Coronary blood flow and cardiac adenine nucleotides in E. coli endotoxemia in dogs: effects of oxygen radical scavengers.
The purposes of this study were to determine the effects of E. coli endotoxin shock on coronary blood flow (CBF) and myocardial adenine nucleotides and to determine if reactive oxygen species are major causal factors in these effects of endotoxin. Twenty-three pentobarbital-anesthetized Beagle dogs were instrumented for recording cardiorespiratory parameters, injected i.v. with saline (time-matched controls; n = 6) or endotoxin (1.5 mg/kg; n = 17), and studied for 4 h. Endotoxin dogs also received either i.v. saline (shock controls; n = 6) or i.v. treatment with either deferoxamine (30 mg/kg; n = 5) or triple therapy (n = 6) with a combination of allopurinol (150 mg/kg), superoxide dismutase (SOD) (5 mg/kg), and catalase (CAT) (5 mg/kg). Cardiorespiratory and tissue blood flow variables were constant in sham-shock controls during the study, whereas endotoxin dogs developed typical canine endotoxemia with decreased left ventricular (LV) function. CBF was decreased by approximately 40% (P less than or equal to 0.5) in all endotoxin groups throughout the 4 h study period. However, based on hemodynamic estimates of myocardial O2 demand and endocardial/epicardial blood flow ratios, it seemed that coronary flow was matched to metabolic rate in all endotoxin groups. Endotoxin significantly lowered LV myocardial concentrations of ADP, AMP, NADH, and NADPH (range = 37 to 54%, P less than or equal to 0.05), but ATP, NAD, and NADP concentrations were not changed. The adenylate charge of the myocardium was between 0.91 and 0.95 in all endotoxin groups, suggesting that adequate energy was available in the myocardium during endotoxin shock. The lack of influence of deferoxamine, allopurinol, SOD, and CAT is indirect evidence that oxygen radicals are not primary pathophysiologic mediators in the cardiac response to gram-negative endotoxemia in this endotoxin model.
Laughlin
M H
MH
Department of Veterinary Biomedical Sciences, College of Veterinary Medicine, Columbia, MO.
Smyk-Randall
E M
EM
Novotny
M J
MJ
Brown
O R
OR
Adams
H R
HR
D000227:Adenine Nucleotides / Q000378:metabolism*; D000493:Allopurinol / Q000494:pharmacology*; D000818:Animals; D002374:Catalase / Q000378:metabolism / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects*; D003676:Deferoxamine / Q000494:pharmacology*; D004285:Dogs; D004731:Endotoxins; D004926:Escherichia coli; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism
D000227:Adenine Nucleotides; D004731:Endotoxins; D013481:Superoxides; D000493:Allopurinol; D002374:Catalase; D013482:Superoxide Dismutase; D003676:Deferoxamine