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Biomedical subjects

B A Reitz

Publications and source records attributed to B A Reitz.

At least 73 records · Page 4Linked to original sources
PubMed1994

Inhibition of platelet adhesion during cardiopulmonary bypass reduces postoperative bleeding.

BACKGROUND: Thrombocytopenia and impaired platelet function after cardiopulmonary bypass (CPB) contribute to postoperative bleeding and may increase blood transfusion requirements. We tested the hypothesis that reversible inhibition of glycoprotein IIb/IIIa integrin-mediated platelet adhesion would reduce postoperative bleeding after CPB. METHODS AND RESULTS: Twelve mongrel dogs (21 to 24 kg) underwent 2.5 hours of hypothermic CPB followed by 6 hours of observation. The study group (n = 6) received a 90-micrograms/kg IV bolus of the glycoprotein IIb/IIIa inhibitor Integrelin, followed by continuous infusion (2 micrograms/kg per minute) during CPB; the control group (n = 6) received only drug vehicle. Platelet number and aggregometry, PaO2, and chest tube output were assessed serially. Lung wet weight, histology, and myeloperoxidase activity were also measured. At 120 minutes after CPB, the control group had significantly lower platelet counts (expressed as percent of pre-CPB values) when compared with the Integrelin group (control, 35.2 +/- 4.6%; Integrelin, 68.2 +/- 4.9%; mean +/- SEM; P < .05). Three hundred sixty minutes after CPB, platelet function (expressed as percent of pre-CPB aggregation induced by 10 mumol/L ADP) was better preserved in the Integrelin group (Integrelin, 20.8 +/- 3.0%; control, 43.9 +/- 10.4%; P < .05). The Integrelin group also had less total postoperative blood loss (control, 447 +/- 97 mL; Integrelin, 248 +/- 30 mL; P < .05). PaO2, lung wet weight, histology, and myeloperoxidase activity did not differ significantly between groups. CONCLUSIONS: This study demonstrates that inhibition of platelet adhesion during CPB results in (1) less platelet consumption, (2) better preservation of platelet function, and (3) less postoperative bleeding. Reversible platelet inhibition may have clinical utility in minimizing postoperative bleeding and reducing blood transfusions.

Animals↗
PubMed1994

Mitral valve operation in patients with the Marfan syndrome.

Optimal surgical treatment of mitral regurgitation in the Marfan syndrome (valve repair versus replacement) is controversial because the underlying connective tissue defect theoretically might compromise repair durability. To examine the results of mitral valve repair in these patients, we did a retrospective review of 160 patients with the Marfan syndrome who had cardiac surgical procedures between January 1983 and January 1993. Thirty-six patients had mitral procedures, 29 of which were repairs. Mitral valve replacement was necessary in seven patients because of extensive annular calcification and/or severe anterior leaflet abnormalities. The 18 men and 11 women undergoing mitral valve repair had a mean age of 26.5 +/- 2.6 years (range 9 months to 54 years); seven patients were less than 18 years of age. Twenty-four of the 29 patients had concomitant aortic root replacement because of aortic dilation or valvular insufficiency. All 29 repairs included annuloplasty, and 11 patients also required leaflet resection. There were no operative deaths. At mean follow-up of 26.6 +/- 4.8 months, there have been three late deaths, two caused by arrhythmia and one by complications of type III aortic dissection. All survivors are in New York Heart Association class I or II. In three patients recurrent mitral regurgitation developed (grade III or IV); 5-year actuarial freedom from significant mitral regurgitation was 88.3%. One patient required repeat mitral annuloplasty after endocarditis of the composite aortic graft spread to the mitral valve. No patient required late mitral valve replacement. These results demonstrate that (1) 22% of patients with the Marfan syndrome who undergo cardiac operation require a mitral valve procedure, (2) most can be treated by mitral repair rather than replacement, and (3) at early follow-up, results of mitral repair in this population are satisfactory.

Actuarial Analysis↗
PubMed1994

Glutamate excitotoxicity: a mechanism of neurologic injury associated with hypothermic circulatory arrest.

Glutamate, the major central nervous system neurotransmitter, may have potent neurotoxic activity under conditions of metabolic stress. By receptor autoradiography, we have demonstrated that brain regions most vulnerable to injury during prolonged hypothermic circulatory arrest have the highest density of glutamate receptors. To test the hypothesis that such injury could be mediated by glutamate excitotoxicity, we used dizocilpine (MK-801), a selective N-methyl-D-aspartate-glutamate receptor antagonist in a canine survival model of hypothermic circulatory arrest. Eighteen male dogs (20 to 25 kg) were supported by closed-chest cardiopulmonary bypass, subjected to 2 hours of hypothermic circulatory arrest at 18 degrees C, and rewarmed on cardiopulmonary bypass. All were mechanically ventilated and monitored for 20 hours before extubation and survived for 3 days. Group A dogs (n = 9) received a prearrest intravenous bolus of dizocilpine (0.75 mg/kg) followed by continuous infusion (75 micrograms/kg per hour), resulting in electroencephalographic silence. Dizocilpine was weaned before extubation. Group B dogs received vehicle only. According to a species-specific behavior scale that yielded a neurologic deficit score ranging from 0 (normal) to 500 (brain dead), all animals were neurologically assessed every 12 hours. After the dogs were killed at 72 hours, brains were examined by receptor autoradiography and histologically for patterns of selective neuronal necrosis; they were scored blindly from 0 (normal) to 100 (severe injury). Group A dogs had better neurologic function than group B (neurologic deficit score 21 +/- 15 versus 192 +/- 40, p < 0.001) and had less neuronal injury (7.3 +/- 3 versus 48.3 +/- 9, p < 0.0001). Densitometric receptor autoradiography revealed preservation of neuronal N-methyl-D-aspartate-glutamate receptor expression in group A only. These results represent the first direct evidence of a role for glutamate excitotoxicity in the development of hypothermic circulatory arrest-induced brain injury and suggest that selective glutamate receptor antagonists may have a neuroprotective capacity in prolonged periods of hypothermic circulatory arrest.

Animals↗
PubMed1993

Valvular disease in the elderly: influence on surgical results.

Aortic valve disease in the elderly is primarily calcific stenosis with preservation of left ventricular function. In contrast, mitral valve disease in the elderly often is ischemic in nature with damage occurring to both valve and myocardium. The present study was undertaken to compare results of aortic (AVR) and mitral valve replacement (MVR) in the elderly and to ascertain predictors of poor outcome. Because patients who had concomitant coronary artery bypass grafting (CABG) are included (51% for AVR, 55% for MVR), patients who had isolated CABG were used as a comparison group. Between January 1, 1984, and June 30, 1991, 1,386 patients aged 70 years and older underwent CABG (n = 1,043), AVR (n = 245), or MVR (n = 98). The operative mortality rates were 5.3% for AVR, 20.4% for MVR, and 5.8% for CABG. Late follow-up of patients undergoing operation in 1984 and 1985 was available for 98% (231/237). Overall survival was comparable for all three groups through the first 5 years of follow-up (AVR, 68% +/- 8%; MVR, 73% +/- 8%; CABG, 78% +/- 3%). After 5 years, survival for patients having AVR and MVR was less than that for those having CABG. Patient age, sex, New York Heart Association functional class, concomitant CABG, prosthetic valve type, native valve pathology, and preoperative catheterization data were examined as possible predictors of outcome by multivariate logistic regression.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

Superior cerebral protection with profound hypothermia during circulatory arrest.

The optimal temperature for cerebral protection during hypothermic circulatory arrest is not known. This study was undertaken to test the hypothesis that deeper levels of cerebral hypothermia (< 10 degrees C) confer better protection against neurologic injury during prolonged hypothermic circulatory arrest ("colder is better"). Twelve male dogs (20 to 25 kg) were placed on closed-chest cardiopulmonary bypass via femoral artery and femoral/external jugular vein. Using surface and core cooling, tympanic membrane temperature was lowered to 18 degrees to 20 degrees C (deep hypothermia, n = 6) or 5 degrees to 7 degrees C (profound hypothermia, n = 6). After 2 hours of hypothermic circulatory arrest, animals were rewarmed to 35 degrees to 37 degrees C on cardiopulmonary bypass. All were mechanically ventilated and monitored in an intensive care unit setting for 20 hours. Neurologic assessment was performed every 12 hours using a species-specific behavior scale that yielded a neurodeficit score ranging from 0% to 100%, where 0 = normal and 100% = brain dead. After 72 hours, animals were sacrificed and examined histologically for neurologic injury. Histologic injury scores were assigned to each animal (range, 0 [normal] to 100 [severe injury]). At the end of the observation period, profoundly hypothermic animals had better neurologic function (neurodeficit score, 5.7% +/- 4.0%) compared with deeply hypothermic animals (neurodeficit score, 41% +/- 9.3%; p < 0.006). Every animal had histologic evidence of neurologic injury, but profoundly hypothermic animals had significantly less injury (histologic injury score, 19.2 +/- 1.2 versus 48.3 +/- 1.5; p < 0.0001).

Animals↗
PubMed1993

Perforin expression localizing cytotoxic lymphocytes in the intimas of coronary arteries with transplant-related accelerated arteriosclerosis.

Accelerated arteriosclerosis is the major long-term complication of cardiac transplantation. It has been demonstrated recently that accelerated arteriosclerosis is caused, in part, by rejection-related, cell-mediated immunity. However, the role of cytotoxic T lymphocytes in this process is a subject of controversy. Perforin is a specific marker of functionally active cytotoxic lymphocytes because it is a functional component of the cytotoxic granules of these cells. We examined 11 coronary arteries from seven autopsied and four retransplanted heart transplant recipients for the presence of perforin-containing lymphocytes. Immunohistochemical stains for perforin were performed using a monoclonal antibody against human perforin. Eight of the 11 coronary arteries examined were found to contain perforin-positive cells. These perforin-positive cells were present in subendothelial spaces of the coronary arteries, and the staining seen was cytoplasmic and granular. The granules often were polarized to the endothelial surface. Furthermore, the cells identified were usually in close proximity to, or in direct contact with, coronary artery endothelial cells. These results suggest that cell-mediated endothelial injury by perforin-positive cytotoxic lymphocytes may contribute to the development of accelerated arteriosclerosis in heart transplant recipients.

Adolescent↗
PubMed1993

Immunologic and surgical developments in cardiac transplantation.

Clinical work in cardiac transplantation has focused on combating the major complications of this procedure, namely graft rejection and infection. Retrospective analyses suggest that prospective HLA typing, as is done in renal transplantation, may improve patient survival. Trials using FK 506 in cardiac transplantation have demonstrated some benefit using this agent over cyclosporine. Innovative immunologic interventions using novel monoclonal antibodies, methotrexate, total lymphoid irradiation, or photochemotherapy have shown promise in treating allograft rejection. Finally, prophylactic ganciclovir appears to prevent cytomegalovirus disease in seropositive transplant recipients; however, prevention of primary infection in seronegative patients may prove more difficult.

Child↗
PubMed1993

Late cyclosporine treatment ameliorates established coronary graft disease in rat allografts.

The development of post-transplantation coronary graft disease (CGD) is a major cause of late morbidity and mortality. Recent reports have suggested that CGD is a type of chronic vascular rejection, possibly enhanced by cofactors such as concurrent CMV infection and hyperlipidemia. It remains controversial whether established CGD can be improved by modifications in immunosuppressive therapy. The purpose of this study was to examine whether CsA could reverse or halt the progression of CGD after it was already established. Lewis to Fisher (F-344) heterotopic heart allografts develop CGD resembling human disease. Group 1 (n = 29) had no CsA therapy for chronic rat CMV (RCMV) infection in recipients for 8 weeks before transplant. Group 2 (n = 17) had chronic RCMV infection along with CsA therapy from days 15 to 28 post-transplant. Allografts were killed at 2 and 4 weeks and 90 days post-transplantation. In group 1, leukocyte adhesion to arterial endothelium and intimal hyperplasia were well established at 2 weeks and progressed to stenotic, proliferative arterial lesions at 4 weeks. In group 2, CsA therapy was effective in significantly reversing histologic parameters of vascular rejection such as leukocyte adhesion, intimal proliferation, and periarterial edema at 4 weeks. By 90 days, however, arterial pathology was as severe as in group 1. In conclusion, these results support the hypothesis that CGD is a form of chronic vascular rejection, and once established, can be significantly modified by CsA therapy. These effects are not permanent, and progressive CGD recurs after CsA therapy is discontinued.

Animals↗
PubMed1993

Randomized, prospective assessment of bioprosthetic valve durability. Hancock versus Carpentier-Edwards valves.

BACKGROUND: Although the major limitation of porcine valves is their finite durability, no controlled clinical data exist regarding the relative durability of the two porcine bioprostheses implanted most commonly today, the Carpentier-Edwards (C-E) and Medtronic Hancock I (H) valves. METHODS AND RESULTS: To assess this question, 174 patients undergoing aortic (AVR) or mitral (MVR) valve replacement with a bioprosthesis between March 1980 and March 1982 were randomized to receive either a C-E or a H valve. There were 102 AVRs (54 C-E and 48 H) and 74 MVRs (39 C-E and 35 H). For both the AVR and MVR cohorts, the average patient age was 58 +/- 14 years (+/- SD). The male/female ratio was 2.2:1 for AVR and 0.57:1 for MVR. Clinical follow-up was undertaken periodically; the most recent follow-up closing interval was July through October 1992, and current follow-up was 96% complete. Cumulative follow-up totaled 1369 patient-years (mean, 7.7 +/- 3.6 years; median, 9.1 years; maximum, 12.0 years). The main focus of this analysis was bioprosthetic durability, using the AATS/STS guidelines defining "Structural Valve Deterioration" (SVD). Multivariate analysis revealed that (younger) age was the only significant (P = .024) independent predictor of SVD. Valve manufacturer (C-E versus H) and valve site (aortic versus mitral) did not emerge as significant independent risk factors for SVD. Actuarial rates (Cutler-Ederer) expressed as percent free of SVD (+/- SEM) at 10 years (n = number of patients remaining at risk) were 71 +/- 7% and 59 +/- 9% for the C-E (n = 26) and H (n = 17) groups, respectively, for the AVR cohort; for the MVR cohort, these estimates were 60 +/- 10% (n = 12) and 72 +/- 10% (n = 11), respectively, but these differences were not statistically significant (P = NS, Lee-Desu). CONCLUSIONS: After 10 years, there was no statistically significant difference in durability or other valve-related complications between the H and C-E aortic or mitral valves. Based on current information, the choice of a porcine bioprosthesis should be based on factors other than durability, including ease of implantation, hemodynamic performance, and cost.

Aortic Valve↗
PubMed1993

Clinical trial of cefamandole, cefazolin, and cefuroxime for antibiotic prophylaxis in cardiac operations.

A relatively large number of comparative trials of antibiotic prophylaxis in cardiac surgery have been published, many of which have serious design flaws. Despite the large number of studies, no single antibiotic regimen has emerged as clearly superior in preventing postoperative site infections. To determine if a superior regimen could be identified with a study designed to avoid flaws found in previous studies, we undertook a randomized, double-blind clinical trial of three cephalosporins. From March 1987 to February 1990, 2759 adults underwent median sternotomies: 1641 completed study participation, 203 were enrolled but were dropped from the study for protocol violations, and 815 were excluded. The characteristics of all 2759 patients were recorded with respect to case mix and infection risk factors, and the patients were followed-up by the same nurse throughout hospitalization and for 6 weeks after discharge for the assessment of infection outcome status. Of the 1641 participants, 141 (8.6%) had one or more operative site infections: 46 of 549 (8.4%) cefamandole recipients, 46 of 547 (8.4%) cefazolin recipients, and 49 of 545 (9.0%) cefuroxime recipients (p = 0.92). The sites of infection and the depth of tissue involvement were not significantly different across groups. Because no differences in effectiveness in preventing postoperative site infections were demonstrated in a rigorously designed trial, the costs of the drugs, including the costs of their preparation and delivery, may be the only variables by which to choose among these three antibiotic prophylaxis regimens.

Adult↗
PubMed1992

The declining risk of post-transfusion hepatitis C virus infection.

BACKGROUND: The most common serious complication of blood transfusion is post-transfusion hepatitis from the hepatitis C virus (HCV). Blood banks now screen blood donors for surrogate markers of non-A, non-B hepatitis and antibodies to HCV, but the current risk of post-transfusion hepatitis C is unknown. METHODS: From 1985 through 1991, blood samples and medical information were obtained prospectively from patients before and at least six months after cardiac surgery. The stored serum samples were tested for antibodies to HCV by enzyme immunoassay, and by recombinant immunoblotting if positive. RESULTS: Of the 912 patients who received transfusions before donors were screened for surrogate markers, 35 seroconverted to HCV, for a risk of 3.84 percent per patient (0.45 percent per unit transfused). For the 976 patients who received transfusions after October 1986 with blood screened for surrogate markers, the risk of seroconversion was 1.54 percent per patient (0.19 percent per unit). For the 522 patients receiving transfusions since the addition in May 1990 of screening for antibodies to HCV, the risk was 0.57 percent per patient (0.03 percent per unit). The trend toward decreasing risk with increasingly stringent screening of donors was statistically significant (P less than 0.001). After we controlled for the method of donor screening, the risk of seroconversion was strongly associated (P less than 0.001) with the volume of blood transfused, but not with the use of particular blood components. CONCLUSIONS: The incidence of post-transfusion hepatitis C has decreased markedly since the implementation of donor screening for surrogate markers and antibodies to HCV. The current risk of post-transfusion hepatitis is about 3 per 10,000 units transfused.

Alanine Transaminase↗
PubMed1992

Surgical treatment of postinfarction ventricular septal defect with aortic stenosis.

A 69-year-old man with an acute postinfarction ventricular septal defect was also found to have aortic stenosis. Successful management required closure of the postinfarction ventricular septal defect and replacement of the stenotic aortic valve. The contribution of aortic stenosis to the cause of the infarction and the postinfarction ventricular septal defect, as well as the implications for surgical management, are discussed.

Aged↗
PubMed1992

Hypothermic circulatory arrest as a surgical adjunct: a 5-year experience with 60 adult patients.

As a surgical adjunct, the technique of hypothermic circulatory arrest (HCA) is well established in pediatric cardiac surgery but is used less frequently in adults. This study was undertaken to review the application, utility, and safety of HCA in adult surgery at a single institution. Between January 1985 and October 1990, 60 adult patients (greater than 18 years old) underwent surgical procedures that included HCA. There were 30 men and 30 women; mean patient age was 56.4 years (range, 20 to 81 years). Operative procedures were thoracic aortic aneurysm repair (35 patients, 58%), resection of intraabdominal malignancy (15 patients, 25%), coronary artery bypass (4 patients, 7%), and other miscellaneous procedures (6 patients, 10%). Eighty-two percent of the procedures were elective, whereas 18% were emergencies. Mean circulatory arrest time was 28.5 minutes (range, 2 to 64 minutes). Operative mortality was 15%; by multivariate analysis, risk factors for death included prolonged cardiopulmonary bypass time (p less than 0.05), higher post-HCA rectal temperature (p less than 0.05), and intraoperative hypotension (p less than 0.001). Patient age, sex, emergency status, duration of HCA, and perfusion variables on cardiopulmonary bypass did not predict operative mortality. The incidence of perioperative neurologic injury was 15%. The only risk factor for neurologic injury was intraoperative hypotension (p less than 0.05). One- and 3-year actuarial survival for patients undergoing operation on the heart or great vessels was 75.9% and 70%, respectively, whereas patients with intraabdominal malignancy had 75% and 23.4% 1- and 3-year survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Spinal cord stimulation evoked potentials during thoracoabdominal aortic aneurysm surgery.

Although monitoring of somatosensory evoked potentials elicited from stimulation of lower extremity peripheral nerves has been suggested as a method for assessing neural function during thoracoabdominal aortic aneurysm surgery, this technique has been reported to yield a large number of false positives. It was believed that direct stimulation of the spinal cord would eliminate some of the problems associated with peripheral evoked potentials. The present study compared in 18 patients the use of scalp recorded evoked potential following stimulation of either the posterior tibial nerve via percutaneous needles or the spinal cord via an epidural electrode previously placed fluoroscopically. In 10 patients in whom distal bypass or shunt was not used, peripheral evoked potentials totally disappeared within 5-30 min of aortic clamping. Spinal cord stimulation evoked potentials disappeared permanently in 2 patients shortly after aortic cross-clamping; 1 died shortly after the procedure, and the other awoke densely paraplegic and died the next day. When distal perfusion was maintained by shunt or bypass, the disappearance of both peripheral and spinal evoked potentials accurately predicted the neurologic outcome of 1 paralyzed patient. Loss of spinal cord stimulation evoked potentials was found to be correlated with adverse neurologic outcome. Over the period of aortic clamping a gradual decrease in mean amplitude (50% at 45 min [P less than 0.05]) and a 20% increase in mean latency time were observed. Maintenance of adequate distal perfusion may permit the use of peripheral evoked potentials in the assessment of spinal cord ischemia during aortic cross-clamping.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Effects of cyclosporine on cerebral blood flow and metabolism in dogs.

Neurological side effects associated with cyclosporine immunosuppressive therapy are generally believed to occur with CsA blood concentrations above the therapeutic range. The effects of high blood CsA levels on cerebral hemodynamics, metabolism, and electrophysiologic activity were studied in acute (no CsA prior treatment) and chronic (with CsA prior treatment) dogs. In acute animals, when parenteral CsA (10 mg/kg or 25 mg/kg) was administered intravenously (CsA blood level 2000-22,000 ng/ml), slight but significant time-dependent decreases in cerebral blood flow (CBF), prolongation of absolute latencies of somatosensory-evoked potential (SSEP), and brainstem auditory-evoked responses (BAER) were noted. In the CsA chronically administered animals (oral CsA 25 mg/kg/24 hr for 14 days, CsA blood level 1077 ng/ml), baseline cerebral physiologic parameters were normal, and the cerebral responses to further administration of CsA (25 mg/kg, CSA blood level 56,000 ng/ml) intravenously were similar to those of the acute animals. Animals given Cremophor EL, the solvent for parenteral CsA preparation, showed similar cerebral responses to those observed in animals given CsA. Thus this study showed that CsA, regardless of the dose given, whether chronically or acutely administered, or the solvent for CsA all induced similar cerebral physiologic responses. We suggest that the cerebral physiologic and functional changes associated with parenteral CsA administration were small and were likely caused by its solvent, Cremophor EL, rather than CsA itself. Furthermore on the basis of our results, it is unlikely that high blood CsA per se can account for neurological side effects that occur in immunosuppressed patients.

Animals↗
PubMed1992

Demonstration of cytomegalovirus nucleic acids in the coronary arteries of transplanted hearts.

Cytomegalovirus (CMV) infection has been associated with the development of accelerated arteriosclerosis in heart transplant recipients. This association prompted the authors to examine, using in situ hybridization techniques, the coronary arteries of 19 patients who had received heart transplants for the presence of CMV nucleic acids. Two probes were employed on formalin-fixed paraffin-embedded tissues. The first was an S35-labeled nick translated probe derived from CMV DNA. CMV nucleic acids were identified in the arterial intima of 5 (45%) of 11 transplanted hearts examined with this probe. Hybridization to cells morphologically consistent with endothelial cells, lymphocytes, and smooth muscle cells was identified. Hybridization was not detected in any of the hearts when a control probe, a vector without CMV DNA, was employed. The second probe that was used was a tritium-labeled strand-specific ribo-probe derived from the immediate early (IE1) gene of CMV. Using this second probe, hybridization was detected in the coronary arteries of three of five hearts that were positive with the DNA probe, in one of the hearts that was negative with the DNA probe, and in three (38%) of eight additional transplanted hearts. The pattern of hybridization was the same as that seen with the DNA probe, and no hybridization was detected when a control sense probe for the IE1 gene of CMV was employed. These results suggest that CMV nucleic acids are present in the coronary arteries of heart transplant recipients.

Adolescent↗