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Biomedical subjects

R E Michler

Publications and source records attributed to R E Michler.

At least 145 records · Page 8Linked to original sources
PubMed1993

Safety of heparin-coated circuits in primates during deep hypothermic cardiopulmonary bypass.

The purpose of this study is to evaluate the biologic impact of heparin-coated circuits without systemic heparinization during deep hypothermia. Baboons (n=6) were placed on a heparin-coated pediatric closed-circuit cardiopulmonary bypass (CPB) system and cooled to 18 degrees C. A control group (n=7) underwent similar protocol with a non heparin-coated circuit and received systemic heparin. Either low flow at 0.5 L/min/m 2 (n=8; 4 in each group) or circulatory arrest (n=5; 2 in experimental group and 3 in control group) was used during deep hypothermia. Samples for complete blood count (CBC), hepatic and renal function tests, activated clotting time (ACT) and thrombelastogram (TEG) were obtained before, during, and after bypass. Cerebral blood flow was measured using Xenon-133 and autopsies were performed to assess end-organ damage. The ACT returned to baseline in both groups, and renal and hepatic function were within normal limits. There was no significant difference between the TEG values between the groups post bypass. Fibrin split products were absent and fibrinogen levels were normal in both groups following bypass. Cerebral blood flows were equivalent in both groups before and after bypass, although in the heparin-coated group cerebral blood flows were significantly higher during CPB. There were no brain histologic changes in the heparin-coated group and one focal cortical infarct in the control group. This study suggests that hypothermia induced a state of anticoagulation that did not result in thrombus formation or end organ dysfunction during CPB with a heparin-coated circuit.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Sixteen years of cardiac transplantation: the Columbia Presbyterian Medical Center experience 1977 to 1993.

Cardiac transplantation is currently recognized as the best therapy available for the treatment of endstage heart disease. Since 1977, more than 650 cardiac transplants have been performed at CPMC, with a one-year survival rate currently approaching 85% and a 5-year survival rate approaching 65%. Throughout the 16-year experience with cardiac transplantation at CPMC, the criteria of eligibility for both donor and recipient candidates have been expanded to include older patients. In addition, pediatric patients requiring complex arterial or venous reconstruction and patients with elevated, but reversible pulmonary vascular resistance have been transplanted with excellent results. With the evolution of prolonged posttransplant survival has come a new group of complications associated with chronic long-term immunosuppressive therapy. These, and issues relating to cardiac retransplantation, continue to increase, largely because of the critical lack of organ donors. Continued efforts are being developed to optimize and reduce the total amount of immunosuppression administered postoperatively. Currently, research interests at CPMC include therapy for transplant coronary artery disease, left ventricular assist devices, and xenotransplantation. Ongoing investigations in these and other areas of transplantation have been established to encourage continued growth both within the field and at CPMC through the 21st century.

Academic Medical Centers↗
PubMed1993

Decreasing incidence of coronary disease in pediatric cardiac transplant recipients using increased immunosuppression.

BACKGROUND: Coronary artery disease (CAD) is a limiting factor to long-term survival in cardiac transplant recipients, affecting from 30% to 50% of patients by 4 years after surgery. Can the incidence of CAD be lowered with augmentation of immunosuppression? METHODS AND RESULTS: We compared the incidence of CAD in our pediatric transplant population with nine potential risk factors, including immunosuppressive regimen. The study group consisted of 55 patients who survived more than 1 year (or to first angiogram) or had autopsies. Coronary angiograms were performed yearly and compared sequentially. The mean follow-up of 55 patients was 36 months. Mean age was 10.3 +/- 6 years (range, 4 months to 18 years). Thirteen patients received double immunosuppression with cyclosporine and prednisone, and 42 received triple therapy with cyclosporine, prednisone, and azathioprine. Significant CAD occurred in 10 grafts (6 deaths and 3 retransplants). Cause for graft loss in 6 patients with CAD was acute rejection. CAD was detected by angiogram in only 2 patients. Nine of 10 patients received double therapy (P < .001). There was no difference in mean follow-up between immunosuppression groups. There was a higher rejection frequency for double therapy (0.19 +/- 0.16 rejections per patient month) compared with triple therapy (0.07 +/- 0.11). Ten patients were rejection free in the triple therapy group. CONCLUSIONS: We experienced a significant decrease in the incidence of CAD in our pediatric cardiac transplant recipients using increased immunosuppressive therapy. Type of immunosuppressive regimen (double) and rejection frequency were independent predictors for CAD by multivariate analysis.

Azathioprine↗
PubMed1993

Exercise performance after pediatric heart transplantation.

BACKGROUND: Children awaiting heart transplantation have severe limitations in their ability to exercise. The purpose of this study was to assess exercise capacity after pediatric heart transplantation and to identify factors influencing exercise performance. METHODS AND RESULTS: Progressive cycle ergometry testing was performed in 31 patients at 1.3 +/- 0.8 years after transplantation, and in 16 patients, follow-up studies were performed at 3.3 +/- 1.3 years after transplantation. Maximum work load (Wmax), peak oxygen consumption (VO2), and maximum heart rate (HRmax) were measured. Exercise capacity was defined as normal if Wmax was > or = 75% of predicted values and decreased if Wmax was < 75% of predicted values. Differences in age at transplantation, sex, diagnosis, duration of heart failure, New York Heart Association class before transplantation, resting cardiac index, body mass index, and rejections per patient month were compared between patients with normal and decreased exercise capacity. At initial study, Wmax was 62 +/- 38 W or 61% of that predicted, peak VO2 was 20 +/- 6 mL.kg-1 x min-1 (63% of that predicted), and HRmax was 136 +/- 22 beats per minute (66% of that predicted) for all 31 patients. Six patients had normal exercise capacity, and 25 patients had decreased exercise capacity. Peak VO2 was significantly higher in the normal versus the decreased exercise capacity patients (26 +/- 5 vs 19 +/- 5 mg.kg-1 x min-1). The mean age at transplantation was significantly less in patients with normal exercise capacity: 8.2 +/- 4.6 versus 12.5 +/- 3.6 years for patients with decreased capacity. On follow-up study, no significant differences in Wmax, peak VO2, or HRmax were found from the initial test. CONCLUSIONS: Similar to results obtained in adult patients, exercise capacity was decreased but stable in pediatric patients after heart transplantation.

Cardiomyopathies↗
PubMed1993

Clinical experience with cardiac retransplantation.

Although more than 560 patients worldwide have undergone cardiac retransplantation, few studies of this population have been reported. To evaluate the risk of cardiac retransplantation and to better establish selection criteria, we reviewed the records of all patients who underwent retransplantation at the Columbia-Presbyterian Medical Center. Of 431 patients who underwent transplantation between February 1977 and March 1991, 408 underwent the procedure in the era of cyclosporine-based immunosuppression. Thirteen of these 408 patients underwent retransplantation (including one patient who received a third graft). Indications for the 14 retransplantations included transplant coronary artery disease (n = 8), rejection (n = 5), and intraoperative graft failure (n = 1). Immunosuppression and follow-up protocols used in this cohort were similar to those in the primary transplantation population. No significant differences were found in either actuarial survival between primary transplant recipients (75.1% +/- 2.2% at 1 year and 71.3% +/- 2.4% at 2 years) and patients who underwent retransplantation (71.4% +/- 12.1% at 1 year and 59.5% +/- 14.8% at 2 years) or in linearized rates of rejection and actuarial freedom from rejection between the two groups. No differences between these groups were found with regard to age, sex, race, origin of end-stage heart disease, or early (< 30 day) mortality. The origin of primary graft failure did not correlate with survival outcome in the retransplantation cohort. Follow-up time for patients having primary transplantation ranged from 0 to 8 years (mean 24 months) with a cumulative patient follow-up of 830 patient-years; follow-up time for patients who underwent retransplantation ranged from 0 to 3 years (mean 8.1 months) with a cumulative patient follow-up of 9.5 patient-years. Approximately 50% of patients in both groups had at least one rejection episode by 3 months. Within the limited time period studied after retransplantation, only one patient had transplant coronary artery disease, approximately 27 months after her first retransplantation procedure for acute rejection. These results indicate that the prognosis for patients undergoing cardiac retransplantation is good for patients for whom the indication for retransplantation is identified more than 30 days after initial transplantation.

Adolescent↗
PubMed1992

The implantable defibrillator: an electronic bridge to cardiac transplantation.

BACKGROUND: Sudden cardiac death (SCD) is common among patients awaiting heart transplantation. Medical management of SCD may fail due to lack of efficacy or adverse side effects. The implantable cardioverter-defibrillator (ICD) may extend patient survival until a donor heart is available. METHODS AND RESULTS: We reviewed 16 patients listed for transplantation between November 1988 and October 1991 who underwent ICD implantation for ventricular arrhythmias refractory to medical management. Mean age was 51.4 +/- 11.4 years (range, 19-66 years), mean ejection fraction was 15.4 +/- 3.0% (range, 10-21%), and underlying cardiomyopathy was ischemic (12 patients), valvular (one patient), or dilated (three patients). There was no mortality from ICD insertion. Fourteen patients were discharged before transplantation, and two patients remained in the hospital until transplantation. Twelve patients underwent transplantation after a mean of 155.7 +/- 113.7 days (range, 3-319) on the transplant list. The ICD delivered shocks for tachyarrhythmia associated with near syncope in 15 of 16 patients. ICD shocks numbered > 10 in five patients, 5-9 in three patients, and 1-4 in seven patients. There was no morbidity or mortality attributed to patch electrode removal. CONCLUSIONS: We conclude that the ICD can be implanted with minimal morbidity in transplant candidates, allowing the patients to be ambulatory and to leave the hospital while awaiting heart transplantation. In patients at risk of SCD, the ICD is an effective electronic bridge to transplantation.

Anti-Arrhythmia Agents↗
PubMed1992

University of Wisconsin solution versus crystalloid cardioplegia for human donor heart preservation. A randomized blinded prospective clinical trial.

We have previously shown the safety and efficacy of University of Wisconsin solution for hypothermic preservation of the human donor heart in a pilot group of 16 transplant recipients. The present study is a randomized clinical trial comparing University of Wisconsin solution to conventional preservation using crystalloid cardioplegia and saline storage within a 4-hour limit of ischemia. Heart transplant recipients (n = 42) were randomized into two groups: those receiving hearts preserved by University of Wisconsin solution, the UWS group (n = 22), and those receiving hearts preserved in the conventional manner, the CCS group (n = 20). Recipient age, gender, heart disease, and preoperative inotropic support and donor age, gender, and mean ischemic time in hours (UWS 2 hours 36 minutes, range 1 hour 36 minutes to 2 hours 53 minutes; CCS 2 hours 20 minutes, range 1 hour 20 minutes to 2 hours 44 minutes; p = not significant) were similar. Significant differences observed between the two groups included (1) mean time (minutes) from reperfusion to achieve a stable rhythm, (2) need for intraoperative defibrillations, (3) need for transient cardiac pacing, and (4) integrated postoperative creatinine kinase and aspartate aminotransferase release over 48 hours. There was no difference in postoperative electrocardiogram, endomyocardial biopsy, or hemodynamics. One UWS patient died of sepsis and another of a ruptured cerebral aneurysm. UWS is safe for donor organ arrest and preservation despite high viscosity and potassium concentration. When compared with CCS hearts, hearts preserved in UWS regained electrical activity more rapidly and had better myocardial protection as demonstrated by enzymatic analysis. Further investigation is required to determine the effects of UWS preservation on long-term survival, to determine the prevalence of rejection and graft atherosclerosis, and to test the ability of UWS to extend donor ischemic time in human cardiac transplantation.

Adenosine↗
PubMed1988

Transmembrane action potentials and intracellular potassium activity of baboon cardiac tissues.

Preparations of baboon cardiac tissue were studied using standard microelectrode and double barrelled potassium ion selective microelectrode techniques. Transmembrane action potentials were recorded from Purkinje fibres and from atrial and ventricular muscle cells. Purkinje fibres were impaled frequently on the ventricular septum but were sparse on the endocardium of the free wall. Purkinje fibres had longer action potential durations than ventricular muscle cells, and endocardial muscle cells had longer action potential durations than epicardial muscle cells. Tissue bundles resembling the false tendons of the canine heart were found in the ventricles. Most of these false tendons consisted of ventricular muscle as indicated by transmembrane action potentials. On rare occasions, false tendon preparations were studied in which the cells had action potentials similar to those of canine Purkinje fibres. In these preparations, normal automaticity occurred from maximum diastolic potentials greater than or equal to -85 mV. Intracellular potassium activity in the baboon ventricular muscle cells was 96(3) mmol.litre-1 (mean(SEM), n = 32), which is lower than that reported for canine tissues but higher than that reported for feline or rabbit tissues. It is concluded that, although the cellular electrophysiology of primate and canine cardiac tissues is superficially similar, consistent and perhaps important differences do occur.

Action Potentials↗
PubMed1987

Imaging of cardiac allograft rejection in dogs using indium-111 monoclonal antimyosin Fab.

The acute rejection of cardiac allografts is currently diagnosed by the presence of myocyte necrosis on endomyocardial biopsy. We evaluated the efficacy of noninvasive scintigraphic imaging with indium-111-labeled anticardiac myosin Fab fragments (indium-111 antimyosin) to detect and quantify cardiac allograft rejection. Six dogs that had intrathoracic heterotopic cardiac allograft transplantation were injected with indium-111 antimyosin and planar and single photon emission computed tomographic (SPECT) images were obtained in various stages of acute and subacute rejection. Four dogs had an allograft older than 8 months and had been on long-term immunosuppressive therapy; two dogs had an allograft less than 2 weeks old and were not on immunosuppressive therapy. Count ratios comparing heterotopic with native hearts were calculated from both SPECT images and in vitro scans of excised and sectioned hearts and were compared with the degree of rejection scored by an independent histopathologic review. Indium-111 antimyosin uptake was not visible in planar or SPECT images of native hearts. Faint diffuse uptake was apparent in cardiac allografts during long-term immunosuppression and intense radioactivity was present in hearts with electrocardiographic evidence of rejection. The heterotopic to native heart count ratios in SPECT images correlated significantly with the count ratios in the excised hearts (r = 0.93) and with the histopathologic rejection score (r = 0.97). The distribution of indium-111 antimyosin activity in right and left ventricles corresponded to areas of histopathologic abnormalities. Immunoperoxidase studies showed deposition of indium-111 antimyosin only in areas of myocyte necrosis. The results demonstrate that indium-111 antimyosin imaging can noninvasively detect the presence, location and severity of canine cardiac allograft rejection.

Animals↗
PubMed1987

Prolongation of primate cardiac xenograft survival with cyclosporine.

Cardiac xenotransplantation in nonprimates using traditional immunosuppression (azathioprine and prednisone) or cyclosporine has been unsuccessful or has required doses of immunosuppressants not tolerated by man. This study sought to determine if primate hearts could be transplanted successfully across genus boundaries using a dose of cyclosporine applicable to human transplantation. The hearts of outbred cynomolgus monkeys (Macaca fascicularis) were heterotopically transplanted into the necks of outbred baboons (Papio anubis). Hyperacute rejection did not occur and there were no cyclosporine-induced malignancies or nephrotoxicity. A 12-fold prolongation of mean cardiac xenograft survival to 77 days was accomplished using parenteral cyclosporine and steroids. The histology of rejection was notable for the appearance of reversible rejection on the 30-day biopsies. The histopathologic and immunologic data support the role of both cell-mediated and humoral mechanisms in primate cardiac xenograft rejection. Neither mixed lymphocyte cultures or cytotoxic antibody assays were predictive of graft loss, but there was a significant increase in their respective levels at the time of cessation of graft function. Thus, significant prolongation of primate cardiac graft survival across a genus boundary was accomplished using a dose of cyclosporine similar to that used in human transplantation.

Animals↗
PubMed1987

Cardiac xenotransplantation in primates.

Successful cardiac xenotransplantation would alleviate the severe shortage of donor organs that presently limits the availability of cardiac transplantation. Early attempts at human xenotransplantation achieved minimal success. However, the effectiveness of cyclosporine in nonhuman xenotransplant models has received little experimental investigation. We have therefore studied the effect of cyclosporine-based immunosuppression in primate cardiac xenograft models using cynomolgus monkey donors and baboon recipients. Donor hearts were transplanted heterotopically into the necks of recipients or in the orthotopic position. Recipients were treated with no immunosuppression (controls), cyclosporine and steroids, or cyclosporine, steroids, azathioprine, and antithymocyte globulin. Statistically significant prolongation of graft survival compared to the control group was observed in the heterotopic groups. Mean survival time of the cyclosporine-treated and steroid-treated heterotopic grafts was 61 days compared to 6 days for grafts in the control group (p = 0.01); the addition of azathioprine and antithymocyte globulin yielded a mean survival of 84 days (p less than 0.01). No significant increase in graft survival was noted in the orthotopic groups treated with either immunosuppressive regimen. Although long-term use of human xenografts as an alternative for heart replacement is not supported by these data, further investigation of the orthotopic model is clearly justified.

Animals↗