Search PubMed⌕ Search

Biomedical subjects

R L Kormos

Publications and source records attributed to R L Kormos.

At least 19 recordsLinked to original sources
PubMed2001

Downregulation of matrix metalloproteinases and reduction in collagen damage in the failing human heart after support with left ventricular assist devices.

BACKGROUND: Left ventricular assist device (LVAD) support of the failing heart induces salutary changes in myocardial structure and function. Matrix metalloproteinases (MMPs) are increased in the failing heart and are induced by stretch in cardiac cells in vitro. We hypothesized that mechanical unloading may affect LV plasticity by regulating MMPs and their substrates. METHODS AND RESULTS: LV samples were collected from patients with dilated cardiomyopathy (DCM, n=14) or ischemic cardiomyopathy (ICM, n=16) at the time of implantation of the LVAD and again during cardiac transplantation. MMP-1, -3, and -9 were measured by ELISA, MMP-2 and -9 gelatinolytic activity by gelatin zymography, and tissue inhibitors of metalloproteinases (TIMPs) by Western blot. Total soluble and insoluble collagens were separated by pepsin solubilization, and the contents were determined by quantification of hydroxyproline. The undenatured soluble collagen was measured by Sircol collagen assay. The results showed that MMP-1 and -9 were decreased, whereas TIMP-1 and -3 were increased, but there was no change in MMP-2 and -3 and TIMP-2 and -4 after LVAD support. The undenatured collagen was increased, with the ratio of undenatured to total soluble collagens increased in ICM and that of insoluble to total soluble collagens increased in DCM after LVAD support. CONCLUSIONS: The reduced MMPs and increased TIMPs and ratios of undenatured to total soluble collagens and insoluble to total soluble collagens after LVAD support suggest that reduced MMP activity diminished damage to the matrix. These changes may contribute to the functional recovery and LV plasticity after LVAD support.

Adult↗
PubMed2001

Database: relevant or not.

Progress in the field of ventricular assist devices requires a more rigorous and systematic method of collecting outcomes data. A worldwide registry of device implants and results is proposed. With widespread participation, data from this registry would improve the identification of risk factors and complications, and allow for the creation of predictive models that would enhance patient selection. Professional societies should lead the development of a registry in close partnership with government and industry. Data collection using the Web, with rigorous security measures to protect patient privacy, would offer numerous advantages in efficiency and immediacy of communication for all participants.

Databases, Factual↗
PubMed2001

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

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

Equipment Design↗
PubMed2001

Relapsing bacteremia in patients with ventricular assist device: an emergent complication of extended circulatory support.

BACKGROUND: Ventricular assist devices (VAD) are currently approved for use as a bridge for transplantation. Although reports have suggested acceptable rates of survival of patients with VAD, there is little information regarding the mechanism and etiology of bacteremia in these patients. METHODS: We prospectively followed patients who underwent VAD implantation and developed bacteremia during VAD support at the University of Pittsburgh Medical Center. Relapsing bacteremia was defined as at least two episodes of positive blood cultures with a genetically related organism on 2 different days. Species identification and susceptibility testing were performed on all isolates. Pulse field gel electrophoresis was performed on selected blood and VAD isolates. RESULTS: Between January 1998 and August 1999, 3 patients with VAD developed relapsing bacteremia, which was treated with full courses of antibiotic agents, 2 of whom also developed VAD endocarditis. All 3 patients had documented driveline or device pocket infections with these isolates. Consecutive blood and VAD isolates were found to be genetically related within each patient. CONCLUSIONS: These patients with bacteremia after VAD implantation had relapse due to the same strain, which may have originated from indolent driveline infection. Endovascular infection in this setting is difficult to eradicate with antibiotic agents and carries a high mortality. These patients should be considered to have priority for orthotopic heart transplantation.

Adult↗
PubMed2001

Quality of life outcomes after heart transplantation in individuals bridged to transplant with ventricular assist devices.

BACKGROUND: Increasing numbers of individuals receive ventricular assist devices (VADs) as bridges to heart transplantation. Physical morbidity risks and benefits, and quality of life (QOL) during VAD support have been documented. Effects of pre-transplant VAD support on functional and QOL outcomes after transplantation have received no empirical attention. METHODS: Sixty-three VAD patients who received heart transplants underwent QOL evaluations of physical functioning, emotional and cognitive well-being, and social functioning at 2, 7, and 12 months after transplant (response rate = 95%). Ninety patients who had not received VADs--matched to the VAD group on cardiac-related and sociodemographic characteristics--served as longitudinal controls. RESULTS: Both VAD and non-VAD groups showed similar levels and similar, statistically significant (p < 0.05) improvement in physical functioning (sleep, body care, mobility, ambulation, overall functional status, number of somatic complaints) across the study period. Emotional well-being (elevated depressive, anxiety, and anger symptoms; post-traumatic stress disorder rate) was stable or improved in both groups, and VAD patients showed significantly lower anxiety rates. The VAD patients' post-transplant cognitive status was significantly poorer. The VAD patients were significantly less likely to return to employment; other social functioning measurers (daily concerns, interpersonal activities/involvement, role function) showed mixed effects. Cognitive impairment explained much of the association between VAD support and post-transplant employment. CONCLUSIONS: Although post-transplant physical and emotional recovery is similar in VAD and non-VAD patients, VAD patients retain more cognitive impairment and show mixed changes in social functioning. Increased attention to strategies to maximize VAD patients' cognitive capacity is required to facilitate social reintegration.

Cognition↗
PubMed2001

The role of diastolic pump flow in centrifugal blood pump hemodynamics.

We tried to verify the hypothesis that increases in pump flow during diastole are matched by decreases in left ventricular (LV) output during systole. A calf (80 kg) was implanted with an implantable centrifugal blood pump (EVAHEART, SunMedical Technology Research Corp., Nagano, Japan) with left ventricle to aorta (LV-Ao) bypass, and parameters were recorded at different pump speeds under general anesthesia. Pump inflow and outflow pressure, arterial pressure, systemic and pulmonary blood flow, and electrocardiogram (ECG) were recorded on the computer every 5 ms. All parameters were separated into systolic and diastolic components and analyzed. The pulmonary flow was the same as the systemic flow during the study (p > 0.1). Systemic flow consisted of pump flow and LV output through the aortic valve. The ratio of systolic pump flow to pulmonary flow (51.3%) did not change significantly at variable pump speeds (p > 0.1). The other portions of the systemic flow were shared by the left ventricular output and the pump flow during diastole. When pump flow increased during diastole, there was a corresponding decrease in the LV output (Y = -1.068X + 51.462; R(insert)(2) = 0.9501). These show that pump diastolic flow may regulate expansion of the left ventricle in diastole.

Analysis of Variance↗
PubMed2000

Cardiac transplantation in survivors of lymphoma: a multi-institutional survey.

BACKGROUND: Cardiac transplantation has been successfully performed in patients with a history of presumably cured Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL). Though the risk of recurrence is a major concern, the long-term influence of prior cancer and cancer therapy on posttransplant outcome has not been previously investigated. METHODS: Questionnaires were sent to 130 cardiac transplant centers in the United States registered with the United Network for Organ Sharing. Data collected included patient demographics; type, stage, and timing of HD/NHL; treatment for HD/NHL; posttransplant immunosuppressive regimen, rejection history, and outcomes; and Epstein-Barr virus status. RESULTS: Thirty-four cardiac transplant recipients with a previous history of HD (n=16) or NHL (n=18) were identified. HD patients averaged 41+/-15 years of age, with a mean disease-free interval of 15+/-9 years at the time of transplantation. NHL patients averaged 42+/-17 years of age with a mean disease-free interval of 10+/-9 years at the time of transplantation. The mean follow-up for the entire group was 50 months (range, 2 days to 136 months), and mean follow-up for the survivors was 67 months (range, 23-136 months). The 1-, 3-, 5-, 7-, and 10-year actuarial survival estimates for the entire group are 77%, 64%, 64%, 64%, and 50%, respectively. Actuarial survival was lower in HD patients (P=0.04) and in patients who had previously undergone splenectomy (P=0.008). Cox regression analysis identified only prior splenectomy (P=0.02) as an independent risk factor for mortality after cardiac transplantation with an adjusted relative risk of 6.2 (1.7-21.9, 95% confidence intervals). CONCLUSIONS: Although the numbers are small, these data strongly suggest that there is an increased mortality risk for cardiac transplant recipients with prior HD who have undergone splenectomy.

Actuarial Analysis↗
PubMed2000

Effects of donor bone marrow infusion in clinical lung transplantation.

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

Adult↗
PubMed2000

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

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

Acute Disease↗
PubMed2000

Continuously maintaining positive flow avoids endocardial suction of a rotary blood pump with left ventricular bypass.

This study showed the usefulness of maintaining positive pump flow to avoid endocardial suction and as an assist bypass. Three calves were implanted with centrifugal pumps. Hemodynamics and pump parameters were measured at varying pump speeds (from 1,100 to 2,300 rpm). In each test pump, speed was adjusted to create 3 hemodynamic states: both positive and negative flow (PNF), positive and zero flow (PZF), and continuously positive flow (CPF). The pump flow volume was determined during systole (Vs) and diastole (Vd). Vs in PNF was 29.6 ml and was not significantly different from Vs in PZF (p > 0.15). Vd in PNF was significantly different from Vd in PZF (p < 0.05). All bypass rates of PNF were over 30% of pulmonary flow. All PZF bypass rates were between the PNF rate and the CPF rate. These data showed that PZF satisfied the minimum requirement of assist flow and was under 100% bypass. Thus, PZF may avoid endocardial suction.

Analysis of Variance↗
PubMed2000

Blood biocompatibility analysis in the setting of ventricular assist devices.

Ventricular assist devices (VADs) are increasingly applied to support patients with advanced cardiac failure. While the benefit of VADs in supporting this patient group is clear, substantial morbidity and mortality occur during the VAD implant period due to thromboembolic and infective complications. Efforts at the University of Pittsburgh aimed at evaluating the blood biocompatibility of VADs in the clinical, animal, and in vitro setting over the past decade are summarized. Emphasis is placed on understanding the mechanisms of thrombosis and thromboembolism associated with these devices.

Biocompatible Materials↗
PubMed2000

Psychosocial assessments and outcomes in organ transplantation.

A qualitative review was conducted to define the term psychosocial as applied to transplant patients and to summarize evidence regarding the role and impact of psychosocial assessments and outcomes across the transplant process. English-language case series and empirical studies from January 1970 through April 1990 that were abstracted in Medline and Psychological Abstracts or listed in publications' bibliographies were used as data sources. A qualitative analysis was performed to determine the depth of the case reports and whether the empirical reports obtained statistically reliable, clinically significant findings. The authors conclude that psychosocial assessments differ in content and application to candidate selection depending on the transplant program. Psychosocial status before transplant does not consistently affect medical outcomes after transplant. Psychosocial status generally improves with transplant, although difficulties are prevalent in psychological adjustment and in compliance with medical regimens. Psychiatric history can predict psychological outcomes after transplant but does not consistently predict compliance. Social supports and coping strategies strengthen psychosocial outcomes. Posttransplant psychosocial outcomes may predict physical morbidity and mortality.

Humans↗
PubMed2000

Standardized ejection fraction as a parameter of overall ventricular pump function.

To evaluate the pump function of the ventricle, a parameter which (i) incorporates systolic and diastolic function and (ii) separates the heart from preload and afterload is needed. This study utilized ejection fraction (EF), calculated from the end-systolic (ES) and end-diastolic (ED) pressure-volume relationship (PVR) using an arbitrary set of loading conditions. Ten isolated canine hearts with a balloon placed inside the left ventricle were used to determine the ESPVR and EDPVR. An end-diastolic volume (EDV) at a pressure of 15 mmHg and an end-systolic volume (ESV) at 70 mmHg were obtained from the EDPVR and ESPVR, respectively. EF was calculated as (EDV-ESV)/EDV. With low-dose (8 microg/min) and high-dose (40 microg/min) dobutamine infusion, the EF increased from 0.25+/-0.16 to 0.33+/-0.13 and 0.57+/-0.08 (p<0.01), respectively, in conjunction with increases in end-systolic elastance from 3.11+/-0.83 to 3.48+/-1.08 and 5.38+/-1.91 mmHg/ml (p<0.01). It was thus concluded that because the estimation of EF separates the heart from preload and afterload, this method may facilitate comparing overall pump function of hearts beating under different loading conditions.

Animals↗
PubMed1999

Evaluation of the potential role of color-coded tissue Doppler echocardiography in the detection of allograft rejection in heart transplant recipients.

BACKGROUND: Color-coded tissue Doppler (TD) echocardiography can noninvasively quantify alterations in left ventricular (LV) systolic and diastolic function. The objective of this study was to test the hypothesis that TD may play a role in the detection of LV dysfunction associated with allograft rejection in heart transplant recipients. METHODS AND RESULTS: Seventy-eight consecutive transplant recipients underwent 89 TD studies of posterior wall myocardial velocity gradient and mitral annular velocity within 1 hour of endomyocardial biopsy. Color TD echocardiographic images were digitized for semiautomated computer analysis. Histologic analysis revealed no significant rejection in 75 biopsies and significant rejection in 14. TD posterior wall peak systolic and diastolic velocity gradients were reduced significantly with rejection: 3.9 +/- 2.0 s(-1) versus 2.6 +/- 0.9 s(-1) and 5.4 +/- 2. 4 s(-1) versus 3.5 +/- 1.6 s(-1), respectively (P <.05 vs the nonrejecting group). Peak systolic and diastolic mitral annular velocities by TD were also reduced with rejection: 63 +/- 14 mm/s versus 49 +/- 12.4 mm/s and 90 +/- 23 mm/s versus 60 +/- 21 mm/s, respectively (P <.001 vs the nonrejecting group). A TD peak-to-peak mitral annular velocity >135 mm/s had 93% sensitivity, 71% specificity, and 98% negative predictive value for detecting rejection. Although TD was unable to discriminate between rejection and other causes of low velocity values, high TD velocity values were supportive of excluding rejection. CONCLUSIONS: These data suggest that color-coded TD may play a potential role as a screening test to exclude rejection in heart transplant recipients. Although this method has the potential to decrease the number of biopsies, further testing in a larger series of transplant recipients with rejection is warranted.

Biopsy↗