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Biomedical subjects

B P Griffith

Publications and source records attributed to B P Griffith.

At least 433 records · Page 24Linked to original sources
PubMedDate not supplied

Indexes of hemolysis in human recipients of the Jarvik-7 total artificial heart: a cooperative report of fifteen patients.

The degree of red cell destruction in human recipients of the total artificial heart has not previously been described. Fifteen patients implanted with a Jarvik-7 total artificial heart for either temporary or permanent heart replacement were reviewed. Clinically significant elevations of plasma free hemoglobin and serum lactate dehydrogenase were demonstrated in patients receiving the standard (100 ml) Jarvik-7 containing Medtronic-Hall valves and powered by pulses of compressed air delivered at a dP/dT of 6000 mm Hg/sec to 8000 mm Hg/sec. Reduction of the dP/dT by drive unit modification greatly reduced the plasma free hemoglobin and lactate dehydrogenase in subsequent patients. Introduction of the smaller (70 ml) total artificial heart was not associated with greater hemolysis once dP/dT had been reduced. With the current driver delivering systolic pulses at less than 4500 mm Hg/sec, both size hearts are free of clinically relevant hemolysis. In addition, it appears that attempts to eliminate hemolysis completely by lowering heart rates, cardiac outputs, or driving pressures are potentially dangerous. The eventual development of embolic cerebrovascular accidents is associated statistically with heart rates below 80 beats/min. These data reassure implanting physicians that the updated Jarvik-7 total artificial heart system does not induce worrisome hemolysis. In addition, this study has uncovered a link between eventual cerebrovascular accident and low heart rate, implying that purposeful application of heart rates around 100 beats/min may provide a significant margin of protection against cerebrovascular accident during implantation.

Adult↗
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Management of cyclosporine toxicity by reduced dosage and azathioprine.

While cyclosporine immunosuppression has improved the results of heart transplantation, nephrotoxicity and hypertension occurred in a large percentage of surviving patients. The potential irreversibility of these toxicities was noted in patients chronically exposed to cyclosporine. The immunosuppressive protocol was modified in those patients with a serum creatinine greater than 2.5 mg/100 mL. Azathioprine was added to the immunosuppressive regimen, and the dose of cyclosporine was steadily decreased until the creatinine was lowered. The combination of low-dose cyclosporine and azathioprine provided effective immunosuppression and was associated with a significant decrease in serum creatinine level, in systolic and diastolic blood pressures. Although it is premature to assess the long-term results of this immunosuppressive protocol, the early results are encouraging.

Azathioprine↗
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Five years of heart transplantation in Pittsburgh.

Looking over the five years of HTx experience in Pittsburgh we conclude that a reasonable success has been achieved and that the promise of Cy superiority has been realized. Although certain naivete about the likely panacea property of Cy occurred early, major adjustments in the original immunosuppressive protocol were required and included the use of rescue ATG, the measurement of Cy levels in the blood, the use of less Cy, and the perioperative avoidance of Cy. We anticipate a continued 80% one year survival with a likely survival in excess of 66% at five years. Furthermore, it is believed that the avoidance of early nephrotoxicity combined with the use of less Cy chronically will result in far fewer problems with nephrotoxicity. While we have been conservative with our immunosuppression, we have aggressively broadened the criteria for candidacy to include patients mortally ill, patients with elevated pulmonary vascular resistances, and those in their sixth decade. We believe that challenges for the future will include the development of selective immunosuppressants and coordinated networks for donor procurement so that more patients will have the opportunity for cardiac replacement.

Age Factors↗
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Bronchoalveolar lavage in heart-lung transplantation.

Distinguishing lung rejection from infection in patients who have undergone heart-lung transplantation is difficult. Since bronchoalveolar lavage has been safely used to investigate other pulmonary conditions, its safety and the value of the cellular data obtained were evaluated on 44 occasions in ten heart-lung transplant recipients. This study established that bronchoalveolar lavage is safe after heart-lung transplantation, that it reliably diagnoses infection, and lastly that serial lavages are valuable in finding subclinical Pneumocystis carinii infections. The study failed to distinguish pulmonary infection from rejection. Nevertheless, the functional analysis of the cells obtained by bronchoalveolar lavage may yield information about the immune status of the allograft.

Bacterial Infections↗
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Lymphocytes of bronchoalveolar lavages from heart-lung transplant recipients.

Bronchoalveolar cells from 13 lavages done in six heart-lung transplant recipients were tested for spontaneous proliferation, Interleukin-2 response and secondary allogeneic proliferation measured by primed lymphocyte testing. In most instances the bronchoalveolar cells responded to Interleukin-2 suggesting the presence of activated T-cells in the lavage. The lavage cells from several patients exhibited primed lymphocyte testing responses suggesting the presence of alloreactive T-cells. A high degree of spontaneous cellular proliferation was observed in several lavages, which appeared to be due to a macrophage-lymphocyte reaction. Two mechanisms may be responsible for this reactivity; a macrophage-lymphocyte reaction as a result of recipient lymphocyte responses to donor macrophages in the lavage during the early post-transplant period, or a macrophage-lymphocyte reaction related to an ongoing infection. Thus, functional assays on bronchoalveolar lavage cells may have diagnostic value in monitoring heart-lung recipients for lung rejection and infection.

Bronchi↗
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HLA phenotype of lung lavage cells following heart-lung transplantation.

A transplanted lung contains a full complement of immunocompetent lymphocytes and macrophages that are able to react immunologically with recipient lymphocytes and macrophages. In this study, the origin of lymphocytes and macrophages recovered from sequential bronchoalveolar lavages of six heart-lung transplantation recipients was determined by histocompatibility phenotyping. We found that during the first four weeks after transplantation there is a rapid replacement of the donor cells with those of the recipient. Since lung rejection rarely occurs after this transition is complete, donor lymphocytes and macrophages may be an important component of the rejection process. Furthermore, the transition from donor to recipient phenotype indicates that the vast majority of human alveolar macrophages originate from bone marrow precursors.

HLA Antigens↗
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Blalock shunt: procedure of choice in infants.

This report summarizes our experience in 39 infants less than three months of age who underwent a Blalock anastomosis. Mortality in the 16 infants under one week of age was 25% (4/16) and the overall mortality was 26% (10/39). Early patency was 87% (34/39) and late, 83% (24/29). No patient developed congestive heart failure or pulmonary hypertension. For the infant with diminished pulmonary blood flow, the Blalock shunt is the procedure of choice.

Follow-Up Studies↗
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Evaluation of an implantable ventricular assist system for humans with chronic refractory heart failure. Study overview. LVAS Study Group. Left Ventricular Assist System.

In this summary, the authors provide the background of and proposed protocol for a clinical evaluation of the safety and efficacy of the Novacor N120 Left Ventricular Assist System, sponsored by the National Heart, Lung, and Blood Institute. Although the clinical trial was never carried out, the protocol developed for this trial may be useful to other investigators considering a clinical trial of a circulatory support device. The protocol is summarized here and in five more detailed articles in this issue.

Clinical Protocols↗
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Heat shock protein-induced T-lymphocyte propagation from endomyocardial biopsies in heart transplantation.

BACKGROUND: Recent studies have shown that heat shock proteins can be recognized by T cells during various immunologically mediated inflammatory processes. Injurious stimuli to cells induce an increased production of heat shock proteins which could lead to their cell surface expression and subsequent recognition by the immune system. We have postulated that allograft infiltrating cells may recognize heat shock proteins, especially during rejection. METHODS: This hypothesis was tested by incubating heart transplant biopsy specimens from 89 heart transplant recipients with soluble Mycobacterium tuberculosis extracts, a source of heat shock proteins or recombinant mycobacterial heat shock protein 65. T cell phenotypes were determined by flow cytometry. RESULTS: Mycobacterium tuberculosis extract can induce lymphocyte propagation from heart transplant biopsy specimens especially during rejection. A highly significant correlation was seen between Mycobacterium tuberculosis extract and interleukin-2-induced lymphocyte growth and an accelerated growth was seen for cultures incubated with Mycobacterium tuberculosis extract + interleukin-2. A second series of experiments has also shown the propagation of lymphocytes induced by recombinant mycobacterial heat shock protein-65. T-cell phenotype analysis of biopsy propagated lymphocytes has shown higher frequencies of CD8 cells in Mycobacterium tuberculosis extract and heat shock protein-65 propagated lymphocytes from early posttransplantation biopsy specimens, whereas, later on, most cultures showed a predominance of CD4 cells. T-cell receptor gamma delta cells were more frequently found in biopsy-derived lymphocyte cultures from long-term survivors, especially after propagation with Mycobacterium tuberculosis extract and heat shock protein-65. These gamma delta cells expressed primarily the delta 1 rather than the gamma 9 phenotype. CONCLUSIONS: These observations provide first evidence for the presence of heat shock protein-reactive lymphocytes in cellular infiltrates of transplants undergoing rejection.

Adult↗
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Assessment of the response of right ventricular performance to decreasing levels of mechanical assistance by on-line pressure area relationships.

The rapid assessment of the response of right ventricular (RV) performance to decreasing levels of mechanical assistance may be an important adjunct in determining if a patient can tolerate the removal of such a device. This report describes the use of on-line pressure area relationships to assess RV function in a patient supported with an RV assist device (RVAD). Mid RV short axis cross-sectional area was measured on-line by transesophageal echocardiography with an automated endocardial border detection feature. RV pressure was measured with a high fidelity catheter. Pressure and area were plotted simultaneously on a computer workstation interfaced with the pressure and echo systems to yield on-line pressure area loops. The following indices of RV performance were calculated while RVAD flow was decreased in 1 L/min increments: stroke work' (SW' = integral of PdA)[mmHg*cm2], stroke area (SA = Maximum Area-Minimum Area)[cm2], and fractional area change (FAC = SA/Maximum Area*100)[%]. SW', SA, and FAC significantly increased with decreasing RVAD flow: SW'(from 32 to 61 mmHg*cm2), SA (from 2.58 to 4.37 cm2), and FAC (from 20 to 32%). In conclusion, the increase in these parameters of RV performance with decreasing mechanical assistance suggested that this patient would tolerate removal of the RVAD, which was subsequently successful. This method of on-line pressure area relationships may be useful to predict the need for further mechanical assistance.

Analog-Digital Conversion↗
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A sheep model for the study of hemorheology with assisted circulation. Effect of an axial flow blood pump.

Hemorheologic investigations were performed on nine sheep during the in vivo evaluation of a new axial flow ventricular assist device, the Nimbus AxiPump (Nimbus, Inc., Rancho Cordova, CA). Blood hematocrit, plasma and whole blood viscosity, red blood cell (RBC) deformability and aggregation, plasma fibrinogen, and free hemoglobin (hemolysis) levels were measured. Changes in the main rheologic parameters of sheep blood relative to the pre-implant values were minor and transient. The exception was RBC aggregation, which appeared on the third day of implantation. (Sheep blood does not normally demonstrate RBC aggregation.) Sheep RBCs started to form classic rouleaux typically on the third post-operative day simultaneously with increasing fibrinogen level. To investigate the relative effects of mechanical stress and elevated fibrinogen levels on RBC aggregability, in vitro studies were conducted with blood from control sheep. These studies indicated that neither mechanical trauma nor elevated fibrinogen alone caused RBC aggregation as seen in vivo. However, combined mechanical stress and elevated fibrinogen did cause this unusual effect for sheep blood.

Animals↗
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Development of an intravenous membrane oxygenator: a new concept in mechanical support for the failing lung.

An intravenous membrane oxygenator is being developed to supplement oxygen and carbon dioxide exchange in patients with temporary and potentially reversible lung failure in either a lung transplantation setting or in cases of acute respiratory distress from multiple causes. Our device incorporates a pulsatile balloon that is centrally located and around which are mounted microporous hollow fibers. Oxygen is vaccuumed through the fibers with resultant gas exchange. The rhythmic pulsations of the balloon enhance cross-flow and three-dimensional convective mixing at the blood-fiber interface and thus promote more efficient oxygen-carbon dioxide exchange. Seven intravenous membrane oxygenator prototypes have been designed and fabricated. Modifications in design have led to a progressive improvement in gas flux. Gas exchange performance measured in vitro and with both saline solution and fresh ox blood have shown gas exchange as high as 203 ml/min/m2 for oxygen and 182 ml/min/m2 for carbon dioxide. In vivo dog experiments with the device positioned in the inferior vena cava and right atrium have shown over a 50% increase in oxygen flux with balloon activation versus the static situation without changes in hemodynamics. The size of the prototype tested in animals can be scaled up fivefold for anticipated human trials. Our results indicate that our intravenous membrane oxygenator prototypes now under development may be an alternative to extracorporeal membrane oxygenation in the treatment of temporary respiratory failure.

Animals↗