Effects of felodipine on isolated failing rat heart

This study was designed to examine the effects of the dihydropyridine calcium antagonist, felodipine, on the isolated, foiling rat heart Wistar rats underwent uninephrectomy to induce hypertension and heart failure and, after 10 days' observation, deoxycorticosterone (DOCA; 30mg/kg s.c) was given once a week for five weeks, during which time 1% NaCl solution was supplied as drinking water. After five weeks the hearts were excised and perfused according to the Langerdoff technique. Heart rate (HR), systolic (SVP) and diastolic ventricular pressures (DVP), dP/dT and coronary flow (CF) were checked or baseline and every five minutes during a 30-minute period and perfusate norepinephrine (NE) levels were measured. The hearts were randomly allocated to two groups of 10: Group 1: perfused with Krebs-Henseleit solution only; Group 2: perfused with Krebs-Henseleit solution plus felodipine 40ng/ml. Group 1 showed no significant change in SVP, DVP, CF, HR or dP/dT. Group 2 showed a significant reduction of dP/dT (60%, p=0.018) and SVP (30%, p=0.035) and a significant increase of DVP (25%, p<0.001). No significant differences were seen in CF and NE levels were not reduced in either group or between the groups. Our data suggest that these negative inotropic effects ore exclusively due to felodipine, but the reported beneficial effects ore probably due to a more complex mechanism.