Effect of inhibition of nitric oxide release on the diaphragmatic oxygen delivery-consumption relationship

Abstract

Purpose: In the vascularly isolated resting and contracting (3 Hz) canine hemidiaphragm, the hypothesis that nitric oxide (NO) is an important regulator of diaphragmatic O 2 extraction was tested. Methods: The effect of an intra-arterial infusion of an NO-synthase inhibitor N G -nitro- l-arginine ( l-NA) on the critical O 2 delivery (Qo 2c), below which O 2 consumption becomes dependent on O 2 supply, was assessed in two groups of animals in which either saline or l-NA (6 · 10 −4 mol/L) was infused into the phrenic artery over 20 minutes. The diaphragm was then perfused either by left femoral arterial blood (autoperfusion) or by pump perfusion with blood from the femoral artery. Qo 2 was reduced by stepwise hemorrhage in the autoperfusion groups and by reducing the pump rate in the pump perfusion groups. Results: During autoperfusion, Qo 2c in the saline- and l-NA-treated groups was not different (0.88 ± 0.15 and 0.98 ± 0.12 mL/min/100 g, respectively) for the resting diaphragm. Critical O 2 extraction ratios were not different (64.5% ± 9.9% and 67.8% ± 6.4%, respectively). In the saline group, Qo 2c during 3-Hz stimulation was 5.03 ± 0.9 mL/min/100 g. In the l-NA group, diaphragm flow was lower than the saline group, and no Qo 2c was found. In the pump-perfused contracting diaphragm, Qo 2c in both groups did not differ (3.1 ± 0.5 and 4.05 ± 0.65 mL/min/100 g, respectively). O 2 extraction ratios at these O 2 deliveries were different (63.3% ± 5.2% and 77.4% ± 4.3%, respectively). However, NO-synthase inhibition had no effect on maximum diaphragmatic O 2 extraction ratio. Conclusions: These results indicate that NO release is an important modulator of the tone of diaphragmatic resistance vessels, but it does not appear to regulate the processes by which O 2 extraction is enhanced to compensate for decreased O 2 delivery.