Distribution of Capillary Transit Times in Isolated Lungs of Oxygen-Tolerant Rats

Abstract

Rats pre-exposed to 85% O2 for 5–7 days tolerate the otherwise lethal effects of 100% O2. The objective was to evaluate the effect of rat exposure to 85% O2 for 7 days on lung capillary mean transit time (t̄c) and distribution of capillary transit times (hc(t)). This information is important for subsequent evaluation of the effect of this hyperoxia model on the redox metabolic functions of the pulmonary capillary endothelium. The venous concentration vs. time outflow curves of fluorescein isothiocyanate labeled dextran (FITC-dex), an intravascular indicator, and coenzyme Q1 hydroquinone (CoQ1H2), a compound which rapidly equilibrates between blood and tissue on passage through the pulmonary circulation, were measured following their bolus injection into the pulmonary artery of isolated perfused lungs from rats exposed to room air (normoxic) or 85% O2 for 7 days (hyperoxic). The moments (mean transit time and variance) of the measured FITC-dex and CoQ1H2 outflow curves were determined for each lung, and were then used in a mathematical model [Audi et al. J. Appl. Physiol. 77: 332–351, 1994] to estimate t̄c and the relative dispersion (RDc) of hc(t). Data analysis reveals that exposure to hyperoxia decreases lung t̄c by 42% and increases RDc, a measure hc(t) heterogeneity, by 40%.

Differential Lung Uptake of 99mTc-Hexamethylpropyleneamine Oxime and 99mTc-Duramycin in the Chronic Hyperoxia Rat Model

“…In vivo lung uptake of duramycin reported in this study likely reflects overall cell death (32). In fact, the time course of increased duramycin uptake during the hyperoxic lung injury observed here (figure 5) appears to parallel the rate of loss of endothelial cells reported previously by Crapo (9) as well as the loss of body weight of the animals in this study (figure 1). Our proposed interpretation of the above results is that out to 7 days both HMPAO and duramycin lung uptake in hyperoxic rats increase due to increases in the redox status and apoptosis/necrosis respectively.…”

“…It is a well-documented acute lung injury model, especially for studies of oxidant-induced lung injury (2,5,6,8,9). Studies by Crapo et al provide a detailed description of histologic and morphometric changes in lungs of rats exposed to 85% O 2 for up to 14 days (6).…”

Detection of hydrogen peroxide production in the isolated rat lung using Amplex red

“…The following experimental protocols were carried out in a dark room to minimize the photo-oxidation of AR. For all experimental protocols, the total volume of the system was 25 ml, 5 ml of which were the perfusion system tubing and the lung vasculature (~ 0.8 ml) [27, 28]. To start the experiment, the perfusate in the reservoir was emptied and replaced with 19 ml of perfusate with horseradish peroxidase (HRP, 5 U/ml), Amplex red (AR, 25 µM), and ascorbate oxidase (1 U/ml).…”

Microcirculatory dysfunction and tissue oxygenation in critical illness

“…It should be kept in mind that changes in capillary transit time patterns of the lung affects blood saturation in the same way as they affect blood deoxygenation in other tissues 22, 80. Successful strategies for the protection of capillary wall integrity are therefore expected to improve both blood saturation and tissue oxygenation 81.…”