Effect of prostacyclin and prazosin in the treatment of congestive heart failure; With special reference on the sympathetic nervous system.

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Abstract
Therapy to decrease the load in congestive heart failure is now classified as acute and chronic vasodilator therapy. In this symposium, we presented prostacycline (PG I2) as an acute and prazosin as a chronic vasodilator. Their hemodynamic and clinical effectiveness were evaluated and their effect on the sympathetic nervous system was also studied. We studied the effect of intravenous prostacyclin infusion in doses of 22±11 ng/kg/min in nine patients with severe congestive heart failure refractory to digitalis and diuretic drugs. After prostacyclin infusion, mean pulmonary capillary wedge pressure decreased from 21.0±7.9 to 15.0±6.6 mmHg (p-5 (p-5 (p-5 (p2 (p2 (p<0.001). Moreover, prostacyclin therapy counteracted the sensation of coldness of the limbs and face, and patients felt warmth and mild flushing of the face. The effect of prazosin on the exercise duration time until dyspnea was evaluated by the treadmill test. In comparison with a placebo, prazosin significantly increased this time from 11.4±5.6 min to 13.0±5.8 (p<0.005) and significantly reduced systolic blood pressure from 121±22 mmHg to 114±20 (p<0.005). These data suggest that prazosin is effective in treating chronic left ventricular failure. The effect of vasodilators on the sympathetic nervous system in congestive heart failure is not known. After prostacyclin therapy, plasma norepinerphrine levels did not change significantly (824±375 pg/ml vs 880±468, NS). During chronic therapy with prazosin, plasma norepinerphrine levels increased significantly (766±209 pg/ml vs 416±209 with placebo, p<0.001). When mean pulmonary capillary wedge pressure was maintained at around 15 mmHg by oral prazosin administration, prazosin increased the plasma norepinerphrine level significantly. (384±141 to 450±121 [1 hr, p<0.001], 580±161 [2 hr, p<0.001], 504±98 [3 hr, p<0.001]). These results suggest that the sympathetic nervous system may play an important role in congestive heart failure during both acute and chronic vasodilator therapy.

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