Preservation of post-transplant lung function with aerosol cyclosporin.

Post-lung transplant use of aerosol cyclosporin (ACsA) is considered by examining the relationship between deposited aerosol dose and effect. In a sub-study of placebo controlled trials of ACsA as a rejection prophylaxis, 15 drug subjects received aerosol dose quantification tests to gage their ability to effectively deposit the nebulised drug in their transplanted lung(s). A total of seven placebo subjects received mock deposition tests. The deposited doses and mock doses were compared to changes in the forced expiratory volume in one second, at six time points during the 2-yr trial period (ACsA was started within 6 weeks post-transplant). Linear relationships were demonstrated between deposited dose and improvement in lung function in the drug subjects at all intervals. Mock dose data from placebo subjects did not demonstrate similar correlation. Based on these results, subjects were grouped by dose and compared. Subjects depositing > or = 5 mg of the drug in the periphery of their transplant(s) had improving pulmonary function on average. Low-dose and placebo subjects demonstrated declines, more A2-A4 rejection events in the latter portion of the trial, and more chronic rejection beyond the end of the trial. A dose-to-effect relationship is demonstrated for aerosol cyclosporin in terms of pulmonary function and biopsy proven rejection.

Aerosol cyclosporin therapy in lung transplant recipients with bronchiolitis obliterans.

The majority of patients who develop bronchiolitis obliterans, after lung transplantation, die within 2-3 yrs after onset since treatment with conventional immunosuppression is typically ineffective. A case/control study was conducted in lung transplant recipients with biopsy-documented bronchiolitis obliterans to determine whether aerosol cyclosporin use contributed to increased survival. The cases comprised 39 transplant recipients who received open-label aerosol cyclosporin treatment in addition to conventional immunosuppression. The controls were transplant recipients treated with conventional immunosuppression alone. There were 51 controls from the University of Pittsburgh Medical Center and 100 from a large multicentric database (Novartis Lung Transplant Database). Forced expiratory volume in one second expressed as a percentage of the predicted value was an independent predictor of survival in all patients with bronchiolitis obliterans. Cox proportional-hazards analysis revealed a survival advantage for aerosol cyclosporin cases compared to the Pittsburgh control group. A survival advantage was also seen when comparing study cases to multicentric controls. Aerosol cyclosporin, given with conventional immunosuppression to lung transplant recipients with bronchiolitis obliterans, provides a survival advantage over conventional therapy alone.

Minimally invasive coronary bypass without general endotracheal anesthesia.

This report describes the case of a 51-year-old man with myocardial ischemia resulting from in-stent restenosis of the left anterior descending coronary artery who underwent a minimally invasive direct coronary artery bypass using thoracic epidural analgesia while awake, without general endotracheal anesthesia.

Sustained angina relief 5 years after transmyocardial laser revascularization with a CO(2) laser.

BACKGROUND: Although transmyocardial laser revascularization (TMR) has provided symptomatic relief of angina over the short term, the long-term efficacy of the procedure is unknown. Angina symptoms as assessed independently by angina class and the Seattle Angina Questionnaire (SAQ) were prospectively collected up to 7 years after TMR. METHODS: Seventy-eight patients with severe angina not amenable to conventional revascularization were treated with a CO(2) laser. Their mean age was 61+/-10 years at the time of treatment. Preoperatively, 66% had unstable angina, 73% had had >/=1 myocardial infarction, 93% had undergone >/=1 CABG, 42% had >/=1 PTCA, 76% were in angina class IV, and 24% were in angina class III. Their average pre-TMR angina class was 3.7+/-0.4. RESULTS: After an average of 5 years (and up to 7 years) of follow-up, the average angina class was significantly improved to 1.6+/-1 (P=0.0001). This was unchanged from the 1.5+/-1 average angina class at 1 year postoperatively (P=NS). There was a marked redistribution according to angina class, with 81% of the patients in class II or better, and 17% of the patients had no angina 5 years after TMR. A decrease of >/=2 angina classes was considered significant, and by this criterion, 68% of the patients had successful long-term angina relief. The angina class results were further confirmed with the SAQ; 5-year SAQ scores revealed an average improvement of 170% over the baseline results. CONCLUSIONS: The long-term efficacy of TMR persists for >/=5 years. TMR with CO(2) laser as sole therapy for severe disabling angina provides significant long-term angina relief.

Macrophage accumulation associated with rat cardiac allograft rejection detected by magnetic resonance imaging with ultrasmall superparamagnetic iron oxide particles.

BACKGROUND: Acute cardiac allograft rejection continues to be the cause of graft loss and contributes to the morbidity and mortality after cardiac transplantation. In this study, we report a new method for detecting organ rejection in transplantation with an MR-based technique using dextran-coated ultrasmall superparamagnetic iron oxide (USPIO) particles. These particles ( approximately 27 nm in diameter) are known to shorten relaxation times in MRI experiments. METHODS AND RESULTS: A new rat model of heterotopic heart and lung transplantation has been developed for MRI experiments. Allotransplantations (DA-->BN) were performed (n=8), with syngeneic transplantations (BN-->BN) serving as controls (n=8). MR images were obtained with a gradient echo method. At postoperative day 7, allotransplants developed moderate rejection as determined histopathologically. A significant reduction in MR signal intensity was observed after USPIO injection into rats with allotransplanted hearts. Syngeneic transplants showed no differences in MR signal intensity before and after USPIO injections. After injection of USPIO particles at postoperative day 6, a group of allotransplanted rats was treated with cyclosporin A (3 mg/kg). Animals treated with cyclosporin A for 7 days showed no reduction in MR signal intensity after USPIO reinjection at day 14, whereas animals treated for 4 days showed a significant decrease in MR signal intensity in the transplanted hearts indicative of acute graft rejection. Pathological analysis of these animals revealed that dextran-coated USPIO particles were taken up by the infiltrating macrophages that accumulated within the rejecting cardiac graft. CONCLUSIONS: This MRI method offers promise as a noninvasive method for detecting transplant allograft rejection.

Atrial fibrillation: prevalence after minimally invasive direct and standard coronary artery bypass.

BACKGROUND: This study identified and compared the prevalence of new-onset atrial fibrillation (AFIB) following standard coronary artery bypass grafting (SCABG) with cardiopulmonary bypass (CPB) and minimally invasive direct vision coronary artery bypass grafting (MIDCAB) without CPB. A further comparison was made between AFIB prevalence in SCABG and MIDCAB subjects with two or fewer bypasses. METHODS: This is a retrospective, comparative survey. Patients with new-onset AFIB who underwent SCABG or MIDCAB alone were identified electronically using a triangulated method (International Classification of Diseases, 9th revision, Clinical Modification [ICD-9 CM] code; clinical database word search; and pharmacy database drug search). RESULTS: The total sample (n = 814; 94 MIDCAB, 720 SCABG) exhibited a trend toward lower AFIB prevalence in MIDCAB (23.4%) versus SCABG (33.1%) subjects (p = 0.059). AFIB prevalence in the SCABG subset with two or less vessel bypasses (n = 98; n = 18 single vessel, n = 80 double vessels) and MIDCAB subjects (n = 94; n = 90 single vessels, n = 4 double vessels) was almost identical (SCABG subset 24.5% versus MIDCAB 23.4%, p = 0.860). Slightly more than half (56.9%) of new-onset AFIB subjects were identified by ICD-9 CM codes, with the remainder by word search (37.7%) or procainamide query (5.4%). CONCLUSIONS: In this sample, the number of vessels bypassed seemed to have a greater influence on AFIB prevalence than the application of CPB or the surgical approach. Retrospective identification of AFIB cases by ICD-9 CM code grossly underestimated AFIB prevalence.

The effect of cytokine gene polymorphisms on pediatric heart allograft outcome.

BACKGROUND: Cytokines play a major role in the inflammatory and immune responses that mediate allograft outcome. Several studies have shown that the production of cytokines varies among individuals and these variations are determined by genetic polymorphisms, most commonly within the regulatory region of the cytokine gene. The aim of this study was to assess the effect of these allelic variations on acute rejection after pediatric heart transplantation. METHODS: We performed cytokine genotyping using polymerase chain reaction-sequence specific primers in 93 pediatric heart transplant recipients and 29 heart donors for the following functional polymorphisms: tumor necrosis factor-alpha (TNF-alpha) (-308), interleukin (IL)-10 (-1082, -819, and -592), TGF-beta1 (codon 10 and 25), IL-6 (-174), and interferon-gamma (INF-gamma) (+874). The distribution of polymorphisms in this population did not differ from published controls. The patients were classified as either non-rejecters (0 or 1 episode) or rejecters (> 1 episode) based on the number of biopsy proven rejection episodes in the first year after transplantation. RESULTS: Forty-two of the 69 TNF-alpha patients (61%) in the low producer group were non-rejecters, while 9 of the 24 (37.5%) with high TNF-alpha were non-rejecters (p = 0.047). In contrast, IL-10 genotype showed the opposite finding. Forty-two of the 66 patients (64%) in the high and intermediate IL-10 group were non-rejecters, while 9 of the 26 (35%) in the low IL-10 group were non-rejecters (p = 0.011). The combination of low TNF-alpha with a high or intermediate IL-10 genotype was associated with the lowest risk of rejection (34/49 or 69% non-rejecters). Neither the distribution of the IL-6, INF-gamma, and TGF-beta1 genotype in recipients nor the donor genotype showed any association with acute rejection. CONCLUSION: Genetic polymorphisms that have been associated with low TNF-alpha and high IL-10 production are associated with a lower number of acute rejection episodes after pediatric heart transplantation.

HeartMate II left ventricular assist system: from concept to first clinical use.

The HeartMate II left ventricular assist device (LVAD) (ThermoCardiosystems, Inc, Woburn, MA) has evolved from 1991 when a partnership was struck between the McGowan Center of the University of Pittsburgh and Nimbus Company. Early iterations were conceptually based on axial-flow mini-pumps (Hemopump) and began with purge bearings. As the project developed, so did the understanding of new bearings, computational fluid design and flow visualization, and speed control algorithms. The acquisition of Nimbus by ThermoCardiosystems, Inc (TCI) sped developments of cannulas, controller, and power/monitor units. The system has been successfully tested in more than 40 calves since 1997 and the first human implant occurred in July 2000. Multicenter safety and feasibility trials are planned for Europe and soon thereafter a trial will be started in the United States to test 6-month survival in end-stage heart failure.

Cardiopulmonary transplantation for congenital heart disease in the adult.

BACKGROUND: Patients surviving into adulthood with congenital heart disease (CHD) often succumb to progressive cardiopulmonary dysfunction. For these patients transplantation is often considered. METHODS: We performed a retrospective review of 69 adults (age >18 years) with CHD transplanted between 1984 and 1999. RESULTS: We evaluated 31 heart-lung (HLTxp), 30 lung (LTxp), and 8 heart (HTxp) transplants performed in 22 men and 47 women with CHD. Mean age was 37 +/- 10 years with a mean follow-up of 3.1 +/- 3.5 years. A concomitant cardiovascular procedure was performed in 1 HLTxp, 23 LTxp, and 2 HTxp. Early mortality (>30 days) was 26% (8/31) for HLTxp, mostly due to bleeding. Early LTxp mortality was 23% (7/30), largely due to graft failure. One and 3-year survival was similar in adults transplanted for CHD and adults transplanted for other disease. Early mortality among HTxp recipients was 50% (4/8) from rejection or technical complications. Survival for patients undergoing HLTxp versus LTxp with cardiac repair was similar. When examined by era, the survival of patients transplanted for CHD between 1992 and 1999 was greater than that of patients transplanted between 1984 and 1991. CONCLUSIONS: Adults undergoing HLTxp and LTxp for CHD can expect survival comparable to that of non-CHD adults. In the presence of a reparable cardiac lesion, LTxp with cardiovascular repair for CHD is an attractive option, optimizing organ allocation. Specific technical concerns are discussed. Survival of adults undergoing cardiopulmonary transplantation for CHD has improved over time.

P-glycoprotein (P-gp) is upregulated in peripheral T-cell subsets from solid organ transplant recipients.

Immunosuppressive agents such as cyclosporine, tacrolimus, sirolimus, and corticosteroids are substrates for the transmembrane multidrug resistance pump P-glycoprotein (P-gp). Experience in oncologyhas suggested that chronic exposure to P-gp substrates induces upregulation of P-gp activity, which could result in resistance to immunosuppressive drugs. The authors investigated P-gp function in CD4+ and CD8+ T cells from the peripheral blood of solid organ transplant recipients (SOTX). Subjects included 14 stable SOTX (10 liver, 4 lung) and 16 healthy controls. Four-color flow cytometry was used to simultaneously measure intracellular concentration of the fluorescent P-gp substrate Rhodamine 123 (Rh123) and surface expression of CD45RO (nominal memory/effector), CD45RA (naive), and either CD4 or CD8. P-glycoprotein function was measured by a dye efflux assay in which activity was inferred from a decrease in Rh123 fluorescence. CD4+ and CD8+ T cells from patients and control subjects eliminated Rh123, and this activity was inhibited by verapamil, a known P-gp substrate. CD8+ T cells had greater P-gp activity than CD4+ cells, and naive and transitional T cells displayed greater activity than memory T cells. Activity was bimodal in CD8+ CD45RO+ T cells, with a subset of these cells expressing the greatest P-gp activity. Patient CD8+ naive and transitional T cells had upregulated P-gp activity compared to control subjects. We conclude that (1) P-gp activityis significantly upregulated in specific T-cell subsets (CD8+/CD45RA+) in the peripheral blood of SOTX, and (2) the bimodal nature of P-gp response in CD8+ T cells complicates analysis of the effect of chronic administration of P-gp substrates to SOTX.

A novel approach with magnetic resonance imaging used for the detection of lung allograft rejection.

OBJECTIVE: Although various techniques have been explored for the detection and quantification of allograft transplant rejection, a practical and reliable method that is noninvasive is still elusive. METHODS: For our magnetic resonance imaging experiments, we have developed a new rat model of heterotopic lung transplantation to the inguinal region. Allogeneic transplants (DA to Brown Norway) were performed with and without cyclosporine A (INN: ciclosporin) treatment, with syngeneic transplants (Brown Norway to Brown Norway) serving as controls (n = 6 per group). Magnetic resonance images were obtained with a gradient echo method before and after injection of ultra-small superparamagnetic iron oxide particles. RESULTS: At day 5, allogeneic transplants without cyclosporine A treatment showed a grade 4 rejection histologically. A significantly lower magnetic resonance signal was seen 24 hours after injection of ultra-small superparamagnetic iron oxide particles compared with the preinjection image (346 +/- 7.6 vs 839 +/- 43.4 arbitrary units; P <. 05). Syngeneic transplants showed no evidence of rejection histologically and no differences in magnetic resonance imaging signals between the images before and after injection of ultra-small superparamagnetic iron oxide particles (863 +/- 18.8 vs 880 +/- 22.5). Allotransplants treated with cyclosporine A showed a grade 2 rejection histologically. The change in magnetic resonance signals in that group was small but showed a significant decrease in signal intensity after injection (646 +/- 10.5 vs 889 +/- 23.5, P <.05). Immunohistochemistry and iron staining of the allografts indicated that ultra-small superparamagnetic iron oxide particles were taken up by the infiltrating macrophages that accumulated at the rejection site. CONCLUSIONS: We have demonstrated a novel approach for the detection of acute lung allograft rejection using magnetic resonance imaging coupled with injection of ultra-small superparamagnetic iron oxide particles. Despite its limitations, our method might be a first step toward a potential clinical application.

Effects of donor bone marrow infusion in clinical lung transplantation.

BACKGROUND: We have demonstrated that donor cell chimerism is associated with a lower incidence of obliterative bronchiolitis (OB) in lung recipients, and that donor chimerism is augmented by the infusion of donor bone marrow (BM). We herein report the intermediate results of a trial combining the infusion of donor BM and lung transplantation. METHODS: Clinical and in vitro data of 26 lung recipients receiving concurrent infusion of donor bone marrow (3.0 to 6.0 x 10(8) cells/kg) were compared with those of 13 patients receiving lung transplant alone. RESULTS: Patient survival and freedom from acute rejection were similar between groups. Of the patients whose graft survived greater than 4 months, 5% (1 of 22) of BM and 33% (4 of 12) of control patients, developed histologic evidence of OB (p = 0.04). A higher proportion (but not statistically significant) of BM recipients (7 of 10, 70%) exhibited donor-specific hyporeactivity by mixed lymphocyte reaction assays as compared with the controls (2 of 7, 28%). CONCLUSIONS: Infusion of donor BM at the time of lung transplantation is safe, and is associated with recipients' immune modulation and a lower rate of obliterative bronchiolitis.

Traumatic rupture of an aberrant right subclavian artery.

We describe a patient who sustained a traumatic rupture of an aberrant right subclavian artery. An interposition graft was used to restore continuity of the artery to the descending thoracic aorta.

A clinical trial combining donor bone marrow infusion and heart transplantation: intermediate-term results.

BACKGROUND: Donor chimerism (the presence of donor cells of bone marrow origin) is present for years after transplantation in recipients of solid organs. In lung recipients, chimerism is associated with a lower incidence of chronic rejection. To augment donor chimerism with the aim to enhance graft acceptance and to reduce immunosuppression, we initiated a trial combining infusion of donor bone marrow with heart transplantation. Reported herein are the intermediate-term results of this ongoing trial. METHODS: Between September 1993 and August 1998, 28 patients received concurrent heart transplantation and infusion of donor bone marrow at 3.0 x 10(8) cells/kg (study group). Twenty-four contemporaneous heart recipients who did not receive bone marrow served as controls. All patients received an immunosuppressive regimen consisting of tacrolimus and steroids. RESULTS: Patient survival was similar between the study and control groups (86% and 87% at 3 years, respectively). However, the proportion of patients free from grade 3A rejection was higher in the study group (64% at 6 months) than in the control group (40%; P =.03). The prevalence of coronary artery disease was similar between the two groups (freedom from disease at 3 years was 78% in study patients and 69% in controls). Similar proportions of study (18%) and control (15%) patients exhibited in vitro evidence of donor-specific hyporesponsiveness. CONCLUSIONS: The infusion of donor bone marrow reduces the rate of acute rejection in heart recipients. Donor bone marrow may play an important role in strategies aiming to enhance the graft acceptance.

Regional low-flow perfusion provides cerebral circulatory support during neonatal aortic arch reconstruction.

OBJECTIVE: Because of concerns regarding the effects of deep hypothermia and circulatory arrest on the neonatal brain, we have developed a technique of regional low-flow perfusion that provides cerebral circulatory support during neonatal aortic arch reconstruction. METHODS: We studied the effects of regional low-flow perfusion on cerebral oxygen saturation and blood volume as measured by near-infrared spectroscopy in 6 neonates who underwent aortic arch reconstruction and compared these effects with 6 children who underwent cardiac repair with deep hypothermia and circulatory arrest. RESULTS: All the children survived with no observed neurologic sequelae. Near-infrared spectroscopy documented significant decreases in both cerebral blood volume and oxygen saturations in children who underwent repair with deep hypothermia and circulatory arrest as compared with children with regional low-flow perfusion. Reacquisition of baseline cerebral blood volume and cerebral oxygen saturations were accomplished with a regional low-flow perfusion rate of 20 mL x kg(-1) x min(-1). CONCLUSIONS: Regional low-flow perfusion is a safe and simple bypass management technique that provides cerebral circulatory support during neonatal aortic arch reconstruction. The reduction of deep hypothermia and circulatory arrest time required may reduce the risk of cognitive and psychomotor deficits.

Optimal dosing of intravenous tacrolimus following pediatric heart transplantation.

BACKGROUND: Early experience with intravenous tacrolimus at high doses (0.1-0.15 mg/kg/day) was associated with frequent clinical toxicity. The optimal dosing regimen after pediatric heart transplantation is unknown. METHODS: We retrospectively reviewed data on the last 45 pediatric heart transplant recipients to document the time required to achieve therapeutic blood levels and the safety of 2 differing intravenous dosing regimens (tacrolimus 0.03 & 0.05 mg/kg/day as continuous i.v. infusion). Target plasma levels were (1.2-1.7 ng/ml) with levels >2.0 ng/ ml considered toxic, and target whole blood levels were 15-20 ng/ml with levels >25 ng/ml considered toxic. RESULTS: Mean age at transplantation was 7.5 +/- 5.6 years (0.1-18), and 14 were infants. Intravenous tacrolimus was commenced at a mean of 7 +/- 3 hours (range 2-16) after arrival in the ICU. Eight patients were excluded from analysis because of protocol modifications. Of the remaining 37 pts, 9 received initial infusion at 0.03 mg/kg/day; 3 (33%) achieved 'therapeutic' levels within 48 hours and 1 patient had a toxic level (27 ng/ml) at 36 hours. Twenty-eight patients received 0.05 mg/kg/day; 18 (64%) achieved therapeutic levels within 48 hours and 9 (32%) developed toxic levels. Patients with toxic whole blood levels had higher tacrolimus levels on first blood assay compared to those who did not develop toxicity (16.4 +/- 3.4 vs 9.3 +/- 3.9, p < .0001; level >10 ng/ml on first assay in 7/7 toxic patients vs 7/19 without toxicity, p = .004). Patients receiving the higher dose regimen had fewer episodes of moderate or severe rejection (> or =Grade 3A) at first biopsy than those receiving the lower dose infusion (32% vs 75%; p = .046). No patient required renal dialysis. CONCLUSIONS: Dosing below 0.05 mg/kg/day may result in clinically important delay in achieving therapeutic levels. Toxicity may be reduced by frequent monitoring of levels for the first 48 hours after transplantation especially when the initial level is >10 ng/ml.

Transmyocardial laser revascularization in the patient with unmanageable unstable angina.

BACKGROUND: Transmyocardial laser revascularization (TMR) provides relief for patients with chronic angina, nonamenable to direct coronary revascularization. Unmanageable, unstable angina (UUA) defines a subset of patients with refractory angina who are at high risk for myocardial infarction and death. Patients were classified in the UUA group when they had been admitted to the critical care unit with unstable angina for 7 days with three failed attempts at weaning them off intravenous antianginal medications. METHODS: Seventy-six treated patients were analyzed to determine if TMR is a viable option for patients with unmanageable unstable angina. These patients were compared with 91 routine protocol patients (protocol group [PG]) undergoing TMR for chronic angina not amenable to standard revascularization. The procedure was performed through a left thoracotomy without cardiopulmonary bypass. These patients were followed for 12 months after the TMR procedure. Both unmanageable and chronic angina patients had a high incidence of at least one prior surgical revascularization (87% and 91%, respectively). RESULTS: Perioperative mortality (< or = 30 days post-TMR) was higher in the UUAG versus PG (16% vs 3%, p = 0.005). Late mortality, up to 1 year of follow-up, was similar (13% vs 11%, UUAG vs PG; p = 0.83). A majority of the adverse events in the UUAG occurred within the first 3 months post-TMR, and patients surviving this interval did well, with reduced angina of at least two classes occurring in 69%, 82%, and 82% of patients at 3, 6, and 12 months, respectively. The percent improvement in angina class from baseline was statistically significant at 3, 6, and 12 months. A comparable improvement in angina was found in the protocol group of patients. CONCLUSIONS: TMR carried a significantly higher risk in unmanageable, unstable angina than in patients with chronic angina. In the later follow-up intervals, however, both groups demonstrated similar and persistent improvement in their angina up to 12 months after the procedure. TMR may be considered in the therapy of patients with unmanageable, unstable angina who otherwise have no recourse to effective therapy in the control of their disabling angina.

Early post-transplant medical compliance and mental health predict physical morbidity and mortality one to three years after heart transplantation.

BACKGROUND: Poor medical compliance has been held responsible for a large proportion of deaths occurring subsequent to initial postoperative recovery. However, beyond clinical reports, there has been little empirical examination of this issue, or of the extent to which major psychiatric disorder and failure to adjust to the transplant predict long-term physical morbidity and mortality. We prospectively examined whether a full range of compliance behaviors and psychiatric outcomes during the first year post-transplant predicted subsequent mortality and physical morbidity through 3 years post-transplant. METHODS: A total of 145 heart recipients who had received detailed compliance and mental health assessments during the first year post-transplant were followed up at 3 years post-transplant. Interview data and corroborative information from family members were used to determine compliance in multiple domains, psychiatric diagnoses, and psychiatric symptomatology during the first year post-surgery. Medical record reviews were performed to abstract data on acute graft rejection episodes, incident cardiac allograft disease (CAD) and mortality from 1 to 3 years post-transplant. RESULTS: After controlling for known transplant-related predictors of outcome, multivariate analyses yielded the following significant (p < 0.05) results: (a) risk of acute graft rejection was 4.17 times greater among recipients who were not compliant with medications; (b) risk of incident CAD was elevated by persistent depression (Odds Ratio, OR = 4.67), persistent anger-hostility (OR = 8.00), medication noncompliance (OR = 6.91), and obesity (OR = 9.92); and (c) risk of mortality was increased if recipients met criteria for Post-Traumatic Stress Disorder related to the transplant (OR = 13.74). CONCLUSIONS: The findings, plus data we have previously reported that showed which patients are most likely to have compliance and psychiatric problems early post-transplant, suggest that interventions focused on maximizing patients' psychosocial status in these areas may further improve long-term physical health outcomes in this population.

Alternative approach to multivessel coronary disease with integrated coronary revascularization.

OBJECTIVE: Integrated coronary revascularization combines minimally invasive coronary artery bypass grafting (MICABG) with left internal thoracic artery-left anterior descending artery grafting and percutaneous coronary intervention. We hypothesized that integrated coronary revascularization could result in successful revascularization in suitable patients with multivessel coronary artery disease. METHODS: Between September 1996 and January 1998, 31 consecutive patients underwent integrated coronary revascularization. Twenty-two were male; mean age was 69 years (46-86 years) and 42% were older than 75 years. Eight patients (26%) had a Parsonnet score greater than 20%. Left ventricular ejection fraction was 46.3% +/- 12%; 6 patients (19%) had a left ventricular ejection fraction less than 35%. RESULTS: The anastomosis time for MICABG with the internal thoracic artery was 14.6 +/- 5.2 minutes and the operating time was 105 +/- 20 minutes; 28 patients (90%) were extubated in the operating room. The internal thoracic artery anastomosis was patent in all 31 patients (100%). Percutaneous coronary intervention was performed before MICABG in 2 patients (7%), on the same day of MICABG in 16 patients (52%), on postoperative day 1 in 3 patients (9%), and on postoperative days 2 to 4 in 10 patients (32%). Postprocedure length of stay in the hospital was 2.7 +/- 1.0 days and 13 patients (42%) were discharged home on postoperative day 1 or 2. Three patients (9.6%) required repeat target vessel revascularization in the distribution of the previous percutaneous coronary intervention. All patients are alive without angina at a follow-up of 10.8 +/- 3.8 months. CONCLUSION: Our early results demonstrate that integrated coronary revascularization can be performed safely and effectively. Long-term results will be available from a prospective randomized trial now underway to compare integrated coronary revascularization with coronary artery bypass grafting for multivessel coronary artery disease.

Effect of ischemic time on survival in clinical lung transplantation.

BACKGROUND: While there is convincing evidence that prolonged ischemic times correlate with reduced long-term survival in heart transplantation, the effect of ischemic time on outcome in clinical lung transplantation remains controversial. To assess the effect of ischemic time on outcomes in lung transplantation, we reviewed our experience. METHODS: The study was performed by retrospective chart review. RESULTS: First-time lung transplantation was performed on 392 patients between 1988 and 1998. All grafts were flushed with cold crystalloid preservation solution and stored on ice. Ischemic time data were available for 352 of 392 (90%) patients. Ischemic times were grouped as follows: 0 to 4 hours (n = 91), 4 to 6 hours (n = 201), more than 6 hours (n = 60). Ischemic time did not correlate with survival: 3-year actuarial survival = 56% (0 to 4 hours), 58% (4 to 6 hours), 68% (> 6 hours), p = 0.58. There was no significant difference in the incidence of biopsy-proven diffuse alveolar damage in the first 30 days after transplantation (31%, 32%, 38%), episodes of acute rejection in the first 100 days after transplantation (1.9, 1.8, 1.7), duration of intubation (median 3, 4, 3 days), or incidence of obliterative bronchiolitis (23%, 28%, 26%) between the three groups (0 to 4 hours, 4 to 6 hours, > 6 hours, respectively). A diagnosis of diffuse alveolar damage was associated with a significantly worse outcome (1-year survival = 82% versus 54%, p < 0.0001). CONCLUSIONS: In contrast to heart transplantation, pulmonary allograft ischemic time up to 9 hours does not appear to have a significant impact on early graft function or survival. The presence of diffuse alveolar damage on biopsy early after transplantation does not correlate with prolonged ischemic time, but is associated with substantially reduced posttransplantation survival.