Mechanism Of Cardiac Dysfunction Research Articles

Risk factors affecting cardiac left-ventricular hypertrophy and systolic and diastolic function in the chronic phase of allogeneic hematopoietic cell transplantation

Chronic impairment of cardiac function can be an important health risk and impair the quality of life, and may even be life-threatening for long-term survivors of allogeneic hematopoietic cell transplantation (HCT). However, risk factors for and/or the underlying mechanism of cardiac dysfunction in the chronic phase of HCT are still not fully understood. We retrospectively investigated factors affecting cardiac function and left-ventricular hypertrophy (LVH) in the chronic phase of HCT. Sixty-three recipients who survived for >1 year after receiving HCT were evaluated using echocardiography. Based on simple linear regression models, high-dose TBI-based conditioning was significantly associated with a decrease in left-ventricular ejection fraction and the early peak flow velocity/atrial peak flow velocity ratio, following HCT (coefficient=-5.550, P=0.02 and coefficient=-0.268, P=0.02, respectively). These associations remained significant with the use of multiple linear regression models. Additionally, the serum ferritin (s-ferritin) level before HCT was found to be a significant risk factor for LVH on multivariable logistic analysis (P=0.03). In conclusion, our study demonstrated that a myeloablative regimen, especially one that involved high-dose TBI, impaired cardiac function, and that a high s-ferritin level might be associated with the development of LVH in the chronic phase of HCT.

Mechanisms of cardiac dysfunction in obstructive sleep apnea

Obstructive sleep apnea (OSA) is associated with cardiovascular morbidity and mortality, largely as a result of myocardial anomalies. Numerous mechanisms cause OSA-related myocardial damage. The majority are initiated as a result of OSA-induced, chronic, intermittent hypoxia. The most-important mechanisms that lead to myocardial damage are increased sympathetic activity, endothelial dysfunction, systemic inflammation, oxidative stress, and metabolic anomalies. All these mechanisms promote the development of hypertension, which is common in patients with OSA. Hypertensive cardiomyopathy and coronary heart disease, as well as obesity-related, diabetic, and tachycardia-induced cardiomyopathies, are also associated with OSA. Left ventricular hypertrophy, myocardial fibrosis, atrial dilatation, and left ventricular systolic and diastolic dysfunction in patients with OSA explain the association of the disease with these clinical outcomes. The gold-standard treatment for OSA, nasal continuous positive airway pressure (CPAP), might improve cardiac symptoms and hemodynamic parameters in patients with the disease. However, large clinical trials are required to improve our understanding of the cardiac consequences of OSA, and determine the effect of treatment, particularly CPAP, on myocardial damage in symptomatic patients and primary prevention of cardiovascular disorders.

Effect of haematocrit on echocardiographic indices of cardiac dimension in sickle cell anaemia.

Background: Several mechanisms have been put forward to explain myocardial dysfunction in sickle cell anaemia.Aims and objectives: This study was aimed at examining the effect of haematocrit parameters on echocardiographic indices of cardiac dimension in adult sickle cell anaemia patients.Methods: A descriptive cross sectional study was done using 60 patients and 60 controls at the adult sickle cell clinic of the University of Nigeria Teaching Hospital Enugu, Nigeria. All the participants had haematocrit estimation, haemoglobin electrophoresis, as well as echocardiographic evaluation.Results: The patients had significantly higher mean values than controls in the estimate of left atrial diameter, posterior wall thickness, left ventricular diameters and volumes, left ventricular mass as well as cardiac index, and right ventricular dimension. Significant correlations were demonstrated in the patient between haematocrit and (1) left atrial dimension {-0.418; p = 0.001}, (2) left ventricular mass index {r = - 0.268; p = 0.038 }. Regression model involving haematocrit accounted for 8.00% and 16.07% respectively of the variations in left ventricular mass (F=5.219;P=0.026), and left atrial dimension (F=11.488;P=0.001).Conclusion: The mechanism of cardiac dysfunction in the sickle cell anaemia is multifactorial with the combined effects of anaemia and sickling playing the major role.Key words: haematocrit, echocardiographic indices, cardiac dimension, sickle cell.

Activation of CaMKII as a key regulator of reactive oxygen species production in diabetic rat heart

Diabetes mellitus is a risk factor for heart failure. Increased reactive oxygen species (ROS) have been proposed as a possible mechanism of cardiac dysfunction in diabetic patients. However, the mechanisms of ROS increase are still elusive. We hypothesized that activation of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) induced by impaired intracellular Ca(2+) ([Ca(2+)](i)) metabolism may stimulate ROS production in the diabetic heart. Cultured cardiomyocytes from neonatal rats were exposed to high glucose concentrations (25 mmol/L) and ROS levels were analyzed in 5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate, acetyl ester (CM-H(2)DCFDA)-loaded cells by flow cytometry analysis. Exposure to high glucose concentrations for 24h significantly increased CM-H(2)DCFDA fluorescence, which was significantly inhibited by 1,2-bis (o-aminophenoxy) ethane- N,N,N',N'-tetraacetic acid tetraacetoxymethyl ester (BAPTA-AM), a [Ca(2+)](i) chelator, and KB-R7943, an inhibitor of the Na(+)-Ca(2+) exchanger (NCX) in the reverse mode. These results indicate that [Ca(2+)](i) increase by NCX activation may induce ROS increase following exposure to high glucose concentrations. We confirmed that exposure to high glucose concentrations significantly increased [Ca(2+)](i), which was inhibited by KB-R7943. Na(+)-H(+) exchanger (NHE) is a key factor in [Ca(2+)](i) metabolism, and is known to activate NCX by increasing the intracellular Na(+) ([Na(+)](i)) level. We showed that the expression of NHE isoform 1 and NHE activity increased following exposure to high glucose concentrations by evaluating protein expressions and intracellular pH recovery from acid loading. Exposure to high glucose concentrations up-regulated phosphorylated CaMKII expression in cardiomyocytes that was inhibited by KB-R7943. Further, autocamtide 2-related inhibitory peptide (AIP), a CaMKII inhibitor, significantly attenuated the ROS increase following exposure to high glucose concentrations. We confirmed these results obtained in in vitro experiments in an animal model of diabetes. ROS level and components of NADPH oxidase, p47phox and p67phox were up-regulated in streptozotocin-induced diabetic rat heart, which were attenuated by KN-93, a CaMKII inhibitor. Consistently, expression of phosphorylated CaMKII was increased in the diabetic heart. Activation of CaMKII by impaired [Ca(2+)](i) metabolism may be a mechanism of ROS increase in the heart with diabetes mellitus.

Abstract 18051: High Prevalence of Active Myocarditis in Patients with Takotsubo Cardiomyopathy: A Magnetic Resonance-endomyocardial Biopsy Study

Background: Tako-tsubo cardiomyopathy (TTC) was recently classified as a cardiomyopathy with distinct clinical and angiographic features, but mechanisms of cardiac dysfunction and histological substrate are still largely unclear. We evaluated cardiac magnetic resonance (CMR) and endomyocardial biopsy (EMB) findings in patients with TTC. Methods: Twenty consecutive patients (19 F, 58±12 years) with clinical and angiographic features of TTC underwent CMR with edema (STIR images) and delayed enhancement (DE) studies. Of these, 15 patients also underwent EMB. Myocardial samples obtained from apical akinetic left ventricular segments were processed for histology, immunohistochemistry and polymerase chain reaction (PCR) for cardiotropic viruses. Results: All patients presented acute chest pain with ST-segment elevation in anterior leads and evidence of myocardial necrosis. Symptoms were precipitated by emotional stress in 12 (60%) cases. At CMR DE was observed in 11 patients (55%) in all cases with a subepicardial or midventricular pattern; edema was observed in 10 (50%) patients, associated with DE in 8 cases. Neither DE nor edema was observed in 7 patients. In 11 patients (73%) EMB showed an active lymphocytic myocarditis with evidence of activated T lymphocytes. In 4 patients (27%) contraction band necrosis was observed. PCR identified parvovirus B19 viral genome in 3 patients with myocarditis. Among patients with a histological diagnosis of myocarditis CMR showed DE in 10 and edema in 8 cases. One patient with myocarditis had neither DE nor edema at CMR. Patients with contraction-band necrosis showed no DE or edema at CMR. Three myocarditis virus-negative patients failing to recovery after 6 weeks from clinical presentation, received prednisone and azathioprine for 8 weeks with significant improvement of left ventricular contractility. Conclusions: Acute myocarditis represents a frequent substrate of TTC. CMR may help to identify myocardial inflammation in TTC patients. Immunohistochemical and virological diagnosis through EMB may affect both treatment and prognosis. Further studies are needed to clarify the prevalence of acute myocarditis among TTC patients and the possible association between emotional stress and viral infection.

Pathophysiology and Therapy of Cardiac Dysfunction in Duchenne Muscular Dystrophy

Cardiac dysfunction is a frequent manifestation of Duchenne muscular dystrophy (DMD) and a common cause of death for individuals with this condition. Early diastolic dysfunction and focal fibrosis proceed to dilated cardiomyopathy (DCM), complicated by heart failure and arrhythmia in most patients. Improvements in the management of respiratory insufficiency in DMD have improved lifespan and overall prognosis, but heart failure and sudden death continue to impact survival and quality of life for people with DMD. Since the specific mechanisms resulting in heart failure for people with DMD are poorly understood, current treatments are not targeted, but rely on approaches that are considered standard for DCM. These approaches include angiotensin-converting enzyme (ACE) inhibitors and β-adrenoceptor antagonists. Data from one trial in DMD support the use of ACE inhibitors before the onset of left ventricular dysfunction. Angiotensin receptor blockers have shown similar efficacy to ACE inhibitors in numerous studies of dilated cardiomyopathy, and are a good choice for patients who cannot tolerate ACE inhibition. The pathogenesis of DMD-associated cardiomyopathy may be similar to other genetic disorders of the cytoskeletal complex of ventricular myocytes, though unique features offer targeted opportunities to impact treatment. Novel areas of investigation are focused on the regulatory role of dystrophin in relation to neuronal nitric oxide synthase (nNOS) and transient receptor potential canonical channels (TRPC). Inhibition of phosphodiesterase-5 (PDE5) addresses several aspects of regulatory dysfunction induced by dystrophin deficiency, and studies with PDE5-inhibitors have shown benefits in murine models of DMD. PDE5-inhibitors are currently under investigation in at least one study in humans. This article focuses on mechanisms of cardiac dysfunction, as well as potential targets for pharmacologic manipulation to prevent or improve cardiomyopathy in DMD.

Interval training does not decrease oxidative stress in the heart of mice

Physical exercise is characterized by an increase in O2 consumption by the whole body — particularly by heart tissues — linked with a rise in the production of ROS [ [1] Ascensão A. Ferreira R. Magalhães J. Exercise-induced cardioprotection biochemical, morphological and functional evidence in whole tissue and isolated mitochondria. Int J Cardiol. 2007; 117: 16-30 Abstract Full Text Full Text PDF PubMed Scopus (124) Google Scholar ], which in turn is associated with the mechanisms of cardiac dysfunction [ [2] Lefer D.J. Granger D.N. Oxidative stress and cardiac disease. Am J Med. 2000; 109: 315-323 Abstract Full Text Full Text PDF PubMed Scopus (400) Google Scholar ]. Studies on both involuntary treadmill exercise training [ [3] Silva L.A. Pinho C.A. Scarabelot K.S. et al. Physical exercise increases mitochondrial function and reduces oxidative damage in skeletal muscle. Eur J Appl Physiol. 2009; 105 (a): 861-867 Crossref PubMed Scopus (39) Google Scholar ] and voluntary wheel running [ [4] Allen D.L. Harrison B.C. Maass A. Bell M.L. Byrnes W.C. Leinwand L.A. Cardiac and skeletal muscle adaptations to voluntary wheel running in the mouse. J Appl Physiol. 2001; 90: 1900-1908 Crossref PubMed Scopus (268) Google Scholar ] in animals have consistently demonstrated that endurance with moderate intensity exercise is associated with increased aerobic capacity and improved oxidative stress parameters. Nevertheless, to date, no studies have compared the effect of interval training with continuous training on oxidative stress parameters in cardiac muscle.

Models of cardiac electromechanics based on individual hearts imaging data: image-based electromechanical models of the heart.

Current multi-scale computational models of ventricular electromechanics describe the full process of cardiac contraction on both the micro- and macro- scales including: the depolarization of cardiac cells, the release of calcium from intracellular stores, tension generation by cardiac myofilaments, and mechanical contraction of the whole heart. Such models are used to reveal basic mechanisms of cardiac contraction as well as the mechanisms of cardiac dysfunction in disease conditions. In this paper, we present a methodology to construct finite element electromechanical models of ventricular contraction with anatomically accurate ventricular geometry based on magnetic resonance and diffusion tensor magnetic resonance imaging of the heart. The electromechanical model couples detailed representations of the cardiac cell membrane, cardiac myofilament dynamics, electrical impulse propagation, ventricular contraction, and circulation to simulate the electrical and mechanical activity of the ventricles. The utility of the model is demonstrated in an example simulation of contraction during sinus rhythm using a model of the normal canine ventricles.

Mechanisms for cardiac dysfunction in COPD and respiratory failure

Mechanisms for cardiac dysfunction in COPD and respiratory failure

Circulating blood volumes in diabetic patients.

To examine the mechanism of cardiac dysfunction in diabetes, total circulating blood volume, cardiac and stroke volumes were measured by radioisotope method in 44 patients with type 1 and type 2 diabetes. Considerable difference in actually circulating blood volume could be demonstrated in diabetic patients, which seemed to be dependent on the control of the carbohydrate metabolism. The achievement of well controlled carbohydrate metabolism in diabetics has a great importance with special respect also to the blood volumes.

Effect and mechanisms underlying scorpion toxin action from Androctonus australis garzonii on atrial natriuretic peptide in rat atria: An in vitro study

Scorpion envenomation is considered public health problem in Northern African countries. The mechanisms of cardiac dysfunction following scorpion envenomation are not fully understood. This study examined the effect and mechanisms underlying scorpion toxin action from Androctonus australis garzonii on atrial natriuretic peptide (ANP) release from rat atrium using in vitro organ perifusion. Male Sprague Dawley rats were used in this study. Three experiments were conducted. In experiment 1, atrial tissues were exposed either to Krebs-bicarbonate buffer medium (control) or to scorpion toxin (10 −8 M to 10 −6 M). In experiment 2, animals were chemically sympathectomized with a single intraperitoneal injection of 6-hydroxydopamine (6-OHDOPA) at a dose of 40 μg/g 24 h before sacrifice. Vehicle-treated rats served as control. Atrial tissues were collected and perifused in the presence of 10 −6 M scorpion toxin. In experiment 3, atrial tissues were exposed to 10 −6 M scorpion toxin either in the absence or presence of 10 −6 M propranolol (a β-adrenoceptor blocker), or 10 −6 M tetrodotoxin (a sodium channel blocker). ANP levels released in the perifusion medium were determined by radioimmunoassay. The scorpion toxin at 10 −6 M induced a significant ( p < 0.01) increase (106%) in ANP levels. This effect was decreased (20%) by 6-OHDOPA. Propranolol and tetrodotoxin significantly ( p < 0.01) inhibited 55% and 60%, respectively, the toxin-induced ANP release. The data show that the North African scorpion toxin from Androctonus australis garzonii increases the ANP release in rat atrium through stimulation of sympathetic cardiac nerves and sodium channels activation.

Sepsis and the Heart

Sepsis is generally viewed as a disease aggravated by an inappropriate immune response encountered in the afflicted individual. As an important organ system frequently compromised by sepsis and always affected by septic shock, the cardiovascular system and its dysfunction during sepsis have been studied in clinical and basic research for more than 5 decades. Although a number of mediators and pathways have been shown to be associated with myocardial depression in sepsis, the precise cause remains unclear to date. There is currently no evidence supporting global ischemia as an underlying cause of myocardial dysfunction in sepsis; however, in septic patients with coexistent and possibly undiagnosed coronary artery disease, regional myocardial ischemia or infarction secondary to coronary artery disease may certainly occur. A circulating myocardial depressant factor in septic shock has long been proposed, and potential candidates for a myocardial depressant factor include cytokines, prostanoids, and nitric oxide, among others. Endothelial activation and induction of the coagulatory system also contribute to the pathophysiology in sepsis. Prompt and adequate antibiotic therapy accompanied by surgical removal of the infectious focus, if indicated and feasible, is the mainstay and also the only strictly causal line of therapy. In the presence of severe sepsis and septic shock, supportive treatment in addition to causal therapy is mandatory. The purpose of this review is to delineate some characteristics of septic myocardial dysfunction, to assess the most commonly cited and reported underlying mechanisms of cardiac dysfunction in sepsis, and to briefly outline current therapeutic strategies and possible future approaches.

National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines: Clinical Utilization of Cardiac Biomarker Testing in Heart Failure

### A. Context of Biochemical Marker Testing in Heart Failure Biochemical marker testing has revolutionized the approach to diagnosis and management of heart failure over the past decade. There is an unsurpassed excitement in the heart failure community that significant advances in our understanding of currently available and future cardiac biomarkers will facilitate improved characterization of heart failure disease states and promote individualized therapy in heart failure and beyond. However, like most novel diagnostic tests, the promising findings from pivotal trials have met with ongoing challenges when applied in the clinical setting. The material discussed in this guidelines document addresses clinical use of BNP/NT-proBNP and cardiac troponin testing in the context of heart failure diagnosis, risk stratification and management, including therapeutic guidance in adult (>18 year-old) patients. Together with the associated document titled “ National Academy of Clinical Biochemistry and IFCC Committee for Standardization of Markers of Cardiac Damage Laboratory Medicine Practice Guidelines: Analytical Issues for Biomarkers of Heart Failure ”, …

Increased PP1 and PP2A mediating reduced Ser16 phosphorylated PLB is a possible mechanism for cardiac dysfunction in alveolar hypoxia

We have previously reported right ventricular (RV) and left ventricular (LV) diastolic dysfunction in mice subjected to alveolar hypoxia, possibly mediated by reduced Serine (Ser) 16 phosphorylated phospholamban (PLB). We hypothesized that chronic alveolar hypoxia induces increased levels of circulating mediators which cause changes in the β-adrenergic signaling cascade or in phosphatases leading to reduced Ser16 phosphorylated PLB.

Effects of glutamine on matrix metalloproteinase-3 and tissue inhibitor of metalloproteinase-3 expressions in myocardium of rats with sepsis

The underlying mechanisms for cardiac dysfunction in sepsis include the inhibitory effect of endotoxin and inflammatory factors on myocardium and the decrease in cardiac myocardial cells in number. However, whether there is ventricular remodeling resulted from the abnormalities of extracellular collagen metabolism and whether glutamine (Gln) can protect myocardium from LPS-induced damage as in reperfusion are unknown. The aim of the present study was to examine the effects of Gln on the expressions of matrix metalloproteinase-3 (MMP-3), tissue inhibitor of metalloproteinase-3 (TIMP-3) and their mRNA in myocardium of rats with sepsis. Classical rat model of sepsis was established by intraperitoneal injection of lipopolysaccharide (LPS) (4 mg/kg, from Escherichia coli O(55): B(5), Sigma). from 121 Wistar rats aged 18 days were divided into three groups randomly, 0 h control group (normal saline: 1 ml/kg, n = 11), LPS group (LPS: 4 mg/kg, n = 55) and Gln group (LPS: 4 mg/kg and immediately 13.64% glutamine 1 ml/kg, Fresenus, n = 55). Furthermore, LPS and Gln groups were examined at 2 h, 4 h, 6 h, 24 h and 72 h time points (n = 11). On each time point, rats of LPS and Gln groups as well as control group were anesthetized with 1% chloral hydrate injected intraperitoneally at a dosage of 1 ml/kg. Then, rats were sacrificed, and the hearts were isolated. Eight of them were frozen at minus 80 degrees C to measure the expression of TIMP-3 mRNA by using RT-PCR. The expressions of MMP-3 and TIMP-3 were observed with immunohistochemistry and the expression of MMP-3 mRNA was observed by using in situ hybridization. (1) Compared to 0 h, the mRNA expressions of MMP-3 and TIMP-3 in LPS group significantly increased (P < 0.01) with the peak at 6 - 24 h. While, in Gln group, they were significantly higher than those in controls but significantly lower than those in LPS group with the peak at 24 h (P < 0.01). Even at 72 h, they were still higher than those at 0 h (P < 0.05 and P < 0.01). (2) Compared to 0 h, the expressions of MMP-3 and TIMP-3 in LPS group were significantly lower at any other time point with the lowest at 6 h (P < 0.01). In Gln group, these expressions were also significantly lower than those in controls, but significantly higher than those in LPS group with the lowest being postponed to 24 h (P < 0.01). (3) The ultra structure changed obviously. Z line was unclear and the ridge of mitochondrion disappeared. While, in Gln group, the myocardial injury was slight compared to that in LPS group. MMP-3 mRNA expression was increased and TIMP-3 mRNA expression was depressed in LPS-induced sepsis. Myocardial extracellular matrix was damaged in sepsis. Glutamine might decrease the effects of LPS on MMP-3 and TIMP-3 expressions and postpone the time of myocardial matrix injury.

Mitochondrial Uncoupling: A Key Contributor to Reduced Cardiac Efficiency in Diabetes

Cardiovascular disease is the primary cause of death in individuals with obesity and diabetes. However, the underlying mechanisms for cardiac dysfunction are partially understood. Studies have suggested that altered cardiac metabolism may play a role. The diabetic heart is characterized by increased fatty acid oxidation, increased myocardial oxygen consumption, and reduced cardiac efficiency. Here, we review possible mechanisms for reduced cardiac efficiency in obesity and diabetes by focusing on the potential role of mitochondrial uncoupling.

Predictors of Left Ventricular Regional Wall Motion Abnormalities After Subarachnoid Hemorrhage

Cardiac abnormalities that have been reported after subarachnoid hemorrhage (SAH) include the release of cardiac biomarkers, electrocardiographic changes, and left ventricular (LV) systolic dysfunction. The mechanisms of cardiac dysfunction after SAH remain controversial. The aim of this study was to determine the prevalence of LV regional wall motion abnormalities (RWMA) after SAH and to quantify the independent effects of specific demographic and clinical variables in predicting the development of RWMA. Three hundred patients hospitalized with SAH were prospectively studied with serial echocardiography. The primary outcome measure was the presence of RWMA. The predictor variables included the admission Hunt & Hess grade, age, gender, cardiac risk factors, aneurysm location, plasma catecholamine levels, cardiac troponin I (cTi) level, heart rate (HR), blood pressure, and phenylephrine dose. Univariate and multivariate logistic regression was performed with adjustment for serial measurements, reporting odds ratios (OR) and 95% confidence intervals (CI). In this study, 817 echocardiograms were analysed. RWMA were detected in 18% of those studied. The prevalence of RWMA in patients with Hunt & Hess grades 3 - 5 was 35%. Among patients with a peak cTi level greater than 1.0 m g/L, 65% had RWMA. Multivariate analysis demonstrated that high Hunt & Hess grade (OR 4.22 for grade 3 - 5 versus grade 1 - 2, p = 0.046), a cTi level greater than 1.0 microg/L (OR 10.47, p = 0.001), a history of prior cocaine or amphetamine use (OR 5.50, p = 0.037), and higher HR (OR 1.34 per 10 bpm increase, p = 0.024) were predictive of RWMA. RWMA were frequent after SAH. High-grade SAH, an elevation in cTi levels, a history of prior stimulant drug use, and tachycardia are independent predictors of RWMA.

Myocardial Creatine Concentration in Various Nonischemic Heart Diseases Assessed by 1H Magnetic Resonance Spectroscopy

Previous (31)P magnetic resonance spectroscopy (MRS) studies demonstrated that the myocardial phosphocreatine-to-ATP ratio offered important information concerning the degree of dysfunction and prognosis in patients with cardiomyopathy. In the present study, we investigated total creatine (CR) levels in various diseased hearts using 1H MRS. Fourteen patients with the following conditions were examined: cardiac amyloidosis (n = 2); hypertensive heart disease (4); valvular disease (2); hypertrophic cardiomyopathy (2); dilated cardiomyopathy (2); restrictive cardiomyopathy (1); and post-operative atrial septal defect (1). Myocardial CR was measured using 1H MRS with point-resolved spectroscopy localization. Overall, myocardial CR levels in diseased hearts were significantly lower than those in the control group [16.5+/-6.0 (n = 14) vs 27.1+/-3.2 micromol/g (n = 10), p < 0.001]. There was a positive correlation between myocardial CR and left ventricular ejection fraction (42.9+/-13.8%, range 19.5-69.1%) despite the different mechanisms of cardiac dysfunction (r = 0.60, p < 0.05). Myocardial CR levels in patients who were hospitalized due to heart failure within 1 year were significantly lower than those in other patients [11.3+/-1.0 (n = 4) vs 18.6+/-5.9 micromol/g (n = 10), p < 0.05]. Noninvasive measurement of myocardial CR using 1H MRS may be valuable in the assessment of disease severity and prediction of clinical course in various forms of heart disease.

Impairment of coronary flow reserve and left ventricular function in the brain-dead canine heart

The mechanisms of cardiac dysfunction after brain death, which are thought to be mainly associated with massive catecholamine release, have not been fully elucidated, especially with respect to the coronary circulation. The aim of this study was to investigate the changes in function of the coronary artery and its contribution to hemodynamic deterioration in a canine brain death model. Brain death was induced by rapid inflation of a subdurally placed balloon catheter. Hemodynamic measurements including assessment of left ventricular contractility using pressure-volume relations and biochemical analyses of blood samples were performed in seven dogs. Coronary flow reserve in the same brain death model was assessed by changes in coronary flow and resistance induced by administering a vasodilator directly into the coronary artery in another eight dogs. A hyperdynamic response was transiently observed after induction of brain death, followed by decreases in arterial pressure, cardiac output, and coronary blood flow. Parameters of left ventricular contractility as measured by pressure-volume relations had significantly deteriorated by 60 min after brain death. Percent changes in coronary flow by administration of acetylcholine and sodium nitroprusside were 272 and 209%, respectively, before brain death; these were decreased to 178 and 145% at 30 min after brain death, and to 192 and 153% at 60 min. Coronary resistance ratios were also significantly increased at 30 and 60 min after brain death. Impairment of coronary flow reserve was found in the brain-dead canine heart. This impaired coronary circulation may constitute a disadvantage of prevention and recovery of cardiac dysfunction after induction of brain death.

Transient Cardiac Dysfunction and Pulmonary Edema in Exertional Heat Stroke

Exertional heat stroke is a medical emergency that uncommonly results in severe cardiac dysfunction. The military physician diagnosed a 19-year-old military recruit from an elite unit to have exertional heat stroke. Immediate treatment in the field with rapid ice water cooling and vigorous fluid administration resulted in pulmonary edema. Transthoracic echocardiography on admission to the emergency department revealed moderate reduction in left and right ventricular function. After treatment, within a few days, rapid myocardial recovery was noted and persisted after 6 months of follow-up. Possible mechanisms of cardiac dysfunction in exertional heat stroke and treatment strategies are discussed. It is suggested that intravenous fluid administration to patients with suspected exertional heat stroke should preferably be done with appropriate hemodynamic monitoring and after cardiac dysfunction has been ruled out.