Microvascular Protection Induced by Late Preconditioning Was Abolished in STZ-Induced Acute Diabetic Rats

ABSTRACT

The authors attempted to determine whether ischemic preconditioning (IPC) can provide microvascular protection in skeletal muscle of diabetic rats against injury from a subsequent (24 hr later) prolonged period of ischemia and reperfusion. Male Sprague Dawley rats weighting 80 to 100 g were injected intraperitoneally with either streptozotocin (STZ, 65 mg/kg) or vehicle (sodium citrate, pH 4.5). Rats with a fasting blood glucose level over 300 mg/dl 1 week after injection of STZ were considered acute diabetic. The cremaster muscle of the rats underwent 45 min of IPC and 24 hr later, 4 hr of warm ischemia followed by reperfusion (I/R). Four groups were compared: IPC in normal rats (n=8); sham IPC in normal rats (n=8); IPC in diabetic rats (n=6); and sham IPC in diabetic rats (n=4). Microvascular responses in the cremaster muscle to IPC were determined by measuring the diameter of feeding, terminal arterioles and capillary perfusion using intravital microscopy, and by the evaluation of the endothelium-dependent nitric oxide system in the terminal arterioles.

The average diameter of the feeding and terminal arterioles, as well as capillary perfusion, were significantly decreased in diabetic animals, compared to normal animals. There was a significant endothelial dysfunction detected in the terminal arterioles of diabetic rats. Ischemic preconditioning provided significant microvascular protection against prolonged ischemia/reperfusion in normal rats, but not in diabetic rats. IPC-induced microvascular protection in the normal skeletal muscle was abolished in STZ-induced acute diabetic rats.

KEYWORD

Ischemic preconditioning - I-R injury - protection - diabetic rat model

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