Muscle microvascular oxygenation in chronic heart failure: role of nitric oxide availability

Aim: To test the hypothesis that diminished vascular nitric oxide availability might explain the inability of individuals with chronic heart failure (CHF) to maintain the microvascular PO2's (PO2mv proportional to O-2 delivery-to-uptake ratio) seen in healthy animals. Methods: We superfused sodium nitroprusside (SNP; 300 mu M), Krebs-Henseleit (control, CON) and L-nitro arginine methyl ester (L-NAME; 1.5 mM) onto the spinotrapezius muscle and measured PO2mv by phosphorescence quenching in female Sprague-Dawley rats (n = 26) at rest and during twitch contractions (1 Hz). Seven rats served as controls (Sham) while CHF was induced by myocardial infarction. CHF rats were grouped as moderate (MOD; n = 15) and severe CHF (SEV; n = 4) according to morphological data and baseline PO2mv. Results: In contrast to Sham and MOD, L-NAME did not affect the PO2mv response (dynamics and steady-state) of SEV when compared with CON. SNP restored the PO2mv profile of SEV to that seen in Sham animals during CON. Specifically, the effect of L-NAME expressed as Delta(L-NAME - CON) were: Baseline PO2mv [in mmHg, Delta Sham = -7.0 +/- 1.6 (P < 0.05); Delta SEV =-1.2 +/- 2.1], end-contractions PO2mv [in mmHg, Delta Sham = -5.0 +/- 1.0 (P < 0.05); Delta SEV = -2.5 +/- 0.5] and time constant of PO2mv decrease [in s, Delta Sham = -6.5 +/- 3.0 (P < 0.05); Delta SEV = -3.2 +/- 1.8]. Conclusion: These data provide the first direct evidence that the pathological profiles of PO2mv associated with severe CHF can be explained, in part, by a diminished vascular NO availability.