Effects of linolenic acid on the canine heart

Disturbances in lipid metabolism have been observed during the early phase of acute myocardial ischemia. Accumulation of fatty acids in and around the ischemic cardiac cells has been implicated to play a role in both contractile and electrophysiological abnormalities. Linolenic acid is an essential fatty acid and constitutes the phospholipid moiety of the cell membrane. The purpose of this work was to study the effects of linolenic acid on the heart using canine preparations. A direct left atrial injection was used as the route of administration because intravenous injections of linolenic acid inevitably cause pulmonary edema. A surface lead electrocardiogram (ECG), an epicardial electrogram, femoral arterial pressure, left ventricular pressure and its time derivative (dp/dt) were recorded before and after drug administration. Various dosages of linolenic acid (1 mg, 5 mg, 10 mg, 20 mg, 30 mg and 60 mg/kg) and a control buffer solution were tested. The results showed that linolenic acid has a potent dose-dependent bradycardic and myocardial depression effect starting from a dose of 5 mg/kg (delta HR = -20.1 +/- 4.0 bpm, delta dp/dt = 364.3 +/- 66.0 mmHg, sec-1, p less than 0.01 vs. control). At a high dose of 30 mg/kg, linolenic acid induced premature ventricular complexes. Furthermore, ventricular tachycardia was observed in 5 of the 8 dogs (62.5%) receiving the high dose of 60 mg/kg. We conclude that linolenic acid has profound effects on the canine heart; at a low dose, it causes bradycardia and myocardial depression, while at a high dose, it also produces ventricular irritability.