Biomedical subjects

Stuart W Jamieson

Publications and source records attributed to Stuart W Jamieson.

27 records · Page 2Linked to original sources

PubMed2004

Massive pulmonary hemorrhage after pulmonary thromboendarterectomy.

Pulmonary thromboendarterectomy, the most common surgical treatment of chronic thromboembolic pulmonary hypertension, is being performed with increasing frequency throughout the world. Massive pulmonary hemorrhage is a potentially fatal complication of this procedure. In this report of three such cases, the diagnosis, clinical course, and possible treatments are discussed. Anesthesiologists involved in the care of patients receiving pulmonary thromboendarterectomy must be aware of the possibility of this complication, as well as the various techniques available for its treatment.

Aged↗

PubMed2003

Induction of pulmonary hypertension by an angiopoietin 1/TIE2/serotonin pathway.

Smooth muscle cell proliferation around small pulmonary vessels is essential to the pathogenesis of pulmonary hypertension. Here we describe a molecular mechanism and animal model for this vascular pathology. Rodents engineered to express angiopoietin 1 (Ang-1) constitutively in the lung develop severe pulmonary hypertension. These animals manifest diffuse medial thickening in small pulmonary vessels, resulting from smooth muscle cell hyperplasia. This pathology is common to all forms of human pulmonary hypertension. We demonstrate that Ang-1 stimulates pulmonary arteriolar endothelial cells through a TIE2 (receptor with tyrosine kinase activity containing IgG-like loops and epidermal growth factor homology domains) pathway to produce and secrete serotonin (5-hydroxytryptamine), a potent smooth muscle mitogen, and find that high levels of serotonin are present both in human and rodent pulmonary hypertensive lung tissue. These results suggest that pulmonary hypertensive vasculopathy occurs through an Ang-1/TIE2/serotonin paracrine pathway and imply that these signaling molecules may be targets for strategies to treat this disease.

Angiopoietin-1↗

PubMed2003

Signaling molecules in nonfamilial pulmonary hypertension.

BACKGROUND: Biochemical, genetic, and clinical evidence indicates that smooth-muscle proliferation around small pulmonary vessels is an essential part of the pathogenesis of pulmonary hypertension. Mutations in the bone morphogenetic protein receptor type 2 (BMPR2) have been linked to familial cases of pulmonary hypertension, but the molecular basis of the common nonfamilial forms is unknown. METHODS: We evaluated the pattern of expression of angiopoietin-1, a protein involved in the recruitment of smooth-muscle cells around blood vessels; TIE2, the endothelial-specific receptor for angiopoietin-1; and bone morphogenetic protein receptor type 1A (BMPR1A) and BMPR2 in lung-biopsy specimens from patients with pulmonary hypertension and from normotensive control patients. The effect of angiopoietin-1 on the modulation of BMPR expression was also evaluated in subcultures of human pulmonary arteriolar endothelial cells. RESULTS: The expression of angiopoietin-1 messenger RNA and the protein itself and the phosphorylation of TIE2 were strongly up-regulated in the lungs of patients with various forms of pulmonary hypertension, correlating directly with the severity of disease. A mechanistic link between familial and acquired pulmonary hypertension was demonstrated by the finding that angiopoietin-1 shuts off the expression of BMPR1A, a transmembrane protein required for BMPR2 signaling, in pulmonary arteriolar endothelial cells. Similarly, we found that the expression of BMPR1A was severely reduced in the lungs of patients with various forms of acquired as well as primary nonfamilial pulmonary hypertension. CONCLUSIONS: These findings suggest that all forms of pulmonary hypertension are linked by defects in the signaling pathway involving angiopoietin-1, TIE2, BMPR1A, and BMPR2 and consequently identify specific molecular targets for therapeutic intervention.

Activin Receptors, Type I↗

PubMed2003

Decreased plasma neurohormones and improved cardiac performance after surgical treatment of chronic pulmonary embolism.

The findings of this case report suggest that quantitative assessment of plasma neurohormones and magnetic resonance imaging functional parameters in patients with right ventricular pressure overload due to chronic pulmonary embolism might be used as indicators for right ventricular function before and after intervention. Monitoring of changes in these parameters may provide quantitative follow-up of right ventricular function in these patients.

Biomarkers↗

PubMed2003

Pulmonary endarterectomy: experience and lessons learned in 1,500 cases.

BACKGROUND: The incidence of pulmonary hypertension resulting from chronic thrombotic occlusion of the pulmonary arteries is significantly underestimated. Although medical therapy for the condition is supportive only, surgical therapy is curative. Our pulmonary endarterectomy program was begun in 1970, and 188 patients were operated on in the subsequent 20 years. With the increased recognition of the disease and the success of operative therapy, however, more than 1,400 operations have been done since 1990 at our center. METHODS: The safety and efficacy of the operation was assessed with changes made through increased experience. We examined in detail the results of our last 500 consecutive patients. RESULTS: Median sternotomy, cardiopulmonary bypass, profound hypothermia, and circulatory arrest were found to be essential to the success of the operation. All occluding material could be removed at operation. We currently believe that there is no degree of embolic occlusion within the pulmonary vascular tree that is inaccessible and no degree of right ventricular impairment or any level of pulmonary vascular resistance that is inoperable. With shorter cardiac arrest periods and the use of a cooling jacket to the head, cerebral impairment has been eliminated. The pulmonary artery pressures and pulmonary vascular resistance in a recent cohort of 500 patients is examined. The mortality rate for the operation has been reduced steadily, and was 22 of the last 500 patients operated on (4.4%). CONCLUSIONS: The operation is considered curative and therefore greatly superior to transplantation for this condition. Current techniques of operation make the procedure relatively safe.

Adolescent↗

PubMed2003

Direct comparison of efficiency and stability of gene transfer into the mammalian heart using adeno-associated virus versus adenovirus vectors.

OBJECTIVE: Recent gene therapy strategies have relied on the use of adenovirus or plasmid as vehicles for gene delivery to the heart. These approaches have been limited by low transduction frequencies and transient transgene expression. We sought to determine whether adeno-associated virus produces more stable, higher efficiency gene expression in the rodent heart than did previous conventional methods. METHODS: Two recombinant viral constructs were made: an adeno-associated virus containing the lacZ gene under the control of the cytomegalovirus promoter (AAV-lacZ) and an adenovirus expressing lacZ under the control of the same promoter (Adeno-lacZ). Twenty rats were injected (into the ventricular apex) with 1 x 10(7-8) genomic particles of each virus. Animals were put to death at serial time points and transgene expression quantitated by beta-galactosidase activity, myocardial staining, and Western blot protein analysis. RESULTS: Three months after adeno-associated virus gene transfer, animals demonstrated stable beta-galactosidase expression in 60% of cardiomyocytes without evidence of myocardial inflammation/necrosis. The distribution and degree of protein expression and number of positive cells at 3 months were equivalent to transgene expression at 4 weeks. Adeno-associated virus was not detected in organs other than the heart. In contrast, Adeno-lacZ animals displayed transient beta-galactosidase activity in 60% of cardiomyocytes, which was undetectable 4 weeks after gene transfer. Adenovirus-treated animals manifest significant myocardial inflammation and had transgene expression in other organs. CONCLUSION: Direct intramyocardial injection of an adeno-associated virus vector programs stable, long-term, cardiac-specific transgene expression in the rodent heart for up to 3 months. Our results suggest adeno-associated virus has significant advantages for long-term transgene expression in the heart compared to adenovirus vectors.

Adenoviridae↗

PubMed2003

Tricuspid valvular disease in the patient with chronic pulmonary thromboembolic disease.

Chronic thromboembolic pulmonary hypertension is associated with right ventricular dilatation, high right-sided filling pressures, and functional tricuspid regurgitation. The tricuspid regurgitation resulting from this disease has been postulated to be caused by tricuspid annular dilatation with displacement of the papillary muscles. Pulmonary endarterectomy is an operation that corrects the pulmonary hypertension resulting from chronic thromboemboli. As a result of this operation, most patients show significant improvement in tricuspid valve function. Thus, pulmonary endarterectomy is one of the few cardiac operations in which surgery remote to a valve restores valve function. This review analyzes the factors responsible for changes in tricuspid valve regurgitation after pulmonary endarterectomy and provides a strategy to predict the small subset of patients who will not show improvement in tricuspid valve function after this operation.

Endarterectomy↗

PubMed2002

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.

Adult↗

PubMed2002

Operative classification of thromboembolic disease determines outcome after pulmonary endarterectomy.

OBJECTIVE: We sought to determine whether type and location of thromboembolic disease in the pulmonary vascular tree predicts the hemodynamic result and clinical outcome in patients undergoing pulmonary endarterectomy. METHODS: From 1998 to 2000, 202 patients with pulmonary hypertension and pulmonary vascular resistance ranging from 194 to 2950 dynes-s-cm(-5) underwent pulmonary endarterectomy. Preoperative and postoperative tricuspid valve function, pulmonary artery pressure, and pulmonary vascular resistance were determined by means of transthoracic echocardiography and measurements with a Swan-Ganz catheter (Edwards Lifesciences, Irvine, Calif), respectively. Patients underwent intraoperative classification of thromboembolism as follows: type 1 (76 patients), fresh thrombus in the main-lobar pulmonary arteries; type 2 (81 patients), intimal thickening and fibrosis proximal to the segmental arteries; type 3 (38 patients), disease within distal segmental arteries only; and type 4 (7 patients), distal arteriolar vasculopathy without visible thromboembolic disease. RESULTS: Overall perioperative mortality was 4.5% (9/202 patients). By means of univariate analysis, patients with type 3 or 4 disease (distal pulmonary vasculopathy) had more residual postoperative tricuspid regurgitation (P <.0001), higher postoperative pulmonary artery systolic pressure (P <.0001), and greater postoperative pulmonary vascular resistance (P <.0001) compared with that seen in patients with type 1 or 2 disease, in whom thromboembolic disease was more surgically accessible. Factors such as severity of preoperative tricuspid regurgitation, patient age, and circulatory arrest time had no correlation with postoperative hemodynamic improvement. Patients with distal thromboembolic disease (type 3-4) had higher perioperative mortality, required longer inotropic support, and had longer hospital stays compared with patients with type 1 or 2 thromboembolic disease. CONCLUSION: The degree of improvement in pulmonary hypertension and tricuspid regurgitation after pulmonary endarterectomy is determined by the type and location of pulmonary thromboembolic disease. Classification of thromboembolism is useful for predicting patient outcome after pulmonary endarterectomy.

Endarterectomy↗