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V A Starnes

Publications and source records attributed to V A Starnes.

At least 19 recordsLinked to original sources
PubMed1999

RNA antisense abrogation of MAT1 induces G1 phase arrest and triggers apoptosis in aortic smooth muscle cells.

The human MAT1 gene (ménage à trois 1) is an assembly factor and a targeting subunit of cyclin-dependent kinase (CDK)-activating kinase. The novel mechanisms by which MAT1 forms an active CDK-activating kinase and determines substrate specificity of CDK7-cyclin H are involved in the cell cycle, DNA repair, and transcription. Hyperplasia of vascular smooth muscle cells (SMC) is a fundamental pathologic feature of luminal narrowing in vascular occlusive diseases, and nothing is yet known regarding the cell cycle phase specificity of the MAT1 gene in its involvement in SMC proliferation. To investigate such novel regulatory pathways, MAT1 expression was abrogated by retrovirus-mediated gene transfer of antisense MAT1 RNA in cultured rat aortic SMCs. We show that abrogation of MAT1 expression retards SMC proliferation and inhibits cell activation from a nonproliferative state. Furthermore, we have demonstrated that these effects are due to G1 phase arrest and apoptotic cell death. Our studies indicate a link between cell cycle control and apoptosis and reveal a potential mechanism for coupling the regulation of MAT1 with G1 exit and prevention of apoptosis.

Animals↗
PubMed1999

A comparison of the new preservation solution Celsior to Euro-Collins and University of Wisconsin solutions in lung reperfusion injury.

BACKGROUND: The lung is particularly susceptible to reperfusion injury, both experimentally and clinically after transplantation. The extracellular-type preservation solution Celsior, which has been predominantly studied in cardiac preservation, has components designed to prevent cell swelling, free radical injury, energy depletion, and calcium overload. Using an isolated blood-perfused rat lung model, we investigated whether Celsior would decrease preservation injury and improve lung function after cold ischemic storage and reperfusion compared to Euro-Collins (EC) and University of Wisconsin (UW) solutions. METHODS: Lewis rat lungs were isolated, flushed with the respective cold preservation solution, and then stored at 4 degrees C for 6 or 12 hr. After ischemic storage, the lung block was suspended from a force transducer, ventilated with 100% O2, and reperfused for 90 min with fresh blood via a cannula in the pulmonary artery. Lung compliance, alveolar-arterial oxygen difference, and outflow oxygen tension were all measured. The capillary filtration coefficient (Kf), a sensitive measure of changes in microvascular permeability, was determined. RESULTS: For 6 hr of cold storage, lungs stored in Celsior had lower Kf values than those stored in EC, indicating decreased microvascular permeability. No other significant differences were noted between Celsior and EC or UW. For 12 hr of cold storage, Celsior provided increased oxygenation, decreased alveolar-arterial O2 differences, increased compliance, and decreased Kf values as compared to both EC and UW. CONCLUSIONS: Celsior provides better lung preservation than EC or UW as demonstrated by increased oxygenation, decreased capillary permeability, and improved lung compliance, particularly at 12-hr storage times. These results are highly relevant, inasmuch as EC and UW are the most common clinically used lung preservation solutions. Further studies of Celsior in experimental and clinical lung transplantation, as well as in other solid organs, are indicated.

Adenosine↗
PubMed1999

Addition of a water-soluble alpha-tocopherol analogue to University of Wisconsin solution improves endothelial viability and decreases lung reperfusion injury.

BACKGROUND: Reperfusion injury following lung preservation has been associated with free radical formation and subsequent endothelial cell damage. Trolox is a water-soluble analogue of the free radical scavenger alpha-tocopherol. We hypothesized that addition of this form of vitamin E to University of Wisconsin (UW) solution would decrease reperfusion injury and improve lung function after cold ischemic preservation. MATERIALS AND METHODS: Bovine aortic endothelial cells were cultured and stored at 4 degrees C for 12, 24, and 48 h in UW or UW + Trolox (UWT). Endothelial cell viability after storage was assessed by dimethylthiazole tetrazolium cytotoxicity assay. An isolated rat perfused lung (IPL) model was used and lungs were flushed with the respective solutions with cold storage times of 6 and 12 h. Following storage, the lungs were reperfused with fresh blood and lung function was assessed by blood gas analysis, alveolar-arterial gradient, and compliance. RESULTS: There was no difference in endothelial cell viability between UW and UWT after 12 or 24 h; however, UWT had higher endothelial cell viability than UW with 48 h of cold ischemic storage. Using the IPL model, the pO2 was higher with UWT than UW after 6 and 12 h of cold ischemia. The alveolar-arterial oxygen difference was significantly lower for UWT versus UW at 6 h. UWT provided increased compliance at 6 and 12 h of ischemia. CONCLUSIONS: The addition of a water-soluble vitamin E analogue to UW solution resulted in increased endothelial cell viability after prolonged storage and improved whole lung preservation in the postreperfusion period as evidenced by higher oxygenation and increased compliance. These results are clinically relevant as the lung is extremely sensitive to reperfusion injury and UW solution is being increasingly used in lung transplantation and remains the predominant solution in abdominal organ transplantation.

Adenosine↗
PubMed1999

Indwelling catheter-induced right ventricular rupture.

We describe a case of a 68-year-old man who, because of postoperative mediastinitis, underwent a multiple muscle flap closure of the mediastinum. A chronic indwelling catheter led to erosion and rupture of the anterior wall of the right ventricle. The near exsanguinating hemorrhage was corrected under circulatory arrest. A pericardial patch repair was performed with good results.

Aged↗
PubMed1999

Sirolimus (rapamycin) potentiates cyclosporine in prevention of acute lung rejection.

BACKGROUND: Cyclosporine-based immunosuppressive regimens (INN: ciclosporin) in human lung transplantation continue to result in a high incidence of acute cellular rejection. We investigated the use of sirolimus, a macrolide with structural similarity to tacrolimus, as monotherapy and in combination with cyclosporine in a rodent lung transplant model. METHODS: Orthotopic left lung transplantation was performed in Lewis recipients from Brown-Norway donor rats with syngeneic Lewis-to-Lewis controls. Open biopsies were performed on postoperative day 7, and the severity of acute lung rejection was graded by a pathologist blinded to the protocol. RESULTS: All recipients survived despite the amount of acute rejection seen on examination of the biopsy tissue. Lewis-to-Lewis isografts demonstrated near normal pulmonary architecture. Allogeneic recipients receiving high-dose cyclosporine (25 mg/kg) monotherapy showed mild to moderate acute rejection with some perivascular focal interstitial infiltrates. Recipients receiving low-dose cyclosporine (5 mg/kg) monotherapy or low- or high-dose sirolimus (0.5 or 2.0 mg/kg, respectively) monotherapy demonstrated massive cellular infiltration leading to necrosis and infarction and could not be graded. However, the addition of low-dose sirolimus (0.5 mg/kg) to low-dose cyclosporine (5 mg/kg) demonstrated a significant potentiating immunosuppressive effect, and the addition of high-dose sirolimus (2.0 mg/kg) to low-dose cyclosporine (5.0 mg/kg) demonstrated an even greater effect, with rejection scores better than those obtained with high-dose cyclosporine monotherapy and similar to those obtained with isografts. CONCLUSIONS: This study demonstrates that low-dose sirolimus has a cyclosporine-sparing effect and that a higher dose of sirolimus in combination with cyclosporine strongly protects lung allografts from acute cellular rejection. These results suggest that sirolimus may be indicated as an adjunct to current cyclosporine-based immunosuppressive regimens in clinical lung transplantation.

Acute Disease↗
PubMed1999

Impact of respiratory syncytial virus infection on surgery for congenital heart disease: postoperative course and outcome.

OBJECTIVES: a) To describe the postoperative course and outcome of cardiac surgery in children with recent respiratory syncytial virus (RSV) infection; and b) to evaluate whether timing of surgery has any impact on the outcome. DESIGN: Retrospective case series. SETTING: Intensive care unit and medical and surgical wards of a teaching pediatric hospital. PATIENTS: Twenty-five children (aged 25 days to 3.5 yrs; median, 4 months) with congenital heart disease who had cardiac surgery within 6 months after RSV infection. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We reviewed the clinical course and outcome of all patients. The cardiac diagnoses included ventricular septal defect (n = 11), tetralogy of Fallot (n = 3), atrioventricular canal (n = 3), and others (n = 8). Thirteen patients had surgery during the same admission as RSV infection (group I), and 12 patients had surgery electively after being discharged to home after RSV infection (group II). Two patients in group I died; both of these patients had undergone total repair of tetralogy of Fallot within 2 wks after admission for RSV infection. Postoperative complications in group I patients included pulmonary hypertension (n = 5), adult respiratory distress syndrome (n = 1), tracheal stenosis (n = 1), left ventricular dysfunction (n = 1), pericardial effusion (n = 1), secondary bacterial or fungal infection (n = 7), and deep venous thrombosis (n = 1). Of all group I patients, the ones who were operated on early appeared to be at higher risk for complications, especially for postoperative pulmonary hypertension. No patient in group II died, and only two patients had minor complications (one had reactive airway disease, and the other had a transient superior vena cava syndrome after a bidirectional Glenn operation). CONCLUSIONS: Cardiac surgery performed during the symptomatic period of RSV infection is associated with a high risk of postoperative complications, especially postoperative pulmonary hypertension. These complications appeared to be more frequent and of greater severity in patients who had earlier surgery compared with those who had later surgery. More studies are needed regarding the proper timing of cardiac surgery in patients with congenital heart disease and RSV infection.

Cardiac Surgical Procedures↗
PubMed1998

Addition of aprotinin to organ preservation solutions decreases lung reperfusion injury.

BACKGROUND: Organ preservation injury is associated with endothelial cell damage, destabilization of mitochondrial and cell membranes, and the release of proteolytic enzymes. In addition to its well-known clinical effect of reducing perioperative blood loss, aprotinin has antiproteolytic and membrane-stabilizing properties. We hypothesized that adding aprotinin to Euro-Collins (EC) and University of Wisconsin (UW) solutions would decrease preservation injury in cultured endothelial cells and a whole organ rat lung model. METHODS: Bovine aortic endothelial cells were cultured and stored in the respective solution at 4 degrees C for 12 or 48 hours. Endothelial cell viability after storage was assessed by dimethylthiazole tetrazolium cytotoxicity assay. In the whole organ model, rat lungs were isolated, flushed with the respective solution, and stored at 4 degrees C for 6 or 12 hours. The lungs were ventilated with 100% O2 and reperfused with fresh blood. Alveolar-arterial O2 difference, O2 tension, capillary filtration coefficient, and compliance were determined. RESULTS: Endothelial cell viability was optimized with the addition of aprotinin to EC and UW at a dose of 150 KIU/mL (0.02 mg/mL). In the isolated perfused lung model, after 6 hours of ischemic storage, aprotinin-enhanced (100 KIU/mL [0.014 mg/mL]) EC and UW decreased alveolar-arterial O2 difference, increased O2 tension, and decreased capillary filtration coefficient compared with EC and UW alone. After 12 hours of ischemic storage, aprotinin-enhanced EC and UW decreased alveolar-arterial O2 difference, increased O2 tension, decreased capillary filtration coefficient, and increased compliance compared with EC and UW alone. CONCLUSIONS: The addition of aprotinin to EC and UW solutions increases endothelial cell viability in hypoxic cold storage conditions. In terms of whole organ function, aprotinin improves lung preservation as demonstrated by increased oxygenation and compliance, and decreased capillary permeability. This study is clinically applicable as there is already extensive experience with the use of aprotinin in heart and lung transplant recipients, in addition to its routine use in conventional cardiac operations.

Adenosine↗
PubMed1998

Elective transplant pneumonectomy.

The use of a single lung transplant, modified with removal of the middle lobe of the donor right lung, has been described for a term neonate with respiratory distress secondary to right-sided congenital diaphragmatic hernia. The successful transplant allowed the patient to be successfully weaned from extracorporeal membrane oxygenation. Because of the early age of the patient at transplantation (3 weeks), it was unclear how the patient's left lung would develop, and there was uncertainty regarding the risk of life-time immunosuppression. By the age of 4 years, 10 months, she was demonstrating some failure to thrive, hypertension, and hirsutism, obvious side effects of chronic immunosuppression. The question was raised as to the potential for transplant pneumonectomy. A ventilation-perfusion scan demonstrated a decrease of right lung ventilation compared with the immediate postoperative period (27% versus 43%); right heart catheterization with balloon occlusion of the right main pulmonary artery suggested that the patient would tolerate right pneumonectomy. After discussion with the family, the patient underwent transplant pneumonectomy via a right posterolateral approach. Findings at the time of operation included mild to moderate adhesions as well as recurrence of the diaphragmatic hernia. She tolerated the procedure well and was discharged home on the fifth postoperative day with cessation of her immunosuppression. The immediate and medium-term success of this procedure suggests the potential for temporizing transplantation as a palliation to promote survival until the remaining native lung can provide sufficient ventilation.

Child, Preschool↗
PubMed1998

Addition of a mast cell stabilizing compound to organ preservation solutions decreases lung reperfusion injury.

OBJECTIVE: Research in lung transplant preservation has generally focused on free radicals and enzyme release from neutrophils, parenchymal cells, macrophages, and endothelium. The lung has a large resident population of mast cells that, when activated, release potent inflammatory mediators. We hypothesized that adding an inhibitor of mast cell degranulation, lodoxamide tromethamine (10 micromol/L), to Euro-Collins and University of Wisconsin preservation solutions, would decrease lung preservation injury. METHODS: Rat lungs were isolated, flushed with the respective solution, and stored at 4 degrees C for 6 or 12 hours. The lungs were reperfused with fresh blood and ventilated with 100% oxygen. Alveolar-arterial oxygen difference, oxygen tension, capillary filtration coefficient, and compliance were determined. RESULTS: After 6 hours of ischemic storage: lodoxamide tromethamine-enhanced Euro-Collins solution decreased alveolar-arterial oxygen difference from 539 to 457 (p = 0.004), increased oxygen tension from 119 to 205 mm Hg (p = 0.006), and decreased capillary filtration coefficient from 3.9 to 2.0 (p < 0.001); lodoxamide tromethamine-enhanced University of Wisconsin solution decreased alveolar-arterial oxygen difference from 546 to 317 (p < 0.001), increased oxygen tension from 166 to 335 mm Hg (p < 0.001), and decreased capillary filtration coefficient from 3.0 to 1.7 (p < 0.001). After 12 hours of ischemic storage, lodoxamide tromethamine-enhanced Euro-Collins solution decreased alveolar-arterial oxygen difference from 588 to 485 (p < 0.001), increased oxygen tension from 100 to 161 mm Hg (p = 0.012), decreased capillary filtration coefficient from 6.2 to 2.6 (p < 0.001), and increased compliance from 0.12 to 0.21 (p < 0.001); lodoxamide tromethamine-enhanced University of Wisconsin solution decreased alveolar-arterial oxygen difference from 478 to 322 (p < 0.001), increased oxygen tension from 214 to 335 mm Hg (p < 0.001), decreased capillary filtration constant from 4.2 to 2.0 (p < 0.001), and increased compliance from 0.20 to 0.25 (p < 0.001). CONCLUSIONS: Addition of lodoxamide tromethamine to Euro-Collins or University of Wisconsin solution results in a marked decrease in lung reperfusion injury as demonstrated by increased oxygenation, decreased microvascular permeability, and increased compliance. These results are relevant as Euro-Collins and University of Wisconsin solutions are the most common clinically used lung preservation solutions. This study also highlights the deleterious role of resident mast cells in preservation injury.

Animals↗
PubMed1998

Aortic intramural hematoma presenting as angina.

We present a case of intramural hematoma initially misdiagnosed as angina, and requiring myocardial revascularization. Angiography failed to lead to the proper diagnosis and the original transesophageal echocardiogram was misinterpreted as showing an intimal flap that was actually an echocardiographic artifact. The echocardiographic characteristics and implications of this entity are reviewed.

Aged↗
PubMed1998

Living donor lobar lung transplantation: the pediatric experience.

Living donor (LD) lobar lung transplantation is now an accepted alternative to cadaveric lung transplantation in selected patients with end-stage lung disease. This study reviews the Childrens Hospital Los Angeles LD experience of 17 patients (mean 13.2 +/- 2.7 yrs; range 9.3-18.5 yrs). 12 LD patients had end-stage cystic fibrosis, 4 had primary pulmonary hypertension, and 1 child had bronchiolitis obliterans. LD candidates must meet the same criteria as for cadaveric lung transplant candidates. Donor candidates are rigorously screened (physically and psychologically) prior to acceptance for lobectomy. LD patients receive the same triple immunosuppression regimen as our cadaveric recipients (prednisone, cyclosporine/FK506, and azathioprine/mycophenolate). Comparison of rejection episodes, incidence of bronchiolitis obliterans, pulmonary function tests, exercise stress tests, and cardiac catheterization data was made between LD and cadaveric lung transplantation (CL) pediatric recipients. Donor outcomes were also reviewed. In our pediatric program, the 1-year survival rate for LD recipients is currently 81%, which compares favorably with the ISHLT average of 70% for pediatric transplant patients. The incidence of rejection is about the same for LD and CL recipients, but the episodes are less severe for pediatric LD patients. There have been no histological cases of bronchiolitis obliterans syndrome in our LD recipients. Although there have been questions as to whether transplanted lobes can supply comparable pulmonary reserve to whole cadaveric lungs, the lung volumes (TLC and VC), expiratory flow rates, maximal exercise stress tests, and pulmonary artery pressures (no evidence of pulmonary hypertension) in LD patients are not significantly different to CL recipients in our institution. Besides pain from the thoracotomy, the donors have a decrease of 16% (right lower lobe donor) and 18% (left lower lobe donor) in their vital capacity. Otherwise, there have been no major complications to the donors and most have resumed their usual activities. Based on outcomes, pulmonary function tests, exercise stress tests, and hemodynamic studies as well as low donor morbidity, living donor double lobar lung transplantation is a viable alternative to cadaveric lung transplantation in selected pediatric patients with end-stage lung disease.

Adolescent↗
PubMed1998

Combined carotid endarterectomy and coronary artery bypass grafting in asymptomatic carotid artery stenosis.

The role of combined carotid endarterectomy (CEA) and coronary artery bypass grafting (CABG) in patients with severe asymptomatic carotid artery disease and concurrent symptomatic coronary artery disease is controversial. The objective of this report is to investigate the safety of combined CEA/CABG. The medical records of 30 patients who underwent combined CEA/CABG for coexistent asymptomatic carotid and symptomatic coronary artery occlusive disease were reviewed. All patients were scheduled for either elective or urgent myocardial revascularization due to their symptomatic coronary artery disease. Color-flow duplex scanning identified internal carotid artery stenosis of 80 to 99 per cent in 28 patients (93%) and 50 to 79 per cent in 2 patients (7%). Seventeen patients (57%) were male. The mean age was 64 +/- 10 years (range, 42-84 years). Contralateral internal carotid artery occlusion was present in four patients. Severe left main coronary artery disease was present in 12 patients (40%) and 7 patients (23%) had an ejection fraction of less than 50 per cent. There were no perioperative deaths or strokes. One patient suffered a myocardial infarction on postoperative day 1. This study demonstrates the safety of combined CEA/CABG for coexistent coronary and asymptomatic carotid disease. Using this surgical approach for critical coexistent disease may minimize the incidence of perioperative cerebrovascular complications in patients undergoing CABG.

Adult↗
PubMed1997

Targeting retroviral vectors to vascular lesions by genetic engineering of the MoMLV gp70 envelope protein.

Targeted gene delivery to vascular lesions is a major challenge in the development of gene therapy protocols for cardiovascular diseases. One approach would be to enable retroviral vectors to accumulate at sites of vascular injury and enhance local vector concentration. An early step in wound repair is the adhesion of platelets to collagen exposed from damaged vasculature. Hence, the Moloney murine leukemia virus (MoMLV) envelope (env) protein was engineered to incorporate a high-affinity collagen-binding domain derived from von Willebrand clotting factor, and expressed in Escherichia coli and in mammalian cells. The chimeric env protein bound tightly to collagen, and virions bearing this collagen-binding env protein exhibited viral titers approaching those of virions expressing wild-type (WT) env protein. The chimeric virions were concentrated on collagen matrices, and they retained their infectivity under conditions in which virions bearing WT env protein were washed away. Targeted delivery of the chimeric env protein to injured mouse aorta and selective binding of the collagen-targeted virions to injured rabbit artery were observed. In comparative studies, vascular smooth muscle cell transduction was demonstrated in catheter-injured carotid arteries following infusion of collagen-targeted virions but not of virions bearing WT env protein. Taken together, these observations demonstrate the ability of collagen-targeted virions to localize gene delivery to sites of vascular injury.

3T3 Cells↗
PubMed1997

Downregulation of cyclin G1 expression by retrovirus-mediated antisense gene transfer inhibits vascular smooth muscle cell proliferation and neointima formation.

BACKGROUND: The contemporary treatment of coronary athero-occlusive disease by percutaneous transluminal coronary angioplasty is hampered by maladaptive wound healing, resulting in significant failure rates. Morbid sequelae include smooth muscle cell (SMC) hyperplasia and restenosis due to vascular neointima formation. METHODS AND RESULTS: In this study, we examined the inhibitory effects of a concentrated retroviral vector bearing an antisense cyclin G1 gene on aortic SMC proliferation in vitro and on neointima formation in vivo in a rat carotid injury model of restenosis. Retroviral vectors bearing an antisense cyclin G1 construct inhibited the proliferation of transduced aortic SMCs in 2- to 6-day cultures, concomitant with down-regulation of cyclin G1 protein expression and decreased [3H]thymidine incorporation into DNA. Morphological examination showed evidence of cytolysis, giant syncytia formation, and apoptotic changes evidenced by overt cell shrinkage, nuclear fragmentation, and specific immunostaining of nascent 3'-OH DNA ends generated by endonuclease-mediated DNA fragmentation. Pronounced "bystander effects" including neighboring cells were noted in aortic SMCs transduced with the antisense cyclin G1 vector, as determined by quantitative assays and fluorescent labeling of nontransduced cells. In an in vitro tissue injury model, the proliferation and migration of antisense cyclin G1 vector-transduced aortic SMCs were inhibited. Moreover, in vivo delivery of high-titer antisense cyclin G1 vector supernatant to the balloon-injured rat carotid artery in vivo resulted in a significant reduction in neointima formation. CONCLUSIONS: These findings represent the first demonstration of the inhibitory effects of an antisense cyclin G1 retroviral vector on nonneoplastic cell proliferation. Taken together, these data affirm the potential utility of antisense cyclin G1 constructs in the development of novel gene therapy approaches to vascular restenosis.

Animals↗
PubMed1997

Continuous versus intermittent furosemide infusion in critically ill infants after open heart operations.

BACKGROUND: Use of intravenous furosemide is generally avoided in critically ill neonates and infants soon after open heart operations to prevent fluctuations in intravascular volume and resulting circulatory instability. METHODS: To assess and compare the safety and efficacy of continuous versus intermittent intravenous furosemide, we undertook a prospective, randomized trial in 26 consecutive patients less than 6 months of age. Inclusion criteria were presence of low-output syndrome requiring inotropic support (24/26 patients) or pulmonary hypertension requiring vasodilator therapy (10/26 patients) within 6 hours of discontinuation of cardiopulmonary bypass. Eleven patients received 0.1 mg x kg(-1) x h(-1) continuous intravenous furosemide (group 1) and 15 received 1 mg/kg bolus every 4 hours (group 2) for 24 hours. Mean age (3.7 +/- 3.4 versus 1.8 +/- 2.5 months) and weight (4.6 +/- 2.1 versus 4.3 +/- 1.7 kg) were comparable. RESULTS: Group 2 infants showed slightly greater absolute urinary output (2.5 +/- 1.1 mL/kg per hour versus 3.3 +/- 1.1 mL/kg per hour, p = 0.05). However, urinary output per dose of drug was significantly larger in group 1 infants (1.0 +/- 0.4 versus 0.5 +/- 0.2 mL x kg(-1) x h(-1); p = 0.002) with lesser fluctuations (variance, 1.9 +/- 1.6 versus 3.8 +/- 2.1; p = 0.02) and fluid replacement needs (20.6 +/- 3.8 versus 51.8 +/- 14.4; p = 0.001). Electrolyte replacement requirements were similar. A trend toward greater hemodynamic instability in group 2 patients (heart rate variance 88.4 +/- 79.8 versus 128.3 +/- 82.7; p = 0.09; central venous pressure variance 2.8 +/- 1.90 versus 4.1 +/- 3.7; p = 0.07; mixed venous oxygen saturation variance, 32.3 +/- 27.6 versus 45.7 +/- 20.4; p = 0.06) was noted. All patients who completed the study protocol survived operation and were discharged home. CONCLUSIONS: We conclude that (1) commonly used doses of both intermittent and continuous intravenous furosemide infusion can be safely administered to critically ill neonates and infants as early as 6 hours after operation, (2) continuous infusion yields an almost comparable urinary output with a much lower dose of furosemide, and (3) intermittent administration is associated with greater fluctuations in urinary output and greater needs for fluid replacement therapy.

Cardiac Output, Low↗
PubMed1997

Experience with living-donor lobar transplantation for indications other than cystic fibrosis.

OBJECTIVE: Since development of a living donor bilateral lobar transplantation protocol for patients with cystic fibrosis, our indications have expanded to include recipients with other diagnoses. METHODS: We report on our experience in eight patients with primary pulmonary hypertension, postchemotherapy pulmonary fibrosis, bronchopulmonary dysplasia, idiopathic pulmonary fibrosis, and obliterative bronchiolitis. The average age of the eight patients was 19.1 years (range 9 to 40). The mean preoperative carbon dioxide tension for the four patients who did not have primary pulmonary hypertension was 92 mm Hg (range 64 to 120 mm Hg), and the two patients with pulmonary fibrosis were intubated (one on high-frequency jet ventilation). Each recipient received a right lower lobe (n = 7) or middle lobe (n = 1) and a left lower lobe (n = 8) from a total of 16 donors representing various combinations of the recipient's family (n = 15) and an unrelated friend (n = 1). RESULTS: With an average follow-up of 1 year the overall survival is 75%. For the five patients followed up for at least 1 year, mean forced vital capacity was 80.6%, forced expiratory volume in 1 second was 75.6%, mid-forced expiratory flow was 64%, and diffusing lung capacity corrected for alveolar volume was 73% of predicted. For those patients with primary pulmonary hypertension, preoperative hemodynamics revealed mean pressures as follows: blood pressure 84.8 mm Hg, right atrial pressure 7.8 mm Hg, pulmonary artery pressure 71.3 mm Hg, pulmonary capillary wedge pressure 9.5 mm Hg, cardiac index 2.9 L/min per square meter, and pulmonary vascular resistance index 22.8 Wood units. Postoperative hemodynamics revealed a mean blood pressure of 84.3 mm Hg, right atrial pressure of 2.7 mm Hg, pulmonary artery pressure of 16 mm Hg, pulmonary capillary wedge pressure of 7.3 mm Hg, cardiac index of 4.2 L/min per square meter, and pulmonary vascular resistance index of 1.9 Wood units. CONCLUSIONS: Early results of living-donor bilateral lobar transplantation for diseases other than cystic fibrosis have resulted in satisfactory survival and pulmonary function. Additionally, patients with severe primary pulmonary hypertension have had dramatic normalization of their hemodynamics despite the limited amount of lung tissue transplanted. We believe that the data from this small cohort experience compares favorably with our larger series with cystic fibrosis and supports an expanded role for living-donor lobar transplantation in patients with alternate indications.

Adult↗