Antilipolytic therapy in angina pectoris. Reduction of exercise-induced ST segment depression.

Abstract

A double-blind cross-over study was performed on 12 men sith stable angina pectoris in order to determine the effect of antilipolytic treatment on exercise tolerance and exercise-induced electrocardiographic changes. The men were exercised to the onset of anginal pain using a reproducible and standardized ergometric load. A nicotinic acid analogue was used to reduce plasma free fatty acids and free glycerol before and during exercise testing and to eliminate their post-exercise rise. This was associated with significant reduction of exercise-induced ST segment depression (p less than 0-005), though there was no significant difference in the duration of exercise before the oneset of pain. A change in the prportions of lipid and carbohydrate for oxidation by the ischaemic myocardium, making relatively more glucose available, is a likely explanation.

Amphipathic metabolites and membrane dysfunction in ischemic myocardium.

“…Some reports indicate that infusion of neutral lipid and heparin in dogs with myocardial ischemia exacerbates arrhythmia (Kurien et al, 1969(Kurien et al, , 1971), but results have been inconsistent (Opie et al, 1971). In patients, antipolytic agents decrease ST alterations induced by exercise or ischemia (Luxton et al, 1976;Russell and Oliver, 1978b) with a concomitant reduction of plasma FFA (Russell and Oliver, 1978b). Antiarrhythmic effects are particularly marked when the induced fall in plasma free fatty acids is rapid (Rowe et al, 1975).…”

Prevention of arousal-induced hyperlipidemia by glucose ingestion.

“…According to some investigators (15) the toxic effects of elevated [FFA] may not occur until the plasma level exceeds the level needed to saturate the binding sites on blood albumin. This is thought to correspond with an [FFA] of about 1800 /jmol/liter (16) when the [FFA]/albumin molar ratio exceeds 3. At this concentration there is thought to be an increase in the level of unassociated fatty acids in the blood and interstitial fluid (15).…”

“…Recently it has been shown that cultured bovine aortic endothelial cells accumulate fatty acids from the perfusing medium when [FFA] exceeds only 500 //mol/ liter (11). Furthermore, the reduction of [FFA] from 700 /imol/liter to 350 jtmol/ liter has been found to reduce ST-segment depression in coronary patients undergoing stress tests (16). ST-segment depression measured from an ECG is an index of myocardial oxygenation.…”

“…Since unbound fatty acids in the blood are in equilibrium with those in the intracellular space, a high [FFA] leads to excessive fatty acid accumulation within the endothelial cell membranes and cytoplasms (15). Excessive fatty acids could then produce their toxic effects by altering the fluidity of the lipid bilayer, influencing the action of vital enzymes or receptors, or disrupting membrane transport systems (15,16).…”

Effect of myocardial ischaemia and antilipolytic agents on lipolysis and fatty acid metabolism in the in situ dog heart

“…Antilipolytic treatment has recently been shown to reduce the ischaemic injury in these patients [I 1, 301 and to reduce the exercise-induced ST-segment depression in patients with angina pectoris [15]. In experimental studies elevated plasma FFA concentrations enhance myocar-0036-551 3/79/ 1000-0559$02.00 0 1979 Medisinsk Fysiologisk Forenings Forlag dial oxygen consumption [3, 171, suggesting that the deleterious effect of FFA during myocardial ischaemia may reflect an increased oxygen requirement in ischaemic tissue.…”