Changes in cerebral blood flow and oxygen extraction during post-resuscitation syndrome

INTRODUCTION: Most survivors of out-of-hospital cardiac arrest (OHCA) will die subsequently from post-anoxic encephalopathy. In animals, the severity of brain damage is mainly influenced by the duration of cardiac arrest and also by the cerebral blood flow (CBF) and oxygen extraction (CEO2) abnormalities observed during the post-resuscitation period. The aim of our study was to describe CBF and CEO2 modifications during the first 72 h in OHCA patients treated by induced mild hypothermia. METHODS: Consecutive OHCA patients were studied every 12 h over 72 h. Diastolic flow velocities (dFV), mean flow velocities (mFV) and pulsatility index (PI) were assessed by transcranial doppler (TCD) as an estimate of CBF changes. Simultaneous measurements of CEO2 were obtained using retrograde jugular catheterisation. RESULTS: Eighteen patients (61 [47-74] years) were studied (12 non-survivors and 6 survivors). At admission, mFV values were low (27.3 [21.5-33.6]cm/s) but reached normal values after 72 h (50.5 [36.7-58.1]cm/s). Initial PI values were high (1.6 [1.3-1.9]) but reached normal values after 72 h (1.04 [0.82-1.2]). No differences were found between survivors and non-survivors regarding these CBF estimates. CEO2 values were quite normal at admission (20.4 [11-27%]) but decreased over time in non-survivors until H72 (25.8% [19.3-31.1] versus 5.7% [5.1-11.5], p=0.02). CONCLUSION: Cerebral haemodynamic and oxygenation values are altered considerably but evolve during the first 72 h following resuscitation after cardiac arrest. In particular, these changes may lead to a mismatch between CBF and CEO2 leading to a "luxurous perfusion" in non-survivors.     

Quantification of pain-induced changes in cerebral blood flow by perfusion MRI

The purpose of this study was to assess if the functional activation caused by painful stimuli could be detected with arterial spin labeling (ASL), which is a non-invasive magnetic resonance imaging (MRI) technique for measuring cerebral blood flow (CBF). Because ASL directly measures blood flow, it is well suited to pain conditions that are difficult to assess with current functional MRI, such as chronic pain. However, the use of ASL in neuroimaging has been hampered by its low sensitivity. Recent improvements in MRI technology, namely increased magnetic field strengths and phased array receiver coils, should enable ASL to measure the small changes in CBF associated with pain. In this study, healthy volunteers underwent two ASL imaging sessions, during which a painful thermal stimulus was applied to the left hand. The results demonstrated that the ASL technique measured changes in regional CBF in brain regions that have been previously identified with pain perception. These included bilateral CBF changes in the insula, secondary somatosensory, and cingulate cortices, as well as the supplementary motor area (SMA). Also observed were contralateral primary somatosensory and ipsilateral thalamic CBF changes. The average change in CBF for all regions of interest was 3.68 ml/100 g/min, ranging from 2.97 ml/100 g/min in ipsilateral thalamus to 4.91 ml/100 g/min in contralateral insula. The average resting global CBF was 54 ± 9.7 ml/100 g/min, and there was no change in global CBF due to the noxious thermal stimulus.     

Inner retinal metabolic rate of oxygen by oxygen tension and blood flow imaging in rat

The metabolic function of inner retinal cells relies on the availability of nutrients and oxygen that are supplied by the retinal circulation. Assessment of retinal tissue vitality and function requires knowledge of both the rate of oxygen delivery and consumption. The purpose of the current study is to report a novel technique for assessment of the inner retinal metabolic rate of oxygen (MO(2)) by combined measurements of retinal blood flow and vascular oxygen tension (PO(2)) in rat. The application of this technology has the potential to broaden knowledge of retinal oxygen dynamics and advance understanding of disease pathophysiology.     

Neural mechanism underlying impaired visual judgement in the dysmetabolic brain: an fMRI study

An altered brain metabolism in the parietal and prefrontal regions of the cerebral cortex as well as cognitive alterations have been found in patients suffering from hepatic encephalopathy. The neural mechanisms underlying these metabolically induced cognitive alterations, however, are not known. Since patients with liver cirrhosis without clinically overt encephalopathy already show an impaired performance in a flicker light test, the aim of this study was to analyze the normal and pathologically impaired neural mechanisms of these patients using functional magnetic resonance imaging (fMRI). Nine subjects at the early stage of encephalopathy [nonmanifest hepatic encephalopathy (nmHE)] and ten controls underwent scanning, while they indicated the apparent transition from a steady light to the onset of a flicker light, that is, the critical flicker frequency (CFF). Judgement-related blood oxygenation level-dependent (BOLD) activation was decreased in nmHE compared to controls in the right inferior parietal cortex (IPL). Furthermore, the analysis of psychophysiologic interaction suggests impaired neural interaction in patients with nmHE, especially between the IPL and the parietooccipital cortex (Poc), the intraparietal sulcus, the anterior cingulate cortex (ACC), the right prefrontal cortex (PFC), the medial temporal lobe, and the extrastriate cortex V5. In contrast, nonmanifest patients revealed an enhanced coupling between IPL and the postcentral cortex. Our findings provide evidence of an early-impaired and compensatory neural mechanism during visual judgement already in the earliest stages of hepatic encephalopathy and suggest an aberrant coupling between cerebral regions in the dysmetabolic brain.     

脑血流自动调节功能与最佳脑灌注压

正常人脑的血流量占全身的15％～20％,消耗25％的氧.而脑组织自身无能量储备,需要稳定且持续的脑血流供应,维持结构和功能.脑血管本身具有自动调节功能(cerebral auto regulation,CAR),并通过复杂的代谢性、化学性、神经源性及血管压力系统自身进行调节,以保证稳定的脑血流量[1].当脑外伤(traumatic brain injury,TBI)或卒中等病理状态下,脑血管自动调节功能的完整性受到影响,导致脑缺血或过度充血.损害性脑灌注伴随的细胞氧供不足和代谢障碍,是导致中枢神经疾病恶化的重要病理生理因素[2].因此脑外伤及卒中后,予以严密神经监测及治疗,防止继发性缺血性损害.     

Effects of hyperventilation, hypothermia, and altered blood viscosity on cerebral blood flow, cross-brain oxygen extraction, and cerebral metabolic rate for oxygen in cats

Therapies including hyperventilation (HV) and hypothermia (HT) are currently simultaneously used in brain-injured children at risk for cerebral swelling to reduce cerebral blood flow (CBF) and alter cerebral metabolic rate for oxygen (CMRO2). Since HV and HT may contribute to significant patient morbidity, we evaluated the effects of these treatments in combination on CBF, CMRO2, and cross-brain oxygen extraction (CBO2) using the Kety-Schmidt technique before controlled bleeding to alter blood viscosity in 20 lightly anesthetized, paralyzed cats, and after bleeding in another 17 cats. The degree of HV (PaCO2 24 to 26 torr) and HT (32 degrees and 30 degrees C) used were representative of that employed in pediatric neurointensive care. HV at normothermia resulted in a significant decline in CBF (P less than .05) and an unchanged CMRO2. HV and HT together to 32 degrees C resulted in a further significant fall in CBF and CMRO2 (p less than .05), but an unchanged CBO2. Further cooling of the animal to 30 degrees C during HV, both before and after controlled bleeding, resulted in no further significant fall in CBF, CBO2, or CMRO2. This relationship was found despite a significant fall in Hgb (p less than .001), suggesting that blood viscosity did not significantly influence CBF at this temperature. Our data suggest that HT to 32 degrees C during HV may have therapeutic benefit by decreasing CBF and CMRO2, but further cooling to 30 degrees C may not result in further cerebral protective effects.     

A study on the effects of endogenous nitric oxide on coronary blood flow, myocardial oxygen extraction and cardiac contractility

The purpose of the present study was to clarify how endogenous nitric oxide (NO) affects cardiac contractility and myocardial oxygen consumption (MVO2) in vivo. alpha-Chloralose-anesthetized dogs (n = 18) were instrumented to perform continuous and simultaneous measurements of coronary blood flow (CBF), anterior interventricular vein oxygen saturation (with the use of a fiberoptic catheter), aortic pressure, left ventricular pressure, and left ventricular volume. CBF, myocardial oxygen extraction (O2-extract), MVO2, the relationship between CBF and O2-extract during direct vasodilation induced by intracoronary papaverine (0.1, 0.2, 0.4 mg/kg), and cardiac contractility (Emax) were examined at control, after intracoronary infusion of NG-monomethyl-L-arginine (L-NMMA, 2 mg/kg) and after antagonization of NO by L-arginine (20 mg/kg). L-NMMA decreased CBF from 62.0 +/- 1.7 to 59.7 +/- 2.4 (mL/min/100 g, P < 0.05) and increased O2-extract from 68.2 +/- 1.7 to 79.0 +/- 1.7% (P < 0.05). Emax was increased after L-NMMA from 3.2 +/- 0.2 to 3.7 +/- 0.1 (mmHg/mL/100 g, P < 0.05). These effects of L-NMMA were antagonized by L-arginine (P < 0.05 vs. after L-NMMA, P = NS vs. before L-NMMA). L-NMMA shifted CBF and O2-extract relationship determined by papaverine injection upward and L-arginine antagonized it to its baseline level. Endogenous NO reduces cardiac contractility and decreases MVO2, while increasing CBF.     

Circulatory risk in the transfusion of red blood cells with impaired flow properties induced by storage

Red blood cell (RBC) flow properties (FPs), specifically their deformability, aggregability, and adherence to endothelial cells, play major roles in blood circulation. Their impairment, as occurs under various blood banking conditions, may contribute to circulatory impairment in recipients. Recent studies and meta-analyses show that the transfusion of stored RBCs (stRBCs) may be less beneficial than that of freshly collected units, which may thus adversely affect recipients, especially their circulatory function, thereby pointing to a potential role in the alteration of FPs of stRBCs. In this review, we present an up-to-date summary of the studies on the FP of stRBCs, clearly showing that they may be impaired at an early stage of storage, which may contribute considerably to transfusion-associated circulatory impairment in recipients. The alteration of the FPs of stRBC is attenuated by prestorage leukoreduction and/or poststorage "rejuvenation." However, because these procedures, especially rejuvenation, are costly and are associated with an increased risk of bacterial contamination, there is an urgent need to establish better methods of improving the hemodynamic function of stRBCs before their transfusion. It is therefore proposed that the FPs of stRBC may be important measures of the outcome of RBC transfusions. Monitoring such functions would thereby introduce necessary criteria and new tools for the quality control of stRBC units, making an important contribution to transfusion therapy.     

Prediction of changing cerebral blood flow by use of the conjunctival oxygen tension/arterial oxygen tension index

Current methods of assessing cerebral blood flow (CBF) are limited in their ability to provide data at the bedside in a timely, inexpensive, and continuous fashion. Since the palpebral conjunctiva is perfused by branches of the internal carotid artery, perfusion of this tissue may reflect global CBF. Conjunctival oxygen tension (PcjO2), PaO2, PaCO2, and pH were measured in ten healthy subjects during normal ventilation and active hyperventilation. CBF was measured simultaneously using positron emission tomography. CBF decreased from an average of 64.3 +/- 15.1 ml x 100 g-1 x min-1 during baseline measurements to 33.2 +/- 8.4 ml x 100 g-1 x min-1 during hyperventilation. The ratio of PcjO2 to PaO2 (the PcjO2/PaO2 index) decreased from 0.53 +/- 0.07 to 0.35 +/- 0.09 in the same time period. The PcjO2/PaO2 index was significantly correlated with CBF (r = .78, p less than .001). We conclude that the PcjO2/PaO2 index may reflect the reduction in CBF induced by hyperventilation in normal humans, and should be investigated further as a method of assessing CBF in other settings which can result in globally reduced cerebral perfusion.     

Myocardial perfusion and oxygenation are impaired during stress in severe aortic stenosis and correlate with impaired energetics and subclinical left ventricular dysfunction

Background

Left ventricular (LV) hypertrophy in aortic stenosis (AS) is characterized by reduced myocardial perfusion reserve due to coronary microvascular dysfunction. However, whether this hypoperfusion leads to tissue deoxygenation is unknown. We aimed to assess myocardial oxygenation in severe AS without obstructive coronary artery disease, and to investigate its association with myocardial energetics and function.

Methods

Twenty-eight patients with isolated severe AS and 15 controls underwent cardiovascular magnetic resonance (CMR) for assessment of perfusion (myocardial perfusion reserve index-MPRI) and oxygenation (blood-oxygen level dependent-BOLD signal intensity-SI change) during adenosine stress. LV circumferential strain and phosphocreatine/adenosine triphosphate (PCr/ATP) ratios were assessed using tagging CMR and ³¹P MR spectroscopy, respectively.

Results

AS patients had reduced MPRI (1.1 ± 0.3 vs. controls 1.7 ± 0.3, p < 0.001) and BOLD SI change during stress (5.1 ± 8.9% vs. controls 18.2 ± 10.1%, p = 0.001), as well as reduced PCr/ATP (1.45 ± 0.21 vs. 2.00 ± 0.25, p < 0.001) and LV strain (−16.4 ± 2.7% vs. controls −21.3 ± 1.9%, p < 0.001). Both perfusion reserve and oxygenation showed positive correlations with energetics and LV strain. Furthermore, impaired energetics correlated with reduced strain. Eight months post aortic valve replacement (AVR) (n = 14), perfusion (MPRI 1.6 ± 0.5), oxygenation (BOLD SI change 15.6 ± 7.0%), energetics (PCr/ATP 1.86 ± 0.48) and circumferential strain (−19.4 ± 2.5%) improved significantly.

Conclusions

Severe AS is characterized by impaired perfusion reserve and oxygenation which are related to the degree of derangement in energetics and associated LV dysfunction. These changes are reversible on relief of pressure overload and hypertrophy regression. Strategies aimed at improving oxygen demand–supply balance to preserve myocardial energetics and LV function are promising future therapies.     

Myocardial perfusion reserve assessed by t2-prepared steady-state free precession blood oxygen level-dependent magnetic resonance imaging in comparison to fractional flow reserve

Background- Blood oxygen level-dependent (BOLD) cardiac magnetic resonance imaging (CMR) has been shown to be able to detect myocardial perfusion differences. However, validation of BOLD CMR against fractional flow reserve (FFR) is lacking. The aim of our study was to analyze the potential diagnostic accuracy of BOLD CMR in comparison to invasively measured FFR, which served as gold standard for a hemodynamic significant coronary lesion. Methods and Results- BOLD image was performed at rest and during adenosine infusion in a 1.5-T CMR scanner. Thirty-six patients were analyzed for relative BOLD signal intensity increase according to the 16-segment model. Invasive FFR measurements were performed in the 3 major coronary arteries during adenosine infusion in all patients. An FFR≤0.8 was regarded to indicate a significant coronary lesion. Relative BOLD signal intensity increase was significantly lower in myocardial segments supplied by coronary arteries with an FFR≤0.8 compared with segments with an FFR>0.8 (1.1±0.2 versus 1.5±0.2; P<0.0001). Sensitivity and specificity yielded 88.2% and 89.5%, respectively. Conclusions- CMR BOLD imaging reliably detects hemodynamic significant coronary artery disease and is, thus, an alternative to contrast-enhanced perfusion studies.     

SPECT脑血流灌注显像在脑功能研究中的应用进展

脑血流在脑组织的营养、能量供给和代谢上均具有重要的作用,脑血流的测定无疑是研究脑功能比较重要的方法之一。利用单光子发射型计算机断层仪（SPECT）脑血流灌注显像研究大脑特定功能活跃区是目前神经核医学研究中的热点问题,尤其在近10年来成为神经核医学研究的焦点,各地专家、学者利用不同的干预措施、显像剂进行了大量研究,     

Myocardial perfusion MRI shows impaired perfusion of the mouse hypertrophic left ventricle

There is growing consensus that myocardial perfusion deficits play a pivotal role in the transition from compensated to overt decompensated hypertrophy. The purpose of this study was to systematically study myocardial perfusion deficits in the highly relevant model of pressure overload induced hypertrophy and heart failure by transverse aortic constriction (TAC), which was not done thus far. Regional left ventricular (LV) myocardial perfusion (mL/min/g) was assessed in healthy mice (n = 6) and mice with TAC (n = 14). A dual-bolus first-pass perfusion MRI technique was employed to longitudinally quantify myocardial perfusion values between 1 and 10 weeks after surgery. LV function and morphology were quantified from cinematographic MRI. Myocardial rest perfusion values in both groups did not change significantly over time, in line with the essentially constant global LV function and mass. Myocardial perfusion was significantly decreased in TAC mice (4.2 ± 0.9 mL/min/g) in comparison to controls (7.6 ± 1.8 mL/min/g) (P = 0.001). No regional differences in perfusion were observed within the LV wall. Importantly, increased LV volumes and mass, and decreased ejection fraction correlated with decreased myocardial perfusion (P < 0.001, in all cases). Total LV blood flow was decreased in TAC mice (0.5 ± 0.1 mL/min, P < 0.001) in comparison to control mice (0.7 ± 0.2 mL/min). Myocardial perfusion in TAC mice was significantly reduced as compared to healthy controls. Perfusion was proportional to LV volume and mass, and related to decreased LV ejection fraction. Furthermore, this study demonstrates the potential of quantitative first-pass contrast-enhanced MRI for the study of perfusion deficits in the diseased mouse heart.     

Effects of arterial blood gas levels on cerebral blood flow and oxygen transport

Near Infra-Red Spectroscopy (NIRS) is a non-invasive technique which can be used to investigate cerebral haemodynamics and oxygenation with high temporal resolution. When combined with measures of Cerebral Blood Flow (CBF), it has the potential to provide information about oxygen delivery, utilization and metabolism. However, the interpretation of experimental results is complex. Measured NIRS signals reflect both scalp and cerebral haemodynamics and are influenced by many factors. The relationship between Arterial Blood Pressure (ABP) and CBF has been widely investigated and it central to cerebral autoregulation. Changes in arterial blood gas levels have a significant effect on ABP and CBF and these relationships have been quantified previously. The relationship between ABP and NIRS signals, however, has not been fully characterized. In this paper, we thus investigate the influence of changes in arterial blood gas levels both experimentally and theoretically, using an extended mathematical model of cerebral blood flow and metabolism, in terms of the phase angle at 0.1 Hz. The autoregulation response is found to be strongly dependent upon the carbon dioxide (CO2) partial pressure but much less so upon changes in arterial oxygen saturation (SaO2). The results for phase angle sensitivity to CO2 show good agreement between experimental and theory, but a poorer agreement is found for the sensitivity to SaO2.