EFFECTS OF PROPRANOLOL, PINDOLOL AND CARTEOLOL ON ACUTE REGIONAL MYOCARDIAL-ISCHEMIA IN ISOLATED RABBIT HEARTS

Catecholamines play a major role during initiation and propagation of myocardial ischemia (MI). Therefore their influence on the size of an acute regional MI was investigated in isolated, coronary ligated rabbit hearts during electrical pacing at different rates (Langendorff, constant pressure: 70 cm H2O, Tyrode solution, Ca2+ 1.8 mmol/l). MI was quantified from NADH-surface-fluorescence-photography. After coronary occlusion the stimulation-rate was increased stepwise from 180 beats/min to 300/min. Experiments were performed in hearts of control and reserpinized rabbits (reserpine 7.0 mg/kg i.p. 24 h before preparation). Hearts of control animals were submitted to beta-blockade by propranolol (10(-8) mol/l) or the partial agonists pindolol (10(-6) mol/l) or carteolol (10(-6) mol/l). In untreated control hearts MI was significantly enlarged with increasing heart-rate (p < 0.05). At 300/min MI was doubled as compared to that observed at 1801 min. In hearts of reserpinized animals this effect was absent (p > 0.05). Moreover, in control hearts the growth of MI could be prevented by beta-blockade with propranolol, pindolol or carteolol (p > 0.05), however these hearts became insufficient as indicated by an increase in left ventricular enddiastolic pressure. Therefore we conclude that the pacing-rate dependent growth of MI seems not to be primarily related to myocardial left ventricular pressure nor to the heart rate. Nevertheless the growth of MI is strictly related to the release of catecholamines and might be caused by oxygen free radicals generated from noradrenaline by autoxidation. Propranolol, pindolol or carteolol possess cardioprotective properties independent of their influence on the heart-rate and possibly due to a recently described free radical scavenging effect.