A method for producing regional hypoglycemia in blood perfused tissue

Numerous studies have focused on the metabolic contributions of glucose and other substrates in isolated tissue preparations by examining the effects of eliminating glucose from the physiologic perfusate or bath solution. To date, however, an effective method of glucose removal from the blood supply to selected tissue in the whole animal model has not been available. We have developed a method for blood glucose removal by continuous flow dialysis. This method was used to generate isolated coronary hypoglycemia for an investigation of myocardial metabolic substrate selection during hypoperfusion in open-chest, anesthetized dogs. Arterial blood was passed through the dialysis system against an isotonic and physiologic dialysate solution prior to controlled coronary perfusion. During normal perfusion pressure (100 mmHg), with a coronary blood flow of 32+/-4 ml/min, arterial blood glucose was reduced from 3.26+/-0.31 to 0.54+/-0.14 mM. When blood flow was reduced to 12+/-3 ml/min with lower perfusion pressure (40 mmHg), dialysis reduced arterial glucose from 3.53+/-0.36 to 0.15+/-0.03 mM. We conclude that this is an effective method for producing regional hypoglycemia.