J. Thornhill - Academia.edu (original) (raw)

Papers by J. Thornhill

Regulatory Peptides, 1990

Hemodynamic (blood pressure and heart rate) experiments were conducted in conscious and/or anesth... more Hemodynamic (blood pressure and heart rate) experiments were conducted in conscious and/or anesthetized male Sprague-Dawley (S.D.), heterozygous and homozygous Brattleboro rats given intravenous (iv) dynorphin A(1-13), arginine vasopressin (AVP), norepinephrine (HCl, (NE) or sterile saline before and 10 min after an iv bolus injection of a specific receptor antagonist. These receptor blockers (kappa receptor antagonist Mr2266, alpha adrenoceptor antagonist phentolamine HCl or the AVP-V1 receptor antagonist d(CH2)5Tyr-(Me)AVP were given in equimolar concentrations (15 nmol/kg iv). In all conscious S.D. groups, iv injection of AVP (60 pmol/kg), NE (12.5 nmol/kg) and dynorphin A(1-13) (60 nmol/kg) evoked significant increases in mean arterial pressure (MAP) associated with concomitant bradycardia. The hemodynamic responses to 'both' AVP and dynorphin A(1-13) were blocked if given subsequent to AVP-V1 administration but not following phentolamine or Mr2266 pretreatment. The pressor and bradycardic responses of conscious heterozygous and homozygous Brattleboro rats after iv AVP or dynorphin again were only blocked by the AVP-V1 receptor antagonist. Anesthetized heterozygous and homozygous Brattleboro rats again showed pressor responses following iv AVP, NE or dynorphin A(1-13) but with slight or no associated bradycardia. The rise in blood pressure with AVP 'and' dynorphin A(1-13) in these groups also was only blocked by the d(CH2)5Tyr(Me)AVP antagonist. The results indicate that the pressor responses of rats given intravenous dynorphin A(1-13) involve the interaction of AVP-V1 receptors and suggest a functional interaction of these two neuropeptides in the modulation of vascular tone.

Peptides

Peptides, 1986

Experiments were conducted to compare the blood pressure and heart rate responses of conscious ra... more Experiments were conducted to compare the blood pressure and heart rate responses of conscious rats given intracerebroventricular (ICV) injections of adrenocorticotropin (ACTH 1-24) and corticotropin releasing factor (CRF). Under sodium pentobarbital anaesthesia, rats were implanted with a stainless-steel cannula into the lateral cerebral ventricle and had their right femoral artery and vein cannulated. Upon recovery (24-48 hr later) conscious, unrestrained rats were given ICV injections (total volume 5 microliter by gravity flow) of sterile saline, ACTH (1-24) (0.85 and 1.7 nmoles) or CRF (0.55 and 1.1 nmoles) and blood pressure and heart rate were monitored over the next 2 hr (from the abdominal aorta via the femoral arterial catheter). Both ACTH and CRF caused mean arterial pressure (MAP) to increase, which was paralleled with increases in mean heart rate (MHR). Moreover, these elevations in MAP and MHR were temporally associated with excessive grooming (for ACTH) and locomotor activity (for CRF), which occurred before and lasted as long as MAP and MHR were enhanced. Intravenous (IV) pretreatment whereby naloxone was given 10 min before ICV administration of ACTH (1.7 nmoles) or CRF (1.1 nmoles), showed that naloxone blocked the behavioral, pressor and tachycardic effects of both ACTH and CRF. The results demonstrate that the pressor, tachycardic and locomotor effects evoked in conscious rats by ICV administration of ACTH or CRF are antagonized by naloxone and that their hemodynamic changes may, in part, be mediated by prior behavioral activation.

Prostaglandins, Leukotrienes and Essential Fatty Acids, 1999

Experiments compared the hemispheric neural damage resulting from global hemispheric hypoxic isch... more Experiments compared the hemispheric neural damage resulting from global hemispheric hypoxic ischemia (GHHI, ligation of right common carotid artery plus 35 min of 12% O 2) in groups of anesthetized, male Long Evans rats, 9-10 weeks of age, kept at 37°C, and previously given an intracerebroventricular (i.c.v., 2.5 µl) injection of 28 or 70 pmoles of PGE 2 , PGF 2α or PGD 2 or sterile saline (SS) 30 min beforehand. Mean arterial pressure (MAP), ipsilateral cortical capillary blood flow (CBF), colonic (T c), ipsilateral (T ipsi) and contralateral (T contra), temporalis muscle temperatures were measured before, during and for 15 min after GHHI. Necrotic neural damage was assessed 7 days post-GHHI. All groups given GHHI + PGs showed increased ipsilateral hemispheric damage to GHHI especially due to enhanced neocortical damage, compared to the saline control group given the same insult. PGD 2 was the most potent PG to cause further damage to the global insult. T c , T ipsi , T contra and MAP increased following the i.c.v. injection of PGE 2. Icv PGF 2α transiently decreased MAP, PGD 2 tended to decrease cerebral blood flow and neither evoked changes in temperature compared to respective pre-injection control values. Results demonstrate increased neural damage to GHHI with prior icv PGE 2 , PGF 2α or PGD 2 administration.

Computers in Biology and Medicine, 1992

The designed inexpensive blood pressure recording system (BPRS) gives any microcomputer direct on... more The designed inexpensive blood pressure recording system (BPRS) gives any microcomputer direct on-line blood pressure and heart rate recording capability that will save research time and increase the accuracy of collected data. The data is automatically stored in a file compatible with most graphic and statistical processing software. In vitro testing, over a range of 0-200 mmHg and 0-360 beats per minute showed a 0.999 intraclass correlation. In vivo testing of the BPRS used anaesthetized rats whereby their systolic and diastolic pressures were measured simultaneously with heart rate. The blood pressures and heart rate data, measured by the BPRS demonstrated excellent stability, sensitivity and accuracy when compared to those measured by standard pressure transducers in conjunction with a Grass polygraph and a sphygmomanometer.

Canadian Journal of Physiology and Pharmacology, 1990

Canadian Journal of Physiology and Pharmacology, 2001

Brain temperature is an important variable in determining the outcome of cerebral ischemia; incre... more Brain temperature is an important variable in determining the outcome of cerebral ischemia; increases in core temperature escalate neural damage whereas decreases in core temperature reduce damage. Fever induction often occurs in patients prior to or as a direct or indirect result of the ischemic insult, with a worsened stroke outcome, compared with non-febrile ischemic patients. Most importantly, post-ischemic hypothermia reduces long term neural damage and associated behavioral deficits in animals studied for up to a year after the ischemic insult. This review discusses the importance of monitoring the brain temperature of stroke patients and implemention of therapeutic thermoregulatory strategies to reduce the temperature of ischemic patients.Key words: hypothermia, neuroprotection, fever, neural and behavioral outcomes.

Brain Research, 1998

The thermoresponsiveness of posterior hypothalamic (PH) neurons to localized, incremental thermal... more The thermoresponsiveness of posterior hypothalamic (PH) neurons to localized, incremental thermal heating and cooling between 10-40 degrees C of the abdomen or scrotum was determined in urethane anesthetized, male Sprague-Dawley rats whose core temperature was maintained at 37 degrees C during testing. PH extracellular neuronal activity was recorded along with changes in gastrocnemius muscle EMG activity and temperature (Tms, indicative of shivering thermogenesis) and intrascapular brown adipose tissue temperature (TIBATs, indicative of non-shivering thermogenesis). Seventy-five PH neurons were recorded following both scrotal and abdominal trials of thermal stimulation. Nine percent of PH neurons were classified as warm responsive neurons (WRNs), 20% as cold responsive (CRNs), and 71% as temperature nonresponsive neurons (TNRNs), based on their thermal coefficients (TCs). Mean TC for warm PH neurons was significantly increased with scrotal warming between 30-40 degrees C from the mean TC of the same PH WRNs following abdominal warming. Similarly, the thermal coefficient was increased (i.e., was more negative) for cold responsive PH neurons to scrotal cooling (20-10 degrees C) as opposed to the TC of the same PH CRNs for abdominal cooling. No shivering thermogenesis (no change in temperature or EMG activity from gastrocnemius muscle) or non-shivering thermogenesis (no significant increase in IBAT temperatures) occurred with scrotal or abdominal cooling in these 21 degrees C acclimatized rats. The results indicate that a small population of PH neurons are thermoresponsive to localized physiological changes in temperature of the scrotum and abdomen with greater thermoresponsiveness shown of both warm and cold PH neurons to scrotal vs. abdominal thermal stimulation.

Can J Physiol Pharmacol, 1989

Experiments were conducted to determine (i) how naloxone administration alone could modify the in... more Experiments were conducted to determine (i) how naloxone administration alone could modify the inotropic (in electrically stimulated (ES) rat atria) and both the inotropic and chronotropic responses (in spontaneously beating (SB) rat atria) isolated from normotensive and hypotensive (hemorrhaged) rats, and (ii) how naloxone administration would modify the inotropic and chronotropic responses of isolated rat atria previously administered an opiate agonist (morphine), a muscarinic agonist (carbachol), or an α - and β-adrenergic agonist (noradrenaline). Naloxone (51–340 μM) added to ES atria caused a delayed but dose-related decrease in atrial tension (AT), whereas in SB atria, naloxone caused atrial heart rate (AHR) to fall and atrial tension (AT) to increase. Naloxone (68–340 μM), given to SB atria from acutely hypotensive rats, caused a similar increase in atrial tension as seen in the &amp;amp;amp;quot;normotensive&amp;amp;amp;quot; isolated (SB) atria and a similar decrease in atrial heart rate. Morphine sulphate (MS), 37–375 μM, administered to ES atria caused a delayed fall in AT, which was further decreased when naloxone (340 μM) was also added. In the SB atria, morphine caused a dose-related decrease in atrial heart rate whereas atrial tension increased. In SB preparations, atrial heart rate fell even further when naloxone was added to morphine compared with when morphine sulphate was given alone, whereas atrial tension was increased. Noradrenaline (3 or 12 μM) caused a positive, dose-related inotropic response in the ES atria, effects not influenced by the addition of naloxone. In the SB atria, naloxone caused no change in the dose-related increases in atrial tension and heart rate when combined with the lower dose of noradrenaline but decreased AT when combined with 12 μM noradrenaline, compared with when this dose of noradrenaline was given alone. Carbachol (683 nM – 1.37 μM) caused a dose-related decrease in atrial tension in ES atria, which was reversed completely by the addition of naloxone. In SB atria, carbachol decreased both atrial tension and heart rate, and with the addition of naloxone (340 μM), a further slight drop in atrial heart rate occurred, but concurrently, a marked rise in atrial tension was observed. The results indicate that naloxone can act with receptors directly within atrial tissue to cause changes in atrial tension and heart rate. The comparable delayed responses of morphine and naloxone suggest their effects are mediated by nonopiate receptors which, in time, cause decreases in calcium influx into the atria. The marked rise in atrial tension following naloxone administration in atria previously given carbachol suggest there is an interaction between naloxone- and carbachol-sensitive receptors in the atria. The net result of this interaction may again reflect a change (increase) in calcium influx into myocardial cells.Key words: rat atria, inotropy, chronotropy, morphine, carbachol, noradrenaline, acute hypotension.

The specificity of thermoresponsive ventromedial hypothalamic (VMH) neurons to localized, increme... more The specificity of thermoresponsive ventromedial hypothalamic (VMH) neurons to localized, incremental scrotal thermal cooling and heating of urethane-anaesthetized male Sprague-Dawley rats (maintained at 37°C colonically) was investigated. 2. Ventromedial hypothalamic extracellular neuronal activity and surface (scalp) electroencephalogram (EEG) activity from the parietal region were recorded. Intrascapular brown adipose tissue (TIBAT), surface tail (Tt) and scrotal (T8C) temperatures, where thermal stimulation was evoked, were also monitored. 3. One hundred and twenty-five VMH neurons were recorded, with forty (32%) VMH neurons classified as warm-responsive neurons (WRNs), twenty-three (18%) as coldresponsive neurons (CRNs) and sixty-two (50 %) as thermal non-responsive neurons (TNRNs) based on their thermal coefficients. Of VMH WRNs, 60 % (i.e. 24) were classified as having biphasic neuronal activity responses, as were 60% (i.e. 14 of 23) of the CRNs. Forty per cent of WRNs and CRNs were classified as having monophasic changes in neuronal activity. 4. Scrotal heating or cooling from 5 to 40°C resulted in specific firing rate changes of VMH WRNs and CRNs without any associated change in EEG activity (i.e. no significant change in EEG frequency or amplitude from initial baseline EEG activity when TS was 20°). EEG desynchronization (increased EEG frequency, decreased amplitude) was only observed when scrotal temperatures were at 45°C or after each tail pinch (noxious stimulation) but not with scrotal brushing (mechanical stimulation). 5. With core temperature maintained at 37°C, localized, scrotal heating and cooling of rats did not induce IBAT temperature changes indicative of brown adipose tissue activation, but delayed changes in tail temperature, indicative of vasoactive effector responses, did occur.

The American journal of physiology, 1994

Electrical stimulation of the ventromedial hypothalamic area in rats caused a significant but tra... more Electrical stimulation of the ventromedial hypothalamic area in rats caused a significant but transient increase in interscapular brown adipose tissue temperature. This response was markedly reduced by cimetidine, a histamine H2-receptor antagonist, but not by pyrilamine, an H1-receptor antagonist. Histamine is present in substantial amounts within mast cells in brown adipose tissue as injections of compound 48/80, which cause degranulation of connective tissue mast cells, reduced the tissue histamine content by > 85%. In contrast, histamine content in brown adipose tissue was not affected by loss of sympathetic neural input (with 6-hydroxydopamine) or sensory neural input (with capsaicin). Neither cimetidine nor histamine had any effect on basal and norepinephrine-stimulated rates of O2 consumption by isolated brown adipocytes. These results indicate that histamine released from mast cells acting on H2-receptors may play an important but indirect role in the thermogenic response...

Regulatory Peptides, 1987

Experiments were designed to determine the hemodynamic responses of conscious, unrestrained rats ... more Experiments were designed to determine the hemodynamic responses of conscious, unrestrained rats given intracerebroventricular (i.c.v.) injections of dynorphin A-(1-13) and the possible central receptor mechanisms mediating those changes. Male Sprague-Dawley rats (300 g b. wt.) received i.c.v, injections (by gravity flow in a total volume of 3 or 5/d) of control solutions of sterile saline (SS) or dimethylsulfoxide (DMSO) or 1.5, 3.0 or 6.1 nmol of dynorphin A-(I-13). Blood pressure and heart rate changes were monitored over 2 h after administration; as well, feeding activity was visually assessed and scored over this period. Other groups of conscious rats were pretreated i.c.v, with equimolar doses (3.0-24.4 nmol) of specific receptor antagonists (naloxone HC1, phentolamine HCI, propranolol HC1, yohimbine HC1 or prazosin HC1) 10 min before subsequent i.c.v, administration of SS or DMSO/SS or 6.1 nmol of dynorphin A-(I-13). I.c.v. injection of dynorphin A-(l-13) caused a dose-related pressor response, associated temporally with tachycardia. As well, dynorphin evoked feeding activity and some grooming, which occurred when the rats were hypertensive and tachycardic and decreased as heart rate and blood pressure returned to control levels. I.c.v. pretreatment studies indicated that naloxone HC1 (12.2 nmol), phentolamine HC1 (12.2 nmol) and prazosin HC1 (6.1 nmol) blocked the pressor response, tachycardia as well as feeding activity of rats subsequently given dynorphin. The results suggest the pressor and tachycardic effects of conscious rats following i.c.v, dynorphin administration may, in part, be due to behavioral acti

Peptides, 1985

THORNH1LL, J. A. AND W. S. SAUNDERS. Brood pressure responses of conscious rats to intravenous ad... more THORNH1LL, J. A. AND W. S. SAUNDERS. Brood pressure responses of conscious rats to intravenous administration of enkephalin derivatives (D-ala z methionine and leucine enkephalinamide, and methionine and leucine enkephalinamide). PEPTIDES 6(6) 1253-1256, 1985.-The present study was designed to determine the blood pressure (BP) responses of conscious rats given intravenous (IV) injections of enkephalin derivatives (D-ala2-methionine enkephalinamide, DAMEA;

Life Sciences, 1979

Abstract The effect of acute and chronic administration of naloxone on food acquisition and weigh... more Abstract The effect of acute and chronic administration of naloxone on food acquisition and weight gain in rats was studied in 3 experiments. One injection of a sparingly-soluble salt of naloxone in slow-release vehicle markedly lowered mean food intake over that of control ...

Canadian Journal of Physiology and Pharmacology, 1998

Experiments were conducted to compare the impact of febrile versus nonfebrile lipopolysaccharide ... more Experiments were conducted to compare the impact of febrile versus nonfebrile lipopolysaccharide (LPS) induced bacterial infection at the time of global hemispheric hypoxic ischemia (GHHI) on the neural damage evoked by the GHHI insult. In the first study acute intraperitoneal (i.p.) sterile saline (SS) or LPS Escherichia coli (60 µg/kg) was given to groups of male, conscious Long Evans rats, and core (colonic, Tc) temperatures were monitored over 6 h postinjection. Peak febrile response occurred ~5 h after the LPS E. coli was injected. Upon sacrifice 7 days later, no hemispheric or regional brain damage occurred in the saline or LPS-injected groups of this first study. In the second study, GHHI was applied (ligation of right common carotid artery + 35 min of 12% O2) in groups of anesthetized, male Long Evans rats previously given an acute i.p. injection of sterile saline or 60 µg/kg LPS E. coli 5 h earlier. Temperatures (Tc) were monitored before, during, and 1.5 and 24 h following...

Canadian Journal of Physiology and Pharmacology, 1993

Experiments were conducted to determine whether ventromedial hypothalamic (VMH) neurons were resp... more Experiments were conducted to determine whether ventromedial hypothalamic (VMH) neurons were responsive to thermal warming or cooling of the scrotum. Extracellular neuronal activity of VMH neurons was monitored in anesthetized groups of normothermic (core temperature maintained at 37 °C) or hypothermic (core temperatures allowed to decrease, 33.3 ± 1.1 °C) male, Sprague–Dawley rats along with colonic (Tc), interscapular brown adipose tissue (TIBAT), tail (Tt), and scrotal (Tsc) temperatures during 30-min periods of scrotal cooling (small ice pack) or scrotal warming (small sealed pack containing 40 °C tap water). In the normothermic group (65 VMH neurons recorded in total), 20 VMH neurons (31%) were classified as warm-responsive neurons (WRNs) (i.e., increased firing rate with scrotal warming and (or) decreased firing rates with scrotal cooling); 7 VMH neurons (11%) were classified as cold-responsive neurons (CRNs) (i.e., increased firing rate with scrotal cooling and (or) decreased...

Canadian Journal of Physiology and Pharmacology, 1994

Experiments were designed to determine if a functional ventromedial hypothalamic nucleus was requ... more Experiments were designed to determine if a functional ventromedial hypothalamic nucleus was required for the activation of brown adipose tissue thermogenesis evoked by medial preoptic stimulation. Male, urethane-anesthetized Long–Evans rats, maintained at 37 °C, had temperatures (thermistor probes for gastrocnemius, Tm; intrascapular brown adipose tissue, 7IBAT; colonic, Tc; and tail, Tt), gastrocnemius electromyogram activity (via stainless steel recording electrodes), and systemic blood pressure and heart rate (via a femoral arterial catheter) measured before and after a series of unilateral medial preoptic electrical stimulations (monophasic 0.5-ms pulses of 300 μA at 50 Hz for 30 s). Measurements were made (i) after an initial control medial preoptic electrical stimulation, (ii) after medial preoptic stimulation was applied 1 min following an intracranial injection of 300 nL of sterile saline or buffered 2% Lidocaine into the ipsilateral posterior hypothalamic nucleus or the ip...

Brain Research, 1996

Thermoresponsiveness of ventromedial hypothalamic (VMH) neurons to scrotal thermal stimulation wa... more Thermoresponsiveness of ventromedial hypothalamic (VMH) neurons to scrotal thermal stimulation was determined before and after microinjection of lidocaine into the medial preoptic nucleus (MPO). Male, urethane anesthetized Sprague-Dawley rats, maintained colonically at 37 degrees C had VMH extracellular neuronal activity recorded following 3 cycles of scrotal thermal stimulation (localized, incremental heating and cooling, between 10 and 40 degrees C). Based on their thermal coefficients (TC), warm (WRN), cold (CRN) thermoresponsive and temperature non-responsive (TNRN) VMH neurons had their neuronal activity recorded following each cycle of scrotal thermal stimulation before and after MPO injections of sterile saline (300 nl volume) or 2% buffered lidocaine (200 ng). Thermoresponsiveness of all warm and cold VMH neurons to scrotal thermal stimulation was blocked by prior lidocaine administration into the MPO, effects that were reversed approximately 60 min after. However, MPO lidocaine administration caused no significant change in the thermal coefficients of VMH TNRNs to scrotal thermal stimulation. Results infer that a functional MPO is required for thermal afferent signals arising from the scrotum to reach thermoresponsive VMH neurons.

Brain Research, 1993

Thermoregulation; Thermogenesis Normothermic (37°C), anesthetized Long Evans rats given unilatera... more Thermoregulation; Thermogenesis Normothermic (37°C), anesthetized Long Evans rats given unilateral electrical stimulation (0.5 ms monophasic pulses of 100-300 /zA at 50 Hz for 30 s) of the posterior hypothalamus (PH) had graded, sustained increases in EMG electrical activity of the gastronemius muscle (i.e. shivering). In a current-related manner, gastronemius muscle temperatures (T m) immediately increased following PH stimulation, surface temperatures (T t) did not change and colonic (core, T c) temperatures initially fell, then subsequently rose after the applied stimulus. A biphasic pressor response occurred after PH electrical stimulation associated with tachycardia. PH electrical stimulation (0.5 ms pulses at 50 Hz for 30 s of only 40/zA) induced shivering in anaesthetized, hypothermic Long Evans rats undergoing acute cold exposure. When these same hypothermic rats were cooled further to cause shivering, PH electrical stimulation (0.5 ms pulses at 50 Hz for 30 s of only 40/xA) induced further increases in the shivering response (]" EMG area of gastronemius muscle) from the shivering response before PH stimulation. Results indicate that electrical stimulation of the PH can evoke shivering in anesthetized normothermic rats. Stimulation of the PH with lower current intensity can induce or increase shivering of hypothermic rats previously exposed to the cold.