Law W R, McLane M P, Raymond R M
Department of Surgery and Physiology, Loyola University, Stritch School of Medicine, Maywood, Illinois 60153.
Circ Shock. 1989 Aug;28(4):333-45.
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.
我们最近报道，腺苷在体内可增强胰岛素刺激的心肌葡萄糖摄取（MGU），且腺苷受体阻断会导致心肌胰岛素抵抗。鉴于已有报道称内毒素休克期间会发生心肌胰岛素抵抗，我们决定研究输注腺苷是否能改善这种情况。研究在戊巴比妥麻醉的犬身上进行，这些犬已安装仪器以测量平均动脉血压（MAP）、冠状动脉血流量（Q）、心肌葡萄糖摄取（MGU）和氧摄取（MVO2）。通过静脉推注鼠伤寒沙门氏菌内毒素（1mg/kg）诱导内毒素休克。在高胰岛素血症（4U/min）、正常血糖钳夹（INS）期间测定对胰岛素的反应。在向冠状动脉顺序输注腺苷（0.01μmol/min至10μmol/min）期间或输注单一浓度的腺苷（1.0μmol/min）期间，测量腺苷增强胰岛素刺激的葡萄糖摄取的能力。在对照犬中，INS导致心肌葡萄糖摄取比基础值升高约两倍（2.6±0.4至4.9±0.7mg/min；平均值±标准误）。该组中INS对MAP、Q或MVO2无显著影响。腺苷输注导致胰岛素刺激的MGU增强。在休克期间，INS使MAP、Q和MVO2升高至与对照组无显著差异的水平，但未使MGU升高至内毒素血症前水平之上。在休克组中，与单独使用INS的效果相比，INS + 腺苷并未显著改变MAP和MVO2。从这些结果我们得出结论，腺苷在内毒素休克期间恢复了心肌对胰岛素的葡萄糖摄取反应。氧供需比对内毒素的反应表明，内毒素休克期间心肌腺苷生成可能减少。
