Pulmonary microvascular permeability. Responses to high vascular pressure after induction of pacing-induced heart failure in dogs.
The pressure threshold for injury of pulmonary capillaries is approximately 50 to 55 cm H2O in the canine lung, as measured by changes in the filtration coefficient (Kf,c). Since the pulmonary endothelial basement membrane has been observed to thicken in patients with heart failure and pulmonary venous hypertension, we hypothesized that both baseline permeability and the threshold for high-vascular-pressure injury would be altered as a result. Dogs (n = 12) were chronically paced at 245 beats per minute for approximately 4 weeks, then were paced at 225 beats per minute for an additional 3 weeks. Lung lobes from anesthetized paced dogs and additional control dogs (n = 14) were then isolated, ventilated, and perfused with blood. Although vascular resistance was increased nearly threefold and vascular compliance reduced by 50% in the paced group, Kf,c referenced to 1 g blood-free dry weight was no different from control. Despite this lack of difference at normal pulmonary vascular pressures, several significant results were obtained. First, in the paced group there was a significant increase in the threshold for high-vascular-pressure injury: Kf,c measured at pulmonary vascular pressures commonly seen in heart failure (20 to 50 cm H2O) were significantly less in this group compared with control. Model predictions showed that in vivo, this difference in Kf,c would result in a 50% reduction in the amount of water and protein cleared across the pulmonary capillary endothelial barrier in the paced group.(ABSTRACT TRUNCATED AT 250 WORDS)
Townsley
M I
MI
Department of Physiology, University of South Alabama, Mobile 36688, USA.
Fu
Z
Z
Mathieu-Costello
O
O
West
J B
JB
D000818:Animals; D001794:Blood Pressure; D002199:Capillary Permeability; D002304:Cardiac Pacing, Artificial; D003187:Compliance; D004285:Dogs; D006333:Heart Failure / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D006439:Hemodynamics; D006976:Hypertension, Pulmonary / Q000503:physiopathology; D066298:In Vitro Techniques; D008168:Lung / Q000473:pathology / Q000503:physiopathology* / Q000648:ultrastructure; D008854:Microscopy, Electron; D008954:Models, Biological; D011652:Pulmonary Circulation; D013997:Time Factors; D014655:Vascular Resistance; D016277:Ventricular Function, Left / Q000502:physiology