PCA50941, A NEW 1,4-DIHYDROPYRIDINE, REVERSES ENDOTHELIN-INDUCED CARDIOGENIC-SHOCK IN THE ANESTHETIZED GOAT

This study was designed to test the hypothesis that the properties of novel 1,4-dihydropyridine PCA50941 could favor the recovery of cardiog enic shock. Coronary blood flow (CBF), measured with an electromagneti c flow probe placed on the left circumflex coronary artery, systemic a rterial pressure and heart rate were recorded in 24 anesthetized goats ; left ventricular pressure and dP/dt were also recorded in 19 of thes e goats. Under control conditions, intracoronary injections in 5 goats of PCA50941 (10-120 mu g) caused smaller reductions of CBF than those of Bay K 8644 (0.3-10 mu g) (the reduction of CBF by 120 mu g PCA5094 1 was 25% and that by 10 mu g Bay K 8644 was 43%), and i.v. infusions in 4 goats of PCA50941 (10-300 mu g/min) did not modify CBF nor the ot her hemodynamic variables recorded, whereas i.v infusion of Bay K 8644 (10-30 mu g/min) reduced CBF by 20% and increased arterial pressure, left ventricular pressure and dP/dt. During control conditions and end othelin-induced cardiogenic shock, respectively, the values for 15 goa ts were: for CBF, 33+/-4 vs. 16+/-4 ml/min; for mean arterial pressure , 88+/-4 vs. 60+/-5 mm Hg; for left ventricular systolic pressure, 102 +/-5 vs. 75+/-4 mm Hg; for dP/dt, 1453+/-147 vs. 925+/-101 mm Hg/s (al l P<0.05), and for heart rate, 77+/-6 vs. 81+/-6 beats/min (P>0.05). I ntravenous infusion of PCA50941 (100 mu g/min) reversed the hemodynami c variables from the shock state to control values within 20 min in 5 of 6 animals, whereas i.v. administration of Bay K 8644 (10-30 mu g/mi n) was not effective in 4 of 5 animals, and the vehicle (DMSO) was not effective in none of 4 animals in reversing the hemodynamic shock sta te. Therefore, it is suggested that PCA50941, a novel 1,4-dihydropyrid ine, has a cardiovascular profile that might be suitable for treating cardiogenic shock states.