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Hillel Laks

Publications and source records attributed to Hillel Laks.

At least 37 records · Page 2Linked to original sources
PubMed2005

Does duration of donor brain injury affect outcome after orthotopic pediatric heart transplantation?

OBJECTIVE: We tested the hypothesis that duration of donor brain injury and death would have an adverse effect on recipient rejection and mortality in pediatric heart transplantation. METHODS: Ninety-three cardiac transplants were performed at our center from July 1, 1997, through June 30, 2003. The primary study end points were the number of rejection episodes and the time to first rejection. Secondary outcomes were early and late mortality. RESULTS: Among 88 recipients of 93 cardiac allografts, 5 (6%) and 1 (1%) received second and third allografts, respectively. Overall patient mortality (3 early and 2 late) was 6% (5/88), and overall graft loss was 6% (6/93). Median time from donor brain injury to declaration of brain death (brain injury interval), time from brain death to donor cardiectomy (brain death interval), and graft ischemia time were 38, 24, and 3.3 hours, respectively. Cox regression analysis (adjusting for United Network for Organ Sharing status, ventilator dependence, extracorporeal membrane oxygenation and ventricular-assist device status, diagnosis of congenital heart disease, sex and cytomegalovirus mismatches, and type of immunosuppression) demonstrated that recipients of donor hearts with relatively long periods from brain injury to death declaration or from death to organ removal had significantly improved rejection-free survival (hazard ratios 0.3, P = .01, and 0.5, P = .05, for brain injury and brain death times, respectively). Prolonged donor heart ischemia did not impact rejection rate. Increasing brain injury interval, brain death interval, and graft ischemia time had no significant effect on mortality. CONCLUSION: Longer brain injury and death intervals correlated with improved freedom from rejection but had no effect on mortality.

Adolescent↗
PubMed2005

Noninvasive imaging of ex vivo intracoronarily delivered nonviral therapeutic transgene expression in heart.

We developed a clinically applicable approach for noninvasive monitoring of reporter-therapeutic linked gene expression in the whole heart of large animals using PET imaging and further validated the efficacy and cardiac adverse effects of reporter-therapeutic linked gene transfer in a rabbit cervical heterotopic functional heart transplant model. Cationic liposome complexed with a vector containing a herpes simplex virus type 1 mutant thymidine kinase (HSV1-sr39tk) as the reporter gene and a recombinant human immunosuppressive cytokine, interleukin-10 (hIL-10), as the therapeutic gene was ex vivo intracoronarily delivered into cardiac allografts before implantation. Long-term HSV1-sr39tk and hIL-10 transgene and protein overexpression associated with myocardial PET reporter probe 9-(4-[18F]fluoro-3-hydroxymethylbutyl)guanine ([18F]FHBG) accumulation was observed in the allografts. The expression of the HSV1-sr39tk gene was significantly correlated with the hIL-10 gene expression and the total myocardial [18F]FHBG accumulation quantified as a percentage of intravenously injected [18F]FHBG dose. A homogeneous distribution of [18F]FHBG accumulation was seen in the whole heart similar to the distribution of [18F]fluorodeoxyglucose, a PET glucose metabolism probe. The immunosuppressive therapeutic efficacy remained the same in allografts treated with reporter-therapeutic linked gene and therapeutic gene only. No cardiac adverse effect was found. Our results demonstrate for the first time that PET reporter-therapeutic linked gene imaging is applicable for noninvasively monitoring ex vivo intracoronarily delivered therapeutic transgene expression in the whole heart.

Animals↗
PubMed2004

Increased bronchoalveolar lavage human beta-defensin type 2 in bronchiolitis obliterans syndrome after lung transplantation.

Human beta-defensin-2 (HBD)2 is an antimicrobial peptide that participates in the innate host immune defense. HBD2 is present in bronchoalveolar lavage (BAL) fluid during conditions associated with airway inflammation but not in normal subjects. We measured HBD2 concentrations by semiquantitative Western analysis in BAL of prelung transplant patients (PRE) and postlung-transplant BAL associated with either "quiescent" histopathology (i.e., without acute cellular rejection or infection) (NORMAL POST) or with bronchiolitis obliterans syndrome (BOS). HBD2 levels were not different for PRE (n=9) versus NORMAL POST-transplant BAL specimens (n=22) (204+/-180 vs. 82+/-60 pg/mL; P=NS). The BAL HBD2 concentrations were significantly elevated, however, with BOS (n=8) (1,270+/-430 pg/mL; P<0.001). HBD2 has been previously shown to elicit an adaptive immune response by means of recruitment of immature CD34 dendritic cells and memory (CD4/CD45RO) T lymphocytes through interactions with their chemokine receptor, CCR6. Furthermore, HBD2 with CD14 in human tracheobronchial epithelium can complex with "toll-like receptors" to activate the nuclear factor (NF)-kappaB pathway and therefore promote cytokine gene expression. We therefore speculate that complex interactions between adaptive and innate immunity may contribute to the propagation of airway inflammation in BOS.

Bronchiolitis Obliterans↗
PubMed2004

Signal-averaged electrocardiogram in Ebstein's anomaly.

We sought to establish pathogenetic links between electrophysiology, histopathology, and ventricular tachyarrhythmias in patients with Ebstein's anomaly. The atrialized right ventricle (ARV) is the site of mechanically inducible ventricular tachyarrhythmias, but relations between the arrhythmogenic substrate, the type of tachyarrhythmias, and the trigger(s) have not been established. This study comprised 23 patients (10 men and 13 women; aged 18 to 58 years; mean 32 +/- 3) who did not undergo surgery and 6 pre- and postoperative patients with Ebstein's anomaly, diagnosed by transthoracic and transesophageal echocardiography. Twenty-one patients had classic Ebstein's anomaly and 2 had mild forms. Signal-averaged electrocardiograms (SAECGs) identified slow conduction by using 3 time-domain variables calculated by an automated algorithm and inspected visually. Two variables were required to establish the presence of late potentials. SAECGs were repeated in 6 patients after surgical exclusion of the ARV. Five surgical specimens of the ARV and the true right atrium were examined histologically. Mathematic simulations were used to illustrate anchored and unanchored spiral/scroll waves. SAECGs were positive in 21 patients with classic Ebstein's anomaly and were negative postoperatively in the 6 so studied. The ARV was characterized histologically by clusters of cardiomyocytes isolated within a fibrous matrix. We hypothesize that SAECGs identify slow conduction residing in the ARV, and that excitation of this arrhythmogenic substrate provokes spiral/scroll waves that cannot anchor because clusters of cardiomyocytes are isolated within a fibrous matrix. The waves meander erratically as polymorphic ventricular tachycardia or break up into ventricular fibrillation.

Adolescent↗
PubMed2004

Combined blockade of the chemokine receptors CCR1 and CCR5 attenuates chronic rejection.

BACKGROUND: Chemokine-chemokine receptor interaction and the subsequent recruitment of T-lymphocytes to the graft are early events in the development of chronic rejection of transplanted hearts or cardiac allograft vasculopathy (CAV). In this study, we sought to determine whether blockade of chemokine receptors CCR1 and CCR5 with Met-RANTES affects the development of CAV in a murine model. METHODS AND RESULTS: B6.CH-2(bm12) strain donor hearts were transplanted heterotopically into wild-type C57BL/6 mice (myosin heavy chain II mismatch). Recipients were treated daily with either Met-RANTES or vehicle starting on postoperative day 4 and were euthanized on postoperative days 24 and 56. We found that Met-RANTES significantly reduced intimal thickening in this model of chronic rejection and that Met-RANTES markedly decreased the infiltration of CD4 and CD8 T lymphocytes and MOMA-2+ monocytes/macrophages into transplanted hearts. Met-RANTES also suppressed the ex vivo and in vitro proliferative responses of recipient splenocytes to donor antigens. Finally, Met-RANTES treatment was associated with a marked reduction in RANTES/CCL5 and monocyte chemoattractant protein-1 gene transcript levels in the donor hearts. CONCLUSIONS: Antagonism of the chemokine receptors CCR1 and CCR5 with Met-RANTES attenuates CAV development in vivo by reducing mononuclear cell recruitment to the transplanted heart, proliferative responses to donor antigens, and intragraft RANTES/CCL5 and monocyte chemoattractant protein-1 gene transcript levels. These findings suggest that chemokine receptors CCR1 and CCR5 play significant roles in the development of chronic rejection and may serve as potential therapeutic targets.

Animals↗
PubMed2004

Atrial extracellular matrix remodeling and the maintenance of atrial fibrillation.

BACKGROUND: Remodeling occurs in both ventricle and atrium in dilated cardiomyopathy and heart failure. However, the alteration of atrial extracellular matrix components during remodeling and its effect on the electrical remodeling and atrial arrhythmia have never been explored. METHODS AND RESULTS: Atrial tissue samples of 53 explanted hearts from patients with dilated cardiomyopathy and end-stage heart failure who underwent heart transplantation were examined. Nineteen patients had permanent atrial fibrillation (PmAF), 18 had persistent AF (PsAF), and 16 had no documented AF (NAF). Sixteen donor left atria (LA) were used as controls (CNs). Western Blot analysis revealed a selective downregulation of tissue inhibitor of metalloproteinase (TIMP)-2 in PmAF and PsAF groups compared with the NAF and CN groups and an upregulation of atrial metalloproteinase (MMP)-2 that was most pronounced in the PmAF group followed by the PsAF and NAF groups. Immunofluorescent staining revealed that in the LA, type I collagen volume fraction (CVF-I) increased significantly in the PmAF group followed by the PsAF and NAF groups compared with that in CN. LA CVF-I significantly correlated with LA dimension and TIMP-2 to MMP-2 ratio. In the PsAF group, CVF-I/CVF-III ratio was significantly correlated with AF duration and the frequency of AF recurrence. CONCLUSIONS: Atrial extracellular matrix remodeling manifested by the selective downregulation of TIMP-2 along with upregulation of MMP-2 and CVF-I in the atrium is associated with the development of sustained atrial fibrillation in patients with cardiomyopathy and heart failure.

Atrial Fibrillation↗
PubMed2004

Outcome of patients with double-inlet left ventricle or tricuspid atresia with transposed great arteries.

OBJECTIVES: We sought to determine the long-term outcomes and risk factors for mortality in patients with double-inlet left ventricle (DILV) or tricuspid atresia with transposed great arteries (TA-TGA). BACKGROUND: Patients with DILV or TA-TGA are at risk of systemic outflow obstruction and a poor outcome. The impact of various management strategies on the long-term outcomes of these patients remains unknown. METHODS: We reviewed the outcomes of 164 consecutive pediatric patients with DILV or TA-TGA who underwent surgical palliation between 1983 and 2002. Patients with a Holmes heart or heterotaxy syndrome or who were lost to follow-up (n = 24) were excluded. Risk factors for mortality or the need for orthotopic heart transplantation (OHT) were assessed by multivariate analysis. RESULTS: There were 105 patients with DILV and 35 patients with TA-TGA. The overall mortality rate, including OHT, was 29%. Patients with DILV had a lower mortality rate than patients with TA-TGA (23% vs. 49%, p = 0.007). Multivariate analysis showed the presence of arrhythmia and pacemaker requirement as independent risk factors for mortality, whereas pulmonary atresia or stenosis and pulmonary artery banding were associated with decreased mortality. Gender, era of birth, aortic arch anomaly, and systemic outflow obstruction were not risk factors. The perioperative and overall mortality were similar between patients who underwent the Damus-Kaye-Stansel procedure beyond the neonatal period and those had subaortic resection. CONCLUSIONS: The mortality of patients with DILV or TA-TGA remains high. The outcomes of these patients are influenced by restriction of pulmonary blood flow, arrhythmia, and pacemaker requirement. Surgical palliation to relieve systemic outflow obstruction is not associated with a poor outcome.

Abnormalities, Multiple↗
PubMed2004

Initial experience with the AbioCor implantable replacement heart system.

OBJECTIVE: We sought to evaluate the safety and efficacy of the first available totally implantable replacement heart (AbioCor Implantable Replacement Heart System) in the treatment of severe, irreversible biventricular heart failure in human patients. METHODS: Seven male adult patients with severe, irreversible biventricular failure (>70% thirty-day predicted mortality) who were not candidates for transplantation met all institutional review board study criteria and had placement of the AbioCor Implantable Replacement Heart. All were in cardiogenic shock despite maximal medical therapy, including inotropes and intra-aortic balloon pumps. Mean age was 66.7 +/- 10.4 years (range, 51-79 years). Four of 7 patients had prior operations. Six had ischemic and one had idiopathic cardiomyopathy. All had 3-dimensional computer-simulated implantation of the thoracic unit that predicted adequate fit. At the time of the operation, the internal transcutaneous energy transfer coil, battery, and controller were placed. Biventriculectomy was then performed, and the thoracic unit was placed in an orthotopic position and attached to the atrial cuffs and outflow conduits with quick-connects. The flow was adjusted to 4 to 8 L/min. Central venous and left atrial pressures were maintained at 5 to 15 mm Hg. The device is powered through transcutaneous energy transfer. An atrial flow-balancing chamber is used to adjust left/right balance. The balance chamber and transcutaneous energy transfer eliminate the need for percutaneous lines. RESULTS: There was one intraoperative death caused by coagulopathic bleeding and one early death caused by an aprotinin reaction. There have been multiple morbidities primarily related to preexisting illness severity: 5 patients had prolonged intubation, 2 had hepatic failure (resolved in 1), 4 had renal failure (resolved in 3), and 1 each had recurrent gastrointestinal bleeding, acute cholecystitis requiring laparotomy, respiratory failure that resolved after 3 days of extracorporeal membrane oxygenation, and malignant hyperthermia (resolved). There were 3 late deaths: one caused by multiple systems organ failure (postoperative day 56), one caused by a cerebrovascular accident (postoperative day 142), and one caused by retroperitoneal bleeding and resultant multiple systems organ failure (postoperative day 151). This latter patient was not able to tolerate anticoagulation (no anticoagulation or antiplatelet therapy alone for 80% of the first 60 days) and had a transient ischemic attack on postoperative day 61 and a cerebrovascular accident on postoperative day 130. At autopsy, blood pumps were clean. The 2 patients who had large cerebrovascular accidents had thrombus on the atrial cage struts. These struts have been removed for future implants. There has been no significant hemolysis or device-related infections. The balance chamber has allowed for left/right balance in all patients (left atrial pressure within 5 mm Hg of right atrial pressure). Three patients have taken multiple (>50) trips out of the hospital, and 2 have been discharged from the hospital. Total days on support with the AbioCor are 759. CONCLUSION: The initial clinical experience suggests that the AbioCor might be effective therapy in patients with advanced biventricular failure. There have been no significant device malfunctions. Two of these patients have been discharged from the hospital.

Aged↗
PubMed2004

Sudden, unexpected death in cardiac transplant recipients: an autopsy study.

BACKGROUND: Clinical studies indicate that sudden death (SD) is common after heart transplantation. Autopsy reports of such patients are sparse. METHODS: We performed a retrospective study of clinical and pathologic findings on all autopsied patients who underwent heart transplantation at our institution from January 1984 to July 2002. RESULTS: There were 74 patients who survived >2 months. Of these, 28 (37.8%) died suddenly. The major causes of sudden death (SD) included acute cellular rejection (ACR) (n = 11, 39.3%) and graft coronary artery disease (GCAD) (n = 11, 39.3%). In 9 patients (32.1%), there was no anatomic cause of death. These deaths, assumed to be primary arrhythmic death (PAD), occurred 5 to 36 months post-transplantation. Pre-transplant diagnosis of idiopathic dilated cardiomyopathy (IDCM) was more common in SD (13 of 28, 46.4% vs 9 of 46, 19.6%; p = 0.014). Hypertrophy was not statistically different in SD vs non-SD (79.4% vs 88.4%; p = 0.38). Coronary thrombosis was also not statistically different in sudden GCAD deaths vs non-sudden GCAD deaths (3 of 11, 27.3% vs 8 of 13, 61.5%; p = 0.09). ACR SD patients had fewer episodes of ACR in biopsies than ACR non-SD patients (93 of 190, 48.9% vs 99 of 159, 63.3%; p = 0.01). Biopsies with Quilty lesions (QL) were more frequent in patients with SD (206 of 461, 44.7% vs 243 of 710, 34.2%; p < 0.001). QL were more common in patients with GCAD (44.4%) and ACR (39.6%) than in patients who died of infection (25.7%; P < 0.001 and p < 0.01, respectively). CONCLUSIONS: SD after cardiac transplantation is common (37.8% of all deaths). ACR, in the first year, and GCAD, afterwards, are associated with SD. PAD occurred in 32.1% of SD cases, 5 to 36 months after transplantation. Pre-transplant diagnoses of IDCM and QL are more common in SD. Surprisingly, cardiac hypertrophy is not increased and coronary thrombosis is not more frequent in patients who died suddenly.

Adolescent↗
PubMed2003

Balanced expression of mitochondrial apoptosis regulatory proteins correlates with long-term survival of cardiac allografts.

Abnormal regulation of apoptosis is observed in ischemic injury and may contribute to the pathogenesis of atherosclerosis. However, its role in cardiac allograft vasculopathy (CAV), the fundamental lesion of chronic rejection (CR) in heart transplantation, remains uncertain. To clarify this issue, apoptosis was quantitated in myocardium and coronary arteries from 5 cardiac allograft donors (NL) and explanted hearts of 24 patients with ischemic cardiomyopathy (IsCM) and 15 patients with CR. Tissue samples were analyzed via end-labeling fragmented DNA [via deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)] and immunoblotting for activated caspase-3 and -9. Myocyte apoptosis assessed by TUNEL was similarly increased over NL (0.21%) in both the CR (0.88%; P < 0.01) and IsCM (0.88%; P < 0.01) groups. Activated caspase-9 levels were significantly higher in CR (14.7%) compared with IsCM (6.9%; P < 0.01) and NL (0%) groups, whereas activated caspase-3 levels were similarly elevated in both CR and IsCM (7.8 and 6.5% vs. 0% in NL; P < 0.01 and P < 0.05) groups. Expression of myocardial Bcl-2 and Bax was increased in CR compared with both NL (Bax, 4.3-fold; P < 0.01; Bcl-2, 5.9-fold; P < 0.01) and IsCM (IsCM: Bax, 2.2-fold; P < 0.05; Bcl-2, 3.2-fold; P < 0.01) groups. The rate of apoptosis and the Bcl-2/Bax ratio independently correlated to graft survival in CR (activation of caspase-9: r = 0.87; P < 0.01; Bcl-2/Bax: r = 0.57; P = 0.05). Compared with native atherosclerosis, coronary arteries with CAV showed more medial apoptosis (7.8-fold; P < 0.01) and higher Bcl-2 levels (5.1-fold; P < 0.01) with lower Bax levels (threefold; P < 0.05) in the intima. These results indicate that abnormal Bcl-2 and Bax expression in myocardium and coronary arteries of cardiac allografts with CR is distinct from that in IsCM and suggest that balancing Bcl-2 to Bax in transplanted hearts promotes long-term graft survival.

Adolescent↗
PubMed2003

The AbioCor implantable replacement heart.

The AbioCor implantable replacement heart (IRH) is the first available totally implantable artificial heart. We recently initiated a multicenter trial of this device in patients with severe, irreversible biventricular failure. Patients who were not candidates for other therapies, including transplantation, were evaluated. All candidates were adults with inotrope-dependent biventricular failure, whose 30-day predicted mortality was higher than 70%. A three-dimensional computerized fit study predicted fit of the AbioCor thoracic unit in all recipients. At operation, the internal battery controller and transcutaneous energy transfer unit were placed. The AbioCor thoracic unit was placed in an orthotopic position after incision of the ventricals. There were 2 intraoperative deaths (due to intraoperative bleeding or aprotinin reaction). Four late deaths were recorded, 1 from multisystem organ failure and 3 cerebrovascular accidents. Autopsy revealed thrombus on the atrial struts of the 3 patients with cerebrovascular accident. Blood pumps and valves were clean on all patients. Significant morbidity was observed, primarily related to preexisting severity of illness. However, 3 patients recovered to the point of being able to take multiple trips outside of the hospital. Two patients were discharged from the hospital, with 1 patient being discharged home for more than 7 months. No significant device malfunctions or multi-system organ failure device-related infections were noted. The AbioCor IRH may be effective therapy for patients with end-stage heart failure. Many milestones have been achieved in the initial trial in humans, including the successful discharge of a patient to home and no significant device malfunctions. The occurrence of stroke is likely related to the presence of thrombus on the atrial struts and may be decreased as these atrial struts have been removed for future clinical implants.

Aged↗
PubMed2003

Regulated interleukin-10 expression prevents chronic rejection of transplanted hearts.

OBJECTIVE: Interleukin-10 is a pleiotrophic cytokine with variable effects on the alloimmune response, depending on the experimental model system. The purpose of this study was to determine the role of regulated interleukin-10 expression on the development of chronic rejection in heart transplantation, or cardiac allograft vasculopathy. METHODS: Donor hearts from B6.C-H2(bm12) mice were transplanted into wild-type and interleukin-10 transgenic recipients. In interleukin-10 transgenic recipients, murine interleukin-10 cytokine is produced under the control of human interleukin-2 promoter. Donor hearts were sacrificed at days 7 and 24. No immunosuppression was used. Intimal proliferation was measured morphometrically. Intragraft cellular infiltrate was defined by both immunohistochemistry and flow cytometry. Intracellular cytokine staining assay was performed to determine both the type and source of intragraft cytokines. RESULTS: Hearts transplanted into wild-type recipients developed severe cardiac allograft vasculopathy by 24 days. Intimal lesions were absent in the donor hearts transplanted into interleukin-10 transgenic recipients. The number of graft-infiltrating T lymphocytes and the percentage of interleukin-2/interferon-gamma producing T lymphocytes were markedly reduced in interleukin-10 transgenic recipients. Finally, the overexpression of interleukin-10 resulted in the decline of graft-infiltrating macrophages at all time points. CONCLUSIONS: Regulated expression of interleukin-10 inhibits cardiac allograft vasculopathy development via reduction of mononuclear cell recruitment and alteration of their cytokine profile. This strategy may prove beneficial in controlling the alloimmune response in solid organ transplants.

Animals↗
PubMed2003

Results after transplantation using donor hearts with preexisting coronary artery disease.

OBJECTIVE: Cardiac allografts with coronary artery disease may permit a selective expansion of the donor pool. Twenty-two recipients who received donor hearts with mild to moderate coronary artery disease on angiography were reviewed. All donor organs had preserved left ventricle function on echocardiogram. METHODS: The procedure was explained to the patients in detail. All survivors have at least 1 year of follow-up. If the coronary arteries of the donor heart were significantly occluded, then the implanting surgeon performed coronary revascularization. Donors were allocated to patients facing imminent death (group I, n = 4) or to those who would otherwise not have been transplanted (group II, n = 18). Median recipient age was 57 years old for group I and 68 years old for group II. Median follow-up was 25 months for group I and 44 for group II. RESULTS: Outcome was evaluated using survival and freedom from graft coronary disease as end points. In group I, 3 of the 4 hearts required revascularization. In group II, 10 of the 18 required revascularization. The majority of the revascularizations were recipient saphenous vein grafts (84.6%) to the donor left anterior descending artery (50%). The 1-month and 2-year actual survivals for group I are 75% and 50% and 87.5% and 81.3 for group II. One patient in group I who was in extremis and 3 in group II died at less than 90 days. Group II early deaths had donor risk factor combinations of coronary artery disease, left ventricular hypertrophy, and long distance. Freedom from new graft coronary artery disease was 100% at 2 years in group I and 87.5% in group II. CONCLUSIONS: Selective use of donor hearts with coronary artery disease is acceptable. Early deaths are related to recipient factors as well as associated donor risk factors. Donor hearts with mild or moderate coronary artery disease and preserved function on echocardiogram can be used but may require revascularization with recipient conduit and/or percutaneous transluminal coronary artery angioplasty. Coronary disease in donor hearts requires grading and does not categorically preclude use, particularly in risk-matched recipients.

Adult↗
PubMed2003

Modified reperfusion and ischemia-reperfusion injury in human lung transplantation.

OBJECTIVE: Ischemia-reperfusion injury remains a major cause of mortality and morbidity in clinical lung transplantation. Interaction of activated leukocytes with injured graft endothelial cells participates in the development of ischemia-reperfusion injury. We sought to determine if modification of the reperfusate (with depletion of leukocytes and alteration of its composition) would decrease the incidence of ischemia-reperfusion injury in human lung transplantation when compared with whole blood reperfusion in a historical group of patients. METHODS: Between June 1999 and July 2001, 23 adult patients undergoing lung transplantation consented to modified reperfusion. After implantation, a catheter was inserted into the main or individual pulmonary arteries, and modified reperfusate was administered at a pressure less than 20 mm Hg. The modified reperfusate was depleted of leukocytes, supplemented with nitroglycerin, adjusted for pH and calcium level, and enriched with aspartate, glutamate, and dextrose. After 10 minutes of modified reperfusion, the removal of pulmonary artery clamp or weaning of cardiopulmonary bypass was performed per usual protocol. Age- and diagnosis-matched historical patients served as the control group. Ischemia-reperfusion injury was defined as Pao(2)/Fio(2) < 150 with diffuse infiltrate on the radiograph in absence of other causes. RESULTS: There was no difference in donor age or oxygenation indices, recipient age, the number of patients requiring cardiopulmonary bypass, ischemia time, and recipient oxygenation indices between the modified reperfusate group and the control group. However, none of the patients in the modified reperfusate group developed ischemia-reperfusion injury in contrast to 5 patients in the control group (P <.05). The early survival in the modified reperfusate group was 96% versus 81% in the control group (P = NS). CONCLUSION: This study suggests that modification of the reperfusate content decreases the incidence of ischemia-reperfusion injury in human lung transplantation when compared with whole blood reperfusion in a historical group of patients. Modified reperfusate may allow acceptance of marginal lungs and expansion of the donor pool.

Adult↗
PubMed2003

Staged repair of pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries: experience with 104 patients.

OBJECTIVE: To determine the early and intermediate-term outcome of the staged repair used to treat children with pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries. METHODS: We reviewed a retrospective case series of 104 patients with this complex lesion. Information was obtained from medical records and referring physicians. RESULTS: Of the 104 patients treated with the staged repair, 58 achieved completion of anatomic repair. The 10-year mortality was 16.5%. In the patients with complete repair, the median right-to-left ventricle pressure ratio was 0.5. The overall surgical reoperation rate was 17%, and 15.5% of patients required postoperative interventional cardiac catheterization. In the multivariate analysis, the number of collateral vessels incorporated in the repair was found to be an independent risk factor for postoperative mortality and an elevated right-to-left ventricle pressure ratio after complete repair. CONCLUSION: The staged repair can be successfully used to treat patients with pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries. This method yields a relatively low mortality with good functional results.

Adolescent↗
PubMed2003

Heart transplantation in patients with diabetes mellitus in the current era.

BACKGROUND: In this study, we used a single-institution database to examine the risks of heart transplantation in patients with diabetes mellitus (DM). METHODS: Recipients 18 years and older who underwent cardiac transplantation from July 1994 to December 2000 were reviewed; 101 consecutive patients with insulin-dependent diabetes mellitus and non-insulin-dependent diabetes mellitus were compared with 244 patients who did not have DM and who received standard donor hearts. Survival, renal function (serum creatinine concentration), development of transplant coronary artery disease (TCAD), severe rejection, and infection (requiring hospitalization) were analyzed. RESULTS: Patients with DM were older (mean age, 57.1 years vs 51.4 years), had greater body mass index (mean, 26.7 vs 24.1 kg/m(2), p < 0.02), and more commonly had ischemic cardiomyopathy (58% vs 43%, p = 0.02). We found a trend toward decreased survival for those with DM at 1 year (85.1% vs 90.9%; p = 0.12). Five-year survival was 81.6% for both groups. Mean follow-up time was 4.1 years. Infection rate within 3 months was greater among those with DM (14% vs 3%, odds ration = 5.09; 95% confidence interval, 1.59-16.23). Freedom from infection at 4 years was 71.0% for patients with DM and 85.0% for those without DM (p = 0.02). Freedom from rejection at 4 years was similar (70.6% vs 73.6%, p = 0.69). At 4 years, transplant coronary artery disease (TCAD)-free survival was 69.5% for those with DM and 81.6% for those without (p = 0.23). Mean serum creatinine concentration at 4 years after transplant was 1.5 mg/dl in patients with DM (vs 1.4, p = 0.28). Multivariate analysis showed increased baseline creatinine level as a significant risk factor for survival and showed pre-transplant ischemic cardiomyopathy as a risk factor for TCAD in both groups. Body mass index >30 was a significant risk factor for survival among patients with DM. CONCLUSION: We found an increased risk of serious infections in patients with DM, particularly in the early post-operative period. Careful consideration of obesity and renal function during evaluation of candidacy is indicated.

Body Mass Index↗
PubMed2003

Use of two recipient lists for adults requiring heart transplantation.

OBJECTIVE: An alternate (second) adult recipient list was used to match excluded potential recipients with nonstandard donor hearts that would otherwise be unused. METHODS: The only absolute criterion for entering the alternate recipient list was age: 65 years old before 1998 and 70 years old after that. Group I consisted of alternates who underwent transplantation, and group II consisted of 401 contemporaneous recipients. Hearts were first offered to regularly listed patients. At least one of the following donor risks accounted for allocation to an alternate: coronary artery disease, reused transplanted heart, high-risk behavior, hepatitis seropositivity, decreased left ventricular ejection fraction, high inotropic requirement, left ventricular hypertrophy, age older than 55 years plus another risk, and small donor with no other matches. RESULTS: Of 102 alternates, 82 were listed were because of age. After a median wait of 107 days, 62 alternates underwent transplantation. Median alternate recipient age was 67 years (vs 54 years, P <.001). Median donor age was 45 years (vs 31 years, P <.001). Survival for alternates at 90 days was 82% (vs 91%, P =.04). Significant recipient predictors of early mortality on multivariable analysis (n = 463) were previous cardiac surgery (odds ratio 2.74, 95% confidence interval 1.37-5.48) and renal dysfunction (odds ratio 1.39, 1.10-176). Alternate listing did not independently predict early or late mortality. Late (>90 days) death rates per 1000 person-months were 4.3 and 3.6 for groups I and II (relative risk 1.2, 0.62-2.36). CONCLUSIONS: Use of two adult recipient lists facilitated allocation of unused donor organs. Satisfactory long-term survival supports the use of an alternate recipient list.

Adult↗