Biomedical subjects

R E Michler

Publications and source records attributed to R E Michler.

At least 109 records · Page 6Linked to original sources

PubMed1995

Absence of hyperacute rejection in newborn pig-to-baboon cardiac xenografts.

The shortage of organs for transplantation is especially severe for the critically ill newborn infant, for whom donors of the appropriate size are particularly scarce. One way to overcome this problem is to use animals in lieu of humans as organ donors. The major limitation to using animals for this purpose is the susceptibility of animal organs to hyperacute rejection, a violent rejection reaction thought to be mediated by antidonor antibody and complement. To evaluate the potential application of xenotransplantation to newborns, we tested neonatal humans and neonatal baboons and found that neither population expressed significant levels of xenoreactive anti-pig antibodies. We transplanted heterotopically hearts from newborn pigs into unmanipulated newborn baboons (n = 4). There was no evidence of hyperacute rejection in any of the grafts; the animals were killed with functioning grafts at 15, 81, 82, and 82 hr. This outcome contrasts with that of newborn pig-to-mature baboon and mature pig-to-mature baboon cardiac xenografts, which were rejected within 1 hr of transplantation. The histology of pig graft biopsies from the newborn recipients was normal. Immunohistochemistry revealed only traces of IgM, C3, C4, and the membrane attack complex along graft endothelium. Fibrin deposition along endothelial surfaces was observed early after transplantation and became more extensive with time; in the absence of endothelial bound antibody or complement, this change may represent preservation injury. This study suggests that due to low levels of natural antibody, the newborn infant may permit prolonged xenograft survival.

Animals↗

PubMed1995

Correlative morphologic and molecular genetic analysis demonstrates three distinct categories of posttransplantation lymphoproliferative disorders.

The posttransplantation lymphoproliferative disorders (PT-LPDs) are a morphologically heterogeneous group of Epstein-Barr virus (EBV)-driven lymphoid proliferations of varying clonal composition. Some PT-LPDs regress after a reduction in immunosuppression, while others progress in spite of aggressive therapy. Previously defined morphologic categories do not correlate with clonality, and neither morphology nor clonality has reliably predicted the clinical behavior of PT-LPDs. We investigated 28 PT-LPD lesions occurring in 22 patients for activating alterations involving the bcl-1, bcl-2, c-myc, and H-, K- and N-ras proto-oncogenes and for mutations involving the p53 tumor suppressor gene. We correlated the results of these studies with the morphology of the lesions, their clonality based on Ig heavy and light chain gene rearrangement analysis, and the presence and clonality of EBV infection. We found that the PT-LPDs are divisible into three distinct categories as follows: (1) plasmacytic hyperplasia: most commonly arise in the oropharynx or lymph nodes, are nearly always polyclonal, usually contain multiple EBV infection events or only a minor cell population infected by a single form of EBV, and lack oncogene and tumor suppressor gene alterations; (2) polymorphic B-cell hyperplasia and polymorphic B-cell lymphoma: may arise in lymph nodes or various extranodal sites, are nearly always monoclonal, usually contain a single form of EBV, and lack oncogene and tumor suppressor gene alterations; and (3) immunoblastic lymphoma or multiple myeloma: present with widely disseminated disease, are monoclonal, contain a single form of EBV, and contain alterations of one or more oncogene or tumor suppressor genes (N-ras gene codon 61 point mutation, p53 gene mutation, or c-myc gene rearrangement). The PT-LPDs are divisible into three categories exhibiting distinct morphologic and molecular genetic characteristics. Alterations involving the N-ras and c-myc proto-oncogenes and the p53 tumor suppressor gene may play an important role in the development and/or progression of the PT-LPDs.

Base Sequence↗

PubMed1995

Successful heart transplantation with acquired pulmonary artery atresia.

Orthotopic cardiac transplantation was performed successfully in a patient with acquired atresia of the left pulmonary artery 19 years after repair of tetralogy of Fallot. Only the right lung could be incorporated into the cardiopulmonary circulation at transplantation, resulting in transient right ventricular dysfunction, which resolved with vasodilator therapy. Perfusion of a single pulmonary vascular bed does not preclude successful heart transplantation, provided there is a low pulmonary vascular resistance and pulmonary artery architecture free of stenoses.

Adult↗

PubMed1995

Radical excisional therapy and total cardiac transplantation for recurrent atrial myxoma.

We describe the management of a recurrent atrial myxoma extending to the pulmonary veins and superior vena cava. Deep hypothermia and circulatory arrest with left atrial and caval excision was required to achieve complete resection of the tumor. The patient is alive and well without evidence of tumor recurrence 18 months after transplantation. Radical en bloc cardiac resection is feasible in selected cases of cardiac tumors.

Echocardiography, Transesophageal↗

PubMed1995

Nitric oxide treatment for pulmonary hypertension after neonatal cardiac operation.

This report describes a newborn with transposition of the great arteries who underwent a Blalock-Taussig shunt with transient improvement in oxygenation, but required emergent insertion of a central shunt later the same day due to progressive hypoxia and cardiac arrest. Two hours after central shunt insertion, sudden episodes of hypoxia and hypotension developed that were resistant to all pharmacologic therapy. Inhaled nitric oxide (25 ppm) was then administered with dramatic improvement in oxygenation and hemodynamics within minutes. The patient's condition stabilized after these measures, and nitric oxide therapy was discontinued after 2 days.

Administration, Inhalation↗

PubMed1995

Low-flow cardiopulmonary bypass: importance of blood pressure in maintaining cerebral blood flow.

BACKGROUND: During cardiopulmonary bypass (CPB), global hypoperfusion of the brain has been shown to result in ischemic insult and subsequent neurologic injury. METHODS: We measured cerebral blood flow during independent manipulations of arterial blood pressure and pump flow rate to determine which of these hemodynamic parameters regulates cerebral perfusion during CPB. Seven adolescent baboons were placed on CPB and cooled to 28 degrees C. Pump flow rate and arterial blood pressure were altered in varied sequence to each of four conditions: (1) full flow (2.23 +/- 0.06 L.min-1.m-2, mean +/- standard deviation) at high pressure (61 +/- 2 mm Hg), (2) full flow (2.23 +/- 0.06 L.min-1.m-2) at low pressure (24 +/- 3 mm Hg), (3) low flow (0.75 L.min-1.m-2) at high pressure (62 +/- 2 mm Hg), and (4) low flow (0.75 L.min-1.m-2) at low pressure (23 +/- 3 mm Hg). During each of these hemodynamic conditions cerebral blood flow was measured by washout of intracarotid xenon 133. RESULTS: Cerebral blood flow was greater at high blood pressure than at low pressure during CPB both at low flow (34 +/- 8.3 versus 14.1 +/- 3.7 mL.min-1.100 g-1) and full flow (27.6 +/- 9.9 versus 16.8 +/- 3.7 mL.min-1.100 g-1) (p < 0.01). At comparable mean arterial blood pressure, alteration of pump flow rate produced no significant change in cerebral blood flow. CONCLUSIONS: These results indicate that during low-flow CPB, mean arterial pressure should be maintained within the brain's autoregulatory range to maximize cerebral blood flow.

Animals↗

PubMed1995

De novo solid malignancies after cardiac transplantation.

BACKGROUND: As long-term survival after cardiac transplantation improves, neoplastic complications are increasingly being discovered. Although lymphoproliferative disorders predominate, the incidence and clinical spectrum of solid tumors in a uniform population of heart transplant recipients remains uncertain. METHODS: We reviewed our experience with 712 patients who underwent cardiac transplantation. Clinical charts were reviewed and telephone interviews were conducted, when possible. RESULTS: De novo solid malignancies were identified in 3.3% of patients at risk (21 of 633 patients). Twenty patients were male; mean age was 51.5 +/- 8.6 years. Most patients reported a significant smoking history. Pulmonary, urologic, and Kaposi's sarcoma were the most common malignancies identified. Mean interval from transplantation to diagnosis was 35 months. Six patients were diagnosed within 6 months of transplantation. One-year and 5-year survival after transplantation were 90% and 49%, respectively. One-year and 3-year survival after cancer diagnosis were 60% and 52%, respectively. CONCLUSIONS: De novo solid malignancy after transplantation occurred with about half the frequency of lymphoproliferative disorders. A striking male predominance was noted. The interval from transplantation to the appearance of cancer is variable, and no clustering was identified. A significant smoking history warrants aggressive search for occult malignancy during pretransplantation evaluation of potential heart recipients.

Adolescent↗

PubMed1995

Newborn baboon immunity: lessons in cross-species transplantation.

BACKGROUND: The critical shortage of organ donors has greatly limited the number of heart transplantations performed each year. This is particularly true of the newborn patient, for whom xenotransplantation may provide an alternative therapeutic option to allotransplantation. The role of newborn immunity in xenotransplantation is not clearly understood. METHODS: We examined the humoral immune responses of 9 nonimmunosuppressed newborn baboons (900 to 1200 g) aged 28 to 44 days undergoing heterotopic pig heart transplantation. Grafts were explanted between 1 and 87 hours after transplantation. RESULTS: Despite the degree of species, disparity, hyperacute rejection was not observed in any of the nine transplanted grafts. Whole-cell enzyme-linked immunosorbent assay demonstrated newborn baboon serum to contain very low binding levels of anti-pig natural immunoglobulin M xenoantibody when compared with adult baboon serum. Newborn serum, like adult serum, contained anti-pig natural immunoglobulin G xenoantibody. However, newborn baboon serum was not cytotoxic to pig endothelial cells, suggesting that immunoglobulin M and not immunoglobulin G is the primary xenoreactive antibody. CONCLUSIONS: The low binding levels of anti-pig immunoglobulin M xenoantibody, the absence of cytotoxicity to pig endothelial cells, and the avoidance of hyperacute rejection after heart transplantation suggest that newborn primates may have an immunologic advantage as the recipients of hearts transplanted across species barriers. Whether this advantage can be extended to the human condition is currently being explored in our laboratory.

Animals↗

PubMed1995

Effects of immunosuppressive therapy on expression of inducible nitric oxide synthase (iNOS) during cardiac allograft rejection.

Recent studies have indicated a role for nitric oxide (NO) in alloimmune responses and in allograft rejection. iNOS mRNA, protein and enzyme activity are induced in myocardium during cardiac allograft rejection. NO produced by iNOS is negatively inotropic and has the potential to be cytotoxic to cardiac myocytes. To investigate whether immunosuppressive agents would alter the expression of iNOS during cardiac allograft rejection, hearts from Wistar-Furth rats were transplanted into the abdomen of Lewis recipients. At day 5 allografts from treated and untreated animals were removed for pathological and biochemical examination. At day 5 the untreated allografts exhibited histological evidence of marked rejection (edema, infiltration with macrophages and lymphocytes, necrosis of cardiac muscle fibers). Abundant iNOS mRNA was apparent in Northern blots and iNOS enzyme activity was increased in ventricular homogenates and in cardiac myocytes purified from the untreated rejecting allografts. Incubation of isolated purified cardiac myocytes from normal rats for 24 h with cytokines known to be present during allograft rejection (IL-1 beta, TNF-alpha and IFN-gamma) was also associated with increased iNOS mRNA and enzyme activity. When Wistar-Furth to Lewis allografts were treated from time of transplantation with FK 506, cyclosporine A, dexamethasone or a combination of all three drugs, histological evidence of rejection and the levels of iNOS mRNA and enzyme activity in ventricular homogenates were reduced significantly below those observed in the untreated allografts. The data in a rat model indicate that immunosuppressive drugs reduce myocardial iNOS mRNA and enzyme activity in rejecting cardiac allografts. The results are consistent with the hypothesis that the alloimmune response and cytokine release are involved in the expression of iNOS during cardiac transplantation rejection.

Animals↗

PubMed1995

Heart transplantation in children with congenital heart disease.

OBJECTIVES: The aim of this study was to describe heart transplantation in children with congenital heart disease and to compare the results with those in children undergoing transplantation for other cardiac diseases. BACKGROUND: Reports describe decreased survival after heart transplantation in children with congenital heart disease compared with those with cardiomyopathy. However, transplantation is increasingly being considered in the surgical management of children with complex congenital heart disease. Present-day results from this group require reassessment. METHODS: The diagnoses, previous operations and indications for transplantation were characterized in children with congenital heart disease. Pretransplant course, graft ischemia time, post-transplant survival and outcome (rejection frequency, infection rate, length of hospital stay) were compared with those in children undergoing transplantation for other reasons (n = 47). RESULTS: Thirty-seven children (mean [+/- SD] age 9 +/- 6 years) with congenital heart disease underwent transplantation; 86% had undergone one or more previous operations. Repair of extracardiac defects at transplantation was necessary in 23 patients. Causes of death after transplantation were donor failure in two patients, surgical bleeding in two, pulmonary hemorrhage in one, infection in four, rejection in three and graft atherosclerosis in one. No difference in 1- and 5-year survival rates (70% vs. 77% and 64% vs. 65%, respectively), rejection frequency or length of hospital stay was seen between children with and without congenital heart disease. Cardiopulmonary bypass and donor ischemia time were significantly longer in patients with congenital heart disease. Serious infections were more common in children with than without congenital heart disease (13 of 37 vs. 6 of 47, respectively, p = 0.01). CONCLUSIONS: Despite the more complex cardiac surgery required at implantation and longer donor ischemic time, heart transplantation can be performed in children with complex congenital heart disease with success similar to that in patients with other cardiac diseases.

Adolescent↗

PubMed1995

Age-related development of human anti-pig xenoantibody.

Human cytotoxic natural xenoantibodies are believed to be of the immunoglobulin M class in nature. However, a thorough understanding of the development of these natural antixenodonor xenoantibodies remains incomplete. In this study, serum samples were obtained from newborn, infant, and adult human beings. An enzyme-linked immunosorbent assay was used to determine the binding of human natural immunoglobulin M xenoantibodies to pig aortic endothelial cells and pig lymphocytes. A complement-mediated cytotoxicity assay was used to measure the cytotoxicity of newborn, infant, and adult serum to cultured pig aortic endothelial cells and pig lymphocytes. Adult human serum contained both natural immunoglobulin M and immunoglobulin G xenoantibodies to pig endothelial cells and lymphocytes, whereas newborn infant serum contained only immunoglobulin G xenoantibodies. Only adult human serum was cytotoxic to pig endothelial cells and lymphocytes. Human immunoglobulin M xenoantibodies became detectable by age 1 month. By age 2 months these natural anti-pig xenoantibodies reached serum levels equivalent to those in the human adult and resulted in similar cytotoxicity to that of adult human serum. These findings indicate that (1) natural anti-pig immunoglobulin M xenoantibodies are absent from newborn infant human serum, (2) newborn human serum is not cytotoxic to pig endothelial cells and lymphocytes despite the presence of immunoglobulin G xenoantibodies that bind to pig endothelial cells and lymphocytes, and (3) natural anti-pig immunoglobulin M xenoantibodies begin to develop as early as age 1 month and by age 2 months attain a circulating level comparable to that found in the adult.

Adult↗

PubMed1995

Safety and efficacy of aprotinin under conditions of deep hypothermia and circulatory arrest.

Aprotinin has been successfully used to reduce blood loss and blood product requirements in patients undergoing primary and reoperative cardiac operations. Its safety and efficacy during profound hypothermia and circulatory arrest have been questioned, however. A retrospective review compared 24 patients who received aprotinin during complex aortic procedures under profound hypothermia and circulatory arrest with 24 age-matched patients undergoing similar procedures without aprotinin. Activated clotting time was maintained at longer than 500 seconds (kaolin activating agent) or longer than 750 seconds (celite). We observed no statistically significant difference in the incidence of neurologic events (p not significant) or myocardial infarctions (p not significant), and there was a trend toward reduced in-hospital mortality rate in aprotinin-treated patients. A higher incidence of postoperative renal dysfunction was encountered in aprotinin-treated patients. Aprotinin recipients had a significant reduction in requirements for postoperative homologous erythrocytes (p = 0.01). We conclude that aprotinin may be safely and effectively used in patients undergoing deep hypothermia and circulatory arrest.

Aortic Dissection↗

PubMed1995

Inhaled nitric oxide fails to confer the pulmonary protection provided by distal stimulation of the nitric oxide pathway at the level of cyclic guanosine monophosphate.

It has been suggested that inhaled nitric oxide gas may be beneficial after lung transplantation, because endogenous levels of pulmonary nitric oxide decline rapidly after reperfusion. However theoretical concerns remain about the formation of highly toxic oxidants during the quenching of nitric oxide by superoxide. To determine whether distal stimulation of the nitric oxide-cyclic guanosine monophosphate pathway at the level of cyclic guanosine monophosphate might confer the beneficial vascular effects of nitric oxide without its potential toxicities, we studied an orthotopic rat left lung transplant model. In this model, hemodynamic and survival measurements can be obtained independent of the native right lung. Lungs were preserved for 6 hours at 4 degrees C in Euro-Collins solution alone (control, n = 6) or supplemented with the cyclic guanosine monophosphate analog, 8-(4-chlorophenylthio)-guanosine-3',5'-cyclic guanosine monophosphate (cGMP, n = 4). In additional experiments in which lungs were preserved with Euro-Collins solution alone, inhaled nitric oxide was administered during reperfusion (NO, n = 12). Thirty minutes after transplantation and ligation of the native right pulmonary artery, pulmonary vascular resistance, arterial oxygenation, graft neutrophil infiltration (myeloperoxidase activity), and recipient survival were evaluated. Cyclic guanosine monophosphate decreased pulmonary vascular resistance (1.1 +/- 0.2 vs 12.1 +/- 6.3 mm Hg/ml/min, p < 0.05), improved oxygen tension (369 +/- 56 vs 82.8 +/- 48 mm Hg, p < 0.05), reduced myeloperoxidase activity (1.7 +/- 0.3 vs 3.1 +/- 0.9 delta Abs 460 nm/min, p < 0.05), and improved recipient survival (100% vs 0%, p < 0.005) compared with Euro-Collins solution alone (control group). Animals receiving inhaled nitric oxide during reperfusion did not differ from control animals with respect to any of these parameters. These data suggest that distal stimulation of the nitric oxide-cyclic guanosine monophosphate pathway at the level of cyclic guanosine monophosphate has a protective effect that is not seen with inhaled nitric oxide in the immediate pulmonary reperfusion period.

Administration, Inhalation↗

PubMed1995

Nitroglycerin maintains graft vascular homeostasis and enhances preservation in an orthotopic rat lung transplant model.

Transplanted lungs often fail during the peritransplantation period for poorly understood reasons. Because the nitric oxide pathway regulates pulmonary vascular tone, helps to maintain the integrity of the endothelial barrier, and modulates neutrophil adhesivity and activation, we hypothesized that perturbation of this pathway during the preservation and reperfusion of transplanted lungs might play a critical role in mediating early graft failure. To evaluate whether supplementing the preservation solution with the nitric oxide donor nitroglycerin enhances lung preservation for transplantation, we obtained hemodynamic measurements in a model of orthotopic left lung transplantation in the rat after ligation of the native right pulmonary artery. In these experiments, recipient survival and hemodynamics depended solely on the transplanted lung. The left lung was harvested from 22 rats, flushed with either lactated Ringer's solution alone (control, n = 11) or Ringer's solution supplemented with nitroglycerin (0.1 mg/ml, n = 11), preserved for 4 hours at 4 degrees C, and then transplanted using a rapid cuff technique for bronchial and vascular anastomoses. Nitroglycerin significantly improved arterial blood oxygenation (339 +/- 66 versus 130 +/- 12 mm Hg, p < 0.05), increased pulmonary arterial flow (7.6 +/- 1.9 versus 0.9 +/- 0.2 ml/min, p < 0.005), decreased pulmonary vascular resistance (1.7 +/- 0.4 versus 6.6 +/- 1.9 x 10(3) Wood units, p < 0.05), and enhanced recipient survival (64% versus 0%, p < 0.05). Control grafts had significantly greater neutrophil accumulation (50% greater as quantified by myeloperoxidase activity, p < 0.05) than grafts preserved in the presence of nitroglycerin. These studies show that supplementation of the preservation solution with the nitric oxide donor nitroglycerin maintains graft vascular homeostasis and significantly improves pulmonary function and recipient survival after transplantation.

Animals↗

PubMed1995

The effects of self-hypnosis on quality of life following coronary artery bypass surgery: preliminary results of a prospective, randomized trial.

The effects of complementary techniques and alternative medicine on allopathic therapies is generating much interest and research. To properly evaluate these techniques, well controlled studies are needed to corroborate the findings espoused by individuals practicing complementary medicine therapies. To this end, we evaluated the role of one of these therapies, self-hypnosis relaxation techniques, in a prospective, randomized trial to study its effects on quality of life after coronary artery bypass surgery. Subjects were randomized to a control group or a study group. Study group patients were taught self-hypnosis relaxation techniques the night prior to surgery. The control group received no such treatment. Patients then underwent routine cardiac management and care. The main endpoint of our study was quality of life, assessed by the Profile of Moods Scale. Results demonstrated that patients undergoing self-hypnosis the night prior to coronary artery bypass surgery were significantly more relaxed than the control group (p = 0.0317). Trends toward improvement were also noted in depression, anger, and fatigue. This study demonstrates the beneficial effects of self-hypnosis relaxation techniques on coronary surgery. This study also identifies endpoints and a study design that can be used to assess complementary medicine therapies. Results of this preliminary investigation are encouraging and demonstrate a need for further well-controlled studies.

Affect↗

PubMed1995

Management strategies for pulmonary vein thrombosis following single lung transplantation.

Pulmonary vein thrombosis following lung transplantation is an infrequently reported and often fatal vascular complication. Two cases of early pulmonary vein thrombosis following single lung transplantation are described. Both patients underwent surgical thrombectomy and anastomotic reconstruction following institution of cardiopulmonary bypass, but died of multiorgan failure within 5 days of diagnosis. The efficacy of transesophageal echocardiography as a diagnostic modality, as well as medical and surgical management strategies for thrombectomy, are discussed.

Adult↗

PubMed1995

Immunohistochemical demonstration of 15-lipoxygenase in transplant coronary artery disease.

15-Lipoxygenase (15-LO) catalyzes the oxygenation of arachidonic and linoleic acids and has been implicated in the oxidative modification of low-density lipoproteins (LDL). 15-LO mRNA and protein have previously been demonstrated in macrophages of rabbit and human atherosclerotic lesions. The purpose of this study was to investigate whether 15-LO is also present in the accelerated form of coronary artery disease that can complicate cardiac transplantation (TCAD). Immunohistochemical analysis of coronary arteries with TCAD was carried out by using a rabbit polyclonal antibody raised against human recombinant 15-LO and an avidin-biotin-immunoperoxidase system. Normal coronary and pulmonary arteries showed no immunostaining for 15-LO. Two different types of TCAD were observed. One type consisted of concentric intimal proliferation of smooth muscle cells, without lipid or calcium deposits. No immunoreactivity for 15-LO was present in these lesions. The second type of graft arteriosclerosis consisted of complex atheromatous lesions, containing myointimal cells, lipid-laden foam cells, fragmented internal elastic laminae, and calcifications. 15-LO immunostaining of myointimal cells, lipid-laden foam cells, and endothelial cells was consistently present in these atheromatous lesions. The majority of the myointimal and foam cells positive for 15-LO were recognized by antisera to alpha-smooth muscle actin; the others were identified as macrophages. The results indicate that 15-LO expression is present in endothelial, myointimal, and foam cells in complex atheromatous lesions of TCAD, and suggest that 15-LO may play a role in the pathogenesis of this form of the disease.

Adult↗

PubMed1995

Enhanced preservation of orthotopically transplanted rat lungs by nitroglycerin but not hydralazine. Requirement for graft vascular homeostasis beyond harvest vasodilation.

Nitric oxide (NO) produced within the lungs maintains pulmonary vascular homeostatic properties, modulating leukocyte traffic, platelet aggregation, and vasomotor tone. Because reactive oxygen intermediates generated during reperfusion react rapidly with available NO, we hypothesized that the NO donor nitroglycerin (NTG) would enhance lung preservation for transplantation by improving graft blood flow and reducing graft neutrophil and platelet sequestration. By use of an orthotopic rat left lung transplant model, with ligation of the native right pulmonary artery to ensure that recipient survival and physiological measurements depend entirely on the transplanted lung, transplants were performed in 70 male Lewis rats after 6-hour 4 degrees C preservation in Euro-Collins solution (EC) alone or EC with supplemental NTG. Compared with EC alone, supplemental NTG significantly increased pulmonary arterial flow (2.2 +/- 1.4 to 21.4 +/- 2.9 mL/min, P < .01), decreased pulmonary vascular resistance (7.4 +/- 2.0 to 1.4 +/- 0.1 x 10(3) Woods units, P < .05), improved arterial oxygenation (163 +/- 57 to 501 +/- 31 mm Hg, P < .01), and enhanced recipient survival (17% to 100%, P < .001). These beneficial effects of NTG were dose dependent over a range of 0.001 to 0.1 mg/mL. Although NTG caused significant pulmonary vasodilation during the harvest/flushing period, the direct-acting vasodilator hydralazine caused greater vasodilation than did NTG but was associated with poor graft function, elevated pulmonary vascular resistance, and poor recipient survival. To explore nonvasodilator protective mechanisms of NTG, graft neutrophil and platelet sequestration were studied; supplemental NTG significantly reduced both neutrophil and platelet accumulation compared with either hydralazine or EC alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗