The anesthetic propofol confers cardioprotection against myocardial ischemia-reperfusion injury (IRI) by reducing reactive oxygen species (ROS). However, its cardioprotection on patients is inconsistent. Similarly, the beneficial effect of tight glycemic control during cardiac surgery in patients has recently been questioned. We postulated that low glucose (LG) may promote ROS formation through enhancing fatty acid (FA) oxidation and unmask propofol cardioprotection during IRI. Rat hearts were isolated and randomly assigned to be perfused with Krebs-Henseleit solution with glucose at 5.5 mM (LG) or 8 mM (G) in the absence or presence of propofol (5 μg/mL) or propofol plus trimetazidine (TMZ). Hearts were subjected to 35 minutes of ischemia followed by 60 minutes of reperfusion. Myocardial infarct size (IS) and cardiac CK-MB were significantly higher in LG than in G group (P < 0.05), associated with reduced left ventricular developed pressure and increases in postischemic cardiac contracture. Cardiac 15-F2t-isoprostane was higher, accompanied with higher cardiac lipid transporter CD36 protein expression in LG. Propofol reduced IS, improved cardiac function, and reduced CD36 in G but not in LG. TMZ facilitated propofol cardioprotection in LG. Therefore, isolated heart with low glucose lost sensitivity to propofol treatment through enhancing FA oxidation and TMZ supplementation restored the sensitivity to propofol.

The anesthetic propofol protects against myocardial ischemia‐reperfusion injury (IRI) by reducing reactive oxygen species (ROS)‐induced oxidative stress. However, its cardioprotection in patients is inconsistent. We postulated that low glucose(LG) as seen during tight glycemic control promotes cardiac ROS formation through enhancing fatty acid(FA) oxidation during IRI and unmasks propofol cardioprotection. Rat hearts were isolated and randomly assigned to be perfused with Krebs‐Henseleit solution with glucose at 5.5 mmol/l (LG) in the absence or presence of propofol (5ug/ml) or propofol with trimetazidine (TMZ) unknown to inhibit FA oxidation, or with glucose at 8 mmol/L (group G) in the absence or presence of propofol or propofol plus TMZ. Hearts were subjected to 35 min of global ischemia and 60 min of reperfusion. Myocardial infarct size(IS) was higher in LG than in G group (P<0.05), accompanied with reduced left ventricular (LV) developed pressure and increases in postischemic cardiac contracture. Cardiac 15‐F2t‐isoprostane was higher in LG that was associated with higher cardiac lipid transporter CD36 protein expression than in G group. Propofol reduced IS and improved cardiac function and reduced cardiac CD36 in G but not in LG group. TMZ facilitated propofol cardioprotection in LG. During IRI, LG through enhancing fatty acid oxidation and oxidative stress compromised propofol cardioprotection.