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Biomedical subjects

R G Dacey

Publications and source records attributed to R G Dacey.

At least 73 records · Page 4Linked to original sources
PubMed1988

Effects of calcium antagonists on intracerebral penetrating arterioles in rats.

There is no direct information on the effect of calcium antagonists on intracerebral penetrating arterioles, which are responsible for a significant part of total cerebrovascular resistance. In a study on rats, the effects of four calcium antagonists (diltiazem, verapamil, nifedipine, and nimodipine) on isolated intracerebral penetrating arterioles with mean resting diameters (+/- standard error of the mean) of 52.3 +/- 3.0 micron were investigated. Vessel diameters were monitored in vitro by means of a video microscope dimensional analyzer under constant transmural pressure (60 mm Hg) after cannulation. Each calcium antagonist produced maximal dilation of about 50% (diltiazem 46.4% +/- 5.6%, verapamil 53.1% +/- 6.0%, nifedipine 46.9% +/- 6.1%, and nimodipine 47.1% +/- 5.4%) with varied sensitivity (median effective dose (ED50): diltiazem 1.52 X 10(-6) M, verapamil 1.08 X 10(-7) M, nifedipine 8.65 X 10(-9) M, and nimodipine 1.62 X 10(-9) M). Dilation effects persisted for a significantly longer time after washout with calcium antagonists such as diltiazem (15.5 +/- 1.8 minutes), nifedipine (19.0 +/- 3.9 minutes), and nimodipine (30.0 +/- 1.6 minutes) than after washout with adenosine (8.5 +/- 1.0 minutes). It appeared that the magnitude of vasodilation was greater and the duration of dilation after washout longer in intracerebral penetrating arterioles than that reported for pial arterioles, although sensitivity to each calcium antagonist was quite similar to that reported for larger cerebral arteries. These data provide a possible explanation for the apparent disparity between clinical efficacy and angiographically determined vessel diameter when patients with cerebral vasospasm are treated with calcium antagonists. These agents may have a greater effect on intracerebral penetrating arterioles than on angiographically visible larger arteries.

Animals↗
PubMed1988

Brain xenografts: the effect of cyclosporin A on graft survival.

Animal models of Parkinson's disease and Alzheimer's disease have shown dramatic functional improvement after transplantation of embryonic neurons into denervated regions of the adult brain. Because of the ethical and logistic problems associated with the use of human embryonic brain tissue, cross-species transplants are an attractive alternative. An experimental model of cross-species brain transplantation was developed to evaluate cell survival in untreated and cyclosporin A (CyA)-treated animals. Cholinergic ventral neurons from embryonic mice were transplanted into the frontal lobes of 18 adult Sprague-Dawley rats using a cell suspension technique. Nine animals were treated for 13 days with CyA (10 mg/kg/day) and nine were not treated. Twelve weeks after transplantation, frozen sections through the transplant volume were obtained. Alternate sections were prepared with hematoxylin and eosin and acetylcholine esterase stains. Cell counts through a 2-cu mm volume incorporating the transplant were compared to a contralateral control volume. Eight of the nine untreated transplants were successful (mean transplant cells +/- standard error of the mean: 90.7 +/- 19.4/2 cu mm). All of the nine CyA-treated transplants survived, with mean transplant count 28.7 cells/2 cu mm greater than untreated transplants (mean increase 28.7: p less than or equal to 0.05, Wilcoxon matched-pairs signed ranks test). It is concluded that: 1) this model is useful for quantitating transplant cell survival; 2) untreated xenografts survive well; and 3) a 13-day course of CyA improved long-term graft survival.

Acetylcholinesterase↗
PubMed1987

Histaminergic vasodilation of intracerebral arterioles in the rat.

Histamine from various sources is found in significant amounts around cerebral vessels and may play a significant role in controlling CBF. The effect of histamine on the intracerebral microcirculation has not been examined. We have used an in vitro technique for the isolation and cannulation of intracerebral arterioles from the rat to study the effect of histamine on the spontaneous tone developed by these vessels. Extraluminally administered histamine caused dose-dependent vasodilation of isolated intracerebral arterioles with a maximal dilation of 139 +/- 2.4% of control diameter. The dilation was blocked by the H2 receptor antagonist cimetidine, but was only incompletely attenuated by the H1 receptor blocker chlorpheniramine. Histamine effects a dilation of the spontaneous tone of intracerebral resistance vessels, which is mediated by H2 receptors.

Animals↗
PubMed1987

Cholinergic vasodilation of intracerebral arterioles in rats.

Much morphological and physiological evidence indicates that cholinergic mechanisms play a significant role in the control of cerebral blood flow. Despite in situ data suggesting that an intrinsic cholinergic mechanism produces vasodilation in the intracerebral microcirculation, there is no direct information on the effect of acetylcholine (ACh) on intracerebral arterioles. We investigated cholinergic mechanisms in isolated perfused intracerebral arterioles from pentobarbital sodium-anesthetized Sprague-Dawley rats. In arterioles with resting diameters of 46.8 +/- 6.6 microns (mean +/- SE) ACh produced no significant dilation at pH 7.30. At pH 7.60, however, a significant dose-dependent dilation to a maximum of 119.0 +/- 1.0% of control diameter was observed. Carbachol, a long-acting cholinergic agonist, similarly failed to dilate vessels at pH 7.30 but significantly dilated vessels at pH 7.60. Prostaglandin F2 alpha produced a maximum contraction to 68.3 +/- 2.7% of control diameter (n = 8). ACh at concentrations of 10(-4) and 2 X 10(-4) M induced a significant dilation of this prostaglandin-induced contraction. In vessels similarly preconstricted with serotonin, 10(-4) M ACh produced significant dilation. Atropine, having no effect on vessel diameter when administered alone, blocked cholinergic vasodilation of intracerebral arterioles at pH 7.60. Attempts at endothelial removal, although successful in eliminating endothelial cells from the preparation, significantly impaired smooth muscle contractility. ACh has no significant effect on the spontaneous cerebrovascular tone in this preparation, but in vessels preconstricted by a variety of means it produced vasodilation mediated by atropine sensitive receptors.

Acetylcholine↗
PubMed1986

Neurosurgical complications after apparently minor head injury. Assessment of risk in a series of 610 patients.

A small number of patients with an apparently minor head injury will develop a life-threatening intracranial hematoma that must be rapidly detected and removed. To assess the risk of a significant intracranial neurosurgical complication after apparently minor head injury, the authors collected data prospectively on 610 patients who had sustained a transient posttraumatic loss of consciousness or other neurological function and who had a Glasgow Coma Scale (GCS) score of 13, 14, or 15 in the emergency room. Skull x-ray films were obtained in 583 patients, 66 of whom (10.8% of the study population) had cranial fractures. Eighteen of the 610 patients (3.0%) required a neurosurgical procedure. Three acute subdural hematomas, one epidural hematoma, and one traumatic intracerebral hematoma required craniotomy. Of the 66 patients who had skull fracture, 7.6% required a craniotomy for intracranial hematoma. Thirteen (19.7%) of the 66 patients with skull fracture required an operative procedure as compared to five (1.0%) of the 517 patients without skull fracture. Two patients with a normal GCS score of 15 and normal skull x-ray films subsequently underwent operative treatment. The cost of three alternative management schemes for these patients was estimated. A 50% reduction in cost of management could be effected by the use of computerized tomography (CT) scans (or possibly skull x-ray films) in determining which of the patients who are alert at the time of presentation should be admitted for observation. Several other conclusions can be drawn from this study. First, an initial GCS score between 13 and 15 does not necessarily indicate that a patient has sustained a trivial head injury, since 3% of such patients will require an operative procedure despite an initially normal level of alertness. Second, an abnormal skull x-ray film increases by a factor of 20 the probability that a patient will need neurosurgical treatment. Third, it is very unusual for patients who have a GCS score of 15 and a normal skull x-ray film to have a significant neurosurgical complication. Fourth, the alternative management schemes that depend on selective use of skull films and CT scans may significantly reduce the cost of caring for patients with minor head injury.

Adolescent↗
PubMed1985

Enlargement of an intracranial aneurysm in the eighth decade of life. Case report.

The management of intracranial aneurysms in elderly patients remains controversial, since the natural history of these lesions is not well understood. The authors describe the case of a 76-year-old woman with documented enlargement of an internal carotid artery aneurysm over 3 years. The management of intracranial aneurysms in elderly patients is discussed.

Aged↗
PubMed1984

Effect of norepinephrine on penetrating arterioles of rat cerebral cortex.

Penetrating intracerebral arterioles from the rat with mean resting diameters of 26.3 +/- 2.8 micron and maximal diameters of 37.4 +/- 2.5 (SE) micron were isolated, cannulated, and perfused in vitro. Spontaneous tone development and hydrogen ion reactivity indicated that vessels were relatively undamaged and viable. The norepinephrine (NE) reactivity of intracerebral penetrating arterioles is pH dependent. Vessels studied at extraluminal pH 7.30 were unresponsive to NE up to concentrations of 10(-6) M. At NE concentrations above 10(-6) M, vessels dilated to diameters approximately 110% of control. At pH 7.80, vessels contracted to diameters between 75 and 80% of control in response to extraluminal NE concentrations between 10(-11) and 10(-6) M. Vessels in 10(-6) M phentolamine failed to respond to 10(-8) M NE at pH 7.30 and pH 7.80. An aliquot of 10(-8) M NE solution made up at pH 7.80 failed to induce vessel contraction when the pH was readjusted to 7.30, indicating that a NE breakdown product was not responsible for the contraction. These data suggest that adrenergic mechanisms in penetrating cerebral arterioles are significantly different from those seen in peripheral arterioles of similar size.

Animals↗
PubMed1982

A study of rat intracerebral arterioles: methods, morphology, and reactivity.

Penetrating, intracerebral arterioles from rat were isolated, cannulated, and studied in vitro. Vessel wall elements were found to consist of an endothelial cell layer, one smooth muscle cell layer, and a thin adventitial layer or leptomeningeal sheath. Smooth muscle cell nuclei were oriented perpendicular to the vessel's longitudinal axis; endothelial cell nuclei were parallel to the axis. Mean vessel diameter with the smooth muscle inactivated (passive diameter) was 36.7 +/- 1.6 (SE) micrometer. Spontaneous smooth muscle tone developed at 37 degrees C and reduced vessel diameter to 70 +/- 4% of passive diameter. Vessels were activated by the extraluminal application of 140 mM KCl solution at pH 8.00, which produced a transient contraction that decayed within 30 s to a steady contraction of somewhat less intensity. Changes in intravascular pressure were used to alter wall tension of the vessels. Tension in the vessel wall was computed, and length-tension curves for the arteriolar smooth muscle were approximated. Length-tension relationships similar to those seen in other smooth-muscle preparations were found with maximal estimated force development of 1.29 x 10(-5) N . m-2. Alterations of bath pH caused changes in vessel diameter that were inversely related to extraluminal pH and varied by approximately 77% in the range from pH 6.85 to 8.00. Adenosine dilated vessels to 140 +/- 6% of control diameter at a concentration of 10(-5) M. The mechanical characteristics and the reactivity to H+, K+, and adenosine of these vessels were quantitatively consistent with in vitro data from larger cerebral vessels and in vivo data from pial arteries.

Adenosine↗
PubMed1981

Methods for isolation, cannulation, and in vitro study of single microvessels.

A method is described for the isolation and cannulation of microvessels (12-112 micrometers) that permits study, in vitro, of their physiology and pharmacology. Vessels from the hamster cheek pouch, testis, and mesentery and from rat brain have been isolated at 4 degrees C with specially prepared instruments and viewed with an inverted microscope. The vessels were cannulated at one end by equipment developed for renal tubular perfusion. The uncannulated end of the vessel is sealed, and experiments on reactivity and mechanics are carried out at fixed intravascular pressures. The isolated microvessels studied have a modulus of elasticity that is consistent with that observed in large vessels, and they display similar maximal active tension development (approximately 10(6) dyn/cm2). Reactivity to norepinephrine, acetylcholine, and adenosine are in the normal range for microvessels. Spontaneous tone is present, as evidenced by stable tonic contractions as well as phasic contractions in the frequency range of 3-30/min. The vessels display stress activation (myogenic response) consisting of contraction in response to increased intraluminal pressure. Our findings suggest that this preparation will be very useful in elucidating the physiology and pharmacology of the resistance vessels in the terminal vasculature.

Animals↗
PubMed1980

Cerebrospinal fluid outflow resistance in rabbits with experimental meningitis. Alterations with penicillin and methylprednisolone.

Acute bacterial meningitis may be associated with increased intracranial pressure, neurological sequelae such as communicating hydrocephalus, and a slow response to antibiotic therapy. Alterations in cerebrospinal hydrodynamics are at least partially responsible for these complications. Constant, low-flow short-duration manometric infusion studies through a hollow-bore pressure monitoring device in direct continuity with the supracortical subarachnoid space were performed in rabbits with experimental meningitis. Maximal resistance to cerebrospinal fluid (CSF) outflow from the subarachnoid to vascular space was markedly increaed in acute pneumococcal meningitis when compared to control, uninfected animals (6.77 +/- 3.52 vs. 0.26 +/- 0.04 mm Hg/microliter per min, P less than 0.001). Similar elevations (8.93 +/- 4.15 mm Hg/microliter per min were found in experimental Escherichia coli meningitis. Despite eradication of viable bacteria from the CSF by penicillin therapy during the acute stage of pneumococcal meningitis, resistance remained elevated (6.07 +/- 4.68 mm Hg/microliter per min) and had not returned to normal up to 15 d later. Administration of methylprednisolone during the early stages of acute pneumococcal meningitis reduced mean peak outflow resistance towards control values (0.59 mm Hg/microliter per min) and no "rebound" effect was apparent 24 h later. These hydrodynamic alterations in experimental meningitis prevent normal CSF absorption and decrease the ability of the bran to compensate for changes in intracranial volume and pressure.

Animals↗
PubMed1980

Donor artery changes following anastamosis.

By arteriographic study the authors find there is marked enlargement in diameter of the donor artery and a significant increase in blood flow following superficial temporal-middle cerebral anastamosis.

Cerebral Angiography↗
PubMed1979

Clearance of bacteria from cerebrospinal fluid to blood in experimental meningitis.

The occurrence and importance of secondary bacteremia in the pathogenesis of and response to therapy in meningitis is uncertain. Streptococcus pneumoniae type III was injected into the cerebrospinal fluid of the cisterna magna in anesthetized, curarized dogs, and sequential simultaneous samples were obtained from the superior sagittal sinus, cisterna magna, and peripheral blood. The results show that: (i) bacteria are rapidly transported from the cerebrospinal fluid to blood but only after active multiplication within the cerebrospinal fluid, and (ii) entrance into the blood from the cerebrospinal fluid occurs before the height of the febrile response or cerebrospinal fluid pleocytosis.

Animals↗
PubMed1978

Factors influencing the penetration of antimicrobial agents into the cerebrospinal fluid of experimental animals.

Successful therapy of bacterial meningitis is dependent upon achieving adequate antibacterial activity in the CSF. The percent penetration (CSF concentration/serum concentration X 100) of various antimicrobial agents was determined in a rabbit model of bacterial meningitis. The percent penetration of the penicillin and cephalosporin derivatives was found to vary inversely with the protein binding of the respective drugs. Esterification of ampicillin increased its lipid solubility and likewise increased the penetration into the CSF. Probenecid competitively inhibits the active transport efflux of various organic acids from the CSF and increased the CSF concentrations of penicillin and cephalosporin derivatives. The percent penetration of all drugs was increased in the presence of the inflamed meninges.

Animals↗