Decrease In Regional Blood Flow Research Articles

New Horizons in Temporal Lobe Seizure Control.

In patients with mesial temporal lobe epilepsy, high-frequency, low-amplitude electrical stimulation (ES) was applied during 3 weeks through contacts of intracranial electrodes that defined the epileptogenic zone. This subacute ES induced cessation of spontaneous seizures, decreased the number of EEG interictal spikes, caused a 10-fold increase in threshold to induce postdischarges, and showed a profound decrease in regional blood flow of the stimulated area in SPECT studies. Autoradiography analysis of surgical specimens from these patients demonstrated increased expression of benzodiazepine receptors and in gamma-aminobutyric acid content, particularly in the parahippocampal cortex. These observations provided evidence of a gamma-aminobutyric acid-mediated antiepileptic effect induced by ES. Several reports of long-term hippocampal ES through internalized neurostimulators have confirmed the antiepileptic effect on mesial temporal lobe-initiated seizures, with preservation of neuropsychological performance, in particular memory functions. The experience of the authors is that the response is optimal in patients without hippocampal sclerosis evidenced by MRI, whereas it is less significant and delayed in patients with hippocampal sclerosis. Other studies reported the best result stimulating through the contacts in the subiculum, the transition between the hippocampus and parahippocampal cortex, that usually escapes to the hippocampal sclerosis. Currently, the effect of ES directed at the subiculum and the parahippocampal cortex in patients with hippocampal sclerosis is under investigation.

Neuronal nitric oxide synthase regulates regional brain perfusion in healthy humans.

AimsNeuronal nitric oxide synthase (nNOS) is highly expressed within the cardiovascular and nervous systems. Studies in genetically modified mice suggest roles in brain blood flow regulation while dysfunctional nNOS signalling is implicated in cerebrovascular ischaemia and migraine. Previous human studies have investigated the effects of non-selective NOS inhibition but there has been no direct investigation of the role of nNOS in human cerebrovascular regulation. We hypothesized that inhibition of the tonic effects of nNOS would result in global or localized changes in cerebral blood flow (CBF), as well as changes in functional brain connectivity.Methods and resultsWe investigated the acute effects of a selective nNOS inhibitor, S-methyl-L-thiocitrulline (SMTC), on CBF and brain functional connectivity in healthy human volunteers (n = 19). We performed a randomized, placebo-controlled, crossover study with either intravenous SMTC or placebo, using magnetic resonance imaging protocols with arterial spin labelling and functional resting state neuroimaging. SMTC infusion induced an ∼4% decrease in resting global CBF [−2.3 (−0.3, −4.2) mL/100g/min, mean (95% confidence interval, CI), P = 0.02]. In a whole-brain voxel-wise factorial-design comparison of CBF maps, we identified a localized decrease in regional blood flow in the right hippocampus and parahippocampal gyrus following SMTC vs. placebo (2921 voxels; T = 7.0; x = 36; y = −32; z = −12; P < 0.001). This was accompanied by a decrease in functional connectivity to the left superior parietal lobule vs. placebo (484 voxels; T = 5.02; x = −14; y = −56; z = 74; P = 0.009). These analyses adjusted for the modest changes in mean arterial blood pressure induced by SMTC as compared to placebo [+8.7 mmHg (+1.8, +15.6), mean (95% CI), P = 0.009].ConclusionsThese data suggest a fundamental physiological role of nNOS in regulating regional CBF and functional connectivity in the human hippocampus. Our findings have relevance to the role of nNOS in the regulation of cerebral perfusion in health and disease.

PET Imaging of Crossed Cerebellar Diaschisis after Long-Term Cerebral Ischemia in Rats.

Crossed cerebellar diaschisis (CCD) is a decrease of regional blood flow and metabolism in the cerebellar hemisphere contralateral to the injured brain hemisphere as a common consequence of stroke. Despite CCD has been detected in patients with stroke using neuroimaging modalities, the evaluation of this phenomenon in rodent models of cerebral ischemia has been scarcely evaluated so far. Here, we report the in vivo evaluation of CCD after long-term cerebral ischemia in rats using positron emission tomography (PET) imaging with 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG). Imaging studies were combined with neurological evaluation to assess functional recovery. In the ischemic territory, imaging studies showed a significant decrease in glucose metabolism followed by a progressive recovery later on. Conversely, the cerebellum showed a contralateral hypometabolism from days 7 to 14 after reperfusion. Neurological behavior showed major impaired outcome at day 1 after ischemia followed by a significant recovery of the sensorimotor function from days 7 to 28 after experimental stroke. Taken together, these results suggest that the degree of CCD after cerebral ischemia might be predictive of neurological recovery.

Regional Perfusion in Sickle Cell Subjects and Normal Controls Is a Physiological Biomarker of Mental Stress and Fear of Pain

Introduction: Sickle cell disease (SCD) is a genetic disorder characterized by sudden onset of painful vaso-occlusive episodes (VOC) which can be triggered by stress as reported by sickle cell patients. The exact mechanism of VOC origin is not well understood; however, it could result as a progression of microvascular blockade with rigid sickled red blood cells (RBC). Anything that decreases regional blood flow (RBF) will increase the transit time that it takes the RBC to escape the microvasculature before it gets rigid and entrapped, thus increasing the chances of vaso-occlusion that may progress to VOC. The RBF is controlled by the autonomic nervous system (ANS) which is modulated by stress, and as we have previously shown, SCD patients have augmented autonomic mediated vasoconstriction response (VCR) to sigh and pain. Our studies showed significant VCR when subjects were told they were about to experience pain, suggesting that VCR might be the physiologic link between common VOC triggers like stress and sickled RBC retention in the microvasculature.Objectives: To study the effect of mental stress on autonomic parameters peripheral blood flow (PBF) and heart rate variability (HRV) in SCD.Methods: 19 SCD and 16 control (healthy and sickle cell trait) subjects were studied. Two standard mental stress tasks with graded levels of difficulty (N-back test and Stroop test) were presented to subjects using E-prime (Psychological software). Subjects were also exposed to a novel pain anticipation task, previously shown to induce VCR.PBF was measured using photo-plethysmography (PPG) on the left thumb. Reduction in PPG amplitude indicates vasoconstriction. Cardiac beat-to-beat variability (R-to-R interval;RRI) was extracted from electrocardiogram. ANS balance was derived from the following spectral indices of the RRI: high frequency power (HFP) ≈ parasympathetic activity, low frequency power (LFP), and the low/high ratio (LFP/HFP) representing sympathovagal balance.Average changes in PBF and HRV from the baseline were taken as the responses to the mental tasks.Results: There was a significant decrease in mean PBF, RRI and HFP during all the mental stressors (N-back test, Stroop test and pain fear) compared to the baseline (p<0.01). Based on task accuracy scores, there was clear difference in sublevels of task difficulty (p<0.0001). While PBF decreased during all the sublevels of N-back and Stroop compared to baseline (p<0.01), there was no PBF difference between the task sublevels. However, when subjects were told that they were about to experience severe pain from heat applied to their arm in a sham pain instruction that was given after N-back and Stroop, there was a significant decrease in PBF compared to baseline (p<0.001) and compared to the response during N-back (p<0.01). The parasympathetic withdrawal in response to mental tasks and fear of pain followed a similar pattern.Conclusions: Graded mental stress and fear of pain causes significant decrease in regional blood flow and parasympathetic withdrawal in SCD subjects and normal controls. The vasoconstriction response to "fear of pain" was significantly greater than the VRC caused by N-back and to a lesser extent in Stroop. The pattern of responses were not significantly different between SCD and controls however the consequences of decreased blood flow could be quite different because of the resulted entrapment of sickle cells in the microvasculature. This could explain how stress may play a role in the initiation of VOC in SCD by enhancing ANS mediated vasoconstriction, prolonging microvascular transit time and increasing the likelihood of vaso-occlusion.The 1st signal is mental tasks event marker, 2nd signal is photo-plethysmography (PPG) and the 3rd signal is heart rate variability derived from the electrocardiogram signal. [Display omitted] [Display omitted] DisclosuresWood:Celgene: Consultancy; AMAG: Consultancy; Ionis Pharmaceuticals: Consultancy; Vifor: Consultancy; Ionis Pharmaceuticals: Consultancy; Biomed Informatics: Consultancy; Vifor: Consultancy; World Care Clinical: Consultancy; World Care Clinical: Consultancy; Celgene: Consultancy; AMAG: Consultancy; Apopharma: Consultancy; Apopharma: Consultancy; Biomed Informatics: Consultancy.

Quantifying the effects of external shear loads on arterial and venous blood flow: Implications for pressure ulcer development

IntroductionForces applied to the skin cause a decrease in regional blood flow. This decrease in blood flow can cause tissue necrosis and lead to the formation of deep, penetrating wounds called pressure ulcers. These wounds are detrimental to individuals with compromised health, such as the elderly and spinal-cord injured. Although surface pressure is known to be a primary risk factor for developing a pressure ulcer, a seated individual rarely experiences pressure alone but rather combined loading which includes pressure as well as shear force on the skin. However, little research has been conducted to quantify the effects of shear forces on blood flow. MethodsFifteen men were tested in a magnetic resonance imaging scanner under no load, a normal load, and a combination of normal and shear loads. Changes in arterial and venous blood flow in the forearm were measured using magnetic resonance angiography phase-contrast imaging. FindingsThe blood flow in the anterior interosseous artery and basilic vein of the forearm decreased with the application of normal loads, and decreased further with the addition of shear loads. Marginal to significant differences at a 90% confidence level (P=0.08, 0.10) were observed, and medium to high effect sizes (0.3 to 0.5) were obtained. InterpretationBased on these results, shear force is an important factor to consider in relation to pressure ulcer propagation and prevention, and hence, future prevention approaches should also focus on mitigating shear loads.

Posterior medial corticothalamic connectivity and consciousness

Posterior medial corticothalamic connectivity and consciousness

A Quantitative Pixel-Wise Measurement of Myocardial Blood Flow by Contrast-Enhanced First-Pass CMR Perfusion Imaging: Microsphere Validation in Dogs and Feasibility Study in Humans

The aim of this study was to evaluate fully quantitative myocardial blood flow (MBF) at a pixel level based on contrast-enhanced first-pass cardiac magnetic resonance (CMR) imaging in dogs and in patients. Microspheres can quantify MBF in subgram regions of interest, but CMR perfusion imaging may be able to quantify MBF and differentiate blood flow at a much higher resolution. First-pass CMR perfusion imaging was performed in a dog model with local hyperemia induced by intracoronary adenosine. Fluorescent microspheres were the reference standard for MBF validation. CMR perfusion imaging was also performed on patients with significant coronary artery disease (CAD) by invasive coronary angiography. Myocardial time-signal intensity curves of the images were quantified on a pixel-by-pixel basis using a model-constrained deconvolution analysis. Qualitatively, color CMR perfusion pixel maps were comparable to microsphere MBF bull's-eye plots in all animals. Pixel-wise CMR MBF estimates correlated well against subgram (0.49 ± 0.14 g) microsphere measurements (r = 0.87 to 0.90) but showed minor underestimation of MBF. To reduce bias due to misregistration and minimize issues related to repeated measures, 1 hyperemic and 1 remote sector per animal were compared with the microsphere MBF, which improved the correlation (r = 0.97 to 0.98), and the bias was close to zero. Sector-wise and pixel-wise CMR MBF estimates also correlated well (r = 0.97). In patients, color CMR stress perfusion pixel maps showed regional blood flow decreases and transmural perfusion gradients in territories served by stenotic coronary arteries. MBF estimates in endocardial versus epicardial subsectors, and ischemic versus remote sectors, were all significantly different (p < 0.001 and p < 0.01, respectively). Myocardial blood flow can be quantified at the pixel level (∼32 μl of myocardium) on CMR perfusion images, and results compared well with microsphere measurements. High-resolution pixel-wise CMR perfusion maps can quantify transmural perfusion gradients in patients with CAD.

Is increased perfusion pressure really necessary during cardiopulmonary bypass?

We read with great interest the work by Siepe et al .[ 1] investigating the effect of increased systemic perfusion pressure during cardiopulmonary bypass on cognitive dysfunction and delirium. In this revolutionary study questioning cerebral autoregulation, they found that maintaining mean perfusion pressure during normothermic cardiopulmonary bypass (CPB) at 80–90 mmHg is associated with less early cognitive dysfunction and delirium after coronary artery bypass grafting (CABG), and elevated perfusion pressure is not associated with increased morbidity and mortality. This finding may lead to severe changes in the routine practice of cardiac surgeons and anaesthesiologists including us. However, we believe that there are some issues that need to be addressed. This study lacks a power and sample analysis and seems to have been conducted in a very small group of patients. For this reason, postoperative complications such as atrial fibrillation (19 vs 36%), bleeding requiring reoperation (2 vs 7%), use of blood products (50 vs 70), cessation of catecholamine support (26 vs 14 h), superficial wound infection (4 vs 7%) and pleural effusion (33 vs 48%) which may be statistically significant in a larger group of patients appears to be insignificant. As the low perfusion group needed longer catecholamine support, it is easy to assume that they were in either low cardiac output (LCO) or vasoplegic state. The incidence of preoperative left ventricular dysfunction, which is a predictor of LCO, is not reported and should be included in the statistical analysis. Furthermore, it is well known that preoperative medication by inhibitors of angiotensin-converting enzyme in coronary artery patients is associated with vasoplegic shock early after CABG. This issue also needs to be addressed. If low perfusion pressure during CPB is to be blamed, then the postoperative period should be comparable in both groups. However, as the LP group suffered from LCO postoperatively, measurement of neurochemical markers (S-100 beta and neuronspecific enolase) immediately after CPB might be appropriate. It is clear that patients with delirium had longer CPB, ventilation and intensive care unit (ICU) stay times, and were still in LCO (probably still in ICU and under major depression) at the time of Mini-Mental-State examination. All of these factors have been shown to be associated with postoperative delirium [2, 3]. Cerebral circulation during CPB may be affected by partial arterial oxygen (hyperoxaemia by impairing red cell rheology and microcirculation) and carbon dioxide pressure (by changing cerebral arteriolar reactivity) [4]. Thus, they should be monitored closely (more frequently than every 20 min) and kept similar in both groups. Spot measurements of transcutaneous cerebral oxygen saturation as measured by near-infrared spectroscopy seem to be similar in both groups. However, it is reported that rSo2 desaturation score, which is calculated by multiplying rSo2 below 50% by time (s), is a more sensitive method of predicting early postoperative cognitive decline than spot measurements [5]. Nitric oxide (NO) formed via endothelial NO synthase and neuronal NO synthase plays crucial roles in the regulation of blood flow through vasodilatation and decreased vascular resistance. Endothelial and autonomic nitrergic nerve functions are impaired in patients with diabetes mellitus, resulting in regional blood flow decrease [6]. As the duration of the diabetes mellitus and insulin dependence may change from patient to patient, it seems necessary to exclude these patients or at least compensate for the severity of their disease.

Correlation between crossed cerebellar diaschisis and clinical neurological scales

A common consequence of unilateral stroke is crossed cerebellar diaschisis (CCD), a decrease in regional blood flow (CBF) and metabolism (CMRglu) in the cerebellar hemisphere contralateral to the affected cerebral hemisphere. Former studies indicated a post-stroke time-dependent relationship between the degree of CCD and the clinical status of acute and sub-acute stroke patients, but no study has been performed in post-stroke patients. The objective of this investigation was to evaluate the quantitative correlation between the degree of CCD and the values of clinical stroke scales in post-stroke patients. We measured with positron emission tomography (PET) regional CBF and CMRglu values in the affected cortical regions and the contralateral cerebellum in ten ischaemic post-stroke patients. Based on these quantitative parameters, the degree of diaschisis (DoD) was calculated, and the DoD values were correlated with three clinical stroke scales [Barthel Index, Orgogozo Scale and Scandinavian Neurological Scale (SNS)]. There were significant linear correlations between all clinical stroke scales and the CCD values (Barthel Index and Orgogozo Scale: P < 0.001, for both CBF and CMRglu; SNS: P = 0.007 and P = 0.044; CBF and CMRglu, respectively). The findings indicate that DoD can be used as a quantitative indicator of the functional impairments following stroke, i.e. it can serve as a potential surrogate of the severity of the damage.

Role of the cyclooxygenase 2–thromboxane pathway in 2,3,7,8-tetrachlorodibenzo- p-dioxin-induced decrease in mesencephalic vein blood flow in the zebrafish embryo

Previously, we reported that 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) evoked developmental toxicity required activation of aryl hydrocarbon receptor type 2 (AHR2), using zebrafish embryos. However, the downstream molecular targets of AHR2 activation are largely unknown and are the focus of the present investigation. TCDD induces cyclooxygenase 2 (COX2), a rate-limiting enzyme for prostaglandin synthesis in certain cells. In the present study, we investigated the role of the COX2–thromboxane pathway in causing a specific endpoint of TCDD developmental toxicity in the zebrafish embryo, namely, a decrease in regional blood flow in the dorsal midbrain. It was found that the TCDD-induced reduction in mesencephalic vein blood flow was markedly inhibited by selective COX2 inhibitors, NS-398 and SC-236, and by a general COX inhibitor, indomethacin, but not by a selective COX1 inhibitor, SC-560. Gene knock-down of COX2 by two different types of morpholino antisense oligonucleotides, but not by their negative homologs, also protected the zebrafish embryos from mesencephalic vein circulation failure caused by TCDD. This inhibitory effect of TCDD on regional blood flow in the dorsal midbrain was also blocked by selective antagonists of the thromboxane receptor (TP). Treatment of control zebrafish embryos with a TP agonist also caused a reduction in mesencephalic vein blood flow and it too was blocked by a TP antagonist, without any effect on trunk circulation. Finally, gene knock-down of thromboxane A synthase 1 (TBXS) with morpholinos but not by the morpholinos' negative homologs provided significant protection against TCDD-induced mesencephalic circulation failure. Taken together, these results point to a role of the prostanoid synthesis pathway via COX2-TBXS-TP in the local circulation failure induced by TCDD in the dorsal midbrain of the zebrafish embryo.

Non-selective cyclooxygenase inhibition before periodic acceleration (pGz) cardiopulmonary resuscitation (CPR) in a porcine model of ventricular fibrillation

Whole body periodic acceleration (pGz) along the spinal axis is a novel method of cardiopulmonary resuscitation (CPR). Oscillatory motion of the supine body in a horizontal fashion provides ventilation and blood flow to vital organs during cardiac arrest and pulsatile shear stress to the vascular endothelium. We previously showed in pigs that pGz-CPR affords better overall survival, post resuscitation myocardial function, and neurological outcomes compared to conventional chest compression CPR. pGz through pulsatile shear stress on the vascular endothelium elicits acute production of prostaglandins and endothelial-derived nitric oxide (eNO) in whole animal models and in vitro preparations. The salutary effects associated with pGz-CPR compared to chest compression CPR are in part related to endothelial-derived nitric oxide. Both eNO and prostaglandins are cardioprotective in ischemia reperfusion models. To differentiate between the roles of these mediators, indomethacin a non-selective cyclooxygenase inhibitor (COX) was used as a tool to investigate prostaglandin effects during pGz-CPR by acute outcomes of survival, cardioprotection and regional blood flows (RBF). Two groups of anesthetized, intubated pigs weighing 25-36kg were studied. Prior to electrical induction of ventricular fibrillation (VF) animals received equal volumes of either saline placebo Control (CONT) (n=9) or indomethacin (INDO), (n=8), (2mg/kg). After 3min of unsupported VF, both groups received 15min of pGz-CPR followed by pharmacologic and electrical attempts for resuscitation. Return of circulation (ROSC) to 3h occurred in (78%) in CONT and (63%) in INDO pretreated animals. There was no statistically significant difference in hemodynamics between groups at baseline or during the protocol. At baseline, INDO caused a decrease in brain RBF. Two hours after ROSC, INDO blunted the hyperemia response to brain and heart. Echocardiographic evidence of myocardial dysfunction was most notable for the INDO group in the wall motion score index (WMSI). After 3h of ROSC there was a 4-fold difference in both creatine phosphokinase (CPK) and Troponin I concentration between INDO and CONT. Therefore, non-specific acute inhibition of COX in part blunts the salutary effects of pGz-CPR. These data suggest that prostaglandins in part are involved in the cardio protection induced by pGz during CPR.

Human Placental Lactogen Decreases Regional Blood Flow in Anesthetized Pigs

In 22 pigs anesthetized with sodium pentobarbitone, changes in blood flow caused by infusion of human placental lactogen into the left renal, external iliac, and anterior descending coronary arteries were assessed using electromagnetic flowmeters. In 17 pigs, infusion of human placental lactogen whilst keeping the heart rate and arterial pressure constant decreased coronary, renal and iliac flow. In 5 additional pigs, increasing the dose of human placental lactogen produced a dose-related decrease in regional blood flow. The mechanisms of the above response were studied in 15 of the 17 pigs by repeating the experiment of infusion. The human placental lactogen-induced decrease in regional blood flow was not affected by blockade of cholinergic receptors (5 pigs) or of α-adrenergic receptors (5 pigs), but it was abolished by blockade of β₂-adrenergic receptors (5 pigs). The present study showed that intra-arterial infusion of human placental lactogen primarily decreased coronary, renal and iliac blood flow. The mechanism of this response was shown to be due to the inhibition of a vasodilatory β₂-adrenergic receptor-mediated effect.

Evaluation of extracranial blood flow in Parkinson disease

Decreased cerebral flow velocities in Parkinsonian patients were reported previously. Because of the limited data on vascular changes in Parkinson disease (PD), which may have a vascular etiology, we aimed to disclose any possible cerebral hemodynamic alteration in Parkinsonian patients. We prospectively evaluated 28 non-demented, idiopathic parkinsonian patients and 19 age and sex matched controls with Doppler sonography. Flow volumes, peak systolic flow velocities, and cross-sectional areas of vertebral and internal carotid arteries (ICA) were measured and compared between patients and controls. Correlation of patient age and disease duration with Doppler parameters was observed; and each Doppler parameter of patients within each Hoehn–Yahr scale was compared. There was no significant difference of measured parameters between groups. No correlation was found between disease duration and age with flow volume, cross-sectional area or peak systolic velocity. Hoehn–Yahr scale was not found having significant relation with Doppler parameters. Values of vertebral, internal carotid and cerebral blood flow volumes (CBF), peak systolic velocities, and cross-sectional areas were not significantly different between Parkinsonian patients and age and sex matched controls. Although regional blood flow decreases may be seen as reported previously, Parkinson disease is not associated with a flow volume or velocity alteration of extracranial cerebral arteries.

Acoustic droplet vaporization for temporal and spatial control of tissue occlusion: a kidney study

Acoustic droplet vaporization (ADV) has been introduced with the potential application of tumor treatment via occlusion and subsequent necrosis. New Zealand White rabbits were anesthetized, and their left kidney was externalized. An imaging array and single-element transducer were positioned in a tank with direct access to the kidney's vasculature and renal artery. Filtered droplet emulsions (diameter <6 microm) were injected intra-arterially (IA) into the left heart during insonification of the renal artery, and the extent of blood flow reduction by ADV was compared to the untreated right kidney. Flow cytometry (using colored microspheres) of kidney tissue samples and reference blood from the femoral artery allowed the quantitative estimation of regional blood flow. A maximum regional blood flow reduction in the treated region of >90% and an average organ perfusion reduction of >70% was achieved using ADV. After treatment of the left kidney, the control kidney on the contralateral side showed a maximum decrease in regional blood flow of 18% relative to the pre-ADV baseline. Image-based hyper-echogenicity from ADV of IA injections was monitored for approximately 90 minutes, and cortex perfusion was reduced by >60% of its original value for more than 1 hour. This could be enough time for the onset of cell death and possible tumor treatment via ischemic necrosis. Moreover, currently used radiofrequency tissue ablation-based tumor treatment could benefit from ADV due to the decreased heat loss via vascular cooling.

Isoflurane preserves central nervous system blood flow during intraoperative cardiac tamponade in dogs

The present study tested the hypothesis that the anesthetic technique will influence the changes in regional blood flow (RBF) during intraoperative cardiac tamponade. Twenty-four dogs were divided into three equal groups: Group I, anesthesia was maintained with ketamine (25 mg.kg(-1).hr(-1)); Group II, with fentanyl and midazolam (F-M; 10 mug.kg(-1).hr(-1) and 0.5 mg.kg(-1).hr(-1), respectively); Group III with 1 minimum alveolar concentration (MAC; 1.4%) isoflurane. Radioactive microspheres were used to measure RBF in myocardium, brain, spinal cord, abdominal viscera, skeletal muscle and skin. Cardiac output (CO) was measured by thermodilution and arterial pressure with a catheter situated in the thoracic aorta. Catheters were introduced into the pericardial cavity to infuse isotonic saline and to measure intrapericardial pressure (IPP). Measurements were obtained under control conditions and during tamponade, as defined by an increase in IPP sufficient to reduce mean arterial pressure by 40%. Tamponade caused decreases in CO and RBF that were comparable under the three anesthetics, except that RBF in subcortical regions of the brain and in the spinal cord were maintained under isoflurane but decreased under ketamine or F-M. In dogs, intraoperative cardiac tamponade caused comparable changes in RBF under the different anesthetic techniques except that autoregulation was effective in maintaining RBF within the central nervous system only under isoflurane anesthesia. Our findings provide no compelling reason to recommend one anesthetic over the others for maintenance of anesthesia in situations with increased risk for intraoperative cardiac tamponade. However, they cannot be extrapolated to anesthesia induction in the presence of cardiac tamponade.

The irrelevant speech effect and working memory load

Irrelevant speech impairs the immediate serial recall of visually presented material. Previously, we have shown that the irrelevant speech effect (ISE) was associated with a relative decrease of regional blood flow in cortical regions subserving the verbal working memory, in particular the superior temporal cortex. In this extension of the previous study, the working memory load was increased and an increased activity as a response to irrelevant speech was noted in the dorsolateral prefrontal cortex. We suggest that the two studies together provide some basic insights as to the nature of the irrelevant speech effect. Firstly, no area in the brain can be ascribed as the single locus of the irrelevant speech effect. Instead, the functional neuroanatomical substrate to the effect can be characterized in terms of changes in networks of functionally interrelated areas. Secondly, the areas that are sensitive to the irrelevant speech effect are also generically activated by the verbal working memory task itself. Finally, the impact of irrelevant speech and related brain activity depends on working memory load as indicated by the differences between the present and the previous study. From a brain perspective, the irrelevant speech effect may represent a complex phenomenon that is a composite of several underlying mechanisms, which depending on the working memory load, include top-down inhibition as well as recruitment of compensatory support and control processes. We suggest that, in the low-load condition, a selection process by an inhibitory top-down modulation is sufficient, whereas in the high-load condition, at or above working memory span, auxiliary adaptive cognitive resources are recruited as compensation.

Relationship between the tooth eruption and regional blood flow in angiotensin II-induced hypertensive rats

Objective: The mechanism of action of vasoactive drugs on tooth movement is unknown. The purpose of the present study was to measure simultaneously the axial movement of the mandibular incisor, regional blood flow at the base of the incisor, and systemic arterial blood pressure in angiotensin II-induced hypertensive rats to determine the possible cause of tooth displacement. Design: The measurements were made under artificial respiration with halothane anaesthesia. In the experimental animals, 2.5 μg of angiotensin II in 1 ml of Ringer’s solution was infused at 0.83 ml/h for 12 h from the femoral vein. In the control animals, only Ringer’s solution was infused. Results: Angiotensin II caused an increase of the mean arterial blood pressure from 86 to 119 mmHg, and decreases of the eruption rate from 667 to 494 μm/24 h and the regional blood flow from 262 to 214 mV. There was a positive correlation between the eruption rate and regional blood flow, and a negative correlation between the blood pressure and regional blood flow. Conclusion: These results suggest that angiotensin II caused constriction of the peripheral vascular smooth muscle resulting in an increase of arterial blood pressure and a decrease of regional blood flow, followed by a decrease of fluid volume and then a reduction of either the pressure within the socket or of the eruptive force. We assume that the regional vascular pressure within the socket plays an important role in determining the position of the rat incisor.

Distinguish Between Consciousness and Alertness

Scientists agree about the existence of dramatic global decreases in regional blood flow that occur in non-rapid eye movement (NREM) sleep and about

Decreased brain infarct following focal ischemia in mice lacking the transcription factor E2F1.

E2F1+/- mice subjected to 2 h middle cerebral artery occlusion developed an infarct of 77.0 +/- 3.2 mm3 (mean +/- s.e.m., n = 15) in the ischemic hemisphere after 24 h reperfusion. A significantly smaller infarct of 58.8 +/- 4.8 mm3 (n = 15; p < 0.01) was found in E2F1-/- animals. Both deficient and normal mice had similar cerebral angioarchitecture and intra-ischemic decreases in regional blood flow. Similar areas of hypoxia in both groups of ischemic animals were demonstrated directly by immunohistochemical detection of nitroimidazole adducts. It was concluded that all animals received the same ischemic insult, yet the subsequent damage was different in the mutant mice. This is the first indication that the E2F1 gene plays a role in ischemic death of post-mitotic neurons.

Altered systemic organ blood flow after combined injury with burn and smoke inhalation.

Systemic organ blood flow was longitudinally determined with fluorescent microspheres after severe thermal injury in unanesthetized sheep. After chronic instrumentation, 20 sheep were subjected to combined injury with 40% body surface area third-degree burn and 48 breaths of cotton smoke insufflation. During the next 72 h of the experimental period, all animals were resuscitated with Ringer's lactate following the Parkland formula. To test the effect of systemic administration of ibuprofen, animals were assigned to the control group (n=11) or the ibuprofen group (n=9). In the ibuprofen group, animals received ibuprofen as a 12 mg/kg bolus injection 1 h after injury and 6 mg/kg/h as a continuous infusion for the next 47 h. After this combined injury, animals exhibited a biphasic hemodynamic alteration, with an initial shock period and a later hyperdynamic period, a phenomenon often seen in severely burned patients. Among multiple organs, the splanchnic organs exhibited more dominant and sustained decreases in regional blood flow, whereas heart and kidney blood flow were maintained at more than 90% of baseline level even in the initial hypovolemic phase. In the postresuscitation period, no organ except the heart showed increased regional blood flow, despite a more than 20% increase in cardiac output. Ibuprofen had effects on early recovery from the initial shock period, and it improved intestinal organ blood flow, suggesting a potential benefit of this drug for severe thermal injury.