Early effects of mechanical ventilation on isotonic contractile properties and MAF-box gene expression in the diaphragm

• Published in: Journal of applied physiology (1985) Vol. 99; no. 2; pp. 747 - 756
• Main Authors: Zhu, Ercheng, Sassoon, Catherine S. H, Nelson, Renee, Pham, H. Tony, Zhu, Lei, Baker, Michael J, Caiozzo, Vincent J
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Physiological Soc 01.08.2005; American Physiological Society
• Subjects: Air breathing; Animals; Biological and medical sciences; Cytomegalovirus; Diaphragm - pathology; Diaphragm - physiopathology; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Regulation; Male; Muscle Contraction; Muscle Fibers, Skeletal - pathology; Muscle Proteins - metabolism; Muscular Atrophy - etiology; Muscular Atrophy - pathology; Muscular Atrophy - physiopathology; Rabbits; Respiration, Artificial - adverse effects; Respiratory system: anatomy, metabolism, gas exchange, ventilatory mechanics, respiratory hemodynamics; Ribonucleic acid; RNA; Space life sciences; Ventilation; Vertebrates: respiratory system; Myofibril; atrogin-1; Shortening; Rabbit; Respiratory system; Atrophy; maximum shortening velocity; Respiratory muscle; Positive pressure; Maximum velocity; Myosin; myosin heavy chain; Heavy peptide chain; Contractility; Mechanical properties; Lagomorpha; Gene expression; Striated muscle; myofibril injury; Biomechanics; Vertebrata; Mammalia; muscle atrophy F-box; Diaphragm; Lesion; Mechanical ventilation; Non-programmatic
• ISSN: 8750-7587; 1522-1601
• DOI: 10.1152/japplphysiol.00126.2005

1 Department of Medicine, Veterans Affairs Long Beach Healthcare System, Long Beach; Departments of 2 Medicine, 3 Orthopedic Surgery, and 4 Physiology and Biophysics, University of California, Irvine, California Submitted 1 February 2005 ; accepted in final form 10 April 2005 This study aimed to determine the time-dependent effects of diaphragmatic inactivity on its maximum shortening velocity ( V max ) and the muscle atrophy F-box (MAF-box, atrogin-1) gene expression during controlled mechanical ventilation (CMV). Twenty-four New Zealand White rabbits were grouped into 1 day, 2 days, and 3 days of CMV and controls in equal numbers. The in vitro isotonic contractile properties of the diaphragm were determined. In addition, myosin heavy chain protein and mRNA, myosin light chain, MAF-box mRNA, and volume density of abnormal myofibrils were measured. Tetanic force decreased, and V max increased from control of 6.4 to 6.6, 7.7, and 8.1 muscle lengths per second after 1, 2, and 3 days of CMV, respectively ( P < 0.02). The increased V max compensated for the decreased tetanic force; consequently, compared with the controls, maximum power output was unchanged after 3 days of CMV. V max correlated with the volume density of abnormal myofibrils [ y = 0.1 x + 5.7 ( r = 0.87, P < 0.01)]. In the diaphragm, MAF-box was overexpressed (355% of control) after 1 day of CMV, before the evidence of structural myofibril disarray. In conclusion, CMV produced a time-dependent increase in V max that was associated with the degree of myofibrillar disarray and independent of changes in myosin isoform expression. Furthermore, CMV produced an increase in MAF-box mRNA levels that may be partially or completely responsible for the degree of myofibrillar disarray resulting from CMV. positive pressure; maximum shortening velocity; myosin heavy chain; myofibril injury; muscle atrophy F-box; atrogin-1 Address for reprint requests and other correspondence: C. S. H. Sassoon, Pulmonary and Critical Care Section, VA Long Beach Healthcare System (11/111P), 5901 East 7 th St., Long Beach, CA 90822 (E-mail: csassoon{at}uci.edu )