Regional Blood Flow Distribution Research Articles

Use of enteral nutrition for stress ulcer prophylaxis.

To review the controversies involving the use of enteral nutrition support for stress ulcer prophylaxis and formulate recommendations. A MEDLINE search (1966-December 2000) was conducted using the MeSH of nutrition, ulcer, critical care, and acid to identify relevant articles. References of selected articles were reviewed, and relevant abstracts from critical care or gastrointestinal journals identified. Animal and human data from prospective studies, retrospective studies, and case series were evaluated for the effects of enteral nutrition on gastric pH, intramucosal pH, gastrointestinal blood flow, development of macroscopic mucosal erosions, and hemorrhage. Intragastric administration of enteral nutrition has variable effects on gastric pH, enhances regional distribution of gastrointestinal blood flow, and may lower intramucosal pH. All substrates (carbohydrate, lipid, amino acid), when administered into the stomach, reduce the occurrence of mucosal erosions but do not entirely prevent their development. Few studies of stress ulcer prophylaxis regimens have reported use of enteral nutrition. Limited retrospective data suggest enteral nutrition support may be effective for preventing gastrointestinal hemorrhage, but the results of prospective studies are confounded by poor study design. Definitive recommendations regarding the role of enteral nutrition for stress ulcer prophylaxis are not possible due to the lack of prospective, randomized studies. Therefore, the use of enteral nutrition as the only therapeutic agent for stress ulcer prophylaxis should be discouraged until definitive data are available. Initiation and discontinuation of pharmacologic stress ulcer prophylaxis should be independent of enteral nutrition.

Arterial blood gas management in retrograde cerebral perfusion: the importance of carbon dioxide.

Many interventional physiological assessments for retrograde cerebral perfusion (RCP) have been explored. However, the appropriate arterial gas management of carbon dioxide (CO2) remains controversial. The aim of this study is to determine whether alpha-stat or pH-stat could be used for effective brain protection under RCP in terms of cortical cerebral blood flow (CBF), cerebral metabolic rate for oxygen (CMRO2), and distribution of regional cerebral blood flow. Fifteen anesthetized dogs (25.1+/-1.1 kg) on cardiopulmonary bypass (CPB) were cooled to 18 degrees C under alpha-stat management and had RCP for 90 min under: (1), alpha-stat; (2), pH-stat; or (3), deep hypothermic (18 degrees C) antegrade CPB (antegrade). RCP flow was regulated for a sagittal sinus pressure of around 25 mmHg. CBF was monitored by a laser tissue flowmeter. Serial analyses of blood gas were made. The regional cerebral blood flow was measured with colored microspheres before discontinuation of RCP. CBF and CMRO2 were evaluated as the percentage of the baseline level (%CBF, %CMRO2). The oxygen content of arterial inflow and oxygen extraction was not significantly different between the RCP groups. The %CBF and %CMRO2 were significantly higher for pH-stat RCP than for alpha-stat RCP. The regional cerebral blood flow, measured with colored microspheres, tended to be higher for pH-stat RCP than for alpha-stat RCP, at every site in the brain. Irrespective of CO2 management, regional differences were not significant among any site in the brain. CO2 management is crucial for brain protection under deep hypothermic RCP. This study revealed that pH-stat was considered to be better than alpha-stat in terms of CBF and oxygen metabolism in the brain. The regional blood flow distribution was considered to be unchanged irrespective of CO2 management.

Distribution and hierarchy of regional blood flow during hypothermic cardiopulmonary bypass

Background. Cardiopulmonary bypass (CPB) may decrease oxygen delivery relative to the nonbypass state. We predicted that a hierarchy of regional blood flow could be characterized under hypothermic (27°C) CPB. Methods. Ten pigs underwent bypass at 27°C. Fluorescent microspheres were administered before and during CPB at four randomized flows: 1.9, 1.6, 1.3, and 1.0 L · min −1 · m −2. At completion, tissue samples were obtained from brain, renal cortex and medulla, pancreas, small bowel, and limb muscle for regional blood flow determination. Results. Cerebral blood flow remained unchanged between CPB flows of 1.9 and 1.3 L · min −1 · m −2. Renal perfusion was stable between flows of 1.9 and 1.6 L · min −1 · m −2, whereas perfusion of small bowel decreased linearly with pump flow. Pancreatic perfusion was unchanged over the range of flows studied; muscle blood flow was profoundly reduced at the highest CPB flow and further decreased if pump flow was reduced below 1.6 L · min −1 · m −2. Conclusions. This study characterizes the organ-specific hierarchy of blood flow and oxygen distribution during hypothermic CPB. These dynamics are relevant to clinical decisions for perfusion management.

Using (10)CO2 for single subject characterization of the stimulus frequency dependence in visual cortex: a novel positron emission tomography tracer for human brain mapping.

Carbon-10-labeled carbon dioxide ((10)CO2) with a half-life of 19.3 seconds offers almost ideal characteristics as a positron emission tomography (PET) tracer for assessment of the regional cerebral blood flow (rCBF) distribution, enabling multiple independent measurements at short intervals. To appraise the feasibility of (10)CO2 for localizing and characterizing human brain function in single subjects, the authors chose a well-characterized activation paradigm. In 6 healthy volunteers, 50 to 64 independent PET scans of the rCBF distribution were acquired while viewing an annular reversing checkerboard presented at 10 reversal frequencies between 0.03 and 30 Hz. Changes in regional cerebral activity as a function of reversal frequency were modeled in every subject using a set of polynomial basis functions, which, as predicted, showed highly significant second or third order relations located in the striatal cortex. Correlation coefficients (R2) ranged from 0.46 to 0.63. The average intersubject maximal response relative to the 0.03 Hz condition was 8.0% +/- 1.7% SD occurring at stimulus contrast reversal frequencies between 6 and 15 Hz with an average of 11.8 +/- 3.8 (SD) Hz. From the qualitative and quantitative replication of previous results it is concluded that (10)CO2 PET is a feasible technique for human brain mapping studies and a great improvement compared with the existing oxygen-15-labeled water (H(2)(15)O) PET method, particularly for single subject studies and parametric design.

An autoradiographic study of regional blood flow distribution in the rat kidney during ureteric obstruction--the role of vasoactive compounds.

To determine the changes in regional renal blood flow during ureteric obstruction and to examine the role of vasoactive mediators in effecting these changes. Renal blood flow in Sprague-Dawley rats was assessed after periods of ureteric obstruction using a quantitative autoradiographic technique based on Kety's theory of diffusion of an inert tracer (14C-iodoantipyrine). Prostaglandins, thromboxanes and renin-angiotensin were inhibited pharmacologically using diclofenac sodium and enalapril. Baseline blood flow to the outer cortex, inner cortex and medulla was 807, 258 and 105 mL/100 g/min, respectively. There was an increase in outer cortical blood flow after 10 min of ureteric obstruction which became significant at 30 min (P < 0.05). There was a significant decrease in inner cortical and medullary blood flow at 30 min, to 210 and 68 mL/100 g/min, respectively (P < 0.05). Diclofenac sodium abolished the increase in outer cortical blood flow. After 24 h of unilateral ureteric obstruction, outer cortical blood flow decreased to 492 mL/100 g/min; inner cortical blood flow also decreased but to a lesser extent, to 190 mL/100 g/min. Inhibition of prostaglandins, thromboxanes and the renin-angiotensin system reduced the degree of renal vasoconstriction but there was still a significant decrease in outer cortical perfusion despite the presence of these blocking agents. The control of the renal vasculature involves a complex interplay between a variety of vasoactive mediators. Quantitative autoradiography offers the opportunity to evaluate changes in regional renal perfusion with high resolution and will allow a greater understanding of the pathophysiology of renal diseases.

Neuromodulation therapy does not influence blood flow distribution or left-ventricular dynamics during acute myocardial ischemia

Objectives. Electrical stimulation of the dorsal aspect of the upper thoracic spinal cord is used increasingly to treat patients with angina pectoris refractory to conventional therapeutic strategies. The purpose of this study was to determine whether spinal cord stimulation (SCS) in dogs affects regional myocardial blood flow and left-ventricular (LV) function before and during transient obstruction of the left anterior descending coronary artery (LAD). Methods. In anesthetized dogs, regional myocardial blood flow distribution was determined using radiolabeled microspheres and left-ventricular function was measured by impedance-derived pressure–volume loops. SCS was accomplished by stimulating the dorsal T1–T2 segments of the spinal cord using epidural bipolar electrodes at 90% of motor threshold (MT) (50 Hz, 0.2-ms duration). Effects of 5-min SCS were assessed under basal conditions and during 4-min occlusion of the LAD. Results. SCS alone evoked no change in regional myocardial blood flow or cardiovascular indices. Transient LAD occlusion significantly diminished blood flow within ischemic, but not in non-ischemic myocardial tissue. Left ventricular pressure–volume loops were shifted rightward during LAD occlusion. Cardiac indices were altered similarly during LAD occlusion and concurrent SCS. Conclusions. SCS does not influence the distribution of blood flow within the non-ischemic or ischemic myocardium. Nor does it modify LV pressure–volume dynamics in the anesthetized experimental preparation.

Compensatory increases in cardiac output and SMA blood flows prevent splanchnic hypoperfusion during moderate isovolemic hemodilution in dogs

Intraoperative acute isovolemic hemodilution has been used to decrease the need for homologous blood transfusion. Decreased arterial oxygen content and total oxygen delivery to tissues promote a compensatory increase in cardiac output, related to the hemodilution-induced decrease in viscosity and/or vasodilatation, preserving tissue oxygen delivery. Regional blood flow distribution may vary widely between and within organs. Splanchnic hypoperfusion, particularly at the intestinal mucosal region, has been implicated in systemic inflammatory response and multiple organ dysfunction. We evaluated systemic and splanchnic oxygen-derived variables during a moderate acute isovolemic hemodilution to test the hypothesis that hemodilution may promote gastric mucosal acidosis, despite an apparent adequacy of global markers of oxygen delivery and consumption.

Coronary sinus occlusion enhances coronary collateral flow and reduces subendocardial ischemia.

On the hypothesis that coronary sinus occlusion (CSO) may reduce myocardial ischemia, we examined the effects of CSO on coronary collateral blood flow and on the distribution of regional myocardial blood flow (RMBF) in dogs. Thirty-eight anesthetized dogs underwent occlusion of the left anterior descending coronary artery with or without CSO and intact vasomotor tone. We measured RMBF and intramyocardial pressure (IMP) in the subendocardium (Endo) and subepicardium (Epi) separately. With intact vasomotor tone, CSO during ischemia significantly increased RMBF in the ischemic region (IR), particularly in Endo from 0.17 +/- 0.03 to 0.33 +/- 0.05 ml x min(-1) x g(-1) (P < 0.05), and increased the Endo/Epi from 0.59 +/- 0.10 to 1.15 +/- 0.15 (P < 0.01). These effects of CSO were partially abolished by adenosine. However, the Endo/Epi was still increased from 0.90 +/- 0.13 to 2.09 +/- 0.30 (P < 0.01). The changes in RMBF in IR were significantly correlated with the peak CS pressure during CSO. The Endo/Epi of IMP in IR was significantly decreased during CSO. In conclusion, CSO potentially enhances coronary collateral flow, and preserves the ischemic myocardium, especially in Endo.

Physiology in medicine: importance of hypoxic pulmonary vasoconstriction in maintaining arterial oxygenation during acute respiratory failure.

Hypoxic pulmonary vasoconstriction continues to attract interest more than half a century after its original report because of persistent mystery about its biochemical mechanism and its exact physiological function. Recent work suggests an important role for pulmonary arteriolar smooth muscle cell oxygen-sensitive voltage-dependent potassium channels. Inhibition of these channels by decreased PO2 inhibits outward potassium current, causing membrane depolarization, and calcium entry through voltage-dependent calcium channels. Endothelium-derived vasoconstricting and vasodilating mediators modulate this intrinsic smooth muscle cell reactivity to hypoxia. However, refined modeling of hypoxic pulmonary vasoconstriction operating as a feedback mechanism in inhomogeneous lungs, using more realistic stimulus-response curves and confronted with direct measurements of regional blood flow distribution, shows a more effective than previously assessed ability of this remarkable intrapulmonary reflex to improve gas exchange and arterial oxygenation. Further studies could show clinical benefit of pharmacological manipulation of hypoxic pulmonary vasoconstriction, in circumstances of life-threatening hypoxemia.

Acute renal responses to angiotensin-converting enzyme inhibition in the neonatal pig.

Pharmacological interruption or genetic disruption of the renin-angiotensin system before completion of nephrogenesis produces papillary atrophy and an impaired urinary concentrating ability. The mechanisms involved are yet to be elucidated, but renal hypoperfusion and subsequent ischemia, particularly to the immature renal medulla, may be hypothesized. The acute intrarenal responses to angiotensin-converting enzyme (ACE) inhibition in the newborn piglet were thus investigated by means of regional blood flow distribution, renal interstitial hydrostatic pressure (RIHP), and medullary oxygen tension (PO2) in the anesthetised 4- to 5-day-old piglet. Moreover, the calcium antagonist nifedipine and the nitric oxide synthesis inhibitor L-NAME were also given in order to reduce renal blood flow by other means. The drugs were given intravenously in equipotent pressor doses, mimicking intraperitoneal injections in neonatal rats. Enalaprilat (200 microg/kg) reduced mean arterial pressure (MAP) by 14+/-10% (mean+/-SD, P=0.006) and RIHP by 18+/-18% (P=0.001), whereas total renal blood flow and medullary PO2 remained unchanged. In contrast, nifedipine (0.5 mg/kg) reduced MAP and RIHP by 39+/-8% and 38+/-14%, respectively, total and regional blood flows by 30%-60%, and medullary PO, by 46+/-29% (P=0.001). Acute administration of L-NAME (15 mg/kg) increased MAP by 27+/-10% (P=0.0005), whereas RIHP and renal blood flow decreased by 20%-50%, resulting in a reduction of the medullary PO2 by 10+/-12% (P=0.05). We conclude that the renal abnormalities observed after neonatal ACE inhibition are not likely to be caused by renal ischemia.

Brain activation during mental transformation of size.

Visual comparison between different-sized objects with respect to shape can be done by encoding one of the objects as a mental image, transforming the image to the size format of the other object, and then testing for a match (Bundesen, C., & Larsen, A. [1975]. Visual transformation of size. Journal of Experimental Psychology: Human Perception and Performance, 1, 214-220). To identify the brain structures implicated in mental transformation of size, we measured the distribution of regional cerebral blood flow (rCBF) by positron emission tomography (PET) in 12 normal subjects who compared random stimulus patterns with respect to shape regardless of variations in size in a one-back match-to-sample paradigm. Each subject was PET-scanned 12 times during repetitive injections of H(2)(15)O. In one condition (three scans), all stimulus patterns were small. In a second condition (three scans), all stimuli were large. In the third condition (six scans), the stimuli alternated between small and large. Mental transformation of size should occur in the alternating-size condition but not in the fixed-size conditions. As expected, behavioral measures (reaction time [RT], d', beta) were nearly the same for the two fixed-size conditions but mean RT was longer and d' smaller in the alternating-size condition. Changes in rCBF specific to mental transformation of size were estimated by contrasting the alternating-size with the fixed-size conditions by use of statistical parametric mapping (SPM96) at a threshold of p <. 05 corrected for multiple comparisons. The detected brain structures implicated in mental transformation of size were primarily located in the dorsal pathways, comprising structures in the occipital, parietal, and temporal transition zone (predominantly in the left hemisphere), posterior parietal cortex (bilaterally), area MT/V5 (left), and vermis (bilaterally). Contrasts between the two fixed-size conditions showed significant effects in only the occipital cortex.

Effects of inertial load and countermeasures on the distribution of pulmonary blood flow.

We assessed the influence of cranial-to-caudal inertial force (+G(z)) and the countermeasures of anti-G suit and positive pressure breathing during G (PBG), specifically during +G(z), on regional pulmonary blood flow distribution. Unanesthetized swine were exposed randomly to 0 G(z) (resting), +3 G(z), +6 G(z), and +9 G(z), with and without anti-G suit and PBG with the use of the Air Force Research Laboratory centrifuge at Brooks Air Force Base (the gravitational force of the Earth, that is, the dorsal-to-ventral inertial force, was present for all runs). Fluorescent microspheres were injected into the pulmonary vasculature as a marker of regional pulmonary blood flow. Lungs were excised, dried, and diced into approximately 2-cm(3) pieces, and the fluorescence of each piece was measured. As +G(z) was increased from 0 to +3 G(z), blood flow shifted from cranial and hilar regions toward caudal and peripheral regions of the lung. This redistribution shifted back toward cranial and hilar regions as anti-G suit inflation pressure increased at +6 and +9 G(z). Perfusion heterogeneity increased with +G(z) stress and decreased at the higher anti-G suit pressures. The distribution of pulmonary blood flow was not affected by PBG. ANOVA indicated anatomic structure as the major determinant of pulmonary blood flow.

Electrical Stimulation for Pressure Sore Prevention and Wound Healing

This paper reviews applications of therapeutic electrical stimulation (ES) specific to wound healing and pressure sore prevention. The application of ES for wound healing has been found to increase the rate of healing by more than 50%. Furthermore, the total number of wounds healed is also increased. However, optimal delivery techniques for ES therapy have not been established to date. A study of stimulation current effects on wound healing in a pig model has shown that direct current (DC) stimulation is most effective in wound area reduction and alternating current (AC) stimulation for wound volume reduction at current densities of 127 μA./cm2 and 1,125 μA/cm2, respectively. Preliminary studies have been carried out at two research centers to assess the role of ES in pressure sore prevention. Surface stimulation studies have shown that ES can produce positive short-term changes in tissue health variables such as regional blood flow and pressure distribution. The use of an implanted stimulation system consisting of intramuscular electrodes with percutaneous leads has been found to produce additional long-term changes. Specifically, gluteal muscle thickness increased by 50% with regular long-term ES application concurrent with a 20% decrease in regional interface pressures and increased tissue oxygen levels. These findings indicate that an implantable ES system may have great potential for pressure sore prevention, particularly for individuals who lack sensation or who are physically unable to perform regular independent pressure relief.

Isoflurane alters the recirculatory pharmacokinetics of physiologic markers.

Earlier studies have demonstrated that physiologic marker blood concentrations in the first minutes after administration, when intravenous anesthetics exert their maximum effect, are determined by both cardiac output and its distribution. Given the reported vasodilating properties of isoflurane, we studied the effects of isoflurane anesthesia on marker disposition as another paradigm of altered cardiac output and regional blood flow distribution. The dispositions of markers of intravascular space and blood flow (indocyanine green), extracellular space and free water diffusion (inulin), and total body water and tissue perfusion (antipyrine) were determined in four purpose-bred coonhounds. The dogs were studied while awake and while anesthetized with 1.7%, 2.6%, and 3.5% isoflurane (1.15, 1.7, and 2.3 minimum alveolar concentration, respectively) in a randomized order determined by a Latin square experimental design. Marker dispositions were described by recirculatory pharmacokinetic models based on very frequent early, and less frequent later, arterial blood samples. These models characterize the role of cardiac output and regional blood flow distribution on drug disposition. Isoflurane caused a significant and dose-dependent decrease in cardiac output. Antipyrine disposition was profoundly affected by isoflurane anesthesia, during which nondistributive blood flow was maintained despite decreases in cardiac output, and the balance between fast and slow tissue volumes and blood flows was altered. The isoflurane-induced changes in marker disposition were different than those the authors reported previously for halothane anesthesia, volume loading, or hypovolemia. These data provide further evidence that not only cardiac output but also its peripheral distribution affect early drug concentration history after rapid intravenous administration.

Effects of partial liquid ventilation on regional pulmonary blood flow distribution of isolated rabbit lungs.

Partial liquid ventilation with perfluorocarbons may increase alveolar hydrostatic transmural pressure and may result in a redistribution of pulmonary blood flow from dependent to nondependent lung regions. To test this hypothesis under controlled study conditions, we determined intrapulmonary blood flow distributions during gas and perfluorocarbon ventilation in isolated rabbit lungs. Controlled animal study with an ex vivo isolated lung preparation. Research laboratory for Experimental Anesthesiology at the Heinrich-Heine-University of Düsseldorf. New Zealand White rabbits. The lungs were perfused with autologous blood at constant flow (150 mL/min) and ventilated with 5% C(O2) in air (positive end-expiratory pressure, 2 cm H2O; tidal volume, 10 mL/kg body weight; respiratory rate, 30 breaths/ min) without and with perfluorocarbon administered intratracheally (15 mL/kg). Regional lung perfusion was measured with colored microspheres in apical, central, peripheral, and basal samples before and after bronchial instillation of perfluorocarbons. Compared with gas ventilation, intrapulmonary blood flow during perfluorocarbon ventilation was higher in apical samples (49.4+/-8.6 mL/min/g vs. 38.3+/-6.8 mL/min/g dry weight; p = .03) and lower in basal samples (22.2+/-5.1 mL/min/g vs. 39.9+/-8.2 mL/min/g; p = .04). Our findings suggest that during partial liquid ventilation, intrapulmonary blood flow is redistributed toward less-dependent lung regions. (Crit Care Med 2000; 28:1522-1525)

Gastrointestinal blood flow in the red Irish lord, Hemilepidotus hemilepidotus: long-term effects of feeding and adrenergic control.

Cardiac output, blood flow to the coeliac and mesenteric arteries, dorsal aortic blood pressure and heart rate were recorded simultaneously at rest and postprandial for 6 days in a teleost, the red Irish lord (Hemilepidotus hemilepidotus). We anticipated that gastrointestinal blood flow would increase postprandially, supported by an increase in cardiac output. However, we had no predictions for either the exact time-course of this response, or for the regional distribution of blood flow between to the two major arteries comprising the splanchnic circulation. In resting, unfed animals, blood flow to the coeliac artery and mesenteric artery was 4.1 +/- 0.6 ml min(-1) kg(-1) and 4.9 +/-1.3 ml min(-1) kg(-1), respectively (mean +/- SEM, n = 7), which together represented 34% of cardiac output. Feeding increased blood flow to the coeliac and mesenteric arteries in a time-dependent manner. The increase in coeliac artery blood flow preceded that in the mesenteric artery, a finding that is consistent with the coeliac artery supplying blood to the liver and stomach, while the mesenteric artery supplies blood to the stomach and intestine. Coeliac blood flow had increased by 84 +/- 18% after 1 day and had a peak increase of 112 +/- 40% at day 4 postprandial. Mesenteric blood flow was not significantly elevated at day 1, but had increased by 94 +/- 19% at day 4 postprandial. Cardiac output also increased progressively, increasing by a maximum of 90 +/- 30% at day 4. Because the increase in cardiac output was adequate to meet the postprandial increase in gut blood flow, the postprandial decreases in vascular resistance for the coeliac and mesenteric circulations mirrored the increases in blood flow. Intra-arterial injections of adrenaline and noradrenaline into resting fish more than doubled coeliac and mesenteric vascular resistances, and blood flow decreased proportionately. This adrenergic vasoconstriction was totally abolished by pretreatment with the alpha-adrenoceptor antagonist phentolamine, which in itself approximately halved coeliac and mesenteric vascular resistances. These observations indicate a significant alpha-adrenergic tone in the gastrointestinal circulation of the red Irish lord, the loss of which could not entirely account for the post-prandial increase in gastrointestinal blood flow. Other control mechanisms are suggested.

Clustering of Murine Lung Metastases Reflects Fractal Nonuniformity in Regional Lung Blood Flow

In the experimental metastasis assay certain animals, from groups of similarly treated animals, develop more lung metastases than expected from random chance alone. This clustering of metastases is characterized by a power function relationship, σ² = aμ^b, between the variance, σ², and mean, μ, of the numbers of lung metastases per animal (a and b are constants). To determine whether this clustering could be an artifact of experimental metastasis, whether it could be influenced by different experimental conditions, and to attempt to clarify its cause, 22 published data sets from experimental metastasis utilizing 2,145 mice, as well as 8 data sets from spontaneous metastasis utilizing 1,020 mice were analyzed. In these experiments cell cloning, cell-cell fusion, treatment with a protein kinase C inhibitor, treatment with cell adhesion compounds, and transfection with either the ras oncogene, the sialidase gene, or the urokinase sense and antisense genes were used to influence metastasis. They employed 14 different cell lines and 6 different strains of inbred mice. Clustering of metastasis was evident in animals from the spontaneous metastasis assays as well as from the experimental metastasis assays. It was apparent whether mice were injected with tumor cells derived from clones or from cell lines. Clustering was demonstrated within each data set, regardless of the experimental conditions employed. A single variance to mean power function (with a = 2.2 and b = 1.51) characterized the clustering in the 30 data sets. The regional distribution of blood flow through lungs and other organs is nonuniform, exhibiting a fractal symmetry on change of scale. This symmetry implies that the variance of a region’s blood flow is related to its mean by the same power function as was observed with metastasis. Indeed, measurements of blood flow from isolated canine lungs yield b = 1.56, similar to the corresponding figure from murine lung metastasis. These findings lend support to the hypothesis that the observed clustering of metastases is a consequence of fractal variations in lung blood flow.

Effects of acute hypobaric hypoxia on regional cerebral blood flow distribution: a Single Photon Emission Computed Tomography study in humans

Single Photon Emission Computed Tomography (SPECT) and radiopharmaceutical stabilizing agents allowed us to investigate regional cerebral blood flow (CBF) distribution in six resting healthy subjects during acute laboratory hypobaric hypoxic conditions. In the hypobaric experiment stabilized 99mTc-D, L-hexamethyl-propylene amine oxime was injected 40 min after reaching hypoxic conditions corresponding to an altitude of 5500 m above sea level. Arterial blood sample was taken after five additional minutes. Mean arterial oxygen pressure and haemoglobin saturation were 28 mmHg and 56%, respectively. The control experiment was performed similarly, apart from barometric pressure and blood gas analysis. We analysed CBF distribution in 12 regions of functional interest bilaterally in frontal, parietal, temporal, occipital cortex, in the hippocampus, in the basal ganglia and other central structures of brain. No overall effect of hypoxia on normalized regional CBF distribution in the considered regions was found. Motor cortex (Brodmann 4) and basal ganglia were the only regions in which hypobaric hypoxia significantly increased relative distribution of the radiopharmaceutical [F(1,5)=18.30; P < 0.008 and F(1,5)=10.85; P < 0.022, respectively]. Despite severe hypoxia, we did not observe any major regional CBF redistribution. We found a small relative increase in blood flow to the motor cortex and the basal ganglia, at rest after 40 min of hypobaric hypoxia, suggesting a preferential compensatory mechanism of these functional regions of brain.

Functional brain imaging of tinnitus-like perception induced by aversive auditory stimuli.

Tinnitus is an aversive auditory percept of unknown origin. We tested the speculation that tinnitus may share neuronal processing mechanisms with aversive auditory percepts of known origin. This study revealed the functional neuroanatomy of the perception of aversive auditory stimuli. The stimuli were presented to 12 healthy volunteers so as to mimic the psychoacoustical features of tinnitus and its affective response in tinnitus sufferers. The regional cerebral blood flow distribution was measured by PET during four auditory processing conditions and one control condition. The aversive auditory stimuli activated primary and secondary auditory areas bilaterally, dorsolateral prefrontal attention areas, and structures in the limbic system which subserve emotional processing. Based on these results and findings from other functional neuroimages of tinnitus, we hypothesize that the perception of tinnitus may involve the functional linkage of these brain areas: secondary auditory cortex, dorsolateral prefrontal cortex, and limbic system.

Simulation study of the intercompartmental fluid shifts during hemodialysis.

Hypotension is the most frequent complication during hemodialysis. An important cause of hypotension is a decrease in the intravascular volume. In addition, a decrease in plasma osmolality may be a contributing factor. Modeling of sodium and ultrafiltration (UF) may help in the understanding of underlying relationships. We therefore simulated, in a mathematical model, the intercompartmental fluid shifts during standard hemodialysis (SHD), diffusive hemodialysis (DHD), and isolated ultrafiltration (IU). We analyzed the relative theoretical effect of hydration status, dialysate sodium concentration, the initial plasma concentrations of sodium and urea, and tissue permeation to solutes on the magnitude and direction of intracellular and intravascular volume changes. This theoretical analysis shows that the transcellular fluid shifts taking place during hemodialysis treatment are, to a great part, due to inhomogeneous distribution of regional blood flow and tissue fluid volumes. During hemodialysis treatment, the cellular fluid shifts in tissue groups with relatively high perfusion and small volume occur from the intra- to the extracellular spaces. However, the fluid shift in tissue groups with a low perfusion and large volume takes place in the opposite direction. The UF volume and rates, and the size of the sodium (Na+) gradient between the dialysate and blood side of the dialyzer membrane are the most important factors influencing the fluid shifts. Higher UF volumes and flow rates cause an increasing decline in the plasma volume in both SHD and IU. High dialysate sodium concentration (150 mEq L(-1)) helps plasma refilling slightly when compared with a normal dialysate sodium concentration (140 mEq L(-1)). However, a high dialysate sodium concentration is associated with a high plasma sodium rebound, which in turn may lead to interdialytic water intake resulting from thirst and may cause increased weight gain and hypertension.