Cardiopulmonary bypass affects cognitive brain function after coronary artery bypass grafting.

BACKGROUND: The causes for cognitive impairment after coronary artery bypass grafting (CABG) have long been a topic for debate. METHODS: We prospectively followed 308 consecutive, unselected survivors of CABG at our institution. In addition to determination of clinical measurements, cognitive brain function was measured objectively by P300 auditory-evoked potentials before CABG, at 7-day and at 4-month follow-up. Standard psychometric tests (Trail Making Test A, Mini Mental State Examination) were also performed. RESULTS: At 7-day follow-up cognitive P300 auditory-evoked potentials were significantly impaired compared with preoperative levels (peak latencies: 376 +/- 40 ms versus 366 +/- 37 ms, p = 0.0001). P300 measurements were almost normalized at 4-month follow-up (peak latencies: 369 +/- 33 ms, p = NS versus preoperative). Standard psychometric tests failed to detect this subclinical cognitive impairment. Multiple regression analysis revealed that use of cardiopulmonary bypass was the only independent predictor of impaired cognitive brain function at 7-day (p < 0.0001) and 4-month follow-up (p = 0.0008). The presence of diabetes mellitus (p = 0.0135) or concomitant repair of significant carotid artery stenosis (p = 0.0049) was predictive of late improvement of cognitive brain function at 4-month follow-up. CONCLUSIONS: Objective cognitive P300 auditory-evoked potential measurements demonstrate that the use of cardiopulmonary bypass is the only predictor of short- and long-term cognitive brain dysfunction after CABG. Interestingly, the presence of diabetes mellitus and concomitant repair of a significant carotid artery stenosis were predictive for long-term cognitive benefit.

Glutaraldehyde detoxification of aortic wall tissue: a promising perspective for emerging bioprosthetic valve concepts.

BACKGROUND AND AIMS OF THE STUDY: Due to its superb crosslinking activity, glutaraldehyde (GA) is still the most widely used fixative for bioprosthetic heart valves. At the same time, however, GA is also believed to be partly responsible for tissue calcification and the lack of surface re-endothelialization, both of which may contribute to valve degeneration. Although excess GA has previously been extracted from thin leaflet tissue, this treatment proved insufficient for the detoxification of thick aortic wall tissue of stentless valves or root prostheses. METHODS: In order to establish a detoxification procedure which thoroughly extracts biologically active GA from aortic wall tissue, we used a highly sensitive bioassay where endothelial cells were seeded onto glutaraldehyde-fixed aortic wall discs following various detoxification procedures. Absolute cell numbers and morphologic shape were correlated with shrinkage temperature and shrinkage extent of the tissue to determine the potential of the treatments to reverse crosslinks. To optimize treatment conditions, pH (3.2 versus 4.5), temperature (22 degrees C versus 37 degrees C) and incubation time (48 h versus one week) were varied. In order to identify an optimal detoxification agent, 12 different amino-reagents from four chemical groups were compared: low pKa aromatic amines, amino acids, low pKa N-heterocyclic compounds and amino sugars. RESULTS: Amino-reagent treatment required warm temperature (37 degrees C), prolonged reaction time (one week) and a pH of 4.5 to achieve long-term cell growth on glutaraldehyde-fixed aortic wall. All 12 amino-reagents were able to detoxify aortic tissue satisfactorily; and all mildly reversed crosslinks, although there were differences between candidates. When summarized data were ranked correlating cell growth and quality with shrinkage temperature and shrinkage extent, seven reagents had a rank sum above the overall mean value, and five below with statistically significant differences between candidates. The additional stabilization of the detoxification reaction through borohydride-reduction had no further effect on tissue biocompatibility and crosslinks. CONCLUSIONS: Efficient detoxification of thick aortic wall tissue is possible if a one-week incubation in an acetic acid buffer-based amino-reagent is carried out at 37 degrees C.

Alpha-Gal on bioprostheses: xenograft immune response in cardiac surgery.

BACKGROUND: The alpha-Gal (Galalpha1,3-Galbeta1-4GlcNAc-R) epitope is the major xenoantigen causing hyperacute rejection of pig organs transplanted into primates. Porcine bioprostheses are utilized in cardiac surgery. However, premature degeneration of bioprostheses has limited utilization in younger patients and the immune response remains elusive. We sought to investigate whether a specific alpha-Gal immune response may play a role in this clinical scenario. MATERIALS AND METHODS: We investigated the presence of alpha-Gal-epitope on native and fixed porcine valves by means of confocal laser scanning microscope (CLSM). ELISA was utilized to evidence whether implantation of bioprostheses elicits augmentation of pre-existing cytotoxic anti alpha-Gal IgM antibodies within 10 days of surgery. Patients who underwent coronary artery bypass grafting (CABG) or mechanical valve replacement served as controls (each group, n = 12). To corroborate the clinical relevance of the alpha-Gal immune response in vivo, we studied serum obtained before and after implantation of bioprostheses and its potency to lyse porcine alpha-Gal-bearing PK15 cells. RESULTS: We found the immunogenic alpha-Gal-epitope on fibrocytes interspersed in the connective tissue of porcine valves as determined by vimentin/IB4 lectin binding. Moreover, patients who were provided with a bioprostheses had developed a significant increase of naturally occurring cytotoxic IgM antibodies directed towards alpha-Gal after surgical intervention as compared with control patients (P < 0.0001, respectively). Sera obtained from the patients after the implantation of bioprostheses demonstrated an increased cytotoxicity against alpha-Gal-bearing PK-15 cells as compared with preoperative sera (P < 0.001). The specificity of the cytotoxic effects was proven as soluble Galalpha1-3Galbeta1-4GlcNAc markedly inhibited cell death of alpha-Gal-bearing PK15 cells (P < 0.001). CONCLUSION: Our data suggest that implantation of bioprostheses in cardiac surgery induces a xenograft-specific immune response. Procedures diminishing the presence of alpha-Gal on bioprostheses, such as utilization of genetically manipulated alpha-Gal-deficient xenograft or pretreatment with alpha-Galactosidase, might diminuate the immune response against bioprostheses and extend durability.

Redo surgery for carotid artery stenosis: when and how?

PURPOSE: We analyzed operations performed at our institution retrospectively for recurrent carotid artery stenosis to assess the indication for surgery. We also assessed the techniques used for these operations. PATIENTS AND METHODS: From January 1992 to December 1998 1210 carotid endarterectomies were performed. Forty two (3.4%) of these were for recurrent stenosis. A new vein patch was implanted in 27 cases, PTFE patches were used in nine cases. In six cases an interposition with the great saphenous vein was performed. RESULTS: The mean interval between primary and secondary procedure was 60. 2months (3months to 23yr). Twenty five of our 41 patients had had ipsilateral neurologic symptoms before redo surgery, the remainder were free of symptoms. The grade of stenosis was over 90% in 22 cases, between 75 and 90% in 11 cases and below 75% in nine cases, two cases had aneurysmatic lesions. None of the patients died in the 30day observation period. One patient had a stroke with a permanent neurological deficit. In two cases postoperative bleeding occurred requiring reexploration. Two patients developed hypoglossal neurapraxia and in four patients the recurrent laryngeal nerve was injured. One patient had an apneic episode in the recovery room. CONCLUSION: The reported incidence of recurrent carotid artery stenosis surgery ranges from 3 to 36% and our incidence is at the lower end of this range. The surgical results of reoperating are acceptable with a low incidence of complications.

Predictors of perioperative mortality after coronary artery bypass grafting in the elderly.

BACKGROUND: Coronary artery bypass grafting (CABG) is associated with higher operative risk in the elderly compared to younger patients. The aim of this study was to evaluate risk factors for perioperative mortality after CABG in the elderly. METHODS: We investigated 325 consecutive patients aged 75 or over undergoing isolated CABG at our institution. We analyzed the patients' characteristics and perioperative outcome. Patients were divided into survivors and non-survivors; risk factors and complications were compared. Based on this, we performed a multivariate logistic regression analysis to determine independent risk factors for perioperative mortality. RESULTS: Non-survivors of CABG more often suffered from concomitant extracardiac atherosclerosis (non-survivors, 62.2 %; survivors, 40.6 %; p = 0.013) as well as from renal insufficiency preoperatively (non-survivors, 35.1 %; survivors 8.0 %; p < 0.0001). A trend towards higher incidences of impaired left ventricular function (non-survivors, 37.8 %; survivors, 29.9 %; p = 0.105) and a history of recent myocardial infarction (non-survivors, 29.7 %; survivors, 17.0 %; p = 0.061) were found in non-survivors compared to survivors. Furthermore, non-survivors more often underwent CABG with cardiopulmonary bypass (CPB non-survivors, 96.1 %; survivors 70.6 %; p = 0.0005). Multivariate logistic regression analysis revealed that preoperatively impaired renal function (OR: 2.857, p < 0.0001), use of CPB (OR: 5.952, p = 0.0175), extracardiac atherosclerosis (OR: 1.581, p = 0.0228), and recent myocardial infarction (OR: 1.574, p = 0.0405) were independent risk factors for perioperative mortality. Comparison of patients undergoing CABG with or without CPB reveals that patients operated without CPB had a higher preoperative risk than patients undergoing CABG with CPB. CONCLUSION: These results show that besides impaired renal function, extracardiac atherosclerosis, and history of recent myocardial infarction, the use of CPB is a major risk factor for CABG in the elderly. Perioperative mortality and morbidity can be significantly reduced if CPB is avoided.

It is possible to omit postoperative irradiation in a highly selected group of elderly breast cancer patients.

The purpose of this study was the evaluation of the necessity of routinely applied postoperative radiotherapy in a highly selected patient-group after breast conserving surgery. Between 1983 and May 1994, 356 women over 60 years of age with Stage I or II breast cancer were treated by quadrantectomy and axillary dissection followed by either adjuvant irradiation or no radiotherapy. We have analysed our data retrospectively to investigate whether irradiation has any benefit in elderly patients with respect to locoregional recurrence rates. After a median follow-up of 60 months the multivariate model revealed lymph node status (p = 0.002) as highly significant with regard to local recurrence free survival. We were not able to identify a positive effect of adjuvant irradiation in patients with negative lymph nodes and positive receptor status: both patient groups with or without irradiation had similar locoregional recurrence rates of 3%. In a subgroup of patients who were lymph node negative, receptor positive, and received adjuvant tamoxifen therapy, the local recurrence rates were as low as 2% in both groups. Concerning these results it may be possible to avoid the morbidity and potential psychological side effects of radiotherapy in breast cancer patients over 60 years of age treated by breast conserving surgery (T1, N0, positive hormone receptor, adjuvant tamoxifen) without increasing risk of locoregional recurrence. These data have to be confirmed in a prospectively randomized fashion.