Interaction of chemical and high vascular pressure injury in isolated canine lung

Abstract

Because both chemical and mechanical insults to the lung may occur concomitantly with trauma, we hypothesized that the pressure threshold for vascular pressure-induced (mechanical) injury would be decreased after a chemical insult to the lung. Normal isolated canine lung lobes (N, n = 14) and those injured with either airway acid instillation (AAI, n = 18) or intravascular oleic acid (OA, n = 25) were exposed to short (5-min) periods of elevated venous pressure (HiPv) ranging from 19 to 130 cmH2O. Before the HiPv stress, the capillary filtration coefficient (Kf,c) was 0.12 +/- 0.01, 0.27 +/- 0.03, and 0.31 +/- 0.02 ml.min-1.cmH2O-1 x 100 g-1 and the isogravimetric capillary pressure (Pc,i) was 9.2 +/- 0.3, 6.8 +/- 0.5, and 6.5 +/- 0.3 cmH2O in N, AAI, and OA lungs, respectively. However, the pattern of response to HiPv was similar in all groups: Kf,c was no different from the pre-HiPv value when the peak venous pressure (Pv) remained less than 55 cmH2O, but it increased reversibly when peak Pv exceeded 55 cmH2O (P less than 0.05). The reflection coefficient (sigma) for total proteins measured after pressure exposure averaged 0.60 +/- 0.03, 0.32 +/- 0.04, and 0.37 +/- 0.09 for N, AAI, and OA lobes respectively. However, in contrast to the result expected if pore stretching had occurred at high pressure, in all groups the sigma measured during the HiPv stress when Pv exceeded 55 cmH2O was significantly larger than that measured during the recovery period.(ABSTRACT TRUNCATED AT 250 WORDS)

High Vascular Pressure–Induced Lung Injury Requires P450 Epoxygenase–Dependent Activation of TRPV4

“…Similarly, the response was attenuated in TRPV4 2/2 mice. Though there was a tendency for Ca 21 intensity to increase in these latter groups, HiPv-induced recruitment of Ca 21 entry pathways other than TRPV4 was considered unlikely, since the response to HiPv remained the same in knockout lungs pretreated with the nonspecific Ca 21 entry blocker GdCl 3 .…”

“…*P , 0.05 versus BL; # P , 0.05 versus wild-type control group. when Pv exceeds approximately 30 to 50 cm H 2 O in mammalian lung (2)(3)(4)(20)(21)(22). Using vascular corrosion casting with low viscosity prepolymerized methyl methacrylate, we have shown that the alveolar septal barrier is the site of leak in the pulmonary circulation when HiPv increases permeability (23).…”

“…We have previously shown that the low Ca 21 buffer is completely effective in preventing a permeability response to direct activation of store-operated TRP channels or TRPV4 (8). The filtration coefficient (K f ) was measured as an index of pulmonary endothelial permeability (3,8), in each of several experimental groups:…”

“…In lung, high vascular pressure (HiPv) exceeding a threshold of 30 to 50 cm H 2 O increases endothelial permeability (1)(2)(3)(4). While mechanical stress failure of the alveolar septal barrier can occur at higher pressures, leading to overt alveolar flooding (5), the molecular mechanisms underlying the early HiPv-induced increase in endothelial permeability are not well understood.…”

Physiological determinants of the pulmonary filtration coefficient

“…As shown in Fig. 1, K f,t varies as a function of body weight (BW) for mouse (11,16,32), rat (2,3,18), rabbit (1,4), dog (21,29), and sheep (8,22) as well as a predicted value for a 70-kg human. The relationship of K f,t to body mass is similar to that for alveolar (S ALV ) or pulmonary capillary (S CAP ) surface areas and pulmonary diffusion coefficient for oxygen (D L O 2 ) determined by Weibel and associates using morphometric methods (31).…”