Alterations In Myocardial Metabolism Research Articles

Coronary haemo-dynamics and myocardial metabolism during weaning from mechanical ventilation in cardiac surgical patients

The present clinical study was undertaken to assess the alterations in myocardial metabolism and coronary haemodynamics during weaning from mechanical ventilation in postoperative cardiac surgical patients. Global and regional myocardial blood flow and metabolism were assessed using a dual port coronary sinus-great cardiac vein thermodilution catheter in 17 patients who had undergone coronary revascularization and who were being weaned from mechanical ventilation. Anaerobic myocardial metabolism, as demonstrated by the production of myocardial lactate, manifested in 8 of 17 patients during at least one of the weaning phases. There were no differences in coronary blood flow between patients who produced myocardial lactate and those who maintained aerobic cardiac metabolism. However, lactate producers exhibited larger changes in systemic vascular resistance and mean arterial pressure than the non-lactate producers. This metabolic manifestation of myocardial ischaemia was not accompanied by electrocardiographic changes of ischaemia, nor presence of chest pain, and may represent another form of silent ischaemia. We conclude that despite coronary revascularization, the myocardium may remain vulnerable to ischaemic anaerobic metabolism in the immediate postoperative period.

Left ventricular contractility is depressed in IgE-mediated anaphylactic shock in dogs

To determine whether myocardial dysfunction contributes to vascular collapse in anaphylactic shock, we examined left ventricular (LV) contractility, coronary blood flow, and myocardial lactate metabolism during antigen challenge in eight dogs that were sensitized to ragweed pollen extract (anaphylaxis group). Findings in the anaphylaxis group were contrasted to those in another group of dogs in which mean blood pressure was decreased to the same extent by arteriolar vasodilation with nitroprusside. The animals were examined under nonhypoxic conditions while anesthetized and ventilated. LV mechanics were examined with subendocardial crystals placed primarily along the anterior-posterior minor axis of the LV. During antigen challenge, a depression in LV contractility was observed in the anaphylaxis group as assessed by fractional dimensional shortening, stroke volume, and the slope of the end-systolic pressure-dimension relationship. During anaphylaxis, moreover, coronary vasodilation rather than coronary vasoconstriction was observed, and evidence of myocardial ischemia as assessed by altered myocardial lactate metabolism was not found. Our results indicate that depressed LV contractility occurs in anaphylactic shock. The results further suggest that the mechanism may be due to a direct effect of mediators of anaphylaxis on the myocardium to produce systolic dysfunction.

Myocardial metabolism and ventricular function following cold potassium cardioplegia

Transient alterations in myocardial metabolism and ventricular function were observed after elective coronary bypass grafting despite apparently adequate intraoperative protection with cold potassium cardioplegia. Ninety patients had serial hemodynamic measurements and coronary sinus catheters inserted. Thirty-three patients had thermodilution coronary sinus flow catheters inserted to measure coronary sinus blood flow and to evaluate the myocardial utilization of oxygen and lactate. Nuclear ventriculograms were performed in 43 patients to assess ventricular function. Cardiac index fell after discontinuation of cardiopulmonary bypass and then rose between 2 and 24 hours postoperatively. Myocardial oxygen consumption steadily increased during this period. Myocardial lactate production reverted to lactate extraction 30 minutes after reperfusion. Reactive hyperemia was present during the first 10 minutes after cross-clamp release, and coronary sinus blood flow increased gradually during the first 24 hours postoperatively. The response to the stress of volume loading (the infusion of 250 to 500 ml of a colloid solution) and atrial pacing (at a rate of 110 beats/min) was evaluated 2 to 4 hours postoperatively (EARLY) and between 4 to 6 hours postoperatively (LATE). Volume loading resulted in a decrease in lactate extraction EARLY and an increase LATE (EARLY: -0.07 +/- 0.35 mmol/L; LATE: 0.08 +/- 0.32 mmol/L, mean +/- standard deviation not significant). Atrial pacing resulted in a decrease in lactate extraction EARLY and an increase LATE (EARLY: -0.11 +/- 0.34 mmol/L; LATE: 0.14 +/- 0.36 mmol/L, p less than 0.05). Diastolic compliance (the relation between the end-diastolic volume index) decreased between EARLY and LATE. Systolic function (the relation between the systolic blood pressure and the end-systolic volume index) and myocardial performance (the relation between the left ventricular stroke work index and the end-diastolic volume index) were unchanged. Ejection fraction correlated inversely with the end-diastolic volume index and did not represent an independent index of contractility. After elective coronary bypass grafting and cold crystalloid cardioplegia, myocardial metabolism recovered slowly. Hemodynamic stresses should be avoided in the early postoperative period to prevent progressive ischemic injury.

Transient disappearance of variant angina attacks during atrial fibrillation with fast ventricular rate

Although coronary artery spasm is a well established cause of variant angina, its pathogenetic mechanism is not known. Autonomic nervous system imbalance or alterations in myocardial metabolism may play a role in the pathogenesis of coronary spasm, z,2 We describe a patient with variant angina in whom transient remission of ischemic attacks (IAs) was observed during atrial fibrillation (AF), suggesting that changes in autonomic nervous tone and myocardial metabolism associated with AF prevented coronary spasm.

Acute effects of ketanserin on left ventricular function, metabolism and coronary blood flow.

An acute intravenous bolus of 10 mg ketanserin (a specific 5-HT antagonist) caused an abrupt fall in left ventricular systolic pressure of 17 +/- 9.2 mm Hg (P less than 0.025) in ten patients undergoing cardiac catheterisation for chest pains. A fall in pulmonary artery diastolic pressure of 2.1 +/- 0.74 mm Hg (P less than 0.02) was also observed. No changes in resting heart rate occurred and the response to pacing was largely unmodified by ketanserin, except for a reduction in pulmonary vascular resistance (3.70 +/- 1.27 units to 2.97 +/- 1.44 units, P less than 0.05), at the fastest rate (136 +/- 3 beats/min). At the highest pacing rate coronary sinus blood flow fell (83 +/- 12 ml 100 g-1 min-1 to 68 +/- 8 ml 100 g-1 min-1, P less than 0.05), as did myocardial oxygen consumption (18 +/- 2 ml-1 min to 14 +/- 1 ml min-1, P less than 0.05) after the drug. No changes in the parameters of left ventricular contractile function could be attributed to ketanserin, save for a modest increase in the ejection fraction (48 +/- 6% to 57 +/- 6%, P less than 0.05) in seven patients. There were no alterations in myocardial metabolism of lactate, pyruvate, hydroxybutyrate, glycerol nor free fatty acids after ketanserin. The findings are consistent with a peripheral site of action of this drug and its blood pressure lowering effect in the subjects suggest a non-specific hypotensive action rather than an anti-hypertensive effect.

Myocardial metabolic alterations after contrast angiography

Contrast media used during angiography are known to produce transient alterations in cardiovascular physiology. However, little information is available concerning what alterations, if any, occur in myocardial metabolism after contrast angiography. Sixteen patients with symptoms of ischemic heart disease undergoing elective left ventriculography were studied. Coronary sinus and arterial blood samples were obtained for free fatty acids, glucose and lactate before and after performing left ventriculography with Renografin-76. Coronary blood flow was determined by the thermodilution technique. Five minutes after ventriculography, the arterial level of free fatty acids had decreased by 18.0 ± 4.9 percent (mean ± standard deviation) from the baseline (before angiography) samples (probability [p] < 0.001). Associated with this decrease in arterial free fatty acids was an increase in the myocardial uptake of this substrate. At 5 minutes after left ventriculography, the free fatty acid uptake had increased 48.5 ± 33.0 percent compared with the baseline value (p < 0.001). After the injection of contrast medium, there was no significant change in the arterial levels of glucose or lactate. However, significant decreases in the myocardial uptake of glucose and lactate were demonstrated ( −72.5 ± 44.5 percent [p < 0.001] and −43.2 ± 22.9 percent [p < 0.001], respectively) at 5 minutes. The changes in arterial free fatty acids and in the myocardial uptake of the various substrates persisted throughout the sampling period of 20 minutes after ventriculography. These results demonstrate that contrast medium significantly alters myocardial metabolism. These metabolic alterations persist longer than the hemodynamic changes induced by contrast angiography.

Assessment of regional myocardial ischemia by positron-emission computed tomography

Positron-emission computed tomography (PCT) is a new means of studying regional myocardial metabolism. This new device permits quantitative, cross-sectional imaging of the tissue concentrations of positron-emitting tracers of blood flow and metabolism in the myocardium. To examine the potential value of PCT for evaluating regional alterations in myocardial metabolism, acute myocardial ischemia was induced by rapid atrial pacing in open-chest dogs with partial coronary stenoses. Regional myocardial glucose uptake and utilization of free fatty acids were examined with the glucose analog F-18 2-fluoro-2-deoxyglucose (FDG) and C-11-labeled palmitic acid. Myocardial blood flow was evaluated with N-13 ammonia. In the ischemic segment, uptake of C-11 paimitic acid was reduced in proportion to blood flow and its rate of clearance as an index of beta oxidation was delayed. There was a relative or absolute increase in FDG uptake (depending on the uptake of FDG in the normal myocardium). Similar observations were made in patients with ischemic heart disease and anginal symptoms at the time of study. The observed alterations in the regional distribution of positron-emitting tracers of metabolic substrates in ischemic myocardium are in agreement with previously reported animal experimental studies in which a fall in free fatty acid utilization associated with an increase in glycolytic flux was observed. These studies indicate that metabolic alterations associated with acute myocardial ischemia observed previously in destructive animal experiments do indeed occur in humans and can now be demonstrated noninvasively in humans by PCT.

Development of 15-(p-123I-phenyl)-pentadecanoic acid for in-vivo diagnosis of the myocardium

Radioiodinated ω-phenylfatty acids were recently proposed as radiopharmaceuticals for determining myocardial metabolic alterations. Therefore uptake and elimination of different radiohalogenated phenylfatty acids were determined in blood and heart muscle of mice. The structure activity dependence i.e. the effect of length of the carbon chain, position of the substituent at the benzene ring and type of radiohalogen was studied. Highest myocardial accumulation was found in case of a phenylfatty acid with 15 carbon atoms in the alkylgroup and the radiohalogen attached to the benzene ring in the para position. No difference was observed between the radiobrominated and radioiodinated substrates. In contrast to aliphatic radioiodinated fatty acids, the radioactivity in the stomach remained almost constant (i.e. below 1% dose/organ). Thus 15-(123I-phenyl)-pentadecanoic acid (IPPA) could be brought into clinical application with success. Blood clearance and urine excretion of the radioactivity were determined and the results found to agree with the expectations based on the principal metabolic path of phenylfatty acids.

Coronary hemodynamic and myocardial metabolic alterations accompanying coronary spasm

Arterial pressure, coronary sinus blood flow with the thermodilution technique and calculated coronary vascular resistance were measured and coronary arteriography performed at rest and after the administration of ergonovine in 14 patients with atypical chest pain (group I) and 6 patients with variant angina (group II). Mild diffuse narrowing of the left coronary bed in group I was not accompanied by S-T segment shifts, and coronary vascular resistance did not change significantly. In contrast, severe focal spasm (greater than 90 percent narrowing) of the left anterior descending coronary artery in group II patients was accompanied by S-T elevation and a marked overall increase in coronary vascular resistance (from 0.65 ± 0.07 to 1.14 ± 0.10 mm Hg/ml per min) ( P < 0.005). In addition, the myocardial arteriovenous oxygen difference increased and net lactate extraction changed to lactate production in the two patients in group II in whom these measurements were made. Thus, thermodilution coronary sinus blood flow measurement may be a sensitive method for detecting primary increases in coronary vascular resistance due to a high grade focal spasm in the left anterior descending coronary artery.

Derangements of myocardial metabolism preceding onset of ventricular fibrillation after coronary occlusion

To determine alterations in myocardial metabolism and and hemodynamics that occur within the first 30 minutes after coronary arterial occlusion, before the onset of ventricular fibrillation, measurements were compared in two series of dogs. Series A, 90 dogs that did not manifest ventricular fibrillation after coronary occlusion, were considered a control group. Series B consisted of 28 dogs that had ventricular fibrillation within 30 minutes after occlusion. All had similar comprehensive measurements completed preceding the onset of ventricular fibrillation. The animals in series B (subseuqnt fibrillation) had significantly higher heart rates before and after coronary occlusion. In this series cardiac metabolism of the occluded segment judged by transmyocardial lactate extraction, potassium balance, sodium/potassium ratio and blood pH because grossly more abnormal after coronary occlusion than in series A. In 5 animals whose measurements were obtained within 5 minutes of the onset of ventricular fibrillation, a sudden massive lactate production, potassium loss and increased acidosis of the occluded portion supervened minutes before the onset of the fatal arrhythmia. Animals with ventricular fibrillation had higher intracoronary S-T segment elevation that persisted until the onset of ventricular fibrillation. Measurements of abnormal hemodynamic function (left ventricular end-diastolic pressure, peak systolic pressure and first derivative of left ventricular pressure [DP/dt]) were not associated with an increased incidence of ventricular fibrillation. The study indicates that animals that manifest ventricular fibrillation within 30 minutes after coronary occlusion have higher preocclusion heart rates, a more severe metabolic disorder of the coronary occluded segment and more persistent intracoronary S-T segment elevation compared with animals that do not manifest ventricular fibrillation.

Sequential analysis of altered myocardial metabolism and contractility induced by normothermic arrest and reperfusion

Normothermic anoxic arrest by aortic cross clamping, a widely used clinical technique, is associated with metabolic changes in the myocardium which are incompletely understood. Using the isovolumetric balloon model and “stop-freeze” biopsy technique, a study of myocardial contractility and metabolism was performed in 29 intact dogs supported by cardiopulmonary bypass and subjected to 60 min of normothermic anoxic arrest, followed by 30 min of reperfusion. A marked reduction in total high energy phosphates (62%), glycogen (63%), and an increase in lactate production (243%) denote a shift to anerobic metabolism during the period of arrest. Despite 30 min of reperfusion, total high energy nucleotides remained depressed ( P < 0.001). Nevertheless, intermediary metabolic recovery and a reversion to aerobic metabolism was evidenced by falling lactate levels (53%), rising glycogen (51%), and increasing creatine phosphate (1100%). These data suggest that persistent abnormal myocardial carbohydrate metabolism and low levels of high energy nucleotides prevent contractile recovery following normothermic anoxic arrest and reperfusion. While creatine appears to be preserved for the energy pool, the increase in creatine phosphate does not appear to be adequate to overcome depression of the nucleotides.

Myocardial metabolism during acute hemorrhagic or endotoxic shock.

In both hemorrhagic and endotoxic shock, a diminished venous return is probably responsible for the decreased cardiac output. Although the heart eventually fails in both types of shock, it is unclear whether cardiac failure is responsible for the irreversibility of the condition. Also, it is unknown whether alterations of myocardial metabolism precede cardiac failure and, if so, whether they are due to or simply a reflection of myocardial hypoxia.

Biochemical basis of heart function. IV. Energy metabolism and calcium transport in hearts of vitamin E deficient rats.

Feeding a vitamin E deficient diet to rats for 10 weeks was found to decrease myocardial creatine phosphate, ATP, ATP/ADP ratio, NAD+, NADP+, and NADPH, whereas the level of ADP was increased without any changes in the levels of AMP, total adenine nucleotides, NADH, and ATP/AMP ratio. The levels of ATP and pyridine nucleotides were restored fully, whereas creatine phosphate was restored partially on feeding a normal diet for 4 weeks to animals previously on the vitamin E deficient diet for 10 weeks. Vitamin E deficiency was found to increase cardiac lactate, pyruvate, and lactate/pyruvate ratio and decrease the activities of lactate dehydrogenase and malate dehydrogenase. The activity of Na+–K+-stimulated, ouabain-sensitive ATPase was markedly elevated in the hearts of animals on the vitamin E deficient diet. The ATP-dependent calcium accumulation by the sarcoplasmic reticular fraction in the absence and presence of P1 or oxalate was greater in the vitamin E deficient heart. Vitamin E deficiency also increased the Ca2+-stimulated ATPase activity of the cardiac sarcoplasmic reticulum. Although myocardial contractility of the hearts from vitamin E deficient rats was depressed, no damage to the ultrastructures of mitochondria and sarcoplasmic reticulum was apparent. These results indicate marked alterations in myocardial metabolism due to vitamin E deficiency and it is suggested that such changes are due to abnormalities in the processes of both energy production and utilization.

Current status of diastolic augmentation for circulatory support

The hemodynamic effects of alteration of the aortic pressure pulse by diastolic augmentation in experimental acute myocardial infarction and clinical experience with these techniques are described. Both counterpulsation of blood in the aorta or femoral arteries and phased inflation of a thoracic aortic balloon achieve with reasonable predictability the physical aims of the procedure, i.e., diminution of the aortic systolic pressure and increment of the aortic diastolic pressure. However, varying hemodynamic consequences of these effects have been reported in experimental acute myocardial infarction with shock. Despite theoretical considerations, significant increase of the diminished coronary flow has not been found uniformly, particularly when the initial aortic pressure is quite low. Oxygen consumption of the myocardium usually, but not invariably, has been lowered by this technique and variable effects have been reported in reversing the anaerobic myocardial metabolic alterations of acute myocardial infarction. Analysis of the results indicates that the technique achieves optimal physiologic efficacy when it operates with a substrate of adequate central aortic pressure. This is accomplished more readily with balloon pumping than with central aortic counter-pulsation of blood alone, probably because of some circulatory compartmentalization produced by the balloon as well as by its central aortic pumping effects. In addition, balloon pumping as compared to counter-pulsation of blood affords the advantage of easier peripheral arterial cannulation and less destruction of the formed elements of the blood, thus allowing it to be used for longer periods. When the arterial pressure is quite low, additional efficacy can be obtained by utilizing the technique with a method to raise central aortic pressure by means of circulatory compartmentalization with a distal aortic balloon. The clinical results have been too sparse to form valid conclusions concerning the indications for and the ultimate hazerds and benefits of the techniques in acute myocardial infarction with shock. Most of the available experience has been with phasic inflation and deflation of a helium-filled thoracic aortic balloon. This has indicated a variable survival rate (about 30 per cent in the largest series) in patients refractory to conventional medical management. It is stressed that it is necessary to obtain more precise prognostic indications in acute myocardial infarction in the future so that optimum and reasonably early selection of patients who will not respond to other forms of therapy may be accomplished. This may permit initiation of circulatory support before irreversible cardiovascular deterioration has occurred.

Cardiac Resynchronization Therapy: Who is and who is not a Candidate? Who Decides?

It is estimated that nearly 500,000 Canadians are currently living with heart failure, a disease process associated with considerable morbidity and mortality. Despite significant evidence for effective medical therapies, heart failure remains one of the leading causes of hospitalization in Canada and patients with the disease experience an annual mortality of up to 10%.Approximately one in three patients with systolic heart failure have some degree of intraventricular conduction delay, manifest as increased QRS duration on electrocardiogram (ECG), the most common of which is left bundle branch block (LBBB). This conduction delay, or electrical dyssynchrony, can lead to mechanical uncoupling and inefficiency, which, in turn, can lead to exacerbation of systolic dysfunction, altered myocardial metabolism, functional mitral regurgitation, negative remodeling and worsening clinical outcomes.Cardiac resynchronization therapy (CRT), also known as biventricular pacing, involves coordinating contraction between the left (LV) and right ventricles (RV) through programmed pacing of both ventricles. CRT is an established non-pharmacological therapy for patients with systolic heart failure due to a low ejection fraction, who have a QRS &gt;130 ms and who are symptomatic despite optimal medical therapy. In carefully selected patients, CRT has been shown to promote positive LV remodeling, increase functional capacity, improve quality of life, reduce heart failure hospitalizations and reduce mortality.2 CRT systems can include defibrillator capabilities (CRT-D) or act as a stand-alone pacemaker (CRT-P).The insertion of a CRT system consumes significant resource (costs), requires a commitment to regular clinical follow-up, and the acceptance of permanent implantation of a large medical device. Clinicians are tasked with identifying patients who would be expected to benefit from CRT and making the decision whether to proceed with CRT implantation. Therefore a careful consideration of the risks and benefits of this technology is required by both the healthcare providers and the patient.Herein we hope to offer guidance on identifying ideal candidates for CRT and to remind health care providers that the patients’ goals must be taken into consideration when counseling a patient for treatment with CRT.

Acute effects of alcohol on the human myocardium

The effect of acute alcoholic ingestion after 6 oz. of 84 proof Vodka was studied in 11 patients with a known history of chronic alcoholism. No patient had any evidence of vitamin deficiency nor any clinical evidence of heart or liver disease. The results would indicate no significant changes in pulse rate, blood pressure, cardiac output, stroke volume, arterial venous oxygen extraction or respiratory quotient. Despite the lack of these hemodynamic alterations, electrocardiographic changes as evidenced by flattened and inverted T waves occurred 30 minutes after the ingestion of alcohol in 2 of the patients. Metabolically the significant findings included a rise in blood lactate, a decline in arterial pyruvate, a marked fall in blood glucose, a decline in free fatty acids and a rise in triglycerides one half hour after the ingestion of alcohol. Phospholipid blood levels remained unchanged. Coronary arterial and venous contents of magnesium, copper and zinc were essentially unchanged 30 minutes after alcohol; three hours postingestion, peripheral venous contents exceeded that of the 30 minute arterial and coronary venous determination. Zinc was liberated by the heart following alcohol in the majority of patients. Serum alcoholic dehydrogenase activity closely followed that of blood zinc. The myocardial extraction of the substrates was consistent with the rise or decline in arterial blood levels with the exception of lactate and glucose; the former fell and the latter rose significantly. Both alcoholic dehydrogenase and isocitric dehydrogenase coronary venous enzyme activities also frequently exceeded that found in arterial blood in several patients. The implications of these findings were discussed. It is suggested that repeated exposure to acute alcoholism could result in permanent alterations in myocardial metabolism which could lead to the development of irreversible alcoholic cardiomyopathy.

REGULATION OF CORONARY BLOOD FLOW.

New approaches for coronary flow measurement neural control of coronary blood flow role of adenosine in regulation of coronary blood flow role of endothelial cells in coronary circulation ischemia and reperfusion injury in the experimental and clinical studies.