Edema formation and vascular endothelial function in isolated rat lungs

Abstract

ROS, inflammatory factors, and cytoskeletal disarray contribute to endothelial dysfunction, edema, and pulmonary hypertension in transplanted lungs. Attempts to minimize injury in explanted tissue have included varying storage solutions, degree of hypothermia, inflation, and use of vasodilatory drugs. We examined edema formation and endothelial function in rat lungs exposed to hypothermia (12°C, 4–6 hr) followed by rewarming (30 min). Lungs were ventilated and flushed of blood. Perfusion was started in situ, and lungs were subsequently suspended in a temperature-controlled bath. Edema was gauged by gain or loss of perfusate. Ventilation was maintained using low (3 cm H2O, n = 3) or high (9 cm H2O, n = 3) levels of positive end-expiratory pressure (PEEP). Flow was reduced by 50% during hypothermia. After rewarming, PA were removed and hung in a standard myograph. Endothelial function was assessed by acetylcholine relaxation of a norepinephrine contraction. Significant edema formation was noted in all lungs upon resumption of full flow rates. However, acetylcholine relaxation was preserved in both proximal and distal PA segments from low (62 ±18%, 99±13%) and high (74±4%, 80±17%) PEEP lungs. These preliminary findings suggest that endothelial function is maintained even after vascular integrity is compromised. Supported, in part, by a grant from the MedCen Foundation of the Medical Center of Central Georgia.