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Biomedical subjects

H Laks

Publications and source records attributed to H Laks.

At least 19 recordsLinked to original sources

Side-to-side aorto-Gore-Tex central shunt.

BACKGROUND: This report details our experience in 13 patients with a technical modification of the standard central shunt. METHODS: The study was performed using a retrospective chart review approach. In our operation, the aorto-Gore-Tex (W.L. Gore & Assoc, Flagstaff, AZ) anastomosis is created in a side-to-side fashion with the free end of the Gore-Tex shunt being oversewn. RESULTS: All patients had echocardiographic evidence of shunt patency in the immediate postoperative period, and there have been no cases of late shunt occlusion at a mean follow-up period of 10 months. CONCLUSIONS: We believe this approach will yield patency rates equivalent to or better than those of the standard central shunt. The technique has the advantage of creating a short, straight-lying shunt that is less likely to kink or be injured on repeated sternotomy and in which flow may be more reliable.

Aorta

Effects of cardiac allograft vasculopathy on myocardial blood flow, vasodilatory capacity, and coronary vasomotion.

BACKGROUND: Coronary vasculopathy is the third leading cause of death 1 year after cardiac allograft transplantation. This study was designed to assess the hemodynamic effects of transplant vasculopathy on myocardial blood flow and vasomotion. METHODS AND RESULTS: Thirty-two patients were studied 1 to 2 years after cardiac transplantation by use of positron emission tomography (n = 32), intravascular ultrasound (n = 26), coronary angiography (n = 32), and endomyocardial biopsy (n = 32). Twenty healthy individuals served as control subjects. Quantitative intravascular ultrasound was used to compute coronary lumen area, intimal thickness, and intimal index [Intima Area/(Intima + Lumen Area)]. Myocardial blood flow was quantified with the use of 13N-ammonia/positron emission tomography. Mean myocardial blood flow was higher in the transplant patients than in control subjects (0.94 +/- 0.26 versus 0.68 +/- 0.16 mL.min-1.g-1 P < .0005). Cold increased myocardial blood flow to 0.79 +/- 0.18 mL.min-1.g-1 in control subjects but not in patients (0.98 +/- 0.36 mL.g-1.min-1). Hyperemic myocardial blood flow was lower in patients than in control subjects (1.69 +/- 0.78 versus 2.30 +/- 0.32 mL.min-1.g-1; P < .05) and was inversely related to maximal intimal thickness and intimal index (all P < .05). The myocardial flow reserve was reduced in patients (1.82 +/- 0.55 versus 3.45 +/- 1.03; P < .0001). CONCLUSIONS: The degree of intimal thickening is correlated with abnormalities in coronary function in patients with diffuse cardiac allograft vasculopathy. The reduction in vasodilatory capacity and the abnormal blood flow response to cold suggest abnormalities in endothelium-dependent and -independent coronary vasodilation in transplant recipients.

Cold Temperature

The Fontan procedure in adults.

BACKGROUND: A retrospective clinical study was performed to document the course of adult patients undergoing the Fontan procedure. METHODS: Between 1982 and 1994, 21 adults aged 18 to 40 years (mean age, 27 +/- 7 years) underwent a Fontan procedure. Anatomic diagnosis was tricuspid atresia in 9, double-inlet left ventricle in 4, and various single ventricles in 8. Four underwent a right atria-right ventricle connection, 13 had a right atria-pulmonary artery connection, and 4 had a lateral-tunnel Fontan. Three of these 4 had a snare-adjustable atrial septal defect. Preoperative risk factors assessed were left ventricular end-diastolic pressure greater than 10 mm Hg, ejection fraction lower than 0.45, mean pulmonary artery pressure higher than 15 mm Hg, transpulmonary gradient greater than 10 mm Hg, pulmonary artery abnormalities, and atrioventricular valve regurgitation. Mean preoperative risk score was 1.6 /-1.1. Mean New York Heart Association class was 2.6 +/- 0.5. RESULTS: The operative mortality rate was 5% (1/21). Six patients (30%) had a major complication, four being prolonged effusions. One patient was lost to follow-up; the remaining 20 have been followed for a mean of 7.4 +/- 3.8 years. At follow-up, mean New York Heart Association class was 1.7 +/- 0.5. There has been one late death (5%) at 9 2/3 years, which was probably due to ventricular arrhythmia. Three patients (16%) have required and survived reoperation. During follow-up, 7 patients (37%) have had development of atrial arrhythmias requiring medication, and 2 have been treated for ventricular arrhythmias. CONCLUSIONS: These results indicate that properly selected adults can undergo the Fontan procedure with low morbidity and mortality. However, late-developing arrhythmias, need for reoperation, and decreasing ventricular function are serious problems that mandate careful follow-up.

Adult

Multiple left heart obstructions (Shone's anomaly) with mitral valve involvement: long-term surgical outcome.

BACKGROUND: The outcome of children with multilevel left heart obstructions (Shone's anomaly) is generally poor. Literature is scarce, consisting mainly of case reports. The mitral disease may be the predominant factor affecting outcome. METHODS: Surgical results in 19 consecutive patients are presented, with a median follow-up of 8 years. Mitral stenosis was present in all, with parachute deformity in 12 patients. Supramitral rings were found in 9 patients. Other features included subaortic stenosis (15 patients), valvar aortic stenosis (9), bicuspid aortic valve (16), and coarctation (13 patients). The patients underwent 46 surgical procedures, including 18 mitral operations (9 replacements, 9 repairs). RESULTS: There were three in-hospital (16%) and two late (10.5%) deaths. Of the 5 nonsurvivors, 4 patients (80%) had predominant mitral disease and moderate to severe pulmonary hypertension, versus 4 (28.5%) and 5 (36%) survivors, respectively (p = not significant). Valve repair was the final procedure in 9 survivors. The other 5 patients had repeated valve replacements (1), aortoventriculoplasty with valve replacements (2), or no mitral operation (2). Freedom from mitral reoperation was 78% (7 of 9 patients) after repair procedures and 43% (3 of 7 patients) after replacement. At follow-up, 10 patients (71.4%) are in New York Heart Association functional class I and the other 4 in class II and III. Six (43%) await reoperation due to recurrent aortic (4) or subaortic (1) stenosis and recoarctation (2). Echocardiography reveals mild mitral stenosis or regurgitation in 3 patients after repair (33%). Four are considered free of residual disease (21% of all). CONCLUSIONS: Late outcome in Shone's anomaly seems to correlate with the predominance of mitral valve involvement and the degree of pulmonary hypertension. Valve repair is indicated whenever feasible and should be considered before the occurrence of pulmonary hypertension.

Aortic Coarctation

Intracoronary adenovirus-mediated transfer of immunosuppressive cytokine genes prolongs allograft survival.

BACKGROUND: Intracoronary transfer and expression of recombinant genes in the intact heart is now feasible. In the transplant setting, local modulation of host immune responses by a genetically modified allograft may offer an attractive alternative to systemic immunosuppression. METHODS: We tested the efficacy and in vivo effect of intracoronary transfer of two immunosuppressive cytokine genes. First-generation E1-deleted adenoviral vectors expressing the Epstein-Barr virus interleukin-10 (AdSvIL10) or human transforming growth factor--beta 1 (AdCMVTGF-beta) were used. Rabbit cardiac allografts were transduced during cold preservation by slow (1 ml/min) intracoronary infusion of 10(10) pfu/gm diluted viral vectors and then implanted heterotopically. Controls included E1-deleted adenovirus (Ad5dI434) and AdCMVLacZ. Beating allografts were collected on day 4 for analysis of gene transfer efficacy and distribution. Additional grafts were used for evaluation of alloreactivity (n = 34). RESULTS: Mean allograft viral uptake was 81% (up to 91%). Polymerase chain reactions and reverse transcription-polymerase chain reactions confirmed the presence and expression of both genes in the grafts. beta-Galactosidase staining in AdCMVLacZ-infected grafts demonstrated efficient gene expression, which was highest (100%) in subepicardial regions. More homogeneous transmyocardial distribution of the transgene (in 25% to 40% of cells) could be achieved by pulsatile slow delivery. Allograft survival was 6.9 +/- 0.9 days in controls (n = 12), 11.1 +/- 1.7 days in AdCMVTGF-beta-infected grafts (n = 11, p < 10(-4)), and 11.2 +/- 3 days in AdSvIL10-infected grafts (n = 11, p < 10(-4)). Histologic scores (blinded) showed significantly (p < 0.005) higher regression coefficients for rejection in controls compared with both cytokine-transduced groups. Perioperative administration of cyclosporine A (INN: ciclosporin) to recipients had no effect on survival of AdCMVTGF-beta-infected grafts but reduced survival of AdSvIL10-infected grafts. CONCLUSIONS: Intracoronary gene transfer of immunosuppressive cytokines to cardiac allografts is efficient and effectively prolongs graft survival. Vectors that would induce long-term expression of such genes may make this approach clinically applicable.

Adenoviridae

Controlled periadventitial administration of verapamil inhibits neointimal smooth muscle cell proliferation and ameliorates vasomotor abnormalities in experimental vein bypass grafts.

OBJECTIVE: Inhibition of early myointimal proliferation may improve longterm patency of vein grafts, but the clinical use of many experimental drugs is limited by systemic toxicity. To determine whether this goal can be achieved by low-dose targeted drug administration, we constructed a polymeric system delivering verapamil and evaluated the effects on local and downstream vein graft morphology, neointimal smooth muscle cell proliferation, and vasomotor function. METHODS: Ethylene-vinyl acetate polymeric delivery systems were constructed, containing 2% verapamil by weight. These are flexible, biocompatible, and nonbiodegradable matrices, delivering the drug at a rate of 10 micrograms/day. The autologous external jugular vein was used to create a carotid artery bypass graft in hypercholesterolemic (n = 22) rabbits. Verapamil-containing matrices (n = 12) or plain polymers (control, n = 10) were wrapped around the proximal third of the veins after reperfusion. Graft vasomotor function was evaluated and was also compared with function of an additional group of normocholesterolemic vein grafts (n = 8). RESULTS: Twenty-eight days after grafting, intimal index (intima/media thickness ratio) was 31% lower, neointima/original lumen surface ratio was 26% lower, and residual luminal area was 71% greater (4.00 +/- 1.2 mm2 versus 2.34 +/- 0.9 mm2, all p < 0.01) under verapamil matrices compared with control grafts. Neointimal smooth muscle cell content was reduced from 45.4% to 28.2%, and net neointimal smooth muscle cell thickness was reduced by 47% (30 microns vs 15.8 microns, both p < 0.01). Verapamil-treated segments distal to the matrices also showed significantly lower neointimal smooth muscle cell density and increased lumen size. Sensitivity to serotoin and vasomotor responses to serotonin, norepinephrine, and sodium nitroprusside in distal segments were significantly lower in verapamil-treated grafts than in controls. CONCLUSIONS: Periadventitial controlled administration of verapamil below 1% of the systemic dose effectively inhibits myointimal hyperplasia in vein grafts. Local polymeric drug delivery may be readily applicable to coronary revascularization operations.

Animals

Intracoronary gene transfer of immunosuppressive cytokines to cardiac allografts: method and efficacy of adenovirus-mediated transduction.

OBJECTIVE: Allograft-targeted immunosuppressive gene therapy may inhibit recipient immune activation and provide an alternative to systemic immunosuppression. We studied the optimal technique and efficacy of intracoronary gene transfer of viral interleukin-10 and human transforming growth factor-beta 1 in a rabbit model of heterotopic heart transplantation. METHODS: Replication-defective adenoviral vectors were constructed, expressing viral interleukin-10 (AdSvIL10) or transforming growth factor-beta 1 (AdCMVTGF-beta 1). Intracoronary delivery of vectors was accomplished ex vivo by either bolus injection or slow infusion. The allografts were implanted heterotopically in recipient rabbits and collected 4 days after the operation. Vector dose was 4 x 10(9) to 6 x 10(10) pfu/gm of donor heart. Transfer was confirmed by DNA amplification for both genes. Gene product expression in tissue was quantified by immunoassay and visualized by immunohistochemical staining. RESULTS: Allograft viral uptake was only 9.9% +/- 2.4% with bolus injection, but increased to 80.5% +/- 6.8% at 1 ml/min infusion rate (p = 5 x 10(-14)). Uptake ratio was not affected by vector quantity or slower infusion rates. Transforming growth factor-beta 1 was consistently detected in allografts infected with AdCMVTGF-beta 1, but not with control adenovirus or AdSvIL10. Expression was proportional to infused vector quantity and reached 10 ng/gm of allograft at infused 10(10) pfu/gm. Transforming growth factor-beta 1 was also detected in recipient's serum at less than 1 ng/ml. Viral interleukin-10 was detected in minor amounts only (< 1 ng/gm) in allografts infected with AdvIL10 up to 5 x 10(10) pfu/gm. Nevertheless, it was detected in recipient serum at concentrations up to 0.4 ng/ml. CONCLUSIONS: Intracoronary gene transfer of immunosuppressive cytokines to cardiac allografts during cold preservation is feasible. Slow infusion is superior to bolus injection. In vivo effects on allograft rejection remain to be determined.

Adenoviridae

Benefits of early surgical repair in fixed subaortic stenosis.

OBJECTIVES: We sought to determine whether early resection can improve outcome in fixed subaortic stenosis. BACKGROUND: The diagnosis of subaortic stenosis (SAS) is often made before significant gradients occur. Whereas resection is the accepted treatment, it remains uncertain whether surgical intervention at this early stage can reduce the incidence of recurrence or influence the progression of aortic valve damage. METHODS: Follow-up was available for 75 of 83 consecutive patients operated on for fixed SAS; the average duration of follow-up was 6.7 years. The lesion was discrete in 68 patients (91%) and of a tunnel type in 7, with associated ventricular septal defect in 28 (37%). All underwent transaortic resection. RESULTS: There were no deaths. There were 18 recurrences of SAS in 15 patients (20%). Thirteen patients (17%) underwent 17 reoperations for recurrence or aortic valve disease. The cumulative hazard of recurrence was 8.9%, 16.1% and 29.4% +/- 2.3% (mean +/- SEM), and the hazard of events, including recurrence and reoperation, was 9.2%, 18.4% and 35.1% +/- 3.5% at 2, 5 and 10 years, respectively. Residual end-operative left ventricular outflow tract (LVOT) gradients (> 10 mm Hg, n = 8) and tunnel lesions were univariate predictors of recurrence (p = 0.0006 and p = 0.003, respectively). Multivariate predictors included higher preoperative LVOT gradient (p < 10(-4)) and younger patient age (p = 0.002). Only two recurrences (0.87 per 100 patient-years of follow-up) were noted in patients with a preoperative peak LVOT gradient < or = 40 mm Hg (n = 40), whereas higher gradients (n = 35) were associated with a greater than sevenfold recurrence rate (6.45 events per 100 patient-years, p = 0.002). The aortic valve required concomitant repair in 17 cases in the high gradient group (48.6%) but in only 8 in the low gradient group (20%, p = 0.018). Despite relief of the obstruction, progressive aortic regurgitation was noted at follow-up after 14 procedures in the high gradient group (40%) but after only 5 procedures in the low gradient group (12.5%, p = 0.014). CONCLUSIONS: The data suggest that surgical resection of fixed subaortic stenosis before the development of a significant (> 40 mm Hg) outflow tract gradient may prevent recurrence, reoperation and secondary progressive aortic valve disease.

Aortic Stenosis, Subvalvular

Primum atrial septal defect.

UNLABELLED: The purpose of this report is to review our surgical experience with primum atrial septal defect. Since 1982, infants with primum atrial septal defect have undergone complete repair consisting of closure of the cleft of the left atrioventricular valve and atrial septal defect with a pericardial patch. Ages at operation ranged from early neonatal period until 5 years. In most patients, echocardiography was diagnostic and cardiac catheterization was performed in children with associated defects. Severe congestive heart failure and left atrioventricular valve regurgitation necessitated earlier correction. Infants with coarctation of the aorta and primum atrial septal defect underwent a two-stage procedure involving coarctation resection followed by complete repair. The early mortality rate is less than 1% and has a reoperation rate of less than 3%. The overall long-term survival of patients with primum atrial septal defect matches that of the general population. CONCLUSION: The diagnosis of primum atrial septal defect can easily be made by echocardiography with cardiac catheterization reserved for patients with associated left-sided obstruction. For patients in stable condition, the total repair can be performed before 2 to 3 years of age with minimum mortality. In infants with severe congestive heart failure, earlier correction should be contemplated, although it carries a higher morbidity. The associated coarctation of aorta is infrequent, but requires resection before intracardiac repair. The long-term results with this lesion repair are excellent.

Aortic Coarctation

Intermediate and complete forms of atrioventricular canal.

The surgical management of patients with complete atrioventricular canal has evolved over the past 20 years from a staged approach with preliminary pulmonary artery banding and eventual definitive repair, to an era of complete repair in early infancy. Although once considered high risk, the early mortality is now low and is primarily related to pulmonary hypertension secondary to a prolonged delay in diagnosis and referral. While controversy still exists over the techniques of repair, evaluation of outcome of atrioventricular canal should now be focused on the long-term function of the mitral valve, and the overall long-term survival. A detailed description of the single-patch technique and management of the atrioventricular valve, as well as an indepth discussion of outcome is presented.

Atrioventricular Node

Unbalanced atrioventricular septal defects.

Complete atrial ventricular septal defects (AV canal) generally have right and left valve components equally divided. However, in unbalanced AV canal either right or left ventricle dominance may occur. The spectrum may vary between those readily able to undergo biventricular repair at no increased risk to those requiring a single ventricle approach in cases with severe hypoplasia of the ipsilateral ventricle. The most challenging diagnostic cases fall within the gray area between the two ends of the spectrum, in which one ventricle is not clearly hypoplastic. Diagnostic modalities that are used to evaluate these ventricles include echocardiography and angiographic ventriculography using volume formulae. Magnetic resonance imaging (MRI) has also recently been found to be a useful technique with which further experience is being developed. Once the determination of a single ventricle physiology has been made, early intervention (ie, pulmonary artery banding) to protect both the pulmonary vasculature and the ventricular function is performed. Follow-up with catheterization and bidirectional Glenn should be completed usually by around 4 to 6 months of age. This palliation and subsequent Fontan completion has had good results based largely on two factors: ventricular dominance, left being better than right, and the absence of pulmonary vascular hypertension.

Aortic Valve Insufficiency

Defining obesity in patients undergoing orthotopic heart transplantation: body mass index versus percent body fat.

We examined body mass index (BMI) as a proxy for percent body fat among 26 men and women successfully undergoing orthotopic heart transplantation. Percent body fat was determined by use of bioelectrical impedance techniques. We found that, although BMI was well correlated with percent body fat (r = 0.58, p < 0.01), use of a BMI of greater than 27 kg/m2 to define obesity potentially misclassified patients when compared with defining obesity as a percentage of body fat as both greater than 30% (BMI = 9 of 26 patients vs percent body fat = 6 of 26 patients) and greater than 40% (BMI = 9 of 26 versus percent body fat = 1 of 9). We conclude that percent body fat measurements are more methodologically appropriate means for J Heart Lung Transplant 1997;16:563-5.

Adult

The alternate recipient list for heart transplantation: does it work?

BACKGROUND: One quarter of patients awaiting heart transplantation die while on the waiting list. This is largely due to the shortage of donor organs. The alternate recipient list was created to establish a means by which patients who would otherwise be turned down for heart transplantation solely because of age over 65 or a need for a third heart transplantation can receive organs considered marginal that may otherwise be wasted. The hope is that these patients may achieve improved survival with these substandard hearts than they would achieve with medical therapy alone. METHODS: Twenty-two patients ages 47 to 71 years (mean 66.7 years) were listed on the alternate recipient list at the University of California at Los Angeles Medical Center from 1991 to 1996. Seventeen patients underwent heart transplantation from the alternate waiting list. The outcome of this group was compared with the outcome of a contemporaneous group of 266 patients ages 18 to 66 years (mean age 52.1 years) from the standard heart transplantation waiting list. RESULTS: The early mortality rate for the patients in the alternate group was 11.8% (2/ 17). Actuarial survival from time of orthotopic heart transplantation at 6 months and 1 year was the same 74.5% at a mean follow-up was 13.4 months. In comparison, the early mortality rate for the patients on the standard list was 5.6% (15/266), and actuarial survival at 6 months and 1 year was 86.8% and 83.1%, respectively (mean follow-up was 30 months). There was no significant difference in early mortality rate or actuarial survival between the two groups. CONCLUSION: The alternate recipient list for heart transplantation is a valid and ethical option for patients who would otherwise be denied heart transplantation. It provides these patients with similar early and medium-term outcomes in comparison to patients on the standard list, and organs that may otherwise be wasted are used.

Adolescent

Experience of patients with end-stage heart failure who underwent heart transplant at UCLA.

From 1993 to 1997, nine Japanese heart transplant candidates were accepted by the University of California at Los Angeles (UCLA) Medical Center, because no donor heart was available in Japan from a brain-dead patient. In all nine heart transplant patients described in this investigation, the preoperative diagnosis was dilated cardiomyopathy. One patient underwent implantation with a Novacor left ventricular assist device (Baxter Japan, Tokyo, Japan) as a bridge to heart transplant. All patients survived surgery and for a long-term period. The actuarial 1-year and 3-year survival curves of these patients were both 100%. The postoperative functional status was New York Heart Association Class 1 in all patients (100%). Immunosuppressive triple drug therapy (azathioprine, steroids, and cyclosporine) was given in seven patients; in two patients, cyclosporine was withdrawn and replaced by FK506 due to refractory rejection. The incidence of acute rejection per patient of more than grade 3 according to the International Society for Heart and Lung Transplantation was 6% within 3 months and 4.5% in 3-6 months; there was no rejection episode more than 6 months after transplantation. Post-transplant coronary artery disease was seen in two patients. However, no disease progression was seen after diltiazem therapy. These results may encourage heart transplantation in Japan.

Adult

Pretransplant panel reactive-antibody screens. Are they truly a marker for poor outcome after cardiac transplantation?

BACKGROUND: The effect of pretransplant sensitization on outcome after cardiac transplant has been controversial. Sensitization, defined as a positive panel-reactive antibody (PRA) screen in patients awaiting transplant, represents circulating antibodies to a random panel of donor lymphocytes (usually T lymphocytes). The significance of pretransplant circulating antibodies to B lymphocytes has not been reported, and many centers disregard its use. METHODS AND RESULTS: We retrospectively reviewed the pretransplant PRA screens for 311 patients who underwent cardiac transplant at our institution. The PRA screen was performed by use of the lymphocytotoxic technique treated with dithiothreitol to remove IgM autoantibodies. Patients with PRA > or = 11% against T or B lymphocytes had significantly lower 3-year survival (T lymphocytes, 39%; B lymphocytes, 56%) than those patients with PRA = 0% and PRA = 1% to 10% (T lymphocytes, 76% and 78%; B lymphocytes, 78% and 74%, respectively) (P < .001). For this high-risk group, the rejection episode tended to occur earlier than in those patients with PRA = 0% and PRA = 1% to 10% (T lymphocytes, 2.3 versus 4.0 and 3.8 months; B lymphocytes, 2.1 versus 4.1 and 3.4 months, respectively), and there were more clinically severe rejections that required OKT3 therapy. CONCLUSIONS: Cardiac transplant patients with pretransplant T- and/or B-lymphocyte PRA > or = 11% despite negative donor-specific crossmatch at the time of transplant appear to have earlier and more severe rejection with significantly lower survival after transplant surgery. Modification of immunosuppression in these high-risk patients may be warranted.

Adult