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To compare the effects of isoflurane on ischemic myocardium in acutely and chronically instrumented animals, 12 mongrel dogs were monitored with electromagnetic or Doppler ultrasonic flow transducers and hydraulic occluders around the left circumflex coronary artery, pressure transducers in the left ventricle, and heparin-filled catheters in the descending aorta. Regional function of normal and ischemic myocardium was assessed by sonomicrometry. The hemodynamic effects of isoflurane (2% inspired concentration) were more pronounced in the acutely than in the chronically instrumented dogs. Decreases in mean arterial pressure (−47% ± 5% in the acute and −22% ± 4% in the chronic preparation, P < 0.01), left ventricular contractility (−51% ± 6% and −33% ± 4%, P < 0.01), and coronary perfusion pressure (−59% ± 6% and −12% ± 9%, P < 0.01) were more distinct in the acutely instrumented animals. Although the reduction of regional function during isoflurane anesthesia was similar in normal myocardium in both preparations (−33% ± 4% acute and −34% ± 6% chronic preparation, not a significant difference), an exaggerated dysfunction was observed in the ischemic myocardium of the acutely instrumented dogs (−66% ± 2% and −30% ± 4%, P < 0.01). It is concluded that acutely instrumented dogs respond to the hemodynamic effects of isoflurane, resulting in ischemic myocardial dysfunction, significantly more than do chronically instrumented dogs.