Effects of Unilateral Phrenic Nerve Denervation on Diaphragm Contractility in Rat.

Abstract

We examined the early effects of phrenic nerve denervation on the diaphragm muscle 1, 3, 7 and 14 days after unilateral denervation in rats. In the denervated hemidiaphragms, force frequency curves at 3, 7 and 14 days decreased significantly by 51%, 50% and 38% respectively of the peak tension of the force frequency curves of the diaphragms of rats with sham operation. Twitch tensions increased significantly at 14 days, and contraction times and half relaxation times slowed significantly at 3, 7 and 14 days. The tensions of denervated diaphragms at 5 min during the fatigue runs was significantly increased at 14 days. As determined by histological staining, the mean cross sectional area of fast-twitch fibers (type II) decreased significantly from 2,742 (sham) to 1,599,um2 (14 days), but that of the slow-twitch fibers (type I) did not change significantly during the same period. These findings suggest that, during the first two weeks of denervation, fast twitch fibers (type II) atrophy more rapidly than slow twitch fatigue resistant fibers (type I), as confirmed by the contractile properties and histological findings. twitch kinetics; muscle atrophy; muscle plasticity Hemidiaphragmatic paralysis due to acute phrenic nerve injury is well known as a cause of respiratory muscle failure. Concerning the denervation of skeletal muscles, previous studies have shown that denervation of the skeletal muscles induced muscle fiber atrophy, with an increase in cell membrane resistance (Albuquerque et al. 1971), an enhanced extrajunctional acetylcholine (ACh) sensitivity (Axelsson and Thesleff 1959) and a depolarization of the resting membrane potential in the myocyte (Redfern and Thesleff 1971). Furthermore, recent studies have shown that denervation induces changes in the messenger RNA

Improved Calcium Utilization at Motor Nerve Terminals Exposed to Botulinum Neurotoxin in Mice

“…by the increase of directly induced tetanic force (data not shown). A similar selective increase in DT beyond the control was reported in the denervated diaphragm by Shindoh and co-workers [13]. Observing the prolonged time course of twitch contraction and histological staining patterns of the denervated diaphragm, they ascribed the recovery to be a consequence of the selective atrophy of fast-twitch muscle fibers.…”

Diaphragm Muscle Weakness in an Experimental Porcine Intensive Care Unit Model

“…All results from the experimental animals were compared with sham-operated control animals. According to the literature, sepsis [15], administration of CS [16] or denervation [17] alone, are sufficient to provoke respiratory muscle cell modifications such as atrophy and a decrease in maximal force production normalized to CSA. In consequence, we hypothesized that, when the above ICU setting factors are associated to mechanical ventilation and sedation, separately or in combination, they have important additive negative effects on diaphragm muscle function.…”

Small-Molecule Inhibition of MuRF1 Prevents Early Disuse-Induced Diaphragmatic Dysfunction and Atrophy

“…In rodent models, even brief periods (e.g., 12–72 h) of MV significantly reduce the diaphragm fiber’s contractile function and cross-sectional area (CSA) [ 9 , 10 ]. Similar levels of diaphragmatic force loss are also observed in the first days of unilateral diaphragm denervation (UDD) in rats [ 11 , 12 ]. Furthermore, both UDD and MV experimental models result in a rapid and preferential loss of sarcomeric proteins, particularly the myosin heavy chain (MHC) isoforms [ 9 , 10 , 11 , 12 ].…”