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.

KÖPEKLERDE DENEYSEL MİYOKARD ENFARKTÜSÜNDE SERUM LIpID, KOLESTEROL, GLİKOZ, Na, K, ve Ca DÜZEYLERİ

“…Yapılan birçok araştırmada enfarktüsü takip eden günlerde dolaşımda serum lipidleri düzeyi artmaktadır (11,12,18,22) Ancak yaptığımız bu çalışmada serum lipidlerinde artış kaydedilmesine rağmen' (Şekil 2B) literatürde belirtildiği gibi (11,12,18,22) bu artışın, aritmilerin şiddeti ile ilgili bulunamamıştır. Sadece operasyon yapılan hayvanlarda sadece lipid seviyesinde benzer artış olmasına rağmen aritmiye rastlanmaması bu sonucu desteklemektedir (Şekil 2e).…”

On-line Cardiovascular Applications of Microcomputers in Intensive Care

“…These alterations result in a disturbance of glucose utilization, socalled stress hyperglycemia. Moreover, under these conditions and due to the accumulation of free fatty acids in the ischemic myocardium, severe ventricular arrhythmias as well as a progression of myocardial cell damage are likely to occur (Kurien and Oliver 1970;Kurien et al 1971;Oliver et al 1968). Glucose-insulin-potassium infusions (GIK) in AMI have been used in a number of clinical trials in order to overcome these deleterious effects (Mantle et al 1981;Rogers et al 1976Rogers et al ,1979Sodi-Palleres et al (1962)).…”

“…Some of the postulated benefits of GIK treatment in AMI are: a decrease of FFA, a reduction of potassium efflux, a repletion of intracellular potassium stores, an enhancement of myocardial glucose utilization, a reduction of myocardial oxygen consumption, and an improvement in coronary perfusion. These changes should reduce severe life-threatening arrhythmias, limit infarct size, improve left ventricular function, and reduce hospital mortality (von Arnim and Bolte 1980;Brachfeld 1973;Kurien et al 1971;Manke et al 1981;Oliver 1973). With an "open loop" fixed GIK regime as in the studies mentioned above, severe hyperglycemia as well as hypoglycemia were not infrequently seen, because the degree of impairment of the insulin sensitivity could not be predicted.…”

Anti‐arrhythmic effects of (‐)‐carnitine chloride and its acetyl analogue on canine late ventricular arrhythmia induced by ligation of the coronary artery as related to improvement of mitochondrial function

“…Recently much attention has been focused on the arrhythmogenicity of FFA under conditions of ischaemia as a result of many clinical and experimental observations (Oliver et al, 1968;Kurien et al, 1969Kurien et al, , 1971Willebrands et al, 1973;Cowan & Vaughan Williams, 1977;. Loss of (-)-carnitine from the myocardium and accumulation of FFA and its intermediates such as long chain acyl CoA esters and long chain acyl (-)-carnitine in the cardiac tissue during ischaemia (Whitmer et al, 1978) and consequent inhibition of the translocation of adenosine 5'-triphosphate (ATP) and adenosine 5'-pyrophosphate (ADP) across the inner mitochondrial membrane (for references see: Shug, 1979) have been advocated as a cause of the mitochondrial respiratory dysfunction, culminating in the deterioration of the myocardial mechanical performance and serious cardiac arrhythmias (Kjekshus & Mj0s, 1972;Folts et al, 1978) and it was postulated that replenishment of (-)-carnitine would reduce the incidence of serious arrhythmias by improving fatty acid metabolism.…”