Effect of Propranolol on Early Postischemia Arrhythmias and Noradrenaline and Potassium Release of Ischemic Myocardium in Anesthetized Pigs

In anesthetized open-chest pigs, DL- or D-propranolol (1 mg/kg i.v.) was administered 15 min prior to ligation of the left anterior descending coronary artery (LAD) about halfway from its origin. Sequential myocardial tissue samples were obtained before and after LAD occlusion. The samples were analyzed histofluori-metrically to determine the density of catecholamine containing neurons (quantified morphometrically), and radioenzymatically for total tissue noradrenaline content. The extracellular K concentration was measured using K -sensitive polyvinyl chloride (PVC)-membrane electrodes on the surface of the ischemic myocardium. Under control conditions, ventricular arrhythmias (VA) occurred in a typical la and lb phase. Pretreatment with propranolol diminished the number of VA generated in the lb phase but not those in the la phase; however, these differences were statistically not significant. Neither pretreatment with DL- nor D-propranolol influenced the time course or probability of development of ventricular fibrillation (VF). Coronary artery occlusion led to a significant reduction in noradrenaline concentration of the ischemic myocardium in control animals (from an initial concentration of 526 ± 65 ng/g w/w to 368 ± 75 ng/g w/ w) within the first 5 min of ischemia, whereas noradrenaline concentration remained nearly unchanged in drug-treated animals (from 838 ± 86 to 811 ± 61 ng/g w/w in the DL group and from 701 ±36 to 709 ± 31 ng/g w/w in animals that received D-propranolol). A significant decrease in the density of fluorescing fibers was observed in control animals (from 1.25 ± 0.2% to 0.70 ± 0.1% at 15 min); however, there was no significant change in animals pretreated with DL- or D-propranolol (0.94 ± 0.15% to 0.76 ± 0.06% and from 0.57 ± 0.12% to 0.63 ± 0.13%, respectively) within the same period of time. Thus, the early release of noradrenaline from adrenergic nerve fibers in the ischemic myocardium was prevented by pretreatment with propranolol, whereas the total number of VA occurring until the development of VF was not influenced. The triphasic increase of [K ]e in the center of the ischemic myocardium, reaching [K ]e values of about 15 mmol/L after 6 min of ischemia, was not significantly altered following (J-blockade. These findings support the view that the [K ]e increase in the ischemic myocardium is the predominant arrhythmogenic factor rather than the activation of p-adrenoceptors