ISCHEMIC AND NONISCHEMIC TISSUE CONCENTRATIONS OF FELODIPINE AFTER CORONARY VENOUS RETROINFUSION DURING MYOCARDIAL-ISCHEMIA AND REPERFUSION- AN EXPERIMENTAL-STUDY IN PIGS

Tissue and plasma concentrations of felodipine, a dihydropyridine (DHP ) calcium antagonist, retroinfused through the coronary venous system were studied in 27 pigs. The animals underwent 45-min myocardial ische mia followed by 4-h reperfusion. Felodipine (7 nmol/ kg body weight) w as administered in the coronary vein for 30 min, 5 min before reperfus ion. Concentrations of felodipine in the ischemic and nonischemic myoc ardium and in plasma were determined by gas chromatography. In the isc hemic area, felodipine concentration at start of reperfusion was 304 /- 285, 171 +/- 160, and 52 +/- 47 nmol/ kg (mean +/- SD) in the subep icardial, midmyocardial, and subendocardial layer, respectively. Corre sponding concentrations in the nonischemic area were 15 +/- 13, 17 +/- 14, and 16 +/- 15 nmol/kg (p < 0.05 vs. ischemic area). Subepicardial concentration was highest at start of reperfusion, whereas concentrat ions in other layers peaked at the end of retroinfusion. The transmura l concentration gradient of felodipine in the ischemic area decreased progressively during the reperfusion period. The nonischemic tissue co ncentration increased slightly during the reperfusion period. The plas ma concentration was very low throughout the study (peak = 3.2 +/- 1.4 nM at 30 min). Coronary venous retroinfusion of felodipine resulted i n profound accumulation of the drug, specifically in ischemic myocardi um. The plasma concentration was low and did not affect systemic hemod ynamics. Coronary venous retroinfusion is considered an advantageous t echnique for selective drug delivery.-