Intracoronary infusion of Gd3+ into ischemic region does not suppress phase Ib ventricular arrhythmias after coronary occlusion in swine
American Journal of Physiology. Heart and Circulatory Physiology
Soler. Intracoronary infusion of Gd 3ϩ into ischemic region does not suppress phase Ib ventricular arrhythmias after coronary occlusion in swine. .-Increased mechanical tension in the ischemic region during acute coronary occlusion might favor the occurrence of phase Ib ventricular arrhythmias. We aimed to investigate whether intracoronary administration of Gd 3ϩ , a stretch-activated channel blocker, into the ischemic zone reduces the incidence of these arrhythmias. In thiopentalanesthetized,
... pen-chest pigs, the left anterior descending coronary artery (LAD) was ligated for 45 or 48 min. Phosphate-free, HEPESbuffered saline bubbled with 100% N 2 was infused into the ischemic region for 4 min, starting 5 min (series A; n ϭ 16) or 20 min (series B; n ϭ 16) after coronary occlusion, at a rate doubling the baseline blood flow. Animals were blindly allocated to receive 40 M Gd 3ϩ or only the buffer during the final 2 min of the infusion. There were no differences between groups with respect to hemodynamic variables, plasma K ϩ levels, or size of the ischemic region. In neither series was the number of phase Ib premature ventricular beats reduced by Gd 3ϩ (46 Ϯ 20 in untreated vs. 91 Ϯ 37 in Gd 3ϩ -treated animals in series A and 19 Ϯ 7 vs. 22 Ϯ 13, respectively, in series B; both P ϭ not significant). The occurrence of ventricular tachycardia or fibrillation was significantly associated with the magnitude of early ischemic expansion of the LAD region, as measured by ultrasonic crystals, but was also not prevented by Gd 3ϩ . These results argue against a major role of stretch-activated channels inside the area at risk in the genesis of phase Ib ischemic ventricular arrhythmias. ischemia; stretch; mechanoelectrical coupling; ventricular dilation; sudden death VENTRICULAR FIBRILLATION secondary to acute myocardial ischemia is one of the major causes of sudden cardiac death in humans, but the mechanisms of ischemic ventricular arrhythmias remain unclear (43). There is special uncertainty on the determinants of the Ib phase of arrhythmias, which takes place ϳ12 to 40 min after interruption of coronary flow (23) and accounts for most early lethal arrhythmias in animal studies (4, 5, 12, 13, 23, 36) . Because phase Ib arrhythmias coincide with the rise in tissue resistivity and are facilitated by connexin deficiency, it has been suggested that cellular uncoupling favoring inhomogeneous conduction and reentry might be the underlying mechanism (12, 14, 15, 25, 28, 36) , although nonreentrant mechanisms and neural influences have been proposed as well (1, 10, 23, 32, 34, 35) .