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Fourteen patients with normal, global, left ventricular function scheduled for elective myocardial revascularization were studied at rest and during atrial pacing before and during isoflurane anesthesia (0.5% end-tidal) plus 50% nitrous oxide. Rapid atrial pacing was performed in a stepwise fashion until the onset of angina pectoris in the awake patients. The same step increase in pacing rate was applied in the anesthetized patients. Compared with prepacing baseline values, isoflurane significantly decreased systemic blood pressure, coronary perfusion pressure, the rate-pressure product, and cardiac index. No patient had ST-segment depression while awake or during isoflurane anesthesia before pacing was started. Prepacing left and right ventricular filling pressures and wave forms were normal, both while awake and during isoflurane anesthesia. The mean pacing rate at which first signs of myocardial ischemia appeared (V5 ST-segment depression ≥0.1 mV, increase in pulmonary capillary wedge pressure (PCWP) to ≥15 mmHg, and prominent PCWP v-waves ≥20 mmHg) was significantly higher during isoflurane anesthesia than in the awake patients (128 ± vs. 115 ± 5 beats/min). With the exception of one patient, the individual pacing rates inducing first signs of ischemia in the awake patients were below the anginal threshold. None of the patients had a reduced ischemic threshold during anesthesia. Eleven anesthetized patients tolerated a higher pacing rate until initial signs of ischemia appeared. In four of these patients, the pacing rate required to induce first signs of ischemia was above the heart rate at which chest pain had been induced while they were awake. At a peak atrial pacing rate of 129 ‡ 5 beats/min, which had induced angina pectoris in the awake patients, the increase in PCWP was significantly smaller during pacing with isoflurane than during control pacing. Prominent PCWP v-waves (>20 mmHg) appeared in 12 of the 14 patients during initial pacing to angina and in eight patients paced during isoflurane anesthesia. In six of these eight patients, the abnormal v-waves were less prominent than those observed during control pacing. Ischemic ST-segment changes developed in 13 of 14 patients during initial pacing and in nine patients during pacing with isoflurane. Mean V5 ST-segment depression during the two pacing periods was significantly different, averaging 0.19 and 0.11 m V, respectively. The authors conclude that a low concentration of isoflurane plus nitrous oxide improves the tolerance to pacing-induced myocardial ischemia in patients with significant coronary artery disease.