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Biomedical subjects

Satoshi Furukawa

Publications and source records attributed to Satoshi Furukawa.

At least 19 recordsLinked to original sources
PubMed2006

Donor tricuspid annuloplasty during orthotopic heart transplantation: long-term results of a prospective controlled study.

BACKGROUND: Development of tricuspid regurgitation after orthotopic heart transplantation can cause heart failure along with renal and hepatic impairment and portends a poor prognosis. If tricuspid regurgitation causes significant symptoms, tricuspid valve repair or replacement is often required. This study was designed to study the effects of prophylactic tricuspid valve annuloplasty (TVA) during orthotopic heart transplantation on long-term survival, renal function, and amount of tricuspid regurgitation. METHODS: Between April 1997 and March 1998, 60 patients (aged 18 to 70 years; 22 female) randomly received either standard bicaval orthotopic heart transplantation (group STD; n = 30) or bicaval orthotopic heart transplantation with DeVega TVA (group TVA; n = 30). Tricuspid valve annuloplasty was performed on the donor heart before implantation using pledgeted 2-0 polypropylene and sized to an annulus of 29 mm. Echocardiographic measurements, laboratory values, and hemodynamics were obtained prospectively and reviewed by an independent data analyst. RESULTS: Follow-up of patients as of December 2003 was complete. Although there was a perioperative mortality advantage in group TVA, there was no difference between groups in long-term survival. At the end of the study, however, there was a statistical difference (group STD versus group TVA, p < 0.05) with regard to cardiac mortality (7 of 30 versus 3 of 30), average amount of tricuspid regurgitation (1.5 +/- 1.3 versus 0.5 +/- 0.4), percentage of patients with 2+ or greater tricuspid regurgitation (34% versus 0%), serum creatinine (2.9 +/- 2.0 versus 1.8 +/- 0.7), and difference in serum creatinine over baseline (2.0 +/- 2.1 versus 0.7 +/- 0.8). CONCLUSIONS: Prophylactic DeVega TVA of the donor heart is durable and decreases the incidence of cardiac-related mortality and tricuspid regurgitation after orthotopic heart transplantation. In addition, there is improved protection of renal function. Considering the ease and safety of TVA and its advantages, it should be performed as a routine adjunct to orthotopic heart transplantation.

Adolescent↗
PubMed2005

Factors affecting survival after heart transplantation: comparison of pre- and post-1999 listing protocols.

BACKGROUND: Listing status for heart transplantation (Tx) patients was changed in 1999 from Status 1 and 2 to Status 1A, 1B and 2. Because the selection process was modified in favor of seriously ill patients, it was not clear whether this change would affect survival or other aspects of transplant management. METHODS: We examined outcomes in 551 patients transplanted at our institution between 1986 and 2002 (pre-1999: n = 419; post-1999: n = 132) to determine the effects of change in listing protocol on transplant outcome. RESULTS: Using Cox proportional hazard analysis, survival was not different between pre-1999 (pre) and post-1999 (post). Overall waiting-list times were longer post-1999 (pre: 134 +/- 10.5 days, post: 172 +/- 15.6 days; p = 0.044), and were longer post-1999 for blood groups A (177 vs 123 days), B (96 vs 84 days) and O (229 vs 172 days), but were shorter post for blood group AB (42 vs 68 days). Survival was not affected by age (pre: 53.7 +/- 0.52 years, post: 53.1 +/- 1.04 years; hazard ratio [HR] 1.00; 95% confidence interval [CI] 0.996 to 1.023; p = 0.181), male gender (HR 1.132; 95% CI 0.822 to 1.56; p = 0.447) or waiting-list time. Serum creatinine was similar between the 2 groups (pre: 1.25 +/- 0.02, post: 1.26 +/- 0.04; p = 0.794), whereas pulmonary artery (PA) diastolic pressure was increased post-1999 (pre: 24.9 +/- 0.46, post: 27.0 +/- 0.74; p = 0.023). Survival was not affected by PA pressure (HR 1.00; 95% CI 0.986 to 1.014; p = 0.976), but an elevated pre-transplant creatinine reduced survival (HR 1.484; 95% CI 1.139 to 1.933; p = 0.003). CONCLUSIONS: The change in listing status implemented in 1999 caused an increase in wait times for patients with blood types A, B and O, and shortened wait time for type AB; however, no differences occurred in overall post-transplant survival after the change in listing protocol. Age, gender and PA pressure had no effect on survival in either time period, whereas pre-transplant serum creatinine decreased survival in both patient groups.

Blood Group Antigens↗
PubMed2005

Successful transplantation of an older donor heart with documented myocardial bridging: a case report.

Myocardial bridging, the overlying of myocardial tissue onto epicardial coronary arteries, is an anatomic variant that is widely present in the general population. This condition can be associated with reduced forward coronary flow. Once these hearts are identified in potential donors by either visual inspection or coronary catheterization, they may no longer be considered suitable for transplantation. We present a case study that successfully utilized such a heart explanted from an older donor with "bench" myotomy repair before implantation.

Contraindications↗
PubMed2005

Potential suitability for transplantation of hearts from human non-heart-beating donors: data review from the Gift of Life Donor Program.

BACKGROUND: Organ availability limits use of heart transplantation for treatment for end-stage heart disease. Hearts are currently obtained from donors declared brain dead (heart-beating donors [HBDs]). Although use of hearts from non-heart-beating donors (NHBDs) could reduce the shortage, they are considered unusable because of possible peri-mortem ischemic injury. METHODS: To project how use of NHBD hearts could increase heart donation, we retrospectively reviewed donor databases from the Gift of Life Donor Program (GLDP), our local organ procurement organization, from 2001 through 2003. We screened the NHBD population using conservative donor criteria, assuming an acceptable hypoxic/ischemic time (time from withdrawal of care to cross-clamp) of 30 minutes. RESULTS: During the study period, there were 894 HBDs, 334 heart transplants and 119 NHBDs. NHBDs were similar to HBDs with respect to gender and ethnicity, but NHBDs were proportionately younger. Of 119 NHBDs, 55 did not meet the age criteria (< or =45 years) and 20 were eliminated because of incomplete data. Eighty-two NHBDs were cross-clamped within 30 minutes of care withdrawal. Twenty NHBDs met all cardiac donor criteria, and 14 of these 20 had hypoxic/ischemic times < or =30 minutes. Pro rata estimation for the 20 NHBDs with incomplete data suggested 7 potential additional donors. CONCLUSIONS: Based on our assumptions, 12% to 18% of NHBDs in the study period (14 to 21 of 119 total) were potential heart donors, representing a 4% to 6% increase over of the number of heart transplants performed during the same time interval.

Adolescent↗
PubMed2005

Left ventricular assist devices as destination therapy: a new look at survival.

OBJECTIVE: The REMATCH trial compared the use of left ventricular assist devices with optimal medical management for patients with end-stage heart failure. When the trial met its primary end point criteria in July 2001, left ventricular assist device therapy was shown to significantly improve survival and quality of life. With extended follow-up, 2 critical questions emerge: (1) Did these benefits persist, and (2) did outcomes improve over the course of the trial, given the evolving nature of the technology? METHODS: We analyzed survival in this randomized trial by using the product-limit method of Kaplan and Meier. Changes in the benefits of therapy were analyzed by examining the effect of the enrollment period. RESULTS: The survival rates for patients receiving left ventricular assist devices (n = 68) versus patients receiving optimal medical management (n = 61) were 52% versus 28% at 1 year and 29% versus 13% at 2 years ( P = .008, log-rank test). As of July 2003, 11 patients were alive on left ventricular assist device support out of a total 16 survivors (including 3 patients receiving optimal medical management who crossed over to left ventricular assist device therapy). There was a significant improvement in survival for left ventricular assist device-supported patients who enrolled during the second half of the trial compared with the first half ( P = .03). The Minnesota Living with Heart Failure scores improved significantly over the course of the trial. CONCLUSION: The extended follow-up confirms the initial observation that left ventricular assist device therapy renders significant survival and quality-of-life benefits compared with optimal medical management for patients with end-stage heart failure. Furthermore, we observed an improvement in the survival of patients receiving left ventricular assist devices over the course of the trial, suggesting the effect of greater clinical experience.

Aged↗
PubMed2005

Effect of indole-3-acetic acid derivatives on neuroepithelium in rat embryos.

Indole-3-acetic acid (IAA), a natural auxin, induces microencephaly in rats exposed to IAA during gestation days (Days) 12-14, corresponding to the early stage of cerebral cortex development. The purpose of this study was to examine the effects of 5 IAA derivatives administration in pregnant rats on neuroepithelial cells in the embryos. N-Methylindole-3-acetic acid (1Me-IAA), 2-Methylindole-3-acetic acid (2Me-IAA), 2-Methyl-5-methoxyindole-3-acetic acid (2Me-5MeO-IAA), 5-Methoxyindole-3-acetic acid (5MeO-IAA), Indole butyric acid (IBA), and IAA were administered at 1,000 mg/kg except for 2Me-IAA at 500 mg/kg on Days 12, 13 and 14, and then embryos/fetuses were harvested on Day 14.5 or 21. The dams in the 1Me-IAA and 2Me-IAA groups exhibited rigidity and a decrease in locomotor activity. Although a decrease in the absolute brain weight was observed in the 1Me-IAA, 5MeO-IAA, IBA and IAA groups, a decrease in the relative brain weight was observed in only the IAA group. Histopathologically, apoptotic cells were observed mainly in the medial and dorsal layer of the neuroepithelium in the 5MeO-IAA and IAA groups on Day 14.5. The degree of induced neuroepithelial cell apoptosis was less in the 5MeO-IAA group than in the IAA group. However, it was confirmed that the histopathological changes induced by 5MeO-IAA were quite similar to the lesions induced by IAA and may have resulted from the same mechanisms.

Administration, Oral↗
PubMed2005

Effect of bilateral lung volume reduction surgery on FEV1 decline in severe emphysema.

STUDY OBJECTIVE: To examine whether lung volume reduction surgery (LVRS) alters the anticipated natural rates of decline in FEV1. DESIGN: Retrospective analysis of spirometry results (188 studies) in patients before and after bilateral LVRS. Setting. Large, urban, academic medical center. PATIENTS: 25 patients with severe emphysema (mean (SD) age 60+/-8 yrs; FEV1 0.74+/-0.29 L, 29% predicted). INTERVENTIONS: Bilateral LVRS performed via median sternotomy, with areas targeted for resection based on preoperative evaluation using high-resolution computed tomography, quantitative perfusion scans, and intraoperative inspection of the lungs. Linear regression analysis was performed on each patient using all serial postbronchodilator FEV1 values from before and after LVRS. RESULTS: Lung function data were available between 2-1001 days prior to LVRS and 71-1169 days after LVRS. Comparison of single pre- and post-LVRS FEV1 results confirmed a significant post-operative (3 month) improvement in lung function. The calculated rate of decline in FEV1 prior to LVRS was 202+/-205 mL/yr. Following LVRS, the rate of decline in FEV1 was unchanged at 178+/-150 mL/yr (p = 0.64). CONCLUSIONS: In patients with severe emphysema, bilateral LVRS does not appear to significantly alter the rate of FEV1 decline.

Aged↗
PubMed2004

Small airway morphometry and improvement in pulmonary function after lung volume reduction surgery.

We examined small airway morphometry from resected lung specimens in 25 patients with severe emphysema undergoing lung volume reduction surgery (LVRS) and correlated their pathologic findings to changes in FEV(1) 6 months after LVRS. Patients were classified into two groups: responders had a more than 12% and a more than 200-ml change in FEV(1) at 6 months, and nonresponders had 12% or less and/or 200 ml or less change in FEV(1). Epithelial height (EH) and perimeters and areas of peribronchial smooth muscle, epithelium, and subepithelial space were measured quantitatively. The degrees of interstitial fibrosis, vascular sclerosis, goblet cell hyperplasia, squamous metaplasia, chronic inflammation, peribronchial fibrosis, and bullous disease were assessed semiquantitatively. Despite similar baseline characteristics, nonresponders had a greater EH (0.045 vs. 0.035 mm, p = 0.025), greater EH adjusted for basement membrane perimeter (0.040 vs. 0.011, p = 0.016), greater epithelial area adjusted for basement membrane area (0.561 vs. 0.499, p = 0.040), and less bullous disease (1.7 vs. 2.6, p = 0.011) compared with responders. We found a linear relationship between percentage change in FEV(1) and bullous disease and inverse relationships between percentage change in FEV(1) and interstitial fibrosis, goblet cell hyperplasia, peribronchial fibrosis, and vascular sclerosis. We conclude that small airway morphometry and lung histopathology in patients with severe emphysema have an important influence on changes in FEV(1) 6 months after LVRS.

Basement Membrane↗
PubMed2004

Use of LeVeen pleuroperitoneal shunt for refractory high-volume chylothorax.

We present a case of intractable high-volume (> 2L/d) chylothorax after transhiatal esophagectomy treated successfully with the simultaneous insertion of both Denver (Denver Biomedical, Golden, CO) and LeVeen (Becton-Dickinson, Rutherford, NJ) pleuroperitoneal shunts. The patient initially had chemoradiotherapy for a T4N1 squamous cell carcinoma of the thoracic esophagus. Re-staging showed a dramatic shrinkage of tumor, and a transhiatal esophagectomy was performed. Sequential bilateral thoracotomies were performed on postoperative days 19 and 26 for attempted control of high-volume chylothorax, but these were unsuccessful. Subsequent pleuroperitoneal shunt insertion was used, which immediately controlled the effusion. A shunt study was performed shortly after hospital discharge, which showed an occluded Denver shunt and a patent LeVeen shunt. The patient succumbed to metastatic carcinoma 18 months after discharge, but no pleural effusion had recurred.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

Effect of older donor age on risk for mortality after heart transplantation.

BACKGROUND: Despite the increasingly common use of donor hearts at least 50 years of age, controversy still remains regarding long-term outcome. Our goal was to determine if older donor age is associated with an increased risk of mortality and specifically if the use of donor hearts at least 50 years of age reduces survival. METHODS: We retrospectively studied records of all primary heart transplants performed between January 1990 and July 2002. Fifty-six patients who had received donor hearts at least 50 years of age were compared with 611 recipients of donor hearts less than 50 years of age. Clinicopathologic parameters were analyzed for their effect on mortality using the Cox proportional hazard model with calculation of hazard ratios (HR). Cut-point analysis of donor age was used to determine which donor age is associated with the greatest risk of mortality after transplant. RESULTS: Recipients of donor hearts at least 50 years of age were older (58.5 years +/- 7.0 vs 53.2 +/- 11.6; mean +/- standard deviation [SD]; p < 0.0001), suffered more often from ischemic cardiomyopathy (69% vs 50%, p = 0.01), and experienced a longer waiting time (192.2 days +/- 301.0 vs 138.6 +/- 190.8, p < 0.0001). Donor hearts at least 50 years of age (age 54.1 +/- 3.5 years) were more often female (50% vs 34%, p = 0.03), died less often of "head trauma" (9% vs 42%, p < 0.0001), and exhibited fewer cytomegalovirus (CMV) mismatches (29% vs 39%, p = 0.04) than donor hearts less than 50 years of age (age 26.8 +/- 12.3 years). Multivariate predictors of mortality were rejection index (HR 1.90 per unit [rejections/100 survival days], p < 0.0001), donor age (HR 1.16 per 10-year increment, p = 0.002), and recipient age (HR 1.24 per 10-year increment, p = 0.04). Recipients of donor hearts at least 50 years of age had reduced 1-year and 5-year survival ([65.7% vs 81.7%, p < 0.05] and [48.3% vs 68.4%, p < 0.05], respectively), as well as a higher proportion of deaths occurring within 1 month of transplant (41% of total deaths vs 23%, p = 0.06). Cut-point analysis indicated the characteristic of donor age of at least 40 years (categorical variable) to predict mortality with the same degree of fit as age used as a continuous variable. CONCLUSIONS: Although we observed a substantial reduction in survival among patients who were allocated donor hearts at least 50 years of age, this difference was not solely attributable to the categorical variable of donor age 50 in this group. Donor age as a continuous variable, however, was determined to be a notable predictor of survival and use of the donor age cut-point of 40 years (categorical variable) allowed risk stratification with similar accuracy. The use of a donor age cut-point of 40 years may be a useful clinical criterion for graft-related risk assessment.

Adult↗
PubMed2004

Left ventricular assist device performance with long-term circulatory support: lessons from the REMATCH trial.

BACKGROUND: Left ventricular assist device (LVAD) failure and malfunction rates are critical gauges for establishing LVADs as a long-term therapy for end-stage heart failure patients. These device performance measures, however, have been inadequately characterized in the bridge-to-transplantation literature. METHODS: REMATCH is a randomized trial that compares optimal medical management with LVAD implantation for patients with end-stage heart failure. An independent committee adjudicated patient outcomes. The primary endpoint--survival--was analyzed by intention to treat using the log-rank statistic. Frequency of event occurrence was analyzed by Poisson regression. The time to first event was analyzed by the product limit method. Device performance was disaggregated into confirmed malfunctions and system failures. The latter were events in which patients could not be rescued with backup circulatory support measures. RESULTS: The 1-year survival rate was 52% (95% confidence limit [CL]; 40%-63%) for LVAD patients versus 28% (95% CL; 17%-39%) for medical patients and the 2-year survival rate was 29% (95% CL; 19%-40%) for LVAD patients versus 13% (95% CL; 5%-22%) for medical patients. System failure was 0.13 per patient per year and the confirmed LVAD malfunction rate was 0.90. Freedom from device replacement was 87% at 1 year and 37% at 2 years. CONCLUSIONS: Despite the observed rates of device malfunction and replacement, LVAD implantation confers clinically significant improvement with regard to survival as compared with medical management. Device modifications and innovations for infection management exhibit great promise of improving device performance in the near future.

Aged↗
PubMed2004

A one-year comparison of prophylactic donor tricuspid annuloplasty in heart transplantation.

BACKGROUND: The bicaval technique for orthotopic heart transplantation decreases the incidence of tricuspid valve regurgitation when compared with the standard biatrial technique. This study was designed to study the effects of prophylactic tricuspid valve annuloplasty during bicaval orthotopic heart transplantation on survival, renal function, and amount of tricuspid valve regurgitation. METHODS: Between April 1997 and March 1998, 60 patients (age 18 to 70 years, 22 women) randomly received either bicaval orthotopic heart transplantation (n = 30) or bicaval orthotopic heart transplantation with DeVega tricuspid valve annuloplasty (n = 30). Tricuspid valve annuloplasty was performed on the donor heart before implantation using pledgeted 2-0 polypropylene suture and sized to an annulus of 29 mm. Echocardiographic variables, laboratory values, and hemodynamics were obtained prospectively and reviewed by an independent data analyst. RESULTS: Intraoperatively, the group undergoing tricuspid valve annuloplasty had a shorter reperfusion time (46 +/- 29 minutes versus 65 +/- 48 minutes; p < 0.05) and higher mean pulmonary artery to central venous pressure difference (11.8 +/- 3.7 mm Hg versus 15.3 +/- 4.1 mm Hg; p = 0.001). Additional differences between the two groups included early mortality from donor dysfunction (4 of 30 patients versus 0 of 30 patients; p < 0.05), amount of tricuspid valve regurgitation at 1 year (1.3 +/- 1.0 versus 0.2 +/- 0.3; p < 0.05), and percentage of patients with 2+ or greater tricuspid valve regurgitation (34% versus 0%; p < 0.05). CONCLUSIONS: Tricuspid valve annuloplasty of the donor heart before bicaval orthotopic heart transplantation improves immediate donor heart function as demonstrated by better right ventricular performance, lower perioperative mortality, and shorter reperfusion times. At 1 year, there is less tricuspid valve regurgitation but no difference in renal function. Considering the ease and safety of tricuspid valve annuloplasty and its advantages, it should be performed as a routine adjunct with bicaval orthotopic heart transplantation.

Adult↗
PubMed2004

Successful treatment of esophageal cancer with transhiatal esophagectomy after heart transplantation.

A 55-year-old heart transplant recipient with reflux esophagitis presented for routine endoscopic surveillance of an area of Barrett's metaplasia initially seen 3 years previously. Esophagogastroduodenoscopy revealed adenocarcinoma at 33 cm from the incisors. The preoperative clinical stage was T1N0M0 by endoscopic ultrasound. Transhiatal esophagectomy was performed with R0 resection of the cancer, and the patient recovered uneventfully. Pathologic examination confirmed esophageal adenocarcinoma (T1N0M0) in Barrett's mucosa. The patient is doing well, and has no evidence of disease after 18 months.

Adenocarcinoma↗
PubMed2004

Histopathological findings of cleft palate in rat embryos induced by triamcinolone acetonide.

Triamcinolone acetonide (TAC), a synthetic glucocorticoid, induces cleft palate resulting from poor development of palatal shelves in mice. However, TAC has no effect on medial edge epithelial cells (MEE cells) in secondary palatal shelves. In the present study, we examined the relationship between the pathogenesis of cleft palate and the effects on MEE cells and palatal mesenchymal cells in rat embryos/fetuses exposed to TAC. Pregnant Wistar Hannover rats were given TAC intramuscularly at 0.5 mg/kg at gestation days (Day) 12, 13, and 14, then embryos/fetuses were harvested on Days 14.5, 15, 16 and 20. The effects of TAC were as follows; an inhibition of palatal mesenchymal cell proliferation on Day 14.5, a decrease in the density of palatal mesenchymal cells and MEE cells, and expression of epidermal growth factor (EGF) receptors in MEE cells on Day 15, and stratified squamous differentiation of MEE cells with expression of cytokeratin and EGF receptors on Day 16. These findings indicated that TAC inhibited the proliferation of mesenchymal cells and affected the differentiation of MEE cells into stratified squamous epithelia in the palatal shelves of rat embryos. However, these stratified squamous MEE cells partially fused with each other. Thus, we suspected that a major contributing factor to the formation of TAC-induced cleft palate might not be the altered differentiation of MEE cells, but the inhibition of mesenchymal cell proliferation.

Animals↗
PubMed2004

In vitro chemosensitivity of hepatocellular carcinoma for hepatic arterial infusion chemotherapy using the MTT assay with the combinations of antitumor drugs.

Despite the hepatic arterial infusion chemotherapy (HAI) has been advocated as an effective therapy for hepatocellular carcinoma (HCC) with multiple intrahepatic metastases, chemosensitivity of HCC for HAI with multidrug regimen has not been sufficiently investigated. The purpose of this study was to evaluate the in vitro chemosensitivity of HCC using 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT) assay with the combinations of various antitumor drugs, and compared with the clinical results of HAI for patients with multiple intrahepatic recurrences of HCC. To evaluate the in vitro chemosensitivity of HCC to the combinations of antitumor drugs, 54 resected specimens of HCC were assayed using MTT assay with seven antitumor agents, 5-fluorouracil (5-FU), mitomycin C (MMC), adriamycin (ADM), etoposide (VP-16), cisplatin (CDDP), methotrexate (MTX) and CPT-11 (SN-38), exposed singly, or in combination. The data were compared with the clinical results of HAI for patients who manifested the multiple intrahepatic recurrence. In addition, the in vitro combined effect of CDDP and 5-FU for human hepatocellular carcinoma cell, KYN-1 and KYN-2, was analysed quantitatively. Of 54 resected specimens, 40 specimens assayed successfully, and an increased in vitro chemosensitivity of HCC when treated with combinations of antitumor drugs was observed: single drug 12.2%, two drugs combined 50.9% and three drugs combined 67.0%. The results of in vitro assay were well correlated, 85.7% in predicting accuracy, with the clinical results of 14 patients who underwent HAI for multiple recurrence of HCC, and also correlated with the experimental results of the combined use of CDDP and 5-FU in KYN-1 and KYN-2 in terms of pharmacokinetic reactions, i.e. synergism or antagonism. The MTT assay with the combinations of antitumor drugs represents an informative chemosensitivity test to HAI with multidrug regimen for recurrence of HCC.

Adult↗
PubMed2003

Off-pump technique for Thoratec left ventricular assist device insertion.

We present a case of left ventricular assist device (Thoratec; Thoratec Laboratories Corp, Pleasanton, CA) insertion performed through a left thoracotomy without cardiopulmonary bypass in a patient with severe end-stage congestive heart failure with renal and respiratory dysfunction and a history of multiple cardiac operations.

Assisted Circulation↗
PubMed2003

Cardiac transplantation across a positive prospective lymphocyte cross-match in sensitized recipients.

BACKGROUND: Although there is an increasing body of evidence for a deleterious effect of mismatched donor HLA antigens on the outcome of human cardiac transplantation, the role of anti-HLA lymphocytotoxic antibodies remains controversial. Thus, their appearance after cardiac transplantation has been associated with poor outcome by some groups; whereas others have reported them to be of no clinical significance. Furthermore, their presence prior to cardiac transplantation has also been the subject of similarly conflicting reports. The deleterious effect of such pre-existing antibodies has been predicted by a positive lymphocyte cross-match (LCM), which, for most patients awaiting renal transplantation and in many requiring a cardiac allograft, leads to cancellation of the operation. The reason for undertaking the current study was to test the hypothesis that the constraints which a positive LCM result impose in preventing renal transplantation may not apply to orthotopic heart transplantation (OHT). PATIENTS AND METHODS: Four sensitized patients underwent OHT across a positive prospective LCM. Three were females, and one of those females also underwent cadaveric renal transplantation at the time of OHT. All four patients received aggressive early post-transplant immunosuppressive therapy, which included plasmapheresis, intravenous immunoglobulin (IVIg), antiproliferative agents (cyclophosphamide, basiliximab) and cytokine down-regulators (calcineurin inhibitors, muromonab-CD3) and anticell antibodies (OKT3, ATG). They also received standard immunosuppressive therapy which included corticosteroids. Complement-dependent cytotoxicity (CDC) was used for the identification of anti-HLA lymphocytotoxic antibodies. Reactivity of the latter against more than 10% of a panel of well-characterized T cells was considered sensitization, and required LCM to be performed prospectively, which test was also performed using the CDC technique. RESULTS: Three of the patients exhibited evidence suggestive of acute or hyperacute rejection in endomyocardial biopsy specimens by postoperative day (POD) 7. Two of the three patients with rejection also exhibited haemodynamic instability (elevated filling pressures and reduced cardiac index) on POD 1, which improved with inotropic support. One patient sustained a cardiac arrest on POD 7, and was successfully resuscitated without sequelae. All patients are now doing well, postoperatively (follow-up: 17-57 months) post-transplant. Two patients have normal left ventricular function and one patient has mild left ventricular dysfunction. Two have no further evidence of sensitization (PRA < 10%). CONCLUSIONS: Although the number of patients in this study is small, the long-term successful outcome of OHT following positive prospective cross-matches suggests that such a test result, in contrast to the restraints it imposes on renal transplantation, may not be a contra-indication to transplantation of the human heart. If OHT proceeds after the LCM is reported positive, aggressive immunotherapy should not only be initiated early, but should also be targeted at humoral-vascular rejection in particular.

Adult↗