M.F. Oliver

Bio: M.F. Oliver is an academic researcher. The author has contributed to research in topics: Myocardial infarction & Electrocardiography in myocardial infarction. The author has an hindex of 7, co-authored 10 publications receiving 1226 citations.

The role of free fatty acids in the production of ventricular arrhythmias after acute coronary artery occlusion.

Abstract: After After coronary artery occlusion had been produced in intact dogs, marked elevation of plasma FFA was usually associated with the development of frequent ventricular ectopic systoles and sometimes with ventricular tachycardia or even ventricular fibrillation. These arrhythmias occurred 10–30 min. after the maximum recorded level of FFA.— Elevation of plasma FFA was achieved by inducing plasma lipolysis with heparin. The increased frequency of ventricular ectopic systoles could be reduced and ventricular tachycardia abolished by the administration of protamine sulphate, which has no known anti‐arrhythmic effect on spontaneous arrhythmia, but suppresses heparin‐induced plasma lipolysis.— No haemodynamic changes occurred with the administration of heparin and Intralipid. While infusion of Intralipid and heparin caused reduction in pH of approximately 0.04, evidence is presented that this is not a stimulus for increased arrhythmia.—The administration of noradrenaline to dogs with coronary artery occlusion can also cause arrhythmia even when administered in extremely small doses. The effect is a biphasic one. An immediate initial arrhythmia may occur and is associated with a rise in blood pressure and a reflex bradycardia but not with any significant elevation of FFA. Such arrhythmias disappear when sinus bradycardia is prevented. Arrhythmia can recur during the infusion of nor‐adrenaline in the absence of haemodynamie change and this is associated with marked elevation of plasma FFA. This late arrhythmia can be suppressed or prevented by the administration of a drug which reduces adipose tissue lipolysis.—It is concluded that elevated plasma FFA can have an ar‐rhythmogenic action when there is associated myocardial hypoxia and this effect can be independent of catecholamine activity.

Triglyceride accumulation protects against fatty acid-induced lipotoxicity

Abstract: Excess lipid accumulation in non-adipose tissues is associated with insulin resistance, pancreatic β-cell apoptosis and heart failure. Here, we demonstrate in cultured cells that the relative toxicity of two common dietary long chain fatty acids is related to channeling of these lipids to distinct cellular metabolic fates. Oleic acid supplementation leads to triglyceride accumulation and is well tolerated, whereas excess palmitic acid is poorly incorporated into triglyceride and causes apoptosis. Unsaturated fatty acids rescue palmitate-induced apoptosis by channeling palmitate into triglyceride pools and away from pathways leading to apoptosis. Moreover, in the setting of impaired triglyceride synthesis, oleate induces lipotoxicity. Our findings support a model of cellular lipid metabolism in which unsaturated fatty acids serve a protective function against lipotoxicity though promotion of triglyceride accumulation.

Myocardial Fatty Acid Metabolism in Health and Disease

Abstract: There is a constant high demand for energy to sustain the continuous contractile activity of the heart, which is met primarily by the β-oxidation of long-chain fatty acids. The control of fatty acid β-oxidation is complex and is aimed at ensuring that the supply and oxidation of the fatty acids is sufficient to meet the energy demands of the heart. The metabolism of fatty acids via β-oxidation is not regulated in isolation; rather, it occurs in response to alterations in contractile work, the presence of competing substrates (i.e., glucose, lactate, ketones, amino acids), changes in hormonal milieu, and limitations in oxygen supply. Alterations in fatty acid metabolism can contribute to cardiac pathology. For instance, the excessive uptake and β-oxidation of fatty acids in obesity and diabetes can compromise cardiac function. Furthermore, alterations in fatty acid β-oxidation both during and after ischemia and in the failing heart can also contribute to cardiac pathology. This paper reviews the regulation of myocardial fatty acid β-oxidation and how alterations in fatty acid β-oxidation can contribute to heart disease. The implications of inhibiting fatty acid β-oxidation as a potential novel therapeutic approach for the treatment of various forms of heart disease are also discussed.

Direct detection of free radicals in the reperfused rat heart using electron spin resonance spectroscopy.

Abstract: The purpose of this study was to use a direct method, that of electron spin resonance (ESR) spectroscopy, to demonstrate that reperfusion after a period of ischemia results in a sudden increase in the production of free radicals in the myocardium. The isolated buffer-perfused rat heart was used with N-tert-butyl-alpha-phenylnitrone (PBN) as a spin-trapping agent. Samples of coronary effluent were taken and extracted into toluene for detection of radical adducts by ESR spectroscopy. After 15 minutes of total, global ischemia, aerobic reperfusion resulted in a sudden burst of radical formation that peaked at 4 minutes. When hearts were reperfused with anoxic buffer, no dramatic increase in radical production was observed. Subsequent reintroduction of oxygen, however, resulted in an immediate burst of radical production of a similar magnitude to that seen in the wholly aerobic reperfusion experiments. The ESR signals obtained (aN = 13.60 G, aH = 1.56 G) are consistent with the spin-trapping by PBN of either a carbon-centered species or an alkoxyl radical, both of which could be formed by secondary reactions of initially-formed oxygen radicals with membrane lipid components.