Increase In Regional Blood Flow Research Articles

A cerebral blood flow study on tonic pain activation in man

This study examined brain areas involved in tonic pain perception. Cerebral blood flow was assessed by dynamic Xenon-133 inhalation single-photon emission tomography (SPET) in 7 healthy right-handed male volunteers undergoing the cold pressor test (CPT). In single experimental sessions, each subject was scanned twice, once in the resting state and once while immersing the left hand in freezing water (0° C ± 1). Immersion of the hand induced severe pain (visual analogue scale: 6.9 ± 1.9) in all subjects. After correction for pCO 2, cerebral blood flow was analyzed by placing a template of square regions of interest (ROIs) over 5 selected tomographic slices. Relative to the resting-state values, during the CPT, flow determinations revealed a 7–8% regional blood flow increase in the contralateral frontal lobe and bilateral temporal regions and a 15% flow increase in a ROI located over the primary sensorimotor cortex in the tomogram at 80 mm above the orbito-meatal line (corresponding to the cortical somatotopic representation of the hand) contralateral to the stimulated side. The tonic pain induced by the CPT thus appears to activate the contralateral frontal and bilateral temporal regions and more prominently, the primary sensorimotor cortex. This pattern of activation suggests that tonic painful stimuli activate the cortex partly via complex circuits and partly via direct somatosensory pathways.

Pharmacological actions of "kyushin," a drug containing toad venom(2): effects on urinary volume and electrolyte excretion.

A study was conducted on the pharmacological actions of the toad venom-containing drug "Kyushin" (KY-2 and KY-R) on urinary volume and electrolytes excretion, regional blood flow, renal artery blood flow and carrageenin-induced hind-paw edema. In rabbits, KY-2 and KY-R significantly increased urinary volume after intravenous administration of 8 mg/kg. In guinea pigs, KY-2 and KY-R produced a significant increase in urinary volume after intraduodenal administration (i.d.) of 80 mg/kg. In guinea pigs treated with propranolol, KY-2 at 20 and 40 mg/kg p.o. and KY-R at 40 mg/kg p.o. increased urinary volume. At 40 mg/kg i.d. both KY-2 and KY-R produced an increase in regional blood flow, as determined by the hydrogen gas clearance method, of the brain areas including the amygdaloid nucleus, but did not affect regional blood flow in liver, kidney and skeletal muscle, or renal artery blood flow. In rats, carrageenin-induced hind-paw edema was inhibited by KY-2 or KY-R at 600 mg/kg p.o.

Gas exchange and regional redistribution of pulmonary blood flow during resuscitation of acute pulmonary bead embolization

Acute pulmonary embolism (PE) was induced by injecting polystyrene beads into the right atrium of 18 anaesthetized dogs. The animals were resuscitated for 45 min with either Ringer's Lactate (RL), norepinephrine (NE) or isoproterenol (IP). The multiple inert gas elimination technique (MIGET) was used to estimate the distributions of ventilation ( V dot ) and blood flow ( Q dot ) to different V dot Q dot regions. Measurements were made prior to embolism, 10 min after PE and during the resuscitative phase. Microspheres with three different radioactive labels were also used to mark blood flow distribution to different lung regions in these three phases. The data show that cardiac output decreases after PE, while perfusion to shunt and low V dot Q dot regions increases. Pulmonary blood flow heterogeneity, estimated from the MIGET data, is also increased after PE. Resuscitation by RL or NE consistently increases cardiac output but IP does so inconsistently and is associated with systemic hypotension. All three methods of resuscitation cause increases in perfusion to the shunt and low V dot Q dot regions but no change in perfusion heterogeneity in the remaining V dot Q dot units. Increases in regional blood flow during resuscitation occur preferentially in the less embolized areas. The concomitant increase in perfusion to shunt and low V dot Q dot units suggests that increased perfusion to these less embolized regions results in further hypoxemia despite improvement in cardiac output.

Effect of age on cardiovascular responses to static muscular contraction in beagles.

Induced muscular contraction in anesthetized animals results in significant hemodynamic and regional blood flow (RBF) changes. Although reflex cardiovascular responses initiated in contracting muscle have been firmly established, little is known about the effects of age on these responses. Because other reflex responses that involve sympathetic activation appear to be attenuated with age, it was hypothesized that reflex efferent cardiovascular responses that normally occur during muscular contraction would be impaired in senescent dogs. Therefore, hemodynamic and RBF responses to induced static hindlimb contraction (HLC) were evaluated in 8- to 14- and 2- to 3-yr-old beagles during alpha-chloralose anesthesia. Most baseline hemodynamic parameters were similar in both groups, but heart rate was significantly (P < 0.05) higher in old dogs. During HLC, heart rate and blood pressure increased in the young and old dogs. However, increases in stroke volume and cardiac output were greater in old dogs, combined with a reduction in systemic vascular resistance not observed in young dogs. No age-related difference in baseline RBF (microspheres) was observed in six of eight abdominal regional circulations and in each of four skeletal muscle groups. During HLC, RBF reductions occurred in six of eight abdominal organs in young and old dogs. However, the reduction in RBF and concomitant increase in vascular resistance in all eight abdominal regions combined was almost twice as great in young vs. old dogs. In noncontracting skeletal muscle, RBF decreased and vascular resistance increased four times more in young vs. old dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Motor practice and neurophysiological adaptation in the cerebellum: a positron tomography study

We have used positron tomography (PET) to demonstrate that some parts of the motor system exhibit physiological adaptation during the repeated performance of a simple motor task, but others do not. In contrast to the primary sensori-motor cortex, the cerebellum exhibits a decrease in physiological activation (increases in regional blood flow during performance) with practice. A new application of factorial experimental design to PET activation studies was used to make these measurements in four normal males. This design allowed adaptation to be examined by testing for an interaction between regional cerebral blood flow (rCBF) increases brought about by a motor task and the number of trials (time). These findings are interpreted as the neurophysiological correlates of synaptic changes in the cerebellum associated with motor learning in man.

Brain adaptation to chronic hypobaric hypoxia in rats.

Rats were exposed to hypobaric hypoxia (0.5 atm) for up to 3 wk. Hypoxic rats failed to gain weight but maintained normal brain water and ion content. Blood hematocrit was increased by 48% to a level of 71% after 3 wk of hypoxia compared with littermate controls. Brain blood flow was increased by an average of 38% in rats exposed to 15 min of 10% normobaric oxygen and by 23% after 3 h but was not different from normobaric normoxic rats after 3 wk of hypoxia. Sucrose space, as a measure of brain plasma volume, was not changed under any hypoxic conditions. The mean brain microvessel density was increased by 76% in the frontopolar cerebral cortex, 46% in the frontal motor cortex, 54% in the frontal sensory cortex, 65% in the parietal motor cortex, 68% in the parietal sensory cortex, 68% in the hippocampal CA1 region, 57% in the hippocampal CA3 region, 26% in the striatum, and 56% in the cerebellum. The results indicate that hypoxia elicits three main responses that affect brain oxygen availability. The acute effect of hypoxia is an increase in regional blood flow, which returns to control levels on continued hypoxic exposure. Longer-term effects of continued moderate hypoxic exposure are erythropoiesis and a decrease in intercapillary distance as a result of angiogenesis. The rise in hematocrit and the increase in microvessel density together increase oxygen availability to the brain to within normal limits, although this does not imply that tissue PO2 is restored to normal.

Treatment of Thalamic Pain by Chronic Motor Cortex Stimulation

All forms of therapy, including chronic stimulation of the thalamic relay nucleus, can provide satisfactory pain control in only 20%-30% of cases of thalamic pain syndrome. In order to develop a more effective treatment for thalamic pain syndrome, we investigated the effects of stimulation of various brain regions on the burst hyperactivity of thalamic neurons recorded in cats after deafferentiation of the spinothalamic pathway. Complete, long-term inhibition of the burst hyperactivity was induced by stimulation of the motor cortex. Based on this experimental finding, we treated seven cases of thalamic pain syndrome by chronic motor cortex stimulation employing epidural plate electrodes. Excellent or good pain control was obtained in all cases without any complications or side effects. During the stimulation, an increase in regional blood flow of the cerebral cortex and thalamus, a marked rise in temperature of the painful skin regions, and improved movements of the painful limbs were observed. These results suggest that thalamic pain syndrome can be most effectively treated by chronic motor cortex stimulation.

Effects of Islet Isografts on Hemodynamic and Vascular Filtration Changes in Diabetic Rats

To assess the reversibility of diabetes-induced increases in regional vascular albumin permeation and blood flow and changes in kidney filtration function, islet isografts were given via the portal vein after 2 mo of streptozocin-induced diabetes in male Lewis rats. One month later, vascular function was assessed in control rats, islet-transplanted diabetic rats, and untreated diabetic rats (6-9 rats/group). Untreated diabetic rats were markedly hyperglycemic, hyperphagic, and polyuric. Transplanted rats were euglycemic within 6 days; 24-h urine volumes were virtually normalized by 2 wk and food consumption was normalized 4 wk after transplantation. Vascular albumin permeation in diabetic rats was significantly increased 1.4- to 1.7-fold in anterior uvea, choroid, retina, sciatic nerve, new granulation tissue, and kidney and was increased 1.1- to 1.3-fold in diaphragm, cecum, and optic nerve. Albumin permeation was not increased in aorta, brain, heart, or forelimb skeletal muscle. Islet transplants significantly reduced but did not completely normalize vascular albumin permeation in most tissues in which it was increased by diabetes but had no effect on albumin permeation in optic nerve, sciatic nerve, and diaphragm. Urinary excretion of endogenous albumin and IgG in diabetic rats was significantly increased 19- and 14-fold, respectively, and was virtually normalized 4 days after islet transplantation. Marked (1.8-fold) increases in glomerular filtration rate (GFR) in diabetic rats were also substantially reduced by islet transplants but remained elevated 1.4-fold control values. Likewise, diabetes-induced increases in regional blood flow were reduced in general but not normalized by islet transplants. These observations indicate that 1) diabetes-induced hemodynamic changes and alterations in vascular filtration function are not rapidly reversed by euglycemia after islet transplantation, 2) diabetes-induced increases in urinary albumin and IgG excretion are more readily normalized by euglycemia than increases in GFR and renal 125I-labeled bovine serum albumin (125I-BSA) filtration, and 3) significant increases in GFR and renal 125I-BSA filtration may not be manifested by albuminuria.

Modulation of Hemodynamic and Vascular Filtration Changes in Diabetic Rats by Dietary myo-inositol

To assess the potential of myo-inositol-supplemented diets to prevent diabetes-induced vascular functional changes, we examined the effects of diets supplemented with 0.5, 1, or 2% myo-inositol on blood flow and vascular filtration function in nondiabetic control rats and rats with streptozocin-induced diabetes (STZ-D). After 1 mo of diabetes and dietary myo-inositol supplementation, 1) 131I-labeled bovine serum albumin (BSA) permeation of vessels was assessed in multiple tissues, 2) glomerular filtration rate (GFR) was estimated as renal plasma clearance of 57Co-labeled EDTA, 3) regional blood flows were measured with 15-microns 85Sr-labeled microspheres, and 4) endogenous albumin and IgG urinary excretion rates were quantified by radial immunodiffusion assay. In STZ-D rats, 131I-BSA tissue clearance increased significantly (2- to 4-fold) in the anterior uvea, choroid-sclera, retina, sciatic nerve, aorta, new granulation tissue, diaphragm, and kidney but was unchanged in skin, forelimb muscle, and heart. myo-Inositol-supplemented diets reduced diabetes-induced increases in 131I-BSA clearance (in a dose-dependent manner) in all tissues; however, only in new granulation tissue and diaphragm did the 2% myo-inositol diet completely normalize vascular albumin permeation. Diabetes-induced increases in GFR and in urinary albumin and IgG excretion were also substantially reduced or normalized by dietary myo-inositol supplements. Increased blood flow in anterior uvea, choroid-sclera, kidney, new granulation tissue, and skeletal muscle in STZ-D rats also was substantially reduced or normalized by the 2% myo-inositol diet. myo-Inositol had minimal if any effects on the above parameters in control rats. These observations indicate that diabetes-induced increases in regional blood flow, 131I-BSA permeation, GFR, and urinary protein excretion can be markedly reduced or normalized by consumption of myo-inositol-supplemented diets that raise plasma myo-inositol levels approximately fivefold. The failure of the 2% myo-inositol diet to normalize GFR and blood flow and albumin permeation in several tissues despite markedly elevated plasma myo-inositol levels and normal or elevated tissue myo-inositol levels indicates that if vascular functional changes in these tissues are linked to altered myo-inositol levels, they are resistant to normalization by elevation of plasma myo-inositol levels. These results suggest that other factors independent of changes in relative or absolute tissue myo-inositol levels may play an important role in the pathogenesis of diabetes-induced vascular functional changes in these tissues.(ABSTRACT TRUNCATED AT 400 WORDS)

Central Hemodynamic and Regional Blood Flow Changes in the Newborn with Right Ventricular Hypertension

To evaluate the central hemodynamic and regional blood flow changes associated with right ventricular hypertension in the newborn, 13 anesthetized, mechanically ventilated piglets less than 3 d old were acutely instrumented to permit measurements of central vascular pressures, cardiac output, and regional blood flow (radio-labeled microsphere technique). After initial measurements, right ventricular afterload was progressively increased by means of a pulmonary arterial mechanical occluder until right-to-left foramen ovale shunt was observed. An increase in pulmonary arterial pressure from 32 +/- 2 to 55 +/- 3 mm Hg was associated with a decrease in PaO2 from 364 +/- 16 to 88 +/- 9 mm Hg and an increase in the shunt fraction from 13 +/- 1 to 28 +/- 1% (p less than 0.01) during ventilation with oxygen. Right ventricular hypertension induced a significant decrease in systemic arterial pressure from 79 +/- 3 to 63 +/- 4 mm Hg, and left ventricular cardiac output from 156 +/- 10 to 112 +/- 11 mL.min-1.kg-1 (p less than 0.01), likely secondary to a reduction in left ventricular compliance. Oxygen delivery to the brain and heart were unaffected, due to a substantial increase in regional blood flow, but a significant reduction in delivery to the bowel and kidneys were observed. Contrary to what has been reported in the adult, myocardial blood flow to the right ventricle increased during hypertension. Metabolic acidosis was seen in all animals and the changes in serum bicarbonate and whole body oxygen consumption were directly related to the magnitude of decline in systemic O2 delivery.(ABSTRACT TRUNCATED AT 250 WORDS)

Myocardial and systemic responses to arterial hypoxemia during cardiac tamponade.

Experiments were performed on 14 anesthetized, open-chest dogs to assess myocardial and systemic responses to cardiac tamponade alone (TAMP) and combined with arterial hypoxemia (HYP). Regional blood flow (RBF) was measured with radioactive microspheres and used to compute regional O2 supply. Myocardial oxygen and lactate extraction were determined. Myocardial oxygen consumption (MVO2) was calculated with Fick equation. An increase in pericardial pressure, sufficient to reduce mean aortic pressure (MAP) by 20%, caused proportional decreases in myocardial RBF and MVO2 but had no effect on endo-to-epi flow ratio or on myocardial lactate extraction. TAMP alone decreased RBF and O2 supply in kidney, splanchnic organs, skeletal muscle, and skin, but it had no effect in brain. HYP (arterial PO2, 35 +/- 2 mmHg) during TAMP restored MAP and caused transmurally uniform increases in myocardial RBF that were adequate to maintain MVO2 and lactate extraction. RBF increased sufficiently in brain to maintain regional O2 supply, whereas unchanged or inadequate increases in RBF in other tissues accentuated reductions in O2 supply. During combined TAMP and HYP, local vasodilator mechanisms were capable of maintaining adequate oxygen supply in myocardium and brain but not apparently in the nonvital tissues where these mechanisms were antagonized by reflex vasoconstriction.

Effect of stimulation of trigeminal ganglion on regional cerebral blood flow in cats.

Regional cerebral blood flow was studied in the cat, with and without trigeminal ganglion stimulation, by the intravenous injection of the tracer [14C]iodoantipyrine and subsequent regional brain dissection. Electrical activation of the trigeminal ganglion led to a selective increase in regional blood flow in the frontal and parietal cortex that was bilateral without change in the posterior cortex, deep cerebral nuclei, white matter, or brain stem. Unilateral intracranial section of the facial nerve blocked the response in the ipsilateral frontal and parietal cortex, whereas bilateral facial nerve section blocked the contralateral frontal cortical response. The contralateral parietal cortical increase in blood flow was not affected by facial nerve section and may thus represent the result of metabolic activation of sensory cortex.

Central and Regional Vascular Hemodynamics Following Intravenous Milrinone in the Conscious Rat

This study examined the hemodynamic and regional vascular profile of intravenous (i.v.) milrinone during increasing doses (3, 6, 12 micrograms/kg/min, n = 8) and by intraindividual comparison of milrinone and dobutamine (n = 10) in normal conscious rats. At 3 micrograms/kg/min, Milrinone increased coronary and cerebral blood flow (radioactive microspheres 15 +/- 5 microns) (7.7-9.8 and 1.05-1.27 ml/min/g respectively, both p less than 0.05) without significant changes in systemic hemodynamics. At 6 micrograms/kg/min milrinone increased skeletal muscle blood flow (0.19-0.24 ml/min/g, p less than 0.05) along with increases in cardiac output, stroke volume, and stroke work (all p less than 0.05), while systemic vascular resistance decreased (-51%, p less than 0.05). When compared with dobutamine, milrinone caused a greater increase in cardiac output (+26% vs. +17%) and a greater reduction in systemic vascular resistance. Milrinone and dobutamine increased renal, intestinal, cerebral, and coronary flow to a similar extent, but only milrinone enhanced hepatic arterial blood flow (+26%, p less than 0.05) and tended to increase flow to skeletal muscle (+35%, p = 0.07). We conclude that milrinone exerts significant regional vasodilating effects in a conscious rat model, being most prominent in the coronary and cerebral circulations at a dosage that does not alter central hemodynamics. At higher doses, milrinone causes a balanced increase in regional blood flow including enhanced flow to skeletal muscle. The hemodynamic (particularly as compared with dobutamine) and regional vascular profile of milrinone suggests a predominant vasodilating effect in the rat. Given a similar limited response of rat and diseased human myocardium to milrinone, these findings may have important clinical implications.

A New Molecule with Vasodilating and β-Adrenoceptor Blocking Properties

Carvedilol is a new substance displaying beta-sympatholytic and vasodilating activities in the same dose range. Data obtained from a considerable number of animal experiments show that the beta-blocking properties of carvedilol resemble those of propranolol. However, in contrast to propranolol the arterial blood pressure decreases dose dependently after single doses of carvedilol due to a reduced total peripheral resistance. The vasodilating activity of carvedilol can be demonstrated in a variety of experimental models. According to the present state of knowledge neither alpha-blockade, nor Ca antagonism, serotonin antagonism, prostaglandin-mediated vasorelaxation, or endothelial-derived relaxing factor (EDRF)-dependent activity are responsible for the antihypertensive effect. Thus, although the mechanism of vasodilation has still not been completely clarified, a postreceptor mechanism seems likely. The acute vasodilating properties in humans have been shown as a dose-dependent increase of the finger pulse amplitude in healthy subjects after both intravenous and oral administration, and as a decrease of the regional resistances and an increase of regional blood flow. The pharmacokinetics of carvedilol are dose linear and peak concentrations are reached within 1-1.5 h after oral administration. The elimination half-life after single oral doses varies from 6-7 h. The renal clearance of 4 ml/min is negligible in comparison with the total body clearance of 590 ml/min. Therefore, the absolute bioavailability of 24% indicates some degree of first-pass extraction. The highly lipophilic drug is extensively distributed to the tissues, as shown by the distribution volume of 132 l. In patients with hypertension, single doses of carvedilol (25-50 mg) decrease systolic and diastolic blood pressure for more than 10 h, whereas heart rate is only slightly decreased. In hypertensive patients treated from 7 days up to 1 year, carvedilol proved to be an effective and safe antihypertensive drug. In contrast to conventional beta-blockers, the reduced vascular resistance, in particular of the renal circulation, observed after both acute and chronic administration of carvedilol, indicated the useful hemodynamic profile of this compound. In addition, patients not sufficiently controlled with conventional beta-blockers responded promptly to carvedilol. At the same time left ventricular performance is not depressed. In a 1-year open clinical trial with hypertensives WHO I and II, the responder rate was about 85% with carvedilol as monotherapy.(ABSTRACT TRUNCATED AT 400 WORDS)

Prostacyclin protects ischemic reperfused myocardium in the dog by inhibition of neutrophil activation

Prostacyclin (PGI 2) and the stable PGI 2 analogue SC39902 (6,9α-epoxy, 5S-fluoro-11α, 15S-dehydroxyprosta-6, 13E-dien-1-oic acid, sodium salt) were studied in anesthetized open-chest dogs subjected to 90 minutes of left circumflex coronary artery (LCCA) occlusion and 6 hours of reperfusion. PGI 2 (50 ng/kg/min, infused into the left atrium) reduced infarct mass by 59% compared to control, but SC39902 (1.5 μg/kg/min) failed to produce a significant reduction in infarct size. Both PGI 2 and SC39902 reduced mean arterial blood pressure, heart rate, and rate-pressure product to the same extent. Regional myocardial blood flow measured with radiolabelled tracer microspheres did not demonstrate an increase in regional blood flow to the ischemic myocardium during the 90 minutes of LCCA occlusion in the PGI 2 and control treatment groups. Canine neutrophils were isolated from whole blood and activated with opsonized zymosan. PGI 2 produced a concentration-dependent inhibition of neutrophil activation as measured by superoxide production in vitro, whereas SC39902 failed to effectively inhibit neutrophil activation. Neutrophil migration into inflammatory skin lesions was effectively attenuated when dogs were pretreated with PGI 2 (50 ng/kg/min, intravenously). Therefore, it is suggested that the cytoprotective effect of PGI 2 during myocardial ischemia and reperfusion is related to an inhibition of neutrophil migration and the production of cytotoxic activated oxygen species.

Evidence that secondary mixed leukocyte culture supernatant mediates changes in cellular recruitment, blood flow, and vascular permeability.

Lymphokines produced as a result of allostimulation may play an important role in allograft rejection, mediating changes in cellular infiltration and migration, regional blood flow, and vascular permeability in a manner similar to that of delayed type hypersensitivity reactions. Changes in cellular recruitment (CR), regional blood flow (RBF), and vascular permeability (VP) were studied in paired healed subcutaneous urethane sponge grafts inoculated with secondary mixed leukocyte culture supernatant (2 degrees MLC SN), a rich source of a variety of lymphokines secreted in response to allostimulation. Intravenous injection of Indium-111-labeled unsensitized lymphocytes (UL), Rubidium-86-chloride, and Iodine-125-labeled albumin were used to assess CR, RBF, and VP, respectively. An increase in CR (P less than 0.001), RBF (P less than 0.05), and VP (P less than 0.001) could be demonstrated at the site of injection of allogeneically restimulated 2 degrees MLC SN compared with the syngeneically restimulated 2 degrees MLC SN. The quantitative response and the kinetics of CR using 2 degrees MLC SN were similar to previous studies in which specifically sensitized lymphocytes were injected with target cells bearing the sensitizing alloantigen, but the increase in RBF and VP were less. Injection of purified human interleukin, 2 serotonin, histamine, and bradykinin had no significant effect on CR. Injection of purified human interleukin 1 resulted in a moderate increase in CR. These results are consistent with previous studies suggesting that the in vivo elaboration of lymphokines during allogeneic cellular interactions leads to an increase in CR, RBF, and VP. The small changes in RBF and VP in these experiments, however, do not account for the greater magnitude of the changes in CR. It is likely that other specific or nonspecific chemoattractants or inhibitors of cell migration also play a significant role in CR in vivo.

The microsphere method facilitates statistical assessment of regional blood flow.

When microspheres are injected into the circulation, they are trapped in the arteriolar or capillary system within various organs. It has been confirmed in animal experiments that the number of microspheres in a myocardial sample approximately follows a Poisson distribution, under adequate experimental conditions. On the basis of this result, we arrived at the following hypothesis: When regional blood flow is measured under a steady state by the reference sample method, the 95% relative error can be approximated by +/- 196 square root 1/v + 1/w, where v and w represent the number of microspheres in blood sample and myocardial sample, respectively. The equation is valid if v and w are greater than 400 and 49, respectively. We obtained an expression of the relation among the percent of increase or decrease in regional blood flow being verified, the probability of increase or decrease, as a statistically significant variation and the number of microspheres in a myocardial sample. An investigator can work out an approximate experimental design using this expression. For instance, when the increase in regional blood flow required for verification is expected to be 20% and he wants this increase to be verified by 90%-probability and as a statistically significant increase, he can predict from this expression that the number of microspheres in a myocardial sample should be 472 and 567 before and after the experimental intervention on the coronary circulation, respectively. The expression is useful as index for experiments involving use of the microsphere method.

Norepinephrine kinetics during insulin-induced hypoglycemia

Norepinephrine (NE) kinetics (plasma appearance rate, clearance, and forearm extraction) were measured during insulin-induced hypoglycemia in six healthy subjects. NE clearance did not change during hypoglycemia, indicating that the increase in plasma NE during hypoglycemia is due to an increased plasma appearance rate of NE. Forearm extraction of 3H-NE and of endogenous plasma epinephrine decreased significantly during hypoglycemia, probably due to an increase in regional blood flow.

An increase in cerebral blood flow elicited by electrical stimulation of the solitary nucleus in rats with cervical cordotomy and vagotomy.

The effect of monopolar electrical stimulation of the intermediate portion of the solitary nucleus (SOL) on brain circulation was investigated in 48 anesthetized (N2O), artificially ventilated Wistar rats. The cervical spinal cord and bilateral vago-sympathetic trunks were severed to eliminate any change in arterial blood pressure mediated by the autonomic nervous systems on stimulating the SOL. Blood pressure was kept within the physiological range by intravenous phenylephrine infusion. Current intensity of the stimulus was set at 60 +/- 4 microA (mean +/- S.E.; n = 9), which was equivalent to 2.5 times threshold for vasopressin-induced pressor response. A sufficient dose of vasopressin-antagonist given to each rat shortly before determination of cerebral blood flow, prevented vasopressin-induced hypertension from stimulating the medulla. Stimulation elicited an increase in regional blood flow (14C-iodoantipyrine technique) by 72%, and 39% on average in the frontal and occipital cortices, respectively, and 25% in the caudate-putamen (p less than 0.05; n = 12 in control, and 9 in the stimulation studies). It was found that observed results included little detectable contribution from current spread of the stimulus toward the adjacent structures (dorsal medullary reticular formation and cuneate fasciculus) surrounding the SOL and from retrograde activation of the cerebellar fastigial nucleus. Overall, the present study suggests that a certain vasomotor mechanism, which is activated upon excitation of the intermediate portion of the SOL, regulates the blood vessels of the brain as a vasodilator.

Effects of acute left anterior descending occlusion on regional myocardial blood flow and wall thickening in the presence of a circumflex stenosis in dogs

In this study, 2 hypotheses were tested: (1) Myocardium supplied by a stenosed circumflex coronary artery (LC) does not demonstrate compensatory increases in regional blood flow and systolic thickening when the left anterior descending coronary artery (LAD) is acutely occluded. (2) Blood flow to myocardium in the distribution of an acutely occluded LAD is lower in the presence of a stenosed than in the presence of an unstenosed LC. Fifty-three open-chest, anesthetized dogs were studied. Regional coronary blood flow (8 to 10-μ micro-spheres) and wall thickening (sonomicrometer crystals) were measured before and after LAD occlusion in the presence of an unstenosed LC artery, and a moderate and severe LC stenosis. Acute LAD occlusion in the presence of an unstenosed LAD was not accompanied by a significant increase in regional blood flow to the remote LC bed; posterior myocardial wall thickening, however, increased from 0.22 ± 0.02% to 0.24 ± 0.02% (p = 0.04). In the presence of a moderate LC stenosis (gradient 29 ± 1 mm Hg), LAD occlusion was associated with a 9% (p = 0.02) decrease in endocardial flow and an 11 % decrease in the endocardial/epicardial flow ratio (p = 0.002). Transmural flow was unchanged and there was no compensatory increase in posterior wall thickening. In the presence of a more severe LC stenosis (gradient 49 ± 1 mm Hg), central LC endocardial flow decreased by 32% (p = 0.0008) at the time of LAD occlusion. Similar alterations were noted in the peripheral LC region. Posterior wall thickening did not increase significantly with LAD occlusion (0.27 ± 0.01 to 0.30 ± 0.03%, p = 0.12). Stepwise regression analysis showed that the changes in remote LC blood flow were related to the distal LC pressure at the time of LAD occlusion and to changes in LC pressure and LC stenosis resistance that occurred after the LAD was occluded. Regional blood flow to the bed of the acutely occluded LAD was lower in the presence of a stenosed LC artery than in the presence of an unstenosed LC. This may have been related, in part, to an impairment of collateral flow from the stenosed LC to the distal LAD bed. Thus, acute LAD occlusion in the presence of a stenosed LC is associated with adverse blood flow alterations in the remote LC bed as well as worsening of the flow diminution in the LAD bed compared with blood flow alterations observed when the LAD is occluded in the setting of an unstenosed, fully patent LC vessel. These changes may be clinically relevant to patients with acute myocardial infarction who have underlying multivessel coronary artery disease.