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predetermined limits. Isoflurane and alfentanil were discontinued 10 min before the anticipated end of surgery. Nitrous oxide was discontinued at the end of surgery, and residual muscle relaxation was antagonized using neostigmine (60 micro gram/kg) and glycopyrrolate (8 micro gram/kg). Baseline blood pressure and heart rate were determined by averaging three noninvasive measurements taken at least 5 min apart the night before surgery. Arterial cannula was inserted the morning of surgery, and hemodynamic monitoring was started at least 5 min before the study drug infusion. During the study drug infusion, preceding induction of anesthesia, hemodynamic changes were treated only if clinically judged to be detrimental to the patient's health. Systolic blood pressure and heart rate were maintained within predetermined limits. Intraoperatively, bradycardia was defined as heart rate < 40 beats/min. tachycardia as greater or equal to 20% increase in heart rate. hypertension as greater or equal to 20% increase in systolic blood pressure, and hypotension as greater or equal to 20% decrease in systolic blood pressure, from preoperative noninvasive baseline values. After establishing an adequate level of anesthesia (lack of movement, sweating, lacrimation) with isoflurane, tachycardia was treated by administration of esmolol, bradycardia by administration of glycopyrrolate, and hypertension by increasing the inspired isoflurane concentration. Hypotension initially was treated by decreasing the inspired isoflurane concentration; if persistent, by administration of phenylephrine. Inadequate level of anesthesia (spontaneous movement, sweating, lacrimation), as determined by the anesthesiologist, was treated by increasing the inspired isoflurane concentration. Arterial hemoglobin oxygen saturation (SpO2) less than 95% was managed by increasing the inspired oxygen concentration. Postoperatively, tachycardia was defined as heart rate greater or equal to 100 beats/min, bradycardia as heart rate < 40 beats/min, hypertension as systolic blood pressure > 160 mmHg, and hypotension as systolic blood pressure < 90 mmHg. Postoperative tachycardia was treated by administration of esmolol, bradycardia with glycopyrrolate, hypertension with nitroprusside, and hypotension with phenylephrine. SpO2of less than 95% was treated by increasing the inspired oxygen concentration. Postoperatively, routine medications (including oral nitrates) were restarted as clinically indicated. Intravenous nitroglycerin was used only to treat documented (12-lead ECG) myocardial ischemia. Arterial blood pressure (systolic, diastolic, and mean) and heart rate were continuously measured during the 1-h infusion period preceding induction of anesthesia, intraoperatively, and for 60 h postoperatively, using a Marquette 7000 hemodynamic monitor (Marquette Electronics, Milwaukee, WI). Arterial blood pressure was measured via a radial artery cannula connected to a Transpac II transducer (Abbott Laboratories, North Chicago, IL) zeroed 5 cm posterior to the sternum. Hemoglobin oxygen saturation was measured noninvasively using an Ohmeda Biox 3700 pulse oximeter (Ohmeda, Luisville, CO) with the probe placed on a distal phalanx. End-tidal isoflurane concentrations were measured using a Chemetron Medspect mass spectrometer (PPG, Kansas City, KS). Hemodynamic and end-tidal isoflurane data were recorded at 1-min intervals from the clinical monitors through an automated data acquisition system (ARKIVE Series 2000, Diatek, San Diego, CA). SpOsub 2 data were recorded every minute intraoperatively and hourly postoperatively. Blood samples for analysis of hematologic and biochemical values and urine for urinalysis were collected preoperatively and on postoperative days 1, 5, and 14 or on discharge from the hospital, whichever was sooner. The samples were analyzed at the central laboratory of the San Francisco Veterans Affairs Medical Center Hospital. A 12-lead ECG was obtained and reviewed before surgery and on postoperative days 1, 2, 3, and 5, then weekly, on discharge, and whenever clinically indicated. Cardiac enzymes were measured before surgery and every 12 h for 72 h postoperatively.
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