Biomarkers of neuronal damage in saturation diving-a controlled observational study

PURPOSE: A prospective and controlled observational study was performed to determine if the central nervous system injury markers glial fibrillary acidic protein (GFAp), neurofilament light (NfL) and tau concentrations changed in response to a saturation dive. METHODS: The intervention group consisted of 14 submariners compressed to 401 kPa in a dry hyperbaric chamber. They remained pressurized for 36 h and were then decompressed over 70 h. A control group of 12 individuals was used. Blood samples were obtained from both groups before, during and after hyperbaric exposure, and from the intervention group after a further 25-26 h. RESULTS: There were no statistically significant changes in the concentrations of GFAp, NfL and tau in the intervention group. During hyperbaric exposure, GFAp decreased in the control group (mean/median - 15.1/ - 8.9 pg·mL-1, p < 0.01) and there was a significant difference in absolute change of GFAp and NfL between the groups (17.7 pg·mL-1, p = 0.02 and 2.34 pg·mL-1, p = 0.02, respectively). Albumin decreased in the control group (mean/median - 2.74 g/L/ - 0.95 g/L, p = 0.02), but there was no statistically significant difference in albumin levels between the groups. In the intervention group, haematocrit and mean haemoglobin values were slightly increased after hyperbaric exposure (mean/median 2.3%/1.5%, p = 0.02 and 4.9 g/L, p = 0.06, respectively). CONCLUSION: Hyperbaric exposure to 401 kPa for 36 h was not associated with significant increases in GFAp, NfL or tau concentrations. Albumin levels, changes in hydration or diurnal variation were unlikely to have confounded the results. Saturation exposure to 401 kPa seems to be a procedure not harmful to the central nervous system. TRIAL REGISTRATION: ClinicalTrials.gov NCT03192930

Protein tau concentration in blood increases after SCUBA diving: an observational study

PURPOSE: It is speculated that diving might be harmful to the nervous system. The aim of this study was to determine if established markers of neuronal injury were increased in the blood after diving. METHODS: Thirty-two divers performed two identical dives, 48 h apart, in a water-filled hyperbaric chamber pressurized to an equivalent of 42 m of sea water for 10 min. After one of the two dives, normobaric oxygen was breathed for 30 min, with air breathed after the other. Blood samples were obtained before and at 30-45 and 120 min after diving. Concentrations of glial fibrillary acidic, neurofilament light, and tau proteins were measured using single molecule array technology. Doppler ultrasound was used to detect venous gas emboli. RESULTS: Tau was significantly increased at 30-45 min after the second dive (p < 0.0098) and at 120 min after both dives (p < 0.0008/p < 0.0041). Comparison of matching samples showed that oxygen breathing after diving did not influence tau results. There was no correlation between tau concentrations and the presence of venous gas emboli. Glial fibrillary acidic protein was decreased 30-45 min after the first dive but at no other point. Neurofilament light concentrations did not change. CONCLUSIONS: Tau seems to be a promising marker of dive-related neuronal stress, which is independent of the presence of venous gas emboli. Future studies could validate these results and determine if there is a quantitative relationship between dive exposure and change in tau blood concentration

Cardiovascular function and tissue-type plasminogen activator kinetics during aortic cross-clamping or positive end-expiratory pressure ventilation. An experimental study in the pig

Background: Aortic cross-clamping (AXC) and declamping (DC) are associated with homeostatic alterations, some of which are among the determinantsfor perioperative outcome. Myocardial and thromboembolic complications are predominant causes of perioperative morbidity and mortality. Impairmentof the fibrinolytic system has been postulated as the cause of the hypercoagulable state related to major surgery. We aimed to analyze: thepharmacological modulation by isoflurane (ISO), sodium nitroprusside (SNP) and milrinone (MIL) of the cardiovascular responses to AXC; the impact ofan acutely lowered cardiac output on the AXC-induced hemodynamic response pattern; the dynamic regulation of the endothelial derived tissue-typeplasminogen activator (t-PA, the key enzyme for initiation of fibrinolysis); and the impact of AXC and positive end-expiratory pressure ventilation(PEEP) on endogenous fibrinolysis. Methods: In multiple-organ porcine models, that included an infra-renal aortic snare and a system for graded pericardial infusion, we measured cardiacoutput, coronary sinus (antegrade and retrograde thermodilution, respectively), hepatic arterial, renal arterial and portal venous blood flows (perivascularultrasound ). Arterio-venous concentration gradients of both total and active t-PA, and respective plasma flows were obtained simultaneously for thecoronary, pulmonary, splanchnic and hepatic vascular beds, thereby allowing determinations of regional net release or uptake rates of t-PA . For precisequantifications of t-PA, a porcine standard was developed for the employed enzyme-linked immunosorbent assay. Results: Increases in mean arterial pressure induced by AXC were not attenuated by either ISO, SNP or MIL, although the AXC-induced increase insystemic vascular resistance was attenuated by 1.4% ISO. During a moderate decrease in stroke volume (produced by pericardial infusion), no regionalvasoconstriction was observed in response to AXC, while a more pronounced decrease in stroke volume totally abolished all circulatory responses toAXC. Plasma concentrations of both total and active t-PA differed among vascular regions, with the highest level in portal venous and the lowest level inhepatic venous blood. Marked differences in regional net fluxes of t-PA were found, with a high basal net release across the splanchnic vasculature, and aprominent net uptake across the liver. Although AXC did not induce significant alterations in regional net fluxes of t-PA, following DC, an acuteprofibrinolytic response occurred across preportal organs. However, hepatic t-PA net uptake was sufficient to preclude preportal t-PA net release toinfluence systemic plasma levels. With PEEP, a rapid increase in preportal net release of t-PA was induced. Despite a pronounced decrease in total liverblood flow, a significant increase in hepatic net uptake of t-PA was induced during PEEP, and hepatic venous t-PA plasma concentrations were thus notaltered. Notwithstanding, PEEP was associated with increased systemic levels of t-PA. Conclusions: AXC-induced cardiovascular responses are open to modulation through different pharmacological actions. The prevailing cardiac outputis decisive for circulatory adaption during AXC. The dynamic regulation of regional t-PA fluxes is organ- specific. The acute AXC/DC sequence and PEEPare associated with a profibrinolytic response in the splanchnic vascular bed

Impaired myocardial t-PA release in patients with coronary artery disease

AIMS: Myocardial ischemia remains a significant perioperative complication in coronary artery disease (CAD) patients. We hypothesized that noxious stimuli during major surgery are associated with an acute release of tissue-type plasminogen activator (t-PA) into the coronary circulation, and that this response is reduced by CAD. METHODS AND RESULTS: Two patient groups, with (n=14) and without (n=8) CAD, were studied during the initial phase of heart surgery. After retrograde great cardiac vein catheterizations during closed-chest conditions, coronary arterial-venous concentration gradients of t-PA and plasminogen activator inhibitor type-1 (PAI-1) were measured together with coronary blood flow measurements, allowing derivation of coronary net release rates. Pre-surgery atrial pacing, performed to evaluate the influence of increases in heart rate (+ 40 beats/min) and coronary blood flow (+ 80 ml/min), did not significantly alter coronary net release of t-PA or PAI-1 in either patient group. Sternotomy induced a prominent increase in coronary net release of both total and active t-PA in the non-CAD group. This response was considerably reduced in the CAD group. CONCLUSIONS: This study provides the first analysis of coronary t-PA release during major surgery and demonstrates a deficient local endothelial t-PA release in patients with CAD. This suggests a reduced local fibrinolytic capacity in CAD patients, which may explain the increased risk for coronary thrombosis in this patient group.Osterlund, B Jern, S Jern, C Seeman-Lodding, H Ostman, M Johansson, G Biber, B Research Support, Non-U.S. Gov't England Acta anaesthesiologica Scandinavica Acta Anaesthesiol Scand. 2008 Nov;52(10):1375-84