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Biomedical subjects

O H Frazier

Publications and source records attributed to O H Frazier.

At least 127 records · Page 7Linked to original sources

Cutaneous T-cell lymphoma in a cardiac transplant recipient.

Mycosis fungoides, an uncommon form of cutaneous T-cell lymphoma, arises in the skin and frequently progresses to generalized lymphadenopathy Although the cause of cutaneous T-cell lymphoma is unknown, chronic immunosuppression may play a role. A few cases have been reported in renal transplant recipients; however, ours appears to be the 1st report of cutaneous T-cell lymphoma in a cardiac transplant recipient. In our patient, cutaneous manifestations of the disease were noted less than 1 year after transplantation. Seven years after transplantation, Sézary syndrome, a variant form of mycosis fungoides, was diagnosed by tissue biopsy and flow cytometry analysis. Photopheresis improved symptoms but was not well tolerated because of hemodynamic sequelae. Psoralen and ultraviolet A therapy also improved the patient's skin condition, but a generalized lymphadenopathy developed. The maintenance immunosuppressive regimen was changed from cyclosporine (3 mg/kg/day) and azathioprine to cyclosporine (1.5 mg/kg/day) and cyclophosphamide. Although effective in the short-term, the results of this therapeutic strategy could not be fully evaluated because the patient died of acute myocardial infarction.

Aged↗

First permanent implant of the Jarvik 2000 Heart.

BACKGROUND: Heart failure is a major public-health concern. Quality and duration of life on maximum medical therapy are poor. The availability of donor hearts is severely limited, therefore an alternative approach is necessary. We have explored the use of a new type of left-ventricular assist device intended as a long-term solution to end-stage heart failure. METHODS: As part of a prospective clinical trial, we implanted the first permanent Jarvik 2000 Heart--an intraventricular device with an innovative power delivery system--into a 61-year-old man (New York Heart Association functional class IV) with dilated cardiomyopathy. We assessed the effect of this left-ventricular assist device on both native heart function and the symptoms and systemic characteristics of heart failure. FINDINGS: The Jarvik 2000 Heart sustained the patient's circulation, and was practical and user-friendly. After 6 weeks, exercise tolerance, myocardial function, and end-organ function improved. Symptoms of heart failure have resolved, and continuous decreased pulse-pressure perfusion has had no adverse effects in the short term. There has been no significant haemolysis and no device-related complications. The skull-mounted pedestal is unobtrusive and has healed well. CONCLUSIONS: The initial success of this procedure raises the possibility of a new treatment for end-stage heart failure. In the longer term, its role will be determined by mechanical reliability.

Blood Pressure↗

The implications for cardiac recovery of left ventricular assist device support on myocardial collagen content.

BACKGROUND: To define the beneficial cellular changes that occur with chronic ventricular unloading, we determined the effect of left ventricular assist device (LVAD) placement on myocardial fibrosis. METHODS: We obtained paired myocardial samples (before and after LVAD implantation) from 10 patients (aged 43 to 64 years) with end-stage cardiomyopathy. We first determined regional collagen expression of an explanted heart by a computerized semiquantitative analysis of positive picro-sirius red stained areas. RESULTS: We found that there was no statistically significant difference in collagen content between regions of the failed heart studied. Next we determined collagen content in these paired myocardial biopsies pre- and post-LVAD implantation. All 10 patients had significant reductions in collagen content after LVAD placement with a mean reduction of 82% (percent of tissue area stained decreased from 32% +/- 4% to 4% +/- 0.8%, P < 0.001). CONCLUSION: In summary, these data demonstrate that chronic mechanical circulatory support significantly reduces fibrosis in the failing myocardium.

Adult↗

Partial left ventriculectomy: which patients can be expected to benefit?

BACKGROUND: Although some patients with end-stage heart disease will benefit from a partial left ventriculectomy, no criteria have been found for identifying this group preoperatively. Our experience with partial left ventriculectomy at two institutions-the Texas Heart Institute in Houston, TX, USA, and Dedinje Cardiovascular Institute in Belgrade, Yugoslavia-showed a higher survival rate and better postoperative myocardial function in the Yugoslavian patients. METHODS: We reviewed data from 42 patients (21 at each center) who had idiopathic cardiomyopathy, a left ventricular end-diastolic dimension of more than 70 mm, wall thickness of 1 cm or greater, and New York Heart Association class III or IV symptoms. The only significant difference in preoperative status between the two groups was duration of symptoms. Histologic specimens, blinded as to origin, were graded with regard to myocyte hypertrophy, cytoplasmic vacuolation, and fibrosis. Computer-assisted myocyte and nuclear morphometry was also performed. RESULTS: Immediately postoperatively, there were no significant intergroup differences in the reduction in cardiac dimension or in corrections of mitral regurgitation. During 6-month follow-up, however, the Texas Heart Institute patients had a lower cardiac index (1.8 versus 3.0 L x min(-1) x m(-2); p = 0.001) and left ventricular ejection fraction (24% versus 34%; p = 0.006) than the Dedinje Cardiovascular Institute patients. The Texas Heart Institute patients differed from the Dedinje Cardiovascular Institute patients in the degree of severe or moderate changes in myocyte hypertrophy (90% versus 29%; p = 0.0003) and fibrosis (71% versus 29%; p = 0.006), as well as in the measurements of median myocyte diameter (35 +/- 7 microm versus 27 +/- 4 microm; p = 0.0002) and median nuclear size (15 +/- 4 microm versus 12 +/- 2 microm; p = 0.0029). CONCLUSIONS: In the Texas Heart Institute patients, the significant intergroup difference in clinical outcome may have been related to increased myocyte hypertrophy and fibrosis. Further studies should be performed to determine the usefulness of these criteria in selecting patients for partial left ventriculectomy.

Adult↗

Normalization of native heart function years after heterotopic transplantation.

We describe a patient whose native heart function has normalized several years after heterotopic heart transplantation. The native heart sustained the patient's circulation at a time when the donor heart was temporarily dysfunctional. Native heart improvement, let alone normalization, is considered rare after heterotopic transplantation but has been noted with increased frequency after long-term unloading with left ventricular assistance.

Cardiomyopathies↗

Left ventricular reduction in a Jehovah's Witness.

For Jehovah's Witnesses with severe heart failure, left ventricular reduction surgery may be a satisfactory alternative to cardiac transplantation. Compared with transplantation, left ventricular reduction surgery can involve less blood loss thus decreasing the need for blood-volume replacement. More importantly, left ventricular reduction surgery obviates the need for a donor organ.

Cardiomyopathy, Dilated↗

Single-clamp technique for aneurysms of the descending thoracic aorta: report of 132 consecutive cases.

OBJECTIVE: To determine the efficacy of a single-clamp technique in preventing spinal cord ischemia during repair of aneurysms of the descending thoracic aorta. PATIENTS AND METHODS: From January 1989 to May 1999, 132 consecutive patients (91 men and 41 women, aged 31-86 years), with aneurysms of the descending thoracic aorta underwent repair using a single-clamp technique and temporary partial distal exsanguination. The diseased aortic segment was replaced with a Dacron graft. Blood was re-infused from an auto-transfusion device, and the segmental vessels were over-sewn but not implanted into the graft. RESULTS: The average aortic cross-clamp time was 26.4 min (range, 11-67 min) for the overall group and 37.4 min for patients who had spinal cord complications. An average of 2066 ml of blood was auto-transfused (range, 450-6100 ml). During the first 30 postoperative days, 17 patients (12.9 %) died. Eleven patients (8.3%) had spinal cord dysfunction, six patients (4.5%) had lower-extremity paraparesis, and five patients (3.8%) had paraplegia. Nine patients (6.8%) had renal failure necessitating hemodialysis. Other complications included bleeding in 15 cases (11.4%), respiratory failure in 12 cases (9.1%), wound-related sequelae in five cases (3.8%), distal embolism in five cases (3.8%), and bowel ischemia in two cases (1.5%). CONCLUSION: The single-clamp technique yielded an acceptable complication rate, and the mortality was comparable to that seen after the use of more complex methods. For satisfactory results, the cross-clamp time should not exceed 30 min.

Adult↗

Future directions of cardiac assistance.

During the past decade, mechanical circulatory support has gained increased acceptance as a treatment for patients with severe heart failure who are unresponsive to conventional treatment. Steady progress has been made with respect to technology, patient selection, and postoperative management. Currently, a wide array of circulatory assist pumps offers various levels of assistance and degrees of postoperative mobility. These devices not only save lives (lowering the mortality of heart transplant candidates by 55%) but, in some long-term bridge-to-transplant cases, permit hospital discharge and cardiac rehabilitation. More than 4000 patients have been supported by long-term assist pumps worldwide. In addition to being used for bridging to transplantation or bridging to the use of some other bridging device, long-term circulatory assist devices are being evaluated as bridges to recovery or alternatives to transplantation in selected patients with severe heart failure. Moreover, several total artificial hearts have shown considerable potential in calves and will soon undergo clinical trials aimed at permanent heart replacement. Eventually, as cardiac support or replacement devices become smaller, more durable, and less obtrusive, they may become as conventional and commonplace as pacemakers are today.

Animals↗

Mechanical cardiac assistance: historical perspectives.

Cardiac transplantation remains the therapeutic option of choice for treating patients with chronic, progressive, end-stage heart failure. However, over the past 40 years, a number of mechanical assist systems have been developed with the goal of treating and rehabilitating patients with severe circulatory compromise. Today, a wide array of devices is available to provide increasing levels of circulatory support. When used as bridges to heart transplantation, long-term circulatory support systems are a reliable means of keeping heart-failure patients alive as they await suitable donor hearts. Initially, transplant candidates who were receiving this type of support were unable to leave the hospital; today, however, because of advances in mechanical support technology and the portability of the current systems, these patients may return to their homes and even to their jobs while awaiting transplantation. Although heart transplantation may now be considered a routine procedure, the demand for donor hearts will always outweigh the supply, creating a definite need for long-term mechanical circulatory support. Already, clinical trials are underway to test the effectiveness of left ventricular assist devices as long-term support. As smaller, more effective cardiac assist devices become available, they should benefit even more the number of patients who may need permanent circulatory support. The fact that myocardial function can improve enough with chronic ventricular unloading to allow removal of the device may further broaden the use of this technology.

Heart Failure↗

Surgical therapies for heart failure.

Heart transplantation remains the best hope for patients with end-stage heart failure unresponsive to conventional therapy, but the number of transplant candidates continues to exceed the number of available donor hearts. Despite major advances in the medical management of heart failure, researchers continue to explore alternative surgical therapies designed to augment cardiac function. Many of these surgical therapies are still in the experimental or clinical trial phases. Surgical approaches include coronary revascularization, mitral valve repair or replacement, cardiomyoplasty, left ventricular volume reduction surgery, and bridging to recovery with the use of ventricular assist devices. Although cardiac surgeons have gained considerable experience in the treatment of patients with heart failure, many improvements and innovations lie ahead.

Cardiomyoplasty↗

Impact of membrane oxygenators on pulsatile versus nonpulsatile perfusion in a neonatal model.

We investigated the effects of two new hollow-fiber membrane oxygenators, the Capiox SX10 and the Lilliput 901, on pulsatile versus nonpulsatile perfusion in an in vitro model designed to simulate a 3 kg infant. The experiments were divided into eight groups (six pulsatile and two nonpulsatile), according to the equipment and settings used. Each group included six tests. In all experiments, the pseudo-patient's mean arterial pressure was 40 mmHg, and the pump flow rate was 550 ml/min. During pulsatile cardiopulmonary bypass, the pump's base flow was set at 30%, and the pump rate was set at 80, 100, 120, 140, or 150 beats/min. The PUMP START and PUMP STOP timing points were adjusted to produce different pulse-width settings. We were especially interested in evaluating the pre- and postoxygenator extracorporeal circuit pressure (ECP), the oxygenator pressure drop, and the precannula ECP. When used with a pulsatile roller pump, the Capiox produced a significantly lower preoxygenator ECP than the Lilliput (p < 0.001); moreover, the Capiox yielded a significantly lower oxygenator pressure drop (p < 0.001). During nonpulsatile perfusion, the Capiox again produced a lower preoxygenator ECP than the Lilliput (p < 0.001). These results suggest that the Capiox may be more suitable than the Lilliput when the pulsatile flow is employed, and pulsatile flow does not increase the ECP with either oxygenator.

Equipment Design↗

Effects of myocardial contractility on microemboli production by mechanical heart valves in a bovine model.

Microemboli caused by mechanical heart valves have the potential to cause cerebrovascular events. We investigated the effects of myocardial contractility and heart rate on microemboli production in association with conventional and experimental mechanical heart valves implanted in the mitral position in a bovine model. In 10 calves, the mitral valves were replaced with mechanical valves. Doppler recordings were analyzed for high-intensity transient signals, which are ultrasound reflections from circulating microemboli. The animals were studied at rest, during pacing at 160 bpm, after dobutamine infusion, and after esmolol infusion. The incidence of high intensity transient signals was expressed as signal frequency (signals per hour) and as signal rate (signals per 100 heart cycles). With a 68% increase in the heart rate, signal frequency increased by 135%, but signal rate increased by only 41 %. With a 144% increase in myocardial contractility, signal rate increased by 264 %. With a 31 % decrease in contractility, signal rate decreased by 62 %. We conclude that microemboli production by mechanical heart valves varies with myocardial contractility and heart rate. The fact that contractility affects the incidence of high-intensity transient signals suggests that the microemboli are gaseous in nature, that their production is pressure driven, and that cavitation is a possible cause. It is likely that mechanical heart valve design is responsible for the quantity of microemboli production.

Adrenergic beta-Agonists↗

Transmyocardial revascularization with a carbon dioxide laser in patients with end-stage coronary artery disease.

BACKGROUND: The construction of subendocardial channels to perfuse ischemic areas of the myocardium has been investigated since the 1950s. We assessed the safety and efficacy of transmyocardial revascularization with a carbon dioxide laser in patients with refractory angina and left ventricular free-wall ischemia that was not amenable to direct coronary revascularization. METHODS: In a prospective, controlled, multicenter trial, we randomly assigned 91 patients to undergo transmyocardial revascularization and 101 patients to receive continued medical treatment. The severity of angina (according to the Canadian Cardiovascular Society [CCS] classification), quality of life, and cardiac perfusion (as assessed by thallium-201 scanning) were evaluated at base line and 3, 6, and 12 months after randomization. RESULTS: At 12 months, angina had improved by at least two CCS classes in 72 percent of the patients assigned to transmyocardial revascularization, as compared with 13 percent of the patients assigned to medical treatment who continued medical treatment (P<0.001). Patients in the transmyocardial-revascularization group also had a significantly improved quality of life as compared with the medical-treatment group. Myocardial perfusion improved by 20 percent in the transmyocardial-revascularization group and worsened by 27 percent in the medical-treatment group (P=0.002). In the first year of follow-up, 2 percent of patients assigned to undergo transmyocardial revascularization were hospitalized because of unstable angina, as compared with 69 percent of patients assigned to medical treatment (P<0.001). The perioperative mortality rate associated with transmyocardial revascularization was 3 percent. The rate of survival at 12 months was 85 percent in the transmyocardial-revascularization group and 79 percent in the medical-treatment group (P=0.50). CONCLUSIONS: In patients with angina refractory to medical treatment and coronary artery disease that precluded coronary-artery bypass surgery or percutaneous transluminal coronary angioplasty, transmyocardial revascularization improved cardiac perfusion and clinical status over a 12-month period.

Aged↗

Safety, tolerability and efficacy of cyclosporine microemulsion in heart transplant recipients: a randomized, multicenter, double-blind comparison with the oil based formulation of cyclosporine--results at six months after transplantation.

BACKGROUND: The introduction of cyclosporine has resulted in significant improvement in the survival of cardiac allograft recipients due to decreased mortality from infection and rejection. The original oil-based cyclosporine formulation exhibits variable and unpredictable bioavailability that correlates with an increased incidence of acute and chronic rejection in those patients in whom this is most pronounced. The primary objectives of this prospective, multicenter, randomized, double-blind study in cardiac transplant patients were: to compare the efficacy of cyclosporine microemulsion (CsA-NL) with oil-based cyclosporine (CsA-SM) as measured by cardiac allograft and recipient survival and the incidence and severity of acute rejection episodes; and to assess the safety and tolerability of CsA-NL compared with CsA-SM in this population. This report represents the analysis of results 6 months after transplantation. METHODS: A total of 380 patients undergoing their first cardiac transplant at 24 centers in the United States, Canada, and Europe were enrolled in this double-blind, randomized trial examining the safety and efficacy of CsA-NL versus CsA-SM. Rejection was diagnosed using endomyocardial biopsy and were graded according to standardized criteria of the International Society of Heart and Lung Transplantation (ISHLT). Clinical parameters were monitored during the study. Survival and freedom from were used for analysis as was Fisher's exact test for comparisons between groups. RESULTS: At 6 months after transplantation, allograft and patient survival were the same for both groups. The frequency of ISHLT grade 3A or greater episodes in the two groups was identical. Fewer CsA-NL patients (5.9%) required antilymphocyte antibody (ATG or OKT-3) therapy for rejection compared with the CsA-SM-treated patients (14.1%, P=0.01). Females with ISHLT rejection grade > or = 3A treated with CsA-NL had a 46% lower incidence of rejection compared with the CsA-SM-treated group (31.3% vs. 57.6%, P=0.032). Fewer infections were seen in the CsA-NL. With the exception of baseline and 1 week posttransplant creatinines which were higher in the CsA-NL group, the overall creatinine was not significantly different between the two groups. CONCLUSIONS: This multicenter, randomized study of cardiac transplant recipients documented less severe rejection (in particular those requiring antibody therapy) and a lower incidence of infection in CsA-NL-treated patients. Results from the female subgroup analysis suggest that the improved bioavailability of CsA-NL might reduce the frequency of rejection episodes in female patients. The use of CsA-NL was not associated with an increased risk of adverse events.

Adolescent↗

Decreased expression of tumor necrosis factor-alpha in failing human myocardium after mechanical circulatory support : A potential mechanism for cardiac recovery.

BACKGROUND: An increasing number of observations in patients with end-stage heart failure suggest that chronic ventricular unloading by mechanical circulatory support may lead to recovery of cardiac function. Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine capable of producing pulmonary edema, dilated cardiomyopathy, and death. TNF-alpha is produced in the myocardium in response to volume overload; however, the effects of normalizing ventricular loading conditions on myocardial TNF-alpha expression are not known. We hypothesize that chronic ventricular unloading by the placement of a left ventricular assist device (LVAD) may eliminate the stress responsible for persistent TNF-alpha expression in human failing myocardium. METHODS AND RESULTS: Myocardial tissue was obtained from normal hearts and from paired samples of 8 patients with nonischemic end-stage cardiomyopathy at the time of LVAD implantation and removal. Tissue sections were stained for TNF-alpha, and quantitative analysis of the stained area was performed. We found that TNF-alpha content decreased significantly after LVAD support. Furthermore, the magnitude of the changes did not correlate with the length of LVAD support, although greater reductions in myocardial TNF-alpha content were found in patients who were successfully weaned off the LVAD who did not require transplantation. CONCLUSIONS: These data show for the first time that chronic mechanical circulatory assistance decreases TNF-alpha content in failing myocardium; furthermore, we suggest that the magnitude of the change may predict which patients will recover cardiac function.

Adult↗

The role of flow cytometry-detected IgG and IgM anti-donor antibodies in cardiac allograft recipients.

BACKGROUND: At our transplant center, cardiac allograft recipients undergo transplantation following a negative IgG anti-human globulin (AHG) crossmatch (XM). Flow cytometry crossmatching (FCXM) is a more sensitive XM procedure than the AHG XM procedure, yet there is limited information regarding the clinical relevance of FCXM to cardiac allograft outcome. METHODS: FCXM was performed retrospectively using the pretransplant sera from 140 recipients of primary cardiac allografts who underwent transplantation after AHG-IgG-NEG XM. The FCXM results were correlated to posttransplant rejection and patient survival. RESULTS: All of the patients were auto-XM-NEG. Twenty-two of 140 patients (16%) displayed IgG(+) FCXM and had a significantly poorer 1-year survival rate than did 57 of the FCXM-NEG recipients (68% vs. 86%, P<0.02). Moreover, 50% of the IgG(+) FCXM recipients experienced early rejections (< or =14 days postoperatively) compared with only 16% for the FCXM-NEG recipients (P<0.01). The survival rate of 92% for IgM(+) FCXM recipients (n=37) was significantly improved compared with the 86% survival rate for FCXM-NEG control recipients (P<0.05), suggesting a protective role for IgM. Consistent with this interpretation is that the 1-year survival rate of 79% for the IgG, IgM FCXM(+) recipients (n=24) was significantly better than the 68% survival rate for the IgG(+) FCXM recipients (P<0.02). CONCLUSIONS: These data suggest that IgG(+) FCXM identifies a subset of AHG-IgG-NEG XM cardiac allograft recipients who are at risk for early rejections and poor survival. In contrast, the presence of IgM may be beneficial to survival.

Aged↗

Intraoperative arrhythmias and tissue damage during transmyocardial laser revascularization.

BACKGROUND: Transmyocardial laser revascularization creates transmural channels to improve myocardial perfusion. Different laser sources and ablation modalities have been proposed for transmyocardial laser revascularization. We investigated the incidence of cardiac arrhythmias and laser-tissue interactions during transmyocardial laser revascularization of normal porcine myocardium with three different lasers. METHODS: We used a continuous-wave, chopped CO2 laser (20 J/pulse, 15 ms/pulse) synchronized with the R wave; a holmium:yttrium aluminum garnet (Ho:YAG) laser (2 J/pulse, 250 micros/pulse, 5 Hz); and a xenon-chloride (excimer, Xe:Cl) laser (35 mJ/pulse, 20 ns/pulse, 30 Hz). Each laser was used 30 times as the sole modality in four consecutive pigs, yielding 120 channels. RESULTS: The average number of pulses needed to create a channel was 1, 11 +/- 4, and 37 +/- 8 for the CO2, Ho:YAG, and Xe:Cl lasers, respectively. All Ho:YAG and Xe:Cl channels had premature ventricular contractions. Ventricular tachycardia occurred in 70% of the Xe:Cl and 60% of the Ho:YAG channels. Only 36% of the CO2 channels had premature ventricular contractions, and only 3% of the CO2 channels had ventricular tachycardia (p < 0.001 versus Ho:YAG and Xe:Cl). Ho:YAG channels were highly irregular: each had a 0.6-mm-wide central zone surrounded by a ring of coagulation necrosis (diameter, 1.84 +/- 0.67 mm) with effaced cellular architecture in a thin hemorrhagic zone. The Xe:Cl sections exhibited the same patterns on a smaller scale (diameter, 0.74 +/- 0.18 mm). The CO2 channels were straight and well demarcated. The zone of structural and thermal damage extended over half the channel's diameter, measuring 0.52 +/- 0.25 mm. CONCLUSIONS: During transmyocardial laser revascularization, the CO2 laser synchronized with the R wave is significantly less arrhythmogenic than the Ho:YAG and Xe:Cl lasers not synchronized with the R wave. In addition, the interaction of the CO2 laser with porcine cardiac tissue is significantly less traumatic than that of the Ho:YAG and the Xe:Cl lasers.

Animals↗