Biomedical subjects

T K McIntosh

Publications and source records attributed to T K McIntosh.

At least 199 records · Page 11Linked to original sources

PubMed1986

Efficacy of polyglycolic acid mesh sling in keeping the small bowel in the upper abdomen after abdominal surgery: a 12-month study in baboons.

The purpose of this study was to determine if a "sling" made of polyglycolic acid (PGA) would be a reliable method of preventing small bowel descent into the pelvis following abdominal surgery. Baboons were used, as they respond to infection and ambulate similarly to humans. Animals had the small bowel mobilized to the upper abdomen and had the PGA "sling" sewn into place. Documentation of small bowel position was evaluated by upper gastrointestinal series over the 12-month study. Small bowel descent into the pelvis was prevented by utilization of the PGA "sling." Animals were sacrificed and autopsied, and sections of small bowel were taken. There was no evidence of mesh, obstruction, sepsis, fistulae, or herniation in animals at autopsy. Small bowel sections were considered normal histologically. Utilization of PGA sling appears to be a safe and reliable method of preventing small bowel descent into the pelvis after abdominal surgery.

Abdomen↗

PubMed1986

Endorphins in primate hemorrhagic shock: beneficial action of opiate antagonists.

The endogenous opiate beta-endorphin is released concomitantly with adrenocorticotropin from the pituitary during stress. In the present study we investigated the possible involvement of opiate receptors in the cardiovascular depression associated with hypovolemic shock in the nonhuman primate. Changes in circulating levels in beta-endorphin were monitored during hemorrhagic shock in 18 female baboons. Plasma levels of beta-endorphin increased significantly during hemorrhagic shock and were significantly correlated with a decrease in cardiac output (P less than 0.05). Single bolus administration of the opiate receptor antagonist naloxone (2 or 5 mg/kg) produced a transient but significant improvement in cardiac output (P less than 0.05) and mean arterial pressure (P less than 0.05). Hemodynamic improvement was maintained with a constant infusion of naloxone. Opiate receptor blockade with the longer acting antagonist naltrexone (2 or 5 mg/kg) significantly increased mean arterial pressure (MAP; P less than 0.05), and CO (P less than 0.05), and decreased heart rate. Our results suggest that the baboon is an excellent model for the study of hemorrhagic shock and provide further evidence for endogenous opiate involvement in the cardiovascular pathophysiology of hemorrhagic shock.

Animals↗

PubMed1986

Opiate antagonist in traumatic shock.

In experimental animal studies, opiate receptor antagonists (such as naloxone) and physiological opiate antagonists (thyrotropin-releasing hormone [TRH] have been used with some success to improve outcome and physiological variables following traumatic shock associated with hypovolemia, spinal cord trauma, and head injury. Naloxone at high doses (in the mg/kg range) improves blood pressure and survival following hypovolemic shock in some species subjected to fixed-pressure shock. Similarly, naloxone treatment in the same dose range improves blood pressure and outcome following traumatic spinal shock as well as shock associated with traumatic head injury in selected animal models. The high doses of naloxone required in these studies suggest that the beneficial effects may be due to actions at relatively naloxone-insensitive opiate receptors, such as the kappa-receptor. Changes in the putative kappa-receptor ligand dynorphin are found after hypovolemic shock and traumatic injury to the brain or spinal cord. Opiate receptor antagonists with increased selectivity for the kappa-receptor may be superior to naloxone in the treatment of these conditions. TRH or TRH analogs similarly improve blood pressure and outcome following hypovolemic or spinal shock. Clinical trials of naloxone (at high doses) in human spinal cord injury have begun, and there are plans for clinical trials of naloxone in human head trauma and of TRH in human spinal cord injury.

Animals↗

PubMed1986

Endogenous opioids, opiate receptors and traumatic brain injury.

The present study examined the role of endogenous opioid peptides in the pathophysiological sequelae of fluid percussion head injury in the cat. Two hours following injury, tissue concentrations of dynorphin-like immunoreactive material (ir-Dyn) were significantly elevated in specific brain regions where injury, as evidenced by histological examination, was most severe. Changes in ir-Dyn but not beta-endorphin-like immunoreactive material (ir-End) were significantly correlated with a fall in regional cerebral blood flow (CBF) that occurred 2 h following injury. Administration of the opiate antagonist WIN44,441-3 (with enhanced activity at kappa-receptors) stereospecifically increased cerebral blood flow to the injured regions.

Animals↗

PubMed1986

Thyrotropin-releasing hormone (TRH) and circulatory shock.

Recent research has focused on the potential role of the central nervous system (CNS) in the pathophysiology of circulatory shock. Although the precise role of the brain in shock remains controversial, a number of neuropeptides--through actions within the CNS--appear to play a role in mediating cardiovascular responses to a variety of shock states. Thyrotropin-releasing hormone (TRH) is a neuropeptide that has potent cardiovascular effects within the CNS. Recently, it has been used successfully to reverse shock of varying etiologies in a number of species. Here we review the cardiovascular actions of TRH, its interaction with endogenous opiate systems, and its potential role in the treatment of circulatory shock.

Anaphylaxis↗

PubMed1985

Naloxone versus placebo in treatment of septic shock.

Treatment of septic shock with naloxone was evaluated in a prospective, randomised, double-blind, placebo-controlled study in which ten episodes of shock were treated with naloxone (0.4 to 1.2 mg intravenously) and 13 with the vehicle for injection. Treatment groups were similar in terms of demographic characteristics, type of primary infection, prevalence of septicaemia, type of underlying disease, duration in shock, and vasopressor therapy. Mean systolic blood pressure rose by 13.3% in the naloxone group and 11.3% in the placebo group. Two-way analysis of variance for repeated measures of blood pressure, obtained over 30 min periods before and after treatment, revealed no significant difference (p greater than 0.10) between treatment groups. Survival rates in the two groups at 48 h and 7 days after the start of treatment were similar. Naloxone, 0.4 to 1.2 mg intravenously, was no better than placebo in ameliorating hypotension in septic shock.

Aged↗

PubMed1985

Prolonged disruption of plasma beta-endorphin dynamics following surgery.

The purpose of the present study was to examine the effects of surgery on plasma beta-endorphin dynamics. Plasma beta-endorphin levels were measured by liquid chromatography/radioimmunoassay in seven patients undergoing elective surgery. Blood samples were obtained every 4 hr for two 24-hr periods: one beginning 48 hr before surgery and the other beginning 48 hr after surgery. Computer analysis of beta-endorphin levels as a function of clock time demonstrated a true circadian rhythm preoperatively with a mean of 28.0 +/- 5.9 pg/ml. In the postoperative period mean beta-endorphin levels were significantly elevated (85.6 +/- 20.7 pg/ml, P less than 0.005). Surgical procedures caused significant phase shifting in the grouped mean circadian rhythm of plasma beta-endorphin (mean = 2.4 hr). When the data was analyzed individually, plasma circadian rhythms were found to be totally abolished in the three patients with the longest operative times (mean = 3.8 hr) and significantly displaced in time in the remaining four patients. These prolonged alterations in plasma endogenous opioid peptide levels following surgery have not been previously reported, and should be considered in the management of the postsurgical patient.

Adult↗

PubMed1985

Beta-endorphin, cortisol and postoperative delirium: a preliminary report.

A transient delirium, including hallucinations and disorientation, occurred at some time during a 48 to 72 hr postoperative period in patients recovering from elective surgery in an intensive care unit. The occurrence of delirium in these patients was associated with a significant and unusually prolonged postoperative increase in circulating levels of beta-endorphin (B-endorphin) and cortisol, and a total disruption of normal plasma circadian rhythms of B-endorphin and cortisol. Postoperative mean 24-hr plasma levels of B-endorphin and cortisol were not significantly different from preoperative baseline levels in those patients who did not exhibit post-surgical delirium. Circadian rhythms of B-endorphin and cortisol in the non-delirious patients also remained normal following surgery, although peak plasma concentrations were significantly phase-shifted to later in the day. A disruption in circadian rhythms of the endogenous opiate/hypothalamic-pituitary-adrenal axis may represent an important component of post-operative psychological changes that are frequently observed in the intensive care unit setting.

Adult↗

PubMed1985

Menopausal syndrome: plasma levels of beta-endorphin in post-menopausal women measured by a specific radioimmunoassay.

beta-Endorphin (beta-EP) levels were measured in 13 post-menopausal women (7 surgical, 6 physiological) using a new highly specific and accurate radioimmunoassay, and were found to be significantly lower than among 10 normally menstruating controls (48.6 +/- 13.8 pg/ml vs. 70.0 +/- 18 pg/ml, P less than 0.005). beta-EP levels were measured prior to and 5 days after surgery in 3 of the oophorectomized women, and were found to have decreased by an average of 41%. beta-EP levels were measured immediately after hot flashes experienced by 4 of the post-menopausal women during regular clinic visits, and were found to be significantly elevated above baseline levels (P less than 0.02). Our data confirmed the findings of Genazzani et al. [10], a significant lowering of beta-EP at menopause. Also, the data from the small number of beta-EP plasma levels we studied during hot flashes, suggests a possible role of beta-EP either directly or indirectly on the genesis of hot flashes.

Adult↗

PubMed1985

Effect of an opiate antagonist (naloxone) and an agonist/antagonist (nalbuphine) in primate hemorrhagic shock: relationship to catecholamine release.

Recent evidence has suggested a relationship between the endogenous opioid peptides and the pathophysiology of various shock states. In the present study, we investigated the relationship between the effectiveness of naloxone (an opiate antagonist) and nalbuphine (an opiate agonist/antagonist), and the changes in circulating levels of catecholamines in the nonhuman primate subjected to hemorrhagic shock. Plasma levels of catecholamines were measured using high-performance liquid chromatography (HPLC) during hemorrhagic shock in 15 female baboons. Plasma levels of both epinephrine and norepinephrine increased significantly during hemorrhagic shock (p less than 0.05), which correlated with an increase in heart rate. Bolus administration of naloxone (5 mg/kg) significantly increased both plasma epinephrine (p less than 0.01) and norepinephrine (p less than 0.05) over shock levels along with a transient but significant increase in cardiac output (p less than 0.05) and mean arterial pressure (p less than 0.05), and a significant decrease in heart rate (p less than 0.05). Improvements in hemodynamics were maintained with a constant infusion of naloxone (5 mg/kg/hr), which also caused a further significant increase in plasma epinephrine (p less than 0.01). Administration of a single bolus of the opiate agonist/antagonist nalbuphine (5 mg/kg) dramatically decreased cardiac output and mean arterial pressure and had no effect on circulating catecholamines. Our results suggest that (1) the beneficial action of high-dose naloxone in primate hemorrhagic shock may be attributable in part to a drug-induced increase in circulating endogenous catecholamines; and (2) the failure of high-dose nalbuphine to improve cardiovascular function may be related to its partial agonist (cardiodepressant) properties at higher doses.

Animals↗

PubMed1984

Brain monoaminergic control of male reproductive behavior. I. Serotonin and the post-ejaculatory refractory period.

The present experiment was performed to examine the role of serotonergic mechanisms in the control of copulation and the post-ejaculatory refractory period in the male rat. Disruption of central serotonergic systems in two separate groups of animals was achieved by: (1) selective electrolytic lesions of the midbrain raphe nuclei, or (2) localized intraventricular or intracerebral injection of a specific serotonergic neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT). A third group of animals was tested for sexual behavior following intraperitoneal injection of p-chlorophenylalanine (PCPA), an inhibitor of serotonin synthesis. Both electrolytic and neurochemical lesions localized in the dorsal raphe nucleus produced a highly significant shortening of the ejaculatory latency, and the post-ejaculatory refractory period. Disruption of serotonergic mechanisms following intraventricular injection of 5,7-DHT or systemic administration of PCPA also caused a significant reduction in the length of the refractory period. These results support the hypothesis that central serotonergic systems are normally inhibitory to certain facets of male copulatory behavior and suggest the existence of a serotonergic control system which normally exerts an inhibitory influence over the resumption of mating following ejaculation.

5,7-Dihydroxytryptamine↗

PubMed1984

Brain monoaminergic control of male reproductive behavior. II. Dopamine and the post-ejaculatory refractory period.

This study was designed to examine the role of central dopaminergic mechanisms in the control of copulation and the subsequent post-ejaculatory refractory period in the male rat. Disruption of central dopaminergic pathways was achieved in two separate groups of animals by: (1) selective electrolytic lesions of the substantia nigra (the major locus for dopamine cell bodies in the brain); or (2) localized intracerebral injection of 6-hydroxydopamine, a specific neurotoxin for catecholaminergic pathways. A third group of animals was tested for sexual behavior following administration of the dopamine receptor blocker pimozide. Both electrolytic and neurochemical lesions localized in the substantia nigra produced a significant increase in the length of the post-ejaculatory refractory period. Dopamine receptor blockade following administration of pimozide also caused a significant increase in refractory period duration. These results support the hypothesis that central dopaminergic pathways are involved in the motivational or arousal component of copulation and may be integral to the maintenance of a normal post-ejaculatory refractory period.

Amygdala↗

PubMed1984

Brain monoaminergic control of male reproductive behavior. III. Norepinephrine and the post-ejaculatory refractory period.

The present study was performed to examine the role of brain norepinephrine in the control of copulation and the post-ejaculatory refractory period in the male rat. Disruption of central noradrenergic systems was achieved by (1) selective electrolytic lesion of noradrenergic cell bodies in the locus coeruleus or (2) administration of specific inhibitors of norepinephrine synthesis, sodium diethyldithiocarbamate (DDC) or 1-phenyl-3-(2-thiazolyl)-2 thiourea (U-14, 624). Electrolytic lesions of the locus coeruleus produced a significant increase in the duration of the post-ejaculatory refractory period and its concomitant 22-kHz ultrasonic vocalization. Administration of norepinephrine synthesis inhibitors significantly increased both mount and intromission latencies and caused a dramatic increase in the length of the post-ejaculatory refractory period. These findings support the hypothesis that norepinephrine-containing neural pathways are involved in the control of sexual arousal and suggest that a functional noradrenergic system is essential to the integrity of normal masculine copulatory behavior.

Animals↗

PubMed1984

Electrophysiological and ultrasonic correlates of reproductive behavior in the male rat.

The purpose of the present study was to examine the electrophysiological correlates of copulatory behavior in the rat and correlate brain electroencephalographic (EEG) activity with the ultrasonic vocalizations that have been shown to play a major role in the integration of mating behavior. Ultrasonic vocalizations of male rats with chronically implanted hippocampal and cortical electrodes were monitored during mating with a female rat. Hippocampal theta rhythms were significantly correlated with high activity, mounting, intromissions, and preejaculatory excitatory behavior and were also significantly associated with 50-kHz short ultrasonic vocalizations. Postmount or postintromission behaviors (grooming, exploration) were closely correlated with an absence of ultrasonic vocalizations and the onset of irregular low-amplitude hippocampal EEG recordings. Long 22-kHz vocalizations occurred in all tests during the postejaculatory refractory period. Shorter 22-kHz vocalizations occurred during mating and were associated with unsuccessful intromissions or mounting attempts. Postejaculatory long 22-kHz vocalizations were significantly associated with irregular high-amplitude hippocampal EEG tracings, and preejaculatory short 22-kHz vocalizations were also accompanied by sleep-like irregular high-amplitude hippocampal EEG tracings with cortical spindling. The correlation of ultrasonic vocalizations with electroencephalographic and behavioral manifestations of central arousal and inhibitory processes suggests that these vocalizations are indicators of the sexual arousal of the mating pair.

Animals↗

PubMed1983