Increased permeability of pulmonary arterioles after cardiopulmonary bypass

Timea Beleznai, Laura Walker, Raimondo Ascione, Kim Dora

Research output: Contribution to journalArticle (Academic Journal)

Abstract

Pulmonary injury is a common complication after cardiopulmonary bypass (CPB) in patients undergoing cardiac surgery. The major causes of tissue damage arise from systemic inflammatory responses, and/or factors released by the ischaemic collapsed lungs. To date, there is no evidence to demonstrate whether this CPB-related pulmonary injury can influence both the permeability and function of the pulmonary arterioles. We developed a method to isolate, cannulate and pressurize porcine pulmonary arterioles to study their vasomotor function, the leak of fluorescent dyes through the arterial wall, and the expression of key proteins. All arterioles were imaged using linescan confocal microscopy. The fluorescent indicators carboxyfluorescein (CF, 0.1 µM, mw 376.3) or FITC-dextran (1 µM, mw 59,000 - 77,000) were perfused into the lumen of arterioles, and increases in fluorescence immediately outside the arteriolar wall (permeability) measured. Tight junction (Zo-1) and caspase 3 staining was performed on the same arterioles, and imaged while still cannulated, to assess the continuity of cell-cell connections and the onset of apoptosis. Arterioles were studied from pigs which had undergone CPB or sham surgery under anaesthesia and categorized into 4 groups: control (lungs collapsed to air with no ventilation during CPB, equivalent to the current method in patients); IPP-ILFV (intermittent pulmonary perfusion with intermittent low frequency ventilation during CPB); IPP-CLFV (intermittent pulmonary perfusion with continuous low frequency ventilation during CPB); and sham (chest opened only). From each group two samples were obtained, one soon after median sternotomy (baseline) and one at 1 hour of recovery after surgery (reperfusion). All baseline and sham pulmonary arterioles had low permeability to CF and FITC-dextran. When studying reperfused arterioles, the arterioles studied following IPP-ILFV and IPP-CLFV were less permeable to CF when compared to control arterioles. The permeability to FITC-dextran was not increased in any group studied, although a TRPV4 agonist did increase permeability to dextran. Furthermore, tight junction staining showed continuous, uniform cell-cell connections in the endothelium of all baseline arterioles. Interestingly, and consistent with the CF leak data, reperfused lung arterioles from the control group did appear to have gaps in tight junction staining and some caspase 3 staining was evident. These data suggest that cardiopulmonary bypass and concomitant lung collapse leads to increased permeability of pulmonary arterioles due to damaged cell-cell adhesions, which can be prevented by intermittent pulmonary perfusion with low frequency ventilation of the lungs during CPB.
Original languageEnglish
JournalProceedings of The Physiological Society
Publication statusPublished - 2013

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