Protamine-induced pulmonary venoconstriction in heparinized pigs.
Reversal of heparin anticoagulation with protamine may be associated with acute pulmonary vasoconstriction. The specific site of pulmonary vasoconstriction has not been determined. This study was designed to determine the site of protamine-induced pulmonary vasoconstriction and the role of nitric oxide (NO) after protamine injection. Pigs were anesthetized and instrumented with catheters for monitoring pulmonary arterial, systemic arterial, and central venous pressures. Pulmonary capillary pressure was estimated using the arterial occlusion concept, while left atrial pressure was estimated from the equilibrium wedge pressure. Hemodynamic measurements were made during baseline, before and after heparin (200 U/kg), at peak pressure response after protamine injection (2 mg/kg), and 10 and 30 min thereafter. In the control group, pulmonary vascular resistance (PVR) values during baseline and after heparin were identical (2.7 +/- 0.4 mm Hg.L-1.min-1). At peak protamine response (1-2 min) PVR increased to 8.0 +/- 1.6, but returned to baseline value after 10 min (2.8 +/- 0.3) and remained stable for 30 min (2.2 +/- 0.3). The increase in PVR after protamine was primarily due to an increase in venous resistance from 1.0 +/- 0.2 to 4.9 +/- 1.4 mm Hg.L-1.min-1, and a much smaller increase in arterial resistance from 1.7 +/- 0.3 to 3.4 +/- 0.6 mm Hg.L-1.min-1. A second group was treated with nitrow-L-arginine (LNA, 20 mg/kg) to inhibit NO release, and then heparin and protamine were administered as in the first group. Heparin had no effect on pressures, but protamine increased PVR by the same magnitude as in Group 1.(ABSTRACT TRUNCATED AT 250 WORDS)
Hakim
T S
TS
Department of Surgery, State University of New York Health Science Center, Syracuse 13210, USA.
Picone
A
A
Oleary
C E
CE
Camporesi
E M
EM
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002496:Central Venous Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D006493:Heparin / Q000008:administration & dosage*; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000503:physiopathology; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology; D019335:Nitroarginine; D011479:Protamines / Q000009:adverse effects / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000187:drug effects; D011667:Pulmonary Veins / Q000187:drug effects*; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000009:adverse effects / Q000494:pharmacology*
D011479:Protamines; D014662:Vasoconstrictor Agents; D019335:Nitroarginine; D009569:Nitric Oxide; D006493:Heparin; D001120:Arginine