Hydrogen Gas Clearance Method Research Articles

Comparison of CCD-equipped laser speckle flowgraphy with hydrogen gas clearance method in the measurement of optic nerve head microcirculation in rabbits

The aim of this study was to verify the correlation between mean blur rate (MBR) obtained with CCD-equipped laser speckle flowgraphy (LSFG) and capillary blood flow (CBF) obtained by the hydrogen gas clearance method in rabbit optic nerve head (ONH). Using Japanese white rabbits under systemic anesthesia, a hydrogen electrode was inserted an area of the ONH free from superficial capillaries. MBR was measured with LSFG near the hydrogen electrode. CBF and MBR were measured in the range of 32.4–83.5 mL/min/100 g and 3.5–6.0, respectively. MBR and CBF were significantly correlated (r = 0.73, P < 0.01, n = 14). After inhalation of carbon dioxide (CO2) or intravenous administration of endothelin-1 (ET-1), MBR and CBF were changed in the relative range of 0.74–1.27 and 0.76–1.35, respectively. The relative changes in MBR and CBF induced by CO2 and ET-1 were also significantly correlated (r = 0.67, P < 0.01). The current results suggest that MBR may correlate with CBF and also change with CBF, as an index of blood flow in the ONH, linearly.

Feasibility of Measuring Human Pancreatic Perfusion In Vivo Using Imaging Techniques

The objective of this study was to demonstrate the feasibility of pancreatic perfusion computed tomography (CT) and review pancreatic perfusion measurements by various imaging modalities. Dynamic CT data from 8 patients (4 men; mean age, 64.8 [SD, 12.1] years; range, 40-80 years) with normal pancreas were analyzed using 2 analytical models: the maximum-slope and compartment-model methods. Literature search was also performed. Although the perfusion value estimated by the maximum-slope method (88.1 [SD, 42.1] mL/min per 100 mL) was significantly smaller than that of the compartment-model method (127.0 [SD, 70.5]; P < 0.001), there was a linear correlation between them (r = 0.97, P < 0.001). In the literature review, 15 studies that reported the absolute values of normal pancreatic perfusion, by using perfusion CT, dynamic magnetic resonance imaging, hydrogen gas clearance method, and 15O-H2O-positron emission tomography were found. The reported mean values of normal pancreatic perfusion ranged from 38.4 to 356 mL/min per 100 mL, and there was a great deal of individual variation. Perfusion CT may provide reliable perfusion measurements of the pancreas, and the normal value was estimated at around 100 mL/min per 100 mL with a great deal of individual variation. The maximum-slope method may provide a lower perfusion value compared with the compartment-model method.

Use of laser speckle flowgraphy in ocular blood flow research

Laser speckle flowgraphy (LSFG) allows for the quantitative estimation of blood flow in the optic nerve head, choroid, retina and iris in vivo. It was developed to facilitate the non-contact analysis of ocular blood flow in living eyes, utilizing the laser speckle phenomenon. The technique uses a fundus camera, a diode laser, an image sensor, an infrared charge-coupled device (CCD) camera and a high-resolution digital CCD camera. Normalized blur (NB), an approximate reciprocal of speckle contrast, represents an index of blood velocity, and shows a good correlation with tissue blood flow rates determined with the microsphere method in the retina, choroid or iris, as well as blood flow rates determined with the hydrogen gas clearance method in the optic nerve head. The square blur ratio (SBR), another index for quantitative estimation of blood velocity, is proportional to the square of the NB. The SBR is theoretically a more exact measurement which is proportional to velocity, whereas the NB is an approximation. Normalized blur was calculated in earlier versions of LSFG because of technical limitations; the SBR is used in current versions of the LSFG instrument. As these values are in arbitrary units, they should not be used to make comparisons between different eyes or different sites in an eye. Clinical protocols, calibration, evaluation procedures and possible limitations of the LSFG technique are described and the results of ocular blood flow studies using LSFG are briefly summarized. The LSFG method is suitable for monitoring the time-course of change in the tissue circulation at the same site in the same eye at various intervals, ranging from seconds to months. Unresolved issues concern the effect of pupil size on measurement results, the effects of various stimulations, and how to measure choroidal and retinal blood flow velocity separately without using the blue-component of argon laser.

Effects of Estrogen and Progrestin on Hypothalamic Blood Flow Autoregulation

The consequences of female sex hormone deficiency and the effects of hormone replacement therapy are controversial because individual hormones and their derivates can result in partially antagonistic activities. This intricate system involving cerebral autoregulatory mechanisms caused by ovariectomy and female sex hormone replacement was studied in rats. The lower limit of cerebral blood flow autoregulation was determined by stepwise reduction of systemic arterial pressure while simultaneously measuring the changes of the hypothalamic blood flow (HBF) using the hydrogen gas-clearance method. In ovariectomized rats resting HBF decreased substantially and the threshold of cerebrovascular autoregulation decreased to 40 mm Hg. Estrogen replacement prevents the former change and shifts the latter upwards. Similarly, progestin replacement restores autoregulation to the physiological levels found in control animals, whereas it has no influence on the ovariectomy-induced reduction of resting blood flow. Steady-state HBF and compensatory changes of regional cerebral vascular autoregulation are altered significantly following ovariectomy. Estrogen or progestin replacement has an opposite effect on these cerebral circulatory parameters. Our observations highlight the essential role of female sex hormones in hypothalamic autoregulation during hypotensive stress.

Quantitative estimation of renal blood flow by power Doppler ultrasonography in renovascular hypertensive dogs

We estimated the value of power Doppler (PD) imaging analysis for the quantitative assessment of renal cortical blood flow (RCBF) in chronic two-kidney, one-clip (2K-1C) hypertensive dogs. To evaluate the correlation between RCBF and PD signals, RCBF and the mean pixel intensity (MPI) of PD signals were simultaneously obtained at same region in renal cortex under progressive constriction of left main renal artery in five mongrel dogs. RCBF was measured by electrolytic hydrogen gas clearance method, and PD images were transferred to computer and analyzed by the image-analysis software Openlab. To assess the value of quantitative PD imaging analysis on RCBF in renovascular hypertension, in six mongrel dogs with chronic 2K-1C hypertension, PD images in both of clipped kidneys (CK) and non-clipped kidneys (NK) were obtained and analyzed before and 60 minutes after the intravenous infusion of captopril or sodium nitroprusside at 10-minute intervals. There was a linear correlation between RCBF and MPI (r= 0.878, P < 0.0001). MPI in both CK and NK significantly increased after the infusion of captopril, while no significant change was observed in both CK and NK after the infusion of sodium nitroprusside, despite similar reduction of mean arterial blood pressure. Our data suggest that the acute inhibition of angiotensin-converting enzyme increased RCBF in both CK and NK of chronic 2K-1C dogs. The quantitative analysis of PD flow signals in kidney is noninvasive and a useful method to evaluate regional changes of renal tissue blood flow in various renal diseases.

Interactions between the heme oxygenase, cyclooxygenase and nitric oxide synthase pathways in the regulation of the resting hypothalamic blood flow

The heme-oxgenase (HO) – carbon monoxide (CO) pathway has been reported to evoke direct vascular effects and to influence other vasoregulatory mechanisms like the cyclooxygenase (COX) and nitric oxide synthase (NOS) systems. Since the hypothalamus expresses relatively high HO, COX and NOS levels compared to other brain regions, we have hypothesized interactions among these pathways in the regulation of the resting local hypothalamic tissue blood flow (HBF). Therefore, we have investigated whether inhibition of the COX and NOS pathways influences the alterations of the HBF that develop after HO blockade. Adult male Wistar rats were anaesthetized with 1.3 g/kg urethane. The femoral arteries were cannulated for measurement of the mean arterial pressure (MAP) and for blood sampling. HBF was measured by use of the hydrogen gas-clearance method. HO-blockade was induced by ip. injection of 45 imol/kg zinc deuteroporphyrin 2,4-bis glycol (ZnDPBG). In the first group of the animals HBF, MAP and blood gas measurements were performed under physiological conditions. In the second and third experimental groups the animals received diclofenac (10 mg/kg iv.) or NG-nitro-L-arginine methyl ester (L-NAME, 50 mg/kg iv.) pretreatment in order to inhibit prostanoid- or NO-synthesis, respectively. In the fourth group the animals received combined diclofenac and L-NAME pretreatment. In all groups HBF values were determined before and after the pretreatment as well as after the induction of HO-blockade. Baseline arterial pO2, pCO2 and pH values were within the physiological range and did not change throughout the experiments. In animals pretreated with L-NAME or with diclofenac+L-NAME the MAP was significantly higher (1435 mmHg and 1386 mmHg, respectively) than in controls (995 mmHg) or after diclofenac pretreatment alone (957 mmHg). ZnDPBG administration, however, did not influence the MAP in any of the experimental groups. L-NAME and diclofenac+L-NAME pretreatments markedly reduced the HBF (from 0.900.10 to 0.550.09 ml/g/min and from 0.790.11 to 0.440.11 ml/g/min, respectively) while diclofenac alone had no significant effect (0.840.09 vs. 0.880.10 ml/g/min). ZnDPBG administration in control animals did not influence the HBF (-0.34.1 %), but significantly increased it by 15.52.9 % after diclofenac pretreatment. In contrast, ZnDPBG induced a marked reduction (-20.65.6 %) of the HBF in animals pretreated with L-NAME. In animals receiving both diclofenac and L-NAME pretreatment the HBF remained unchanged after ZnDPBG administration (+5.95.4 %). Our observations indicate that the HO pathway interacts with both the COX and the NOS systems in the regulation of the hypothalamic circulation. Endogenous CO production appears to increases the HBF via a COX-dependent mechanism, but at the same time suppresses NOS activity which leads to the reduction of HBF. These effects of CO may neutralize each other under physiological conditions. In pathophysiological states, however, which are associated with altered COX or NOS activity, the HO pathway may significantly influence the resting CBF.

Neural regulation of hepatic blood flow in rats: an in vivo study

The aim of the present study was to elucidate the influence of the hepatic sympathetic and parasympathetic (vagal) nerves on the hepatic blood flow (HBF), both tonically and when stimulated, using urethane-anesthetized rats as an in vivo experimental model. HBF was measured at the surface of the lateral left lobe of the liver using laser Doppler flowmetry and the hydrogen gas clearance method. Denervation of the hepatic sympathetic nerves had no influence on the HBF, while electrical stimulation of the hepatic sympathetic nerves caused the HBF to decrease in a frequency-dependent manner. This decrease was shown to occur via α-adrenergic receptors. In contrast, neither denervation nor electrical stimulation of the hepatic vagal nerves elicited significant changes in the HBF. These results demonstrate that the sympathetic and vagal hepatic nerves have little or no tonic influence on the HBF of rats under urethane anesthesia, whereas the HBF decreases in response to activation of the hepatic sympathetic nerves.

Efficacy of prostaglandin E 1 in combination with volume replacement therapy in the treatment of hemorrhagic shock in dogs

Objective: The aim of the present study was to assess the effects of prostaglandin E 1 (PGE 1) on hemodynamic and splanchnic blood flow in a canine model of hemorrhagic shock and volume replacement therapy. Methods: Hemorrhagic shock was induced in 14 anesthetized dogs by withdrawing blood into a reservoir until the mean arterial pressure stabilized at 50 mm Hg for 30 minutes. During oligemia, the drawn blood was stored at room temperature in plastic bags containing citrate-phosphate-dextrose solution. The shock period was then terminated and the remainder of the drawn blood was reinfused within a 2-minute period. The dogs were divided into 2 equal groups. Group P received PGE 1 0.1 μg/kg per minute; group S received saline in an amount equal to the diluent in group P (0.6 mL/kg per hour). The efficacy of both therapies in maintaining hemodynamic variables and splanchnic blood flow (renal cortex, renal medulla, liver, and pancreas) was investigated over 180 minutes. Splanchnic blood flow was determined by the hydrogen gas clearance method. Results: Sixty to 180 minutes after resuscitation, the cardiac index and left ventricular stroke work index values in group P were significantly greater than those in group S ( P < 0.05), and systemic vascular resistance in group P was significantly lower than that in group S during the resuscitative period ( P < 0.05). Splanchnic organ blood flow decreased significantly with hemorrhagic shock. Splanchnic blood flow to all organs in group P returned to baseline values when resuscitative therapy was performed, but the values in group S were decreased significantly compared with baseline despite resuscitation ( P < 0.05). Moreover, all splanchnic blood flow values were significantly greater in group P than in group S. Conclusions: The results of this study in dogs demonstrate that PGE 1 added to volume replacement therapy is a useful adjuvant with respect to hemodynamic and splanchnic recovery in hemorrhagic shock.

Effect of diet on changes in small intestinal blood flow following intracolonic administration of indomethacin to rats.

Liquid diet (LD) is known to be protective against indomethacin-induced enteropathy, which is thought to be associated with ischemic change. We tested the hypothesis that the solid component of diet modulates small intestinal blood flow (SIBF) following indomethacin administration. In the first experiment, male Wistar rats were divided into 18-hr-fasted and normal diet groups. Indomethacin (20 mg/kg) or vehicle was administered intracolonically. SIBF was measured on both the mesenteric and antimesenteric sides of the intestine, using the hydrogen gas clearance method. In the second experiment, rats were given LD alone or LD with increasing concentration of soluble/insoluble fiber for seven days. The baseline SIBF was significantly higher in the groups with normal diet and LD with fiber than in the fasting and LD groups. Following indomethacin administration, SIBF gradually decreased in the groups with normal diet and LD with insoluble fiber, while neither liquid diet nor fasting reduced SIBF. There was no difference in SIBF between the mesenteric and antimesenteric sides of the intestine in any group. Our findings suggest that solid components of diet increase basal SIBF and decrease SIBF following indomethacin administration.

A preventive effect of a selective endothelin-A receptor antagonist, S-0139, on the erythropoietin-induced reduction of the renal cortical blood flow.

We have confirmed that renal cortical blood flow (RCBF) is significantly decreased by recombinant human erythropoietin (EPO). Endothelin-1 (ET(1)) is thought to be a mediator because its level increased significantly when EPO was administered. The present study was performed to clarify the effect of a selective ET-A receptor antagonist, S-0139, on EPO-induced RCBF reduction. Ten-week-old male Wistar rats, weighing about 250 g, were divided into five groups. Group 1 (n = 5), a control group, received normal saline solution (NSS). Group 2 (n = 5) received 200 U/kg body weight (BW) per hour of EPO. Group 3 (n = 5) received 400 U/kg BW per hour of EPO. Group 4 (n = 5) received both 200 U/kg BW per hour of EPO and 4 mg/kg BW per hour of S-0139. Group 5 (n = 5) received both 200 U/kg BW per hour of EPO and 40 mg/kg BW per hour of S-0139. Drugs were administered intravenously via the right femoral vein using a microinfusion pump for 4 h under urethane anesthesia. The RCBF was measured every 30 min by the hydrogen gas clearance method. When the 4 h had elapsed, the concentrations of plasma creatinine (Cr), ET1 and renin activity (RA) were measured. Compared with group 1, groups 2 and 3 showed significant (P < 0.001) decreases of RCBF, while the ET1 levels of these two groups increased significantly (P < 0.03). The ET1 of groups 4 and 5 also increased significantly (P < 0.03), however, the RCBF of these two groups did not decrease. No significant differences were observed in either Cr or RA between the five groups. EPO induces ET(1) secretion. The reduction of RCBF is due to ET(1)-derived vasoconstriction. S-0139 has potential for preventing EPO-induced and ET(1)-mediated RCBF reduction.

Role of calcitonin gene-related peptide and capsaicin-sensitive afferents in central thyrotropin-releasing hormone-induced hepatic hyperemia

The involvement of capsaicin-sensitive afferent neurons and calcitonin gene-related peptide (CGRP) in the central thyrotropin-releasing hormone (TRH)-induced hepatic hyperemia was investigated in urethane anesthetized rats. Both systemic capsaicin pretreatment and intravenous administration of CGRP receptor antagonist, human CGRP-(8–37), completely abolished the stimulatory effect of hepatic blood flow induced by intracisternal injection of TRH analog (RX-77368; p-Glu-His-(3,3′-dimethyl)-Pro-NH2, 100 ng), assessed by the hydrogen gas clearance method. These data demonstrate the involvement of capsaicin-sensitive afferent neurons and CGRP in the central TRH-induced stimulation of hepatic blood flow.

Effect of pancreastatin on cerulein-stimulated pancreatic blood flow and exocrine secretion in anaesthetized rats.

Pancreastatin (PST) is an inhibitor of pancreatic exocrine secretion in vivo but not in vitro, which suggests that the inhibitory effect of PST is indirect, that is, not mediated by a specific receptor on pancreatic acinar cells. In this study, we investigated the effects of PST on pancreatic exocrine secretion and local pancreatic blood flow in anaesthetized rats to elucidate the participation of PST in indirect regulation of pancreatic exocrine function through blood supply. Pancreastatin (100, 200 or 500 pmol/kg per h) was administered intravenously under background infusion of cerulein (0.5 microg/kg per h), a cholecystokinin analogue. Pancreatic exocrine secretion was monitored by volume and protein output of the pancreatic juice and local pancreatic blood flow was measured by the hydrogen gas clearance method. Pancreastatin significantly reduced cerulein-induced local pancreatic blood flow in a dose-dependent manner. Pancreatic exocrine secretion was also reduced significantly by PST dose-dependently. Pancreastatin did not change systemic blood pressure. These results suggested that the reduction of pancreatic blood flow is associated with the reduction of pancreatic exocrine secretion. We conclude that the mechanism of PST-induced inhibition of pancreatic exocrine secretion is, at least, partly mediated by the reduction of local pancreatic blood flow through blockade, caused by the action of cerulein on pancreatic blood flow.

Mucosal blood flow and generation of superoxide in rat experimental colitis induced by succinic acid.

As we consider succinic acid to be an exacerbating factor in ulcerative colitis, we investigated its influence on rat colonic mucosa in terms of mucosal blood flow and superoxide generation. We measured mucosal blood flow by the hydrogen gas clearance method and superoxide generation by the chemiluminescence method, and observed histopathological findings to determine the effects of succinic acid. After the instillation of succinic acid of any concentration tested to the colon, mucosal blood flow decreased. Histopathologically, the higher the concentration of succinic acid, the greater was the erosion formation in the colonic mucosa, while significant polymorpho-nuclear cell infiltration superoxide generation from colon tissue were observed with 0.01% succinic acid compared with higher or lower concentrations. Succinic acid, at fecal concentrations found in active stage ulcerative colitis, appears to be implicated in mucosal injury, mediated by a decrease in colonic mucosal blood flow and infiltration of superoxide-generating polymorpho-nuclear cells into the mucosa.

Effect of dibutyryl cyclic adenosine monophosphate on skeletal muscle reperfusion injury in the rat.

To clarify the action of dibutyryl cyclic adenosine monophosphate (DBcAMP) on reperfused ischemic muscle, experiments were conducted using the hindlimbs of 18 male Lewis rats. At the midportion of the thigh all tissues except for the femoral artery and vein were transected, and a route for continuous intravenous infusion was secured in a contralateral limb vein. After inducing total ischemia by clamping the femoral artery and vein with a vascular clamp for 4 h, the limb was reperfused for 1 h. Blood flow was then compared using the hydrogen gas clearance method in a group in which DBcAMP 10 mg was continuously infused from a vein in the contralateral hindlimb from 1 h prior to the induction of ischemia to 1 h after the completion of ischemia (DBcAMP group), a group in which saline was infused in the same manner (control group), and a group which was subjected to biopsy alone (biopsy group). The percent change in blood flow was significantly higher in the DBcAMP group than in the control group at 15 and 30 min after the release of the clamp. Adenosine triphosphate (ATP), phosphocreatine (PCr), and lipid peroxide (LPO) were measured in tissue samples obtained 1 h after reperfusion. Serum LPO was measured in blood samples collected at the same time. ATP values were higher in the DBcAMP group than in the control group. PCr was significantly higher in the DBcAMP group than in the control group. LPO levels in skeletal muscle tissue did not differ significantly between the DBcAMP and control groups. In contrast, serum LPO levels were significantly lower in the DBcAMP group than the control group. On morphologic analysis the control and DBcAMP groups showed normal vascular endothelial cells and absence of the 'no-reflow' phenomenon. These data confirm that in this reperfusion model the administration of DBcAMP enhances the viability of skeletal muscle cells. Moreover, mediated by an effect on vascular endothelial cells this agent is thought to be of help in mitigating the vascular endothelial cell injury occurring in acute ischemic injury. DBcAMP may be a useful agent in mitigating skeletal muscle ischemia-reperfusion injury.

Effects of infrasound on gastric mucosal blood flow in rats

To clarify the effects of infrasound on gastric mucosal blood flow, rats were exposed to infrasound for 20 minutes. The sounds were pure tones of 8, 16 and 32 Hz, at sound levels ranging from 80 dB to 130 dB. Gastric mucosal blood flow was determined by the inhaled hydrogen gas clearance method. Norepinephrine and epinephrine concentrations in the plasma were also measured. The exposed rats showed decreased gastric mucosal blood flow with increasing sound levels of infrasound at each octave-band frequency. To significantly decrease the gastric mucosal blood flow, infrasound at 32, 16 and 8 Hz needed sound levels of 100, 110 and 130 dB, respectively. These findings suggest that, as the frequency of infrasound decreases, an increased sound level is necessary to decrease the gastric mucosal blood flow. The norepinephrine and epinephrine concentrations in the plasma were 0.65±0.47n.g/ml and 0.35±0.43 ng/ml, respectively, in the control rats, while the corresponding values were 0.91±0.87 ng/ml and 0.74±0.81 ng/ml, respectively, in the exposed rats. There were significant increases (p>0.05) in norepinephrine and epinephrine. Thus, it is probable that exposure to infrasound stimulates the sympathetic nervous system and causes a decrease in gastric mucosal blood flow.

New chronic pancreatitis model with diabetes induced by cerulein plus stress in rats.

To establish a new experimental model of chronic pancreatitis (CP) with diabetes, we investigated pancreatic endocrine function, blood flow, and histopathology in CP induced by repetition of cerulein injection plus water immersion stress in rats. CP rats were treated with water immersion stress for 5 hr and two intraperitoneal injections of 20 micrograms/kg body weight of cerulein once a week for 16 weeks. In the CP group, pancreatic contents of protein, amylase, elastase, and lipase significantly decreased to 64, 38, 23, and 68% of the control group, respectively. In oral glucose tolerance test (glucose 2 g/kg body wt), blood glucose level in the CP group was 212.1 +/- 97.8 mg/dl (mean +/- SD) at 30 min and was significantly higher than the control group (126.3 +/- 15.4 mg/dl)(P < 0.05). Two of seven rats in the CP group showed an obvious diabetic insulin in the CP group was 640.1 +/- 148.7 pM, significantly lower than in the control group (1133.4 +/- 242.0 pM)(P < 0.001). However, insulin content in the pancreas was 12.37 nmol/pancreas). In CP rats, winding and dilatation of surface blood vessels and gland atrophy were evident. Marked fibrosis, fatty changes, and destruction of lobular architecture were also demonstrated microscopically, although the structure of each pancreatic islet was preserved and each islet was fully stained with anti-insulin antibody. In the CP group, pancreatic blood flow by the hydrogen gas-clearance method was 197.6 +/- 33.0 ml/min/100 g, which was significantly less than the control group (276.2 +/- 19.1 ml/min/100 g) (P < 0.001). Thus, we conclude that the CP model induced by cerulein plus stress is a new CP model with diabetes in rats, in which the glucose tolerance was impaired without loss of insulin reserve.

Measurement of hepatic blood flow using 111In colloid.

The reduced hepatic blood flow calculated from hepatic scintigram with 198Au colloid was elucidated as the primary responsible factor for postoperative hepatic insufficiency. However 198Au colloid is no longer in use because of the high levels of radiation. Although 99mTc-phytate behaves similarly to 198Au on imaging, there were discrepancies between the hepatic blood flow index (KL) value and the severity of cirrhosis determined by laboratory data or by histology. In the measurement of hepatic blood flow using a radioactive colloid, factors like organ distribution, stability and uniformity of the colloid particles influence the values. In the present study, a 111In colloid was prepared and administered to rats to investigate the usefulness: as much as 95.4 (0.8) [Mean (+/- SD)]% of the colloid accumulated in the liver at pH 6.8. The distribution of particle diameter was within a relatively narrow range with the peak at 0.2 to 0.4 microns. Moreover, the KL values were not affected by condition of the reticuloendothelial system. The values showed a significant correlation with the measurements of the hepatic tissue blood flow obtained by the hydrogen gas clearance method (gamma = 0.83, P < 0.001). Thus, the 111In colloid can be clinically used as a substitute for 198Au colloid in the preoperative examination for estimation of the limit of resection.

Effect of intracarotid administration of 6-aminonicotinamide on cerebral blood flow in cats.

We evaluated the effects of an adenosine triphosphate blocker, 6-aminonicotinamide (6-ANA), on the cerebral blood flow (CBF), cerebral metabolism, and electroencephalogram of cats. Catheters were inserted into the common carotid artery of 16 adult cats anesthetized with ketamine via the lingual artery. We measured CBF in the infused area by the inhaled hydrogen gas clearance method and analyzed the electroencephalogram frequency. Cerebral metabolism was estimated by oxygen extraction (vol/%) and glucose utilization (millimoles) using data arterial (aorta) and sagittal sinus blood samplings. A solution of 6-ANA (6.0 mg/mL) (n = 8) or saline (n = 8) was infused via catheter at 2.0 mL/min for 3 minutes followed by a 60-minute observation of CBF, cerebral metabolism, vascular resistance, and the electroencephalogram components, alpha-2 ratio [= alpha-2/(alpha-1+alpha-2)]. The effect of 6-ANA on capillaries was evaluated by extravasation of Evans blue dye and electron microscopic findings. Moderate reductions in CBF, cerebral metabolism, and the alpha-2 ratio were observed during the infusion of 6-ANA versus saline infusion (P < .05 by paired t test and ANOVA). Vascular resistance was significantly increased (P < .05). No abnormalities were observed in the capillaries of the infused hemisphere. Results indicated that 6-ANA produced a downregulation of cerebral blood flow in cats.

Effect of peptide YY on intestinal and hepatic blood flow in dogs

Objective: To investigate the effect of peptide YY (PYY) on the flow of splanchnic blood and bile in dogs. Methods: Under general anaesthesia, the dogs received porcine PYY at doses of 100, 400, or 800 pmol/kg/h for 1.5 h. Blood flow was measured in the subserosa of the jejunum, ileum, and colon as well as in the liver, using the hydrogen gas clearance method, before, during, and after PYY infusion. Choledochal bile was collected and its volume measured. Results: Colonic blood flow was significantly inhibited by 100, 400, and 800 pmol/kg/h PYY compared with the pre-infusion levels (P < 0.05, P < 0.05, and P < 0.01, respectively). It was also inhibited by 800 pmol/kg/h PYY (P < 0.05) compared with the non-infusion group

Vascular bed‐dependent roles of the peptide CGRP and nitric oxide in acid‐evoked hyperaemia of the rat stomach.

1. Acid back-diffusion through a disrupted gastric mucosal barrier is known to increase gastric mucosal blood flow via a neural mechanism. The present study examined how the acid-evoked change in the gastric microcirculation compares with blood flow changes in the left gastric artery, one of the major arteries supplying the stomach, and whether the dilator mediators in the left gastric artery are identical to those in the gastric mucosa. 2. The experiments were performed on rats anaesthetized with urethane. Blood flow in the left gastric artery was measured by the ultrasonic transit time shift technique, and blood flow in the gastric mucosa was assessed by the hydrogen gas clearance method. 3. Gastric acid back-diffusion evoked by perfusion of the stomach with 15% ethanol in 0.15 M HCl increased blood flow in the left gastric artery by a factor of 4.7, which was significantly larger than the 2.9-fold increase in blood flow through the gastric mucosa. Blood pressure and heart rate were not altered appreciably. 4. The acid-evoked hyperaemia in the left gastric artery was left unaltered by atropine and the substance P receptor antagonist RP-67580. 5. The calcitonin gene-related peptide (CGRP) antagonist CGRP (8-37) had no effect on gastric blood flow but prevented the dilator action of CGRP and inhibited the acid-evoked hyperaemia in the gastric mucosa to a larger degree than the hyperaemia in the left gastric artery. 6. Blockade of nitric oxide synthesis by N omega-nitro-L-arginine methyl ester (L-NAME) caused constriction of the left gastric artery and the gastric mucosal microvessels. The acid-evoked vasodilatation in the gastric mucosa was blocked by L-NAME, whereas the dilator response in the left gastric artery was not significantly depressed. 7. The data show that the gastric hyperaemic response to acid back-diffusion results from dilatation of mucosal microvessels and extramural arteries. The dilator mechanisms, however, differ between the two vascular beds. CGRP and nitric oxide are important vasodilator mediators in the gastric mucosa but are of less relevance in the left gastric artery.