Left ventricular oxygen utilization efficiency is impaired in chronic streptozotocin-diabetic sheep.
OBJECTIVE
Energy metabolism is altered in the diabetic heart. However, direct in vivo evidence that diabetes impairs energetics at the chamber level is lacking. Therefore, we investigated the effect of diabetes on left ventricular (LV) energetics in a chronic ovine model.


METHODS
Diabetes was induced in Merino-cross sheep with streptozotocin. Experiments were performed in five animals following 12 months untreated diabetes and six animals served as controls. Open-chest anesthetized sheep were instrumented to determine the LV pressure-volume relationship, oxygen consumption and free fatty acid uptake.


RESULTS
Diabetes impaired LV contractility (1.5+/-0.5 vs. 2.3+/-0.5 mmHg/ml, P<0.01). Stroke work was preserved but stroke work efficiency (stroke work/pressure-volume area) deteriorated (52+/-4 vs. 58+/-3%, P<0.01). Plasma free fatty acid levels increased (1885+/-1078 vs. 354+/-203 mmol/l, P<0.01) as did LV free fatty acid uptake (312+/-278 vs. 90+/-47 micromol/beat per 100 g LV, P=0.04). Contractile efficiency decreased (31.9+/-1.4 vs. 50.0+/-8.7%, P<0.01) while unloaded oxygen consumption did not change significantly. Therefore, LV oxygen utilization efficiency (stroke work/LV oxygen consumption) was compromised in the diabetic heart (14.9+/-2.8 vs. 24.3+/-4.0%, P<0.001).


CONCLUSIONS
This is the first study to demonstrate that diabetes alters ventricular energetics in vivo. LV oxygen utilization efficiency is impaired as a consequence of decreased contractile efficiency and stroke work efficiency. Impaired efficiency of oxygen utilization may explain in part the increased sensitivity of the diabetic heart to ischemia and the accelerated deterioration of ventricular function in diabetic patients.
Ramanathan
Tharumenthiran
T
Cardiac Technology Centre, Department of Cardiology, Block 4, Level 3, Royal North Shore Hospital, St Leonards, Sydney, NSW 2065, Australia. indranrama@yahoo.com
Shirota
Kazuaki
K
Morita
Shin
S
Nishimura
Takashi
T
Huang
Yifei
Y
Zheng
Xing
X
Hunyor
Stephen
S
D000818:Animals; D002908:Chronic Disease; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000503:physiopathology; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005260:Female; D006352:Heart Ventricles / Q000503:physiopathology; D008297:Male; D023421:Models, Animal; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption; D012756:Sheep; D013318:Stroke Volume
D005230:Fatty Acids, Nonesterified