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.
Conclusion: 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.