REDUCTION OF ISCHEMIA-INDUCED ELECTROPHYSIOLOGIC ABNORMALITIES BY GLUCOSE-INSULIN INFUSION

Objectives. This study was designed to determine the effects of glucos e-insulin infusion on ischemia-induced changes in extracellular potass ium ([K+]o) accumulation and the associated electrophysiologic abnorma lities in the canine heart. Background. Although glucose-insulin-potas sium infusion has been shown to limit myocardial injury in acute ische mia, its effect on ischemia-induced electrophysiologic alterations has not been investigated. Methods. Recordings of [K+]o and local electro grams from the normal, border and ischemic zones were obtained during serial (10-min) left anterior descending coronary artery occlusions in the control state and after infusion of glucose-insulin (eight dogs), glucose alone (six dogs) or insulin alone (eight dogs).Results. Gluco se-insulin infusion caused significant reduction in the rise of [K+]o during the entire period of ischemia in both ischemic and border zones associated with significant improvement in the degree of intramyocard ial conduction delay. At 10 min of ischemia, [K+]o was reduced from a mean control level of 15.9 +/- 3.7 to 10.1 +/- 4.3 mmol/liter (p < 0.0 05) in the ischemic zone and from 6.8 +/- 1.9 to 5.5 +/- 1.1 mmol/lite r (p < 0.05) in the border zone. The electrogram duration was shortene d from a mean control value of 102 +/- 13 to 78 +/- 12 ms in the ische mic zone and from 79.2 +/- 7.8 to 58.1 +/- 6.6 ms in the border zone ( p < 0.005). Glucose alone caused significant reduction in [K+]o during the initial 6 min of ischemia, only in the ischemic zone. Conversely, insulin caused no changes in [K+]o accumulation during ischemia. Neit her glucose nor insulin alone had any effect on ischemia-induced intra myocardial conduction delay. Conclusions. The present study demonstrat ed that the combination of glucose and insulin is essential for the sa lutary effect of reducing [K+]o accumulation during ischemia and impro ving the associated intramyocardial conduction delay. It could be post ulated that glucose in the presence of insulin increases the glycolyti c flux, thereby providing adequate adenosine triphosphate for suppress ing the cardiac adenosine triphosphate-sensitive potassium ion channel s. The latter are, at least partially, responsible for the [K+]o rise in the early phase of ischemia. This study highlights the antiarrhythm ic potential of interventions that modulate the metabolic consequences of ischemia.