Comparison of postoperative course of S100 protein and neuron-specific enolase in patients after implantation of axial and pulsatile flow LVADS.
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Biomedical subjects
Publications and source records attributed to C Harke.
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Neonates who undergo cardiac surgery of d-transposition of the great arteries by means of hypothermic cardiopulmonary bypass (CPB) represent a group at increased risk to develop brain injury and altered psychomotor development in early life. Measurement of protein S-100beta, an astrocytic calcium binding protein, in serum may provide information on transient astroglial cell activation and disintegration of the related blood-brain barrier due to oxidative stress during and after CPB. Conflicting results have been reported that concern the neuroprotective effect of the NO liberator sodium nitroprusside (SNP) in vitro. We evaluated the effect of continuous treatment with SNP on the serum kinetics of S-100beta in infants and children after corrective cardiac surgery. The data on 25 neonates treated intraoperatively and postoperatively and 28 without treatment were analyzed. SNP was infused (1-5 microg/kg body weight/minute depending on the haemodynamic status) after the induction of anesthesia, and during and after the termination of CPB for 2 days. Serum concentrations of S-100beta were analyzed by the use of a commercially available immunoluminometric kit (Byk-Sangtec, Dietzenbach, Germany). There were no significant differences in the bypass data between the SNP-treated and non-treated group. In comparison to the pre-bypass values, a similar increase in the concentration of protein S-100beta was found 2 hours after the termination of CPB in the SNP-treated and non-treated neonates, which decreased over the subsequent 48 postoperative hours. However, significantly lower post-bypass serum levels of S-100beta were found in the SNP-treated group after 24 hours (p = 0.0009) and 48 hours (p = 0.04) of treatment. In conclusion, the significant elevation of serum levels of protein S-100beta may indicate increased astroglial cell reactivity and increased passage into the blood stream. Longer-lasting treatment with NO liberator SNP seemed to decrease the release of S-100beta into the blood stream and may have delayed protection on the astroglial cells. The neurological significance of such an observation, however, should be evaluated in further follow-up studies, which need to include additional neurophysiological and neurodevelopmental tests.
Contact of blood with artificial surfaces activates pro-inflammatory responses and the complement cascade. This may have broad implications on the post implantation fate of patients needing mechanical circulatory support. Therefore, we investigated the course and prognostic value of complement factors C3a and C5a in 66 patients supported with pulsatile ventricular assist devices. All patients were in severe cardiogenic shock, i.e., catecholamine dependent and in the intensive care unit, before implementation of mechanical circulatory support. Isolated left ventricular support (Novacor [Oakland, CA] or Thermo Cardiosystems, Inc. [TCI; Woburn, MA]) was used in 28 patients, and biventricular support (Berlin Heart [Mediport, Berlin, Germany]) in 38 patients. Before initiation of mechanical circulatory support, no statistically significant differences in C3a or C5a between surviving and nonsurviving patients with left ventricular assist devices (LVADs) were found. Patients with biventricular assist devices (BVADs) had significantly higher C3a (804 +/- 364 ng/L) levels than patients with LVADs (536 +/- 204 ng/L, p = 0.02) before mechanical circulatory support. Only C5a, only in the BVAD group, was able to predict patients' post implantation course before implantation of a ventricular assist device (p = 0.02). Three weeks after initiation of mechanical circulatory support, complement factors remained increased in all groups. There was no difference, however, in complement activation between patients with LVADs and those with BVADs. Patients not reaching transplantation had significantly higher C3a levels at this point than those successfully supported (p = 0.007). The degree of complement activation mainly depends on the severity of cardiogenic shock before initiation of mechanical circulatory support, and not on the device used. Patients with extremely high levels of complement activation before implantation of the device could be saved with BVAD rather than LVAD support. Patients who continued to have highly elevated complement levels 3 weeks after initiation of mechanical circulatory support had unfavorable prognoses. Complement activation indicates the severity of cardiogenic shock before implementation of mechanical circulatory support and the degree of recovery from secondary organ dysfunction while on the device. It is fairly independent of the system used for mechanical circulatory support, and therefore can be applied to predict patients' post implantation course and outcome.
Thromboembolism is a major complication in patients with ventricular assist devices (VAD). Anticoagulation with heparin, coumarin, and anti-platelet agents, particularly the development of biocompatible surfaces such as inner pseudo-endothelial layers or a coating with heparin, are intended to reduce these complications. However, the administration of heparin can lead to heparin induced thrombocytopenia type II (HIT II). Predominantly heparin/platelet factor 4 (HPF4) antibodies are responsible for the development of HIT II. The goal of the present investigation was to assess the prevalence of these antibodies in patients with heparin coated and noncoated VADs. Fifty-five patients were enrolled in the investigation. A heparin coated system was implanted in 30 patients, and a noncoated system was implanted in 25 patients. Antibodies were evaluated before, on days 7 and 14, and 3 months after implantation. Testing was performed with the Heparin/Platelet factor 4 enzyme-linked immunosorbent assay (ELISA) (Stago, France). In 40 of the 55 patients, the formation of HPF4 antibodies was observed (73%). In 35 of these patients (88%), HPF4 antibodies were present before surgery. There were no differences between the groups. In 11 patients (equal from both groups), the antibodies disappeared after termination of systemic heparinization. We conclude that in a rather high percentage of patients with VADs HPF4 antibodies are found. This finding may be explained by the repetitive and prolonged exposure of these patients to heparin. Immobilized heparin, as presently used in the carmeda coating, seems not to influence the formation and persistence of HPF4 antibodies. Further studies will have to prove whether HPF4 antibodies contribute to thromboembolic complications in these patients.