Dose-Effect Relationships of Prostaglandin E1 in Severe Endstage Chronic Heart Failure.

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Prostaglandin E1 is a potent vasodilator in severe chronic heart failure. To evaluate the time sequence and magnitude of prostaglandin E1's hemodynamic effects a dose finding study was performed in 24 patients. Right heart catheterization was performed and prostaglandin E1 was administered via a central venous line in incremental doses of 2.5, 10, 20, 30 and 40ng/kg/min, each dose, lasting 15min before hemodynamic evaluation. The first significant change was a∼20% decrease in systemic vascular resistance index accompanied by a∼18% increase in cardiac index at an infusion rate of 2.5ng/kg/min of prostaglandin E1, which was sustained at 5ng/kg/min in all patients. A dose response-curve with cumulative doses ranging from 2.5 to 25ng/kg/min of prostaglandin E1 was established in a subset of 14 patients due to 10 drop-outs at lower dosages. At 2.5 and 5ng/kg/min of prostaglandin E1, cardiac index increased by 18% (p<0.05) and peripheral resistance decreased by 18% (p<0.01). These changes were sustained up to a maximal dose of 25ng/kg/min, which was tolerated by all patients in this group. At 15 and 20ng/kg/min of prostaglandin E1 a significant decrease in blood pressure of -4mmHg (p<0.05) was observed which was reversed at the next dose step. In a second analysis maximal tolerated dosages of prostaglandin E1 were evaluated in all 24 patients (group A, 26±2ng/kg/min), and in two subsets using a maximum tolerated dose of 20ng/kg/min as a cutpoint (B: 14 patients, 34±2ng/kg/min; C: 10 patients, 15±2ng/kg/min) Then the respective peak dosages were halved for continuous infusion through 12 hours. In the acute study pulmonary capillary wedge pressure (by A: -11%, p<0.01; B: -4%, p<0.01; C: -22%, p<0.01) and systemic vascular resistance (by A: -32%, p<0.0001; B: -25%, p<0.001; C: -43%, p<0.001) decreased significantly in all three groups and cardiac index increased (by A: +38%, p<0.0001; B: +33%, p<0.0001; C: +59%, p<0.0001). In the chronic study these changes were sustained. Furthermore, mean arterial pressure (by A: -14%, p<0.0001; B: -13%, p<0.001; C: -13%, p<0.05), right atrial pressure (by A: -36%, p<0.0001; B: -36%, p<0.01; C: -30%, p<0.01), pulmonary artery pressure (by A: -16%, p<0.0001; B: -16%, p<0.01; C: -19%, p<0.01) and pulmo-nary vascular resistance (by A: -28%, p<0.01; B: -31%, p<0.01; C: -25%, p<0.01) were significantly reduced after 12 hours. Conclusion. These results demonstrate potent hemodynamic effects of low-dose prostaglandin E1 in severe heart failure. While systemic effects appear rapidly, a slow onset of the pulmonary effects was observed.

Dose-Effect Relationships of Prostaglandin E1 in Severe Endstage Chronic Heart Failure.

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