PubMed Health⌕ Search

Biomedical subjects

W A Baumgartner

Publications and source records attributed to W A Baumgartner.

At least 127 records · Page 7Linked to original sources

Pseudo-graft-versus-host disease in heart and heart-lung recipients.

Autopsies from nine patients who had received a cardiac allograft transplant and one with a combined heart-lung transplant were assessed for histologic evidence of pseudo-graft-versus-host disease (pseudo-GVHD). Five of the ten patients had GVHD-like changes in two or more tissues, including prominent lymphocyte-associated bile duct injury consistent with marked hepatic pseudo-GVHD and mild cutaneous changes resembling GVHD. A sixth recipient had marked changes in the liver, but autopsy restrictions prevented examination of the skin. A seventh recipient had only mild pseudo-GVHD changes limited to the skin. In contrast, a series of six patients who were candidates for cardiac transplant had no specific pathologic changes suggesting pseudo-GVHD. The majority of those with pseudo-GVHD had received nonirradiated blood product transfusions, raising the possibility of posttransfusion engraftment and GVHD. Unlike the posttransfusion GVHD, however, two of the six developed GVHD-related complications late with a latent period of five and 9.5 months, and two recipients received no transfusions. All were receiving only modest doses of immunosuppressive agents at the time they developed liver function abnormalities, including low or tapering doses of cyclosporine (CsA). In some of these recipients, therefore, the pseudo-GVHD changes may well represent an autoimmune reaction resembling the post-CsA model of autoimmune disease.

Adult↗

Immediate enhancement of left ventricular relaxation by coronary artery bypass grafting: intraoperative assessment.

We investigated the effect of coronary artery bypass grafting on the rate of left ventricular relaxation as defined by the time constant for isovolumetric relaxation, T, measured in milliseconds. Completeness of relaxation at rapid heart rates was determined by comparison of the relationship between left ventricular pressure and echocardiographic left ventricular cross-sectional cavity area during rapid ventricular pacing with that obtained after a prolonged diastole when the ventricle was maximally relaxed. Twelve patients with coronary artery disease had significantly higher T values (94.5 +/- 6.2) than six patients without coronary artery disease who were undergoing other open heart procedures (39.5 +/- 5.0, p less than .001). T was significantly reduced after coronary artery bypass grafting (68.2 +/- 5.1, p = .007), but was unchanged in the six control patients after cardiopulmonary bypass (37.8 +/- 4.5, p = .54). Similar changes were found during rapid pacing to 100, 120, and 140/min. Incomplete relaxation was detected in three of 10 (heart rate 120 beats/min) and nine of 11 (heart rate 140 beats/min) patients with coronary artery disease and this decreased to 0 of 10 (heart rate 120 beats/min) and six of 11 (heart rate 140 beats/min) patients after coronary artery bypass. Incomplete relaxation before bypass at a heart rate of 120 beats/min averaged 0.9 +/- 0.3 mm Hg. At a heart rate of 140 beats/min, incomplete relaxation averaged 5.6 +/- 1.6 mm Hg before and 1.4 +/- 0.5 mm Hg after bypass. Intake of beta-blockers or calcium-channel blockers, body temperature, and systolic blood pressure were not found to be related to these changes. We conclude that immediately after coronary artery bypass relaxation of left ventricular muscle is enhanced and incomplete relaxation at rapid heart rates is less likely. The most probable cause of this improvement in ventricular relaxation after coronary artery bypass grafting is relief of ischemia.

Blood Vessel Prosthesis↗

Increase of the 40,000-mol wt pertussis toxin substrate (G protein) in the failing human heart.

Human heart failure is associated with a diminished contractile response to beta-adrenergic agonists. We hypothesized that alterations in the activity of a guanine nucleotide-binding regulatory protein (G protein) might be partially responsible for this abnormality. We therefore measured the activity of G proteins in failing human myocardium utilizing bacterial toxin-catalyzed ADP ribosylation. The activity of a 40,000-mol wt pertussis toxin substrate (alpha G40) was increased by 36% in failing human hearts when compared with nonfailing controls. In contrast, there was no change in the level of the stimulatory regulatory subunit (Gs). The increased activity in alpha G40 was associated with a 30% decrease in basal as well as 5'-guanylyl imidodiphosphate-stimulated adenylate cyclase activity. These data suggest that increased alpha G40 activity is a new marker for failing myocardium and may account at least in part for the diminished responsiveness to beta 1-adrenergic agonists in the failing human heart.

Adenosine Diphosphate Ribose↗

Metabolic changes preceding functional and morphologic indices of rejection in heterotopic cardiac allografts. A 31P nuclear magnetic resonance study.

Eight beagles receiving heterotopic (cervical) cardiac allografts from outbred donors were evaluated by serial 31P NMR, septal endocardial biopsy, and left ventricular pressure measurements for signs of rejection. Early postoperative myocardial energy levels, as assessed by ratios of phosphocreatine to inorganic phosphate (PCr/Pi) and phosphocreatine to beta-ATP (PCr/B-ATP), were acceptable in all recipients. In these nonimmunosuppressed animals, the mean ratios of PCr/Pi and PCr/B-ATP progressively decreased, with a greater than 25% reduction noted by postoperative day two and greater than 50% reduction by day three. In sharp contrast, left ventricular end-diastolic pressures remained stable and at baseline levels for the first three postoperative days, and only then markedly increased. Likewise, histologic evidence of rejection did not become prominent until postoperative day four. These results suggest that metabolic abnormalities significantly precede either functional or histologic changes in rejecting allografts. The early detection of these metabolic changes by 31P NMR appears to have important potential for the noninvasive diagnosis of cardiac allograft rejection.

Animals↗

Diagnosis of lung allograft rejection by bronchial intraepithelial Leu-7 positive T lymphocytes.

Currently there is no reliable technique for the diagnosis of lung allograft rejection. The presence of intraepithelial lymphocytes expressing the Leu-7 antigen is a specific marker of renal rejection. We examined whether immunoperoxidase techniques that detect Leu-7 positive lymphocytes could be used to diagnose lung rejection in heart-lung transplant recipients. In lungs from two autopsied patients with lung allograft rejection, numerous Leu-7 positive lymphocytes were present in the donor bronchial mucosa (32 and 65 cells/section), submucosa (23 and 80 cells/section), and submucosal glands (7 and 19 cells/section). These Leu-7 positive lymphocytes were associated with proximal airway injury, including squamous metaplasia, destruction of submucosal glands, and ulceration. In one case, there was bronchiectasis. Both cases also had distal airway bronchiolitis obliterans. In contrast, Leu-7 positive lymphocytes were not identified in the epithelium of the native trachea of these two patients; nor were they found in the bronchial epithelium of two sets of transplanted lungs without evidence of rejection. Only rare Leu-7 positive lymphocytes were evident in the epithelium (0 to 2 cells/section) and submucosal glands (0 to 1 cell/section) of 20 lungs from autopsied patients who had not received a transplant. Application of this technique to epithelial biopsy specimens obtained at bronchoscopic examinations demonstrated that it could be applied to the diagnosis of rejection in living heart-lung transplant recipients.

Adult↗

31P nuclear magnetic resonance determination of changes in energy state in lung preservation.

The significance of dynamic changes in energy state during lung harvesting and preservation has not been extensively studied. Phosphorus 31 nuclear magnetic resonance spectra at 81 MHz were obtained from degassed rabbit lungs. Changes in the adenosine 5'-triphosphate-to-inorganic phosphate peak-intensity ratios were used to measure changes in energy state. Two groups of rabbit preparations were studied to evaluate the effect of hypothermia during the initial 120 minutes of harvesting (n = 8 at 36 degrees C and n = 5 at 4 degrees C). The significance of these changes was assessed in a second experiment in which lungs were reperfused in vitro at selected intervals of hypothermia (5, 12, and 24 hours) and assessed for injury. Hypothermic preservation sustained a significantly higher energy state. The depletion of energy state was correlated with injury, particularly as measured by lung edema (r2 = -0.715). Short periods of warm ischemia (30 minutes) result in a significant depletion of energy state, which may be a component of pulmonary injury during harvesting and preservation.

Adenosine Triphosphate↗

Predictors of perioperative mortality in patients with unstable postinfarction angina.

Factors associated with increased operative mortality in patients with postinfarction angina have not been defined. Two hundred twenty-five patients underwent urgent coronary artery bypass grafting from 1982 through 1986. One hundred sixty-two men and 63 women averaged 62 years of age (range, 35-87 years). Operative mortality was 5.3%. To assess the predictors of perioperative mortality, 16 variables were evaluated by univariate and multivariate analyses. Significant independent predictors of perioperative mortality were the presence of a transmural anterior myocardial infarction (p less than 0.0005) and the need for preoperative intra-aortic balloon pumping for angina or congestive heart failure (p = 0.009). All perioperative mortalities (12 patients) occurred in this subset (anterior myocardial infarction, intra-aortic balloon pumping, or both) that included 101 patients. The mean follow-up period was 27.8 months (range, 1-69 months). There were 11 late deaths, resulting in an actuarial survival of 92 +/- 2%, 91 +/- 2%, 88 +/- 2.6%, and 88 +/- 4% at 1,2,3, and 4 years, respectively. Ninety-six percent of survivors were assigned to New York Heart Association Class I or II for congestive heart failure, and 96% were assigned to Class I or II for angina. Urgent coronary artery bypass grafting can be performed in patients with unstable postinfarction angina with acceptable mortality, although a significant increase in risk exists for patients with preoperative transmural anterior myocardial infarction, intra-aortic balloon pumping, or both.

Adult↗

Depletion of bronchus-associated lymphoid tissue associated with lung allograft rejection.

Pulmonary infections remain one of the major complications of lung transplantation. The bronchus-associated lymphoid tissue (BALT) forms a local immune system that normally protects the lung from infection. The effects of lung transplantation and lung allograft rejection on the BALT were examined using immunoperoxidase techniques. The BALT was evaluated by quantifying the number of immunoglobulin-bearing plasma cells in the lamina propria of sections of trachea and mainstem bronchus. Sections of donor mainstem bronchus from 2 patients with allograft rejection were compared with sections of native trachea from these same patients, and with sections of mainstem bronchus from 2 transplanted lungs without rejection and 20 controls. Lung allografts from the 2 patients with rejection had a marked depletion of submucosal IgA-bearing and IgG-bearing plasma cells. Two sets of transplanted lungs without evidence of rejection showed only a mild reduction of the BALT. The depletion of BALT associated with allograft rejection may contribute to the increased incidence of pulmonary infections seen in these patients.

Bronchi↗

Assessment of myocardial blood flow by real-time infrared imaging.

In order to evaluate the applicability of infrared imaging for the assessment of myocardial perfusion, 10 open-chested dogs were studied by a real-time infrared imaging system. The left anterior descending coronary artery was occluded for 90 min followed by 210 min of reperfusion. During the experiment, myocardial surface temperature was mapped by an infrared imaging system with a thermal resolution power of 0.1 degree C and correlated with regional myocardial blood flow measured using radiolabeled microspheres. Following the experiment, acute myocardial injury was evaluated using triphenyltetrazolium chloride staining. After 90 min of ischemia, there was a significant correlation between myocardial blood flow and myocardial surface temperature (R = 0.694, P less than 0.001). After reperfusion, temperature did not correlate with blood flow, but there was a significant correlation between temperature and ischemic myocardial injury (R = 0.551, P less than 0.05). Temperature changes during acute regional ischemia and reperfusion may be regulated by the changes in myocardial blood flow and myocardial metabolism. Temperature analysis using real-time infrared imaging may be a useful means for the evaluation of myocardial blood flow and myocardial injury during ischemia and reperfusion.

Animals↗

Ten-year analysis of the Björk-Shiley standard aortic valve.

Long-term performance characteristics of the Björk-Shiley standard aortic valve were determined by analyzing the follow-up of 514 patients undergoing operation between 1971 and 1981. Cumulative follow-up was 2,601 patient-years (average, 5.3 +/- 3.8 years); 53% (238/452) of hospital survivors have been followed more than 5 years. Valve-related complications expressed as both actuarial event-free percents (+/- standard error at 10 years) and first-event linearized determinations (percent per patient-year) occurred at the following rates: thromboembolism, 82 +/- 3 and 2.3 +/- 0.3, respectively; anticoagulant-related hemorrhage, 60 +/- 4 and 5.6 +/- 0.5; prosthetic valve endocarditis, 94 +/- 2 and 0.8 +/- 0.2; valve thrombosis, 97 +/- 1 and 0.4 +/- 0.1; reoperation, 94 +/- 2 and 0.6 +/- 0.2; valve failure, 82 +/- 4 and 1.6 +/- 0.2; and composite valve-related morbidity and mortality, 46 +/- 4 and 8.8 +/- 0.2. Overall survival was 72 +/- 2% at 5 years and 55 +/- 3% at 10 years; valve-related complications accounted for 22% of the late deaths. Although no instance of structural valve failure could be identified, 25% of valve-related complications resulted from valve failure, of which 67% were fatal. By 10 years, 54% of patients had experienced at least one form of major valve-related complication, 16% of which proved fatal. The Björk-Shiley standard aortic valve has late valve-related complications similar to other existing mechanical prostheses that have been subjected to long-term analysis.

Adult↗

Present expectations in cardiac transplantation.

The clinical introduction of cyclosporine has resulted in increased enthusiasm for cardiac transplantation. Since July, 1983, 61 patients (50 male and 11 female) have undergone orthotopic cardiac transplantation for cardiomyopathy (48 patients), ischemic heart disease (11), or congenital heart disease (2). Mean age was 39 years (range, 1.5 to 57 years). Median hospital stay was 26 days (range, 4 to 60 days). Maintenance immunosuppression consisted primarily of prednisone and cyclosporine; it was modified in 9 patients because of a pre-existing clinical condition. The incidence of rejection was 0.44 episode/patient-month within 3 months of cardiac transplantation and 0.10 episode/patient-month subsequently. The incidence of infection was 0.05 episode/patient-month. Major side effects of cyclosporine included renal dysfunction (63%) and hypertension (61%). No recipient required dialysis for renal dysfunction. Ten patients died (rejection, 4; infection, 3; carcinoma, 1; lymphoma, 1; and pulmonary hemorrhage, 1); actuarial survival at 1 and 2 years was 84 +/- 6% and 76 +/- 8%, respectively. Patient follow-up (cumulative, 719 patient-months) revealed that 96% of recipients were rehabilitated and 50% had returned to work. With increasing understanding of cyclosporine immunosuppression, recipients can continue to look forward to an extended life with nearly complete rehabilitation.

Adolescent↗

Histologic predictors of acute cardiac rejection in human endomyocardial biopsies: a multivariate analysis.

To identify specific histologic abnormalities that could predict early cardiac rejection before the development of myocyte necrosis, 167 consecutive endomyocardial biopsy samples from 18 cardiac transplant recipients were retrospectively analyzed and 17 histologic variables were semiquantitatively graded from 0 to 3. Forty-five biopsy samples contained foci of myocyte necrosis and were labeled Rejectors. The two samples immediately preceding Rejector biopsies were labeled Predictors (n = 44). All remaining samples were labeled Others (n = 78). Endocardial and interstitial infiltrates, interstitial mononuclear cells, pyroninophilic mononuclear cells, polymorphonuclear leukocytes and other cells (eosinophils and plasma cells) were significantly increased in graded severity in Rejector biopsy samples as compared with Predictors or Others (p less than 0.001, ANOVA testing). These variables cannot distinguish Predictor biopsy specimens from Others. On the other hand, interstitial edema, perivascular karyorrhexis and perivascular infiltrate with intermyocyte extension are histologic abnormalities that can distinguish Predictor biopsy samples from Others (p less than 0.001, ANOVA testing). Multiple logistic regression analysis indicates that the relative risk of developing myocyte necrosis when a biopsy sample contains interstitial edema is 8.1. With perivascular infiltrate with intermyocyte extension in addition, the relative risk is 41.4. In summary, three histologic abnormalities have been identified that help predict the future development of myocyte necrosis within the next two endomyocardial biopsies. Biopsy specimens with these abnormalities probably represent early cardiac rejection before the development of myocyte necrosis.

Biopsy↗

Successful extended cardiopulmonary preservation in the autoperfused working heart-lung preparation.

Myocardial and pulmonary preservation can be prolonged in the autoperfused working heart-lung (AWHL) preparation by metabolic substrate enhancement. However, uncontrolled pulmonary hypertension following denervation may result in extensive lung injury and occasional early failure of the preparation. To determine whether cardiopulmonary preservation could be reliably extended without development of pulmonary hypertension, six heart-lung blocks were harvested from calves, placed in a normothermic AWHL circuit, and studied. Continuous infusions of isoproterenol and dextrose/insulin were administered for the duration of the preparation. Thirteen heart-lung preparations received neither isoproterenol nor metabolic substrate and served as controls. Myocardial function was assessed by sonomicrometric techniques and pulmonary preservation was evaluated by extravascular lung water, arterial oxygenation on 100% inspired oxygen, static lung compliance, and pulmonary vascular resistance. Pulmonary hypertension developed in the control group and these animals did not survive beyond 7.5 hours. The addition of isoproterenol and metabolic substrate increased organ survival from 4.8 +/- 0.4 to 18.0 +/- 1.4 hours (p = 0.0001) and significantly reduced postexplant pulmonary vasoconstriction (p less than 0.05). Addition of isoproterenol and metabolic substrate to the AWHL model prolonged support of cardiorespiratory function and provided a reliable method for distant procurement in heart-lung transplantation.

Animals↗

A no-flush, core-cooling technique for successful cardiopulmonary preservation in heart-lung transplantation.

In order to determine whether a no-flush, core-cooling technique could provide extended heart-lung preservation, we placed donor calves on cardiopulmonary bypass and instituted rapid cooling to 15 degrees C during the continuous infusion of isoproterenol. The heart and lungs were harvested after the administration of a cardioplegic solution through the aortic root. In the control group (N = 5), heart and lungs were orthotopically allotransplanted immediately. In the preserved group (N = 5), heart and lungs were similarly excised but were stored in a normal saline bath at 4 degrees C for approximately 4 hours and then transplanted. Both groups received isoproterenol during reperfusion and were studied for 6 hours after implantation. A load independent analysis of myocardial function was done by determining with a sonomicrometer the ratio of the end-systolic pressure to the end-systolic dimension. Pulmonary preservation was evaluated by measurement of extravascular lung water with a double-indicator dilution method, arterial oxygenation on 100% inspired oxygen, and serial lung biopsies. Myocardial and pulmonary function after 4 hours of static preservation was found to be similar to controls. No-flush, core-cooling with cardiopulmonary bypass provides adequate cardiorespiratory function after acute bovine heart-lung allotransplantation. With the use of this technique, successful extended cold ischemic cardiopulmonary preservation for heart-lung transplantation may be achieved.

Animals↗