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Biomedical subjects

M H Evans

Publications and source records attributed to M H Evans.

At least 19 recordsLinked to original sources
PubMed1989

Penetration of antibiotics into the surgical wound in a canine model.

The dose and timing of antimicrobial agents given for surgical wound prophylaxis should be based on the concentration-time profile of the drug in tissue at the site of contamination. However, concentrations of antimicrobial agents in surgical wounds are difficult to determine accurately. Since a surgical wound is a unique extravascular compartment with increased vascular permeability and a high surface area/volume ratio, antibiotic concentrations in sera and surgical wounds should be similar. To test this hypothesis, the pharmacokinetics of single intravenous doses of cefazolin (40 mg/kg) and gentamicin (4 mg/kg) in sera and surgical wounds in a clinically relevant surgical model using dogs were compared. Drug concentrations were determined in interstitial fluid in muscle biopsies taken randomly from wound surfaces and serial wound fluid samples collected after the incisions were closed. Protein binding of cefazolin and gentamicin in sera and wound fluids was low (less than or equal to 29 +/- 9%) in this canine model. Cefazolin and gentamicin equilibrated rapidly (less than or equal to 30 min) between serum and the surgical wound, and concentrations in the two sites declined in parallel. Values for the area under the concentration-time curve, mean residence time, and terminal half-life in serum and the surgical site for each drug were similar. Cefazolin concentrations in serum underestimated the time during which concentrations in surgical wounds exceeded the susceptibility breakpoint MIC for important pathogens by an average of 58 min (range, 26 to 109 min; P = 0.036); for gentamicin, the underestimation averaged 30 min (range, 10 to 60 min; P = 0.036). These data support the concept that the concentration-time profiles of antimicrobial agents in serum may prove valuable clinically as guides to determining the and timing of antibiotic administration necessary for effective antimicrobial prophylaxis in surgery. Further studies are needed to determine the surgical wound pharmacokinetics of highly protein-bound antibodies.

Animals↗
PubMed1986

The mechanism of the vagal bradycardia evoked by diencephalic stimulation in the rabbit.

Blood pressure, in the rostral arterial system, was varied in the range 38-122 mm Hg by impeding the flow through the descending thoracic aorta in rabbits, anaesthetized with urethane and chloralose, in whom the spinal cord had been transected at mid-cervical level. Resting heart rate (H.R.) varied inversely with mean rostral arterial blood pressure (B.P.). The linear regression of H.R. on B.P. had a slope that averaged -0.38 beats X min-1 X mm Hg-1. Electrical stimulation in the lateral hypothalamic area, using 10 s trains of 300 microA X 1 ms constant current cathodal pulses at 60 Hz, caused H.R. to slow, provided that B.P. was above a threshold value and that the baroreceptor afferent pathway was intact. The mean threshold pressure was 49.5 mm Hg. Above threshold, the linear regression of the fall in H.R. during stimulation (delta H.R.) on B.P. had a slope that averaged -1.33 beats X min-1 X mm Hg-1. Linearity was good (r = 0.96). The results suggest that an inflow of baroreceptor impulses is essential for electrical stimulation of the cardioinhibitory region in the lateral hypothalamic area of the rabbit to cause bradycardia. This action is brought about by an increase in the gain of the vagal cardiodecelerator limb of the baroreceptor reflex.

Animals↗
PubMed1985

An oscilloscope spot intensifier, to improve photographic recordings of action potentials.

A circuit diagram is shown for a semiconductor device to intensify the brightness of an oscilloscope during the rapidly rising and falling phases of signals such as action potentials. Brightening pulses proportional in amplitude to the rate of change in the Y-axis are available for connection to an oscilloscope with an external intensity ('Z') modulation input. The circuit requires one transistor, one dual operational amplifier and two single fast operational amplifiers.

Action Potentials↗
PubMed1985

Effects of some alpha-adrenoceptor antagonists on central cardio-decelerator mechanisms in the rabbit.

Bradycardia was evoked in rabbits anaesthetized with chloralose-urethane by electrical stimulation (200 or 300 microA, 1 ms, 60 s-1 for 9 s, repeated every 5 min) of a selected point in the caudal hypothalamus 1.5 mm from the midline dorsal to the mammillary bodies. Phenoxybenzamine, prazosin and yohimbine solutions were infused intracerebroventricularly at a rate of 20 microliters min-1. Phenoxybenzamine did not cause any effects additional to those attributable to the solvent alone. Prazosin attenuated the evoked bradycardia at all doses (40 to 300 micrograms) and altered resting heart rate (HR) and arterial blood pressure (BP) after the higher doses. Yohimbine (200 + 300 micrograms) attenuated the bradycardia with negligible effects on HR and BP. Prazosin and yohimbine were given intravenously. Both caused dose-related attenuation of evoked bradycardia but prazosin also lowered BP sufficiently for this action alone to account for almost all the loss of bradycardia. The weaker hypotensive action of yohimbine was insufficient to account for the attenuation, a conclusion confirmed in animals whose BP was maintained constant by noradrenaline infusion after cervical spinal transection. In this preparation yohimbine caused dose-related attenuation of the bradycardia. The experiments have shown that yohimbine and probably prazosin also, can prevent hypothalamic stimulation from evoking bradycardia. The results suggest the presence of an alpha-adrenergic pathway from this region of the hypothalamus which projects caudally to increase the gain of the cardio-decelerator baroreceptor reflex in the rabbit.

Adrenergic alpha-Antagonists↗
PubMed1984

Bradycardia evoked by hypothalamic stimulation in the rabbit: dependence upon the arterial blood pressure.

The spinal cord was transected in adult New Zealand White rabbits anaesthetized with urethane plus chloralose. The level of transection was in the mid-cervical region. The animals were than ventilated mechanically and the arterial blood pressure was maintained with an intravenous infusion of noradrenaline solution. Stimulation of the hypothalamus 1-2 mm lateral to the third ventricle and 1.5-3 mm dorsal to the mammillary nuclei, in a region known to evoke pressor responses and bradycardia in normal anaesthetized rabbits, never evoked pressor responses in the spinally transected rabbits. Bradycardia was evoked only when the mean arterial blood pressure was maintained above 44-49 mmHg. At higher pressures stimulation evoked a greater bradycardia and the relationship between bradycardia and pressure was approximately linear over much of the range of pressures tested (up to 116 mmHg). Because the threshold mean arterial blood pressure at which hypothalamic stimulation evoked bradycardia was similar to the threshold pressures reported in the literature for baroreceptor activation in the rabbit and because the curve of bradycardia:pressure was similar to published curves of baroreceptor and baroreflex activity against blood pressure, it is concluded that the bradycardia evoked by hypothalamic stimulation in the rabbit is mediated by a neural pathway in the hypothalamus that can increase the gain of the cardio-inhibitory baroreceptor reflex.

Animals↗
PubMed1983

Evidence for central alpha-adrenergic transmission in a cardio-inhibitory response from the rabbit hypothalamus.

The heart rate of the anaesthetized rabbit was slowed by electrical stimulation of the hypothalamus with 7-9 sec trains of 250-330 microA pulses, duration 1 msec, frequency 60 Hz. This vagally-mediated cardio-decelerator response was attenuated in a dose-dependent manner after intravenous administration of phenoxybenzamine (0.01-5 mg/kg), phentolamine (0.01-3 mg/kg) or yohimbine (0.1-5 mg/kg). The attenuation of the cardio-decelerator response was not due to any vagolytic action of these drugs nor to block of the baroreceptor reflex, but appeared to be due to a central block of pathways descending from the hypothalamus. Propranolol, haloperidol, pimozide and spiperone did not show this central blocking action except in very large doses when there was evidence of some alpha-adrenoceptor blockade.

Adrenergic alpha-Antagonists↗
PubMed1983

Endogenous prostaglandin synthesis and glucose-induced insulin secretion from the adult rat pancreatic islet.

Although exogenous prostaglandins are recognized modulators of insulin secretion, the relationship between their endogenous synthesis and insulin secretion has not been rigorously studied in isolated adult rat islets. Using 3H-arachidonic acid as a tracer, we evaluated the effect of glucose stimulation upon the incorporation of this fatty acid into islet phospholipids and prostaglandins (separated by extraction and sequential silicic acid, thin-layer and paper chromatography). We observed that 3H-arachidonic acid was incorporated into islet phospholipids and prostaglandins under basal conditions (0.3 mg/ml glucose). Furthermore, exposure of islets to a stimulatory glucose concentration led to significant increases in the recovery of 3H-arachidonic acid-derived radioactivity in islet phosphatidylethanolamine, phosphatidylserine, sphingomyelin, and phosphatidylinositol as well as into all of the measured prostaglandins (A2, B2, D2, E2, and F2 alpha). The most marked increases in recovered radioactivity resulting from a stimulatory glucose concentration were in islet phosphatidylethanolamine and prostaglandin A2 (which we believe to be derived, in large part, from endogenously synthesized prostaglandin E2). These glucose-induced increases in 3H-arachidonic acid-derived radioactivity in both the phospholipid and the prostaglandin fractions were eliminated by the inhibition of phospholipase A2 activity with mepacrine or by the inhibition of cyclooxygenase activity with sodium salicylate. When islets prelabeled with 3H-arachidonic acid were exposed to a high glucose concentration in a perifusion system, there was a brisk extracellular release of radioactivity (presumably representing unidentified prostaglandins) that began within 1 min and that peaked slightly before the peak of the first phase of insulin secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1981

Effects of methysergide on some cardiovascular responses in the anaesthetized rabbit.

Methysergide (0.1-5 mg/kg i.v.) caused dose-dependent reductions in the resting heart rate of anaesthetized rabbits. Resting mean arterial blood pressure was reduced only after the maximum dose. Methysergide 5 mg/kg significantly enhanced the pressor responses to i.v. phenylephrine and enhanced the accompanying bradycardia disproportionately. There was no evidence for a central increase in baroreflex gain, so an action of methysergide on baroreceptor sensory endings is suggested as a possible explanation.

Anesthesia↗
PubMed1981

Substrate requirements for the phosphoinositide response in rat pancreatic islets.

The relationship between phosphatidylinositol hydrolysis and the first phase of insulin secretion has been investigated by briefly exposing rat pancreatic islets that had been prelabelled with myo-[2-3H]inositol to various agonists and antagonists of insulin secretion. The recovery of lipid-bound radioactivity progressively decreased as the D-glucose concentration of the incubation medium was increased. Those carbohydrates that stimulated insulin secretion evoked a phosphoinositide response, whereas non-stimulatory carbohydrates did not. With the notable exception of amino acids, non-carbohydrate secretagogues were also found to decrease the islet lipid-bound radioactivity. Inhibition of islet glucose metabolism was found to decrease the recovery of lipid-bound radioactivity, largely as a result of impaired de novo phosphoinositide synthesis. The phosphoinositide response to glucose was not affected by inhibition of microtubular function, but was dependent upon the availability of extracellular calcium ions. We conclude that the phosphoinositide response in carbohydrate-stimulated islets is not directly related to the activation of membrane-associated glucose receptors, but may occur as a consequence of the subsequent transmembrane movement of calcium ions. Finally, the observation that stimulatory amino acids did not evoke a phosphoinositide response suggests that, under certain circumstances, this phenomenon can be dissociated from insulin secretion.

Animals↗
PubMed1980

Vasoactive sites in the diencephalon of the rabbit.

Stimulation of the brain stem of the anaesthetized rabbit, in the lateral hypothalamic area and the zona incerta 0.5-3 mm from the midline and a similar distance dorsal to the lateral mammillary nucleus, evoked vasoconstriction in the skin of the ear and of the hindpaw. Only weak and inconstant effects on muscle blood flow were evoked from this region of the brain stem. Muscle vasodilatation was obtained by stimulation of more medial regions of the brain stem, extending almost all the way from the supramammillary nucleus to the dorsal surface. This vasodilatation was not diminished by atropine. Alpha-adrenergic blocking agents diminished the cutaneous vasoconstrictor responses and also reduced or even reversed the bradycardia that could be evoked by hypothalamic stimulation.

Animals↗
PubMed1980

An effect of hypothalamic stimulation on cardiac output in the rabbit.

Electrical stimulation of a discrete region of the rabbit brainstem, in the lateral hypothalamic area near the mammillothalamic tract, caused an increase in arterial blood pressure accompanied by bradycardia in anaesthetized animals. The cardiac output, measured by a thermodilution technique, was found to fall when the stimulus strength was great enough to evoke strong bradycardia. Threshold current for this effect varied in different animals in the range: 50-350 microA (1 msec pulse duration and 60 pulses/sec repetition rate). Bilateral vagotomy eliminated almost all the negative chronotropic effects of hypothalamic stimulation, but reversed only about one-third of the fall in cardiac output during strong stimulation. It is suggested that negative chronotropic, and possibly inotropic, vagal effects on the heart play a relatively minor role in reducing cardiac output. The major factor in causing output to fall may be left ventricular overload during the widespread peripheral vasoconstriction that accompanies stimulation of this region of the rabbit hypothalamus.

Animals↗
PubMed1978

Potentiation of a cardioinhibitory reflex by hypothalamic stimulation in the rabbit.

Repetitive stimulation of an area within the lateral hypothalamus, near the mammillothalamic tract, evoked pressor responses with bradycardia in anaesthetized rabbits. With weak stimulation (cathodal pulses below 75--150 microamperemeter, 1 msec duration, 60--100 per sec for 5--9 sec) the pressor responses were accompanied by bradycardia similar in intensity to that evoked by i.v. administration of noradrenaline. Stronger stimulating currents evoked an intense bradycardia that could not have arisen solely through the baroreceptor reflex. With these stronger currents the heart rate sometimes fell, transiently, to less than 20% of the resting rate. After denervation of the 4 main buffer nerves (sinus and aortic nerves), hypothalamic stimulation could not readily evoke bradycardia, although the pressor, respiratory and other effects remained. When the baroreceptor afferents were activated, either by evoked pressor responses in rabbits whose buffer nerves were intact or by electrical stimulation of the central ends of divided aortic nerves, strong hypothalamic stimulation augmented the bradycardia evoked reflexly from these baroreceptor afferents. This evidence suggests that electrical stimulation of this area in the hypothalamus may facilitate the cardioinhibitory component of the baroreceptor reflex in the rabbit.

Afferent Pathways↗
PubMed1977

Diameter distribution spectral of myelinated axons in the median and ulnar nerves of the Soay sheep.

An ulnar and a median nerve were taken from each of three Soay sheep, two aged 13 months and one aged 6 years. The axon diameter distribution spectra in these six nerves were determined by measurement of transverse sections stained by the Weigert-Pal technique. The histograms of myelinated axon diameters, between 1-17 micron, were unimodal in all the ulnar nerves. The mode lay between 4-5 micron in the nerves from the young sheep and between 6-7 micron in the old animal. The histograms of the median nerve axon diameters, between 1-18 micron, were all tri-modal. The nerves from the young sheep had modes between 2-3, 4-5 and 9-11 micron, and in the nerve from the old animal the modes were between 3-4, 6-7 and 12-13 micron. These findings are correlated with the conduction velocities recorded from these nerves in an earlier series of experiments.

Age Factors↗
PubMed1976

Measurement of current spread from microelectrodes when stimulating within the nervous system.

Tungsten stimulating microelectrodes have been tested in monopolar, bipolar and concentric configurations for the extent to which unwanted current spread occurred. Current spread from monopolar electrodes in close conformity with the predictions of the inverse square law, both in vitro in vivo. The bipolar and concentric configurations, tested only in vitro, had current-spread characteristics which did not follow the inverse square law so closely. The bipolar configuration gave little reduction in spread, compared wpith a monopolar electrode, but the concentric configuration did reduce the extent of stimulus spread. The extent of spread depends greatly upon a number of experimental variables, including the dimensions of the microelectrode tip. For studies requiring precise localization with low stimulus currents, it is advisable to determine the inverse square law constant for each experimental situation. For more generalized stimulation purposes within the mammalian C.N.S., employing monopolar microelectrodes of moderate tip size, brief pulses of 10 muA can be expected to stimulate myelinated axons with about 0.15 mm of the tip, and 100 muA WILL Stimulate with a radius of about 0.5 mm.

Animals↗