左肺反向循环逆转终末期肺动脉高压

摘要

Objective Reversed circulation has been widely applied in clinical treatment; the purpose of this study is to inves-tigate whether reversal of pulmonary blood flow is compatible to improve pulmonary vascular resistance and to reveal its mechanism.Methods Thirty mongrel dogs were randomly divided into control, pulmonary hypertension (PH) and reversed pulmonary circulationgroups. Hemodynamic data and blood gas measurements were recorded 1 week after reversal of operation. Blood sample were collectedfor detection of the content of nitric oxide, endothelin and nitric oxide synthase. Quantification of nitric oxide synthase mRNA and pre-proendothelin mRNA were detected by reverse transcriptase real-time PCR. Results After induced pulmonary hypertension in dogs bydehydromonocrotaline, these dogs underwent an operation for reversal of the pulmonary blood flow, showing lower pulmonary arterypressure [(17.3±3.5) mmHg, P<0.01] than before surgical procedure but higher than normal [(12.6±4.2) mm Hg, P<0.05 ]. The level of systemic arterial oxygen tension increased significantly from (80.7±6.6) mm Hg to (96.5±6.4) nan Hg ( P <0.01), and the plasma concentrate of nitric oxide synthase increased [ ( 1.53±0.56) μg/ml, P < 0.01], and that of nitric oxide al-so increased [(36.25±6.94) μmol/L, P<0.01]and contrarily endothelin decreased [(21.37±3.82)pg/ml, P<0.01]. Thedownregulation of preproendothelin mRNA and upregulation of endothelial nitric oxide synthase mRNA were found after reversal leftblood flow in end-stage pulmonary hypertension animal model. Conclusion In vivo studies on retrograde perfusion of left lung circu-lation in end-stage pulmonary hypertension animal model shows a significant decrease in pulmonary vascular resistance, which maychange the site of oxygenation, increase arterial oxygen tension and saturation, upregulate expression of endothelial nitric oxide syn-thase mRNA and downregulate expression of preproendothelin mRNA to regulate the vasomotor tone.%目的 探讨反向肺循环逆转终末期肺动脉高压的机制.方法 选杂种犬30只,随机分成正常对照组(n=10)、肺动脉高压组(n=10)和肺高压反向组(n=10).观察各组的血流动力学参数、动脉血气、外周血一氧化氮(NO)、一氧化氮合酶(eNOS)、内皮素及其肺组织mRNA表达的变化.结果 终末期肺高压模型犬上行左肺反向循环手术后,平均肺动脉压(MPAP)降低[(17.3±3.5)mm Hg,P<0.01],但与正常犬MPAP[(12.6±4.2)mm Hg]相比仍偏高(P<0.05);动脉血氧分压上升到(96.5±6.4)mm Hg(P<0.01),血浆中eNOS升高[(1.53±0.56)μg/ml,P<0.01],NO分泌量增加[(36.25±6.94)μmol/L,P<0.01],ET的含量减少[(21.37±3.82)pg/ml,P<0.01].eNOS-mRNA在术后表达上调,PEET-mRNA在肺高压时表达上调,而在术后表达下调.结论 左肺反向循环具有可行性,可能通过转换血气交换的解剖位置、提高血氧含量、抑制血管收缩因子的产生,增加血管舒张因子的产生降低肺动脉高压.