NEUROHUMORAL AND HEMODYNAMIC-EFFECTS OF IBOPAMINE IN A RAT MODEL OF CHRONIC MYOCARDIAL-INFARCTION AND HEART-FAILURE

There is increasing evidence that both neurohumoral and hemodynamic factors play a role in disease progression in chronic heart failure (CHF). To examine the influence of the oral dopamine agonist ibopamine on these factors, we studied 20 rats with chronic myocardial infarction and CHF, and compared them with 20 normal rats. After 6 weeks, rats were randomly divided between control treatment (50%) or ibopamine (50%) for 3 weeks. At the end of the study, plasma and tissue neurohumoral parameters, as well as hemodynamics, were determined. In infarcted rats, the elevated plasma norepinephrine (PNE) levels were reduced by ibopamine (251 +/- 19 vs. 138 +/- 32 pg/ml; p <0.05). Other plasma neurohormones measured (epinephrine, renin, aldosterone, and angiotensin converting enzyme [ACE]) were not significantly increased in rats with myocardial infarction and were not affected by ibopamine. Cardiac (tissue) ACE was increased in infarcted rats (12.1 +/- 1.9 U/l/min) and was significantly lowered by ibopamine (9.6 +/- 1.0 U/l/min; p <0.05); renal ACE was unaffected. Blood pressure and heart rate were similar in the two groups and were not influenced by ibopamine treatment. In conclusion, in chronic myocardial infarction and CHF in rats, ibopamine reduces the elevated levels of PNE and cardiac ACE. Further research will be needed to determine whether this effect may lead to a favorable influence on disease progression in CHF.