[Effects of insulin on cardiac function and coronary circulation in acute myocardial ischemia and reperfusion experiment with dogs].
OBJECTIVE
To study the effect of insulin on cardiac functional recovery, coronary blood flow (CBF), coronary arterial function and coronary vascular endothelial cell apoptosis following acute myocardial ischemia/reperfusion (MI/R).


METHODS
In adult dogs, the left anterior descending coronary artery (LAD) was partially occluded (80% reduction in its blood flow) for 50 min and reperfused for 4 h. Vehicle (0.9% NaCl), GIK (glucose: 250 gxL(-1), insulin: 60 UxL(-1), potassium: 80 mmolxL(-1)), or GK (glucose: 250 gxL(-1), potassium: 80 mmolxL(-1)) were intravenously infused (2 mlxkg(-1)xh(-1)) 5 min before reperfusion, and CBF and left ventricular pressure were monitored. At the end of 4 h reperfusion period, coronary arteries were isolated, and the coronary vascular dysfunction, nitric oxide (NO) production and endothelial apoptosis were determined.


RESULTS
During reperfusion, compared with the vehicle, GIK increased CBFLAD (19.2 ml/min +/- 2.2 ml/min) vs (14.6 ml/min +/- 1.8 ml/min) of vehicle at the end of reperfusion, P < 0.05, improved recovery of LVSP and +/- LVdP/dtmax. In vivo ischemia/reperfusion caused significant coronary vascular endothelial dysfunction as evidenced by reduced endothelium dependent vasorelaxation, decreased total NO production, and endothelial cell apoptosis as determined by TUNEL staining. Reperfusion with GIK, but not GK, markedly improved the endothelium-dependent vasorelaxation (80.3% +/- 3.8%) vs. vehicle (28.1% +/- 2.3%, P < 0.01) of coronary artery in response to ACh. GIK significantly increased total NO production (17.19 micromol/L +/- 2.18 micromol/L) versus vehicle (4.74 micromol/L +/- 2.01 micromol/L, P < 0.01) and inhibited apoptosis in coronary arterial endothelial cell (12% +/- 4%) vs vehicle (45% +/- 7%, P < 0.01). GK failed to show any significant vasculoprotection against MI/R-induced coronary vascular injury.


CONCLUSIONS
These results demonstrate that insulin exerts cardioprotective effect by increasing CBF, reducing coronary artery injury and improving cardiac functional recovery during reperfusion, which may be partly attributable to the coronary vasculoprotective effect of insulin. The insulin-induced, NO-mediated anti-endothelial apoptotic effect may play a critical role in the insulin-induced coronary artery protective effect in MI/R.
Ma
Heng
H
Department of Physiology, Fourth Military Medical University, Xi'an 710032, China.
Huo
Jian-hua
JH
Zhang
Hang-xiang
HX
Bian
Jie-fang
JF
Wang
Yue-min
YM
Xiong
Li-ze
LZ
Guo
Wen-yi
WY
Wang
Hai-chang
HC
Gao
Feng
F
D000208:Acute Disease; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001783:Blood Flow Velocity / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects*; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D004285:Dogs; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D009569:Nitric Oxide / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology
D007328:Insulin; D009569:Nitric Oxide; D005947:Glucose; D011188:Potassium