DIFFERENT EFFECTS OF CALCIUM-ANTAGONISTS IN A RAT MODEL OF HEART-FAILURE

Calcium antagonists have, to date, shown disappointing effect in chron ic heart failure (CHF), possibly due to their cardiodepressant effects and/or reflex increases in sympathetic tone. Mibefradil is a new, sel ective T-channel calcium antagonist which has no relevant effects on c ardiac contractility, sympathetic activity or neurohormonal levels. Th is study compares the effect of mibefradil with an angiotensin-convert ing enzyme (ACE) inhibitor on systemic and cardiac hemodynamics, cardi ac structure and survival in a rat model of CHF. Rats underwent corona ry artery ligation followed by 9 months treatment with mibefradil, cil azapril or no treatment. Both mibefradil and cilazapril increased surv ival rate to a similar extent over the study treatment period. Both pe riods reduced systolic blood pressure compared with untreated rats, al though the reduction was slightly more marked with cilazapril than mib efradil. Both treatments decreased left ventricular (LV) end-diastolic and central venous pressures without any change in the first derivati ve LV pressure over time or heart rate. Mibefradil decreased LV weight without effecting right ventricular (RV) weight. Both drugs normalize d LV collagen density. The data from this study show that long-term tr eatment with mibefradil results in a survival benefit comparable to th at observed with an ACE inhibitor in a rat model of CHF. Mibefradil wa s also associated with improvements in cardiac hemodynamics, a reducti on in LV weight and fibrosis. Mibefradil may be beneficial in the trea tment of CHF.