Protective effects of long-term bradycardial pacing against catecholamine-induced myocardial damage in rabbit hearts

Abstract

A high intravenous dose of norepinephrine (4 micrograms/kg/min for 60 minutes) to New Zealand Red rabbits produced patchy subendocardial damage (estimated stereologically in frozen sections) of about 5% of the heart volume 2 days after application. The damaged areas showed loss of staining for alkaline phosphatase, an enzyme present in normal capillary endothelium. Heart performance (cardiac output index, cardiac work [i.e., cardiac output X mean blood pressure], and dP/dtmax) were significantly lower than in control hearts. Capillary density distribution estimated in nondamaged areas of the left ventricular free wall was inhomogeneous favoring subepicardial regions, while homogeneous transmural distribution was found in control hearts. Bradycardial pacing (reduction of heart rate to 50% of normal) performed for 3-4 weeks prior to norepinephrine administration showed a protective effect against catecholamine damage manifested in a smaller extent of necrosis, in the maintenance of homogeneous transmural capillary distribution in nondamaged areas, and, most importantly, in the maintenance of normal cardiac pump performance at rest and during maximal work in response to acutely administered norepinephrine.