The effects of single lung transplantation in rats with monocrotaline-induced pulmonary hypertension

Abstract Acute haemodynamic change after single lung transplantation for primary pulmonary hypertension was evaluated using a rat transplantation model. Inbred Fisher 344 rats were administered with 40 mg/kg monocrotaline in order to induce pulmonary hypertension. The rats whose mean pulmonary arterial pressure (PAP) was over 30.0 mmHg received a left lung isograft from a normal donor after right heart catheterization. In the control group, PAP increased after single lung transplantation. On the other hand, in the pulmonary hypertensive group, PAP was significantly decreased 60 min after the transplantation, but 3 and 6 h after the transplantation, the PAP significantly increased again. On the day after the operation, it again decreased significantly. Left-to-right lung blood flow ratio was significantly increased in rats with pulmonary hypertension compared to rats with normal pulmonary pressure on both the 1st and 3rd postoperative days. The oedema of the grafted lung was more severe in the pulmonary hypertensive group than in the control group in the acute phase. In conclusion, single lung transplantation for pulmonary hypertension shifted pulmonary blood perfusion to the grafted lung and this shift made pulmonary oedema of the grafts more severe in the acute phase. These oedematous changes, which were more pronounced in the grafts in the pulmonary hypertensive rats, might have contributed to the transient rise in PAP in those rats after single lung transplanation.     

Reversibility of fixed pulmonary hypertension in left ventricular assist device support recipients

Objective: Conflicting data still exist concerning the reversibility of secondary severe ‘fixed’ pulmonary hypertension (PH) by the use of left ventricular assist device (LVAD) support in terms of time necessary to provide a bridge to ‘transplantability’. Methods: We retrospectively reviewed 145 patients with heart failure and severe PH treated by LVAD support between 2000 and 2009. There were 133 men (91.7%) and 12 women (8.3%) with a mean age of 52.95 ± 12.01 years. Patients were divided into two groups depending on preoperative PH reversibility. Fixed PH was defined by a mean pulmonary arterial pressure (mPAP) >25 mmHg, a pulmonary vascular resistance (PVR) >2.5 Wood Unit (WU) and a transpulmonary gradient (TPG) >12 mmHg, despite pharmacological treatment. Results: Fifty-six patients had fixed PH (group A) and 89 reversible PH (group B). Only 27 patients of group A underwent right heart catheterization evaluation during LVAD support; the remaining 29 patients had other contraindications to heart transplantation (HTx). The 27 patients were divided into three subgroups on the basis of examination time during LVAD support: <6 months (11 patients), between 6 and 12 months (six patients) and >12 months (10 patients). The mPAP, PVR, and TPG decreased significantly during LVAD support (mPAP, 37.26 ± 6.35 mmHg vs 21.00 ± 7.51 mmHg, p = 0.007; PVR, 3.49 ± 1.47 WU vs 1.53 ± 0.66 WU, p = 0.000; and TPG, 15.04 ± 5.22 mmHg vs 7.78 ± 3.21 mmHg, p = 0.019). A significant reduction of all parameters was observed during the first 6 months and later on there was no further decrease. There were no significant differences between the three subgroups (mPAP, p = 0.680; PVR, p = 0.723; and TPG, p = 0.679) in terms of time of reversibility. LVAD support allowed 19 patients to be transplanted. Conclusions: Patients with fixed PH can be treated with LVAD support. Our data suggest that 6 months after LVAD implantation it is possible to observe an important reduction of PH and evaluate the potential transplantability of patients. Longer support does not add any effect of LVAD on PH.     

Pulmonary hypertension is not a risk factor for grade 3 primary graft dysfunction after lung transplantation

Grade 3 primary graft dysfunction (PGD3) represents the most important risk factor for patient mortality during the first year after lung transplantation (LTX). We investigated whether pretransplant pulmonary hypertension (PH) is a risk factor for the development of PGD3. This retrospective, single‐center cohort study included 96 candidates undergoing right heart catheterization (RHC) prior to being listed for LTX between March 2000 and October 2015. Based on their mean pulmonary artery pressure (mPAP) levels, the patients were classified into 3 groups: (1) <25 mm Hg, (2) 25‐34 mm Hg and (3) ≥35 mm Hg. Forty‐seven patients were classified in group 1, 31 in group 2, and 18 in group 3. Fifteen recipients (16%, 95%‐CI 8‐23) developed PGD3. In the univariate analysis, the diagnosis of interstitial lung disease (ILD) compared to COPD (OR: 7.06, P = .005), blood transfusion >1000 mL during surgery (OR: 5.25, P = .005), the need for intra‐operative cardio‐pulmonary bypass (CPB) or extra‐corporeal membrane oxygenation (ECMO) (OR: 4, P = .027), mPAP (OR 1.06, P = .007) and serum high density lipoprotein‐cholesterol (HDL‐C) (OR 0.09, P = .005) were associated with PGD3. In the multivariable logistic regression analysis, only HDL‐C (OR 0.10, P = .016) was associated with PGD3 based on our single‐center cohort data analysis.     

Living‐donor liver transplantation for congenital biliary atresia with porto‐pulmonary hypertension and moderate or severe pulmonary arterial hypertension: Kyoto University experience

Porto‐pulmonary hypertension with moderate or severe pulmonary arterial hypertension (PAH) is viewed as a contraindication to liver transplantation (LT) because of associated poor outcomes; however, patients with biliary atresia (BA) are generally good candidates for LT. Ten patients with moderate/severe PAH underwent living‐donor liver transplantation (LDLT) at our institution; eight of these patients had BA and were the focus of this study. Preoperative therapies, including prostaglandin (PG)I₂, were introduced. When mean pulmonary arterial pressure (mPAP) after treatment was <40 mmHg or initial mPAP without therapy was <35 mmHg, we performed an acute volume challenge test to evaluate right ventricular function. LDLT was performed when mPAP after anesthetic induction was confirmed at ≤35 mmHg. Six patients had favorable responses to preoperative treatment and catheter testing, but two patients showed poor responses. The two patients with poor responses had poor clinical courses with unstable mPAP after LDLT. The other six patients had successful courses with well‐controlled mPAP, and PGI₂ was withdrawn or weaned following LDLT. Survival did not significantly differ between the eight BA recipients with moderate/severe PAH and 77 age‐matched BA recipients without PAH from the same time period. LDLT has major benefits for BA patients with well‐controlled PAH.     

Inhaled carbon monoxide abrogates pulmonary hypertension

Background: Pulmonary hypertension poses a significant clinical challenge. Our current therapies are limited and not efficacious. Carbon monoxide (CO), which is produced endogenously by heme oxygenases, has been shown to possess vasoregulatory properties. Therefore, we hypothesized that inhaled low dose CO would prevent and reverse pulmonary vascular hyperplasia and right ventricular hypertrophy (RVH) in an animal model of pulmonary hypertension. Methods: Monocrotaline (MCT)-treated rats were divided into 4 groups (n = 3-6 per group). Group A received MCT (50 mg/kg, s.c.) alone. Group B was treated with 1 hour daily of inhaled CO (250 ppm) days 1-14 after MCT administration. Group C received CO from days 15-28 and Group D received CO from days 29-42. All animals were sacrificed on day number 43 and their hearts and lungs harvested for morphometric and histologic evaluation. Body weight, right and left ventricular masses, and mean pulmonary arterial pressure (mPAP) were evaluated. Results: MCT caused progressive pulmonary hypertension. By day 42, MCT-treated rats had a mPAP of 35 ± 3.3 compared to untreated controls whose mPAP was 16 ± 2.1 and CO-treated rats which had a mPAP of 20 ± 7.1 (p < 0.05, ANOVA). CO prevented RVH in all treatment groups, even when normalized for body weight (Table) (p < 0.05, Fisher’s Least Significant Difference). Rats treated with MCT alone displayed significant muscularization of the ventricular wall and pulmonary neointimal hyperplasia; CO therapy abrogated these effects. Conclusion: Our data show that low dose inhaled CO decreases mPAP, and prevents RVH and vascular changes in MCT-induced pulmonary hypertension. CO therapy was effective even after the development of cardiac and pulmonary disease. CO may be a useful adjunct in the treatment or prevention of pulmonary hypertension.     

Extracorporeal life support in lung and heart–lung transplantation for pulmonary hypertension in adults

After bilateral lung and heart–lung transplantation in adults with pulmonary hypertension, hemodynamic and oxygenation deficiencies are life‐threatening complications that are increasingly managed with extracorporeal life support (ECLS). The primary aim of this retrospective study was to assess 30‐day and 1‐year survival rates in patients managed with vs without post‐operative venoarterial ECLS in 2008–2013. The secondary endpoints were the occurrence rates of nosocomial infection, bleeding, and acute renal failure. Of the 93 patients with pulmonary hypertension who received heart‐lung (n=29) or bilateral lung (n=64) transplants, 28 (30%) required ECLS a median of 0 [0–6] hours after surgery completion and for a median of 3.0 [2.0–8.5] days. Compared to ECLS patients, controls had higher survival at 30 days (95.0% vs 78.5%; P=.02) and 1 year (83% vs 64%; P=.005), fewer nosocomial infections (48% vs 79%; P=.0006), and fewer bleeding events (17% vs 43%; P=.008). The need for renal replacement therapy was not different between groups (11% vs 17%; P=.54). Venoarterial ECLS is effective in treating pulmonary graft dysfunction with hemodynamic failure after heart‐lung or bilateral lung. However, ECLS use was associated with higher rates of infection and bleeding.     

Initial experience using continuous intravenous treprostinil to manage pulmonary arterial hypertension in patients with end-stage liver disease

Treprostinil is a prostacyclin analog and has been used on idiopathic pulmonary arterial hypertension (PAH). There is only limited clinical experience using treprostinil to manage PAH in patients with end-stage liver disease (ESLD). We report three ESLD patients with PAH, who were treated with continuous intravenous treprostinil. A 59-year-old woman with ESLD secondary to alcoholic hepatitis had portopulmonary hypertension with mean pulmonary arterial pressure (mPAP) of 44 mmHg and transpulmonary gradient (TPG) of 23 mmHg. Treprostinil at 45 ng/kg/min for 6 months decreased mPAP to 23 (TPG to 8). A 53-year-old man had ESLD secondary to alcoholic hepatitis with PAH caused by multiple pulmonary embolisms (mPAP of 32 and TPG of 23). Treprostinil at 36 ng/kg/min for 3 months decreased mPAP to 23 and TPG to 14. Both patients underwent uneventful liver transplantation. A 48-year-old man had ESLD secondary to hepatitis C and portopulmonary hypertension with mPAP of 60 and TPG of 44. Two years after intravenous treprostinil at 106 ng/kg/min, his mPAP decreased to 44 and TPG to 30. These results demonstrate that for a selected group of ESLD patients with PAH, a continuous intravenous infusion of treprostinil appears to be safe and effective.     

Pulmonary Hypertension in Patients with Bronchiolitis Obliterans Syndrome Listed for Retransplantation

Bronchiolitis Obliterans Syndrome (BOS) is a major cause of morbidity and mortality post-lung transplantation. Pulmonary hypertension (PH) may complicate the course of patients with advanced lung disease. We sought to characterize the prevalence of PH in patients with BOS.
We performed a retrospective analysis of lung transplant recipients with BOS relisted for transplantation with the United Network for Organ Sharing (UNOS). Right heart catheterization (RHC) data were required for analysis. Eighty patients with BOS qualified for the analysis. PH was present in 32.5% of patients with an average mean pulmonary artery pressure (mPAP) of 32.3 mmHg (range: 26–63 mmHg). Of these, 42.3% had an elevated pulmonary capillary wedge pressure. There was no difference in PH prevalence between bilateral (26.5%) and single lung recipients (41.9%), nor did it differ by primary disease. There was no correlation between pulmonary function data and the presence or severity of PH. There was no difference in oxygen requirements or 6-min walk distance between patients with and without PH. This is the first report of PH in patients with BOS. Many of these cases occur in association with diastolic dysfunction. Although no impact on functional status or outcomes was discerned, further studies appear warranted.     

Clinical Ex Vivo Lung Perfusion—Pushing the Limits

Ex vivo lung perfusion (EVLP) provides the ability to evaluate donor lungs before transplantation. Yet, limited prospective clinical data exist with regard to its potential to recondition unacceptable donor lungs. This paper summarizes the results of a prospective study of lung transplantation using only initially unacceptable donor lungs, which were improved by EVLP for 2–4 h. From March 2010–June 2011, 13 lungs were evaluated ex vivo. Median donor PaO₂ at FiO₂1.0/PEEP5 was 216 mmHg (range 133–271). Four lungs, all with trauma history, showed no improvement and were discarded. Nine lungs improved to a ΔPO₂ higher than 350 mmHg. Median PvO₂ at final assessment in these lungs was 466 mmHg (range 434–525). These lungs were transplanted with a median total ischemic time of 577 min (range 486–678). None of the patients developed primary graft dysfunction grades 2 or 3 within 72 h after transplantation. One patient with secondary pulmonary hypertension was left on a planned prolonged extracorporeal membrane oxygenation postoperatively. Median intubation time was 2 days. Thirty‐day mortality was 0%. During the observation period, 119 patients received standard lung transplantation with comparable perioperative outcome. EVLP has a significant potential to improve the quality of otherwise unacceptable donor lungs.     

肺移植治疗儿童肺动脉高压的临床疗效

目的 探讨同种异体肺移植治疗儿童肺动脉高压(PAH)的临床疗效.方法 受者例1、2为特发性肺动脉高压( IPAH)患儿,均经右心导管术确诊为IPAH,术前心功能不全Ⅳ级,肺动脉收缩压、平均压分别为110、70 mm Hg(1 mm Hg =0.133 kPa)和148、72 mm Hg,在全麻体外膜肺氧合(ECMO)支持下行序贯式双侧单肺移植术,术中ECMO支持时间分别为550 min和450 min,出血量分别为3000 ml和1200 ml.受者例3为先天性心脏病室间隔缺损合并艾森曼格综合征心内直视探查术后,超声心动图(UCG)提示先天性心脏病室间隔缺损,双向分流,肺动脉收缩压、平均压为110、60 mm Hg,在全麻低温体外循环(CPB)下行室间隔缺损修补术同期右侧单肺移植术,术中CPB时间244 min.3例受者与供者体型较匹配,ABO血型相同.结果 受者例1、2术后ECMO分别维持16h、13 h后撤离,术后第3、4天均出现不同程度的血流动力学不稳定,诊断为急性左心衰,均于术后第3、6天行气管切开呼吸机辅助正压通气,经强心、利尿、扩血管等治疗,分别于术后第33天、12天脱离呼吸机.受者例3术后3天内移植肺出现中等程度再植反应性肺水肿,术后第7天气管切开,第12天撤离呼吸机;术后第14天出现急性排斥1次,治疗后缓解.3例受者术后UCG提示心脏形态和心功能明显改善,受者例3室间隔缺损修补完整,无残余分流.分别于术后第93天、32天、62天康复出院,心功能均达Ⅰ级,肺动脉收缩压、平均压分别降为54、32 mm Hg,60、36 mm Hg和53、39 mm Hg.术后已随访41、21、82个月,患儿正常工作学习,至今生活质量良好.结论 对终末期经内科保守治疗效果欠佳的PAH患儿行肺移植能很好改善生活质量.     

Sildenafil for portopulmonary hypertension in a patient undergoing liver transplantation.

Liver transplantation (LT) may be indicated in cirrhotic patients with underlying pulmonary artery hypertension. However, severe pulmonary artery hypertension with mean pulmonary artery pressure (mPAP) above 50 mmHg has even been considered a contraindication to LT. We present a cirrhotic patient with an mPAP of 56 mmHg measured using right heart catheterization (RHC) and with severely compromised physical capacity. She was first treated with sildenafil (Viagra), a potent novel vasodilator, and successfully transplanted later. The mPAP decreased with sildenafil to the level of 28-31 mmHg and her general condition improved markedly. An LT using piggyback technique was performed 16 weeks later. Despite 2 reoperations for bleeding, the outcome has been excellent. In conclusion, treatment of severe portopulmonary hypertension (PHT) with sildenafil is effective. If a decrease in mPAP is achieved with sildenafil, it may improve the result of LT, even though no evidence of reversibility of PPHTN exists.     

Single lung transplantation in rats with chemically induced pulmonary hypertension.

Physiologic effects of single lung transplantation on pulmonary hypertension were studied in rats with monocrotaline-induced pulmonary hypertension. Inbred rats treated with monocrotaline (40 mg/kg) received a left lung isograft from a normal donor 2 weeks later, when pulmonary hypertension became significant (transplant group; n = 6). These rats and control rats treated with monocrotaline (mediated control group; n = 11) or vehicle alone (normal control group; n = 9) were followed up weekly by metabolic treadmill testing for exercise tolerance and oxygen consumption up to 6 weeks after monocrotaline (4 weeks after transplantation), when all rats underwent hemodynamic and histologic examinations. Whereas maximal oxygen consumption and exercise tolerance consistently deteriorated in the medicated control group of rats, indices in the transplant group stopped deteriorating 2 weeks after lung transplantation and remained at levels similar to those of normal control rats. Severe pulmonary hypertension (68 +/- 19 mm Hg) and right ventricular hypertrophy (right ventricular/left ventricular weight ratio, 0.95 +/- 0.19) were confirmed in medicated control rats in contrast to transplant animals, in which these two indices remained at normal control levels. Whereas left-to-right lung perfusion ratio was constant among rats not receiving transplants (0.69 +/- 0.16), it was significantly elevated (2.27 +/- 0.65; p less than 0.001) in those receiving transplants, suggesting preferential flow through the lung isograft. The results suggest that, in the early phase of pulmonary hypertension, single lung transplantation shifts pulmonary perfusion to the grafted lung, avoiding right ventricular pressure overload and thereby preserving exercise tolerance at a nearly normal level in rats with monocrotaline-induced pulmonary hypertension.     

Severe pulmonary hypertension in liver transplant candidates

Advanced liver disease with portal hypertension may be associated with pulmonary hypertension. A review of 1,205 consecutive liver transplant patients was made to assess the incidence and severity of pulmonary hypertension in patients with end-stage liver disease. Postoperative data were reviewed to determine if outcome was influenced and, in patients with severe pulmonary hypertension, whether pulmonary hypertension was reversed after transplantation. The hemodynamic data of 5 patients who were found to have severe pulmonary hypertension before transplantation and did not receive transplants were also reviewed. The incidence of pulmonary hypertension in the patients who received transplants was 8.5% (n = 102; mean pulmonary artery pressure, > 25 mmHg). The incidence of mild pulmonary hypertension was 6.72% (n = 81; systolic pulmonary artery pressure, 30 to 44 mmHg); that of moderate pulmonary hypertension was 1.16% (n = 14; systolic pulmonary artery pressure, 45 to 59 mmHg); and that of severe pulmonary hypertension was 0.58% (n = 7; systolic pulmonary artery pressure, > 60 mmHg). Mild and moderate pulmonary hypertension did not influence the outcome of the procedure. Severe pulmonary hypertension was associated with mortality rates of 42% at 9 months posttransplantation and 71% at 36 months posttransplantation. Only 2 of 7 patients with severe pulmonary hypertension have survived liver transplantation with a good quality of life. The remaining 5 patients continued to deteriorate with progressive right heart failure with no evidence of amelioration of the pulmonary hypertension. This experience supports the view that in most patients who have severe pulmonary hypertension associated with advanced liver disease, it is caused by fixed pathological changes in the pulmonary vasculature, is not reversible with liver transplantation, and is associated with a very high perioperative mortality rate. (Liver Transpl Surg 1997 Sep;3(5):494-500)     

Extracorporeal membrane oxygenation for lung transplant recipients with primary severe donor lung dysfunction

Primary severe donor lung dysfunction (DLD) is a significant complication after lung transplantation (LTx), and a high mortality is reported with conventional therapy. The purpose of this report is to review the experience of the University of Pittsburgh with extracorporeal membrane oxygenation (ECMO) for primary severe DLD after LTx. From September 1991 to May 1995, 220 LTx were performed at our center. Eight patients (8/220=3.6%) with severe DLD after LTx required ECMO support. The age of LTx recipients was 44±5 years (mean±SD); seven patients were female and one was male. Indications for LTx were: chronic obstructive pulmonary disease in four patients, bronchiectasis in two, and pulmonary hypertension in two. There were three single LTx and five bilateral LTx. The interval from LTx to institution of ECMO was 5.6±3.2 h (range 0–10 h). Three patients were supported with veno-venous (v-v) ECMO and five had veno-arterial (v-a) ECMO. The duration of ECMO support was 7.3±4.8 days (range 3–15 days). activated glotting time (ACT) was maintained between 110 and 180 s with intermittent use of heparin. Seven patients (7/8=87%) were successfully weaned from ECMO and six patients (6/8=75%) were discharged home; they are currently alive after a follow-up of 17±10.1 months. One patient died on ECMO support for refractory DLD and another died 2 months after ECMO wean from multisystem organ failure. At 6 months follow-up, forced expiratory volume in 1 s (FEV1) is 2.35±0.91 (75%±17.4% predicted) and mean forced vital capacity (FVC) is 2.53±0.81 (64%±14% predicted). We conclude that ECMO can be lifesaving when instituted early after primary severe DLD. The v-v ECMO support is preferred when the patient is hemodynamically stable and adequate long-term function of the allograft is anticipated.     

Extracorporeal Membrane Oxygenation Rescue Therapy in a Case of Portopulmonary Hypertension During Liver Transplantation: A Case Report

Portopulmonary hypertension has been reported in 2% to 9% of candidates for liver transplantation (OLT). If it is moderate to severe, it represents a contraindication to the procedure until pulmonary vasodilatative therapy has been optimized. We report the case of a 43-year-old man, scheduled for OLT due to alcoholic cirrhosis with hemosiderosis. His Model for End-Stage Liver Disease was 25 at that time. The preoperative evaluation showed a severe alteration of diffusion (pO₂ 68 mm Hg), without hepatopulmonary syndrome or portopulmonary hypertension (PPH) upon basal and dobutamine stress echocardiography. At the beginning of the OLT the hemodynamic profile showed mean pulmonary artery pressure (mPAP) 38 mm Hg, wedge pressure (WP) 19 mm Hg, cardiac output (CO) 9.1 L/min, pulmonary vascular resistance (PVR) 166 dyne s/cm⁵, transpulmonary gradient (TPG) 19 mm Hg, which lead us to promptly initiate inhaled nitric oxide (iNO) and intravenous epoprostenol 2 to 5 ng/kg/min. Upon graft reperfusion the hemodynamic profile was: mPAP 47 mm Hg, WP 23 mm Hg, CO 14.2 L/min, PVR 135 dyne s/cm⁵, TPG 24 mm Hg, and at the end of surgery, mPAP 39 mm Hg, WP 20 mm Hg, CO 10.6 L/min, PVR 123 dyne s/cm⁵, TPG 19 mm Hg. On postoperative day (POD) 3, we observed severe worsening of PPH: mPAP 60 mm Hg, WP 10 mm Hg, CO 9.8 L/min, PVR 395 dyne s/cm⁵, TPG 50 mm Hg even with maximal pulmonary vasodilatatory therapy (ambrisentan 5 mg, intravenous sildenafil 20 mg × 3 and epoprostenol 22 ng/kg/min, iNO). Severe acute respiratory distress syndrome (ARDS) was presents. Therefore we decided to begin veno-venous extracorporeal membrane oxygenation (v-v ECMO) to correct the hypoxic vasoconstriction. Subsequent weaning from inotropic support with iNO and epoprostenol was possible on POD 7 due to mPAP 42 mm Hg, WP 15 mm Hg, CO 7.9 L/min, PVR 273 dyne s/cm⁵, and TPG 27 mm Hg. On POD 11 he was weaned from ECMO due to: mPAP 40 mm Hg, WP 16 mm Hg, CO 6.5 L/min, PVR 295 dyne s/cm⁵ and TPG 24 mm Hg. The patient was extubated on POD 17. The cardiac catheterization 1 month after OLT showed: mPAP 28 mm Hg, WP 13 mm Hg, CO 5.4 L/min, PVR 220 dyne s/cm⁵ and TPG 15 mm Hg. ECMO rescue therapy in this “extreme” case allowed us to correct hypoxemia responsible for worsening of pulmonary hypertension allowing time to reach the goal of vasodilatatory therapy.     

Pulmonary thromboendarterectomy in patients with chronic thromboembolic pulmonary hypertension: hemodynamic characteristics and changes

Objective: To see whether degree of pulmonary hypertension or severity of cardiac failure affect the success of pulmonary thromboendarterectomy (PTE) in chronic thromboembolic pulmonary hypertension. Methods: From May 1996 to June 1999, 33 patients, all in New York Heart Association (NYHA) class 3 or 4 were treated with PTE. Preoperative hemodynamic values were: central venous pressure (CVP) 8±6 (1–23), mean pulmonary artery pressure (mPAP) 50±10 (30–69), cardiac output (CO) 3.3±0.9 (1.8–5.2), pulmonary vascular resistance (PVR) 1056±344 (523–1659), and right ventricle ejection fraction (RVEF) 12±5 (5–21). To establish whether some hemodynamic or cardiac variables correlate with surgical failure (early death or functional non-success), these patients were divided into a low risk or a high risk group for each variable: CVP (<9 or ≥9), mPAP (<50 or ≥50), CO (≥3.5 or <3.5), PVR (≥1100 or <1100), and RVEF (≥10 or <10). The duration of 3–4 NYHA class period (<24 or ≥24 months) was also included in the study. Results: Three patients (9.1%) died in hospital, one (3.0%) underwent lung transplant shortly after PTE, and in five cases (15.2%) mPAP and PVR at the 3-month follow-up examination corresponded with our definition of functional nonsuccess (mPAP and PVR decreased by less than 40% of preoperative values). One of the five functional nonsuccess patients underwent lung transplant 3 months after the operation and another died 17 months after the operation from a non-related cause. Thus PTE was successful in 24 patients and unsuccessful in nine. None of the hemodynamic variables considered was found to be associated with the disparate outcomes. At the 3-month examination, all surviving patients were in NYHA class 1 or 2 except for three in NYHA class 3. At 2 years, hemodynamic values were: CVP 2±2 (0–4), mPAP 16±3 (12–21), CO 5.0±1.0 (3.4–6.5), PVR 182±51 (112–282), and RVEF 35±5 (26–40). All differences were significant with respect to baseline values (P<0.001). Preoperative mPAP and RVEF values had a strict linear correlation (R=0.45; P=0.014). Conclusions: None of the variables considered was correlated with early death or functional nonsuccess. Neither preoperative severity of pulmonary hypertension nor degree of cardiac failure influenced the outcome of the operation. PTE leads to hemodynamic recovery even in very compromised patients.     

急性肺栓塞致右心功能不全兔模型的建立

目的建立一种制作简单、可重复性高的急性肺栓塞(APE)伴有右心功能不全(RVD)的动物模型。方法采用实验用新西兰白兔12只,利用明胶海绵可压缩特性经股静脉注入5mm×5mm×10mm明胶海绵条2条,随血流栓塞肺动脉。监测血流动力学参数,行CT肺血管成像(CTPA)及肺组织病理学分析。结果所有明胶海绵条均恒定栓塞于双侧下肺动脉。建模前平均肺动脉压(mPAP)[(9.75±1.75)mmHg]与建模后即刻mPAP[(20.58±5.86)mmHg]、建模后1h的mPAP[(18.78±4.80)mmHg]差异均有统计学意义(P均0.001)。建模前后体循环收缩压(sBP)变化不显著(P=0.640)。建模前右心室/左心室横径比(RV/LV)为0.67±0.09,建模后45min复查为1.90±0.28,差异有统计学意义(P0.001)。结论本研究建立的兔伴有RVD的APE动物模型制作简单,可重复性高,适用于APE诊治的相关研究。     

体外膜肺氧合在原发性及继发性肺动脉高压肺移植中的应用

目的 探讨体外膜肺氧合(ECMO)在肺移植围手术期应用的方法及疗效.方法 2005年11月至2009年7月,对30例原发性及终末期肺病伴继发性肺动脉高压的患者在肺移植术中应用了ECMO辅助,完成单肺移植18例,不横断胸骨序贯式双肺移植12例.2例患者在术前经股动静脉切开置ECMO管道,分别维持19 d和6 d,术中仍在ECMO支持下进行肺移植;其余患者在麻醉完成后置ECMO管道,开始肺移植术.移植完成后,受者在氧合和血流动力学平稳后撤除ECMO.结果 所有受者均顺利完成移植.27例受者于移植手术结束后顺利撤除ECMO;3例受者术后继续使用ECMO,直至血流动力学稳定,其中2例分别于术后36 h和7 d时顺利撤除,另1例术后用ECMO维持5 d后出现急性肾功能衰竭,术后2周时死于多器官功能衰竭.术后股动静脉切开处伤口感染2例,股动脉血栓形成(中度)1例,经治疗后均好转出院.结论 体外膜肺氧合可安全有效地应用于伴有原发性或继发性肺动脉高压患者的肺移植手术.术中应用ECMO能控制肺动脉高压,同时进行呼吸和循环支持,减少了肺移植手术的并发症.     

Impact of Left Ventricular Diastolic Dysfunction on Lung Transplantation Outcome in Patients With Pulmonary Arterial Hypertension

Diastolic dysfunction may influence perioperative outcome, early graft function, and long‐term survival. We compared the outcomes of double lung transplantation (DLTx) for patients with pulmonary arterial hypertension (PAH) with preoperative left ventricular (LV) diastolic dysfunction with the outcomes of patients without diastolic dysfunction. Of 116 consecutive patients with PAH (who underwent transplantation between January 1995 and December 2013), 44 met our inclusion and exclusion criteria. Fourteen (31.8%) patients with diastolic dysfunction pretransplantation had a higher body mass index (29 [IQR 21.5–32.6] vs 22.4 [IQR 19.9–25.3] kg/m²) and mean pulmonary arterial pressure (54.6 ± 10 mmHg vs 47 ± 11.3 mmHg) and right atrial pressure (16.5 ± 5.2 mmHg vs 10.6 ± 5.2 mmHg). The patients received extracorporeal life support more frequently (33% vs 7% [p = 0.02]), had worse APACHE II scores (21.7 ± 7.4 vs 15.3 ± 5.3 [p = 0.02]), and a trend toward worse ventilator‐free days (2.5 [IQR 6.5–32.5] vs 17 [IQR 3–23] [p = 0.08]). There was no effect on development of primary graft dysfunction or intensive care unit/hospital survival. One‐year survival was worse (hazard ratio [HR] 4.45, 95% confidence interval [CI] 1.3–22, p = 0.02). Diastolic dysfunction was the only variable that correlated with overall survival (HR 5.4, 95% CI 1.3–22, p = 0.02). Diastolic dysfunction leads to early postoperative morbidity and worse survival in patients with PAH after DLTx.     

Role of Oral Sildenafil in the Treatment of Right Ventricular Dysfunction After Heart Transplantation

Objective

Right ventricular dysfunction (RVD) after heart transplantation is a major complication, especially in patients with pulmonary hypertension (PH). Herein we have presented our initial experience with oral sildenafil for RVD following heart transplantation.

Materials and Methods

From February 2006 to February 2008, 10 patients (7 males and 3 females) of overall mean age of 56.7 ± 9.5 years suffered from acute RVD immediately after heart transplantation. Preoperative hemodynamic data before and after a vasodilatation test (sodium nitroprusside; NTP) showed: systolic pulmonary arterial pressure (SPAP) 59.5 ± 12.9 and 44.2 ± 12.4 mm Hg; cardiac output (CO) 3.3 ± 0.9 and 3.7 ± 0.8 L/min; transpulmonary gradient (TPG) 11.7 ± 3.9 and 8.7 ± 3.6 mm Hg; and pulmonary vascular resistance (PVR) 3.9 ± 2.1 and 2.4 ± 1.3 wood units (WU), respectively. All patients required inotropes and inhaled nitric oxide (iNO) to be weaned from cardiopulmonary bypass (CPB).

Results

Intravenous (IV) or inhaled vasodilators could be weaned using oral sildenafil in all patients. The hemodynamic data obtained during IV or inhaled drugs (between postoperative days 5 and 10) compared with those obtained on sildenafil therapy alone (about 1 month after transplantation) showed a significant decrease in SPAP (39.0 ± 8.2 vs 32.0 ± 6.5 mm Hg; P = .049).

Conclusion

These data suggested that oral sildenafil may have a role in the treatment of RVD after heart transplantation.