The role of the adrenergic nervous system in the response to coronary artery occlusion has been examined using surgical and chemical denervation techniques. Experiments were conducted on four groups of dogs (n = 18): 1) untreated controls; 2) intrapericardial denervation immediately prior to coronary ligation; 3) surgical denervation 2 weeks prior to the experiment; and 4) chemical sympathectomy 5 days prior to the experiment with 6-hydroxydopamine (50 mg/kg). Small artery and vein O2 saturations were obtained microspectrophotometrically and combined with radioactive microsphere blood flow determinations to calculate regional myocardial O2 consumption in open chest dogs. Denervation significantly reduced the preocclusion heart rate from 165 +/- 16 beats/min in the control to 114 +/- 13 in the chronic surgically denervated and to 137 +/- 15 in the chemically sympathectomized groups. After 2 hours of occlusion, the O2 consumption and flow were similar in the nonischemic area except for lower values in the surgically denervated group. Total coronary blood flow and O2 consumption in the occluded regions were not significantly affected by chronic denervation. However, significant elimination of areas with low venous O2 saturation (less than 20%) were found in the ischemic myocardium of the chronically denervated groups as compared with the control or with the acutely denervated dogs. The mean venous O2 saturation was found to be significantly higher in all regions of these two groups as compared with the control. The O2 extraction was also lowered. Thus, chronic denervation reduced microregional heterogeneity of oxygenation in the ischemic myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)