Sustained effect of glucose-insulin-potassium on myocardial performance during regional ischemia. Role of free fatty acid and osmolality.

Abstract

A B S T R A C T To evaluate the influence of glucose infusate administered with insulin and potassium on left ventricular function during 4 h of ischemia, as well as mechanism of action, four groups of intact anesthetized dogs were studied. Acute crease of plasma FFA in contrast to controls which manifested a significant rise. To examine the postulate that the decrease in FFA was important to therapeutic action, a third group was infused wvith Intralipid (Cutter Laboratories, Inc., Berkeley, Calif.) and heparin, simultaneously with the glucose infusate, to effect an elevation of plasma FFA durinig ischenmia. Changes in myocardial function and electrolyte composition, as well as precordial electrocardiograimi mapping, were similar to that of animals receiving glucose alone. Because serum osmolalitv wvas increased approximately 40 mosmol during the glucose infusion, the potential role of' hyperosmolalitv was assessed by infusion of 20% mannitol during acute ischemia in a fourth group. After a transient small increase, there was a moderate decline in ftunction by 4 h, suggesting that the response to glucose is not dependent upon extracellular osmolality. Thus, it is concluded that dutring the initial hours after the onset of myocardial ischemia the gltucose infusate improves ventricular performance without evidence of arrhythmia induction or intensification of isclemiiic injury. Evoltution of irreversible necrosis appears to be delayed rather than prevented uinder the circumilstances of this study.

Enhanced utilization of exogenous glucose improves cardiac function in hypoxic rabbit ventricle without increasing total glycolytic flux.

“…Our findings are consistent with the majority of studies which have concluded that a benefit of GIK cannot be attributed exclusively to an osmotic effect (7,11,12,16), since osmolarity was balanced with sucrose in all of the solutions we used.…”

Effects of high-dose insulin infusion on left ventricular function in normal subjects

“…1,21 In intact animals, high-dose insulin administration preserved regional LV function during 3 and post ischaemia. [3][4][5] One study attributed the effect solely to insulin. 1 In patients undergoing cardiac surgery, GIK infusion resulted in higher postoperative cardiac indices compared with patients receiving standard treatment.…”

“…Most of these studies were performed in animal models [1][2][3][4][5] but also in patients undergoing cardiac surgery. [6][7][8][9][10] Dobutamine enhances overall myocardial performance and contraction, and high-dose insulin (HDI) infusion improves left ventricular systolic function in patients with left ventricular impairment due to ischaemic coronary disease.…”

Effects of perhexiline on myocardial deformation in patients with ischaemic left ventricular dysfunction

“…Increasing metabolism of glucose through glycolysis results in development of intracellular acidosis and accumulation of Ca +2 ions within the myocytes, which together lead to impairment of myocardial contractile function, myocyte injury and development of arrhythmias. Hence, inhibition of free fatty acid metabolism or increasing glucose delivery to the ischaemic myocyte has been shown to be beneficial both during ischaemia as well as during reperfusion [13][14][15][16][17]. It appears that in chronic LV dysfunction, the function of myocardium that shows contractile reserve can be improved by improving substrate supply [17].…”