Progressive chronic heart failure slows the recovery of microvascular O₂pressures after contractions in the rat spinotrapezius muscle

Abstract

Chronic heart failure (CHF) induces muscle fiber-type specific alterations in skeletal muscle O(2) delivery and utilization during metabolic transitions. As a result, the recovery of microvascular Po(2) (Pmv(O(2))) is prolonged in slow-twitch skeletal muscle but not fast-twitch skeletal muscle in rats with CHF. We tested the hypothesis that CHF slows Pmv(O(2)) recovery in rat skeletal muscle of a mixed fiber-type analogous to human locomotory muscles and that the degree of slowing correlates with central indexes of heart failure. Healthy control [n = 6, left ventricular end-diastolic pressure (LVEDP): 10 ± 1 mmHg], moderate CHF (n = 6, LVEDP: 18 ± 2 mmHg), and severe CHF (n = 4, LVEDP: 34 ± 2 mmHg) female Sprague-Dawley rats had their right spinotrapezius muscles (41% type I, 7% type IIa, and 52% type IIb and d/x) exposed, and Pmv(O(2)) was measured via phosphorescence quenching during 180 s of recovery from 180 s of electrically induced twitch contractions (1 Hz, 4-6 V). CHF progressively slowed the mean response time (MRT; the time to reach 63% of the overall dynamic response) of Pmv(O(2)) recovery (MRT(off); control: 60.2 ± 6.9, moderate CHF: 72.8 ± 6.6, and severe CHF: 109.8 ± 6.6 s, P < 0.05 for all). MRT(off) correlated positively with central hemodynamic (LVEDP: r = 0.76, P < 0.01) and morphological (right ventricle-to-body weight ratio: r = 0.74, P < 0.01; and lung weight-to-body weight ratio: r = 0.79, P < 0.01) indexes of heart failure. The present investigation suggests that slowed Pmv(O(2)) kinetics during recovery in CHF constitutes a mechanistic link between impaired circulatory and metabolic recovery after contractions in CHF.

In vivo Ca2+ buffering capacity and microvascular oxygen pressures following muscle contractions in diabetic rat skeletal muscles: fiber-type specific effects

“…This is an important observation with respect to the present findings, in part, because diseaseassociated changes in the on-kinetics often presage derangements in the off-kinetics. For instance, in the spinotrapezius (mixed fiber type) of rats in congestive heart failure, a condition that impacts Pmv O 2 on-kinetics (14), the off-kinetics were slowed in proportion to the degree of left ventricular dysfunction (10).…”

Sildenafil improves microvascular O2 delivery-to-utilization matching and accelerates exercise O2 uptake kinetics in chronic heart failure

“…To keep a sufficiently high PO 2mv , however, O 2 delivery should be spatially and temporally matched to V O 2 of individual fibers. In this context, seminal studies found that intramuscular PO 2mv in rodents with CHF was critically low either at rest-to-contractions transition (7,14) or during early recovery (12), i.e., when V O 2 should be increasing or decreasing most rapidly, respectively. Importantly, it was demonstrated that reduced nitric oxide (NO) bioavailability exerted a key mechanistic role on on-and off-exercise O 2 delivery-toutilization uncoupling in these animal preparations (24,25).…”

Integrative research: the key to unlocking the mysteries of chronic heart failure and skeletal muscle dysfunction

“…A recognized limitation of this study is the finding that the correlations of off-transient and central indexes of cardiac failure were likely driven by the inclusion of four animals with the most severe heart failure; this group could be increased in number to solidify these conclusions. Despite this concern regarding the relatively small cohort of severe CHF in the study of Copp et al (1), these findings have potential importance in terms of functional capacity and may provide insight into why work and exercise tolerance as well as the ability to perform activities of daily living are reduced in patients with CHF.…”

“…In this issue of the American Journal of Physiology-Heart and Circulatory Physiology, Copp et al (1) employed an integrative approach to examine peripheral dysfunction in CHF as measured by the off-transient or recovery kinetics of microvascular O 2 pressure (Pmv O 2 ) and coupled this peripheral measure with central hemodynamic and morphological indexes of heart failure. The most novel and important findings of this study were that 1) progressive CHF increasingly slowed the recovery of Pmv O 2 in a mixed fiber-type muscle, 2) mean response time of the off-transient (MRT off ) and the MRT off-on differences (a measure of the asymmetry between on-and off-transients) correlated with central hemodynamic and morphological indexes of heart failure, and 3) off-transient differences may be present despite a lack of on-transient alterations.…”

“…The technique of phosphorescence quenching (20), as used by Copp et al (1), allowed the direct determination of Pmv O 2 during the transition from exercise to rest in the muscle of mixed fiber type (spinotrapezius). The spinotrapezius was chosen since the muscle fiber-type composition and oxidative capacity are similar to the human quadriceps (21), thereby making this model a relevant and potentially translational animal model.…”