The Journal of Heart and Lung Transplantation

Editorial Board

2012-06-01

A call for a policy change regarding publications based on transplantation of organs from executed prisoners

Jacob Lavee, Lori J. West — 2012-04-09

In 2005 a Status 1 candidate for heart transplantation, who had been at the top of the Israeli candidates list for more than 1 year with continuous hospitalization while on catecholamines, approached one of us (J.L.) with an unusual message. He reported being told by his medical insurance company to travel to China in 2 weeks' time as he was scheduled for heart transplantation on a specific date. When the patient was asked how such an operation could be scheduled ahead of time, he indicated that he had not bothered to inquire. Indeed, he traveled to China and underwent the operation on the exact date promised in advance.

Mechanisms of pulmonary hypertension in chronic obstructive pulmonary disease: A pathophysiologic review

Jeremy P. Wrobel, Bruce R. Thompson, Trevor J. Williams — 2012-04-16

Chronic obstructive pulmonary disease (COPD) is a major cause of mortality and morbidity worldwide and is often complicated by the development of pulmonary hypertension (PHT). The presence of PHT in COPD subjects is associated with increased mortality, morbidity and use of health-care resources. Thus, there has been significant effort to treat PHT in COPD patients to achieve improved clinical outcomes, but with only minimal success. There is renewed interest in understanding the mechanisms contributing to PHT in COPD as the basis for exploring new therapeutic strategies. In this study we review the evidence supporting the postulated mechanisms contributing to PHT in COPD. Hypoxia plays a pivotal role in the development of COPD-associated PHT. However, other mechanisms are also likely involved in the pathogenesis of increased pulmonary vascular resistance in this cohort, including acidemia, dynamic pulmonary hyperinflation, parenchymal destruction, pulmonary vascular remodeling, endothelial dysfunction and inflammation. These mechanisms are interdependent, modulated by genetic factors, and may be confounded by comorbidities such as sleep-disordered breathing, left heart failure and pulmonary thromboembolism. Despite significant research in recent decades, there is surprisingly little evidence of a causal relationship between many of these factors and the development of COPD-associated PHT. The pathogenesis of PHT in COPD is complex and multifaceted. Ultimately, as we obtain better information on COPD phenotypes, we may be able to more precisely account for the varied pathologic mechanisms of PHT occurring in various COPD patients. This may ultimately enable targeted PHT therapy for each COPD phenotype.

Cyclosporine lowering with everolimus versus mycophenolate mofetil in heart transplant recipients: Long-term follow-up of the SHIRAKISS randomized, prospective study

2012-02-17

Background: Cyclosporine nephrotoxicity negatively impacts long-term outcome after heart transplantation (HT). We previously reported 1-year results from a randomized study showing that cyclosporine-lowering strategies based on everolimus or mycophenolate mofetil (MMF) are equally effective for reducing progression of renal dysfunction. It is unknown whether this efficacy could be maintained over the long term. Methods: Thirty-four recipients 1 to 4 years after HT and with 25 to 60 ml/min of creatinine clearance (CrCl) were randomized to everolimus with a very low dose (C0: 50 to 90 ng/ml, n = 17) or MMF with low dose of cyclosporine (C0: 100 to 150 ng/ml, n = 17). Follow-up was prolonged up to 3 years, and calculated CrCl was the main efficacy measure. Results: Cyclosporine was maintained at 70% and 30% lower than baseline in the everolimus and MMF arms, respectively, throughout the 3-year study period. CrCl remained stable in the everolimus patients (+7% from baseline; p = 0.7), but improved in the MMF patients (+20% from baseline; p < 0.01), with a trend toward improved values compared with everolimus patients (46 ± 12 vs 56 ± 15 ml/min; p = 0.06). Subgroup analysis revealed that baseline proteinuria markedly influenced the renal function response to everolimus: whereas in patients with baseline proteinuria CrCl significantly worsened (−20%; p = 0.04), it improved in those without (+15%; p = 0.03). Safety was comparable between the two study arms. Conclusions: Cyclosporine nephrotoxicity improved after a prolonged dose reduction in patients receiving MMF. The everolimus-based strategy provided a similar benefit only to patients without baseline proteinuria. While raising caution against the universal use of everolimus for kidney protection, our long-term results support the need for customized approaches in the management of drug toxicities in maintenance HT recipients.

Quality of life in pediatric heart transplant recipients: A comparison with children with and without heart disease

2012-03-01

Background: Little is known about the quality of life (QOL) of children with heart disease who undergo life-saving surgery. The aim of this multicenter study was to examine self- and parent-reported QOL outcomes in pediatric heart transplant recipients. Methods: Pediatric heart transplant recipients/families (n = 174) from 7 transplant programs completed the Pediatric Quality of Life Inventory Generic Core Scales and Cardiac Module. Scores for the heart transplant sample were compared with non-transplant patients who had undergone conventional cardiac surgery and with a healthy child sample. Within the cardiac surgery group, heart disease/surgery was further categorized by severity/complexity. Results: Heart transplant recipients were a mean age of 10.6 ± 4.7 years at a mean time post-transplant of 6.0 ± 4.1 years. By both self-report and parent proxy report, mean scores for heart transplant recipients were significantly lower than those in healthy children for physical and psychosocial QOL, including emotional and social functioning (p < 0.001), with 31.3% self-reporting significantly impaired psychosocial QOL scores. By self-report, there were no significant differences in emotional and social mean scores between the transplant and cardiac surgery groups. Transplant recipients reported significantly fewer cardiac symptoms than children with cardiac surgery (p < 0.01). Their self-reported school functioning scores were not significantly different from children with moderate to severe disease. Conclusion: Although pediatric heart transplant recipients experience significant symptomatic improvement, they remain at-risk for impaired psychosocial QOL, similar to children with residual or palliated heart disease. Assessment is needed to identify children at-risk and improve psychosocial outcomes.

Donor B-type natriuretic peptide predicts early cardiac performance after heart transplantation

2012-03-05

Background: Decision processes in heart donation remain difficult and are often based on subjective evaluation. We measured B-type natriuretic peptide (BNP) in heart donors and analyzed its value as a discriminator for early post-transplant cardiac performance. Methods: Blood samples were prospectively obtained in 94 brain-dead patients, among whom 56 were scheduled for heart donation. BNP values were not available prior to donor selection. BNP of heart donors was related to invasively measured cardiac output and hemodynamic parameters, early after transplantation. Results: BNP, expressed as median (interquartile range), was 65 (32 to 149) pg/ml in brain-dead donors scheduled for heart donation. BNP was higher (287 pg/ml, range 65 to 457; p = 0.0001) in donors considered ineligible for heart donation. In 45 heart recipients, cardiac output (CO) of 5.6 (4.8 to 6.2) liters/min was measured at Day 12 (10–15). In the univariate analysis, recipient CO correlated significantly with donor BNP (r = −0.34, p = 0.025). Stepwise multiple regression, including donor variables such as body mass index, age, BNP, norepinephrine dose, gender and total ischemic time, identified donor BNP and age as the best independent predictors of CO in recipients (p = 0.02 and p = 0.005, respectively, R2 of the model = 0.27). Donor BNP of >160 pg/ml had 89% accuracy to predict poor cardiac performance in the recipient (cardiac index <2.2 liters/min/m2). High donor BNP was independently correlated with a longer hospital stay. Conclusions: Donor BNP was found to be related to cardiac performance, early after cardiac transplantation. BNP measurement in heart donors could become a useful tool in the evaluation of donor hearts.

Bronchial carcinoma after lung transplantation: A single-center experience

2012-03-16

Background: Lung transplantation (LTx) remains the best option for selected patients with end-stage lung disease. Long-term survival is hampered by the development of chronic allograft dysfunction, which is the main reason for mortality at 3 to 5 years after LTx. Prevalence of and mortality due to solid-organ tumors also increases and we specifically investigated the development of primary bronchial carcinoma (BC) and its outcome after LTx. Methods: From January 2000 until June 2011, 494 lung and heart–lung transplantations were performed. Among this population, 13 patients developed bronchial carcinoma at 41 ± 27 (mean ± SD) months after LTx. Of these 13 patients, there were 9 men and 4 women. They were transplanted at a mean age of 59 ± 2.8 years; 8 patients were transplanted for emphysema and 5 for pulmonary fibrosis. Results: Nine of 92 single LTx patients (transplanted for emphysema or lung fibrosis) developed a bronchial carcinoma in their native lung, whereas only 4 of 224 bilateral LTx patients (also for emphysema or fibrosis) developed a bronchial carcinoma (p = 0.0026). At diagnosis, 4 patients had local disease (cT1N0M0 and cT2N0M0), whereas all others had locoregionally advanced or metastatic disease. Five patients were surgically treated; however, 1 had unforeseen N2 disease with additional pleural metastasis at surgery. All other patients (except 2 who died very soon after diagnosis) were treated with chemotherapy with or without radiotherapy. The median survival after diagnosis was only 10 ± 7 months, with a significant survival difference between patients with limited and extensive disease (p = 0.037). The latter had a median survival of only 6 months compared with 21 months for patients with limited stages of bronchial carcinoma. Conclusions: Bronchial carcinoma, especially of the native lung after single LTx, is a significant problem and the survival after diagnosis is very poor, although patients with limited (operable) disease tend to have better results.

Hepatic dysfunction and survival after orthotopic heart transplantation: Application of the MELD scoring system for outcome prediction

2012-03-29

Background: The prevalence of heart failure (HF) is rising and the only corrective treatment is cardiac transplantation. Advanced HF is associated with congestive hepatopathy and progressive functional and ultrastructural changes of the liver. We hypothesized that hepatic dysfunction is associated with impaired clinical outcome after heart transplantation. Methods: Data of 617 adult patients (75% men, mean age 53 ± 12 years, mean BMI 25 ± 4, mean ejection fraction 19 ± 9%) undergoing orthotopic heart transplantation (OHT) were analyzed retrospectively. Deviation from institutional normal ranges was used to define abnormal liver function. Standard Model for End-stage Liver Disease (MELD) scores were calculated and a modified MELD score with albumin replacing INR (modMELD) was created to eliminate the confounding effects of anti-coagulation. Results: Before OHT, AST, ALT and total bilirubin were elevated in 20%, 18% and 29% of the population, respectively. Total protein and albumin were decreased in 25% and 52% of the population, respectively. By 2 months post-transplantation, percentages of individuals with pathologic values decreased significantly, except for ALT, total protein and albumin, all of which took longer to normalize. Individuals with a higher pre-transplantation MELD or modMELD score had worse outcome 30 days post-transplant and reduced long-term survival over a 10-year follow-up. Conclusions: In this large, single-center retrospective study, we demonstrated the dynamics of liver dysfunction after cardiac transplantation and that elevated MELD scores indicating impaired liver function are associated with poor clinical outcome after OHT. Thus, pre-operative liver dysfunction has a significant impact on survival of patients after cardiac transplantation.

Liver dysfunction as a predictor of outcomes in patients with advanced heart failure requiring ventricular assist device support: Use of the Model of End-stage Liver Disease (MELD) and MELD eXcluding INR (MELD-XI) scoring system

2012-03-29

Background: Liver dysfunction increases post-surgical morbidity and mortality. The Model of End-stage Liver Disease (MELD) estimates liver function but can be inaccurate in patients receiving oral anti-coagulation. We evaluated the effect of liver dysfunction on outcomes after ventricular assist device (VAD) implantation and the dynamic changes in liver dysfunction that occur during VAD support. Methods: We retrospectively analyzed 255 patients (147 with pulsatile devices and 108 with continuous-flow devices) who received a long-term VAD between 2000 and 2010. Liver dysfunction was estimated by MELD and MELD-eXcluding INR (MELD-XI), with patients grouped by a score of ≥ 17 or < 17. Primary outcomes were on-VAD, after transplant, and overall survival. Results: MELD and MELD-XI correlated highly (R ≥ 0.901, p < 0.0001) in patients not on oral anti-coagulation. Patients with MELD or MELD-XI < 17 had improved on-VAD and overall survival (p < 0.05) with a higher predictive power for MELD-XI. During VAD support, cholestasis initially worsened but eventually improved. Patients with pre-VAD liver dysfunction who survived to transplant had lower post-transplant survival (p = 0.0193). However, if MELD-XI normalized during VAD support, post-transplant survival improved and was similar to that of patients with low MELD-XI scores. Conclusions: MELD-XI is a viable alternative for assessing liver dysfunction in heart failure patients on oral anti-coagulation. Liver dysfunction is associated with worse survival. However, if MELD-XI improves during VAD support, post-transplant survival is similar to those without prior liver dysfunction, suggesting an important prognostic role. We also found evidence of a transient cholestatic state after LVAD implantation that deserves further examination.

The CentriMag ventricular assist device in acute heart failure refractory to medical management

2012-06-01

Background: The CentriMag ventricular assist device (VAD) has gained popularity in the last several years as rescue support for patients with decompensated heart failure. We have used the CentriMag VAD as a bridge to decision device. We describe our experience with device placement, use and outcomes. Methods: This is a retrospective study of all patients who underwent CentriMag placement at our institution from January 2007 to August 2009. Sixty-three patients had placement of a CentriMag device, with 43% (n = 27) of these being placed due to failure of medical management. These cases were the focus of our study. Results: Primary diagnoses were ischemic cardiomyopathy (n = 17), dilated cardiomyopathy (n = 7) or other (n = 3). Mean age was 47.1 (range 7 to 72) years. Prior to implant, 85% of patients were on intra-aortic balloon pump (IABP) support, 70% were on vasopressors, and 44% were on more than one inotrope. INTERMACS score was 1 in 67% of patients and 2 in 33% of patients. Six patients were bridged to a long-term device, 8 to transplantation and 10 to recovery. Eighty-nine percent (24 of 27) of patients survived to explant and 74% (20 of 27) survived to hospital discharge, with a 1-year survival of 68%. Thromboembolic complications occurred in 10 patients, including 6 strokes. Compared with patients who survived to discharge, those who died had a significantly higher body mass index (30.8 vs 24.1 kg/m2, p = 0.003). Survivors to discharge demonstrated significant improvements in hepatic and renal function over the course of device support while non-survivors did not. Conclusions: The CentriMag demonstrates promising results when used in patients with acute heart failure refractory to medical management.

Bridging cardiogenic shock patients with short-term ventricular support at a community hospital to long-term ventricular support at a tertiary hospital

2012-02-10

Background: Patients in cardiogenic shock require immediate circulatory support. Outcomes of patients who underwent short-term ventricular assist device (STVAD) implantation in a community hospital (CH) as a bridge to a long-term VAD (LTVAD) were compared with those who received both implants at the same tertiary hospital (TH). Methods: Data were retrospectively reviewed for patients with a STVAD who were bridged to a LTVAD in a TH from 1997 to 2010. We studied outcomes and survival censored for cardiac transplantation. Results: Thirty-seven patients (73% male) were identified. Mean age was 52 ± 16 years, 30% were diabetic, and 65% had intra-aortic balloon pump support. Reasons for STVAD implantation were an acute myocardial infarction, 38%; post-cardiotomy, 38%, decompensated chronic heart failure, 19%; and others, 5%. A STVAD was implanted in a CH in 20 patients (54%), and they had fewer cardiovascular risk factors than those whose STVAD was implanted at the TH. All patients at the CH were at Interagency Registry for Mechanically Assisted Circulatory Support 1 compared with 71% at the TH (p = 0.014). Patients from the CH tended to die sooner after LTVAD implant, although long-term survival was similar. At the 1-year follow-up, 65% from the CH were alive or had received a transplant vs 60% from the TH. Conclusion: Patients with cardiogenic shock in whom a STVAD was implanted in a CH and then were bridged to a LTVAD in a TH had similar long-term survival as those bridged to LTVAD at the TH.

Association of pre-operative interleukin-6 levels with Interagency Registry for Mechanically Assisted Circulatory Support profiles and intensive care unit stay in left ventricular assist device patients

2012-03-05

Background: Inflammatory mechanisms are associated with worse prognosis in end-stage heart failure (ESHF) patients who require left ventricular assist device (LVAD) support. Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profiles describe patient condition at pre-implant and outcome. This study assessed the relationship among inflammation patterns and INTERMACS profiles in LVAD recipients. Method: Thirty ESHF patients undergoing LVAD implantation as bridge to transplant were enrolled. Blood and urine samples were collected pre-operatively and serially up to 2 weeks post-operatively for assessment of inflammatory markers (plasma levels of interleukin [IL]-6, IL-8, IL-10, and osteopontin, a cardiac inflammatory-remodeling marker; and the urine neopterin/creatinine ratio, a monocyte activation marker). Multiorgan function was evaluated by the total sequential organ failure assessment (tSOFA) score. Outcomes of interest were early survival, post-LVAD tSOFA score, and intensive care unit (ICU) length of stay. Results: Fifteen patients had INTERMACS profiles 1 or 2 (Group A), and 15 had profiles 3 or 4 (Group B). At pre-implant, only IL-6 levels and the IL-6/IL-10 ratio were higher in Group A vs B. After LVAD implantation, neopterin/creatinine ratio and IL-8 levels increased more in Group A vs B. Osteopontin levels increased significantly only in Group B. The tSOFA score at 2 weeks post-LVAD and ICU duration were related with pre-implant IL-6 levels. Conclusions: The INTERMACS profiles reflect the severity of the pre-operative inflammatory activation and the post-implant inflammatory response, affecting post-operative tSOFA score and ICU stay. Therefore, inflammation may contribute to poor outcome in patients with severe INTERMACS profile.

Different prognostic impact of the tissue Doppler-derived E/e′ ratio on mortality in Chagas cardiomyopathy patients with heart failure

2012-02-03

Background: Risk assessment of Chagas cardiomyopathy patients is essential for clinical decision making. The ratio of the ratio of early transmitral velocity to tissue Doppler mitral annular early diastolic velocity (E/e′) is a powerful predictor of adverse outcome in patients with heart failure. However, its prognostic value remains to be established in the setting of Chagas cardiomyopathy. This study investigated the effect of E/e′ on mortality according to different degrees of left ventricular (LV) systolic function in patients with Chagas cardiomyopathy. Methods: The study prospectively enrolled 232 patients (143 men) with Chagas cardiomyopathy (mean age, 48 ± 12 years). End points were death or cardiac transplantation. Results: During a mean follow-up of 3.4 years, 107 patients had an adverse cardiac event, with an overall events rate of 13.2/year. Cox proportional hazards model was used with New York Heart Association functional class, LV ejection fraction, right ventricular function, indexed left atrial volume, E/e′ ratio, and the statistical interaction term between E/e′ ratio and LV ejection fraction. The effect of E/e′ ratio on mortality depended on the degree of LV systolic dysfunction. An increasing E/e′ ratio was a strong predictor of outcome in patients with mild to moderate LV dysfunction but was inversely associated with mortality in patients with severe systolic dysfunction. Conclusion: This study demonstrated the role of the interaction between LV ejection fraction and E/e′ ratio in predicting prognosis in Chagas cardiomyopathy patients. The E/e′ ratio had a stronger prognostic value in patients with mild and moderate LV dysfunction and was inversely associated with mortality in patients with advanced systolic heart failure.

Systemic endothelial dysfunction in children with idiopathic pulmonary arterial hypertension correlates with disease severity

2012-03-23

Background: Idiopathic pulmonary arterial hypertension (IPAH) is a life-threatening disease manifested by progressive pulmonary vascular remodeling, compromised pulmonary blood flow and right heart failure. Most studies have explored how pulmonary endothelial function modulates disease pathogenesis. We hypothesize that IPAH is a progressive panvasculopathy, affecting both pulmonary and systemic vascular beds, and that systemic endothelial dysfunction correlates with disease severity. Recent studies have demonstrated systemic endothelial dysfunction in adults with pulmonary hypertension; however, adults often have additional comorbidities affecting endothelial function. Systemic endothelial function has not been explored in children with IPAH. Methods: In this single-center, prospective, cross-sectional study we examined brachial artery flow-mediated dilation (FMD), a nitric oxide–mediated, endothelial-dependent response, in children with IPAH and matched controls. FMD measurements were compared with clinical and echocardiographic measures of IPAH severity. Results: Thirteen patients and 13 controls were studied, ranging in age from 6 to 20 years. FMD was decreased in IPAH subjects compared with controls (5.1 ± 2.1% vs 9.7 ± 2.0%; p < 0.0001). In IPAH subjects, FMD correlated directly with cardiac index (R2 = 0.34, p = 0.035), and inversely with tricuspid regurgitation velocity (R2 = 0.57, p = 0.019) and right ventricular myocardial performance index (R2 = 0.44, p = 0.028). Conclusions: The presence of systemic endothelial dysfunction in children with IPAH and its strong association with IPAH severity demonstrate that IPAH is a global vasculopathy. Although morbidity in IPAH is typically associated with pulmonary vascular disease, systemic vascular changes may also relate to disease pathogenesis and progression. Further study into shared mechanisms of systemic and pulmonary endothelial dysfunction may contribute to future therapies for IPAH.

Long-term support with an ambulatory percutaneous paracorporeal artificial lung

2012-03-26

Background: Conventional extracorporeal membrane oxygenation is bulky and non-ambulatory and requires multiple blood transfusions. We hypothesized that a percutaneous, paracorporeal artificial lung (PAL) could be established through a single venous cannulation to provide long-term ambulatory respiratory support. Methods: Our PAL system was tested in 11 healthy sheep. An Avalon Elite dual-lumen cannula (DLC), inserted through the right jugular vein into the superior vena cava, right atrium, and inferior vena cava, was connected to a CentriMag pump and compact hollow-fiber gas exchanger, forming a short-circuit PAL system. All sheep were moved to intensive care unit and were ambulatory after anesthesia recovery. Hemodynamics and device performance were measured daily. Results: The ambulatory PALs were successfully established in all sheep. The sheep were awake, ate, and moved freely in the metabolic cage, with no need of artificial nutrition or blood transfusion. All sheep had stable hemodynamics, with 2 liters/min of average circuit flow and hemoglobin levels exceeding 9.2 g/dl throughout the experiment. A progressive decrease of oxygen transfer and carbon dioxide removal capacity was observed. Sheep were euthanized between 10 and 24 days for bleeding (n = 2), gas exchanger failure (n = 6), and DLC issues (n = 3). Conclusions: We successfully established long-term ambulatory PAL for up to 24 days in 11 animals using our patented DLC through a single-site percutaneous venous cannulation. Critical bleeding/thrombosis formation and gas exchanger durability remain two major challenges for long-term-ambulatory PAL.

Intratracheal administration of p38α short-hairpin RNA plasmid ameliorates lung ischemia-reperfusion injury in rats

Xiangqi Lv, Jing Tan, Dongdong Liu, Ping Wu, Xiaoguang Cui — 2012-04-16

Background: Lung ischemia–reperfusion injury (LIRI) remains a significant problem after lung transplantation. A crucial signaling enzyme involved in inflammation and apoptosis during LIRI is p38 mitogen-activated protein kinase (MAPK). Gene silencing of p38α by short hairpin RNA (shRNA) can downregulate p38α expression. The lungs have an extremely large surface area, which makes the absorption of shRNA highly effective. Therefore, we evaluated the therapeutic efficacy of p38α shRNA plasmids in a rat model of lung transplantation. Methods: The delivery of p38α shRNA plasmid was performed by intratracheal administration 48 hours before transplantation into donor rats. Control animals received scrambled shRNA plasmids. Reverse-transcription polymerase chain reaction and Western blots were used to assess gene silencing efficacy. The therapeutic effects of shRNA plasmids were evaluated by lung function tests. We determined the levels of inflammatory cytokines, the level of intercellular adhesion molecule 1 (ICAM-1), c-Myc mRNA expression, and ICAM-1 protein expression, and the presence of cell apoptosis. Results: Rats administered p38α shRNA plasmids showed a significant downregulation in lung expression of p38α transcripts and protein levels. Compared with the control group, the p38α shRNA group showed a higher pulmonary vein oxygen level, lower wet weight-to-dry weight ratio, lower lung injury score, and lower serum levels of tumor necrosis factor-α, interleukin-6, and interleukin-8. Messenger RNA levels of ICAM-1 and c-Myc in the p38α shRNA group were dramatically lower than in the control group. Levels of ICAM-1 protein expression exhibited a similar trend. Cell apoptosis decreased in the p38α shRNA group vs the control group. Conclusion: Intratracheal administration of p38α shRNA plasmids provided therapeutic effects in a rat model of lung transplantation.

S262A mutation abolishes protective effects of connexin 43 against hypothermic preservation–induced injury in cardiomyocytes

2012-06-01

Background: Alleviation of cold preservation–induced injury is a critical part of the heart transplantation process. In this study we investigate the protective effect of connexin 43 (Cx43) overexpression against hypothermic preservation–induced injury in cardiomyocytes. Methods: Total RNA was prepared from H9c2 cells using TRIzol reagent to construct a recombinant vector pEGFP-c1-Cx43, which was then transformed into Escherichia coli DH5α competent cells. The S262A Cx43 containing a mutant site was obtained by RT-PCR. The protein expression of total Cx43 and p-S262 Cx43 were assessed by Western blot. Cell viability and LDH release in the culture medium was measured. Results: Restrictive enzyme reaction assay and DNA sequencing confirmed that the recombinant vector pEGFP-c1-Cx43 and pEGFP-c1-S262A-Cx43 were constructed correctly. After H9c2 cells were hypothermically preserved in Celsior solution for 12 to 48 hours, the cell viability decreased and LDH release increased. Compared with empty vector cells, overexpression of Cx43 prevented the hypothermic preservation–induced decrease in cell viability and increase in LDH release, which was independent of the absence of gap junctions. S262A mutation prevented S262 phosphorylation of Cx43 and also abolished protection of Cx43 overexpression against cold preservation–induced cardiomyocyte injury. Conclusions: In H9c2 cells hypothermically preserved for up to 48 hours, overexpression of Cx43 could protect against cold preservation–induced injury. Phosphorylation of Cx43 at S262 may play an essential role in the preservation of donor hearts.

Impact of low-dose B-type natriuretic peptide infusion on urine output after total artificial heart implantation

2012-03-16

The total artificial heart (TAH) orthotopically replaces a recipient's native ventricles and all four cardiac valves, interrupting neural and hormonal signaling pathways that are dependent upon the intact ventricular myocardium. B-type natriuretic peptide (BNP) is a cardiac neurohormone primarily secreted from ventricular cardiomyocytes in response to cardiac stretch. In healthy individuals, BNP decreases vascular tone, increases renal blood flow, promotes natriuresis and suppresses the renin–aldosterone axis.

Fate of retained right ventricular assist device outflow grafts after right ventricular recovery

2012-04-06

Right heart failure (RHF) after left ventricular assist device (LVAD) implantation is a common problem in the immediate post-operative period and a significant cause of increased morbidity and death. Worsening of right ventricular (RV) function after LVAD insertion has been attributed to changes in RV geometry and flow dynamics after left ventricular (LV) unloading. The various factors contributing to this RV dysfunction are ameliorated in the post-operative period as RV/LV equilibrium is reached. Temporary right ventricular assist device (RVAD) support can facilitate the peri-operative management of RHF after LVAD insertion. Our technique for temporary RVAD support employs a cannulation strategy that permits minimally invasive separation without mediastinal re-entry. With this approach a segment of outflow graft remains in situ on the pulmonary artery. Although some evidence exists in support of the safety of leaving LVAD components in situ at the time of device explantation, little is known about retained RVAD components. Thus, we evaluated the fate of retained RVAD outflow grafts in patients who received temporary RVAD support in conjunction with HeartMate (HM) II LVAD implantation.