Dries Testelmans1, Karen Maes1, Patrick Wouters2, Scott K Powers3, Marc Decramer1, Ghislaine Gayan-Ramirez4. 1. Respiratory Muscle Research Unit, Laboratory of Pneumology and Respiratory Division, Katholieke Universiteit Leuven, O&N 1, bus 706, Herestraat 49, 3000, Leuven, Belgium. 2. Department of Anesthesiology, Katholieke Universiteit Leuven, UZ Gasthuisberg, Herestraat 49, 3000, Leuven, Belgium. 3. Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL, USA. 4. Respiratory Muscle Research Unit, Laboratory of Pneumology and Respiratory Division, Katholieke Universiteit Leuven, O&N 1, bus 706, Herestraat 49, 3000, Leuven, Belgium. ghislaine.gayan-ramirez@med.kuleuven.be.
Abstract
OBJECTIVE: Aminosteroidal and benzylisoquinoline neuromuscular blocking agents are used in the intensive care unit to facilitate mechanical ventilation. The use of these agents has been associated with development of critical illness myopathy; however, the relative frequency of myopathy development among agents is not known. The aim of our study was to compare the effects of 24 h infusion of rocuronium or cisatracurium on the diaphragm in mechanically ventilated rats. DESIGN: Randomized, controlled experiment. SETTING: Basic animal science laboratory. SUBJECTS: Male Wistar rats, 14 weeks old. INTERVENTIONS: Rats were divided into four groups to receive either saline, rocuronium (low dose) or cisatracurium (low or high dose). MEASUREMENTS AND RESULTS: After 24 h, in vitro diaphragm tetanic force was decreased after rocuronium (-33% vs. saline), while the force was more preserved after cisatracurium, even in the high-dose group. Cross-sectional areas of the different diaphragm and gastrocnemius fibers were unaltered. Diaphragmatic MURF-1 mRNA was increased after rocuronium (+44% vs. saline), while unchanged in both cisatracurium groups. Calpain activity was increased after rocuronium (+75% vs. saline) and unchanged in the cisatracurium groups. MURF-1 mRNA expression and calpain activity were negatively correlated with diaphragm force. CONCLUSIONS: Cisatracurium infusion during controlled mechanical ventilation exerted less detrimental effects on diaphragm function and proteolytic activity than infusion of rocuronium, even with the higher effective dose. These data suggest that increased calpain activity and increased activation of the ubiquitin proteasome system play a role in the different effects of these agents.
OBJECTIVE: Aminosteroidal and benzylisoquinoline neuromuscular blocking agents are used in the intensive care unit to facilitate mechanical ventilation. The use of these agents has been associated with development of critical illness myopathy; however, the relative frequency of myopathy development among agents is not known. The aim of our study was to compare the effects of 24 h infusion of rocuronium or cisatracurium on the diaphragm in mechanically ventilated rats. DESIGN: Randomized, controlled experiment. SETTING: Basic animal science laboratory. SUBJECTS: Male Wistar rats, 14 weeks old. INTERVENTIONS:Rats were divided into four groups to receive either saline, rocuronium (low dose) or cisatracurium (low or high dose). MEASUREMENTS AND RESULTS: After 24 h, in vitro diaphragm tetanic force was decreased after rocuronium (-33% vs. saline), while the force was more preserved after cisatracurium, even in the high-dose group. Cross-sectional areas of the different diaphragm and gastrocnemius fibers were unaltered. Diaphragmatic MURF-1 mRNA was increased after rocuronium (+44% vs. saline), while unchanged in both cisatracurium groups. Calpain activity was increased after rocuronium (+75% vs. saline) and unchanged in the cisatracurium groups. MURF-1 mRNA expression and calpain activity were negatively correlated with diaphragm force. CONCLUSIONS:Cisatracurium infusion during controlled mechanical ventilation exerted less detrimental effects on diaphragm function and proteolytic activity than infusion of rocuronium, even with the higher effective dose. These data suggest that increased calpain activity and increased activation of the ubiquitin proteasome system play a role in the different effects of these agents.
Authors: Joseph B Shrager; Yoyo Wang; Myung Lee; Shannon Nesbit; Winston Trope; Harrison Konsker; Emmanuel Fatodu; Mark S Berry; George Poulstides; Jeffrey Norton; Thomas Burdon; Leah Backhus; Roger Cooke; Huibin Tang Journal: Respir Med Date: 2021-09-21 Impact factor: 3.415