[Effects of glucose-insulin-potassium cocktail on cardiac myocyte death and post-ischemic recovery cardiac functional recovery: the critical role of insulin].
OBJECTIVE
To study the effect of glucose-insulin-potassium (GIK) cocktail on cardiac myocyte death (i.e., necrosis and apoptosis) and cardiac functional recovery following myocardial ischemia/reperfusion (MI/R), and to further investigate the role of insulin in the GIK-induced cardioprotective effect.


METHODS
Male Sprague-Dawley rats were subjected to 30 min myocardial ischemia followed by reperfusion for 4 h (for cardiac function and cardiomyocyte apoptosis study) or 6 h (for myocardial infarction measurement). Anesthetized rats were randomly treated with continuous infusions of saline, GIK (Glucose: 200 g/L, Insulin: 60 U/L and KCl: 60 mmol/L), GK or insulin at 4 ml.kg(-1).h(-1), beginning 5 min before reperfusion and continuing through the 4-h reperfusion. Arterial blood pressure, ECG and left ventricular pressure were monitored throughout the experiment. Myocardial DNA fragmentation and myocardial infarction were determined at the end of reperfusion.


RESULTS
MI/R caused significant cardiac dysfunction and myocardial death (both necrosis and strong DNA ladder formation). Compared with the vehicle treated rats, the GIK-treated rats showed protection against MI/R injury as evidenced by reduced myocardial infarction [(41.3 +/- 8.3)% vs. (54.4 +/- 10.4)% of vehicle, P < 0.05, n = 10], marked decrease of DNA fragmentation, and improved recovery of cardiac systolic/diastolic function at the end of reperfusion [left ventricular developed pressure: (94 +/- 6) mm Hg vs. (86 +/- 5) mm Hg of vehicle, P < 0.05; +LVdP/dt(max): (2 940 +/- 114) mm Hg/s vs. (2 733 +/- 132) mm Hg/s, P < 0.05; -LVdP/dt(max): (2 629 +/- 156) mm Hg/s vs. (2 463 +/- 133) mm Hg/s, P < 0.05]. Insulin exerted the similar cardioprotective effects with GIK; whereas the rats receiving GK failed to show any significant, cardioprotection against MI/R injury.


CONCLUSIONS
GIK exerts cardioprotective effect against postischemic myocardial injury. Insulin, mainly through its anti-apoptotic effect, plays a critical role in the GIK-elicited myocardial protection in MI/R.
Gao
Feng
F
Department of Physiology, The Fourth Military Medical University, Xi'an 710032, China. fgao@fmmu.du.cn
Shi
Dong-wei
DW
Wang
Xiao-ming
XM
Dong
Ling
L
Wang
Yue-min
YM
Ma
Xin-liang
XL
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001786:Blood Glucose / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000473:pathology*; D011188:Potassium / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D016277:Ventricular Function, Left / Q000187:drug effects
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; C030396:glucose-insulin-potassium cardioplegic solution; D005947:Glucose; D011188:Potassium