Cerebral oxygenation and autoregulation during rewarming on cardiopulmonary bypass.

BACKGROUND: Rewarming on cardiopulmonary bypass (CPB) is associated with increased metabolic demands; however, it remains unclear whether cerebral autoregulation is affected during this phase. This RCT aims to describe the effects of 20% supranormal, compared to normal CPB flow, on monitoring signs of inadequate perfusion, oxygenation, and disturbed cerebral autoregulation, during the rewarming phase of CPB. METHOD: Thirty two patients scheduled for coronary artery bypass grafting were allocated to a Control group (n = 16) receiving a CPB pump flow corresponding to preoperatively measured cardiac output, and an Intervention group (n = 16) receiving the corresponding CPB pump flow increased by 20% during rewarming. Cerebral Oximetry Index (COx) was calculated with the aid of Near Infrared Spectroscopy. RESULTS: Twenty five patients were included in the data. Results show a median COx value of 0.0 (IQR -0.33-0.5) (Control) and 0.0 (IQR -0.15-0.25) (Intervention), respectively; p = .85 with individual variations within groups. The median cerebral perfusion pressure (CPP) was 55 (52-58) (Control) and 61 (54-66) mmHg (Intervention); p = .08. No significant difference in rSO2 values was observed between the groups (58.5% (50-61) versus 64% (58-68); p = .06). CONCLUSION: The present study showed no difference between increased and normal CPB pump flow with respect to cerebral autoregulation during rewarming. Large variations in cerebral autoregulation were seen at individual level.

Influence of blood/tissue differences in contrast agent relaxivity on tracer-based MR perfusion measurements.

PURPOSE: Perfusion assessment by monitoring the transport of a tracer bolus depends critically on conversion of signal intensity into tracer concentration. Two main assumptions are generally applied for this conversion; (1) contrast agent relaxivity is identical in blood and tissue, (2) change in signal intensity depends only on the primary relaxation effect. The purpose of the study was to assess the validity and influence of these assumptions. MATERIALS AND METHODS: Blood and cerebral tissue relaxivities r1, r2, and r2* for gadodiamide were measured in four pigs at 1.5 T. Gadolinium concentration was determined by inductively coupled plasma atomic emission spectroscopy. Influence of the relaxivities, secondary relaxation effects and choice of singular value decomposition (SVD) regularization threshold was studied by simulations. RESULTS: In vivo relaxivities relative to blood concentration [in s(-1) mM(-1) for blood, gray matter (GM), white matter (WM)] were for r1 (2.614 ± 1.061, 0.010 ± 0.001, 0.004 ± 0.002), r2 (5.088 ± 0.952, 0.091 ± 0.008, 0.059 ± 0.014), and r2* (13.292 ± 3.928, 1.696 ± 0.157, 0.910 ± 0.139). Although substantial, by a nonparametric test for paired samples, the differences were not statistically significant. The GM to WM blood volume ratio was estimated to 2.6 ± 0.9 by r1, 1.6 ± 0.3 by r2, and 1.9 ± 0.2 by r2*. Secondary relaxation was found to reduce the tissue blood flow, as did the SVD regularization threshold. CONCLUSION: Contrast agent relaxivity is not identical in blood and tissue leading to substantial errors. Further errors are introduced by secondary relaxation effects and the SVD regularization.

Mechanical Reperfusion Following Prolonged Global Cerebral Ischemia Attenuates Brain Injury.

Previous experiments demonstrated improved outcome following prolonged cerebral ischemia given controlled brain reperfusion using extracorporeal circulation. The current study further investigates this. Young adult pigs were exposed to 30 min of global normothermic cerebral ischemia, achieved through intrathoracic clamping of cerebral arteries, followed by 20 min of isolated mechanical brain reperfusion. Leukocyte-filtered blood was delivered by a roller-pump at fixed pressure and flow. One experimental group additionally had a custom-made buffer solution delivered at 1:8 ratio with the blood. Hemodynamics including intracranial pressure were monitored. Blood gases were from peripheral arteries and the sagittal sinus, and intraparenchymal brain microdialysis was performed. The brains were examined by a neuropathologist. The group with the added buffer showed lower intracranial pressure as well as decreased intraparenchymal glycerol and less signs of excitotoxicity and ischemia, although histology revealed similar degrees of injury. A customized mechanical reperfusion improves multiple parameters after prolonged normothermic global cerebral ischemia. Graphical Abstract The current study investigates if it possible to improve neurological outcomes following prolonged global brain ischemia. The results indicate that a customized mechanical reperfusion protocol can attenuate neurological injury.

Mechanical reperfusion with leucocyte-filtered blood does not prevent injury following global cerebral ischaemia.

Objectives: Prolonged global cerebral ischaemia leads to irreversible injury, often with lethal outcome. Brain injuries are partly caused by the uncontrolled reperfusion that occurs once the circulation is re-established. Recent animal experiments suggest that controlled reperfusion following lengthy ischaemia might prevent severe brain injury. This study aimed at further exploring cerebral alterations and outcome following prolonged global cerebral ischaemia and mechanically manipulated reperfusion. Methods: Three groups of pigs were included; one sham operated ( n = 3) and two that underwent 30-min global cerebral ischaemia. All vessels that supply the brain were isolated intrathoracically, after which they were occluded for 30 min in the ischaemic groups. In one of the ischaemic groups uncontrolled reperfusion was applied (URep, n = 6), i.e. normal circulation was restored 30 min after arrested cerebral circulation. The second ischaemic group received mechanical reperfusion (MRep, n = 6) with leucocyte-filtered blood at constant flow and pressure for 20 min using extracorporeal circulation following the 30-min ischaemia, after which normal blood flow resumed. All animals were monitored for 3 h after start of uncontrolled reperfusion. Haemodynamic parameters, arterial and sagittal sinus blood gases, cerebral oxygen extraction rates and intraparenchymal biomarkers using microdialysis were measured. Brain histology was performed post-mortem. Results: Global brain ischaemia led to the same extent of severe morphological changes at the level of light microscopy in the two ischaemic experimental groups, regardless of reperfusion protocol. Furthermore, no significant differences were found between the URep and MRep groups regarding cerebral blood gases or microdialysis biomarkers. Conclusions: Mechanical reperfusion following the current protocol does not modify brain alterations caused by 30 min of arrested cerebral circulation.

Blood Flow Quantitation by Positron Emission Tomography During Selective Antegrade Cerebral Perfusion.

BACKGROUND: Perfusion strategies during aortic surgery usually comprise hypothermic circulatory arrest (HCA), often combined with selective antegrade cerebral perfusion (SACP) or retrograde cerebral perfusion. Cerebral blood flow (CBF) is a fundamental parameter for which the optimal level has not been clearly defined. We sought to determine the CBF at a pump flow level of 6 mL/kg/min, previously shown likely to provide adequate SACP at 20°C in pigs. METHODS: Repeated positron emission tomography (PET) scans were used to quantify the CBF and glucose metabolism throughout HCA and SACP including cooling and rewarming. Eight pigs on cardiopulmonary bypass were assigned to either HCA alone (n = 4) or HCA+SACP (n = 4). The CBF was measured by repeated [15O]water PET scans from baseline to rewarming. The cerebral glucose metabolism was examined by [18F]fluorodeoxyglucose PET scans after rewarming to 37°C. RESULTS: Cooling to 20°C decreased the cortical CBF from 0.31 ± 0.06 at baseline to 0.10 ± 0.02 mL/cm3/min (p = 0.008). The CBF was maintained stable by SACP of 6 mL/kg/min during 45 minutes. After rewarming to 37°C, the mean CBF increased to 0.24 ± 0.07 mL/cm3/min, without significant differences between the groups at any time-point exclusive of the HCA period. The net cortical uptake (Ki) of [18F]fluorodeoxyglucose after rewarming showed no significant difference between the groups. CONCLUSIONS: Cooling autoregulated the CBF to 0.10 mL/cm3/min, and 45 minutes of SACP at 6 mL/kg/min maintained the CBF in the present model. Cerebral glucose metabolism after rewarming was similar in the study groups.

Experimental treatment of superior venous congestion during cardiopulmonary bypass.

OBJECTIVES: Superior venous outflow obstruction affects cerebral perfusion negatively by reducing cerebral perfusion pressure (CPP). We present a randomized study designed to compare two alternative strategies to preserve the CPP during superior vena cava (SVC) congestion and cardiopulmonary bypass (CPB). METHODS: Fourteen pigs on bi-caval CPB were subjected to 75% occlusion of the SVC flow. CPP was restored either by vasopressor treatment (VP, n = 7) or by partial relief (PR) of the congestion (n = 7). The cerebral effects of the interventions were studied for 60 min with intracranial pressure (ICP) monitoring, cerebral blood flow measurement, the near-infrared light spectroscopy tissue oxygen saturation index (StO2), arterial and venous blood gas analyses and serial measurements of the glial cell damage marker protein S100ß. RESULTS: Both strategies restored the CPP to baseline levels and no signs of severe ischaemia were observed. In the PR group, the venous and ICPs were normalized in response to the intervention, while in the VP group those parameters remained elevated throughout the experiment. The haemoglobin oxygen saturation in the sagittal sinus (SsagO2) was increased by both VP and PR, while significant improvement in the StO2 was observed only in the PR group. The S100ß concentrations were similar in the two groups. CONCLUSIONS: Experimental SVC obstruction during CPB may reduce the CPP, resulting in impaired cerebral perfusion. Both vasopressor treatment and improved venous drainage can, in the short term, individually restore the CPP during these circumstances.

Minimal safe arterial blood flow during selective antegrade cerebral perfusion at 20° centigrade.

BACKGROUND: Selective antegrade cerebral perfusion (SACP) enables surgery on the aortic arch, where cerebral ischemia may cause neurologic sequels. This study aims to identify the minimum arterial flow level to maintain adequate cerebral perfusion during SACP in deep hypothermia in the pig. METHODS: Two groups of pigs were subjected to SACP at 20(°)C α-stat. In group 1 (n = 6), flow was stepwise adjusted from 8-6-4-2-8 mL · kg(-1) · min(-1) and in group 2 (n = 5), flow was kept constant at 6 mL · kg(-1) · min(-1). Magnetic resonance imaging and spectroscopy were performed at each flow level together with hemodynamic monitoring and blood gas analysis. The biochemical marker of cerebral damage protein S100ß was measured in peripheral blood. RESULTS: Decreased mixed venous oxygen saturation and increased lactate in magnetic resonance spectroscopy was seen as a sign of anaerobic metabolism below 6 mL · kg(-1) · min(-1). No ischemic damage was seen on diffusion-weighted imaging, but the concentrations of S100ß were significantly elevated in group 1 compared with group 2 at the end of the experiment (p < 0.05). Perfusion-weighted imaging showed coherence between flow setting and cerebral perfusion, increase of blood volume across time, and regional differences in perfusion during SACP. CONCLUSIONS: The findings suggest an ischemic threshold close to 6 mL · kg(-1) · min(-1) in the present model. Regional differences in perfusion during SACP may be of pathogenic importance to focal cerebral ischemia.

Venous obstruction and cerebral perfusion during experimental cardiopulmonary bypass.

To investigate the effects on cerebral perfusion by experimental venous congestion of the superior vena cava (SVC) during bicaval cardiopulmonary bypass (CPB) at 34 °C, pigs were subjected to SVC obstruction at levels of 75%, 50%, 25% and 0% of baseline SVC flow at two arterial flow levels (low, LQ, high, HQ). The cerebral perfusion was examined with near-infrared spectroscopy (NIRS), cerebral microdialysis and blood gas analysis. SVC obstruction caused significant decreases in the NIRS tissue oxygenation index (TOI) and in SVC oxygen saturations (P<0.05, both groups), while the mixed venous saturation was decreased only in the LQ group. Sagittal sinus venous saturations were measured in the HQ group and found significantly reduced in response to venous congestion (P<0.05). No microdialysis changes were seen at the group level, however, individual ischemic patterns in terms of concomitant venous desaturation, decreased TOI and increased lactate/pyruvate occurred in both groups. The total venous drainage remained stabile throughout the experiment, indicating increased flow in the inferior vena cava cannula. The results indicate that SVC congestion may impair cerebral perfusion especially in the case of compromised arterial flow during CPB. Reduced SVC cannula flow may pass undetected during bicaval CPB, if SVC flow is not specifically monitored.