The Impact of Sildenafil on the Pulmonary Circulation in Healthy Trained and Untrained Humans

Summary

There is emerging evidence suggesting that the pulmonary vasculature and right heart may play a role in the limitation of exercise capacity in healthy individuals. It is well established that aerobic training improves cardiovascular function. While the pulmonary system is integral to the function of the cardiopulmonary system, it has been traditionally accepted that lung function does not respond to exercise training. However, recent research suggests pulmonary vascular function adaptations may occur with aerobic training, and this may contribute to enhanced exercise tolerance. Research has highlighted that increased capillary blood volume (Vc) and diffusion capacity for carbon monoxide (DLCO) are correlated with higher cardiorespiratory fitness at rest. Additionally, endurance trained participants have increased exercise DLCO concomitant to higher resting Vc when compared to untrained participants, and during exercise this difference seems to be driven by higher membrane diffusing capacity (Dm), independent of Vc or VA (alveolar volume). Of importance is also the evidence that highlights endurance trained participants having reduced pulmonary arterial pressures at rest and during exercise. Reduced pulmonary arterial pressure in endurance trained participants despite endurance trained participants consistently displaying increased diffusion capacity/pulmonary perfusion at rest and during exercise suggests a lower threshold pressure for pulmonary capillary recruitment. Together, this cross-sectional evidence suggests improvements in the pulmonary circulation due to exercise training in order to facilitate gas exchange. Whether this apparent improvement in pulmonary circulation is due to enhanced pulmonary vascular function via NO mediated vasodilation must be determined experimentally. If sildenafil administration improves DLCO, Vc, and Dm, this would provide evidence that the NO mediated vasodilatory pathway plays a role in the regulation of vascular tone, function, and perfusion across the pulmonary vasculature. Should a larger response to sildenafil be observed in untrained persons, this would suggest better baseline vascular function in trained participants compared to untrained. This would provide strong evidence that aerobic training improves pulmonary vasculature function which is contrary to the conventional understanding of aerobic training on the cardiopulmonary system.

Conditions

• Healthy

Interventions

DRUG

Sildenafil 50 mg

Sildenafil is a phosphodiesterase type-5 inhibitor, which augments/prolongs the naturally occurring nitric oxide mediated vasodilatory pathway. Sildenafil pill is over-encapsulated to be identical in appearance to the placebo intervention.

DRUG

Placebo

Medical-grade placebo pill, over-encapsulated to be identical in appearance to the sildenafil intervention.

Sponsors & Collaborators

• University of Alberta

  lead OTHER

Principal Investigators

• Sean van Diepen, MD · University of Alberta

• Michael K Stickland, PhD · University of Alberta

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

TRIPLE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

40 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2021-07-01

Primary Completion

2024-07-05

Completion

2024-07-05

Countries

• Canada

Study Locations