Abstracts of Posters Presented at the International Anesthesia Research Society; 72nd Clinical and Scientific Congress; Orlando, FL; March 7-11, 1998: Cardiovascular Anesthesia
Introduction: Previous studies conducted in vitro have demonstrated that nitric oxide (NO) can reduce tissue O2 utilization by directly inhibiting enzymes in the electron-transport chain.  However, the importance of this mechanism in the physiological regulation of tissue O2 utilization in vivo is controversial. [2,3] The present study was conducted to evaluate the effect of the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), on whole-body oxygen consumption (VO2) in anesthetized dogs.
Methods: The studies adhered to APS/NIH guidelines. Ten dogs were anesthetized with either 1 MAC isoflurane (1.4 % in O2) or with fentanyl and midazolam (10 [micro sign]g/kg/hr and 0.5 mg/kg/hr, respectively). Vecuronium bromide was used to facilitate mechanical ventilation and to prevent muscle fasciculations. A catheter was implanted in the thoracic aorta for measurements of mean aortic pressure (MAP; mmHg) and heart rate (HR; beat/min) and for collection of samples of arterial blood. A catheter was implanted in the pulmonary artery for measurements of cardiac output (CO; ml/min/kg), and for collection of samples of mixed venous blood. VO2 (ml/min/kg) was calculated by multiplying CO and the arteriovenous O2 difference (A-VO2; vol %). Systemic vascular resistance (SVR; mmHg/ml/min/kg) was calculated by dividing AOP by CO. Values were obtained under three conditions in each dog: 1) Control, 2) after L-NAME (10 mg/kg i.v., and 3) during i.v. infusion of adenosine (ADEN) to normalize CO after L-NAME.
Results: Because the results under isoflurane and fentanyl anesthesia were similar, they were combined (Table 1). L-NAME increased MAP and SVR, and it decreased CO. However, VO2 did not change because the decreases in CO were accompanied by proportional increases in the A-VO2. ADEN after L-NAME restored CO, but it had no effect on VO2.
Conclusions: 1) Endogenous NO, released basally, did not influence tissue O2 utilization in vivo, although it was important in maintaining the peripheral vasculature in a dilated state. This latter effect reduced ventricular afterload thus facilitating cardiac ejection. 2) The inability of L-NAME to increase VO2 was not because it had reduced CO (O2 supply) below the critical level.
1. Am J Physiol 1991;260:C910-C916
2. Circ Res 1994;75:1086-1095
3. Am J Physiol 1996;270:H1568-76