Biomedical subjects

W A Baumgartner

Publications and source records attributed to W A Baumgartner.

At least 55 records · Page 3Linked to original sources

PubMed1996

Bioprosthetic versus mechanical prostheses for aortic valve replacement in the elderly.

BACKGROUND: Many centers advocate bioprosthetic valves in the elderly to avoid anticoagulation, in particular when patient survival is less than the expected valve durability. Because expected survival in the elderly is increasing and age-specific risk of anticoagulation in the elderly is not known, we examined valve- and anticoagulation-related morbidity in elderly patients after aortic valve replacement (AVR) with bioprostheses or mechanical prostheses. METHODS AND RESULTS: Between January 1980 and June 1994, 211 patients age > or = 70 years underwent isolated AVR; there were 109 men (52%) and 102 women (48%). Mean age was 75.9 +/- 4.8 years. Aortic stenosis was present in 194 (92%) patients. Bioprostheses were used in 145 (69%) and mechanical prostheses were used in 66 (31%). Chronic anticoagulation was maintained in all patients with a mechanical valve and in 18 patients (12%) with a bioprosthetic valve. Follow-up data were obtained for 98% (194 of 197) of hospital survivors at a mean follow-up of 3.8 years. Operative mortality was 6.6%; survival at 3 and 5 years was 75.3 +/- 3% and 64.6 +/- 4%, respectively. There was no significant difference in operative or late mortality between patient groups. Rates of freedom from thromboembolic events, endocarditis and anticoagulant-related hemorrhage for bioprosthetic and mechanical valve patients were similar. Prosthetic failure was identified in three bioprosthetic valves (2%); furthermore, the 4 patients in the series who required reoperation had received bioprostheses at the first operation. CONCLUSIONS: In conclusion, (1) elderly patients undergoing isolated AVR can be managed with either mechanical or bioprosthetic valves with similar early and late risk, as long as there are no specific contraindications to anticoagulation; (2) anticoagulation-related risk of hemorrhage is low in this group of elderly patients; and (3) the low but significant risk of reoperation following the use of bioprostheses suggests that mechanical valves may be underused in the elderly.

Aged↗

PubMed1996

Induction of heat shock protein in cardiac allograft rejection--a cyclosporine-suppressible response.

The cellular response to a wide variety of stresses results in the synthesis of a family of proteins termed heat shock proteins (HSPs). To determine if acute allograft rejection could induce these proteins in a transplanted graft, we examined the HSP response to acute cardiac allograft rejection and analyzed the effect of immunosuppression upon this response. Donor hearts obtained from either Lewis (LEW) or ACI rats were heterotopically transplanted in recipient LEW rats. There were 4 experimental groups: untreated isografted (LEW to LEW) animals (n = 14), untreated allografted (ACI to LEW) animals (n = 14), cyclosporine-treated (10 mg/kg SQ/day) isografted animals (n = 12), and cyclosporine-treated allografted animals (n = 12). Animals were sacrificed on posttransplantation day 2, 4, or 6 (time of rejection for untreated allografts); n = 4-5 for each time point per group. At these times tissue obtained from the transplanted heart was examined histologically and analyzed for HSP72 by quantitative Northern and Western blots. The level of HSP72 in the untreated allografts progressively increased between 2, 4, and 6 days posttransplantation and was significantly greater than that of the untreated isografts at all time points. The HSP72 response in cyclosporine-treated allografts was significantly reduced at 4 and 6 days posttransplantation compared with the untreated allografts. In contrast, there was no difference in the HSP response in treated versus untreated isografts. Additionally, there was no difference in HSP levels in cyclosporine-treated isografts and allografts. These findings demonstrate that HSP expression in the transplanted heart correlates directly with the evolution of acute allograft rejection, and that immunosuppressive therapy inhibits the HSP response. These studies also raise the possibility of a functional role for HSPs in the allogeneic immune response.

Animals↗

PubMed1996

Neurologic injury in cardiac surgical patients with a history of stroke.

BACKGROUND: Controversy still exists as to whether patients with previous stroke are at increased risk for neurologic complications after heart operations. METHODS: We performed a prospective analysis of 1,000 consecutive patients undergoing cardiac operations requiring cardiopulmonary bypass, without hypothermic circulatory arrest. Of the 1,000 patients, 71 had previously documented stroke (study group); 2 control patients with no history of stroke were selected for each of these patients (control group, n = 142). There were no significant differences between the study and control patients with respect to established risk factors for neurologic complications. RESULTS: Compared with controls, study patients took longer to awaken (12.6 +/- 10.9 versus 3.5 +/- 2.1 hours; p < 0.0001) and longer to extubate (29.5 +/- 29.3 versus 9.1 +/- 5.2 hours; p < 0.001), and had a greater incidence of reintubation (7 of 71, 9.9% versus 2 of 142, 1.4%; p < 0.01) and postoperative confusion (26 of 71, 36.6% versus 7 of 142, 4.9%; p < 0.001). There was a higher incidence of focal neurologic deficit among study patients (31 of 71, 43.7% versus 2 of 142, 1.4%; p < 0.001). These deficits included new stroke (6 of 71, 8.5%) as well as the reappearance of previous deficits (19 of 71, 26.8%) or worsening of previous deficits (6 of 71, 8.5%), without new abnormalities on head computed tomography or magnetic resonance imaging. Study patients with neurologic deficit had longer cardiopulmonary bypass times than did study patients without deficit (146 +/- 48.5 versus 110 +/- 43.3 minutes; p < 0.001). The 30-day mortality rate was greater in study patients than in controls (5 of 71, 7% versus 1 of 142, 0.7%; p < 0.02), with four deaths among the 6 study patients with a new stroke (66.7%). CONCLUSION: This analysis identifies a group of patients at high risk for neurologic sequelae and confirms the vulnerability of the previously injured brain to cardiopulmonary bypass, as evidenced by reappearance or exacerbation of focal deficits in such patients.

Aged↗

PubMed1996

Valve replacement in patients with endocarditis and acute neurologic deficit.

BACKGROUND: Acute neurologic deficits occur in up to 40% of patients with left heart endocarditis. Appropriate evaluation and management of patients with acute neurologic dysfunction who require valve operations for endocarditis remain controversial. This retrospective review was undertaken to develop recommendations for the evaluation and treatment of these challenging patients. METHODS: From 1983 to 1995, 247 patients underwent operations for left heart native valve endocarditis at the Johns Hopkins Hospital. From a review of medical and pathology records, 34 patients (14%) with preoperative neurologic deficits were identified. Data on these 34 patients were recorded and analyzed. RESULTS: Causes of neurologic dysfunction included embolic cerebrovascular accident (n = 23, 68%), embolic cerebrovascular accident with hemorrhage (n = 4, 12%), ruptured mycotic aneurysm (n = 3, 9%), transient ischemic attack (n = 2, 6%), and meningitis (n = 2, 6%). Preoperative diagnostic studies included computed tomography (32 patients), magnetic resonance imaging (11 patients), cerebral angiogram (14 patients), and lumbar puncture (2 patients). Computed tomography demonstrated structural lesions in 29 of 32 patients; in only 1 patient did magnetic resonance imaging reveal a lesion not already seen on computed tomography. Of 14 patients having cerebral angiograms, 7 had a mycotic aneurysm. Three mycotic aneurysms had ruptured, and these were clipped before cardiac operations. The mean interval from onset of neurologic deficit to cardiac operation was 22.2 +/- 2.8 days for all patients and 22.1 +/- 3.0 days for those with embolic cerebrovascular accident. The hospital mortality rate was 6%. New or worse neurologic deficits occurred in 2 patients (6%). CONCLUSIONS: Neurologic deficits are common in patients with endocarditis referred for cardiac operations. Despite substantial preoperative morbidity, most of these patients do well if the operation can be delayed for 2 to 3 weeks. Computed tomography scan is the preoperative imaging technique of choice, as routine magnetic resonance imaging and cerebral angiogram are unrewarding. Cerebral angiogram is indicated only if computed tomography reveals hemorrhage.

Acute Disease↗

PubMed1996

One-month histologic response of transmyocardial laser channels with molecular intervention.

BACKGROUND: Transmyocardial revascularization reduces the symptoms and morbidity of patients with endstage ischemic heart disease. The mechanism is postulated to be the formation of transmural left ventricular channels through which oxygenated blood directly perfuses the myocardium. New techniques for molecular enhancement of angiogenesis and endothelial cell motility may represent strategies to augment this clinical benefit. METHODS: Triads of transmyocardial revascularization channels were placed in eight separate nonischemic sites on the hearts of 7 pigs weighing 68 to 78 kg, which were allowed to recover and were then sacrificed at 28 days. In addition, one triad pair was injected with vascular endothelial growth factor, and two triad pairs received an adenovirus vector with or without the gene encoding for human profilin, which increases endothelial cell motility and adhesion. The remaining triad pair stood untreated (laser only). The histologic changes were graded (0 through 3) by an independent pathologist without knowledge of the treatment modality. Profilin production and vascular endothelial growth factor activation using a tyrosine kinase assay were monitored. RESULTS: Transmyocardial revascularization alone resulted in a significant injury response (p < 0.01), including increased vascularity without patent channels. Vascular endothelial growth factor increased surrounding inflammation (p < 0.01) without improving vascularity or patency. Profilin content in tissues was increased but nonspecifically because inflammation resulting from adenovirus also induces higher profilin concentrations. CONCLUSIONS: The clinical benefit of transmyocardial revascularization may result simply from a nonspecific histologic response to injury. Molecular interventions appear to stimulate more inflammation but no additional angiogenesis. Further improvement in the clinical benefit of transmyocardial revascularization awaits the successful stimulation of a true angiogenic response.

Adenoviridae↗

PubMed1996

Induction of neuronal nitric oxide after hypothermic circulatory arrest.

BACKGROUND: Although hypothermic circulatory arrest (HCA) has become routine practice in cardiac surgery, it is associated with substantial neurotoxicity. We tested the hypothesis that increased nitric oxide production during HCA participates in neuronal death. We previously described a canine survival model of HCA that produces a consistent neurologic deficit and histopathologic pattern of selective neuronal death. METHODS: Adult male hound dogs (n = 17) were subjected to 2 hours of HCA at a brain temperature of 18 degrees C and reperfused to normothermia; they were sacrificed at various intervals up to 74 hours. Using in vivo cerebral microdialysis, dogs (n = 5) were given a simultaneous infusion of artificial cerebrospinal fluid containing L-[14C]arginine or L-[14C]arginine and L-nitroarginine methyl ester (a nitric oxide synthase inhibitor) in contralateral hemispheres while undergoing 2 hours of HCA and reperfusion to normothermia. RESULTS: L-[14C]citrulline recovery, a coproduct of nitric oxide, significantly increased during HCA in the hemisphere without the inhibitor (at 300 minutes: control, 236 +/- 94 fmol/min versus L-nitroarginine methyl ester, 6 +/- 6 fmol/min; p < 0.05). Citrulline production in vitro from canine cortical homogenates in the presence of calcium (n = 12) was significantly greater 8 and 20 hours after reperfusion (5.11 +/- 0.54 x 10(-7) mmol.mg-1.min-1 and 7.52 +/- 0.59 x 10(-7) mmol.mg-1.min-1, respectively) than before HCA (1.51 +/- 0.09 x 10(-7) mmol.mg-1.min-1; p < 0.05). Nitric oxide metabolites in the serum were also increased significantly early after reperfusion (baseline, 6.72 +/- 0.95 mmol/L; at 4 hours, 17.58 +/- 1.46 mmol/L; p < 0.05). Immunocytochemical staining of the cortex with neuronal nitric oxide synthase-specific monoclonal antibodies (Transduction Labs) revealed increased neuronal nitric oxide synthase expression 6 to 18 hours after HCA. Darkfield analysis demonstrated neuronal nitric oxide synthase localization to neuronal processes with widespread formation of dense plexi of nitric oxide synthase fibers. CONCLUSIONS: We conclude that neurotoxicity after HCA involves a significant, early induction in neuronal nitric oxide synthase expression in neuronal processes leading to widespread augmented nitric oxide production in the brain.

Animals↗

PubMed1996

The WAF1-mediated p53 growth-suppressor pathway is intact in the coronary arteries of heart transplant recipients.

It has been suggested that the interaction of cytomegalovirus (CMV) with the p53 tumor suppressor gene product plays a role in the development of coronary artery restenosis after angioplasty. CMV nucleic acids have been observed in the coronary arteries of allografted hearts, suggesting a possible role for the interaction of CMV with p53 in the development of accelerated graft arteriosclerosis in transplant recipients. Formalin-fixed, paraffin-embedded sections of coronary arteries from 19 transplanted hearts were immunostained for the p53 gene product using Target Unmasking Fluid (TUF)-mediated immunohistochemistry and the anti-p53 antibodies CM1 and DO7. Fresh-frozen sections of coronary arteries were also available from six of the 19 hearts, and these fresh-frozen sections were immunostained for the p53 gene product with the DO7 antibody and for WAF1 using the anti-WAF1 antibody EA10. Focal and weak staining for p53 was observed in smooth muscle and endothelial cells in two of 19 vessels, whereas the remaining 17 did not stain. CMV nucleic acids were previously shown in six of 13 of these hearts by in situ hybridization. The fresh-frozen sections of coronary arteries also did not stain for p53, but the smooth muscle cells in these vessels did stain intensely for WAF1. These results suggest three possibilities: (1) CMV-p53 interactions are not important in the development of accelerated graft arteriosclerosis; or (2) there is an interaction, but it is transient and not detectable at the time points examined in this study; or (3) there is an interaction, but binding of CMV to p53 leads to accelerated degradation of p53, as occurs with HPV-E6. The expression of WAF1 further suggests that the WAF1-mediated antiproliferative signal is intact in these vessels.

Coronary Artery Disease↗

PubMed1996

Single doses of intravenous protamine result in the formation of protamine-specific IgE and IgG antibodies.

BACKGROUND: Protamine reactions are a well-recognized and serious complication of intravenous protamine administration. IgE-mediated anaphylaxis occurs after initial sensitization and subsequent re-exposure to antigens. Subcutaneous protamine in insulin preparations is associated with protamine-specific IgE and IgG antibody production. In contrast, the influence of intravenous protamine administration on protamine-specific IgE and IgG antibody formation has never been investigated. METHODS: Sera from 93 patients were analyzed for protamine-specific IgE and IgG antibodies both before and 4 to 6 weeks after exposure to single doses of intravenous protamine. Specific clinical variables were assessed by univariate and multivariate analyses to determine independent predictors of protamine-specific antibody production. RESULTS: In patients who were previously seronegative, intravenous protamine administration resulted in protamine-specific IgE and IgG antibody production in 17 of 93 (18%) and 15 of 93 (16%) patients, respectively. As determined by multivariate analysis, male gender (p = 0.06) and insulin-dependent diabetes mellitus (p = 0.002) were associated with protamine-specific IgG but not IgE antibody production. CONCLUSION: Single-dose intravenous protamine resulted in protamine-specific IgE and/or IgG antibody production in 26 of 93 (28%) of patients. Seroconversion was associated with male gender and insulin-dependent diabetes mellitus. Patients responding immunologically to protamine may be at increased risk for experiencing reactions on subsequent exposure.

Aged↗

PubMed1995

Drug testing by urine and hair analysis: complementary features and scientific issues.

Hair analysis and urinalysis are complementary tests for establishing drug use. Hair analysis provides long-term information, from months to years, concerning both the severity and pattern of drug use. In contrast to this, urinalysis can indicate only drug use, and then generally only that which has occurred within the last 2-3 days. Field studies have demonstrated that hair analysis is considerably more effective than urinalysis at identifying drug users. This difference is due to the wider surveillance window of hair analysis and to the susceptibility of urinalysis to evasive maneuvers. The main concerns with urinalysis are endogenous evidentiary false positives caused by passive drug exposure, e.g., ingestion of poppy seed. This problem arises from the hypersensitivity of the urine test, i.e. the need to use low cut-off levels in order to compensate for the temporary recording of drug use. This problem does not occur with hair analysis since its wide window of detection and permanent record of drug use ensure that the detection efficiency of the test is not compromised by the use of more effective cut-off levels guarding against passive endogenous drug exposure. On the other hand, exogenous evidentiary false positives due to external contamination of hair by drugs present in the environment (e.g., smoke) are the main concern of hair analysis. This problem, however, can be effectively avoided by washing the hair specimen, by kinetic analyses of the wash data, and by measurement of metabolites. The possibility of bias due to race and/or hair color is avoided by the exclusion of melanin from the analysis of hair. The safety and effectiveness of hair testing has been established by extensive field studies with over 400,000 specimens.

Hair↗

PubMed1995

Neutrophil modulation results in improved pulmonary function after 12 and 24 hours of preservation.

Neutrophils are important mediators of reperfusion injury, and suppression of neutrophil function or numbers can reduce reperfusion injury and improve long-term organ preservation in transplantation. NPC 15669, a leumedin, is a novel compound that prevents recruitment of neutrophils at inflammatory foci by inhibiting CD11b/CD18 adhesion molecule expression. NPC 15669 was used to inhibit neutrophil adhesion during reperfusion of isolated rabbit lungs after 12 and 24 hours of cold storage. Lungs (New Zealand White male rabbits, 2 to 3 kg) were flushed with 4 degrees C Euro-Collins (EC) solution, harvested en bloc, stored under various study conditions, and reperfused for 3 hours with fresh whole blood at 37 degrees C in an isolated perfusion system at constant flow and an inspired oxygen fraction of 1. Four groups (n = 6 each) were studied. Group I underwent immediate whole blood reperfusion. Group II were stored for 12 hours in 4 degrees C EC solution before reperfusion. Group III were stored for 12 hours in 4 degrees C EC solution and reperfused with whole blood containing NPC 15669 (10 mg/kg whole body weight). Group IV were stored for 24 hours in 4 degrees C EC solution and reperfused with whole blood containing NPC 15669 (10 mg/kg). Pulmonary artery and peak airway pressures were significantly lower and compliance higher in groups III and IV lungs after 3 hours of reperfusion (p < 0.05) compared with group I. Group I and III lungs had significantly less edema than group II (p < 0.05). The arterial partial pressure of oxygen was similar in all stored groups (II to IV).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Thalidomide as replacement for steroids in immunosuppression after lung transplantation.

Steroids have been implicated in postoperative complications after lung transplantation: infections, delayed wound healing, and poor bronchial anastomotic healing. Thalidomide (alpha-phthalimidoglutarimide), a sedative drug with known immunomodulatory properties, was used to replace corticosteroids after canine lung transplantation. Fifteen mongrel dogs underwent single-lung transplantation: group I (n = 5) received cyclosporin A (20 mg/kg twice a day), azathioprine (2.5 mg/kg once a day), and thalidomide (50 mg/kg twice a day). Group II (n = 5) received standard immunosuppression of cyclosporin A (20 mg/kg twice a day), azathioprine (2.5 mg/kg once a day), and prednisone (2 mg/kg once a day), and group III (n = 5) received cyclosporin A (10 mg/kg twice a day), azathioprine (2.5 mg/kg once a day), and thalidomide (50 mg/kg twice a day). Open lung biopsy and bronchoscopy were performed weekly until sacrifice on day 28. Serum thalidomide and cyclosporin A levels were followed up weekly. Group I showed essentially no rejection until week 2 and minimal rejection (grade 1) until day 28. Group II had moderate rejection (grade 2) of the graft at all time points. Group III animals had moderate to severe rejection (grades 3 to 4) after 21 days (p < 0.05 for group I versus groups II and III). The number of clinically evident episodes of pneumonia was also significantly lower in group I than in groups II and III (p < 0.05). We conclude that thalidomide appears to replace corticosteroids effectively in early postoperative immunosuppression after lung transplantation and is associated with a decreased incidence of pneumonia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

AMPA glutamate receptor antagonism reduces neurologic injury after hypothermic circulatory arrest.

Pharmacologic inhibition of the N-methyl-D-aspartate (NMDA) glutamate receptor can reduce the neurologic injury associated with hypothermic circulatory arrest; however, other receptor subtypes, such as the alpha-amino-3-hydroxy-5-methylisoazole-4-propionic acid/kainate or AMPA/kainate subtype, may predominate in the adult brain. In this experiment, a selective AMPA antagonist, NBQX, was used in a canine survival model of hypothermic circulatory arrest. Twelve male dogs (20 to 25 kg) were placed on 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. Six dogs received NBQX beginning 2 hours after arrest (3 mg/kg for 3 hours then 1.5 mg/kg for 2 hours). Control dogs received vehicle only. Neurologic recovery was assessed every 12 hours using a species-specific behavior scale that yielded a neurodeficit score ranging from 0 (normal) to 500 (brain dead). After sacrifice at 72 hours, brains were examined by receptor autoradiography and histologically for patterns of selective neuronal necrosis and scored blindly from 0 (normal) to 100 (severe injury). Dogs given NBQX had better neurologic function compared with controls (neurodeficit score, 58.6 +/- 15 versus 204 +/- 30; p < 0.004) and had less neuronal injury (18.2 +/- 3 versus 52.5 +/- 6; p < 0.004). Densitometric receptor autoradiography revealed preservation of neuronal NMDA receptor expression only in dogs given NBQX. These results suggest that antagonism of the non-NMDA glutamate receptor AMPA may be neuroprotective in adults after hypothermic circulatory arrest.

Animals↗

PubMed1995

Postoperative abdominal complications in cardiopulmonary bypass patients: a case-controlled study.

Intraabdominal complications (IAC) after cardiopulmonary bypass often are difficult to diagnose and are associated with high mortality (13% to 67%). From 1984 to 1991 we retrospectively analyzed 53 patients undergoing cardiopulmonary bypass for coronary artery bypass grafting, valve reconstruction, or arch reconstruction who experienced 55 episodes of IAC and compared them with matched control patients (matched for operation, age, and sex). The overall incidence of IAC was 0.65%. Univariate analysis identified the following preoperative variables as significantly (p < 0.05) increasing the risk of IAC: history of congestive heart failure, chronic renal failure, and more than three medical problems. A history of congestive heart failure was the most powerful predictor by multivariate analysis (p = 0.045). Early postcardiopulmonary bypass complications were increased significantly in IAC patients. These included acute renal failure (p < 0.0001), cerebrovascular accidents (p < 0.03), and lower extremity ischemia (p < 0.05). Twenty-eight of 38 laparotomies performed were diagnostic. However, analysis of 58 combined clinical, radiologic, and laboratory tests failed to identify which predicted the diagnostic utility of a laparotomy. Fifteen of the 53 IAC patients (28%) survived: 8 patients had had a therapeutic laparotomy, 1 patient underwent a nondiagnostic laparotomy, and 6 patients were managed nonoperatively. Multivariate analysis identified ventilator dependence (p = 0.004) and acute renal failure with creatinine level greater than 1.9 mg/dL (p = 0.011) as the most powerful predictors of mortality regardless of intervention. These data suggest a profile of cardiac surgical patients at risk for IAC as well as those patients who are most likely to benefit from timely intervention.

Abdomen↗

PubMed1995

Efficacy of autologous fresh whole blood or platelet-rich plasma in adult cardiac surgery.

BACKGROUND: Transfusing fresh autologous blood during cardiac surgery may improve hemostasis and decrease the need for transfusion. STUDY DESIGN AND METHODS: A prospective randomized study was performed with fresh whole blood (WB) obtained by intraoperative hemodilution (IH) and with platelet-rich plasma (PRP) obtained by perioperative apheresis from adult cardiac surgery patients. RESULTS: Seventy patients were randomly assigned to three arms: 24 to the PRP arm, 18 to the IH arm, and 28 to serve as controls. A mean of 924 +/- 130 mL of WB was collected from the IH group, and a mean of 650 +/- 124 mL of PRP was collected from the PRP group (mean, 1.42 +/- 0.74 x 10(11) platelets); these components were transfused after bypass. Preoperative measures were similar among groups. Intraoperatively, the groups did not differ in bypass time, estimated blood loss, number of transfusions, or proportion receiving transfusion(s). Postoperatively, control patients had more mediastinal drainage (736 mL vs. 476 mL [IH] and 463 mL [PRP]; p = 0.014), but there was no difference in the proportion of patients requiring red cell transfusion (p = 0.87), the hemoglobin at discharge (p = 0.20), or the length of hospitalization (p = 0.57). CONCLUSION: Although a hemostatic benefit manifested as reduced postoperative bleeding was observed, this study does not support the use of fresh blood components obtained by IH or PRP collection during low-risk cardiac surgery. Additional studies are needed to assess whether more aggressive component collection or the use of these techniques in high-risk cases may have a greater impact on clinical outcome variables, including transfusion.

Adult↗

PubMed1995

Quality of life in octogenarians after open heart surgery.

OBJECTIVES: To determine the quality of life in octogenarians after open heart surgery. BACKGROUND: Despite an increasing number of cardiac operations on octogenarians, the outcome as measured by functional status, independence of living, and psychological parameters of quality of life remain unproved. METHODS: Two groups of octogenarians (group 1, undergoing operation in 1986; group 2 in 1991) were reviewed retrospectively to determine operative mortality and functional results. RESULTS: Group 1 (n = 15, mean age of 83.2 years) and group 2 (n = 53, mean age 83.0 years) were studied. Operations included isolated coronary artery bypass grafting (group 1, 10; group 2, 29) and valve replacements +/- coronary artery bypass grafting +/- other procedures (group 1: 5; group 2, 24). Group 1 had 9% hospital mortality and 53% actuarial survival after a mean follow-up of 6.3 years. Group 2 had 17% hospital mortality and 72% actuarial survival after a mean follow-up of 1.5 years. At follow-up, significant improvements were observed in New York Heart Association (NYHA) angina class, congestive cardiac failure class, number of cardiovascular symptoms, and indices for satisfaction with overall life and general affect in both groups. Further, group 2 also showed significant improvements in independence of living, ease of life, and Karnofsky dependency category, but these improvements were less evident in group 1 after a longer period of follow-up. At follow-up, 75% of group 1 and 84% of group 2 octogenarians would definitely have made the same decision to undergo open heart surgery in retrospect. CONCLUSION: This study demonstrates improved quality of life after open heart surgery in octogenarians.

Activities of Daily Living↗

PubMed1994

Neutrophil adhesion and complement inhibition prolongs survival of cardiac xenografts in discordant species.

Hyperacute rejection results in rapid destruction of a discordant cardiac xenograft and is characterized by antibody deposition, complement activation, and platelet aggregation. The importance of neutrophils is unclear. Complement inhibition prolongs discordant cardiac xenograft survival. The purpose of this experiment was to determine the relative roles of complement and neutrophils. Selective inhibition of complement and neutrophil adhesion was used in a guinea pig-to-Lewis rat cardiac heterotopic xenotransplant model. NPC 15669 (N-[9H-(2,7-dimethylfluorenyl-9-methoxy)carbonyl]-L-leucine), a member of a new class of antiinflammatory agents termed leumedins, specifically prevents recruitment of neutrophils at inflammatory foci by inhibiting upregulation of the CD11b/CD18 adhesion molecule. Soluble complement receptor type 1 (sCR1, BRL 55730) is a potent inhibitor of the alternative and classical complement pathways. Group I (n = 13) received saline vehicle i.v. Group II (n = 15) was treated with NPC 15669 (10 mg/kg i.v. bolus) prior to reperfusion. Group III (n = 13) was treated with sCR1 (20 mg/kg i.v. bolus) prior to reperfusion. Group IV (n = 13) received both NPC 15669 and sCR1. Two xenografts were harvested at each interval time point (Groups I and II, 1, 2, 4, and 6 min; and Groups III and IV, 6, 15, 30, and 60 min). The remainder were followed to cessation of graft function. Graft survival was significantly increased in group IV and group III-375 +/- 13.4 min (mean +/- SD) and 112 +/- 29.4, respectively (P < .05), compared with 9.9 +/- 6.3 in group II and 8.7 +/- 4.9 in group I. Extreme interstitial hemorrhage and edema and contraction band injury were present in group I-III animals at end-stage, and neutrophil infiltration in group III. In group IV grafts, there was a decrease in these parameters despite the longer survival time, and at end-stage rejection the cellular infiltrate was primarily mononuclear. This study demonstrates that complement is an important mediator in early xenograft HYP injury. Combined treatment with NPC 15669 and sCR1 results in reduced histologic injury at all time points and longer graft survival than with sCR1 alone. These results suggest that neutrophil and complement activation play synergistic roles in the pathogenesis of xenograft hyperacute rejection. Neutrophil inhibition may prove to be an important component of multimodality therapy for hyperacute rejection, particularly in less-discordant transplants.

Animals↗

PubMed1994

Inhibition of neutrophil adhesion during cardiopulmonary bypass.

Blood contact with synthetic surfaces during cardiopulmonary bypass (CPB) causes a diffuse inflammatory reaction that includes neutrophil activation. The purpose of this study was to determine if inhibition of neutrophil adhesion with a new antiinflammatory agent NPC 15669 (N-(9H-(2,7-dimethylfluorenyl-9-methoxy)-carbonyl)-L-leucine) could reduce pulmonary injury in a porcine model of CPB. NPC 15669 blocks adherence of activated neutrophils by inhibiting upregulation of the Mac-1 (CD11b/CD18) adhesion molecule. Sixteen piglets underwent 2 hours of hypothermic CPB followed by 2 hours of observation; 8 received NPC 15669 (10 mg/kg intravenous bolus followed by 6 mg.kg-1.h-1 intravenous infusion) and 8 received equal volumes of vehicle. After 90 minutes of CPB, expression of neutrophil adhesion molecule subunit CD18 increased 118% in control piglets but only 36% in piglets treated with NPC 15669 (p < 0.01). Although neutropenia developed in all animals during CPB, lung tissue myeloperoxidase content was significantly lower in treated than in control animals 2 hours after CPB (94.9 +/- 10.4 versus 46.9 +/- 5.5 mumol.10 mg-1.min-1; p < 0.002). Free radical-mediated lipid peroxidation (quantitated by spectrophotometric assay of plasma conjugated dienes) was significantly reduced by treatment with NPC 15669 during and after CPB. Pulmonary function was better in NPC 15669-treated animals: 2 hours after CPB, pulmonary vascular resistance increased 477% in control piglets but only 140% in piglets receiving NPC 15669 (p < 0.03); arterial oxygen tension was significantly greater in piglets receiving NPC 15669 (428 +/- 33 mm Hg) than in controls (141 +/- 46; p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Complement and neutrophil activation during cardiopulmonary bypass: a study in the complement-deficient dog.

Cardiopulmonary bypass (CPB) is known to cause complement and neutrophil activation, but the relative importance and interaction of these components in CPB-induced inflammation is unknown. In this study, a strain of dogs genetically deficient in the third component of complement (C3) was used to determine the contribution of C3 to neutrophil activation and pulmonary injury after CPB. Eleven dogs (5 C3-deficient and 6 controls) underwent 150 minutes of hypothermic CPB (28 degrees C) followed by 2 hours of observation. Before CPB, C3 levels were normal in controls and less than 1% of normal in C3-deficient dogs. In control dogs, functional activity of C3 decreased to 53.2% of baseline after 1 hour of CPB and there was immunohistochemical evidence of C3 deposition in lung after CPB; C3-deficient dogs had no C3 deposition in lung. Although similar degrees of neutropenia occurred during CPB in the two groups, expression of neutrophil adhesion molecule subunit CD18 was significantly lower in C3-deficient dogs than controls after 1 hour of CPB (45.9 +/- 3.7 versus 82.9 +/- 10.0 mean fluorescence units; p < 0.02). Postbypass lung tissue myeloperoxidase content was also less in C3-deficient dogs (43.8 +/- 4.6 versus 71.1 +/- 8.6 mumol x 10 mg-1 x min-1; p < 0.03). Cardiopulmonary bypass-associated lung injury (assessed by alveolar-arterial oxygen gradient, pulmonary vascular resistance, percent lung water, and light and electron microscopic appearance) was similar between groups. These results demonstrate that (1) C3 is deposited on pulmonary vascular endothelium during CPB and (2) C3 mediates increased expression of neutrophil CD18 and neutrophil sequestration in lung after CPB.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗