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Biomedical subjects

A G Hudetz

Publications and source records attributed to A G Hudetz.

At least 55 records · Page 3Linked to original sources
PubMed1996

Synchronous oscillations in cerebrocortical capillary red blood cell velocity after nitric oxide synthase inhibition.

Low-frequency (4-12 cpm) spontaneous oscillations in cerebral blood flow are well known and their augmentation after nitric oxide synthase inhibition has recently been described. However, the presence of these oscillations in blood flow velocity in the capillary network of the brain has not been demonstrated. In this paper, low-frequency oscillations in red blood cell flow velocity in cortical capillaries using intravital video microscopy were studied before and after infusion of the nitric oxide synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME). Fluorescein isothiocyanate-labeled red blood cells were injected intravenously and served as markers of capillary flow. Red cell velocity was measured by off-line image tracking. After infusion of L-NAME (30 mg/kg), red cell velocity decreased from an average of 1.0 +/- 0.1 mm/sec to 0.53 +/- 0.1 mm/sec. Simultaneously, low-frequency oscillations in velocity emerged as indicated by an 81 +/- 17% increase in standard deviation of the 4- to 8-cpm frequency components. There was a significant temporal correlation (r = 0.58, P < 0.01) in red cell velocity between neighboring capillaries after L-NAME. Principal component analysis suggested that the high temporal correlation was a consequence of low-frequency oscillations rather than phase. These results are consistent with a model in which low-frequency spontaneous oscillations in flow velocity are brought about by precapillary vasomotion. This study provides for the first time direct evidence for low-frequency synchronous oscillations of red cell flow velocity in the cerebral capillary network.

Animals↗
PubMed1996

Inhibition of brain P-450 arachidonic acid epoxygenase decreases baseline cerebral blood flow.

Arachidonic acid (AA) is metabolized by the cytochrome P-450 (P-450) epoxygenase pathway to epoxyeicosatrienoic acids (EETs) in the brain parenchymal tissue and perivascular astrocytes. EETs dilate cerebral microvessels and enhance K+ current in cerebrovascular smooth muscle cells. In the current study, the effect of a subdural administration of miconazole, an inhibitor of P-450 epoxygenase, on microvascular perfusion of rat cerebral cortex was evaluated using laser-Doppler flowmetry (LDF) Baseline cerebral blood flow (CBF) decreased by 29.7 +/- 7.3% (n = 5) after administration of 20 microM miconazole into the subdural space for 30 min. Responses of CBF to sodium nitroprusside and 5-hydroxytryptamine were unaltered by miconazole treatment. Administration of vehicle alone in time-control experiments had no effect on CBF. In other experiments, the effects of miconazole on the metabolism of [14C]AA by cultured rat astrocytes and on nitric oxide synthase activity in homogenates of rat brain were examined. Miconazole inhibited conversion of AA to EETs by cultured astrocytes but had no effect on the conversion of L-arginine to L-citrulline by homogenates of rat brain. These results implicate endogenous P-450 epoxides of AA in the regulation of basal blood flow in cerebral microcirculation.

Animals↗
PubMed1995

Laser-Doppler measurement of the effects of halothane and isoflurane on the cerebrovascular CO2 response in the rat.

We used laser-Doppler flowmetry to compare the effects of the volatile anesthetics, isoflurane and halothane, on the cerebrovascular response to CO2 inhalation in male Sprague-Dawley rats. The effects of 0.5 and 1.5 minimum alveolar anesthetic concentrations (MAC) of halothane and isoflurane on the microcirculatory response to CO2 were compared at 22, 36, and 66 mm Hg end-tidal partial pressure of carbon dioxide (ETCO2). An additional group of animals was anesthetized by continuous barbiturate infusion (10-20 mg.kg-1.h-1). Arterial blood pressure was maintained at control levels throughout the experiment using an infusion of phenylephrine (0.5-5 micrograms.kg-1.min-1). Laser-Doppler flow (LDF) was greater at 1.5 MAC than at 0.5 MAC at each ETCO2 for both anesthetics. The CO2 reactivity (percent LDF change/mm Hg change ETCO2) from hypocapnia to normocapnia was similar to that from normocapnia to hypercapnia. CO2 reactivity with barbiturate infusion and 0.5 MAC isoflurane were 1.78 +/- 0.19 and 2.28 +/- 0.22 (no difference), respectively, both being greater than that with 0.5 MAC halothane at 1.19 +/- 0.14 (P < 0.05). A similar difference was suggested at 1.5 MAC halothane and 1.5 MAC isoflurane (1.99 +/- 0.25 and 2.67 +/- 0.35, respectively). The CO2 reactivity was greater at 1.5 MAC halothane compared to 0.5 MAC halothane. The results of this study suggest that an increase in arterial CO2 may increase cerebrocortical red cell flow more with isoflurane than with halothane, at least at moderate anesthetic concentrations.

Anesthesia↗
PubMed1995

The role of nitric oxide in cerebrocortical laser Doppler flow response to halothane in the rat.

Laser Doppler flowmetry was utilized to investigate whether nitric oxide (NO) plays a role in the cerebrocortical hyperemic effect of halothane in rats. A particular objective was to elucidate whether the increased vascular tone or the removal of basal NO secondary to NO synthase inhibition influenced the response to halothane. The animals were anesthetized with i.p. pentobarbital for surgery and 90 min later were ventilated with 1.0 minimum alveolar concentration (MAC) halothane for 1 h to achieve a steady-state baseline. The control group was infused with either 1 ml of saline or 20 mg/kg of D-NAME, and the treatment group received 20 mg/kg of L-NAME intravenously. In a subset of the treatment group, we restored baseline flow and vascular tone using i.v. sodium nitroprusside (SNP). Mean arterial pressure (MAP) was maintained constant with an infusion of phenylephrine (0.5-5 micrograms/kg/min). Then, 30 to 45 min later, inspired halothane was raised to 1.7 MAC in each group, and the increase in laser Doppler flow (LDF) was measured. On increasing halothane MAC in the control group, LDF increased by 28 +/- 4%. L-NAME increased MAP by 21 +/- 4% and reduced baseline LDF by 26 +/- 2%. In the L-NAME-only treated group, 1.7 MAC halothane increased LDF by 12 +/- 3%, significantly less than control. The decrease in cerebrovascular resistance induced by increasing inspired halothane MAC was similar in the control group and in the L-NAME treated group at 23 +/- 6% and 22% +/- 7, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthetics, Inhalation↗
PubMed1995

Video microscopy of cerebrocortical capillary flow: response to hypotension and intracranial hypertension.

Although autoregulation of cerebral blood flow is well established, the response of cerebral capillary circulation to reduced cerebral perfusion pressure (CPP) is unclear. The objective of this study was to determine whether red cell flow velocity in individual capillaries of the cerebral cortex is maintained during acute decreases in CPP. Microcirculation of the superficial parietal cerebral cortex of adult barbiturate-anesthetized artificially ventilated rats was visualized using a new design of closed-perfused cranial window and epifluorescent-intensified video microscopy. Fluorescein-isothiocyanate-labeled red blood cells (FRBC) injected intravenously were used as markers of capillary flow. CPP, defined as mean arterial pressure minus intracranial pressure, was reduced by controlled hemorrhage or by stepwise elevation of local intracranial pressure. The movement of FRBC in the parenchymal capillary network was video recorded at each pressure level, and FRBC velocity in each capillary was measured off-line with use of the dual-window digital cross-correlation technique. FRBC flux in the capillaries was measured by automated cell counting. FRBC velocity at normal perfusion pressure was 1.47 +/- 0.58 (SD) mm/s and changed little in the perfusion pressure range of 70-120 mmHg. The autoregulatory index in this pressure range was 0.0049 mm.s-1.mmHg-1. Opening of previously unperfused capillaries was not observed. FRBC flux correlated with FRBC velocity, but the latter was maintained in a narrower range than FRBC flux, suggesting a decrease in capillary diameter or hematocrit with decreasing perfusion pressure. The results suggest that flow autoregulation is associated with the maintenance of capillary flow velocity and that capillary recruitment does not contribute to flow autoregulation in the rat cerebral cortex.

Animals↗
PubMed1995

Modification of cerebral laser-Doppler flow oscillations by halothane, PCO2, and nitric oxide synthase blockade.

We investigated whether nitric oxide (NO) played a role in the generation of cerebrocortical flow oscillations and their modification by hypocapnia, hypercapnia, and halothane administration. Parietal cortical laser-Doppler flow (LDF) was monitored transcranially in anesthetized (barbiturate + 0-1.0% halothane), artificially ventilated, adult male Sprague-Dawley rats. Thirty minutes after infusion of N omega-nitro-L-arginine methyl ester (L-NAME, 20 mg/kg i.v.) mean arterial pressure (MAP) increased from 105 +/- 10 to 132 +/- 15 mmHg (P < 0.02), while mean LDF decreased from 159 +/- 36 to 135 +/- 30 perfusion units (PU, P < 0.05). Oscillations in LDF at a frequency of 6.3-7.8 cycles/min and amplitude of 10% were induced or augmented by L-NAME but not by D-NAME or indomethacin (2 mg/kg i.p.). L-arginine (200 mg/kg) abolished the oscillations post-L-NAME at constant MAP. Sodium nitroprusside infusion (10(-5) M, 5-50 microliters/min) reversed the L-NAME-induced increase in MAP and decrease in mean LDF but did not attenuate the flow oscillations. Hypocapnia post-L-NAME decreased LDF to 110 +/- 20 PU (P < 0.001) and augmented the flow oscillations (amplitude: 11-31%). Hypercapnia (5% CO2) or halothane (0.4-1.0%) suspended the oscillations in the presence of L-NAME. The results suggest that NO synthase activity inhibits cerebrocortical flow oscillations, and NO is not an obligatory mediator of the effects of halothane, hypocapnia, and hypercapnia on oscillatory activity.

Amino Acid Oxidoreductases↗
PubMed1994

Architectural alterations in rat cerebral microvessels after hypobaric hypoxia.

We performed 3-dimensional studies of vascular casts of the microvasculature of the cerebral cortex of rats that were exposed to three weeks of hypobaric hypoxia and of control rats. Scanning electron microscopy of the casts gave the qualitative impression of increased vascularity of the cerebral cortex, particularly the deeper layers, in hypoxic rats. Quantitative analysis of capillary segment lengths revealed a significant shift in the frequency distribution to longer lengths (from 77 +/- 8 to 90 +/- 14 microns) in the deep, but not in the superficial, layers of the cerebral cortex of hypoxic rats. These findings agree with previous results reporting increased capillary density in the brain after exposure to prolonged hypobaric hypoxia and suggest that capillary segment elongation plays a role in the increased capillary density in the deeper layers of the cerebral cortex.

Animals↗
PubMed1994

Erythrocyte flow heterogeneity in the cerebrocortical capillary network.

The heterogeneity of erythrocyte flow velocity and erythrocyte flux and their dependence on decreased cerebral perfusion pressure were studied in the rat cerebral cortex using intravital video microscopy. With decreased perfusion pressure, both mean and range of erythrocyte flow velocity of individual capillaries was reduced. Both cell velocity and cell flux decreased more in high flow capillaries than in low flow capillaries. The results are compatible with the hypothesis that redistribution of capillary flow during hypotension may help to maintain the perfusion of arterio-venous capillary flow pathways. Although the data are preliminary, they represent the first direct measurements of capillary flow path length and transit time in the capillary network of the cerebral cortex.

Animals↗
PubMed1994

The effects of halothane and isoflurane on cerebrocortical microcirculation and autoregulation as assessed by laser-Doppler flowmetry.

The effects of volatile anesthetics on red blood cell flow in the cerebral microcirculation have not been compared. We used laser-Doppler flowmetry, which measures red blood cell flow in the microcirculation to compare the effects of differing concentrations of isoflurane and halothane on cerebrocortical microcirculation. Sprague-Dawley rats were anesthetized with pentobarbital (65 mg/kg intraperitoneally). The animals were tracheotomized, paralyzed, and artificially ventilated. In the first protocol laser-Doppler flow (LDF) was recorded at 0.5, 1, 1.5, and 2 minimum alveolar anesthetic concentration (MAC) halothane or isoflurane, with blood pressure controlled by intravenous phenylephrine infusion (0.5-5 micrograms.kg-1.min-1). In the second protocol the effects of 0.5 and 1.5 MAC halothane and isoflurane on LDF changes in response to changes in mean arterial blood pressure (MABP) were compared. MABP was increased by phenylephrine infusion and decreased by hemorrhage. LDF increased with each 0.5 MAC increase in halothane and isoflurane concentration (P < 0.05). LDF was greater at 1.5 and 2 MAC isoflurane than at equi-MAC halothane (P < 0.01). Autoregulation of LDF was present but attenuated at MABP of 60-140 mm Hg at low halothane and isoflurane concentrations. LDF was increased at 1.5 MAC vs 0.5 MAC for both drugs (P < 0.01). The autoregulation coefficients (percent LDF change/mm Hg MABP change) were 0.41 +/- 0.10, 0.42 +/- 0.07, 0.27 +/- 0.04, and 0.20 +/- 0.05 at 0.5 MAC halothane, 0.5 MAC isoflurane, 1.5 MAC halothane, and 1.5 MAC isoflurane, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Percolation phenomenon: the effect of capillary network rarefaction.

The relationship between microvascular network resistance and functional capillary density was investigated by computer simulation. A model of spinotrapezius muscle microcirculatory network was constructed from measured data of vessel length and diameter. Progressive rarefaction was simulated by random stepwise removal of capillaries from the network. The flow distribution in the network was calculated after each step of capillary removal. Network resistance increased little when decreases in functional capillary density were less than 30%. Furthermore, capillary flow did not decrease and its variance across the network was unchanged despite the gradual flow redistribution. However, with further decreases in capillary density, network resistance increased in a double exponential fashion. The resistance approached infinity at a critical value of functional capillary density termed the percolation threshold. The value of this parameter varied between 56 and 62% and it was lower when capillaries with the lowest flow were preferentially removed.

Animals↗
PubMed1993

Imaging system for three-dimensional mapping of cerebrocortical capillary networks in vivo.

A personal computer-based image analysis system was developed for the three-dimensional mapping of cerebrocortical capillary networks from intravital video recordings. Capillary circulation in the parietal cortex of anesthetized rats was visualized to 70 microns depth using a closed cranial window preparation and epi-fluorescent, intensified video microscopy. The circulation was video recorded during slow (0.1 micron/frame) scanning of the focal plane (depth of field = 10 microns) through regions of interest. Capillary networks were traced from still video images of several microscope fields recorded at different X, Y, and Z stage coordinates. The length of vessel segments from five networks ranged between 10 and 178 microns and was best approximated by the Gamma distribution. Vessel diameter (2.5 to 8.7 microns) was best fitted by the lognormal distribution. A specific capillary network contained 51 segments and five anastomosing loops with circumferences between 575 and 1226 microns. Velocity of fluorescently labeled red blood cells ranged from 0.77 to 2.22 mm/sec within the capillary loops. The study demonstrates the feasibility of reconstructing capillary networks from intravital video recordings as deep as 70 microns within the cerebral cortex and finds an anastomosing pattern and heterogeneous red blood cell velocity in the capillary network.

Anastomosis, Surgical↗
PubMed1993

A mathematical model of the intracerebral steal phenomenon in regional and focal ischaemia.

The objective of the present work was to mathematically estimate the extent and dynamics of intracerebral steal which may occur in response to cerebral vasodilation in regional and focal cerebral ischaemia. To this end, a spatially distributed mathematical model of regional cerebral blood flow (rCBF) was developed. The model contained a parallel system of intracerebral vascular resistances which were connected in series to a lumped extracerebral artery resistance and, for the focal ischaemia model, also a lumped pial collateral resistance. The rCBF was measured at 30 min of ischaemia in the following models: (1) bilateral carotid occlusion in spontaneously hypertensive rats (SHR), and (2) occlusion of the middle cerebral artery (MCA) in normotensive rats. The measured 3-dimensional rCBF data were used to set up the initial values of intracerebral resistance components. Cerebral vasodilation induced by inhalation of CO2 was simulated in the model by decreasing the values of both intracerebral and collateral resistance. Vascular responsiveness was specified to decrease with the ischaemic rCBF. In addition, a long term change in rCBF and resistance distribution was introduced to account for: (1) gradual rise in intracerebral resistance due to ischaemic oedema, and (2) adaptive decrease in collateral resistance. The following were predicted by the mathematical model. (1) At 60% maximum intracerebral dilatation a small intracerebral steal (5-10%) occurs at flow levels below 30-50 ml/100 g/min in both ischaemic models. (2) In focal ischaemia, the steal can be compensated by the 5% to 20% decrease in the collateral vascular resistance. (3) The rate of collateral adaptation overcomes the rate of intracerebral resistance rise and, therefore, eliminates the intracerebral steal after an adequately long period of time (on the order of a few hours). (4) An inverse steal effect can be demonstrated at the end of vasodilatation, provided that the time constant of collateral adaptation selected is longer (about 5:1) than the time constant of the intracerebral resistance rise. We conclude that the prediction of rCBF response to vasodilatation in cerebral ischaemia requires a knowledge of resting rCBF and of the response characteristics of both intracerebral and pial arterial segments.

Animals↗
PubMed1992

The role of wall shear stress in microvascular network adaptation.

The possible role of wall shear stress in microvascular network adaptation was investigated by computer simulation in planar polygonal model networks. Adaptation of vessel diameter to local wall shear stress resulted in false geometry and excessive rarefaction of the networks. Adaptation to mean wall shear stress decreased the range of shear stress, decreased the total power dissipation, and prevented network rarefaction. A measure of mean wall shear stress may serve as a control signal for the adaptation of vessel diameter to blood flow in microvascular networks.

Adaptation, Physiological↗
PubMed1992

Computer simulation of erythrocyte transit in the cerebrocortical capillary network.

The relationship between erythrocyte flow path length and transit time was studied using a probabilistic computer simulation of erythrocyte transit in morphometrically reconstructed cerebrocortical microvascular network of the rat. The results suggest (1) a near-cubic relationship between erythrocyte flow and vessel diameter, (2) preferential pathways of erythrocyte flow, (3) an exponential relationship between erythrocyte transit time and flow path length.

Animals↗