Hemodynamic responses to small muscle mass exercise in heart failure patients with reduced ejection fraction

Abstract

To better understand the mechanisms responsible for exercise intolerance in heart failure with reduced ejection fraction (HFrEF), the present study sought to evaluate the hemodynamic responses to small muscle mass exercise in this cohort. In 25 HFrEF patients (64 ± 2 yr) and 17 healthy, age-matched control subjects (64 ± 2 yr), mean arterial pressure (MAP), cardiac output (CO), and limb blood flow were examined during graded static-intermittent handgrip (HG) and dynamic single-leg knee-extensor (KE) exercise. During HG exercise, MAP increased similarly between groups. CO increased significantly (+1.3 ± 0.3 l/min) in the control group, but it remained unchanged across workloads in HFrEF patients. At 15% maximum voluntary contraction (MVC), forearm blood flow was similar between groups, while HFrEF patients exhibited an attenuated increase at the two highest intensities compared with controls, with the greatest difference at the highest workload (352 ± 22 vs. 492 ± 48 ml/min, HFrEF vs. control, 45% MVC). During KE exercise, MAP and CO increased similarly across work rates between groups. However, HFrEF patients exhibited a diminished leg hyperemic response across all work rates, with the most substantial decrement at the highest intensity (1,842 ± 64 vs. 2,675 ± 81 ml/min; HFrEF vs. control, 15 W). Together, these findings indicate a marked attenuation in exercising limb perfusion attributable to impairments in peripheral vasodilatory capacity during both arm and leg exercise in patients with HFrEF, which likely plays a role in limiting exercise capacity in this patient population.

Exercise training in chronic heart failure: improving skeletal muscle O2transport and utilization

“…257,334). Nevertheless, it is important to acknowledge that HFrEF has not produced consistent alterations in bulk (i.e., total, limb) Q m during dynamic submaximal exercise, with investigations reporting decreased (23,66,137,153,228,299) or unaltered (15,198,226,274,278) bulk Q m responses in both human and animal models. The reasons for this discrepancy are not entirely clear but may involve differences in disease severity, variations in pharmacological treatment, distinct exercise modes/intensities, and Q m redistribution within and among muscles and/or muscle groups imposed by HFrEF (i.e., 2Q m to slow-twitch oxidative and 1Q m to fast-twitch glycolytic fibers) (137,203,228).…”

Peripheral vascular function, oxygen delivery and utilization: the impact of oxidative stress in aging and heart failure with reduced ejection fraction

“…Thus, to comprehensively assess the hemodynamic response to small muscle mass exercise in HFrEF patients and healthy age-matched control subjects, a study was recently undertaken that employed exercise paradigms utilizing both upper (HG exercise) and lower (KE exercise) limbs across a wide range of intensities [88]. During HG exercise, both groups exhibited a similar forearm hyperemic and vasodilatory response during lower intensity [15 % maximal voluntary contraction (MVC)] HG exercise, but HFrEF patients exhibited a 15–25 % attenuation in forearm blood flow at higher intensities (30 and 45 % MVC), due to an impaired vasodilatory capacity.…”

“…Despite these divergent findings in the elderly, given the marked elevation in oxidative stress [70, 123] and accompanying reduction in O 2 delivery [88] that has been reported during exercise in HFrEF, it seems plausible that this patient group would be well positioned to benefit from AO administration. Using L-NMMA to inhibit eNOS, Katz et al [124] failed to identify a change in exercise hyperemia during handgrip exercise between eNOS and placebo trials in class II–III HF patients, suggesting that the NO-mediated regulation of exercising forearm blood flow is impaired in this cohort.…”

“…Using L-NMMA to inhibit eNOS, Katz et al [124] failed to identify a change in exercise hyperemia during handgrip exercise between eNOS and placebo trials in class II–III HF patients, suggesting that the NO-mediated regulation of exercising forearm blood flow is impaired in this cohort. As discussed above, based on these earlier observations [88], we examined forearm blood flow during multiple levels of handgrip exercise before and after AO consumption in HFrEF patients and age-matched controls to determine whether disruptions in oxidative stress could “rescue” impaired O 2 delivery in the patient group. Contrary to our hypothesis, there were no differences in forearm blood flow as a consequence of AO administration, though it is noteworthy that the patient group did not exhibit a clear decrement in blood flow compared to age-matched controls in this study [71].…”

Impaired skeletal muscle vasodilation during exercise in heart failure with preserved ejection fraction

“…This limitation may be overcome through use of knee-extensor (KE) exercise, a small muscle mass model that does not provoke significant cardiopulmonary stress (21). While members of our group (22-24) and others (25,26) have utilized KE exercise to examine the regional regulation of exercising leg blood flow in HFrEF, this exercise model has not been employed to examine peripheral hemodynamics in the HFpEF patient population. In view of the well-defined relationship between blood flow, O 2 uptake, and exercise capacity (27,28), disease-related changes in the regulation of skeletal muscle blood flow may be an important contributor to exercise intolerance in this patient group.…”