Changes in diaphragm structure following prolonged mechanical ventilation in piglets.
BACKGROUND
Prolonged mechanical ventilation and inactivity negatively affect muscle function. The mechanisms for this dysfunction are unclear and clinical studies of respiratory muscle are difficult to carry out. An animal model simulating the critical care environment was used to investigate the effects of 5 days' mechanical ventilation and diaphragm inactivity on diaphragm muscle morphology.


METHODS
Twelve 2-4-month-old piglets weighing 23-30 kg were studied. Seven animals received controlled mechanical ventilation and sedation such that spontaneous breathing efforts were inhibited over 5 days. Five control animals were ventilated for only 4-6 h following surgical preparation. Diaphragm biopsies were obtained from the left costal region at the end of all experiments.


RESULTS
Morphometric, morphologic, electron microscopic and enzyme histochemical examination of costal diaphragm biopsies was carried out. Contractile properties were studied over 5 days and the results have been previously reported. Cross-sectional area of alI fiber types was increased compared with controls. The proportion of type IIb/x fibers increased following inactivity (P < 0,05) and the proportion of type I and IIa fibers tended to decrease although not significantly. Focal areas of diaphragm fiber regeneration were found without signs of inflammation. Increased appearance of cytoplasmic vacuoles consisting of lipid accumulation was noted in type I fibers. Several study animals developed focal areas with weak myofibrillar ATPase activity and disrupted fiber organization. There were areas of myofibrillary destruction and loss of sarcomeric pattern, without evidence of selective thick filament loss or a change in the myosin to actin ratio.


CONCLUSIONS
Five days' mechanical ventilation with sedation and complete diaphragm inactivity resulted in changes in muscle fiber structure. A causal relationship can not be concluded but the acute changes in fiber type distribution and structure suggest that previously reported diaphragm contractile impairment occurs at the level of muscle fibers.
Radell
P
P
Department of Pediatric Anesthesia and Intensive Care, Karolinska Hospital and Institute, Stockholm, Sweden. peter.radell@kbh.ki.se
Edström
L
L
Stibler
H
H
Eriksson
L I
LI
Ansved
T
T
D000818:Animals; D003964:Diaphragm / Q000503:physiopathology* / Q000648:ultrastructure*; D004591:Electrophoresis, Polyacrylamide Gel; D007091:Image Processing, Computer-Assisted; D008488:Medical Illustration; D008854:Microscopy, Electron; D023421:Models, Animal; D018485:Muscle Fibers, Skeletal / Q000145:classification; D012121:Respiration, Artificial / Q000009:adverse effects*; D012129:Respiratory Function Tests; D018709:Statistics, Nonparametric; D013552:Swine; D013997:Time Factors