Source: Annual Congress 2011 - Physiology of human pulmonary hypertension
Disease area: Pulmonary vascular diseases

Abstract

Introduction
Recently it was suggested that patients with pulmonary hypertension (PH) suffer from diaphragm dysfunction due to increased loading conditions. In the present study the aim is to determine the contractile strength of the diaphragm muscle in PH and control rats. The extensor digitorum longus (EDL) muscle will serve as a control skeletal muscle.
Methods
PH was induced in Wistar rats by a single injection of monocrotaline (60 mg/kg). The diaphragm and EDL (PH n=5; controls n=5) muscle were excised for determination of in vitro contractile properties. Muscle bundles were treated with a relaxing solution (5ºC) containing 1% Triton X-100 to permeabilize membranes. Single fibers were mounted on a single fiber apparatus. Maximum force (Fmax), rate constant of force redevelopment (Ktr), as a measure of the cross bridge kinetics, and calcium sensitivity (pCa₅₀) were measured in diaphragm and EDL single muscle fibers.Results
In the EDL muscle no significant differences were found in Fmax and pCa₅₀. Ktr was significantly higher in PH fibers: 10.86 ± 0.79 vs 15.09 ± 0.74 (p=0.005). The cross sectional area (CSA) of the fibers measured was significantly decreased in PH fibers: 2563 ± 166.7 vs 1961 ± 88.82 µm² (p=0.013)
Preliminary data on the diaphragm muscle (n=2), suggest a decrease of Fmax, Ktr, pCa₅₀ and CSA. Fmax: 128.6 ± 4.48 vs 105.5 ± 7.03 mN/mm², Ktr: 8.995 ± 1.39 vs 7.601 ± 0.56, pCa₅₀: 5.780 ± 0.069 vs 5.720 ± 0.058, CSA: 2929 ± 162 vs 1700 ± 130 µm².
Conclusions
These data suggest a more pronounced effect of PH on the diaphragm muscle compared to EDL. However, more experiments on the diaphragm muscle and fiber type determination is necessary before final conclusions can be drawn.

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Citations should be made in the following way:
E. Manders, N. Westerhof, A. Vonk-Noordegraaf, F. de Man, C. Ottenheijm (Amsterdam, Netherlands). Diaphragm function in experimental pulmonary hypertension. Eur Respir J 2011; 38: Suppl. 55, 2303

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