Sildenafil: Possible Prophylaxis against Swimming-induced Pulmonary Edema.

Swimming-induced pulmonary edema (SIPE) occurs during swimming and scuba diving, usually in cold water, in susceptible healthy individuals, especially military recruits and triathletes. We have previously demonstrated that pulmonary artery (PA) pressure and PA wedge pressure are higher during immersed exercise in SIPE-susceptible individuals versus controls, confirming that SIPE is a form of hemodynamic pulmonary edema. Oral sildenafil 50 mg 1 h before immersed exercise reduced PA pressure and PA wedge pressure, suggesting that sildenafil may prevent SIPE. We present a case of a 46-yr-old female ultratriathlete with a history of at least five SIPE episodes. During a study of an exercise submerged in 20°C water, physiological parameters before and after sildenafil 50 mg orally were as follows: O2 consumption 1.75, 1.76 L·min; HR 129, 135 bpm; arterial pressure 189/88 (mean 121.5), 172/85 (mean 114.3) mm Hg; mean PA pressure 35.3, 28.8 mm Hg; and PA wedge pressure 25.3, 19.7 mm Hg. She has had no recurrences during 20 subsequent triathlons while taking 50 mg sildenafil before each swim. This case supports sildenafil as an effective prophylactic agent against SIPE during competitive surface swimming.

The HO-1/CO system regulates mitochondrial-capillary density relationships in human skeletal muscle.

The heme oxygenase-1 (HO-1)/carbon monoxide (CO) system induces mitochondrial biogenesis, but its biological impact in human skeletal muscle is uncertain. The enzyme system generates CO, which stimulates mitochondrial proliferation in normal muscle. Here we examined whether CO breathing can be used to produce a coordinated metabolic and vascular response in human skeletal muscle. In 19 healthy subjects, we performed vastus lateralis muscle biopsies and tested one-legged maximal O2 uptake (V̇o2max) before and after breathing air or CO (200 ppm) for 1 h daily for 5 days. In response to CO, there was robust HO-1 induction along with increased mRNA levels for nuclear-encoded mitochondrial transcription factor A (Tfam), cytochrome c, cytochrome oxidase subunit IV (COX IV), and mitochondrial-encoded COX I and NADH dehydrogenase subunit 1 (NDI). CO breathing did not increase V̇o2max (1.96 ± 0.51 pre-CO, 1.87 ± 0.50 post-CO l/min; P = not significant) but did increase muscle citrate synthase, mitochondrial density (139.0 ± 34.9 pre-CO, 219.0 ± 36.2 post-CO; no. of mitochondrial profiles/field), myoglobin content and glucose transporter (GLUT4) protein level and led to GLUT4 localization to the myocyte membrane, all consistent with expansion of the tissue O2 transport system. These responses were attended by increased cluster of differentiation 31 (CD31)-positive muscle capillaries (1.78 ± 0.16 pre-CO, 2.37 ± 0.59 post-CO; capillaries/muscle fiber), implying the enrichment of microvascular O2 reserve. The findings support that induction of the HO-1/CO system by CO not only improves muscle mitochondrial density, but regulates myoglobin content, GLUT4 localization, and capillarity in accordance with current concepts of skeletal muscle plasticity.