Effect of phosphodiesterase III inhibitor (Olprinone) on thoracic duct lymph flow in anesthetized sheep with experimentally induced heart failure by endothelin-1.
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.
Tomoyasu
M
M
Department of Surgery, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan.
Onizuka
M
M
Inagaki
M
M
Sato
Y
Y
Yamamoto
T
T
Ishikawa
S
S
Mitsui
T
T
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D002496:Central Venous Pressure / Q000187:drug effects; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000008:administration & dosage / Q000009:adverse effects*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D006333:Heart Failure / Q000139:chemically induced* / Q000188:drug therapy*; D007093:Imidazoles / Q000494:pharmacology*; D008168:Lung / Q000737:chemistry / Q000187:drug effects; D008297:Male; D008955:Models, Cardiovascular; D011728:Pyridones / Q000494:pharmacology*; D012079:Renal Circulation / Q000187:drug effects; D012756:Sheep; D012770:Shock, Cardiogenic / Q000139:chemically induced / Q000188:drug therapy; D013897:Thoracic Duct / Q000187:drug effects; D013997:Time Factors; D016896:Treatment Outcome; D014655:Vascular Resistance / Q000187:drug effects
D019332:Endothelin-1; D004791:Enzyme Inhibitors; D007093:Imidazoles; D011728:Pyridones; C059498:olprinone; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3