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Biomedical subjects

B P Griffith

Publications and source records attributed to B P Griffith.

At least 361 records · Page 20Linked to original sources

Arteriovenous perfusion with the pulmonary assist membrane oxygenator.

The feasibility of employing a recently developed pulmonary assist membrane oxygenator for partial respiratory support in arteriovenous perfusion was studied using small mongrel dogs rendered hypoxic by oxygen depression. The unit is employed along with the conventional ventilation techniques (such as CPAP and PEEP) when the latter alone cannot maintain adequate gas exchange in the lung. The results indicate that poorly oxygenated arterial blood can be upgraded to life-sustaining levels when the bypass flow rate through the oxygenator is in the range of 18-33% of the total cardiac output. No cardiovascular derangements were noted at these arteriovenous flow rates for perfusion periods of four to six hours. The present results demonstrate the feasibility of providing partial support to pulmonary function using the pulmonary assist membrane oxygenator.

Animals↗

Discrete subvalvular aortic stenosis. An evaluation of operative therapy.

Angiocardiographic and operative observations support the validity of classifying the spectrum of congenital subvalvular aortic stenosis into a membrane, fibromuscular collar, and tunnel. Our current operative method is to excise a thin membrane or thick fibrous ridge, and, if a fibromuscular collar or tunnel is identified, to effect a left ventricular myomectomy as described by Morrow for hypertrophic subaortic stenosis. Data from experience with 35 children indicate that this approach is effective and safe. Gradients are substantially reduced and residual obstruction acceptable. Successive clinical evaluations (100 percent of 33 survivors) over an interval of 1 to 13 years (mean of 6) affirm that amelioration of the obstruction endures.

Angiocardiography↗

Mechanisms of injury to the central nervous system following experimental cytomegalovirus infection.

A guinea pig model was used to determine the mechanisms of injury to the central nervous system by cytomegalovirus. Focal, well-contained, histopathologic responses included the microglial nodule without residua, and the ependymitis with focal residual glial scarring. Higher virus dose infection in the brain resulted in inflammatory necrosis with an astrocytic response to injury. However, monocytes and microglia were the predominant responding cells of host defense. A vasogenic pathogenesis was suggested by the involvement of the vascular endothelium, and separately by central nervous system vasculitis, demonstrated here for the first time in this model. Hence, our studies suggest four potential mechanisms of injury to the central nervous system by cytomegalovirus: viral cytopathology, inflammatory mediators from cells of the monocyte series, two separate types of vascular impairment, and astroglial scarring.

Animals↗

Comparative performance of peptide-, recombinant protein-, and viral lysate-based enzyme immunosorbent assays for the detection of HIV-1 antibodies.

The performance of peptide-, recombinant protein-, and whole virus lysate-based enzyme immunosorbent assays (EIAs) for the detection of antibodies to the human immunodeficiency virus type 1 (HIV-1) was compared on a panel of 245 routine samples, a panel of low-positive samples, four seroconversion panels, and serial dilutions of five known positive samples. Of the 245 routine samples, 83 were confirmed to be HIV-1 antibody positive by Western blot and were reactive in the three EIAs used. Agreement between the three EIA tests was also 100% for all 162 negative samples. Although there was no significant difference in the performance of the three types of assays in seroconversion panels, the whole virus and recombinant protein-based EIAs detected 15 of 15 samples in the low-positive panel whereas only 10 of 15 samples were reactive when the peptide-based EIA was used. In addition, evaluation of diluted positive samples suggested that the virus lysate-based EIA was more sensitive than the peptide- and recombinant-based EIAs. These results show that although the three types of assays performed well on routine serum panels, differences in sensitivities were demonstrated when performance panels were evaluated. The data suggest that seroconversion and low-positive performance panels should be included in evaluations of new generations of EIAs for HIV-1 antibodies.

Evaluation Studies as Topic↗

Psychological symptom levels and their correlates in lung and heart-lung transplant recipients.

This study examined depression, anxiety, and anger-hostility symptom levels, as well as overall quality of life, in a cohort of 50 lung and heart-lung transplant recipients. Only the subjects' mean anxiety symptoms were substantially elevated over normative levels. However, nearly half of the sample showed clinically significant distress in one or more of the three symptom areas. Pretransplant psychiatric history, educational level, posttransplant caregiver support, and health concerns were the most important independent correlates of the recipients' psychological outcome. Low sense of mastery and poorer physical functional status also showed some evidence of association with mental health.

Adult↗

PTSD in heart transplant recipients and their primary family caregivers.

Posttraumatic stress disorder associated with transplantation (PTSD-T) is a complication for some heart transplant recipients. By using a structured, standardized interview and DSM-III-R criteria, the authors examined whether recipients (n = 158) and their family caregivers (n = 142) showed similar PTSD-T rates and clinical characteristics during the first year posttransplant. Among the recipients, 10.5% met full criteria for the disorder and an additional 5% were probable cases. Among the caregivers, 7.7% met full criteria and an additional 11.0% were probable cases. Severity and duration of disorder were similar across the groups. Being female, having a history of psychiatric illness, and having lower friend support were increased risks for PTSD-T.

Adult↗

Acquired right ventricular outflow tract obstruction after lung transplantation: diagnosis by transesophageal echocardiography.

Acute reduction in pulmonary pressures after lung transplantation for severe chronic pulmonary hypertension may produce a sudden decrease in cavity size of a hypertrophied right ventricle resulting in acquired right ventricular outflow tract obstruction. This case illustrates the utility of transesophageal echocardiography with continuous-wave Doppler to make a morphologic as well as hemodynamic diagnosis of acquired right ventricular outflow tract obstruction in a patient after lung transplantation.

Echocardiography↗

Two-dimensional echocardiographic automated border detection accurately reflects changes in left ventricular volume.

The objective of this study was to determine the relationship of on-line measurements of left ventricular cavity area generated by echocardiographic automated border detection to true volume measured by an intraventricular balloon in an isovolumically contracting isolated canine heart preparation. Seven excised dog hearts had placement of an intraventricular balloon and were perfused in an ex vivo apparatus. Left ventricular area data from the midventricular short-axis plane and pressure data were recorded on a computer through a customized hardware and software interface with the ultrasound system. Left ventricular volumes were varied from 5 ml to maximal values (30 to 40 ml) at 1-milliliter increments. Three increasing and decreasing volume ramps were analyzed on each of seven hearts for a total of 1260 simultaneous measurements. Linear regression analysis correlated mean automated border detection area with absolute volume from each preparation. A predominantly linear relationship was observed with an average correlation of r = 0.97 (y = 0.16x-0.69, SEE = 0.31 cm2, p < 0.01). Left ventricular area measures for six of seven dogs varied little during isovolumic contraction (< 0.4 cm2) but did show a systematic cardiac cycle-related variability in one dog (28% change in area, maximum to minimum, over all volumes). In conclusion, the relationship between cross-sectional area and left ventricular volume was predominantly linear and varied little during isovolumic contractions in the normal canine left ventricle. Echocardiographic automated border detection appears to be a promising method to reflect changes in left ventricular volume.

Animals↗

Cytomegaloviral infections in the guinea pig: experimental models for human disease.

The salivary gland virus of guinea pigs, or guinea pig cytomegalovirus (CMV), was first described in The Journal of Infectious Diseases in 1920. Early studies were concerned with the nature of intranuclear and intracytoplasmic inclusions, viral pathogenicity, transmissibility in animals, and similarity to human viral infections. Subsequently, tissue culture techniques and electron microscopy of guinea pig CMV-infected salivary gland and tissue culture cells demonstrated the morphogenesis which closely resembles that of human CMV. By use of tissue culture cocultivation techniques, generalized viremic infection, transplacental transmission of virus, congenital infection, CMV-associated mononucleosis, interstitial pneumonia, and transmission of virus by blood transfusion have been demonstrated. In studies of live attenuated and noninfectious envelope antigen vaccines for the prevention of transplacental transmission of virus and of interstitial pneumonia, the guinea pig model has demonstrated efficacy of such vaccines under experimental conditions. Investigations of polymorphonuclear leukocyte function during primary CMV infections may elucidate mechanisms for bacterial, parasitic, and fungal superinfections in human disease.

Animals↗

Evaluation of right ventricular function during clinical left ventricular assistance.

Hemodynamic and mechanical parameters of right ventricular (RV) performance were measured in eight patients undergoing left ventricular (LV) assistance as a bridge to cardiac transplantation. All patients, even those with impaired RV performance, survived support and transplantation. The reduction of LV afterload produced by the left ventricular assist system (LVAS) results in RV afterload reduction, which permits even the marginal RV to function adequately during LVAS support.

Adult↗

Characteristics of blood rheology in patients during Novacor left ventricular assist system support.

Blood rheologic properties were studied in 11 patients on Novacor LVAS support (1-126 days) as a bridge to transplantation. Overall, these patients showed slight increases in mean blood viscosity and red cell rigidity. Their mean plasma fibrinogen was in the upper normal range. However, the degree of rheologic change observed, and the individual factors affected most, were unique to each patient and hemorheologic results correlated well with the patient's clinical status.

Adult↗

Erythrocyte deformability in patients on left ventricular assist systems.

Preliminary hemorheologic studies using clinical filtration techniques on blood cell suspensions have suggested that changes in erythrocyte (RBC) deformability occur during left ventricular assist system (LVAS) support. In the biophysics literature, it is generally accepted that the elastic properties of the RBC membrane complex affect the microcirculatory deformability of the whole cell (cytoplasmic pathologies excepted). This paper compares single cell measurements of the surface shear elastic modulus, mu, of the RBC membrane complex (determined using micropipette aspiration) to available clinical filtration pressure data during Novacor LVAS support, over 33 and 126 days in four patients.

Adult↗

Quantitation of right ventricular shape changes after left ventricular assist device implantation.

Complex effects of left (LV) and right ventricular (RV) interaction account for changes in RV function during LV assist device (LVAD) support. It has been hypothesized that changes in RV cross-sectional shape (RVS) may be a contributing factor in the development of RV dysfunction during LVAD support. To test the hypothesis that the RVS would become more circular as a result of septal shift during LVAD support, 13 patients were studied before and after LVAD implantation. The shape of the RV was quantified using a shape factor (SF) that was equal to (4 x pi x area)/P2, where P is the perimeter of RVS. The RV area and perimeter were measured from digitized images of the RV obtained by transesophageal echocardiography in patients before and after LVAD implantation. The group SF increased considerably after LVAD (SFpre = 0.78 +/- 0.12 versus SFpost = 0.88 +/- 0.07, p < 0.05). Patients were divided into three groups: 1) patients whose RV exhibited a low SF pre-LVAD that increased significantly, 2) those with a moderate SF pre-LVAD that increased slightly, and 3) those who had high pre-LVAD SF (< 0.90) that did not change. The decompression of the LV caused by LVAD implantation results in a shift of the septum from right to left, increasing SF. This increase is more pronounced in some patients. Quantitation of the degree of RV SF change may help predict the development of RV failure during LVAD support.

Adult↗

Development of an axial flow blood pump LVAS.

Nimbus, Inc., (Rancho Cordova, CA) and the University of Pittsburgh (Pittsburgh, PA) are collaborating to develop an implantable rotary blood pump that can be used as a left ventricular assist system (LVAS). The short-term goal of this project is to show that an LVAS based on this pump can operate safely and reliably during chronic implantations in animals. Work conducted to date includes in vitro testing of hydraulic performance, hemolysis, endurance demonstration, and flow visualization. Results indicate that the pump is capable of generating an output of up to 10 L/min at physiologic pressures. Associated electrical power to drive these pumps is in the range of 6-10 watts. One integrated pump was placed in a mock flow loop and operated continuously at a fixed speed (10,000 rpm), pressure (100 mmHg), and flow rate (6 L/min) for 90 days with no apparent difficulty. In vitro hemolysis test results have consistently ranged between 3-6 g of liberated hemoglobin/day, which is an acceptable range for chronic use. Two in vivo trials of 7 and 14 days were performed using calves, after which tests have been done using sheep as the animal model. Five short-term sheep experiments have been conducted with good results. Future studies will include implantations in sheep of 3 months duration.

Animals↗

Thrombin activity resides on LVAD Dacron inflow and outflow grafts.

Patients on left ventricular assist devices (LVADs) are at increased risk for thromboembolism, and they experience elevations in platelet release and thrombin activity indices during device implantation. The Dacron grafts that lead from the ventricle to the LVAD and back to the aorta may harbor thrombin activity and protect this thrombin from anticoagulant action. To investigate this possibility, specimens isolated from LVAD grafts at the time of device explantation or implantation were incubated with citrated platelet poor plasma (cPPP), cPPP and 2 U/ml of heparin, cPPP and 2 U/ml of recombinant hirudin (r-hirudin), or cPPP and 50 U/ml of heparin. Thrombin activity was measured by the increase in incubated cPPP fibrinopeptide A (FPA) concentrations over cPPP FPA levels, without material contact. A chromogenic substrate for thrombin verified the effects seen. Thrombin activity was found at comparable levels on both the inflow and outflow LVAD grafts at explantation. This activity was not inhibited by low concentrations of heparin, but 50 U/ml of heparin and 2 U/ml of r-hirudin reduced the activity. At graft implantation (after preclotting), thrombin activity was higher than at explantation, but susceptibility to inhibition by heparin was also significantly greater. These results confirm that the LVAD Dacron grafts harbor surface thrombin activity resistant to anticoagulation that may be a primary source for LVAD thrombogenicity.

Heart Ventricles↗

Differential regional function of the right ventricle during the use of a left ventricular assist device.

The use of a left ventricular assist device (LVAD) as a bridge to transplant is associated with a 52% incidence of RV failure requiring additional inotropic or mechanical support (RVAD). This study evaluated the differential performance of the RV free wall and septum to identify the need for additional RV support. Cross-sectional views of the RV were obtained immediately before, and 1 hr after, Novacor LVAS implantation in 12 consecutive patients using transesophageal echocardiography. Each image was divided into a free wall portion (FW) and a septal portion (SP) by grids drawn from the center of gravity of the end-diastolic endocardial outline to the junction between the FW and the SP. Percentage change between preimplant and postimplant for RV ejection fraction (RVEF), fractional area change for the FW (FAC-FW) and the SP (FAC-SP), and fractional shortening of the FW to SP distance (F-S) is reported for patients based upon the need for RV support: minimal (Group 1), maximal (Group 2). After LVAS implantation, patients showed a reduction in SP fractional area change. However, this reduction was most pronounced in Group 2. The degree of SP impairment may explain the mechanism of RV failure in patients on an LVAD.

Adolescent↗