Epstein-Barr virus associated graft failure following heart/lung transplantation.

A case is described of late pulmonary graft failure in a heart/lung transplant recipient. The major characteristics were alveolar fibrosis and a restrictive physiological deficit. Epstein-Barr virus was implicated as an aetiological agent using immunohistochemical analysis and by a response to treatment with ganciclovir.     

Utility of extracorporeal membrane oxygenation for early graft failure following heart transplantation in infancy.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is widely used for postcardiotomy cardiogenic shock in children. However, the efficacy of ECMO for early post-heart transplant graft failure in infants has not been reported. Our aims were to determine: (1) the utility of ECMO in infants with severe donor-heart dysfunction, (2) predictors for requiring ECMO, and (3) the long-term outcome of surviving ECMO patients. METHODS: All infants (age < 6 months at listing) undergoing heart transplantation were reviewed. Diagnostic categories were hypoplastic left heart syndrome (HLHS) and non-HLHS (complex congenital heart disease and cardiomyopathies). Continuous and categorical comparisons were by Wilcoxon's rank sum test and Fisher's exact test respectively. RESULTS: 14 (12 HLHS, 2 non-HLHS) of 63 (46 HLHS, 17 non-HLHS) infants were placed on ECMO. Ten patients (71%) were successfully weaned from ECMO and 8 (57%) were discharged alive. All ECMO hospital survivors remain alive (mean follow-up 36.2 +/- 21.4 months, range 13.1-77.6 months). Mean duration of ECMO support was 68 hours in weaned patients vs 144 hours (p = 0.19) in nonweaned patients, and 64 hours in survivors vs 123 hours (p = 0.35) in nonsurvivors. ECMO deaths were due to sepsis (n = 3), intractable pulmonary hypertension (n = 2), and intracranial bleed (n = 1). Neurologic deficits occurred in 2 survivors. Median ICU and hospital stays for ECMO survivors were 29 and 33 days vs 7 (p = 0.0003) and 9 (p = 0.0004) days for non-ECMO patients. Age listed, age transplanted, wait time, body weight, donor/recipient weight ratio, total ischemia time, and diagnosis did not predict the need for ECMO. CONCLUSIONS: (1) ECMO is useful for post-heart transplant circulatory support in infants with early graft failure. (2) All survivors were weaned in fewer than 4 days. (3) Three-year survival of ECMO hospital survivors has been high, but neurologic complications are prevalent.     

Right-left atrium by-pass as salvage treatment for graft failure after heart transplantation.

Chronic functional pulmonary hypertension (FPH) secondary to end-stage cardiomyopathy constitutes a risk factor for graft right ventricular failure (RVF) after orthotopic heart transplantation (HTx). A novel form of mechanical assist circuit, the extracorporeal right to left atrium bypass (ECRLAB), has been proposed. Since 1998, at our institution, a total of six patients with FPH who experienced graft RVF after HTx, as ischemic end-stage cardiomyopathy, during the effort to wean from cardiopulmonary bypass, underwent ECRLAB support. There were five men and one woman with a mean age of 55+/-3.5 years (49-59 years). The Jostra Rota Flow pump was used in five patients and the Bio-Medicus in one. Mean duration of support was 94.3+/-17.5 h (75-126 h). All (100%) patients were successfully weaned from ECRLAB support. Hemodynamic parameters improved in all patients. Two patients died from cerebral haemorrhage. Four (66.6%) patients were successfully discharged home. ECRLAB could be proposed during HTx in patients with increased preoperative transpulmonary gradient to promote the functional adaptation of the graft and avoid graft RVF, until the decline of pulmonary resistances.     

Nitric oxide donating aspirins: novel drugs for the treatment of saphenous vein graft failure

BACKGROUND: A new class of nitric oxide donating aspirin (NO-ASA) drugs may increase the therapeutic impact of aspirin in saphenous vein coronary artery bypass grafting (CABG) not only through the inhibition of thrombosis but also through a reduction of vasospasm and inhibition of vascular smooth muscle cell (VSMC) proliferation (effects that are inhibited by NO but not ASA). In order to test this proposal the effect of three NO-ASA drugs (NCX4040, NCX4050, and NCX4060) on in vitro relaxation and cyclic guanosine monophosphate (cGMP) formation in the human isolated saphenous vein and the proliferation of human VSMCs was investigated. METHODS: Saphenous vein segments were obtained from 30 patients undergoing CABG (median age, 59 years; range, 49 to 68). The effect of the NO-ASA adducts, ASA alone, and sodium nitroprusside (NO donor) were investigated on (1) relaxation of phenylephrine-stimulated contraction using an organ bath, (2) cyclic guanosine monophosphate (cGMP) formation using an enzyme-linked immunosorbent assay, and (3) the proliferation of VSMCs derived from saphenous vein using bromo-deoxyuridine (BRDU) incorporation. RESULTS: All three NO-ASA adducts (at concentrations that inhibited responses by 50% [IC50s] between 1 micromol/L and 100 micromol/L) and nitroprusside (at IC50s between 0.5 and 10 micromol/L) elicited relaxation of isolated human saphenous vein, promoted cGMP formation, and inhibited VSMC proliferation whereas ASA alone (up to 100 micromol/L) had no effect on any variable. CONCLUSIONS: These data indicate that the NO-ASA adducts by virtue of their capacity to release NO and stimulate guanylyl cyclase may be useful not only in the prevention of thrombosis following CABG but also the reduction of saphenous vein graft spasm and neointima formation.     

Nitric oxide synthase II mRNA expression in cardiac tissue of patients with heart failure undergoing cardiac transplantation.

OBJECTIVES: To examine whether inducible nitric oxide synthase is expressed in myocardial tissue of patients with heart failure. BACKGROUND: There is increasing evidence that alterations in nitric oxide synthesis are of pathophysiologic importance in heart failure. Nitric oxide (NO) can exert negative inotropic and cytotoxic effects on cardiomyocytes. A number of studies have shown altered nitric oxide production by the endothelial constitutive isoform of nitric oxide synthase (NOS III), but there is little information on the role of NOS II. Expression of NOS II could lead to excessive production of NO in the myocardium and affect cardiac contractility. METHODS: NOS II mRNA expression in myocardial tissue of 18 patients with idiopathic dilated cardiomyopathy (DCM), 7 patients with ischemic cardiopathy and severe ventricular dysfunction (ISCH), 4 patients with acute myocardial infarction (AMI) and 11 controls. Serum concentration of NO2-/NO3- (NOx) was also measured. RESULTS: NOS II gene expression occurred in all the patients with DCM, in 1 out of the 7 ISCH patients, in 2 out of the 4 patients with AMI and in none of the controls. Moreover, DCM patients showed a significant 6-fold increase in NOx concentration (253+/-47 nm/ml) as compared to controls (40+/-2 nm/ml) P < 0.001, a phenomenon not observed in ISCH patients (56+/-3 nm/ml). CONCLUSIONS: NOS II expression occurs in failing human cardiac myocytes and can play an specific role in the pathogenesis of DCM.     

Levosimendan for primary graft failure after heart transplantation: a 3-year follow-up

Background

Primary graft failure (PGF) is a severe complication responsible for 42% of the in-hospital mortality after heart transplantation. It has been postulated that once 30-day survival is achieved, patients with PGF have no increased risk of death. Levosimendan increases the 30-day survival among patients with PGF. Herein we have reported a 3-year follow-up at a single center of a patient cohort including PGF cases treated with levosimendan.

Methods

From September 2005 to December 2006 53 patients underwent heart transplantation at our institution, including 12 patients (22.6%) who presented with PGF and were treated with levosimendan using a 24-hour continuous infusion (0.10 μg/kg/min). Risk factors for 1-year and three-year mortality were analyzed using 30-day as well as 1 and 3-year survivals comparing patients with versus without PGF (n = 41).

Results

There were no significant differences in donor age, weight, height, and serum sodium between the groups. However, the ischemia time (259 ± 53 vs 227 ± 50 min; P = .06) and recipient age (51.6 ± 15 vs 41.5 ± 21 years; P = .07) were greater among the PGF patients. The 30-day survival rate was 92% in both groups. After 1 and 3 years, the survival rate was significantly lower among the PGF cohort (50% vs 80.6% and 41.7% vs 80.6%; P < .05) with 86.5% of PGF patients succunding due to non cardiac reasons, predominantly infections.

Conclusions

Although treatment of PGF with levosimendan increased the 30-day survival, the 1 year and 3-year rates were reduced among this cohort of patients. PGF was associated with poor long-term outcomes, which may be a consequence of systemic malperfusion during the stage of cardiac low-output after transplantation.     

Early graft function following heart and lung transplantation

Abstract. Fifty-one patients underwent heart-lung transplantation between April 1984 and October 1988. The first five donor organs were removed in an adjacent operating theatre. Organs were subsequently removed from distant centres. The method of preservation consisted of cold cardioplegic arrest of the heart using St. Thomas' solution, followed by a simple, cold pulmonary artery flush of a lung perfusate developed at Papworth Hospital. Administration of the solution was preceded by an infusion of prostacyclin into the pulmonary artery during preliminary dissection of the donor organs. The total ischaemic time ranged from 48 to 51 min (mean 49. 6 min) for the near procurement group and from 70 to 249 min (mean 154. 2 min) for the distant procurement group. There were no primary organ failures. Function of the lungs was assessed by gas exchange, pulmonary function tests, time to extubation, and survival data. Serial radiological studies were used to monitor graft performance in the postoperative period. We report here on our clinical experience of early graft function following heart and lung transplantation.     

Early graft function following heart and lung transplantation

Fifty-one patients underwent heart-lung transplantation between April 1984 and October 1988. The first five donor organs were removed in an adjacent operating theatre. Organs were subsequently removed from distant centres. The method of preservation consisted of cold cardioplegic arrest of the heart using St. Thomas' solution, followed by a simple, cold pulmonary artery flush of a lung perfusate developed at Papworth Hospital. Administration of the solution was preceded by an infusion of prostacyclin into the pulmonary artery during preliminary dissection of the donor organs. The total ischaemic time ranged from 48 to 51 min (mean 49.6 min) for the near procurement group and from 70 to 249 min (mean 154.2 min) for the distant procurement group. There were no primary organ failures. Function of the lungs was assessed by gas exchange, pulmonary function tests, time to extubation, and survival data. Serial radiological studies were used to monitor graft performance in the postoperative period. We report here on our clinical experience of early graft function following heart and lung transplantation.     

Nitric oxide treatment for acute respiratory failure in children

Summary
We have used nitric oxide in the treatment of four children admitted to the paediatric intensive care unit with acute, severe respiratory failure. Administration resulted in an improvement in arterial oxygenation range 1.3–18.4 kPa (9.9–140 mmHg): mean 6.7 kPa (51 mmHg) and a reduction in arterial carbon dioxide tension range 0.6–1.2 kPa (4.5–9 mmHg): mean 0.9 kPa (6.8 mmHg). No adverse effects were encountered following administration for a duration of 3–12 days at a dose of 40–64 parts per million.     

Nitric oxide inhalation is useful in the management of right ventricular failure caused by myocardial contusion

We report a severe head injury and blunt chest trauma with sternal and multiple rib fractures with high-energy impact in a 22-year-old man. Twelve hours after the accident, haemodynamic status of the patient rapidly worsened because of right ventricular (RV) failure due to myocardial contusion, requiring increasing doses of catecholamine. Nitric oxide inhalation was used to decrease RV afterload, and produced an immediate improvement in haemodynamic status, permitting a decrease in catecholamine administration. From days 2 through 8, cardiac function continued to improve, and was normal on day 9. Nitric oxide inhalation was stopped on day 4.