Reversal of depressed oxygen consumption accompanying in vivo protamine sulphate-heparin interactions by the prostacyclin analogue, iloprost.
Oxygen consumption (VO2) is known to be depressed 50 to 60% during protamine sulphate reversal of heparin anticoagulation. Accompanying this event are systemic hypotension, pulmonary artery hypertension and thrombocytopaenia. The effect of a pro-stacyclin analogue, iloprost, on protamine-induced changes in VO2 was assessed in this investigation. Three groups of anaesthetised adult mongrel dogs were studied: Group I--control subjects received i.v. normal saline infusions (n = 10); Group II--subjects received low-dose i.v. iloprost infusions (25-50 ng/kg/min) over 30 min (n = 7); and Group III--subjects received high-dose i.v. iloprost infusions (175 ng/kg/min) over 30 min (n = 7). All dogs initially received sodium heparin, 150 IU/kg i.v. Protamine sulphate, 1.5 mg/kg i.v., was subsequently administered over 10 s following the first 20 min of saline or iloprost infusion. Continuous measurements included: mixed venous (SvO2) and arterial (SaO2) oxygen saturation, arterial blood pressure, pulmonary artery pressure, heart rate and carotid artery flow (CaQ). Thermodilution cardiac output (CO) allowed calculation of VO2. Platelet counts were performed before and 3 min after protamine infusion. The VO2 declines in Group II and III subjects compared to Group I controls were markedly less. Maximum VO2 declines in Group I control dogs of -38.2 +/- 26.7% and Group II dogs of -34.1 +/- 36.8% at 75 to 90 s post-reversal contrasted to -2.9 +/- 31.9% in Group III animals at the same time interval. VO2 increases occurred 3 to 10 min after protamine exposure in Group III animals, as did attenuation of systemic hypotensive and pulmonary hypertensive responses in this group.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Surgery, University of Michigan, Ann Arbor.
T W
TW
Wakefield
S K
SK
Wrobleski
J C
JC
Stanley
D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000008:administration & dosage / Q000627:therapeutic use*; D006439:Hemodynamics / Q000187:drug effects; D006494:Heparin Antagonists / Q000633:toxicity*; D016285:Iloprost; D010101:Oxygen Consumption / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D011479:Protamines / Q000494:pharmacology / Q000633:toxicity*
D006494:Heparin Antagonists; D010975:Platelet Aggregation Inhibitors; D011479:Protamines; D011464:Epoprostenol; D016285:Iloprost