Chronic Myocardial Dysfunction Research Articles

20 Chronic Cardiovascular Dysfunction Following Lower Extremity Amputation in Burn Patients

Abstract Introduction Long-term chronic cardiovascular dysfunction is a well-reported outcome in patients who have suffered severe burns associated with diminished muscle mass and hypermetabolism. Devastating burn injuries sometimes warrant extremity amputation to preserve life over limb. A lower extremity amputation can exacerbate the risk of burn-related sequelae due to prolonged recovery and reduced mobility. We queried a large multi-institutional national database to investigate whether lower extremity amputations in those with severe burns were associated with increased incidence of chronic myocardial dysfunction syndromes. Methods We accessed the TriNetX Global Health Research Network and queried ICD-10 codes for burn injuries (T20-25, T30-32) across 41 participating health care organizations. Comparative cohorts of patients who underwent lower extremity amputations and those who did not were identified. A matched case-control analysis of these cohorts accounting for age and gender matching was compared for the subsequent diagnosis of chronic cardiac dysfunction syndromes (I50.22, I50.32, I50.42, I50.812). Results A total of 347,156 patients did not undergo lower extremity amputation, and their demographics showed a mean age of 38 years, 54% males, 60% white and 18% African American. In contrast, 1,535 patients underwent lower extremity amputation with a mean age was 59 years, 73% were male, 60% white and 24% African American. Burn patients who underwent amputations showed a comparative increased risk of 5.77% (p < 0.0001) for developing of chronic cardiac dysfunction compared to those who did not undergo amputations (RR 3.512, 95% CI: 2.39–5.16). One year following injury this comparative risk diminished to 3.45% (p < 0.0001; RR 3.14, 95% CI: 1.96–5.04). The difference in risk was not significant 3 years after burn injury (0.538%, p = 0.2163, RR 1.54, 95% CI: 0.77–3.09). Conclusions Patients who underwent amputations after severe burn are at increased risk of developing chronic cardiac dysfunction compared to those that did not undergo amputation; the significance appears to diminish with time. Further research is indicated to elucidate the mechanism for this relationship.

EFFECT OF RENAL DYSFUNCTION ON THE CARDIACVASCULAR SYSTEM. THE POSSIBILI TIES OF EARLY DIAGNOSIS OF THE RENAL DYSFUNCTION

The review is devoted to the discussion of modern concepts of the role of renal dysfunction in the development of chronic myocardial dysfunction in the context of cardio-renal syndrome (RVC) type 4. At the beginning of the review, the definition of cattle is given, general questions of pathogenesis and diagnosis of the disease are addressed. It is indicated that in patients with the initial stage of CKD, cardiovascular disorders are already registered which in the late stages of development of renal dysfunction are the leading causes of death and the true severity of the disease in patients with renal dysfunction is associated with an increased risk of cardiovascular events, rather than an achievement terminal renal failure and requiring renal replacement therapy. The progression of renal pathology leads to damage to the heart through various mechanisms and factors, both traditional and non-traditional, some of which, at the culmination of the renal continuum, are the result of the dialysis procedure itself in patients with terminal renal dysfunction. Mechanisms for the development of congestive heart failure in type 4 cattle include pressure overload (arterial hypertension) and volume (anemia, edematous syndrome), which increase in proportion to the decrease in renal function. Increase in blood pressure, changes in intracardial hemodynamics, deterioration of arterial compliance contribute to the acceleration of cardiovascular events. The role of laboratory predictors of renal dysfunction in the progression of cardiovascular disorders is discussed. The general approaches of echocardiographic visualization of the heart cavities and its importance in the diagnosis of cardiovascular diseases are discussed. Special attention is paid to the development of pulmonary arterial hypertension, changes in the left and right ventricle of the myocardium with renal dysfunction.

Oral Enoximone as an Alternative to Protracted Intravenous Medication in Severe Pediatric Myocardial Failure.

Phosphodiesterase 3 inhibitors have been used successfully in pediatric patients with acute or chronic myocardial dysfunction over the last two decades. Their protracted continuous intravenous administration is associated with risk of infectious and thromboembolic complications. Weaning intravenous medication and starting oral angiotensin-converting enzyme (ACE) inhibitors and/or beta-blockers can be challenging. We reviewed retrospectively hospital records of 48 patients receiving oral enoximone treatment in a single tertiary pediatric cardiac center between November 2005 and April 2014. Failure to wean from intravenous milrinone infusion and/or intolerance of ACE inhibitors and/or beta-blockers was indications for oral enoximone treatment. Age of the patients ranged between 0.5 and 191months (median 7.5months) at the time of starting enoximone treatment. There were 14 patients (29%) with left ventricular dysfunction due to myocarditis or dilated cardiomyopathy and 34 patients (71%) with myocardial dysfunction complicating congenital heart disease. Fifteen (44%) of these 34 patients had left ventricular dysfunction, 13 (38%) right ventricular dysfunction, and in 6 (18%) both ventricles were failing. Duration of oral enoximone treatment was between 3days and 34months (median of 2.3months). Myocardial functional recovery allowed for weaning of enoximone treatment in 15 patients (31%) after 6days-15months (median 5 months). No adverse hemodynamic effects were noted. Blood stained gastric aspirates encountered in two patients resolved with concomitant milk administration. Based on our limited experience, oral enoximone is a well-tolerated and promising alternative to intravenous medication and/or other commonly used oral medications in selected pediatric patients with chronic heart failure.

The role of hemodynamic parameters in chronic heart failure diagnosis in children

Despite the achievements in this field in recent years, concerning the chronic myocardial dysfunctions, pathogenesis, diagnosis and treatment management, the chronic heart failure continues to hold preeminence in the structure of cardiovascular complications and remains now one of the leading causes of invalidity of young contingent and infant mortality, presenting one of the most pressing public health problems. This requires looking for new methods of noninvasive early diagnosis with application of modern laboratory and investigational tests facilitating the identification in preclinical stages of chronic myocardial dysfunctions (CMD) by assessment of new biomarkers of myocardial injury. Objectives of the study. Hemodynamic parameters changes estimation in the evolution of chronic heart failure in children. Material and methods. The study included 233 patients with chronic heart failure, of which 78 were children and adolescents aged 10-17 years with CMD secondary to arterial hypertension. The diagnosis of arterial hypertension was established according to the ESA (European Society of Cardiology, 2009) recommendations, but the assessment of clinical manifestations of chronic heart failure was evaluated according to NYHA (New York Heart Association classification). The estimation of hemodynamic parameters was performed using echocardiography method using “Ultramark-8” (US device A) under Mand Doppler. Obtained results. In patients with arterial hypertension the types of concentric hypertrophy of left ventricular myocardial index mass (IMMVS) -59.2±14.2 and relative LV wall thickness (GRPVS) -0.46±0.22 cm were assessed. It is important to note that the study assessed the type of eccentric hypertrophy with IMMVS 66.4±7.6 and 0.44±0.25 cm GRPVS. Concentric geometric remodeling variant noted IMMVS average value of 48.4±4.2 and GRPVS- 0.44±0.21 cm. Identification of LV hypertrophy, increased GRPVS, IMMVS increase, the MMV based on echocardiographic examination of the heart reveals the geometric performance called “pathological remodeling” which actually confirms the occurrence of chronic myocardial dysfunction in patients with CHF secondary hypertension. Conclusions. Early identification of changes of cardiac performance parameters (MMV, IMMVS, GRPVS, HVS) under the conditions of the persistent tensional over estimation, reveals the early development of types of early myocardial pathological left ventricular remodeling and facilitates the options and diagnostic criteria of the heart remodeling in children with CMD secondary arterial hypertension in order to choose a selected pathogenetic treatment.

Ischaemic cardiomyopathy: pathophysiology, assessment and the role of revascularisation

### Learning objectives Ischaemic heart disease (IHD) continues to be the most common cause of death globally according to WHO and is the most common cause of heart failure in...

Behavioral disorders in rats with chronic myocardial dysfunction.

Observation of cardiologists and psychiatrists suggest that cardiovascular diseases and depression are the most common and frequent comorbid conditions. Therefore the aim of the study was to identify behavioral disorders in rats on the background of myocardial dysfunction in the experiment. Material of the research: 60 adult male rats of Wistar line, weighing 200-220 g, divided into 2 groups - control and experimental. Myocardial dysfunction was modeled by intraperitoneal injection of doxorubicin by 5 mg/kg of animal weight. To verify the model of myocardial dysfunction ECG and histological examination of the myocardium were performed. Evaluation of higher divisions of the CNS reactions was performed using the open field method by such indicators: vertical and horizontal motor activity (decreased by 71,4%), acts and defecation boluses (down by 85-88%), the number of burrows (decreased by 57-90%), grooming (decreased by 23%), all parameters were reliable (in p<0,05). There was a gradual decline of rats’ emotionality, CNS depression and increased anxiety. It was found that behavioral disorders in the experiment were typical for anxiety and depression states.

INOS induction and PARP-1 activation in human atherosclerotic lesions: an immunohistochemical and ultrastructural approach

Several lines of clinical and experimental evidence have demonstrated that reactive oxygen species and nitrogen species are generated in unregulated amounts during diverse cardiovascular disorders. It has been previously reported by our group and others that augmented expression of nitric oxide synthase isoforms is associated with human atherogenesis and that the activity of the enzymes in an atherosclerotic environment may promote the formation of peroxynitrite. Among the downstream mechanisms triggered by oxidants, poly(ADP-ribose) polymerase-1 activation has recently been implicated in the pathogenesis of acute and chronic myocardial dysfunction, diabetes, hypertension, aging, and various forms of shock. Based on these observations, we performed immunohistochemical and immunogold labeling analyses to evaluate the expression profile and the subcellular localization of inducible nitric oxide synthase and poly(ADP-ribose) polymerase-1 in healthy and atherosclerotic human aortae. We have demonstrated that inducible nitric oxide synthase colocalizes with poly(ADP-ribose) polymerase-1 within vascular cells of atherosclerotic human aortae. We have reported for the first time, to our knowledge, the ultrastructural localization of poly(ADP-ribose) polymerase-1 within the nuclei of lesional smooth muscle cells. Finally, we have evidenced that poly(ADP-ribose) polymerase-1 induction within cells of the diseased aorta strongly correlates with alterations in mitochondrial morphology. Our data imply the possibility of a significant role for cross-talk between inducible nitric oxide synthase and poly(ADP-ribose) polymerase-1 in human atherosclerotic lesions. We conclude that the prooxidant milieu of the plaque might exert damaging effects on mitochondria via a poly(ADP-ribose) polymerase-1-mediated mechanism since the absence of the enzyme results in a corresponding lack of changes in mitochondrial morphology. The present report may open avenues for further researches that could have important therapeutic consequences for the treatment of atherosclerosis and its clinical sequelae.

Dose-dependent improvement in hemodynamic function after BNP administration during cardiac surgery: animal model

Objectives: The etiology of heart failure after cardiopulmonary bypass (CPB) is multifactorial. It is related to ischemia during aortic cross clamping, residual cardioplegia, and chronic myocardial dysfunction.

Effect of L-2286, a Poly(ADP-ribose)polymerase Inhibitor and Enalapril on Myocardial Remodeling and Heart Failure

Increased activation of poly(ADP-ribose) polymerase (PARP) enzyme has been implicated in the pathogenesis of acute and chronic myocardial dysfunction. We have demonstrated the protective effect of PARP inhibitors against postinfarction myocardial remodeling and heart failure. The primary aim of our recent work was to compare the effect and efficacy of a potent PARP-inhibitor (L-2286) to enalapril, a widely used angiotensin-converting enzyme (ACE) inhibitor. in experimental heart failure model. Both L-2286 and enalapril were tested in a rat model of chronic heart failure after isoproterenol-induced myocardial infarction. After a 12-week treatment period, echocardiography was performed, cardiac hypertrophy and interstitial collagen deposition were assessed, and the phosphorylation state of Akt-1/GSK-3beta pathway as well as the PKC and MAPK kinases were determined. Both PARP and ACE inhibition reduced the progression of postinfarction heart failure by attenuating cardiac hypertrophy and interstitial fibrosis. More importantly, PARP inhibition increased the activity of the prosurvival signal transduction factors (Akt-1/GSK-3beta pathway, PKCepsilon). Due to these effects, L-2286 improved the systolic left ventricular function. Enalapril treatment exerted a similar, but weaker protective effect against postinfarction myocardial remodeling and heart failure. In conclusion, we demonstrated in an experimental heart failure model that L-2286 decreased the postinfarction myocardial remodeling more effectively than enalapril treatment.

Stunning, Hibernation, and Assessment of Myocardial Viability

The last 3 decades have witnessed an unprecedented improvement in the outcome of patients with acute coronary syndromes. The widespread use of thrombolytic therapy and percutaneous coronary interventions, in association with increasingly potent antithrombotic agents, has contributed to significant reductions in mortality and morbidity in these patients. Although overall survival has improved, a downside of this success has been the greater number of patients with residual left ventricular (LV) dysfunction undergoing progressive LV remodeling and congestive heart failure. This problem is compounded by the rising age of our population and the higher prevalence of comorbidities such as diabetes mellitus that confer an increased risk of coronary artery disease (CAD) and congestive heart failure. Patients with CAD represent by far the most numerous cohort among those with congestive heart failure, and their treatment remains a partial success.1 Typically, these patients have multivessel disease, increased LV volumes, and variable degrees of regional and/or global systolic dysfunction, although more cases of isolated diastolic dysfunction have been reported recently.2–4 In these patients, coronary revascularization may lead to symptomatic and prognostic improvement, and these clinical benefits are accompanied by evidence of reverse LV remodeling. In this context, the concept of myocardial viability was developed and a number of different techniques have been used to demonstrate the presence of viable tissue before coronary revascularization. The aim of this review article is to summarize our current understanding of the concept of myocardial viability and its clinical implications in patients with CAD and chronic LV dysfunction. Throughout this review, we use the term viability to describe dysfunctional myocardium subtended by diseased coronary arteries with limited or absent scarring that therefore has the potential for functional recovery. Viability is a prospective definition, but it does not imply evidence of functional recovery after interventions. The term hibernation, which …

Post-resuscitation haemodynamics in a novel acute myocardial infarction cardiac arrest model in the pig

Although a considerable amount of promising experimental research has been performed on cardiopulmonary resuscitation, clinical data indicate an ongoing limited outcome in human beings. One reason for this discrepancy could be that experimental studies use healthy animals whereas most human beings undergoing cardiopulmonary resuscitation suffer from acute or chronic myocardial dysfunction. To overcome this problem, we sought to develop a new model of myocardial infarction, that is easy to perform in all kind of laboratories and compromises on the myocardial function significantly. Following approval by the local authorities, 14 domestic pigs were instrumented for measurement of arterial, central venous, left atrial and left ventricular pressures. Myocardial infarction was induced in eight pigs by clipping the circumflex artery close to its origin from the left coronary artery (infarction group; n = 8). Six animals (no infarction group, n = 6) served as no-infarct controls. Following a 4-min period of cardiac arrest, internal cardiac massage was performed in these two groups, and haemodynamics were recorded during the first 30 min of reperfusion. All animals were resuscitated successfully. Compared to the no-infarction group, the infarction group showed significantly decreased myocardial contractility, coronary perfusion pressure and cardiac index (30 min after restoration of spontaneous circulation: infarction group: 57 +/- 7 and 89 +/- 19 mL min-1 kg-1 in the no-infarction group; mean +/- SD; P < 0.05) during reperfusion. Two animals from the infarction group (25%), but none of the animals in the no-infarction group, died during the reperfusion period. These data demonstrate that clipping of the circumflex artery leads to a reduced myocardial performance after successful resuscitation, whereas the rate of restoration of spontaneous circulation is not reduced. Therefore, this set-up provides a reproducible model for future studies of post-resuscitation haemodynamics and treatment.

Activation of the Poly(ADP-Ribose) Polymerase Pathway in Human Heart Failure

Poly(ADP-ribose) polymerase (PARP) activation has been implicated in the pathogenesis of acute and chronic myocardial dysfunction and heart failure. The goal of the present study was to investigate PARP activation in human heart failure, and to correlate PARP activation with various indices of apoptosis and oxidative and nitrosative stress in healthy (donor) and failing (NYHA class III-IV) human heart tissue samples. Higher levels of oxidized protein end-products were found in failing hearts compared with donor heart samples. On the other hand, no differences in tyrosine nitration (a marker of peroxynitrite generation) were detected. Activation of PARP was demonstrated in the failing hearts by an increased abundance of poly-ADP ribosylated proteins. Immunohistochemical analysis revealed that PARP activation was localized to the nucleus of the cardiomyocytes from the failing hearts. The expression of full-length PARP-1 was not significantly different in donor and failing hearts. The expression of caspase-9, in contrast, was significantly higher in the failing than in the donor hearts. Immunohistochemical analysis was used to detect the activation of mitochondrial apoptotic pathways. We found no significant translocation of apoptosis-inducing factor (AIF) into the nucleus. Overall, the current data provide evidence of oxidative stress and PARP activation in human heart failure. Interventional studies with antioxidants or PARP inhibitors are required to define the specific roles of these factors in the pathogenesis of human heart failure.

Screening for isolated diastolic dysfunction ? a bridge too far?

Please see page 85 for the article by Nielsen et al. (doi: 10.1016/j.euje.2004.07.004) to which this editorial pertains . Advances in our ability to reduce the immediate mortality associated with acute coronary syndrome and hypertension have resulted in an inexorable increase in chronic myocardial dysfunction. In the United Kingdom ∼2% of the population have left ventricular systolic dysfunction (LVSD), which develops with an incidence of 10 per 1000 among persons older than 65 and is expanding in absolute terms with the demographic transition.1 The mortality of heart failure approaches 50% for patients with NYHA Class IV symptoms.2 Notable advances in the treatment of LVSD have resulted from widespread implementation of pharmacological, revascularisation, device and rehabilitation therapies; this is especially true if treatment is initiated early in the disease. An inevitable next step is therefore to extend and translate the successes of LVSD to identifying and treating its less familiar co-conspirator “Left ventricular diastolic dysfunction” (LVDD). For this proposition to be practicable, a number of interdependent questions need to be resolved: While rare clinical and experimental causes of “pure” myocardial diastolic dysfunction are recognised, in which active ventricular relaxation fuelled by ATP or passive ventricular distension dependent on myocardial mass and viscoeleastic properties are impaired, LVDD is more heterogeneous. Similar to LVSD, the pathophysiological debate will probably be resolved by recognising that most patients have a varying combination of an abnormally stiff ventricle with an abnormal active relaxation ( τ ) or passive filling (end-diastolic pressure–volume relationship – EDPVR) that is exacerbated by dynamic neurohormonal loading through varying central volume expansion and increased heart rates. This combination chronically raises LV filling and left atrial pressures (LAP) ultimately resulting in …

Improved outcome with composite graft versus homograft root replacement for children with aortic root aneurysms

Review of surgical repair of aortic root aneurysms using composite graft or homograft in children. A consecutive series of 34 children (mean age 10.8+/-5.4 years) who underwent elective aortic root replacement using composite graft or homograft from 1987 to 2003 (mean follow-up 5.7+/-3.7 years). Preoperatively, the aortic annulus and aortic root average z-scores were 4.1+/-2.2 and 9.4+/-4.7, respectively. Composite graft root replacement was performed in 22 patients, and cryopreserved aortic homograft root replacement in 12 patients. There was one perioperative death in the homograft group due to sudden cardiovascular collapse. There was one late death in the composite graft group due to acute aortic dissection, and two late deaths in the homograft root replacement group, one at 7 months postoperatively due to coronary artery thrombosis and one due to severe chronic myocardial dysfunction 5 years postoperatively. One patient who initially had a homograft died due to mechanical valve thrombosis following reoperative composite graft replacement. Five patients had reoperations at a median of 7.1 years after initial surgery. One patient in the composite graft group underwent arch replacement. There were no graft related reoperations after composite graft root replacement, but 4 patients in the homograft group had reoperative composite graft replacement. Predictors of reoperation included age at surgery, lower weight, and longer ICU time (P<0.05). In children with aortic root aneurysms, reoperation is more common after homograft root replacement than composite graft replacement. Composite graft root replacement provides more stable repair of the aortic root.

Preliminary observations on the effects of acute infusion of growth hormone on coronary vasculature and on myocardial function and energetics of an isolated and blood-perfused heart.

Recent studies have shown that growth hormone (GH) deficiency may deteriorate post-ischemic myocardial reperfusion damage. Furthermore, GH has been reported to be a promising therapeutic option in the treatment of chronic myocardial dysfunction. However, the exact mechanisms of action of GH on the cardiovascular system, particularly in the acute setting, are still unclear. The aim of our study consisted of monitoring the acute effects of GH infusion on isolated blood-perfused rabbit heart according to dose-response pattern and during ischemic conditions to test its anti-ischemic property. Seven blood-donors perfused isolated hearts were used as experimental model. The mechanical and metabolic data of the isolated organs were continuously monitored. Under aerobic conditions, dose-response curves were initially tested after intracoronary infusion of GH at increasing dosages (1, 2, 3 mg/l). After a stabilization period, the effects of GH infusion (5 mg/kg) administered 30 minutes prior to acute global myocardial ischemia (30 minutes) were also investigated. At the doses tested, GH did not induce any changes either in the developed or in the diastolic pressures of the isolated organ. However, transient reduction of the coronary perfusion pressure was observed at the dosage of 3 mg/l. During the ischemia/reperfusion study, at the dosages used in this study, GH did not modify either the degree of stunning in the early reperfusion or the recovery of the developed pressure at the end of reperfusion. In addition, GH did not prevent either the increase of diastolic pressure during ischemia or the release of lactate and CPK during reperfusion. Tissue content of high-energy phosphates was also not changed by GH infusion. In our experimental model, acute GH infusion did not reduce the ischemic/reperfusion damage of the myocardium. However, GH transiently induced coronary vasodilation without modifying the myocardial contractility. Acute effects of GH appear, therefore, to predominantly relate to vascular dilation suggesting that the effects on myocardial contractility may require long-lasting intake being likely linked to enhancement of specific protein synthesis or gene expression of cardiac myocytes.

Comparison of simultaneous dobutamine echocardiography and thallium-201 stress-reinjection single-photon emission computed tomography in predicting improvement of chronic myocardial dysfunction after revascularization

Previous studies have shown that ultrasonic integrated backscatter is valuable in characterizing stunned myocardium. Recent investigations have demonstrated that resting cardiac cycle-dependent variation of integrated backscatter closely paralleled the contractile reserve in patients with chronic left ventricular ischemic dysfunction. The purpose of this study was to validate whether ultrasonic tissue characterization (UTC) compared with dobutamine stress echocardiography (DSE) and thallium-201 stress-reinjection single-photon emission computed tomography (Tl-SPECT) could predict reversible myocardial dyssynergy in patients with chronic coronary artery disease. Forty-eight patients with stable coronary artery disease underwent UTC, DSE, and Tl-SPECT simultaneously before successful coronary revascularization and were followed up with echocardiograms at rest >3 months later. Among the 58 investigated segments, the weighted amplitude, a composite parameter derived from the integrated backscatter power curve, was larger for those groups with greater functional recovery (p <0.001). For the persistent akinetic segments, the weighted amplitudes were small with large deviations of the nadir ratios that represented the asynchrony between the intramural contractile events and the global systole. Using the cut-off value 2.0 of the weighted amplitude, the sensitivity and specificity for predicting functional improvement after revascularization were both 82.8% (κ = 0.66) and comparable to the sensitivity and specificity of DSE and Tl-SPECT. UTC, delineating the myocardial physical state and intramural contraction, can be a novel approach in predicting functional improvement of chronic dyssynergy after revascularization.

Metabolic supplementation with orotic acid and magnesium orotate.

Orotic acid (OA), a naturally occurring substance, is a key intermediate in the biosynthetic pathway of pyrimidines. Previous investigations in the heart suggest that orotate can protect recently infarcted hearts against a further ischemic stress and may be beneficial in certain types of experimental cardiomyopathy. At the Hamburg symposium on magnesium orotate, a number of studies of this form of metabolic supplementation were presented that indicate orotic acid and its magnesium salt have a modest beneficial effect on the myocardium under conditions of stress ranging from myocardial infarction to severe physical exercise. The following conclusions can be drawn: (1) Orotic acid can improve the energy status of the recently infarcted myocardium (rat hearts). (2) Orotic acid may improve myocardial purine and pyrimidine levels by stimulating hepatic release of uridine into the bloodstream, which in turn augments depleted myocardial pyrimidines and purines (rat heart). (3) Orotic acid improves the tolerance of the recently infarcted heart to global ischemia (rats). (4) Magnesium orotate may reduce the severity of chronic myocardial dysfunction and structural damage in cardiomyopathy (cardiomyopathic hamsters). (5) Magnesium orotate may improve exercise tolerance in patients with coronary artery disease and in trained athletes (humans). (6) Magnesium orotate has only a weak inotropic effect, if any, on normal hearts (rats). (7) Further clinical testing is indicated to determine if the effects described could be of significant clinical benefit in the treatment of heart disease.

The hibernating myocardium.

Hibernating myocardium represents a chronic myocardial dysfunction at rest associated with reduced coronary perfusion. Although myocardial contraction is depressed, metabolic balance is maintained, myocytes remain viable and myocardial contraction can be restored with myocardial revascularization.