Aging potentiates the effect of congestive heart failure on muscle microvascular oxygenation

Abstract

Congestive heart failure (CHF) is most prevalent in aged individuals and elicits a spectrum of cardiovascular and muscular perturbations that impairs the ability to deliver (Q̇o2) and utilize (V̇o2) oxygen in skeletal muscle. Whether aging potentiates the CHF-induced alterations in the Q̇o2-to-V̇o2 relationship [which determines microvascular Po2 (PmvO2)] in resting and contracting skeletal muscle is unclear. We tested the hypothesis that old rats with CHF would demonstrate a greater impairment of skeletal muscle PmvO2 than observed in young rats with CHF. Phosphorescence quenching was utilized to measure spinotrapezius PmvO2 at rest and across the rest-to-contractions (1-Hz, 4–6 V) transition in young (Y) and old (O) male Fischer 344 Brown-Norway rats with CHF induced by myocardial infarction (mean left ventricular end-diastolic pressure >20 mmHg for YCHF and OCHF). In CHF muscle, aging significantly reduced resting PmvO2 (32.3 ± 3.4 Torr for YCHF and 21.3 ± 3.3 Torr for OCHF; P < 0.05) and in both YCHF and OCHF compared with their aged-matched counterparts, CHF reduced the rate of the PmvO2 fall at the onset of contractions. Moreover, across the on-transient and in the subsequent steady state, PmvO2 values in OCHF vs. YCHF were substantially lower (for steady-state, 20.4 ± 1.7 Torr for YCHF and 16.4 ± 2.0 Torr for OCHF; P < 0.05). At rest and during contractions in CHF, the pressure driving blood-muscle O2 diffusion (PmvO2) is substantially decreased in old animals. This finding suggests that muscle dysfunction and exercise intolerance in aged CHF patients might be due, in part, to the failure to maintain a sufficiently high PmvO2 to facilitate blood-muscle O2 exchange and support mitochondrial ATP production.