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Biomedical subjects

D A Fullerton

Publications and source records attributed to D A Fullerton.

At least 73 records · Page 4Linked to original sources
PubMed1995

Lung transplantation with cardiopulmonary bypass exaggerates pulmonary vasomotor dysfunction in the transplanted lung.

Pulmonary vascular resistance is significantly increased in the transplanted lung. If cardiopulmonary bypass is required, the transplanted lung is reperfused with activated blood elements, which might exacerbate the reperfusion injury. The purpose of this study was to examine the influence of cardiopulmonary bypass on the following mechanisms of pulmonary vasomotor control in a dog model of autologous lung transplantation: (1) endothelium-dependent cyclic guanosine monophosphate-mediated relaxation (response to acetylcholine), (2) endothelium-independent cyclic guanosine monophosphate-mediated relaxation (response to nitroprusside), and (3) beta-adrenergic cyclic adenosine monophosphate-mediated relaxation (response to isoproterenol). Autologous right lung transplants were performed with (n = 4 dogs) and without (n = 5 dogs) bypass. Lungs were stored in cold saline solution (4 degrees C, 3 hours) before reimplantation. Pulmonary vasomotor control mechanisms were studied in isolated pulmonary arterial rings immediately after harvest and 1 hour after reimplantation. Ten rings were studied in each group at each time. Statistical analysis was by analysis of variance. Without bypass, endothelium-dependent cyclic guanosine monophosphate-mediated relaxation and beta-adrenergic cyclic adenosine monophosphate-mediated relaxation were significantly impaired, although endothelium-independent cyclic guanosine monophosphate-mediated relaxation was not. Use of bypass produced significantly greater impairment of both endothelium-dependent cyclic guanosine monophosphate-mediated relaxation and beta-adrenergic cyclic adenosine monophosphate-mediated relaxation. In addition, use of bypass produced significant dysfunction of endothelium-independent cyclic guanosine monophosphate-mediated relaxation as well. We conclude that using cardiopulmonary bypass to perform lung transplantation greatly exaggerates pulmonary vasomotor dysfunction in the transplanted lung. This dysfunction may contribute to significantly higher pulmonary vascular resistance in the transplanted lung if cardiopulmonary bypass is used.

Acetylcholine↗
PubMed1995

Selective inhibition of cyclic adenosine monophosphate-mediated pulmonary vasodilation by acute hypoxia.

BACKGROUND: Adult respiratory distress syndrome is characterized by hypoxia and acute pulmonary hypertension. Therefore we examined the effect of acute hypoxia on the mechanisms of pulmonary vasodilation. METHODS: Isolated rat pulmonary artery rings were suspended on tensiometers in a balanced salt solution. A normoxic gas mixture was bubbled through the solution (21% O2, 5% CO2, 74% N2). Rings were preconstricted with phenylephrine, and the following mechanisms of pulmonary vascular smooth muscle relaxation were studied in a random order: (1) endothelial-dependent cyclic guanosine monophosphate-mediated (acetylcholine, 10(-9) to 10(-6) mol/L), (2) endothelial-independent cyclic guanosine monophosphate-mediated (nitroprusside, 10(-9) to 10(-6) mol/L), and (3) beta-adrenergic receptor cyclic adenine monophosphate-mediated (isoproterenol, 10(-9) to 10(-6) mol/L). Separate rings were preconstricted with phenylephrine, and the gas was switched to a hypoxic mixture (0% O2, 5% CO2, 95% N2). After vasoconstriction to hypoxia reached a plateau, the response to the maximal effective dose of the above vasodilators (10(-6) mol/L) was determined in a random order. Statistical analysis was done with one-way analysis of variance with post hoc Bonferroni-Dunn correction. A p value of less than 0.05 was accepted as significant. RESULTS: Endothelial-dependent and -independent cyclic guanosine monophosphate-mediated relaxation was the same in normoxia and hypoxia. On the other hand, hypoxia inhibited beta-adrenergic receptor cyclic adenine monophosphate-mediated pulmonary vasorelaxation (97.5% +/- 2.5% versus 71.5% +/- 2.3% in hypoxia; p < 0.01). CONCLUSIONS: These data suggest that hypoxia selectively inhibits beta-adrenergic cyclic adenine monophosphate-mediated pulmonary vasorelaxation. This dysfunction of the normal mechanism of pulmonary vasodilation may contribute to the pulmonary hypertension seen in adult respiratory distress syndrome.

Acetylcholine↗
PubMed1995

Chronic posttraumatic thoracic aortic aneurysm presenting with dysphagia.

Chronic posttraumatic thoracic aortic aneurysms are rare. The natural history of these aneurysms is symptomatic enlargement. Herein is reported a chronic posttraumatic thoracic aortic aneurysm that became symptomatic by producing extrinsic compression of the esophagus. Despite the chronic nature of these aneurysms they should be repaired when found.

Adolescent↗
PubMed1995

Inhaled nitric oxide variably improves oxygenation and pulmonary hypertension in patients with acute respiratory distress syndrome.

OBJECTIVE: The purpose of this study was to determine the effect of inhaled nitric oxide (NO) on oxygenation, hemodynamics, and ventilation in patients with adult respiratory distress syndrome (ARDS). METHODS: Sixteen trials of inhaled NO were performed in 14 ARDS patients (age 42.9 +/- 6) who had significant pulmonary hypertension (mean pulmonary artery pressure > 30 mm Hg). Patients were monitored with arterial and pulmonary artery catheters. Volume ventilation was performed by a strict protocol. Data were collected at baseline and 30 minutes after 20 and 40 ppm NO. RESULTS: Overall, the Pao2/FIO2 ratio increased from 69.5 +/- 3.9 to 100.8 +/- 9.5 at 20 ppm, a 42.9 +/- 8.7% increase, and to 97.7 +/- 13.1 at 40 ppm, a 44.1 +/- 14.2% increase over baseline (p = 0.001). However, 5/16 trials demonstrated minimal improvement (Pao2/FIO2 ratio increase < 20%), 5 moderate improvement (20-50%), and 6 marked improvement (> 50%). Overall the mean pulmonary artery pressure (MPAP) decreased from 41.1 +/- 1.8 mm Hg to 34.3 +/- 1.3 at 20 ppm and 33.5 +/- 1.8 mm Hg at 40 ppm, a 15.0 +/- 3.7% decrease, p = 0.002. However, 5/16 trials demonstrated minimal improvement (MPAP decrease < 10%), 7 moderate improvement (10-20%), and 4 marked improvement (> 20%). At 40 ppm NO, 4 patients with moderate improvement in MPAP at 20 ppm NO had marked improvement. There were no changes in systemic oxygen delivery and consumption, intrapulmonary shunt, or lung compliance at 20 or 40 ppm (p > 0.05). Following collection of these data, prolonged NO inhalation (2-20 ppm) was done in 10 of 14 patients for 4.5 +/- 0.7 days (range 1-10 days). Overall, there were 7 deaths (mortality 50%). In patients receiving prolonged NO, there were 3 deaths (mortality 30%). All 4 patients who failed to respond to inhaled NO subsequently died (mortality 100%). CONCLUSIONS: Inhaled NO improves oxygenation and pulmonary hemodynamics in patients with ARDS. However, the improvement to NO is variable.

Adolescent↗
PubMed1995

Dysfunction of cGMP-mediated pulmonary vasorelaxation in endotoxin-induced acute lung injury.

Endothelial-dependent and -independent cGMP-mediated mechanisms of pulmonary vasorelaxation were studied in endotoxin-induced acute lung injury in the rat. Concentration-response curves were generated (10(-9) to 10(-6) M) for acetylcholine (ACh), A23187, and sodium nitroprusside (SNP) and for 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP) (10(-9) to 10(-4) M) in isolated pulmonary arterial rings preconstricted with phenylephrine 6 h after endotoxin treatment (20 mg/kg ip). Endotoxin treatment produced significantly increased lung neutrophil accumulation (myeloperoxidase assay, 28 +/- 6 units/g lung tissue vs. 1.8 +/- 1 in controls) and lung leakage (lung/blood 125I-labeled albumin ratio, 0.06 +/- 0.01 vs. 0.028 +/- 0.01 in controls) as well as histological evidence of pulmonary vascular endothelial damage. The concentration-response curves demonstrated that pulmonary vasorelaxation by mechanisms that require generation of cGMP by either endothelial-dependent (both receptor-dependent, ACh, and receptor-independent, A23187) or endothelial-independent (SNP) pathways were significantly impaired after endotoxin treatment. Relaxation by stimulation with the cGMP analogue 8-BrcGMP was not different from control. Pulmonary vascular smooth muscle is able to relax in response to cGMP after endotoxin treatment, but relaxation by endothelial-dependent and -independent pathways that require generation of cGMP is significantly impaired.

Acetylcholine↗
PubMed1995

Independent ventilation and ECMO for severe unilateral pulmonary edema after SLT for primary pulmonary hypertension.

Single lung transplantation (SLT) is now accepted therapy for selected cases of severe pulmonary hypertension. A recognized complication is the postoperative development of reperfusion edema in the graft, a potentially fatal cause of respiratory failure. Because reperfusion edema may be a reversible process, temporizing support measures can be life-saving. We report the case of a 48-year-old woman who developed severe reperfusion edema following right SLT for primary (unexplained) pulmonary hypertension. Extracorporeal membrane oxygenation (ECMO) was instituted. Independent lung ventilation was later begun and resulted in markedly improved oxygenation allowing withdrawal of ECMO. We conclude that reperfusion edema following SLT for pulmonary hypertension may be uniquely amenable to treatment with independent lung ventilation and ECMO if needed.

Extracorporeal Membrane Oxygenation↗
PubMed1994

Pulmonary vascular smooth muscle relaxation by cGMP- versus cAMP-mediated mechanisms.

The purpose of this study was to examine and compare pulmonary vascular smooth muscle relaxation by clinically used agents as related to cGMP mediation (sodium nitroprusside, nitroglycerin) and cAMP mediation (isoproterenol, prostaglandin E1 (PGE1), and amrinone) in isolated rat pulmonary arterial rings. Isolated rat pulmonary arterial rings were suspended on a fine wire tensiometer in individual organ chambers. After confirming the endothelial integrity of the rings (response to acetylcholine), the rings were preconstricted with phenylephrine 10(-6) M. Dose-response curves for sodium nitroprusside, nitroglycerin, isoproterenol, amrinone, and PGE1 were then generated. Each of these agents was tested on six rings. Each ring was tested with each agent in a random order. The doses of sodium nitroprusside, isoproterenol, and nitroglycerin required to produce relaxation of isolated pulmonary arterial rings were not statistically different, but were significantly less than those required by amrinone and PGE1 (P < 0.05). These data suggest that relaxation of pulmonary vascular smooth muscle is more readily achieved via cGMP by guanylate cyclase activation (sodium nitroprusside, nitroglycerin) and via beta-adrenergic cAMP mediation (isoproterenol) than via cAMP-mediated pathways requiring either prostaglandin receptor activation (PGE1) or phosphodiesterase inhibition (amrinone).

Alprostadil↗
PubMed1994

Transmission of Lactobacillus pneumonia by a transplanted lung.

Herein we report Lactobacillus pneumonia in a lung transplant recipient. The organism may have been normal flora in the donor but was a pathogen in the immunosuppressed recipient. Antibiotic therapy should include penicillin or clindamycin.

Anti-Bacterial Agents↗
PubMed1994

Use of pleural Tenckhoff catheter to palliate malignant pleural effusion.

Malignant pleural effusion and its treatment both cause substantial morbidity in patients with advanced neoplastic disease. We hypothesized that this morbidity might be ameliorated by placement of an indwelling Tenckhoff catheter into the involved pleural space. Catheters were placed in 9 patients under local anesthesia. Three patients underwent bilateral catheter placement, for a total of 12 catheters placed. Four of the 9 patients had undergone previous unsuccessful pleurodesis (using tetracycline or bleomycin). Whenever it became symptomatic, the malignant pleural effusion was simply drained into a calibrated container and the volume recorded. Patients were followed on a weekly basis until their death (mean, 16 weeks). The mean drainage was 477 mL per 24 hours (range, 200 to 1,100 mL). No pleural space infections occurred, although local cellulitis developed in 3 patients around the catheter exit site; all patients responded to oral antibiotics. There were no significant changes in either the serum albumin or total protein levels. No catheters malfunctioned and no patients required further treatment or hospitalization for symptoms of malignant pleural effusion. We conclude that this technique may reduce the morbidity stemming from malignant pleural effusion and its treatment by allowing patients to conveniently and painlessly drain the effusion at home when it becomes symptomatic. This technique may provide superior palliation in patients with malignant pleural effusion.

Adult↗
PubMed1994

Mechanisms of coronary vasomotor dysfunction in the transplanted heart.

The transplanted heart sustains both cold ischemic and reperfusion injuries. These can produce coronary vascular endothelial or smooth muscle injury or both, which, in turn, can produce coronary vasomotor dysfunction. Using a canine model of autologous heart transplantation, we examined the following coronary vasomotor control mechanisms in isolated coronary artery rings: (1) endothelial-dependent cyclic guanosine monophosphate (cGMP)-mediated vasorelaxation (response to acetylcholine); (2) endothelial-independent cGMP-mediated vasorelaxation (response to sodium nitroprusside); and (3) beta-adrenergic cyclic adenosine monophosphate (cAMP)-mediated vasorelaxation (response to isoproterenol hydrochloride). Further, these mechanisms were related to 3 hours of cold ischemia alone and to 3 hours of cold ischemia plus 1 hour of reperfusion. Autologous heart transplantation was performed in dogs, and isolated distal left anterior descending coronary artery rings were studied in individual organ chambers. Cold ischemia alone produced significant dysfunction of beta-adrenergic cAMP-mediated vasorelaxation, which was exacerbated after reperfusion. Neither endothelial-dependent nor endothelial-independent cGMP-mediated vasorelaxation was dysfunctional after cold ischemia alone, but both were significantly impaired after reperfusion. We conclude that cold ischemia and reperfusion each produce coronary vasomotor dysfunction in the transplanted heart. Cumulatively, such coronary vasomotor dysfunction can acutely impair coronary vasodilatation and potentially jeopardize myocardial blood flow in the transplanted heart.

Acetylcholine↗
PubMed1994

Adenosine A1-receptor mechanisms antagonize beta-adrenergic pulmonary vasodilation in hypoxia.

Hypoxic pulmonary vasoconstriction is refractory to beta-adrenergic receptor (beta-AR)-mediated pulmonary vasodilation. We hypothesized that hypoxic pulmonary arteries release adenosine (Ado) that antagonizes beta-AR-mediated pulmonary vasodilation. Using isolated rat pulmonary artery rings, we investigated 1) the effect of hypoxia and exogenous Ado on beta-AR-mediated pulmonary vasodilation, 2) the intracellular site of dysfunctional beta-AR-mediated pulmonary vasodilation in hypoxia, and 3) the Ado receptor subtype responsible for dysfunction of beta-AR-mediated pulmonary vasodilation. Hypoxia attenuated normal beta-AR-mediated pulmonary vasodilation to isoproterenol (97.5 +/- 0.8 vs. 71.5 +/- 2.3%, P < 0.01). In contrast, forskolin induced the same vasorelaxation in hypoxic pulmonary rings as controls (P = 0.09). Incubation of normoxic rings with Ado attenuated the vasorelaxation response induced by beta-AR stimulation (71.5 +/- 5.9%, P < 0.01), similar to the effect observed in hypoxia. Both nonspecific Ado receptor blockade (8-sulfophenyl-theophylline) and specific A1-receptor blockade (8-cyclopentyl-1,3-dimethylxanthine) restored the vasorelaxation response of hypoxic rings induced by beta-AR stimulation (93.3 +/- 2.3 and 92.2 +/- 2.8%, P < 0.01). The effects of hypoxia and Ado were reproduced by a specific A1 agonist (2-chloro-N6-cyclopentyladenosine), demonstrating impaired vasorelaxation induced by beta-AR stimulation in normoxia (70.6 +/- 4.5%, P < 0.01). From these data, we conclude that hypoxia antagonizes beta-AR-mediated pulmonary vasodilation via an Ado A1-receptor mechanism.

Adenosine↗
PubMed1994

Protection of the patent internal mammary artery by-pass graft from subsequent sternotomy.

OBJECTIVE: We describe a technique to protect the patent internal mammary artery graft from injury by repeat sternotomy. INTERVENTIONS: The internal mammary artery is dissected as far proximally as possible. The left pleural space is opened widely thus allowing the left lung to protrude through the pleural defect once mechanical ventilation is resumed. The left lung is then interposed between the internal mammary graft and the sternum. The internal mammary artery is thereby protected from adherence to the sternum and injury upon resternotomy. RESULTS: In two patients in whom this technique was employed repeat sternotomy was easily performed without injury to the internal mammary artery. CONCLUSIONS: This simple technique effectively protects the patent internal mammary artery bypass graft from injury at subsequent sternotomy.

Humans↗
PubMed1994

Use of cytomegalovirus (CMV) hyperimmune globulin for prevention of CMV disease in CMV-seropositive lung transplant recipients.

Our data suggest that CMVIG in combination with ganciclovir effectively reduces the incidence, and delays the onset of CMV infections in seropositive lung transplant recipients. In addition, its use may be associated with less severe CMV infection and a lower incidence of bacterial or fungal opportunistic infection. Although the number of patients in the study is small, high-titer CMVIG may be more effective than standard titer immunoglobulin in the prevention of CMV disease in lung transplant recipients. Several questions remain in addition to these: What is the optimal dosage and duration of treatment with CMVIG for prophylaxis of CMV infection and disease in lung transplant recipients; Is this strategy cost-effective; Will it reduce the incidence of obliterative bronchiolitis following lung transplantation and enhance allograft survival? A prospective, random-assignment trial is warranted to answer these questions.

Acyclovir↗
PubMed1993

Male donor into female recipient increases the risk of pediatric heart allograft rejection.

Sixty-one infants and children, 12 years old or younger, who received an orthotopic cardiac allograft between November 1985 and December 1989 were analyzed for the incidence of rejection. Rejection was diagnosed non-invasively within the first 3 months and during the first year. Rejection episodes were diagnosed by signs and symptoms according to previously reported criteria. Multiple regression analysis with recipient age, donor age, donor-recipient weight ratio, number of HLA mismatches, sex of the recipient, sex-encoded minor tissue antigen incompatibility (H-Y: female recipients receiving male donor organ), graft ischemic time, lowest cyclosporine level during the first 2 postoperative weeks, and prophylactic use of OKT3 showed that H-Y was the only significant contributing factor for rejection at 3 months and 1 year (r = 0.308, p < 0.02; r = 0.308, p < 0.02; respectively). Patients were divided into two groups: group 1, 45 patients who were H-Y compatible (male and female recipients receiving female donor hearts); and group 2, 16 patients who were H-Y incompatible (female recipients with male hearts). Patients in group 2 had significantly more episodes of graft rejection than did patients in group 1 by 3 months and by 12 months after heart transplantation (3 months: 2.75 +/- 1.48 versus 1.67 +/- 1.41, p < 0.05; 1 year: 4.80 +/- 1.87 versus 2.59 +/- 1.93, p < 0.01; respectively). There were six grafts lost due to rejection in group 2 (6/15, 37.5%) and 7 grafts lost (7/45, 15.5%) in Group 1 (not significant). Heart transplantation with H-Y incompatibility resulted in a significantly greater incidence of rejection episodes.

Child↗
PubMed1993

Hemodynamic advantage of left atrial epinephrine administration after cardiac operations.

Cardiac surgical patients frequently require catecholamines, typically administered via the central venous circulation. Potential disadvantages of this route of administration include catecholamine metabolism by the pulmonary vascular bed before gaining access to the heart and pulmonary vasoconstriction producing increased pulmonary vascular resistance. We therefore prospectively compared administration of epinephrine via the left atrium versus central venous administration of epinephrine with particular interest in cardiac output, mean pulmonary artery pressure, and pulmonary vascular resistance. Fifteen consecutive aortocoronary bypass patients were studied after cardiopulmonary bypass. Epinephrine (mean dose, 0.07 +/- 0.02 micrograms.kg-1.min-1) was administered via the central venous route, then via the left atrium, then via the central venous route again. Hemodynamic data were collected 10 minutes after changing the route of administration. Left atrial administration of epinephrine produced a 35% greater cardiac output, 25% lower pulmonary artery pressure, and 32% lower pulmonary vascular resistance when compared with central venous administration (all significant; p < 0.05). Left atrial epinephrine administration may offer hemodynamic advantage in cardiac surgical patients in whom central venous administration does not produce an adequate cardiac output or in patients with pulmonary hypertension to avoid any further increase in pulmonary vascular resistance.

Aged↗