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.

Evidence that an excess of plasma free fatty acids (FFA) might lead to primary ventricular fibrillation and sudden cardiac death has hardened over the 36 years since the hypothesis was proposed. When the sympathetic nervous system is stimulated during the onset of an acute coronary syndrome, catecholamine-induced tissue lipolysis occurs, with a surge of plasma FFA. This may overload the acutely ischaemic myocardium and impair glucose utilization. Myocardial oxygen consumption can increase in regional areas of ischaemia, and could lead to abnormal electrophysiological conduction and refractoriness, with irreversible ventricular arrhythmias. Efforts to combat the adverse effects of excess FFA include beta-blockade, increasing glucose availability and extraction, or inhibition of lipolysis. This last approach appears promising, but no method has yet been clearly shown to prevent primary ventricular fibrillation or sudden cardiac death. The hypothesis remains viable. More research is needed to derive treatment that can be applied as soon as the onset of acute myocardial ischaemia is suspected.

No abstract

Studies were made in anaesthetised dog of the effects of repeated acute occlusions of a branch of the anterior descending coronary artery on ventricular refractory periods in adjacent ischaemic and non-ischaemic myocardium. Differences occurred in refractoriness between normal and ischaemic areas in the ventricle. This was greatest 2.5 min after occlusion, and on release of occlusion, ventricular refractory periods reverted to normal within 5 min. Spontaneous ventricular fibrillation was directly and significantly related to the degree of dispersion of refractoriness in a given dog immediately preceding release and following release of occlusion. Infusion of isoprenaline caused significant shortening of refactory period and increased dispersion of refractoriness during ischaemia. Studies of dispersion of refractoriness should prove valuable in assessing the efficiency of metabolic or antiarrhythmic protection against ventricular fibrillation.

1. Certain analogues of thyroxine have been administered to twenty-six hypothyroid patients and 132 euthyroid hypercholesterolaemic men with coronary heart disease. The analogues studied were d-thyroxine, 3: 5: 3\ m=' \ : 5\ m=' \ \ x=req-\ tetraiodothyroformic acid, 3:5:3\m='\:5\m='\-tetraiodothyronamine, 3:5:3\m='\-triiodo-l\x=req-\ thyronine, 3:5:3\m='\-triiodo-d-thyronine,3:5:3\m='\-triiodothyroaceticacid, 3:5-diiodo\x=req-\ l-thyronine, 3:5-diiodo-d-thyronine and 3:5-diiodothyroacetic acid.2. In both hypothyroid and euthyroid patients, most of these analogues reduced the serum cholesterol without necessarily elevating the basal metabolic rate (b.m.r.). Nevertheless, in euthyroid patients with coronary heart disease several produced angina in the absence of any change in b.m.r. and this has been regarded as a sign of increased myocardial metabolism insufficient to be reflected in the overall measure of b.m.r. of all tissues. The possible differential effect of these analogues on the oxygen requirements of various tissues is discussed.3. Although it has been possible to maintain low cholesterol levels for periods up to 3 months during the administration of several of these analogues, the dose required for this purpose was often so close to the dose which provoked angina that most cannot be recommended for widespread administration for the reduction of the hypercholesterolaemia frequently found in patients who have coronary heart disease. d-Thyroxine may prove to be an exception and requires further clinical assessment.