dilation and improved LV systolic function of the reperfused myocardium at 28 days. This improvement was associated with a nonsignificant decrease in scar size (%LV) from 23 ± % in the control group (n = 10) to 16% ± 5.5% in the treated group (n = 9; P = .052). In the short term, the PAR1 inhibitor did not rescue infarct size or LV systolic function after 3 days. The PAR1 inhibition abolished thrombin-mediated ERK1/2 phosphorylation, TGF-β and type I procollagen production, matrix metalloproteinase-2/9 activation, myofibroblasts transformation in vitro, and abrogated the remodeling of 3D tissues induced by chronic thrombin treatment. Conclusion These studies suggest PAR1 inhibition initiated after ischemic injury attenuates adverse LV remodeling through late-stage antifibrotic events. PMID:23598708