Glucose-insulin-potassium solution improves left ventricular energetics in chronic ovine diabetes.
BACKGROUND
Therapeutic modulation of myocardial metabolism improves outcomes in diabetic patients following myocardial infarction and coronary artery surgery. However, the mechanism of this beneficial effect has not been fully elucidated. This study evaluated the effect of glucose-insulin-potassium solution (GIK) on left ventricular (LV) energetics and oxygen utilization efficiency in a chronic ovine model of diabetes.


METHODS
Diabetes was induced in sheep with streptozotocin. Experiments were performed following 12 months untreated diabetes (n = 6) and in controls (n = 6). Open-chest anesthetized sheep were instrumented to determine the LV pressure-volume relationship, oxygen consumption, and free fatty acid uptake. Glucose-insulin-potassium was infused at 1.5 mL x kg(-1) x h(-1) for 60 minutes and assessment repeated.


RESULTS
Glucose-insulin-potassium decreased LV free fatty acid uptake in control: 0.090 +/- 0.047 microg/beat/100 g to 0.024 +/- 0.022 microg/beat/100 g, p = 0.02 and diabetes: 0.33 +/- 0.32 microg/beat/100 g to 0.11 +/- 0.13 microg/beat/100 g, p = 0.04. Similarly, GIK decreased unloaded left ventricular oxygen consumption (LVVO(2)) in both control (0.42 +/- 0.05 to 0.37 +/- 0.13J/beat/100 g, p < 0.001) and diabetic sheep (0.40 +/- 0.24 to 0.23 +/- 0.23J/beat/100 g, p < 0.001). The slope of the LVVO(2)-pressure-volume area relation (contractile efficiency) was unchanged in either group. Glucose-insulin-potassium improved LV contractility 58% +/- 37% (p = 0.005) and stroke work efficiency 18% +/- 10% (p = 0.009) in diabetic animals but not controls. Therefore, oxygen utilization efficiency (stroke work-LVVO(2)) increased only in diabetic animals (16.6% +/- 4.8% to 26.9% +/- 3.6%, p = 0.002) following GIK.


CONCLUSIONS
This study provides in vivo evidence that GIK improves LV energetics in diabetes. Oxygen utilization efficiency is improved as a result of improved stroke work efficiency and decreased unloaded LVVO(2). Improved efficiency of oxygen utilization provides a physiologic rationale for the beneficial effect of GIK in diabetic patients.
Ramanathan
Tharumenthiran
T
Cardiac Technology Centre, Department of Cardiology, Royal North Shore Hospital, Sydney, Australia. indranrama@yahoo.com
Morita
Shin
S
Huang
Yifei
Y
Shirota
Kazuaki
K
Nishimura
Takashi
T
Zheng
Xing
X
Hunyor
Stephen N
SN
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000503:physiopathology; D004734:Energy Metabolism; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology*; D006352:Heart Ventricles / Q000378:metabolism*; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology*; D009200:Myocardial Contraction; D010101:Oxygen Consumption; D011188:Potassium / Q000008:administration & dosage / Q000494:pharmacology*; D012756:Sheep; D013318:Stroke Volume; D016277:Ventricular Function, Left
D005230:Fatty Acids, Nonesterified; D007328:Insulin; C030396:glucose-insulin-potassium cardioplegic solution; D005947:Glucose; D011188:Potassium