• Hubmayr, Rolf Dieter (PI)

Project: Research project

Project Details


The ultimate goal of this proposal is to test the following
hypotheses: a) hypercarbic respiratory failure during weaning
from mechanical ventilation usually results from diaphragm
fatigue, and b) diaphragm fatigue results from an imbalance
between the mechanical load on the respiratory muscles and their
endurance. Three studies are presented. The aim of Protocol 1 is to verify the importance of diaphragm
fatigue in the pathophysiology of hypercarbic respirtory failure in
patients. The response of the diaphragm to bilateral phrenic
stimulations will be evaluated in ventilator-dependent patients
before and after failed weaning attempts. Diaphragm fatigue will
be defined as a fall in the transdiaphragmatic twitch pressure
between pre and postweaning states. The results will determine:
a) the incidence of fatigue, and b) whether fatigue is a failure in
neuromuscular transmission and/or excitation contraction
coupling. This study will also give information concerning: a) the
time necessary for recovery from fatigue, and b) the predictive
value of less invasive measurements such as inspiratory work,
inspiratory muscle strength, airway occlusion pressure,
transdiaphragmatic pressure (PDI), breathing pattern,
thoracoabdominal motion, the power spectral analysis of the
diaphragm EMG, and gas exchange variables. The aim of Protocol 2 is to validate PDI generated by bilateral
phrenic stimulation as an index of diaphragm contractility in
normal man. In normal volunteers, PDI produced by bilateral
phrenic nerve stimulation will be evaluated as a function of lung
volume during relaxation and while thoracoabdominal shape is
being systematically altered by a pneumatic device which
displaces the thorax and abdomen along an isovolume line. It will
thus be determined whether abdominal volume at a constant lung
volume has a significant independent effect on diaphragm
function. The specific aim of Protocol 3 is to determine the relationship
between PDI generated by bilateral phrenic stimulation and
regional diaphragm mechanics in the dog. To assess the
limitations of PDI as an index of global diaphragm function,
regional diaphragm function and its relationship to PDI will be
evaluated in the dog. By adapting the videoroentgenographic
marker technique for studying regional lung function to the
diaphragm, the regional contractility will be evaluated in vivo
under conditions of defined initial lengths and loads.
Effective start/end date9/1/8811/30/92


  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $96,893.00
  • National Institutes of Health


  • Medicine(all)


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