Chronic thromboembolic pulmonary hypertension in pediatric patients.

OBJECTIVE: Chronic thromboembolic pulmonary hypertension is a rare form of pulmonary hypertension that can lead to progressive right heart failure and death. Pulmonary thromboendarterectomy surgery is the treatment of choice resulting in significant improvements in functional status, cardiopulmonary hemodynamics, and survival. This study reports the largest case series of pediatric patients with chronic thromboembolic pulmonary hypertension who underwent pulmonary thromboendarterectomy surgery at one institution. PATIENT AND METHODS: The University of California, San Diego, chronic thromboembolic pulmonary hypertension database identified patients 18 years or younger at the time of pulmonary thromboendarterectomy surgery (n = 17). Medical charts were reviewed for hemodynamics, thromboembolic risk factors, and postoperative outcomes. RESULTS: Pulmonary thromboendarterectomy surgery in pediatric patients resulted in improved functional status and significantly improved cardiopulmonary hemodynamics: mean arterial pressure decreased from 45.5 mm Hg ± 20.7 to 27.3 ± 13.0 mm Hg (P = .00073), pulmonary vascular resistance decreased from 929 ± dynes · s · cm(-5) to 299 ± 307 dynes · s · cm(-5) (P = .0012), and cardiac output improved from 3.8 ± 1.1 L/min to 5.6 ± 1.6 L/min (P = .0061). There were no deaths during surgery or 30 days after surgery, and long-term survival (5+ years) was achieved in 87.5%. As compared to adults with chronic thromboembolic pulmonary hypertension, there was a higher rate of rethrombosis in pediatric patients (38% vs 1%-4%). CONCLUSIONS: This study demonstrates that pulmonary thromboendarterectomy surgery in pediatric patients with chronic thromboembolic pulmonary hypertension is well tolerated with improved postoperative hemodynamics, functional status, minimal postoperative complications, and low perioperative mortality, similar to that reported for adults with chronic thromboembolic pulmonary hypertension, with the notable exception being a higher rate of rethrombosis in pediatric patients.

Successful surgical closure of an arterial duct in 18 children in a third world country.

OBJECTIVES: To perform surgical closure of a clinically significant arterial duct on children in a third world country. BACKGROUND: An arterial duct is one of the most common congenital cardiac defects. Large arterial ducts can cause significant pulmonary overcirculation, causing symptoms of congestive cardiac failure, ultimately resulting in premature death. Closure of an arterial duct is usually curative, allowing for a normal quality of life and expectancy. In western countries, arterial duct closure in children is usually performed by deployment of a device through a catheter-based approach, replacing previous surgical approaches. In third world countries, there is limited access to the necessary resources for performing catheter-based closure of an arterial duct. Consequently, children with an arterial duct in a third world country may only receive palliative care, can be markedly symptomatic, and often do not survive to adulthood. METHODS: We assembled a team of 11 healthcare workers with extensive experience in the medical and surgical management of children with congenital cardiac disease. In all, 21 patients with a history of an arterial duct were screened by performing a comprehensive history, physical, and echocardiogram at the Angkor Hospital for Children in Siem Reap, Cambodia. RESULTS: A total of 18 children (eight male and ten female), ranging in age from 10 months to 14 years, were deemed suitable to undergo surgery. All patients were symptomatic, and the arterial ducts ranged in size from 4 to 15 millimetres. Surgical closure was performed using two clips, and in four cases with the largest arterial duct, sutures were also placed. All patients had successful closure without any significant complications, and were able to be discharged home within 2 days of surgery. Of note, four children with arterial ducts died in the 5 months before our arrival. CONCLUSION: Surgical closure of an arterial duct can be performed safely and effectively by an experienced paediatric cardiothoracic surgical team on children in a third world country. We hope that our experience will inspire others to perform similar missions throughout the world.

Mitral/systemic atrioventricular valve repair in congenital heart disease.

Because there is no ideal substitute for the mitral or the systemic atrioventricular valve (SAVV) in a patient of any age, repair is the optimal treatment for important congenital or acquired mitral/SAVV disease. Valve repair techniques have evolved to the point where early repair may be offered to asymptomatic patients with favorable anatomy. The indications for operation depend on the presence or absence of symptoms and the physiologic consequences of mitral/SAVV pathology. Concomitant arrhythmia surgery may be appropriate in selected cases. Surgical outcomes are good to excellent when appropriate techniques are used. Repair of congenital SAVV abnormalities is safe and durable in many patients.

Bone morphogenetic proteins induce apoptosis in human pulmonary vascular smooth muscle cells.

Pulmonary vascular medial hypertrophy in primary pulmonary hypertension (PPH) is mainly caused by increased proliferation and decreased apoptosis in pulmonary artery smooth muscle cells (PASMCs). Mutations of the bone morphogenetic protein (BMP) receptor type II (BMP-RII) gene have been implicated in patients with familial and sporadic PPH. The objective of this study was to elucidate the apoptotic effects of BMPs on normal human PASMCs and to examine whether BMP-induced effects are altered in PASMCs from PPH patients. Using RT-PCR, we detected six isoforms of BMPs (BMP-1 through -6) and three subunits of BMP receptors (BMP-RIa, -RIb, and -RII) in PASMCs. Treatment of normal PASMCs with BMP-2 or -7 (100-200 nM, 24-48 h) markedly increased the percentage of cells undergoing apoptosis. The BMP-2-mediated apoptosis in normal PASMCs was associated with a transient activation or phosphorylation of Smad1 and a marked downregulation of the antiapoptotic protein Bcl-2. In PASMCs from PPH patients, the BMP-2- or BMP-7-induced apoptosis was significantly inhibited compared with PASMCs from patients with secondary pulmonary hypertension. These results suggest that the antiproliferative effect of BMPs is partially due to induction of PASMC apoptosis, which serves as a critical mechanism to maintain normal cell number in the pulmonary vasculature. Inhibition of BMP-induced PASMC apoptosis in PPH patients may play an important role in the development of pulmonary vascular medial hypertrophy in these patients.

Increased expression of endoarterial vascular cell adhesion molecule-1 mRNA in an experimental model of lung transplant rejection: diagnosis by pulmonary arterial biopsy.

BACKGROUND: Early detection of rejection after lung transplantation may prevent allograft failure. This study determines if mRNA from the cell adhesion molecules intercellular adhesion molecule-1, vascular cell adhesion molecule (VCAM)-1, and E-selectin in pulmonary endovascular tissue samples could be markers of early rejection. METHODS: Single left lung transplants were performed in five dogs. Each dog was treated for 2 weeks with immunosuppression, after which rejection was allowed to occur. Percutaneous biopsies from 2- to 3-mm distal branch pulmonary arteries were obtained in each dog from the normal and the transplanted lungs at the end of immunosuppression therapy and periodically (2-4 times) for 1 to 3 weeks until euthanasia. Levels of cell adhesion molecule mRNA in the biopsy samples were quantitated by reverse-transcriptase polymerase chain reaction and normalized to beta-actin mRNA levels. RESULTS: Between three and five pulmonary endoarterial biopsy samples were obtained from each lung at each catheterization procedure. There was a significant increase in VCAM-1 mRNA levels in the biopsies of the transplanted lungs (which were undergoing rejection) compared with the native right lungs in all dogs. Progressive increases in VCAM-1 mRNA were observed with longer rejection times. VCAM-1 mRNA changes were detected earlier than histologic changes of rejection. CONCLUSIONS: In pulmonary endoarterial biopsy samples obtained in a canine lung transplant model, there was a progressive increase in VCAM-1 mRNA levels with increasing rejection. Changes in VCAM-1 mRNA were observed earlier than histologic changes of rejection. VCAM-1 quantitation by endoarterial biopsy may be useful in surveillance and early diagnosis of rejection in patients who undergo lung transplantation.

Predicting survival of lung transplantation candidates with idiopathic interstitial pneumonia: does PaO(2) predict survival?

OBJECTIVE: To find a parameter that would discriminate between the patients with idiopathic interstitial pneumonia who survived to undergo transplantation and those who died while waiting to undergo transplantation. METHODS: A retrospective review was performed of all lung transplant referrals for idiopathic interstitial pneumonia that were listed with United Network for Organ Sharing at the University of California San Diego from January 1990 to February 1999. Of the 331 patients who were listed, 48 met the eligibility criteria. Patient demographics, radiographic studies, pathology reports, and the results of resting and exercise cardiopulmonary function tests were recorded from each patient's chart. Patients were divided into the following two groups: those patients who survived until transplantation and those still waiting were classified as "alive"; and those patients who died before undergoing transplantation were classified as "deceased." RESULTS: Forty-three of 48 patients had a pathologic diagnosis. The cohort included 25 patients with usual interstitial pneumonitis, 3 patients with nonspecific interstitial pneumonitis, 1 patient with desquamative interstitial pneumonitis, and 14 patients with interstitial lung disease of unknown etiology. The only significant difference between the two groups was resting PaO(2) (p = 0.035). A stepwise multivariate analysis demonstrated that PaO(2) and FEV(1)/FVC ratio were significantly associated with survival (hazards ratio, 1.06; confidence interval, 0.99 to 1.13; p = 0.019). CONCLUSIONS: A survival analysis using PaO(2) and FEV(1)/FVC ratio values proved to be statistically significant, but a prospective trial is needed to determine the clinical relevance of these parameters for predicting survival in patients with idiopathic interstitial pneumonia.

Donor transfer of pulmonary coccidioidomycosis in lung transplantation.

Transplant recipients living in endemic areas are at high risk of aerosol-transmitted fungal infections because of environmental exposure while on immunosuppressive drugs, as well as reactivation of latent infection from either the patient's or the donor's organs. The latter may account for early development of coccidioidomycosis after transplantation. We describe a case of pulmonary coccidioidomycosis in a lung transplant recipient who acquired the infection from the donor lung and presented with fulminant pneumonia in the immediate postoperative period.

Transplante cardíaco na Universidade de Minnesota / Heart transplantation at the University of Minnesota

No período entre janeiro de 1984 e dezembro de 1987, foram realizados 117 transplantes de coraçäo na Universidade de Minnesota. A indicaçäo para transplante foi o estágio final de cardiopatia isquêmica (42%) e miocardiopatia idiopática (41%). A idade média foi de 45,2 anos (6 meses-64 anos). Imunossupressäo com ciclospotina-A, azatioprina e prednisona foi empregada em todos os casos. A curva atuarial de sobrevida no 1§ ano é de 95%, no 5§ ano é de 94%. Sete pacientes faleceram. Treze pacientes sofreram um ou mais episódios de rejeiçäo, comprovados histologicamente através de biopsia endocárdica. Aterosclerose no coraçäo transplantado foi investigada através de coronariografia anual. Foram identificadas anormalidades em 5 pacientes (7%) após o 1§ ano, em 5 pacientes (19%) após o 2§ anos e em otros 5 pacientes (38%) após o 3§ ano. O sucesso desta opçäo terapêutica e deste programa está relacionado â criteriosa seleçäo doador/receptor, à imunossupressäo com terapia tríplice e miticuloso cuidado pós-operatório. Aterosclerose coronária progressiva permanece a principal causa que, atualmente, afeta os resultados a longo prazo do transplante cardíaco