Effects of Constant Flow vs. Constant Pressure Perfusion on Fluid Filtration in Severe Hypothermic Isolated Blood-Perfused Rat Lungs

Abstract

BackgroundVictims of severe accidental hypothermia are prone to fluid extravasation but rarely develop lung edema. We hypothesize that combined hypothermia-induced increase in pulmonary vascular resistance (PVR) and a concomitant fall in cardiac output protect the lungs against edema development. Our aim was to explore in hypothermic-isolated blood-perfused rat lungs whether perfusion at constant pressure influences fluid filtration differently from perfusion at constant flow.MethodsIsolated blood-perfused rat lungs were hanging freely in a weight transducer for measuring weight changes (ΔW). Fluid filtration coefficient (Kfc), was determined by transiently elevating left atrial pressure (Pla) by 5.8 mmHg two times each during normothermia (37°C) and during hypothermia (15°C). The lung preparations were randomized to two groups. One group was perfused with constant flow (Constant flow group) and the other group with constant pulmonary artery pressure (Constant PPA group). Microvascular pressure (Pmv) was determined before and during elevation of Pla (ΔPmv) by means of the double occlusion technique. Kfc was calculated with the formula Kfc = ΔW/ΔPmv/min. All Kfc values were normalized to predicted lung weight (PLW), which was based on body weight (BW) according to the formula: PLW = 0.0053 BW − 0.48 and presented as KfcPLW in mg/min/mmHg/g. At cessation, bronchoalveolar lavage (BAL) fluid/perfusate protein concentration (B/P) ratio was determined photometrically. Data were analyzed with parametric or non-parametric tests as appropriate. p < 0.05 considered as significant.ResultsPerfusate flow remained constant in the Constant flow group, but was more than halved during hypothermia in the Constant PPA group concomitant with a more fold increase in PVR. In the Constant flow group, KfcPLW and B/P ratio increased significantly by more than 10-fold during hypothermia concerted by visible signs of edema in the trachea. Hemoglobin and hematocrit increased within the Constant flow group and between the groups at cessation of the experiments.ConclusionIn hypothermic rat lungs perfused at constant flow, fluid filtration coefficient per gram PLW and B/P ratio increased more than 10-fold concerted by increased hemoconcentration, but the changes were less in hypothermic lungs perfused at constant PPA.

Physiological Changes in Subjects Exposed to Accidental Hypothermia: An Update

“…Investigators have shown that fluids and proteins shifting from the intravascular to the interstitial compartment might result in edema of most organs, except for the lungs, in which fulminant edema often is seen first after rewarming from HCA (131)(132)(133). Therefore, investigators recently wondered if hypothermia-induced increase in pulmonary vascular resistance (PVR) could explain this difference (134). They compared fluid filtration rate in normothermic rat lungs perfused with blood at constant flow with two groups of blood-perfused lungs cooled to 15 • C; one group perfused at constant flow and one group perfused at constant pulmonary artery inflow pressure (PPA).…”

“…The findings were interpreted as the result of a more-fold increase in pulmonary vascular resistance (PVR) in the constant PPA group, which reduced microvascular pressure and fluid filtration rate. A similar mechanism could possibly also provide an early protection against lung edema in humans exposed to AH ( 134 ).…”

Pulmonary Congestion Due to Right and Left Heart Output Mismatching: A Case Report and Literature Review

“…(Huang et al, 1993;Komai et al, 1993;Ross and DiMarco, 2010;Yang et al, 2015;Karmouty-Quintana et al, 2018). Some of these impacts will last for a couple of days after the surgery but some may recover shortly after CPB [e.g., pulmonary vascular resistance will be increased by hypothermia and/or non-pulsatile blood flow and will quickly recover by rewarming and/or resuming pulsatile blood flow (Halsøy et al, 2016;Taylor et al, 1979]. However, when pulmonary artery flow starts to recover after releasing the aortic clamp, it will be much more difficult for the pulmonary artery blood flow to pass through the pulmonary microcirculation unless these closed or nearly closed microcirculations open again.…”