THE EFFECTS OF ENDOTHELIN-1 ON CORONARY PERFUSION-PRESSURE DURING CARDIOPULMONARY-RESUSCITATION IN A CANINE MODEL

Objective: To study the hemodynamic effects of exogenously administere d endothelin-1 (ET-1), a peptide produced by endothelial cells with po tent non-adrenergically mediated vasoconstrictor properties. Methods: A prospective drug intervention study was carried out in a resuscitati on research laboratory, Fifteen mixed-breed dogs were anesthetized and instrumented for hemodynamic monitoring. Asphyxia arrest was produced by clamping the endotracheal tube. Hemodynamic data were collected co ntinuously, Following loss of aortic fluctuations monitored by thoraci c aortic catheter, the animals remained in pulseless electrical activi ty (PEA) for 10 minutes. After 10 minutes of no-flow PEA, closed-chest CPR was begun and the animals were randomized to one of three treatme nt groups (EPI, 0.02 mg/kg epinephrine IV every 3 minutes; ENDO, 100 m u g ET-1 IV at 0 minutes; and EPI/ENDO, a combination of the EPI and E NDO treatments). Results: ENDO and EPI alone produced similar coronary perfusion pressures (CPPs). The EPI/ENDO combination produced signifi cantly improved CPP compared with that of either EPI or ENDO alone. In the EPI group, the best mean CPP was 16 +/- 14 mm Hg and occurred 7 m inutes after drug administration. In the ENDO group, the best mean CPP was 28 +/- 7 mm Hg and occurred 13 minutes after drug administration. In the EPI/ENDO combination group, the best mean CPP was 61 +/- 37 mm Hg and occurred 7 minutes after drug administration (p < 0.05 compare d with the EPI and ENDO groups alone). Conclusion: ET-1 is a potent va soconstrictor. The combination of EPI and ENDO significantly improved CPP compared with that for either agent alone. ET-1 should be investig ated further as a vasoconstrictor in cardiac arrest.