RELATION BETWEEN MYOCARDIAL BETA-ADRENOCEPTOR DENSITY AND HEMODYNAMICAND NEUROHUMORAL CHANGES IN A RAT MODEL OF CHRONIC MYOCARDIAL-INFARCTION - EFFECTS OF IBOPAMINE AND CAPTOPRIL

Objectives: The purpose of this study was to investigate the changes i n beta-adrenoceptor density (B-max) and distribution in a model of chr onic myocardial infarction in rats, and to relate possible changes to hemodynamic and neurohumoral abnormalities. In addition, we examined t he effects of 8 weeks treatment with ibopamine and captopril. Methods: There were 3 experiments: (1) B-max and plasma catecholamines were ex amined (n = 46), (2) B-max was compared in infarcted and non-infarcted tissue (n = 13), and (3) contractile function was evaluated by isolat ed heart perfusion (n = 40). Of rats in Expts. (1) and (3), 50% had my ocardial infarction induced by coronary ligation and 50% were controls . Each group was divided between ibopamine, ibopamine and captopril, o r standard (no drug) treatment. Results: B-max was not decreased in ra ts with myocardial infarction (10.8 +/- 0.8 fmol/mg protein), compared to normal rats (11.4 +/- 0.6 fmol/mg protein), and the ratio beta(1)/ beta(2) was also unaffected. In infarcted tissue, B-max was significan tly (P = 0.03) lower than in non-infarcted tissue. Baseline left ventr icular pressure, systolic and diastolic dP/dT were all impaired (P < 0 .001), and plasma norepinephrine levels were elevated in rats with myo cardial infarction (16.03 +/- 230 vs. 1287 +/- 83 pg/ml; P < 0.05), co mpared to normals. Both ibopamine alone and in combination with captop ril reduced the elevated plasma norepinephrine levels in infarcted rat s (P < 0.001), but only the combination of the 2 drugs significantly i ncreased B-max in infarcted rats (14.7 +/- 0.8 fmol/mg protein; P = 0. 03 vs. untreated myocardial infarction), while ibopamine alone had no significant effect (13.1 +/- 1.1 fmol/mg protein; p = ns). Also, activ e drug treatment had no significant effect on the hemodynamic changes. Conclusions: In this coronary artery ligation model of myocardial inf arction in rats, no beta-adrenoceptor down-regulation is observed, des pite marked abnormalities in baseline left ventricular function and pl asma norepinephrine levels. The combination of ibopamine and captopril significantly increases B-max in infarcted rats, which is accompanied by a reduction in plasma norepinephrine levels, but not by an improve ment in hemodynamic parameters.