Pulmonary microvascular changes during sepsis: Evaluation using intravitalvideomicroscopy

A variety of pulmonary microvascular changes occur during sepsis. These inc lude abnormal vascular reactivity, leukocyte sequestration, and leakage of protein into the alveoli. Based on intravital videomicroscopy we have devel oped a method to directly assess in vivo the changes that occur in the pulm onary microcirculation in a rat model of sepsis. Male Sprague-Dawley rats w ere assigned to control or sepsis groups. Sepsis was induced by cecal ligat ion and perforation. Twenty four hours later, rats were anesthetized, mecha nically ventilated, and their lung prepared for intravital videomicroscopy. A specially designed transparent thoracic window was inserted into the che st wall. The dependent surface of the lung was superfused with saline solut ion and visualized with an inverted microscope. Vascular contractility, to phenylephrine, (PE) and hypoxia of small (15-25 mu m in diameter) and mediu m (40-50 mu m) arterioles was examined. Leukocyte traffic in the pulmonary microcirculation was studied after in vivo labeling of leukocytes with Rhod amine and visualized with fluorescence microscopy. Leak of albumin into the alveolar space was measured with FITC-labeled albumin and fluorescence mic roscopy. Both small and medium sized pulmonary arterioles in septic animals exhibited attenuated vascular contractility to phenylephrine, but only med ium-sized arterioles displayed hypocontractility to hypoxia. Further, in se ptic animals there was an increase in both the number of stationary leukocy tes in the pulmonary microcirculation and an increase in alveolar capillary protein leak. We conclude: (1) direct visualization of the pulmonary micro vascular presser response to hypoxia and PE in the rat is possible using th is technique, (2) similar to previous in vitro studies with larger vessels, pulmonary arterioles have an attenuated contractile response to PE and hyp oxia in sepsis, and (3) there is an increase in both the number of stationa ry leukocytes and protein leak into the alveolus in the lungs of septic ani mals. (C) 2000 Academic Press.