Atrial natriuretic factor release during transient myocardial ischemia: A placebo-controlled study in man

Atrial natriuretic factor (ANF) exerts a vasodilatory effect on the coronary bed in myocardial ischemia. Besides wall stretch, ANF release can also be triggered by endothelin in experimental models. We studied the time course of ANF release and its relationship with endothelin during transient myocardial ischemia in man. Twelve patients subjected to the dipyridamole echocardiography test (DET) in a single-blind, randomly balanced, placebo-controlled setting were studied. Circulating ANF and endothelin were monitored during both dipyridamole and placebo. Dipyridamole caused left ventricular (LV) dyssynergy in 6 patients (group 1: multiple or isolated coronary artery stenosis) and acute left atrial dilation in 5 out of 6. In these 5 patients, a progressive rise of circulating ANF was found soon after LV dyssynergy, starting from time +8 min (55 ± 12 vs. 40 ± 7 at time 0 and 42 ± 8 pmol/l time-matched placebo, p <0.05 for both), becoming highly significantly different from +10 min (72 ± 13 vs. 40 ± 7 at time 0 and vs. 47 ± 5 pmol/l time-matched placebo, p <0.01 for both) up to the end of the study (+40 min). Circulating ANF and echocardiographic parameters did not vary in the other 6 patients undergoing the DET (group 2) as well as during placebo in both groups. The DET caused heart rate and the rate-pressure products to increase to the same extent in both groups(+12 and +13%; +13 and +15%, respectively). Circulating endothelin did not vary. The consistent and long-lasting rise of circulating ANF in patients with coronary artery disease during transient myocardial ischemia indicate that ANF measurements during chest pain may be an important marker of the reduction in myocardial perfusion and LV dysfunction. Further studies will indicate if ANF may play a physiological role to attenuate anginal attacks.