Early Graft Research Articles

Effects of inhaled nitric oxide in a canine living-donor lobar lung transplant model.

In living-donor lobar lung transplantation, early severe graft dysfunction can occur if the size or amount of transplanted lung tissue is insufficient. The purpose of this study was to evaluate the effects of inhaled nitric oxide on early pulmonary function in a canine bilateral living-donor lobar lung transplant model. Sixteen pairs of mongrel dogs with a donor/recipient weight ratio less than 1.2 were used. The donor lung bloc was extirpated after heparinization. Right middle, lower and cardiac lobes were implanted as a right lung of the recipient and left lower lobe was implanted as a left lung without cardiopulmonary bypass. In Group 1 (n = 9), nitric oxide gas was administered continuously at a concentration of 40 parts per million prior to reperfusion of the right lung throughout the 6-hour assessment period after transplantation. In Group 2 (n = 7), nitrogen gas was administered in the same manner as nitric oxide, for control. At the end of assessment, the survival rate was 89% (8/9) in Group 1 and 57% (4/7) in Group 2. The arterial oxygen tension in Group 1 was significantly higher than that in Group 2. The pulmonary arterial pressure and pulmonary vascular resistance index were significantly lower in Group 1 than in Group 2. The aortic pressure and cardiac index did not differ significantly between the two groups. The wet-to-dry weight ratio and myeloperoxidase activity were significantly lower in Group 1 than in Group 2. These data suggested that inhaled nitric oxide improved early pulmonary function in living-donor lobar lung transplantation by vasodilatating the pulmonary vasculature and inhibiting neutrophil activation.

Predictors of Outcome when Reoperating for Early Infrainguinal Bypass Occlusion

The purpose of this study is to identify factors that predict outcome after intervention for early (<30 days) infrainguinal graft thrombosis. We reviewed the medical records, arteriograms, and follow-up studies of patients who underwent infrainguinal bypass for limb salvage between 8/91 and 9/98 and whose graft failed <30 days from the index procedure. Five factors were analyzed: (1) conduit: single segment saphenous vein versus alternative vein or composite conduit (20 vs. 13 patients); (2) repair modality: construction of a new graft at the time of the initial take-back procedure versus local revision and/or thrombectomy alone (12 vs. 21 patients); (3) run-off: good run-off versus poor run-off (20 vs. 13 patients); (4) operative findings: the presence of a correctable problem versus noncorrectable problem (20 vs. 13 patients); and (5) surgical history: previous versus no previous ipsilateral bypass (16 vs. 17 patients). These variables are statistically significant risk factors that can be used in combination to predict outcome. Unless a focal lesion clearly responsible for graft occlusion is found, complete graft replacement should be considered even if the new bypass must be prosthetic. The costs and morbidity of repeated procedures argue for primary amputation when adverse risk factors exist.

Limitations of pediatric donor kidneys for transplantation

BackgroundThe shortage of grafts for kidney transplantation (Tx) has resulted in an expansion of criteria for pediatric donors. However, the limitations of pediatric donors for kidney Tx are not yet clearly established. We investigated the outcomes of recipients with pediatric kidney grafts from Colorado to elucidate the state of pediatric kidney grafts distributed in the nation and to clarify the limitations of pediatric donor kidneys for Tx.MethodsBetween January 1989 and July 1997, 675 organ donors in Colorado were utilized for Tx. Fifty‐seven of these (8.4%) were 10 yr old or younger. Thirty‐two of the 57 pediatric donors provided kidneys for 50 recipients both inside and outside Colorado. Forty‐four of the 50 recipients were followed and are available for this study.ResultsGraft survival rates were 85.6, 77.3, 71.3 and 65.4% for 1, 2, 3 to 5, and 6 yr of follow‐up, respectively. Thirteen recipients lost the grafts, including three graft losses within 2 wk, due to primary nonfunction, venous and arterial thrombosis. The mean serum creatinine value in 31 recipients with functioning grafts was 1.3±0.4 mg/dL at the time with follow‐up of 45.9±28.3 months (5‐96 months). Six grafts from 13‐month to 3‐yr‐old donors were transplanted en‐bloc and 5 of these have survived. Four of the 5 single grafts from 3 to 5‐yr‐old donors have functioned. Of the 33 grafts from donors aged 6‐10 yr. including 30 single and 3 en‐bloc grafts, 22 were still functioning. With respect to donor weight, 4 of the 5 en‐bloc grafts from donors weighting 9‐15 kg, and 6 of the 7 single and the 1 en‐bloc grafts from donors weighing 15‐20 kg were still functioning. Cold ischemic time (CIT) within 37.5 h was not associated with early graft outcome.ConclusionsThe kidneys from donors 1‐3 yr old and/or weighing 9‐15 kg could be successfully transplanted en‐bloc and those from donors more than 3 yr old and/or weighing 15 kg were best transplanted by single grafts.

Dobutamine Stress Echocardiography Early After Heart Transplantation Predicts Development of Allograft Coronary Artery Disease and Outcome

Objectives. This study sought to determine the prognostic significance of serial dobutamine stress echocardiography (DSE) in new heart transplant recipients and to examine the relation between persistent wall motion abnormalities and the eventual development of coronary artery disease (CAD) as assessed by angiography.Background. Allograft CAD is a major cause of graft failure. However, clinical diagnosis of the early disease remains difficult. The reasons for this include the diffuse nature of the disease and its predilection for the microvasculature, which are not easily detected by coronary angiography. Identifying patients at risk for the development of angiographic CAD early after transplantation may allow such patients to be targeted for aggressive treatment options to prevent subsequent cardiac events and early graft failure.Methods. Twenty-two new heart transplant recipients were selected to undergo serial DSE at the time of their regularly scheduled endomyocardial biopsy. In addition, patients underwent scheduled annual coronary angiography. DSE was performed in 5-min stages with infusion of intravenous dobutamine at 5, 10, 20, 30 and 40 μg/kg body weight per min.Results. Twenty-two patients had 91 DSE studies and 45 coronary angiograms. The patients were categorized into three groups based on the echocardiographic results. Group 1 (n = 7) had normal serial stress echocardiographic studies. Group 2 (n = 4) had transient inducible wall motion abnormalities. Group 3 (n = 11) developed persistent wall motion abnormalities. During a mean follow-up time of 32 ± 11 months (range 5 to 50), 8 (73%) of 11 patients in Group 3 developed events. The events included angiographic CAD (n = 7), myocardial infarction (MI) (n = 1) and cardiac death (n = 3). The patient who developed an MI had a normal coronary angiogram. No cardiac event or angiographic disease occurred in either Group 1 or 2 patients.Conclusions. These results suggest that dobutamine-induced wall motion abnormalities, which are persistent in new heart transplant recipients, are predictive of the development of angiographic CAD, MI or death.

National Impact of Pulsatile Perfusion on Cadaveric Kidney Transplantation

Background The simplicity and success of cold storage of cadaveric kidneys have led to the infrequent use of pulsatile perfusion. However, there may be advantages to pulsatile perfusion for less optimal donors. Methods. United Network for Organ Sharing data were analyzed retrospectively to determine the impact of pulsatile perfusion on initial function and 1-year graft survival. The analysis included 60,827 cadaveric kidney transplants performed between 1988 and 1995. Multivariate logistic regression analyses were used to determine the effect of preservation method on both early kidney function (need for first-week dialysis after transplant) and 1-year graft survival, after adjusting for other known risk factors. Results. The preservation method exhibited a highly significant impact on the need for first-week dialysis. Ice-preserved kidneys were associated with a 2.13-fold increase in the odds of requiring dialysis compared with perfused kidneys. If the donor age was <55 years, the odds were 2.33-fold higher for ice-preserved as compared with perfused. If cold ischemic time was <24 hr, there was a 2.19-fold increase in the odds of dialysis for ice-preserved kidneys. African-American recipients of cold-stored kidneys had a 2.29-fold greater odds of first-week dialysis. Conclusions. Based on there findings, it was estimated that the increased cost of perfusing kidneys from all donors <55 years of age would be balanced by the decreased need for posttransplant dialysis if the cost related to dialysis were $14,700 or greater per patient. These facts, coupled with the ability to assess an older donor kidney before transplant, could make pulsatile perfusion for the expanded donor financially as well as medically desirable.

Dermal infiltration by activated monocytes precedes skin thickening and proα1(I) collagen mRNA upregulation in early murine sclerodermatous graft versus host disease (GVHD), a promising model for human scleroderma

Dermal infiltration by activated monocytes precedes skin thickening and proα1(I) collagen mRNA upregulation in early murine sclerodermatous graft versus host disease (GVHD), a promising model for human scleroderma

Clinical, virological, and histologic evolution of hepatitis C virus infection in liver transplant recipients.

We designed a prospective study to assess the time course and evolution of hepatitis C virus (HCV) infection in 152 patients who underwent a liver transplantation (LT) in our institution. Forty-four recipients (29%) were infected by HCV after transplantation: 40 who developed recurrent infection after LT and four who acquired infection during or after LT. No differences were found in survival actuarial rates at 1, 2, and 4 years after transplantation for patients infected by HCV vs. noninfected ones. Graft hepatitis occurred in 66% of HCV-infected recipients: 18 developed chronic active hepatitis (10 of them with intense fibrosis) and 2 developed cirrhosis during the follow-up. Infection by the HCV-1b genotype was found in 79% of the infected recipients and in 100% of those in whom histologic evolution was worst. Fourteen grafts were lost in 44 HCV-infected recipients, in comparison with 12 in 108 HCV-negative patients (P = .007), mostly because of chronic rejection. HCV infection did not affect life expectancy in the midterm follow-up for LT patients. However, it was often associated with the occurrence of early and severe graft hepatitis and with a higher incidence of graft loss due to chronic rejection.

New Immunosuppressive Agents for Maintenance Therapy in Organ Transplantation

Traditional cyclosporin-based immunosuppressive protocols are associated with relatively high incidences of early acute rejection and late graft loss due to chronic rejection. In addition, long-term immunosuppression with cyclosporin and corticosteroids has been associated with significant metabolic, infectious, malignant and cosmetic adverse effects. In the last decade, the goals of immunosuppression strategies have included not only short-term survival but also graft acceptance, with a low incidence of early acute rejection and minimal long-term toxicity. Tacrolimus and mycophenolate mofetil are 2 new immunosuppressive agents that have recently been approved for use. The mechanism of action and toxicity profile of tacrolimus are similar to that of cyclosporin. Tacrolimus reduces early acute rejection and is also effective in salvage of allografts with refractory rejection. A wide spectrum of adverse effects, including nephrotoxic, neurotoxic, gastrointestinal, metabolic and hematological effects, has been reported in association with tacrolimus but, unlike cyclosporin, this agent is not associated with hirsutism or gingival hyperplasia. Mycophenolate mofetil, an antimetabolite, has been effective in reducing early acute rejection and in treatment of refractory rejection when used in combination with cyclosporin instead of azathioprine. Its myelosuppressive and gastrointestinal toxicities are mild and reversible, but it may be associated with an increased risk of infections. Both agents permit early corticosteroid withdrawal. Other new immunosuppressive agents that act on different stages of the cell cycle but that have not yet been introduced for wide clinical use, including sirolimus (rapamycin), brequinar, mizoribine and gusperimus, are also discussed in this review.

Limitations to Survival for Infants with Hypoplastic Left Heart Syndrome before and after Transplant: The Loma Linda Experience

Untreated, hypoplastic left heart syndrome is a lethal cardiac defect. Heart transplant has become an accepted therapeutic option for this condition. However, significant limitations to survival remain for infants with this condition who are referred for heart transplantation. Attention to the prevention, early detection, and management of common problems occurring at each stage of the transplantation process is important for improving survival rates. This study retrospectively reviewed the cases of 195 infants with hypoplastic left heart syndrome registered for heart transplantation at Loma Linda University Medical Center between November 1985 and July 1996 to determine causes of death. During the waiting period, progressive cardiac failure and complications from interventional procedures were the leading causes. In the early postoperative period, technical issues and acute graft failure were most important, whereas late deaths (more than 30 days after transplant) were most often related to rejection and posttransplant coronary artery disease.

Early detection of graft function using hepatic venous oxygen saturation in pig liver transplantation.

In this study, we measured hepatic venous oxygen saturation (Shvo2) in pig liver transplantations in order to evaluate its usefulness as a predictor of early postoperative graft function. Shov2 of the grafts with good function was over 60% after reperfusion, and the mean Shov2 at end of the operations was 69.8+/-6.9%. Shov2 of the grafts with poor function never increased over 60%, and for most of the operation until its end, Shov2 was under 50%. At the end of the operations, the mean Shov2 was 39.7+/-5.5%. Shov2 levels of the grafts with good function were significantly higher than those of the grafts with poor function (P=0.0016). Corresponding with these Shov2 data, glutamic-oxaloacetic transaminase and lactate dehydrogenase levels of grafts with poor function were significantly higher than those of the grafts with good function. Shov2 represents a summation of the hemoglobin oxygen saturation at the venous end of the sinusoids of the liver and indicates adequate hepatic blood flow if the hepatic oxygen is constant. A decrease of Shov2 in poor graft function might indicate a disturbance of microcirculation in the sinusoids. Through the use of Shov2, we are able to recognize conditions of microcirculatory disturbance more quickly than with any other system. In conclusion, Shov2 is a useful indicator for an early and reliable prediction of outcome in liver transplantation.

Use of prostaglandin I2 in three small children at high risk of early renal graft thrombosis

We report the use of prostaglandin I.2. (PGI2) in three small children weighing less than 15 kg at high risk of graft thrombosis after cadaveric renal transplantation complicated by acute tubular necrosis. PGI2 was started at a dose of 5 ng/kg per min within the first 6 h after transplantation, and was continued for 12-15 days. Before and during PGI2 infusion, color-coded and pulsed Doppler sonography was performed. We found immediate restoration of diastolic flow, consistent with a decrease in vascular resistance. During the subsequent days, the sonographically assessed flow pattern and clinical graft function improved gradually. None of the three consecutively treated children developed graft thrombosis or lost his graft; no clinically relevant bleeding or adverse hemodynamic or pulmonary effects were seen.

How valid is emergency liver transplantation for acute liver necrosis in patients with multiple-organ failure?

Multiple-organ failure (MOF), defined as the failure of initially uninvolved organs, is the final step of definitive and massive liver necrosis. Emergency liver transplantation (ELT) has radically modified the outcome of acute liver failure and early primary graft failure, but the results of ELT in cases of MOF are unknown. From May 1988 to June 1993, 243 patients underwent a liver transplantation (LT). Thirty-seven patients (15.2%) who had an acute liver necrosis complicated by a MOF underwent an ELT. Twenty-one patients were children. An emergency retransplantation was performed in 16 patients. Three or 4 organ-system failures (OSF) were present in 13 patients. Before ELT, the mean Acute Physiology and Chronic Health Evaluation (APACHE) II score was 26.3 +/- 5.1. Six-month and 1-year survival rates were 37.8% and 25.9%, respectively, after ELT complicated by MOF, and 78% and 73.5%, respectively, in other cases of LT. Twenty-six patients had surgical complications (70%), whereas thirty-one patients had medical complications (84%). Twenty-two patients died during the postoperative period (60%). Before ELT, infection (P < .05), cardiovascular failure (P < .03), and more than two OSF (P < .05) were more frequent in patients who died after intervention. The APACHE II score (P < .05) and the length of stay in the intensive care unit before ELT (P < .05) were lower among survivors. In the context of liver allograft shortage, our results suggest that an ELT should not be performed in patients with cardiac failure, more than two OSF, or an APACHE II score higher than 30.

Use of prostaglandin I 2 in three small children at high risk of early renal graft thrombosis

Use of prostaglandin I 2 in three small children at high risk of early renal graft thrombosis

Review: Early coronary bypass graft surgery lowers mortality

Review: Early coronary bypass graft surgery lowers mortality

Comparison of saphenous vein graft relaxation between Plasma-Lyte solution and normal saline solution

Venospasm of saphenous vein grafts may damage endothelial cells and compromise early and late graft performance. Hence it is desirable to identify and use storage solutions that minimize vascular spasm during vein preparation. In view of this, we initiated isometric tension-recording studies in isolated canine and human saphenous vein to evaluate the acute, vasoactive effects of two storage solutions, Plasma-Lyte solution and normal saline solution. In initial experiments, canine saphenous veins were mounted in tissue baths containing physiologic salt solution and tonically constricted by 2 x 10(-6) mol/L norepinephrine. The physiologic salt solution in the bath was then replaced by Plasma-Lyte solution or normal saline solution containing the same norepinephrine concentration, and changes in contraction amplitude were recorded for 90 minutes. Storage in Plasma-Lyte solution at 37 degrees C completely relaxed norepinephrine-activated canine saphenous vein within 20 minutes, whereas veins remained partially constricted in normal saline solution. Both Plasma-Lyte solution and normal saline solution relaxed canine saphenous vein less at room temperature (25 degrees C) than at 37 degrees C, implying that warming of storage solutions in the operating room may promote graft dilation. To identify the mechanism by which Plasma-Lyte solution induced relaxation, we replaced its putative vasodilator components of gluconate and acetate with NaCl, but this alteration did not reduce relaxation induced by Plasma-Lyte solution. However, adding 1.6 mmol/L CaCl2 to Plasma-Lyte solution completely reversed the venodilation, suggesting that the low Ca2+ content of Plasma-Lyte solution confers its relaxant action. Finally, we tested the vasoactive effect of Plasma-Lyte solution on human saphenous vein obtained by discard from coronary bypass operations. Plasma-Lyte solution at 37 degrees C effectively dilated norepinephrine-activated human saphenous vein, inducing complete relaxation within 20 minutes. On this basis, we recommend the use of Plasma-Lyte solution as a venodilating storage solution during coronary bypass operations to optimize vein graft relaxation before implantation.

Early postoperative graft dysfunction following transplantation of catecholamine-stimulated donor hearts

Early postoperative graft dysfunction following transplantation of catecholamine-stimulated donor hearts

Preoperative detection of IGG non-cytotoxic antibodies identifies primary renal transplant recipients at risk for early acute rejection and graft loss

Preoperative detection of IGG non-cytotoxic antibodies identifies primary renal transplant recipients at risk for early acute rejection and graft loss

Bleeding time as a predictor of early PTFE graft failure Richard J. Fowl, MD, st]Joseph E. Palascak, MD, Kevin J. Ose, MD, John Blebea, MD, and Richard R. Kempezinski, MD, University of Cincinnati, Cincinnati, Ohio

Bleeding time as a predictor of early PTFE graft failure Richard J. Fowl, MD, st]Joseph E. Palascak, MD, Kevin J. Ose, MD, John Blebea, MD, and Richard R. Kempezinski, MD, University of Cincinnati, Cincinnati, Ohio

The effect of surgical preparation and in-vitro distension on the intrinsic fibrinolytic activity of human saphenous vein

The objective of this study was to assess the effect of distension on the intrinsic fibrinolytic activity of human saphenous vein during its preparation for use as a bypass conduit prior to coronary artery surgery. Fibrinolytic activity was studied using fibrin plate techniques and Chromogenic assays for extractable tPA and uPA. Samples were obtained from patients undergoing routine coronary surgery. Fibrinolytic activity was compared in control vein (untouched) vein that had been prepared for use as a bypass conduit (surgical dissection, ligation of side branches and careful but uncontrolled manual distension) and segments of dissected vein distended in vitro to pressures of 230 or 120 mmHg. Uncontrolled distension and distension to 230 mmHg impaired fibrinolytic activity as determined by areas of lysis on fibrin plates (p < 0.05), (p < 0.005), tPA activity (p < 0.005) (p < 0.005) and uPA activity (p < 0.05), (p < 0.005). Distension to 120 mmHg had no effect on the fibrinolytic activity of human saphenous vein. Impaired fibrinolytic activity caused by uncontrolled distension of saphenous vein prior to its use as a vascular conduit may contribute to early vein graft thrombosis and can be avoided using controlled distension to < 120 mmHg.

Metabolic and physical factors in early coronary artery bypass vein graft occlusion

Metabolic and physical factors in early coronary artery bypass vein graft occlusion