Perivascular fluid cuffs decrease lung compliance by increasing tissue resistance.
OBJECTIVE
Lung inflammation causes perivascular fluid cuffs to form around extra-alveolar blood vessels; however, the physiologic consequences of such cuffs remain poorly understood. Herein, we tested the hypothesis that perivascular fluid cuffs, without concomitant alveolar edema, are sufficient to decrease lung compliance.


METHODS
Prospective, randomized, controlled study.


METHODS
Research laboratory.


METHODS
One hundred twenty male CD40 rats.


METHODS
To test this hypothesis, the plant alkaloid thapsigargin was used to activate store-operated calcium entry and increase cytosolic calcium in endothelium. Thapsigargin was infused into a central venous catheter of intact, sedated, and mechanically ventilated rats.


METHODS
Static and dynamic lung mechanics and hemodynamics were measured continuously.


RESULTS
Thapsigargin produced perivascular fluid cuffs along extra-alveolar vessels but did not cause alveolar flooding or blood gas abnormalities. Lung compliance dose-dependently decreased after thapsigargin infusion, attributable to an increase in tissue resistance that was attributed to increased tissue damping and tissue elastance. Airway resistance was not changed. Neither central venous pressure nor left ventricular end diastolic pressure was altered by thapsigargin. Heart rate did not change, although thapsigargin decreased left ventricular systolic function sufficient to reduce cardiac output by 50%. Infusion of the type 4 phosphodiesterase inhibitor, rolipram, prevented thapsigargin from inducing perivascular cuffs and decreasing lung compliance. Rolipram also normalized pressure over time and corrected the deficit in cardiac output.


CONCLUSIONS
Our findings resolve for the first time that perivascular cuff formation negatively impacts mechanical coupling between the bronchovascular bundle and the lung parenchyma, decreasing lung compliance without impacting central venous pressure.
Lowe
Kevin
K
Department of Surgery, Center for Lung Biology, University of South Alabama, Mobile, Alabama, USA.
Alvarez
Diego F
DF
King
Judy A
JA
Stevens
Troy
T
D055371:Acute Lung Injury / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015633:Extravascular Lung Water / Q000187:drug effects / Q000502:physiology*; D008170:Lung Compliance / Q000187:drug effects / Q000502:physiology*; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011654:Pulmonary Edema / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D015656:Respiratory Mechanics / Q000187:drug effects / Q000502:physiology*; D020889:Rolipram / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology
D004791:Enzyme Inhibitors; D010726:Phosphodiesterase Inhibitors; D019284:Thapsigargin; D020889:Rolipram
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