Complement inhibition attenuates human lung transplant reperfusion injury: a multicenter trial.
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Complement Activation↗
Biomedical subjects
R D Davis
Publications and source records attributed to R D Davis.
Identification of antigens on porcine pulmonary microvascular endothelial cells recognized by human xenoreactive natural antibodies.
Transplantation of organs between species is prevented in part by humoral immune responses triggered by xenoreactive natural antibodies. Although the immune barrier to xenotransplantation of the lung is thought to be qualitatively and quantitatively different than the immune barrier to xenotransplantation of the kidney or heart, the antibody-antigen reactions responsible for rejection of pulmonary xenografts have not been characterized. To begin to address this issue for porcine lungs transplanted into humans, we analyzed the porcine pulmonary endothelial antigens recognized by human xenoreactive natural antibodies. Human and baboon natural antibodies recognized glycoprotein and glycolipid antigens isolated from the membranes of porcine pulmonary microvascular endothelial cells. The antigens included the integrin chains alpha1, alpha2, alpha3, alpha5, alpha(v), beta1, beta 3, the von Willebrand Factor, and fibronectin. These glycoproteins seemed to be recognized by the same antibodies that bind to porcine kidney or cardiac xenografts. Natural antibodies also recognized at least four glycolipids containing from one to five sugar residues, although at a lower level per unit number of cells than glycoprotein antigens. The epitope recognized by natural antibodies was predominantly Gal alpha1-3Gal, a structure expressed by lower mammals but not by humans and baboons. The antigens recognized by human antibodies in the porcine lung may provide insight into the pathogenesis of the rejection reaction. Moreover, the similarity of porcine lung antigens to porcine kidney and heart antigens suggests that differences in the rejection reactions between these organs reflects the distinct responses of the organs to humoral immunity.
Animals↗
Clinical efficacy of two dentin desensitizing agents.
PURPOSE: To compare the clinical effect over 3 months of two commercially available desensitizing agents on the level of discomfort of patients with complaints of dentin sensitivity. MATERIALS AND METHODS: An oxalate-containing pre-polymerized resin suspension (Pain-Free), a 0.7% fluoride solution (DentinBloc), and a distilled water placebo were compared in a clinical setting. Ten volunteer patients exhibiting three or more teeth that were sensitive to touch and to a stream of forced air were enrolled in the study (52 teeth total). Each patient's level of sensitivity to tactile stimuli and to a forced air stream was recorded using a visual analog scale (VAS). The tactile stimulus was a metal probe rubbed across the exposed dentin with a constant pressure of 40 grams. A 1-second blast of air from a dental unit air syringe was used to generate the air stream. The desensitizing agents were applied according to manufacturers' guidelines. Sensitivity measurements were recorded at baseline, immediately after treatment, at 1 week, 1 month, and at 3 months. VAS pain scores were analyzed using a repeated measures ANOVA (alpha = 0.05). RESULTS: The pre-polymerized resin suspension (Pain-Free), the fluoride-containing solution (DentinBloc), and the placebo all decreased dentin sensitivity. No significant difference was found among the desensitizing agents at any time period (P > 0.05).
Adult↗
Comparison of open mitral commissurotomy with mitral valve replacement with or without chordal preservation in patients with mitral stenosis.
BACKGROUND: Percutaneous balloon mitral valvuloplasty and durable mitral prostheses have made the role of open mitral commissurotomy (OMC) uncertain. METHODS AND RESULTS: Results from the use of St Jude mitral valve replacement (SJMVR) were compared with those of the use of OMC in 312 consecutive patients with mitral stenosis between 1983 and the present. OMC and SJMVR patients were well matched for age, sex, and comorbidity except that SJMVR patients had more severe stenosis and were more likely to undergo concurrent aortic valve replacement. Compared with OMC, SJMVR without chordal preservation involved a longer pump time (158 +/- 81 versus 87 +/- 41 min, P < 0.05), more frequent in-hospital complications or death (57 of 219 [26%] versus 4 of 52 [8%], P < 0.01), and longer hospital stay (13 +/- 11 versus 10 +/- 6 days, P = 0.001). Preservation of chordae to at least 1 mitral valve leaflet decreased early morbidity and mortality rates of SJMVR to values comparable to those of OMC (3 of 41 [7%]). Survival was greater at 10 years for OMC versus SJMVR (86 +/- 5% versus 67 +/- 4%, P = 0.03). Ten-year freedom from cardiac events was not different between groups (49 +/- 9% for OMC versus 55 +/- 4% for SJMVR, P = 0.7). Freedom from subsequent mitral procedures at 10 years was better for SJMVR (96 +/- 2% versus 58 +/- 8%, P < 0.001). CONCLUSIONS: In the modern era, SJMVR offers significantly greater durability than does OMC. Chordal preservation at the time of SJMVR may reduce perioperative complications to levels comparable to those of OMC.
Adult↗
Myocardial recovery after ischemia and reperfusion injury is significantly impaired in hearts with transgenic overexpression of beta-adrenergic receptor kinase.
BACKGROUND: beta-Adrenergic receptor kinase 1 (beta ARK1) mediates beta-adrenergic receptor signaling via receptor phosphorylation, which results in functional uncoupling. The physiological importance of beta ARK1 on cardiac performance in the setting of ischemia and reperfusion injury, however, has not been clearly established. In this study, the effects of beta ARK1 overexpression on myocardial recovery after ischemia and reperfusion injury were evaluated in transgenic mice with the use of an isolated work-performing murine heart preparation and computerized analysis of functional data. METHODS AND RESULTS: A controlled, experimental study was performed to compare cardiac function in the hearts of both transgenic mice with a 3-fold overexpression of beta ARK1 (n = 6; weight, 25 to 29 g) and littermate controls (n = 9; weight, 25 to 28 g). Preload-dependent cardiac output, contractility, heart rate, stroke work, and stroke volume were evaluated in the 2 groups before and after a 6-minute period of normothermic ischemia. Before ischemia, significant decreases were observed in all parameters of myocardial performance in beta ARK1 mice compared with control mice. After ischemia and reperfusion, significant decreases in cardiac function were observed in both experimental groups; however, significantly lower percentages of myocardial recovery occurred in beta ARK1 hearts compared with control hearts. CONCLUSIONS: After global normothermic ischemia, significant decreases in cardiac function were observed in both beta ARK1 and control mice; however, significantly lower percentages of myocardial recovery occurred in beta ARK1 mice. These data suggest that myocardial beta ARK1 overexpression significantly impairs cardiac function in the setting of ischemia and reperfusion injury.
Animals↗
Pharmacological strategies for improving diastolic dysfunction in the setting of chronic pulmonary hypertension.
BACKGROUND: Right ventricular (RV) hypertrophy is an adaptive process that occurs in the setting of chronic pulmonary hypertension (CPH) and can lead to alterations in normal RV diastolic properties. This study was designed to investigate the effects of NO and milrinone on RV diastolic dysfunction in the setting of CPH and RV hypertrophy by use of a canine model of monocrotaline pyrrole (MCTP)-induced CPH. METHODS AND RESULTS: Sixteen mongrel dogs (22 to 24 kg) were used. Animals underwent percutaneous pulmonary artery (PA) catheterization to measure pulmonary hemodynamics before and 8 weeks after injection of 3 mg/kg MCTP (n=8) or placebo (control, n=8). Eight weeks after injection, all hearts were instrumented with a PA flow probe, sonomicrometric dimension transducers, and micromanometers. Data were collected at baseline and after both NO and milrinone administration. Diastolic properties were quantified by use of the end-diastolic pressure-volume relationship and the time constant of ventricular isovolumic relaxation. Eight weeks after injection, significant increases in the PA pressure and pulmonary vascular resistance were observed in MCTP dogs. Significant worsening of RV diastolic function occurred in association with significant increases in the ratio of RV dry weight to LV+septal dry weight. NO and milrinone administration both led to significant improvements in RV diastolic properties. CONCLUSIONS: In the setting of MCTP-induced CPH, significant worsening of RV diastolic function was observed in association with significant increases in the ratio of RV dry weight to LV+septal dry weight, suggesting that these changes are partially due to RV hypertrophy. The significant improvement in RV diastolic properties after both NO and milrinone administration suggests that these agents may be effective forms of pharmacological therapy for improving RV diastolic dysfunction in the setting of CPH.
Administration, Inhalation↗
Complement-mediated pulmonary xenograft injury: studies in swine-to-primate orthotopic single lung transplant models.
BACKGROUND: The pathogenesis of acute pulmonary xenograft injury has not yet been determined. The present study evaluates the role of complement in mediating pulmonary xenograft dysfunction by using cobra venom factor (CVF) to deplete recipient complement and transgenic swine, which express human regulators of complement activation (human decay-accelerating factor [hDAF] and hCD59). METHODS: Fifteen orthotopic lung transplants were performed as follows: group I, swine-to-swine (n=5); group II, unmodified swine-to-baboon (n=3); group III, unmodified swine-to-(CVF treated) baboon (n=3); and group IV, hCD59/hDAF swine-to-baboon (n=4). Left pulmonary artery flow and pulmonary vascular resistance were measured at 30-min intervals. Serial lung biopsies were examined by light microscopy and immunofluorescence. The activation of complement was quantified by measurement of baboon plasma CH50 and C4 functional activity. RESULTS: Group II xenotransplants ceased functioning within 30 min of reperfusion. Histopathologic ab normalities included erythrocyte/platelet aggregates and hemorrhagic pulmonary edema. Groups I and IV showed excellent function throughout. hDAF/hCD59 lungs (group IV) showed trace venular fibrin plugs and moderate loss of alveolar architecture. Pretreatment with CVF (group III) was ineffective in preventing xenograft injury. CONCLUSIONS: These results characterize the fundamental features of discordant pulmonary xenotransplantation. Correction of the known defects in the regulation of heterologous complement activation was partially effective in preventing pulmonary xenograft dysfunction, suggesting that complement mediates, in part, some of the features of acute lung injury after discordant lung xenotransplantation.
Animals↗
The role of antibodies in acute vascular rejection of pig-to-baboon cardiac transplants.
Long-term success in xenotransplantation is currently hampered by acute vascular rejection. The inciting cause of acute vascular rejection is not yet known; however, a variety of observations suggest that the humoral immune response of the recipient against the donor may be involved in the pathogenesis of this process. Using a pig-to-baboon heterotopic cardiac transplant model, we examined the role of antibodies in the development of acute vascular rejection. After transplantation into baboons, hearts from transgenic pigs expressing human decay-accelerating factor and CD59 underwent acute vascular rejection leading to graft failure within 5 d; the histology was characterized by endothelial injury and fibrin thrombi. Hearts from the transgenic pigs transplanted into baboons whose circulating antibodies were depleted using antiimmunoglobulin columns (Therasorb, Unterschleisshein, Germany) did not undergo acute vascular rejection in five of six cases. Biopsies from the xenotransplants in Ig-depleted baboons revealed little or no IgM or IgG, and no histologic evidence of acute vascular rejection in the five cases. Complement activity in the baboons was within the normal range during the period of xenograft survival. In one case, acute vascular rejection of a xenotransplant occurred in a baboon in which the level of antidonor antibody rose after Ig depletion was discontinued. This study provides evidence that antibodies play a significant role in the pathogenesis of acute vascular rejection, and suggests that acute vascular rejection might be prevented or treated by therapies aimed at the humoral immune response to porcine antigens.
Acute Disease↗
A comparison of two serological methods for detecting the immune response after rabies vaccination in dogs and cats being exported to rabies-free areas.
Levels of rabies virus neutralizing antibody in sera from dogs and cats were titrated to endpoint by the Rapid Fluorescent Focus Inhibition Test (RFFIT) and retested by the RFFIT and the Fluorescent Antibody Virus Neutralization test (FAVN). The two tests were compared for their ability to detect the 0.5 international units/ml (I.U.) of antibody required by the World Health Organization and the Office International des Epizooties as the minimum response for proof of rabies immunization. No difference was observed in sensitivity or specificity for either method in tests of 168 sera from unvaccinated animals or 70 sera from vaccinated animals with high levels of neutralizing antibody (an initial RFFIT titre of > or = 1.0 I.U.). Test to test variation occurred for results obtained by both RFFIT and FAVN for 95 sera from vaccinated animals with low to moderate levels of neutralizing antibody (RFFIT titre < 1.0 I.U.). No significant differences were detected for the 95 sera in the frequency for one methodology more often than the other to have a positive response (> or = 0.5 I.U.), nor were significant differences detected for the symmetry (P = 0.43) or the marginal homogeneity (P = 0.39) of results obtained by the two methods. Both methods can adequately identity unvaccinated animals, but false positive and false negative results are possible for either method when a single test is used to measure the antibody response of low-responding vaccinated animals. Nucleotide sequence analysis identified several amino acid differences in stocks of the challenge rabies virus from different laboratories. The small differences in neutralizing antibody titre that may result from mutations in the challenge virus are not important for evaluating immunity induced by vaccines which are themselves prepared from a variety of different rabies virus strains, but differences in the challenge virus, rather than differences in methodology, may account for at least some of the discrepant results reported in inter-laboratory surveys. Comparative studies of serological methods for measuring rabies antibodies should use well-characterized unpassaged virus stocks obtained from a single reference laboratory.
Amino Acid Sequence↗
Cardiopulmonary bypass time does not affect cerebral blood flow.
BACKGROUND: A time-dependent decline in cerebral blood flow (CBF) has been reported in cardiac surgical patients despite stable pump flows and arterial carbon dioxide tension. Other studies have failed to support these hypothermic cardiopulmonary bypass (CPB) results, showing preservation of CBF during CPB. The purpose of the study was to define the influence of mildly hypothermic CPB duration on CBF. METHODS: Cerebral blood flow was measured using xenon-133 washout and alpha-stat blood gas management during nonpulsatile CPB. Cerebral blood flow measurements were made after the initiation of CPB and near the end of bypass during pump flows of 2.4 L.min-1.m-2. RESULTS: Fifty-two coronary artery bypass patients were studied. The average time between CBF measurements was 54 +/- 20 minutes (mean +/- standard deviation), with a range of 10 to 100 minutes. Temperature and arterial carbon dioxide tension were controlled: after the initiation of CPB, temperature was 35.5 degrees +/- 0.4 degree C and carbon dioxide tension was 37 +/- 2.8 mm Hg; whereas near the end of bypass temperature was 35.6 degrees +/- 0.5 degree C and carbon dioxide tension was 36 +/- 2.3 mm Hg. We found no correlation between CBF and time on CPB (p = 0.47; r = 0.101), in contrast to other studies suggesting that CPB duration may intrinsically affect CBF. CONCLUSIONS: Our experimental results include the following: (1) during mildly hypothermic bypass, CBF does not decrease in relation to time and (2) cerebral flow-metabolism coupling is intact at 35 degrees C.
Blood Pressure↗
The Ross procedure: shorter hospital stay, decreased morbidity, and cost effective.
BACKGROUND: The Ross procedure has become an accepted and sometimes preferred alternative to mechanical aortic valve replacement. One criticism of the Ross procedure is that it may have a higher operative mortality, morbidity, and cost. Several groups have shown that this operation can be performed safely with less than 3% mortality. The issue of higher cost has not been resolved. In this retrospective study we compared a consecutive group of patients undergoing the Ross procedure with an age- and disease-matched group of patients who underwent mechanical aortic valve replacement. METHODS: From 1993 to 1996, 22 consecutive adult patients (age range, 20 to 57 years; mean, 38 +/- 14 years) underwent the Ross procedure. Twenty-seven patients (age range, 17 to 57 years; mean, 41 +/- 10 years) underwent mechanical aortic valve replacement between 1991 and 1996. The hospital cost (in 1996 dollars) and postoperative length of stay were calculated for each patient using Transition I, a hospital-wide cost accounting system. RESULTS: There was no hospital mortality in either group. The incidence of significant valve-related complication was 5% (1/22 patients) in the Ross procedure group and 22% (6/27 patients) in the mechanical valve group. There were two late deaths in the group with mechanical aortic valve replacement. The length of stay for the Ross procedure group was 5.9 +/- 2.1 days, versus 8 +/- 1.85 days for the mechanical valve group (p < 0.01). The mean hospital costs were not significantly different, $23,140 +/- $7,825 for the mechanical valve group and $23,226 +/- $6,960 for the group having the Ross procedure. CONCLUSIONS: The data from this review demonstrate that the Ross procedure can be done safely, with short hospital stays, decreased morbidity, and costs comparable with those of standard mechanical aortic valve replacement in patients with isolated aortic valve disease.
Adolescent↗
Physiologic effects of extracellular superoxide dismutase transgene overexpression on myocardial function after ischemia and reperfusion injury.
OBJECTIVE: Myocardial injury after ischemia and reperfusion may be mediated, in part, by oxygen-derived free radicals. In this study the protective effects of extracellular superoxide dismutase overexpression were directly assessed in the hearts of transgenic mice, after ischemia and reperfusion injury, using an isolated work-performing murine heart preparation and computerized analysis of functional data. METHODS: A blinded study was performed to compare cardiac function in the hearts of both transgenic mice with a 3.5-fold overexpression of myocardial extracellular superoxide dismutase (n = 6, 22 to 26 gm) and littermate controls (n = 8, 22 to 26 gm). Preload-dependent cardiac output, contractility, heart rate, stroke work, and stroke volume were evaluated in the two groups before and after a 6-minute period of normothermic ischemia. RESULTS: No differences were found between extracellular superoxide dismutase hearts and control hearts in any parameter of myocardial function before ischemia. After ischemia, decreases in cardiac output occurred in both groups; however, this decrease was larger in control mice compared with extracellular superoxide dismutase mice. A higher percentage of recovery was also observed in the contractility, heart rate, stroke work, and stroke volume of extracellular superoxide dismutase hearts compared with control hearts. CONCLUSION: After global normothermic ischemia and subsequent reperfusion, decreases in cardiac function occurred in both extracellular superoxide dismutase and control mice; however, a higher percentage of recovery was observed in the extracellular superoxide dismutase overexpressed hearts. These data suggest that extracellular superoxide dismutase transgene overexpression significantly improves preservation of myocardial function after ischemia and reperfusion injury.
Animals↗
Total respiratory support from swine lungs in primate recipients.
UNLABELLED: The use of nonhuman lung donors, such as swine, has the potential to provide an unlimited supply of organs. However, hyperacute rejection has prevented pulmonary xenotransplantation. OBJECTIVE: Our aim was to test the hypothesis that immunodepletion by pretransplantation swine lung perfusion will prevent hyperacute swine-to-primate pulmonary xenograft rejection and allow for a functional swine pulmonary xenograft. METHODS: Seven baboons underwent left pneumonectomy followed by orthotopic transplantation of the swine left lung. Four baboons received immunodepletion by perfusion with swine lungs before transplantation, and three received no treatment before transplantation. RESULTS: After transplantation, pulmonary xenografts from immunodepleted baboons had a low pulmonary vascular resistance and a high pulmonary blood flow compared with control animals, which had a high pulmonary vascular resistance and a low pulmonary blood flow. After 60 minutes of reperfusion, three of four immunodepleted animals also tolerated complete occlusion of the right pulmonary artery, with the baboon relying completely on the swine pulmonary xenograft for respiratory function for 11 hours. Pathologic analysis of peripheral lung biopsy specimens taken from control lungs displayed alveolar disruption and hemorrhage within small vessels, whereas swine lungs transplanted into immunodepleted baboons displayed little histologic evidence of injury. Furthermore, pulmonary xenografts transplanted into immunodepleted baboons demonstrated excellent respiratory function and adequate hemodynamics during occlusion of the right pulmonary artery. CONCLUSION: Hyperacute pulmonary xenograft rejection can be prevented by pretransplantation swine lung perfusion. Swine pulmonary xenografts can provide complete respiratory support in primates when rejection is prevented.
Animals↗
Lung transplantation for Williams-Campbell syndrome.
Williams-Campbell syndrome is a rare disorder characterized by a deficiency of cartilage in subsegmental bronchi leading to distal airway collapse and bronchiectasis. We report the first case of lung transplantation in a patient with end-stage lung disease secondary to Williams-Campbell syndrome. Although the patient did not have proximal airway collapse prior to transplantation, his posttransplant course was complicated by the development of bronchomalacia of the right and left mainstem bronchi. The patient experienced recurrent pulmonary infections and died of bacterial pneumonia 1 year after transplantation. Autopsy revealed cartilage deficiency in both right and left mainstem bronchi. A hypothesis may be made that a combination of proximal cartilage deficiency and posttransplant airway ischemia led to the development of bronchomalacia after lung transplantation. Thus, in contrast to previous reports, the cartilage deficiency in Williams-Campbell syndrome can involve both proximal and distal airways. Consequently, bilateral sequential lung transplantation may not be an effective therapeutic option in patients with this syndrome.
Adult↗
Community respiratory viral infection in adult lung transplant recipients.
STUDY OBJECTIVE: To define the epidemiology, clinical manifestations, and long-term complications of respiratory viral infections in adult lung transplant recipients. DESIGN: Retrospective review of the records of 122 adult lung transplant recipients over a 5-year period at one institution. RESULTS: Ten episodes of infection with respiratory syncytial virus, parainfluenza, influenza, or adenovirus were identified. All patients presented with symptoms of respiratory tract infection. Two patients died acutely and four patients subsequently had development of obliterative bronchiolitis (OB). CONCLUSIONS: These data suggest community respiratory viral infections cause significant morbidity and mortality in lung transplant recipients. Further prospective studies are warranted to clarify the relationship between respiratory viral infection and OB and to define the optimal therapy for these viral infections.
Adult↗
Short-term clinical evaluation of post-operative sensitivity with bonded amalgams.
PURPOSE: To compare the in vivo short-term post-operative sensitivity of teeth restored with amalgam using a bonded resin liner vs. teeth restored using a copal varnish liner. MATERIALS AND METHODS: 20 patients received Class I or Class II contralaterally paired restorations which were placed at the same appointment. All restorations were placed by the same operator using an identical technique except that, in each randomized pair, one was lined with an adhesive resin (Scotchbond Multi-Purpose Plus) while the other was lined with copal varnish. (Plastodent) Patients were provided visual analog scale response forms, instructed in their use, and requested to complete and return a form reporting their degree of sensitivity at baseline and on days 1, 3, 7, 14, and 30 post-operatively. Data from the response forms were analyzed for differences using a paired t-test. RESULTS: A response rate of 90% (18/20) was achieved for the complete 30-day assessment. Increases in thermal sensitivity beyond baseline were seen in 13 of the 18 subjects involving 12 restorations lined with copal varnish and 10 lined with adhesive resin. Typically, sensitivity peaked on day 1 or day 3 and diminished to pre-operative levels by day 30. Only three subjects reported greater sensitivity at day 30 than at baseline. No significant difference in post-operative sensitivity was found between the two cavity lining materials at any post-operative interval.
Chi-Square Distribution↗
Lung transplantation at Duke University Medical Center.
Lung transplantation is a viable therapy for patients with a variety of end-stage lung diseases. Our active program now includes over 200 lung transplant operations with acceptable one- and 3-year survival rates of 78% and 61%. A major focus of clinical research at this institution is to design strategies to prevent the development of chronic allograft dysfunction. Our preliminary work in this regard has been encouraging. In addition, a major research focus has been to design protocols to prevent the development of posttransplant infections. Our work with aerosolized ABLC represents a major advance at our center, and additional randomized prospective studies are ongoing to define the optimal antifungal prophylaxis after transplantation. Ongoing clinical and basic research at Duke and elsewhere should continue to advance the field of clinical transplantation and ultimately lead to more acceptable long-term outcomes for lung allograft recipients.
Adult↗
Hemodynamic and inotropic effects of milrinone after heart transplantation in the setting of recipient pulmonary hypertension.
BACKGROUND: Right ventricular failure remains an important cause of early morbidity and death after heart transplantation and is commonly related to preexistent recipient chronic pulmonary hypertension, which occurs as a result of long-standing congestive heart failure. In this study, the hemodynamic and inotropic effects of milrinone were assessed after bicaval heart transplantation in the setting of monocrotaline pyrrole-induced recipient chronic pulmonary hypertension. METHODS: Twenty dogs were used for 10 successfully completed transplantation experiments. Recipient animals underwent right atrial injection of 3 mg/kg monocrotaline pyrrole 4 months before transplantation. Hemodynamic and functional data were taken 1 hour after termination of cardiopulmonary bypass and after milrinone infusion. Myocardial function was assessed with load-insensitive means (preload-recruitable stroke work) and pulmonary vascular impedance was calculated with Fourier analysis. RESULTS: At the time of transplantation, before cardiopulmonary bypass, pulmonary hemodynamic indexes in recipient animals were significantly increased when compared with donors and were further significantly increased after cardiopulmonary bypass. Two animals died after transplantation as a result of acute right ventricular failure. In surviving animals milrinone infusion led to significant increases in right ventricular function, which occurred in association with significant improvements in pulmonary vascular impedance and transpulmonary efficiency. CONCLUSIONS: In the setting of monocrotaline pyrrole-induced recipient pulmonary hypertension, milrinone was associated with significant improvements in pulmonary vascular impedance, right ventricular function, and transpulmonary efficiency. These data suggest that milrinone is an effective means to improve right ventricular dysfunction and pulmonary vascular efficiency after bicaval heart transplantation in the setting of recipient chronic pulmonary hypertension.
Animals↗