endothelin-1 and olprinone

Effects of loprinone hydrochloride on plasma ET-1 and TNF-alpha levels were assessed in patients with acute heart failure (AHF).. Thirty patients with AHF were divided into 2 groups and treated with loprinone hydrochloride (0.3 pg/kg/min) (n = 15) or placebo (n = 15). Twenty healthy controls were also included. Plasma ET-1 and TNF-alpha were significantly higher in the 30 AHF patients than in the healthy controls. In AHF patients, loprinone hydrochloride lowered plasma ET-1 and TNF-alpha (p < 0.01).. ET-1 and TNF-alpha may play pathophysiological roles in the progression of AHF. Loprinone hydrochloride is effective in reducing plasma ET-1 and TNF-alpha levels in AHF patients.

Topics: Adult; Cardiotonic Agents; Endothelin-1; Female; Heart Failure; Humans; Imidazoles; Male; Middle Aged; Phosphodiesterase Inhibitors; Pyridones; Tumor Necrosis Factor-alpha

We investigated the short-term effects of a phosphodiesterase III inhibitor (Olprinone) on hemodynamics and thoracic duct lymph flow in anesthetized open-chest sheep with heart failure induced by endothelin-1 (cardiogenic shock). Ultrasound transit-time flow probes were attached to the thoracic duct, the ascending aorta and the renal artery. Arterial, pulmonary and central venous pressures were monitored. Endothelin-1 was infused intravenously at a dosage that reduced cardiac output to 50% or more of baseline (n=11). The effects of Olprinone were examined (n=5) by intravenous infusion after endothelin-1 administration. Other sheep (n=6) were used as controls. Olprinone significantly increased cardiac output that had been decreased by endothelin-1 and further increased thoracic duct flow that had been increased by endothelin-1. Increased arterial and pulmonary pressures induced by endothelin-1 administration were rapidly decreased by Olprinone. Renal arterial flow and central venous pressure were, however, unchanged by Olprinone. Overall, Olprinone acutely improved experimental cardiogenic shock (heart failure) induced by endothelin-1, and maintained thoracic duct lymph flow at a high level after endothelin-1 administration.

Topics: 3',5'-Cyclic-AMP Phosphodiesterases; Animals; Cardiac Output; Central Venous Pressure; Cyclic Nucleotide Phosphodiesterases, Type 3; Disease Models, Animal; Endothelin-1; Enzyme Inhibitors; Female; Heart Failure; Imidazoles; Lung; Male; Models, Cardiovascular; Pyridones; Renal Circulation; Sheep; Shock, Cardiogenic; Thoracic Duct; Time Factors; Treatment Outcome; Vascular Resistance