Lubitz Andrea L, Sjoholm Lars O, Goldberg Amy, Pathak Abhijit, Santora Thomas, Sharp Thomas E, Wallner Markus, Berretta Remus M, Poole Lauren A, Wu Jichuan, Wolfson Marla R
From the Department of Surgery at Temple University Hospital (A.L.L., L.O.S., A.G., A.P., T.S.), Cardiovascular Research Center (T.E.S., M.W., R.M.B.), Department of Physiology (T.E.S., M.W., R.M.B., L.A.P., J.W., M.R.W.), Department of Thoracic Medicine and Surgery (L.A.P., J.W., M.R.W.), Center for Inflammation, Translational and Clinical Lung Research (L.A.P., J.W., M.R.W.), CENTRe: Collaborative for Environmental and Neonatal Therapeutics Research (L.A.P., J.W., M.R.W.), and Temple Lung Center of Lewis Katz School of Medicine at Temple University Philadelphia, PA (L.A.P., J.W., M.R.W.).
J Trauma Acute Care Surg. 2017 Feb;82(2):243-251. doi: 10.1097/TA.0000000000001325.
Hemorrhagic shock and pneumonectomy causes an acute increase in pulmonary vascular resistance (PVR). The increase in PVR and right ventricular (RV) afterload leads to acute RV failure, thus reducing left ventricular (LV) preload and output. Inhaled nitric oxide (iNO) lowers PVR by relaxing pulmonary arterial smooth muscle without remarkable systemic vascular effects. We hypothesized that with hemorrhagic shock and pneumonectomy, iNO can be used to decrease PVR and mitigate right heart failure.
A hemorrhagic shock and pneumonectomy model was developed using sheep. Sheep received lung protective ventilatory support and were instrumented to serially obtain measurements of hemodynamics, gas exchange, and blood chemistry. Heart function was assessed with echocardiography. After randomization to study gas of iNO 20 ppm (n = 9) or nitrogen as placebo (n = 9), baseline measurements were obtained. Hemorrhagic shock was initiated by exsanguination to a target of 50% of the baseline mean arterial pressure. The resuscitation phase was initiated, consisting of simultaneous left pulmonary hilum ligation, via median sternotomy, infusion of autologous blood and initiation of study gas. Animals were monitored for 4 hours.
All animals had an initial increase in PVR. PVR remained elevated with placebo; with iNO, PVR decreased to baseline. Echo showed improved RV function in the iNO group while it remained impaired in the placebo group. After an initial increase in shunt and lactate and decrease in SvO2, all returned toward baseline in the iNO group but remained abnormal in the placebo group.
These data indicate that by decreasing PVR, iNO decreased RV afterload, preserved RV and LV function, and tissue oxygenation in this hemorrhagic shock and pneumonectomy model. This suggests that iNO may be a useful clinical adjunct to mitigate right heart failure and improve survival when trauma pneumonectomy is required.
失血性休克和肺切除术会导致肺血管阻力（PVR）急剧增加。PVR和右心室（RV）后负荷的增加会导致急性RV衰竭，从而降低左心室（LV）前负荷和输出量。吸入一氧化氮（iNO）通过舒张肺动脉平滑肌降低PVR，而对全身血管无明显影响。我们假设在失血性休克和肺切除术中，iNO可用于降低PVR并减轻右心衰竭。
使用绵羊建立失血性休克和肺切除术模型。绵羊接受肺保护性通气支持，并进行仪器安装以连续获取血流动力学、气体交换和血液化学测量值。通过超声心动图评估心脏功能。随机分为研究iNO 20 ppm气体组（n = 9）或氮气作为安慰剂组（n = 9）后，获取基线测量值。通过放血使平均动脉压降至基线的50%来引发失血性休克。复苏阶段开始，包括通过正中胸骨切开术同时结扎左肺门、输注自体血并开始使用研究气体。对动物进行4小时监测。
所有动物的PVR最初均升高。安慰剂组的PVR持续升高；使用iNO后，PVR降至基线。超声心动图显示iNO组的RV功能改善，而安慰剂组的RV功能仍受损。在分流和乳酸最初增加以及SvO2降低后，iNO组的所有指标均恢复至基线，但安慰剂组仍异常。
这些数据表明，在该失血性休克和肺切除术模型中，iNO通过降低PVR降低了RV后负荷，保留了RV和LV功能以及组织氧合。这表明当需要进行创伤性肺切除术时，iNO可能是减轻右心衰竭并提高生存率的有用临床辅助手段。
