Adrenaline improves regional cerebral blood flow, cerebral oxygenation and cerebral metabolism during CPR in a porcine cardiac arrest model using low-flow extracorporeal support.

BACKGROUND: The effects of adrenaline on cerebral blood vessels during cardiopulmonary resuscitation (CPR) are not well understood. We developed an extracorporeal CPR model that maintains constant low systemic blood flow while allowing adrenaline-associated effects on cerebral vasculature to be assessed at different mean arterial pressure (MAP) levels independently of the effects on systemic blood flow. METHODS: After eight minutes of cardiac arrest, low-flow extracorporeal life support (ECLS) (30 ml/kg/min) was started in fourteen pigs. After ten minutes, continuous adrenaline administration was started to achieve MAP values of 40 (n = 7) or 60 mmHg (n = 7). Measurements included intracranial pressure (ICP), cerebral perfusion pressure (CePP), laser-Doppler-derived regional cerebral blood flow (CBF), cerebral regional oxygen saturation (rSO2), brain tissue oxygen tension (PbtO2) and extracellular cerebral metabolites assessed by cerebral microdialysis. RESULTS: During ECLS without adrenaline, regional CBF increased by only 5% (25th to 75th percentile: -3 to 14; p = 0.2642) and PbtO2 by 6% (0-15; p = 0.0073) despite a significant increase in MAP to 28 mmHg (25-30; p < 0.0001) and CePP to 10 mmHg (8-13; p < 0.0001). Accordingly, cerebral microdialysis parameters showed a profound hypoxic-ischemic pattern. Adrenaline administration significantly improved regional CBF to 29 ± 14% (p = 0.0098) and 61 ± 25% (p < 0.001) and PbtO2 to 15 ± 11% and 130 ± 82% (both p < 0.001) of baseline in the MAP 40 mmHg and MAP 60 mmHg groups, respectively. Importantly, MAP of 60 mmHg was associated with metabolic improvement. CONCLUSION: This study shows that adrenaline administration during constant low systemic blood flow increases CePP, regional CBF, cerebral oxygenation and cerebral metabolism.

Effects of different adrenaline doses on cerebral oxygenation and cerebral metabolism during cardiopulmonary resuscitation in pigs.

BACKGROUND: The influence of adrenaline during cardiopulmonary resuscitation (CPR) on the neurological outcome of cardiac arrest survivors is unclear. As little is known about the pathophysiological effects of adrenaline on cerebral oxygen delivery and cerebral metabolism we investigated its effects on parameters of cerebral oxygenation and cerebral metabolism in a pig model of CPR. METHODS: Fourteen pigs were anesthetized, intubated and instrumented. After 5 min of cardiac arrest CPR was started and continued for 15 min. Animals were randomized to receive bolus injections of either 15 or 30 µg/kg adrenaline every 5 min after commencement of CPR. RESULTS: Measurements included mean arterial pressure (MAP), intracranial pressure (ICP), cerebral perfusion pressure (CPP), cerebral regional oxygen saturation (rSO2), brain tissue oxygen tension (PbtO2), arterial and cerebral venous blood gases and cerebral microdialysis parameters, e.g. lactate/pyruvate ratio. Adrenaline induced a significant increase in MAP and CPP in all pigs. However, increases in MAP and CPP were short-lasting and tended to decrease with repetitive bolus administration. There was no statistical difference in any parameter of cerebral oxygenation or metabolism between study groups. CONCLUSIONS: Both adrenaline doses resulted in short-lasting CPP peaks which did not translate into improved cerebral tissue oxygen tension and metabolism. Further studies are needed to determine whether other dosing regimens targeting a sustained increase in CPP, may lead to improved brain oxygenation and metabolism, thereby improving neurological outcome of cardiac arrest patients.

Effects of head-up vs. supine CPR on cerebral oxygenation and cerebral metabolism - a prospective, randomized porcine study.

BACKGROUND: Recent studies have shown that during cardiopulmonary resuscitation (CPR) head-up position (HUP) as compared to standard supine position (SUP) decreases intracranial pressure (ICP) and increases cerebral perfusion pressure (CPP). The impact of this manoeuvre on brain oxygenation and metabolism is not clear. We therefore investigated HUP as compared to SUP during basic life support (BLS) CPR for their effect on brain oxygenation and metabolism. METHODS: Twenty pigs were anaesthetized and instrumented. After 8 min of cardiac arrest (CA) pigs were randomized to either HUP or SUP and resuscitated mechanically for 20 min. Mean arterial pressure (MAP), ICP, CPP, cerebral regional oxygen saturation (rSO2) and brain tissue oxygen tension (PbtO2) were measured at baseline, after CA and every 5 min during CPR. Cerebral venous oxygen saturation (ScvO2) was measured at baseline, after CA and after 20 min of CPR. Cerebral microdialysis parameters, e.g. lactate/pyruvate ratio (L/P ratio) were taken at baseline and the end of the experiment. RESULTS: ICP was significantly lower in HUP compared to SUP animals after 5 min (18.0 ±â€¯4.5 vs. 24.1 ±â€¯5.2 mmHg; p = 0.033) and 20 min (12.0 ±â€¯3.4 vs. 17.8 ±â€¯4.3 mmHg; p = 0.023) of CPR. Accordingly, CPP was significantly higher in the HUP group after 5 min (11.2 ±â€¯9.5 vs. 1.0 ±â€¯9.2 mmHg; p = 0.045) and 20 min (3.4 ±â€¯6.4 vs. -3.8 ±â€¯2.8 mmHg; p = 0.023) of CPR. However, no difference was found in rSO2, PbtO2, ScvO2 and L/P ratio between groups after 20 min of CPR. CONCLUSION: In this animal model of BLS CPR, HUP as compared to SUP did not improve cerebral oxygenation or metabolism.

Anterior cingulate dopamine turnover and behavior change in Parkinson's disease.

Subtle cognitive and behavioral changes are common in early Parkinson's disease. The cause of these symptoms is probably multifactorial but may in part be related to extra-striatal dopamine levels. 6-[(18) F]-Fluoro-L-dopa (FDOPA) positron emission tomography has been widely used to quantify dopamine metabolism in the brain; the most frequently measured kinetic parameter is the tissue uptake rate constant, Ki. However, estimates of dopamine turnover, which also account for the small rate of FDOPA loss from areas of specific trapping, may be more sensitive than Ki for early disease-related changes in dopamine biosynthesis. The purpose of the present study was to compare effective distribution volume ratio (eDVR), a metric for dopamine turnover, to cognitive and behavioral measures in Parkinson's patients. We chose to focus the investigation on anterior cingulate cortex, which shows highest FDOPA uptake within frontal regions and has known roles in executive function. Fifteen non-demented early-stage PD patients were pretreated with carbidopa and tolcapone, a central catechol-O-methyl transferase (COMT) inhibitor, and then underwent extended imaging with FDOPA PET. Anterior cingulate eDVR was compared with composite scores for language, memory, and executive function measured by neuropsychological testing, and behavior change measured using two informant-based questionnaires, the Cambridge Behavioral Inventory and the Behavior Rating Inventory of Executive Function-Adult Version. Lower mean eDVR (thus higher dopamine turnover) in anterior cingulate cortex was related to lower (more impaired) behavior scores. We conclude that subtle changes in anterior cingulate dopamine metabolism may contribute to dysexecutive behaviors in Parkinson's disease.

A dual-tracer study of extrastriatal 6-[18F]fluoro-m-tyrosine and 6-[18F]-fluoro-L-dopa uptake in Parkinson's disease.

6-[(18)F]-Fluoro-L-dopa (FDOPA) has been widely used as a biomarker for catecholamine synthesis, storage, and metabolism--its intense uptake in the striatum, and fainter uptake in other brain regions, is correlated with the symptoms and pathophysiology of Parkinson's disease (PD). 6-[(18)F]fluoro-m-tyrosine (FMT), which also targets L-amino acid decarboxylase, has potential advantages over FDOPA as a radiotracer because it does not form catechol-O-methyltransferase (COMT) metabolites. The purpose of the present study was to compare the regional distribution of these radiotracers in the brains of PD patients. Fifteen Parkinson's patients were studied with FMT and FDOPA positron emission tomography (PET) as well as high-resolution structural magnetic resonance imaging (MRI). MRI's were automatically parcellated into neuroanatomical regions of interest (ROIs) in Freesurfer (http://surfer.nmr.mgh.harvard.edu); region-specific uptake rate constants (Kocc) were generated from coregistered PET using a Patlak graphical approach. The essential findings were as follows: (1) regional Kocc were highly correlated between the radiotracers and in agreement with a previous FDOPA studies that used different ROI selection techniques; (2) FMT Kocc were higher in extrastriatal regions of relatively large uptake such as amygdala, pallidum, brainstem, hippocampus, entorhinal cortex, and thalamus, whereas cortical Kocc were similar between radiotracers; (3) while subcortical uptake of both radiotracers was related to disease duration and severity, cortical uptake was not. These results suggest that FMT may have advantages for examining pathologic changes within allocortical loop structures, which may contribute to cognitive and emotional symptoms of PD.