Background. Chronic arteriovenous fistulae (AVF) create sustained hyperdynamic circulation. It is not known whether hyperdynamic circulation alters myocardial sensitivity to ischemia and reperfusion injury. We tested the hypothesis that AVF activate molecular responses that increase tolerance to infarction in dogs.Methods. Twelve dogs were divided into two groups: 1) AVF group, where an AVF in the femoral region was done; and 2) sham-operated group teach n = 6). After 8 weeks, left ventricular performance was determined from stroke work/end-diastolic length relationship. Myocardial biopsy was obtained to determine heat-shock protein 70 and adenosine triphosphate (ATP) pool. Left anterior descending coronary artery was occluded for 90 minutes at 37 degrees C, followed by 4 hours of reperfusion. Coronary blood flow was determined using different colored microspheres. Results. The fistula group showed improvement of left ventricular performance (p = 0.03). The infarct size was significantly lower in the fistula group; it was 9.2 +/- 2.0% in the fistula group versus 28.4 +/- 5.2% in the sham group (p < 0.05). ATP depletion during ischemia was less in the fistula group (p = 0.02). Regional myocardial blood now was significantly higher in the fistula group (p = 0.03). Conclusions. Peripheral AVF improve the left ventricular performance, and decrease infarct size and ATP depletion. This protective effect is caused by the development of collaterals in the coronary circulation without expression of heat-shock protein 70.