Decreased oxygen consumption as a toxic manifestation of protamine sulfate reversal of heparin anticoagulation.
Protamine sulfate has been observed to interfere with the control of isolated mitochondrial respiration in vitro. This study was designed to determine if oxygen consumption changes in intact animals occur in vivo during protamine administration. Oxygen consumption was assessed in seven dogs anticoagulated with heparin (150 IU/kg) and reversed 30 minutes later with protamine sulfate (1.5 mg/kg). Oxygen saturations measured included arterial (SaO2 arterial), mixed venous (SvO2 systemic), jugular (SvO2 jugular), portal (SvO2 portal), and coronary (SvO2 coronary). Cardiac output (CO) and carotid artery flow determinations allowed calculation of systemic oxygen consumption (VO2 systemic) and cerebral oxygen consumption VO2 cerebral. Hemodynamic measurements included arterial blood pressure (BP), pulmonary artery systolic and diastolic pressures (PAS, PAD), and heart rate (HR). Protamine sulfate administration resulted in hypotension (delta BP -64 mm Hg), pulmonary hypertension (delta PAS + 13 mm Hg, delta PAD + 11 mm Hg), and bradycardia (delta HR -30). Shortly after protamine administration, CO fell 54% and carotid artery flow fell more than 50%, yet declines in SvO2 systemic and SvO2 jugular were not observed. In fact these parameters increased 3% and 2%, respectively. VO2 systemic fell 55% and VO2 cerebral fell 57%. Similarly, SvO2 portal and SvO2 coronary increased 6% and 9%, respectively. Significant correlations existed between changes in VO2 systemic and BP (r = 0.05, p less than 0.001), HR (r = 0.3, p less than 0.01, PAD (r = -0.3, p less than 0.05, and CO (r = 0.8, p less than 0.001). Impaired oxygen utilization was most evident during the first 5 minutes after protamine administration. This investigation, for the first time, establishes that protamine sulfate decreases in vivo oxygen consumption, a finding that may account for certain of the drug's adverse side effects.
Wakefield
T W
TW
Department of Surgery, University of Michigan Medical Center.
Ucros
I
I
Kresowik
T F
TF
Hinshaw
D B
DB
Stanley
J C
JC
D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D002339:Carotid Arteries; D004285:Dogs; D005260:Female; D006439:Hemodynamics; D006494:Heparin Antagonists / Q000494:pharmacology*; D008928:Mitochondria / Q000378:metabolism; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption / Q000187:drug effects*; D010976:Platelet Count; D011479:Protamines / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects
D006494:Heparin Antagonists; D011479:Protamines; D010100:Oxygen