Failure of pindolol and metoprolol to reduce the size of non-reperfused infarcts in dogs using area at risk techniques.

Abstract

Recent studies have shown that long term mortality after acute myocardial infarction is reduced by chronic beta-blocker therapy, however, the mechanism is not well understood. Our objective was to determine whether the selective beta blocker, metoprolol, or the nonselective intrinsic sympathomimetic activity (ISA)-blocker pindolol, reduce infarct size as a function of an area at risk (AR) in a permanent infarction model in dogs and which blocker is preferable in regards to myocardial function. Dogs were instrumented with ultrasonic crystals to measure regional function in nonischaemic and infarct margin segments. Left ventricular (LV) pressures, LV dP/dt and heart rate (HR) were monitored. Dogs were subjected to a 6 h LAD coronary artery occlusion and were randomised to a control (n = 9), pindolol (n = 10), and metoprolol (n = 9) group. At 30 and 90 min post occlusion saline, pindolol (3 micrograms X kg-1 and 12 micrograms X kg-1) or metoprolol (12 micrograms X kg-1 and 48 micrograms X kg-1) were given intravenously. The in vivo AR was determined by autoradiography, the in vitro AR by postmortem dye infusion and the area of necrosis by tetrazolium staining. Pindolol and metoprolol decreased LV dP/dt by 20% (P less than 0.05). Metoprolol also decreased HR by 20% (P less than 0.05) and shortening of nonischaemic segments by 12% (P less than 0.05) following the 1st and 2nd dose. Function in infarct margin segments was not changed in either group. Blood flow, measured by microspheres, was similar in the three groups.(ABSTRACT TRUNCATED AT 250 WORDS)