Nicotine activation of neuronal nitric oxide synthase and guanylyl cyclase in the medulla increases blood flow of the common carotid artery in cats

Individual activation of nicotinic acetylcholine receptor (nAChR) or nitric oxide (NO) synthase in the dorsal facial area (DFA) increases blood flow of common carotid artery (CCA) supplying intra- and extra-cranial tissues. We investigated whether the activation of nAChR initiated the activation of NO synthase and guanylyl cyclase to increase CCA blood flow in anesthetized cats. Microinjections of nicotine (a non-selective nAChR agonist), or choline (a selective α7-nAChR agonist) in the DFA produced increases in CCA blood flow ipsilaterally. These increases were significantly reduced by pretreatment with NG-nitro-arginine methyl ester (l-NAME, a non-specific NO synthase inhibitor), 7-nitroindazole (7-NI, a relatively selective neuronal NO synthase inhibitor) or methylene blue (MB, a guanylyl cyclase inhibitor) but not by that with N5-(1-iminoethyl)-l-ornithine (l-NIO, a potent endothelial NO synthase inhibitor). Control microinjection with d-NAME (an isomer of l-NAME), artificial cerebrospinal fluid or DMSO (a solvent for 7-NI) did not affect resting CCA blood flow, nor did they affect nicotine- or choline-induced response. In conclusion, activation of nAChR, at least α7-nAChR, led to the activation of neuronal NO synthase and guanylyl cyclase in the DFA, which induced an increase in CCA blood flow.     

Influence of posture on middle cerebral artery mean flow velocity in humans

We determined middle cerebral artery, common carotid artery and temporal superficial artery Doppler derived flow velocities in ten subjects for 10 min after change in posture. Maximal changes were observed after about 3 min. The 10° head-down tilt position increased blood velocities in the common carotid artery by 13% (SD 4)% (P < 0.001), in the middle cerebral artery by,6% (SD 3)% (P < 0.001) and in the superficial temporal artery by 70% (SD 26)% (P < 0.001). In the standing position, there was an 18% (SD 9)% (P < 0.001) decrease in the common carotid blood velocities, with 14% (SD 6)% (P < 0.001) and 53% (SD 23)% (P < 0.001) reductions in the middle cerebral and superficial temporal artery velocities, respectively. At 9 min after the changes in posture, velocities in the middle cerebral artery were at the value of supine rest, whereas the common carotid blood velocity was not completely restored and deviations in the temporal artery velocity persisted. The data would suggest that cerebral blood flow is regulated with some delay and that such regulation is partially reflected in the common artery blood flow, since changes in a branch of the external carotid artery flow velocity remained.     

Effect of hyperthermia on the function of thyroid gland

Hyperthermia may be a consequence of environmental conditions, bacterial or viral infections and/or thyroid storm. This study investigates the acute effect of body temperature elevation on thyroid function and on its scintigraphy studies. Thyroid scintigraphy was performed on New Zealand White rabbits weighing approximately 3–3.5 kg. Each rabbit was injected with 115 MBq (3.1 mCi) technetium-99 m pertechnetate (^99mTc pertechnetate). Studies were performed using Gamma camera equipped with a low energy, high resolution, pinhole collimator interfaced with a computer. Static images were acquired 20 min after administration of the radiotracer. Two days later the same protocol was repeated for the same rabbit after increasing the body temperature by 2°C. The experiment was repeated again after a 2-day interval at 3°C, and then after another 2-day interval at 4°C. Plasma free thyroxine (FT₄), free triiodothyronine (FT₃) and thyroid stimulating hormone (TSH) were measured at control and at different hyperthermic temperatures (+2, 3, 4°C). We recorded isometric tension of rabbit thyroid artery strips in organ baths during stepwise temperature elevation. During hyperthermia the decrease in thyroid function and thyroid scintigraphy studies was proportional to body temperature elevation. The recording of isometric tension in rabbit thyroid artery strips in organ baths showed vasoconstriction during hyperthermia which is proportional to the heating temperature. Plasma FT₄ and FT₃ level were decreased while TSH levels were not affected by acute fever. Our results indicate that hyperthermia causes a transient decrease in thyroid gland function and scintigraphic patterns on radionuclide studies. Thus, body temperatures must be measured before radionuclide studies in order to ensure that interpretation of data is not influenced by hyperthermia.     

Effect of spinal cord temperature on carotid blood flow in the Pekin duck

Spinal cord heating in white Pekin ducks increases breathing rate and carotid blood flow. During naturally induced panting, the reverse effect was achieved by spinal cooling. An increased beak and expired air temperature during spinal heating suggest an importance of the increased carotid blood flow in maximizing heat dissipation during polypnoea. The results indicate that both the polypneic response and the increase in carotid blood flow are dependent on the same sensory input, namely the temperature of the spinal cord.     

Effects of intracerebroventricular administration of aminophylline on hyperbaric-induced increase in carotid blood flow

Carotid blood flow was measured in rats by implanted transit-time ultrasonic flowprobes during hyperbaric experiments at up to 70 bar (7 MPa) using an helium-oxygen hyperoxic (partial pressure of O₂ = 400 mbar) mixture. Before the hyperbaric experiment, an intracerebroventricular injection of phosphate saline buffered solution (PBS) or aminophylline, an adenosine receptor blocker, in PBS was given. Throughout the hyperbaric experiment carotid blood flow increased with ambient pressure in both PBS, i.e. control, and aminophylline treated rats. The increase in carotid blood flow was significantly attenuated in aminophylline treated rats. Additional experiments showed that the increased carotid blood flow was independent of hyperoxia as well as of temperature. The hypothesis that the hyperbaric dependent increase in carotid blood flow was mediated by brain adenosine receptors and its implication regarding a cerebral vasodilatation are discussed.     

Cerebral blood flow and histopathological changes following permanent bilateral carotid artery ligation in Wistar rats

Summary Cerebral blood flow and histopathological changes after bilateral carotid artery ligation (BCAL) in Wistar rats were studied. Eight of the 38 rats (21%) died within one week. In the 30 survivors, the incidence of histopathological change was 90% in the caudate nucleus, 23% in the cortex, 30% in the hippocampus, and 0% in the other structures. Local cerebral blood flow (LCBF) was measured using the quantitative autoradiographic ¹⁴C-iodoantipyrine technique in 24 anatomically discrete regions of the brain. BCAL induced ischemia in the entire forebrain. The percent reduction of LCBF was between 25–94% of the control at 2.5 h after BCAL. LCBF tended to recover 1 week after BCAL except for the regions of neuronal damage. These results suggest that neuronal damage does not correlate with the flow rate. In the present study, selective neuronal damage was also observed in rats with chronic cerebral ischemia.     

Regional decline of cerebral blood flow with age in cognitively intact subjects

Cerebral blood flow was measured by the 133Xenon washout method in 44 cognitively intact subjects. Regression analysis of cerebral blood flow with age was performed on data from 33 subjects without arteriosclerotic cardiovascular disease, hypertension, or chronic obstructive pulmonary disease, factors which have been previously shown to lower cerebral blood flow. Changes with normal aging were significant in the left and right hemispheres with bilateral changes in temporal, parietal, and occipital regions. An additional group of 11 cognitively intact subjects with arteriosclerotic cardiovascular disease but no accompanying dementing disease had lower mean flow values at each detector position than did age- and sex-matched controls, although the differences did not always reach statistical significance. Decreased flows in temporal regions seem to be a concomitant of normal aging, and are not related to the presence of vascular disease.     

Fully Automatic Region of Interest Selection in Glomerular Filtration Rate Estimation from <Superscript>99m</Superscript>Tc-DTPA Renogram

Glomerular filtration rate (GFR) is a common accepted standard estimation of renal function. Gamma camera-based methods for estimating renal uptake of ^99mTc-diethylenetriaminepentaacetic acid (DTPA) without blood or urine sampling have been widely used. Of these, the method introduced by Gates has been the most common method. Currently, most of gamma cameras are equipped with a commercial program for GFR determination, a semi-quantitative analysis by manually drawing region of interest (ROI) over each kidney. Then, the GFR value can be computed from the scintigraphic determination of ^99mTc-DTPA uptake within the kidney automatically. Delineating the kidney area is difficult when applying a fixed threshold value. Moreover, hand-drawn ROIs are tedious, time consuming, and dependent highly on operator skill. Thus, we developed a fully automatic renal ROI estimation system based on the temporal changes in intensity counts, intensity-pair distribution image contrast enhancement method, adaptive thresholding, and morphological operations that can locate the kidney area and obtain the GFR value from a ^99mTc-DTPA renogram. To evaluate the performance of the proposed approach, 30 clinical dynamic renograms were introduced. The fully automatic approach failed in one patient with very poor renal function. Four patients had a unilateral kidney, and the others had bilateral kidneys. The automatic contours from the remaining 54 kidneys were compared with the contours of manual drawing. The 54 kidneys were included for area error and boundary error analyses. There was high correlation between two physicians’ manual contours and the contours obtained by our approach. For area error analysis, the mean true positive area overlap is 91%, the mean false negative is 13.4%, and the mean false positive is 9.3%. The boundary error is 1.6 pixels. The GFR calculated using this automatic computer-aided approach is reproducible and may be applied to help nuclear medicine physicians in clinical practice.     

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.     

腺苷负荷脑血流灌注显像的可行性研究

目的 数为参照,分别计算两侧大脑额叶、颞叶、顶叶、枕叶ROI放射性计数与其比值,比较同一组ROI在腺苷负荷状态下与静息状态下放射性计数比值.对视为异常部位的大脑ROI按其对腺苷负荷后脑血流灌注变化的反应进行分类.结果 所有患者进行腺苷负荷显像,没有因出现严重不良反应而终止,部分患者出现轻微不良反应并在腺苷注射结束后迅速消失.共获得视为正常的174组大脑ROI,静息显像的比值与负荷显像的比值比较显示,额叶、颞叶、顶叶差异有统计学意义(0.901±0.100比0.956±0.149,0.923±0.070比0.981±0.090,0.840±0.126比0.887±0.091,均P＜0.05),枕叶差异无统计学意义(1.102±0.146比1.010±0.124,P＞0.05).获得视为异常的49处ROI,其中静息状态局部脑血流量正常,腺苷负荷后局部脑血流量减低的有10处;静息状态局部脑血流量减低,腺苷负荷后局部脑血流量减低更加明显的有9处;静息状态局部脑血流量减低,腺苷负荷后局部脑血流量减低改善的有27处;静息状态局部脑血流量减低,腺苷负荷后局部脑血流量减低区无明显变化的有3处.结论 腺苷能用于负荷脑血流灌注显像,且不良反应少.     

Effects of increasing arterial pressure on cerebral blood flow in the baboon: Influence of the sympathetic nervous system

The influence of stimulation of the cervical sympathetic chain on the response of cerebral blood flow to hypertension induced by the intravenous infusion of angiotensin was studied in anaesthetised baboons. Cerebral blood flow was measured by the intracarotid¹³³Xenon injection technique. Possible lesions of the blood-brain barrier were studied by injecting Evans blue towards the end of the experiment and ischaemic brain damage was assessed following perfusion fixation.In a control group of five baboons blood flow increased by 53±9% (mean ±S.E.) from the base line values in the arterial pressure range 130–159 mm Hg.In four baboons subjected to unilateral sympathetic stimulation flow increased by 16±4% in the same pressure range.In three babbons subjected to bilateral sympathetic stimulation there were not significant increases in flow until the arterial pressure had increased above 159 mm Hg.Disruption of the blood-brain barrier in the parietooccipital regions was only seen in the control animals but not in the stimulated baboons. Ischaemic brain damage was not observed with the exception of one small lesion in a single stimulated baboon.These findings provide strong support for the observations of Bill and Linder (1976) that activation of the cervical sympathetic can modify the level at which breakthrough of cerebral blood flow occurs in association with systemic hypertension.These investigations were supported by the Medical Research Council and Tenovus (Scotland)     

Optimising the methodology of calculating the cerebral blood flow of newborn infants from near infra-red spectrophotometry data

Cerebral blood flow can be measured in neonates by near infra-red spectrophotometry. The tracer is oxyhaemoglobin. The purpose of the study is to compare the test-retest variability of two previously proposed methods (UCH and COP) of analysis, and to investigate the influence of sampling rates, smoothing and integration periods. Under clinical conditions good measurements are often difficult to obtain. Therefore, a second goal is to find ways of determining the quality of individual measurements. 380 cerebral blood flow measurements from 69 infants are analysed. The data set is optimised statistically for the lowest test-retest variability and the following results are obtained. The test-retest variability of measurements at 2 s sampling time data is considerably worse than at 0·5 s sampling time. Smoothing does not change the test retest variability. A 6 s integration period gives higher values and higher test-retest variability than an 8 s integration period. By applying the suggested criteria, a test-retest variability of 17% is achieved, if 50% of the measurements are rejected. The mean cerebral blood flow is 12·2 ml(100 g)⁻¹ min⁻¹ for the UCH method and 97·7 ml(100 g)⁻¹ min⁻¹ for the COP method. The test-retest variability of both methods is comparable for 0·5 s sampling time. For 2 s sampling time the method proposed by Skov et al. is significantly better. These test retest variabilities represent maximum values, part of the observed variability may be due to physiological changes of unknown magnitude.     

Comparative scintigraphic study of <Superscript>99m</Superscript>Tc ciprofloxacin pharmacokinetics after intravenous and lymphotropic administration in experimental pulmonary suppuration

Intravenously injected ^99mTc ciprofloxacin is rapidly accumulated and washed from the septic focus. Lymphotropic injections provide targeted and long-lasting effect of the antibiotic. After injection into the interspinous ligament the drug slowly enters the inflammation area (by-passing the urinary organs and liver), where it is maximally accumulated only after 24 h, which allows to reduce the number of injections and the total dose of the antibiotic.__________This revised version was published online in July 2005 with the addition of the issue titleTranslated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 139, No. 1, pp. 108–112, January, 2005     

Assessment of cardiac contractility during a cold pressor test by using (d<Emphasis Type="Italic">P</Emphasis>/d<Emphasis Type="Italic">t</Emphasis>)/<Emphasis Type="Italic">P</Emphasis> of carotid artery pulses

The ratio of the first derivative (dP/dt) of a carotid artery pulse to the developed pressure (P), (dP/dt)/P, is an easily measurable, noninvasive index of cardiac contractility even in moderate exercise. We examined the effects of transient cold exposure on cardiac contractility in normal reactors (n = 12) and hyperreactors (an increase in systolic or diastolic pressure >15 mm Hg; n = 6) by using this index. Eighteen healthy participants were subjected to the cold pressor test, which required them to immerse the right hand in chilly water (4°C) for 2 min. Although cold stress maximally increased mean blood pressure during the second minute, it maximally increased heart rate and cardiac contractility after 60 s of immersion in both groups of subjects. Comparing normal reactors and hyperreactors by two-way ANOVA revealed a group × time interaction for heart rate but not for cardiac contractility. These findings suggest that the increase in cardiac contractility during cold-water immersion dose not reflect the levels of heart rate and muscle sympathetic nerve activity, and that the specific responses of cardiac function to a cold pressor test in hyperreactors depends on heart rate rather than cardiac contractility.     

The role of adenosine in autoregulation of cerebral blood flow

We have investigated the role of adenosine, a purine nucleoside and potent vasodilator of cerebral pial vessels, during both acute (0–60 sec) and sustained (2–5 min) changes in cerebral perfusion pressure. Brain adenosine concentrations are rapidly increased within 5 sec of the onset of systemic hypotension and parallel, in a temporal fashion, the changes in pial vessel diameter and alterations in cerebral vascular resistance. During sustained hypotension, brain levels of adenosine are increased even within the autoregulatory range. These data are constant with the hypothesis that adenosine is an important metabolic factor in cerebral autoregulation.     

Carotid artery stenosis and tachyarrhythmias: regional cerebral blood flow during high-rate ventricular pacing after one vessel occlusion in rats

The aim of the present study was to investigate the effect of hypotensive tachycardias on cerebral blood flow (CBF) in the presence of significant carotid stenosis. The experiments were performed in 57 spontaneously breathing rats during arterial normoxia and normocapnia anesthetized with thiobarbital. CBF was determined with radio-labeled microspheres during control conditions (normofrequent sinus rhythm, normotension; group A; n = 15), during high-rate left ventricular pacing (660–840 ppm) at normotension (group B₁; n = 13), borderline hypotension (group B₂; n = 15) and severe hypotension (group B₃; n = 7). In addition, CBF measurements were performed during borderline hypotension induced by hemorrhage (group C; n = 7). Global CBF was 1.09 ± 0.29 ml g^–1 min^–1 in group A, 0.93 ± 0.40 in group B₁, 0.68 ± 0.31 in group B₂ (P < 0.05 vs. A), 0.42 ± 0.16 in group B₃ (P < 0.05 vs. A) and 0.83 ± 0.2 in group C. The highest CBF values were found in the cerebellum (A; 1.43 ± 0.5 ml g^–1 min^–) and the lowest in the postocclusive tissue of the ipsilateral hemisphere (A; 0.74 ± 0.2 ml g^–1 min^–1). In all groups a 15% mean CBF reduction in the right hemispherical cerebrum in comparison to the left hemisphere was observed (P < 0.01). In contrast, hemispherical CBF of the cerebellum did not differ. The CBF blood pressure relationship shifted to lower CBF values, the threshold of CBF regulation shifted to higher blood pressure values in the tissue regions distal to the occluded vessel during hypotensive tachycardias. One carotid artery occlusion and high rate ventricular pacing seem to be a reliable model for quantifying cerebral hemodynamics during arrhythmias in the presence of carotid stenoses. Using this experimental approach it was demonstrated that hypotensive tachycardias and obstructions within the ectracranial carotid vascular bed such as arterial vessel stenoses and occlusions have an additive effect on CBF reduction.Abbreviations CBF cerebral blood flow - P_m mean arterial blood pressure Correspondence to: A. Hagendorff     

<Emphasis Type="Italic">In vitro</Emphasis> blood flow in a rectangular PDMS microchannel: experimental observations using a confocal micro-PIV system

Progress in microfabricated technologies has attracted the attention of researchers in several areas, including microcirculation. Microfluidic devices are expected to provide powerful tools not only to better understand the biophysical behavior of blood flow in microvessels, but also for disease diagnosis. Such microfluidic devices for biomedical applications must be compatible with state-of-the-art flow measuring techniques, such as confocal microparticle image velocimetry (PIV). This confocal system has the ability to not only quantify flow patterns inside microchannels with high spatial and temporal resolution, but can also be used to obtain velocity measurements for several optically sectioned images along the depth of the microchannel. In this study, we investigated the ability to obtain velocity measurements using physiological saline (PS) and in vitro blood in a rectangular polydimethysiloxane (PDMS) microchannel (300 μm wide, 45 μm deep) using a confocal micro-PIV system. Applying this combination, measurements of trace particles seeded in the flow were performed for both fluids at a constant flow rate (Re = 0.02). Velocity profiles were acquired by successive measurements at different depth positions to obtain three-dimensional (3-D) information on the behavior of both fluid flows. Generally, the velocity profiles were found to be markedly blunt in the central region, mainly due to the low aspect ratio (h/w = 0.15) of the rectangular microchannel. Predictions using a theoretical model for the rectangular microchannel corresponded quite well with the experimental micro-PIV results for the PS fluid. However, for the in vitro blood with 20% hematocrit, small fluctuations were found in the velocity profiles. The present study clearly shows that confocal micro-PIV can be effectively integrated with a PDMS microchannel and used to obtain blood velocity profiles along the full depth of the microchannel because of its unique 3-D optical sectioning ability. Advantages and disadvantages of PDMS microchannels over glass capillaries are also discussed.     

Lesion based diagnostic performance of dual phase <Superscript>99m</Superscript>Tc-MIBI SPECT/CT imaging and ultrasonography in patients with secondary hyperparathyroidism

Background

We aimed to evaluate the diagnostic performance of ^99mTc-MIBI SPECT/CT and ultrasonography in patients with secondary hyperparathyroidism (SHPT), and explored the factors that affect the diagnostic performance.

Methods

^99mTc-MIBI SPECT/CT and ultrasonography were performed in 50 patients with SHPT within 1 month before they underwent surgery. Imaging results were confirmed by the pathology. Pearson correlation analysis was used to determine the correlation of PTH level with clinical data. The optimal cutoff value for predicting positive ^99mTc-MIBI results was evaluated by ROC analysis in lesions diameter.

Results

Forty-nine patients had a positive ^99mTc-MIBI imaging results and 39 patients had positive ultrasonography results. The sensitivities of ^99mTc-MIBI and ultrasonography were 98.00% and 78.00%, respectively. A total of 199 lesions were resected in 50 patients. Among them, 183 lesions were proved to be parathyroid hyperplasia. On per-lesion basis analysis, the sensitivity and specificity of ^99mTc-MIBI and ultrasonography were 59.34% and 75.00% vs 46.24% and 80.00%, respectively. The Pearson correlation analysis showed that the serum AKP and PTH level had a significant linear association (r?=?0.699, P?<?0.001). The lesion diameter was a statistically significant predictive factor in predicting positive ^99mTc-MIBI SPECT/CT. The optimal cutoff value for predicting positive ^99mTc-MIBI results evaluated by ROC analysis in lesions diameter was 8.05 mm.

Conclusion

Dual phase ^99mTc-MIBI SPECT/CT imaging had a higher sensitivity in patients with SHPT than ultrasonography. Therefore, using ^99mTc-MIBI positioning the lesion could be an effective method pre-surgical in patients with SHPT.

     

Measurements of cardiac output and organ blood flow in rats using 99Tcm labelled microspheres

The cardiac output and regional blood flow have been simultaneously determined in the anesthetized rat by using the reference organ method. ⁹⁹Tc^m labelled dextran 15 μm microspheres were injected in the left ventricle while simultaneously an arterial reference sample was drawn at constant known rate. The values calculated regarding cardiac output agree well with previously recorded series. Regional organ blood flow in the rat is presented as ml. min^-1. g^-1 tissue and values do agree with those reported by others. The results indicate that the reference organ method can be used in the rat for the study of cardiac output and regional blood flow.