PURPOSE: We hypothesized that during acute right ventricular pressure overload (RVPO) hemodynamic perturbations and their consequences may develop in the peripheral vascular territories with weak autoregulation –namely, mesenteric bed –despite the absence of any central systemic circulatory perturbation.
METHODS: The systolic right ventricular pressure was increased in 7 dogs from 28.3±2.8 to 56.2±5.3mmHg and kept constant for 60 minutes (51.3±7.8mmHg; p<0.05) by banding the main pulmonary artery (PAB). Central systemic and mesenteric hemodynamic parameters were monitored. Blood gases, plasma ET-1 levels, H+-donating ability and free radicals were measured at 15min intervals. Mesenteric vascular reactivity was determined before and after 60min PAB.
RESULTS: At 60min PAB: although CO and MAP showed no changes, mesenteric vascular resistance was significantly increased (1.21±0.2 vs. 0.88±0.1mmHg *min/ml at baseline); in spite of stable arterial gas parameters, mesenteric oxygen extraction was also increased (40.8±4% vs. 26.2±5.6% at baseline, p<0.05); systemic arterial ET-1 levels were more elevated (2.54±0.37 pg/ml vs. 0.78±0.08 pg/ml at baseline, p<0.001) than the venous (1.95±0.08 pg/ml vs. 0.94±0.12 pg/ml, p<0.05), whereas arterial H+-donating ability was respectively reduced (24.3±1.8% vs. 47.2±2.9%, p<0.05) and mesenteric venous free radical concentration increased (49.0±0.9 vs. 41±2.1 *106 RLU, p<0.05); endothelium-dependent relaxation of the superior mesenteric artery to Ach was blunted (–51.31±11.76% vs. –95.91±10.44%, p<0.02), whereas endothelium-independent relaxation to SNP was preserved (–85.12±15.16% vs. –95.84± 17.52%).
CONCLUSION: Circulatory deficiency resulting from pulmonary ET-1 overproduction via free radical mechanisms rather than central hemodynamic impairment leads to mesenteric endothelial dysfunction after acute RVPO.
CLINICAL IMPLICATIONS: Chronic right ventricular pressure overload that occurs in several types of heart as well pulmonary diseases may compromise left ventricular function and impair peripheral perfusion through inceased release of Et-1 leading to intestinal hypoperfusion that may act as a trigger of the pro-inflammatory state in worst cases leading to acute respiratory distress syndrome, multiorgan failure, shock and death. Et-1 antagonsists adn ECE hemmers should be considered as possible postoperative therapeutic tools.
DISCLOSURE: Terezia Andrasi, None.