Adenosine restores myocardial responsiveness to insulin during acute endotoxin shock in vivo.
We recently reported that adenosine potentiated insulin-stimulated myocardial glucose uptake (MGU) in vivo and that adenosine receptor blockade resulted in myocardial insulin resistance. Since myocardial insulin resistance has been reported to occur during endotoxin shock, we decided to investigate whether infusion of adenosine could ameliorate this condition. Studies were performed in pentobarbital-anesthetized dogs that were instrumented to measure mean arterial blood pressure (MAP), circumflex arterial blood flow (Q), myocardial glucose uptake (MGU), and oxygen uptake (MVO2). Endotoxin shock was induced by administration of an intravenous bolus of Salmonella typhymurium endotoxin (1 mg/kg). The response to insulin was determined during hyperinsulinemic (4 U/min), euglycemic clamp (INS). The ability of adenosine to potentiate insulin-stimulated glucose uptake was measured during sequential infusions of adenosine (0.01 mumol/min to 10 mumol/min) or during infusion of a single concentration of adenosine (1.0 mumol/min) into the circumflex artery. In control dogs INS resulted in an approximate twofold elevation of myocardial glucose uptake over basal values (2.6 +/- 0.4 to 4.9 +/- 0.7 mg/min; mean +/- S.E.M.). There was no significant effect of INS on MAP, Q, or MVO2 in this group. Adenosine infusions resulted in potentiation of insulin-stimulated MGU. During shock INS elevated MAP, Q, and MVO2 to levels that were not significantly different from the control group, but did not raise MGU above the pre-endotoxin level. Adenosine infusions elevated insulin-stimulated MGU during shock to levels similar to those observed in the control group during respective adenosine infusion rates. MAP and MVO2 were not significantly altered by INS + adenosine in the shock group as compared with the effect of INS alone. From these results we conclude that adenosine restored the myocardial glucose uptake response to insulin during endotoxin shock. The response of the oxygen supply to demand ratio to INS suggests that myocardial adenosine production may be reduced during endotoxin shock.
Law
W R
WR
Department of Surgery and Physiology, Loyola University, Stritch School of Medicine, Maywood, Illinois 60153.
McLane
M P
MP
Raymond
R M
RM
D000241:Adenosine / Q000097:blood / Q000494:pharmacology*; D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D006439:Hemodynamics / Q000187:drug effects; D006946:Hyperinsulinism; D007328:Insulin / Q000097:blood / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D012772:Shock, Septic / Q000097:blood / Q000503:physiopathology*; D013997:Time Factors
D007328:Insulin; D005947:Glucose; D000241:Adenosine