Biomedical subjects

N Tumer

Publications and source records attributed to N Tumer.

24 records · Page 2Linked to original sources

PubMed1987

The role of enkephalins in the production of epileptogenic activity and autonomic dysfunction: origin of arrhythmia and sudden death in the epileptic patient?

Autonomic dysfunction, including arrhythmias, has been shown to be associated with epileptogenic activity. This study examines the potential role for enkephalins in this process. A long lasting elevation of immunoreactive methionine (met)-enkephalin content in the septum, hypothalamus, amygdala, and hippocampus of rats occurs after pentylenetetrazol-induced convulsions (Brain Research 297: 121-125, 1984). Brennan et al (Life Sciences 27: 1097-1101, 1980) reported a greater percent inhibition of potassium-stimulated GABA release with increasing concentrations of met-enkephalin. Snead and Bearden (Science 210: 1031-1033, 1980) found that leucine-enkephalin in the central nervous system may induce epileptogenic activity. In addition, (d-alanine2) met-enkephalin has been shown to produce a centrally mediated vasopressor response as well as attenuation of the baroreceptor reflex in conscious cats (Hypertension 3: 395-407, 1981), possibly leading to autonomic imbalance. The latter may precipitate arrhythmias and sudden unexplained death in the epileptic patient. Resolution of the question of whether enkephalins elicit epileptogenic activity and autonomic dysfunction via inhibition of GABA release is important since an understanding of this mechanism should eventually allow the design of pharmacologic agents to prevent the epileptogenic activity, autonomic dysfunction and the associated sudden death.

Animals↗

PubMed1987

Protection of CGS 10078B against ouabain-induced arrhythmia in the cat.

CGS 10078B (CGS; 1-[2,3-dihydro-1,4-(2S)-benzodioxin-2-yl]-5-[2,3-dihydro-1,4-(2R)- benzodioxin-2-yl]-3-(1R,5S)-aza-1,5-pentanediol methane sulfonate) is an agent with alpha- and beta-receptor and calcium channel blocking actions. To study its antiarrhythmic activity, cats were anesthetized with alpha-chloralose, ventilated, and given atropine and gallamine. CGS (10 or 20 mg/kg, i.v.) was infused 15 min prior to ouabain. Bolus injections of ouabain (25 micrograms/kg, i.v.) were given every 15 min until death (D). Some cats were pretreated with reserpine (R; 5 mg/kg, i.p.) 24 h prior to the experiment. In other cats 6-hydroxydopamine (6-OHDA; 20 mg/kg, i.v.) was administered 3 days prior to CGS 20 mg/kg and ouabain. Data were compared with those of Lathers [Eur. J. Pharmacol. 64: 95, 1980], i.e., with 12 cats who received only ouabain and with 11 pretreated with timolol (T; 5 mg/kg, i.v.) prior to ouabain. After CGS (10 or 20 mg/kg, i.v.), but just prior to the first dose of ouabain, the blood pressure (BP) was decreased (p less than 0.05) from control (165 +/- 6 vs. 96 +/- 7, and 136 +/- 5 vs. 90 +/- 10 mm Hg, respectively). Comparable heart rate (HR) values were also decreased (p less than 0.05) from 225 +/- 17 to 166 +/- 14 and from 193 +/- 8 to 152 +/- 6 beats/min. 11 min after T, BP and HR had decreased (p less than 0.05) from 133 +/- 6 to 103 +/- 7 mm Hg and from 134 +/- 4 to 104 +/- 6 beats/min, respectively. Ouabain did not influence these decreases in BP and HR. CGS (10 or 20 mg/kg, i.v.) increased (p less than 0.05) the time to ouabain-induced arrhythmia (AR) and D. The magnitude of the protection appeared to be similar to that afforded by T. R given prior to CGS (20 mg/kg, i.v.) also increased the time to ouabain-induced AR and D while 6-OHDA increased the time to AR. The CGS protection against ouabain-induced AR was still present in animals pretreated with R or 6-OHDA. This indicates that the antiarrhythmic affect is not dependent upon adrenergic neuronal blockade.

Adrenergic alpha-Antagonists↗

PubMed1987

Absence of age-related changes in the binding of the beta adrenergic antagonist 125I-iodohydroxybenzylpindolol in rat heart.

The effect of age on the density and the affinity of beta adrenergic receptors was determined in the hearts of Fischer 344 rats at three ages, 6, 12, and 24 months old. The binding of the beta adrenergic antagonist 125I-iodohydroxybenzylpindolol (IHYP), was used to quantitate and characterize cardiac beta adrenergic receptors. The maximal number of binding sites (Bmax = F moles/mg of protein) were 26.3 +/- 2.5, 25.4 +/- 0.99, and 24.5 +/- 2.4 and the dissociation constants (Kd = nM) were 0.166 +/- 0.014, 0.126 +/- 0.006, and 0.135 +/- 0.015 for 6, 12, and 24 months old animals, respectively. There were no significant differences among the three ages. These results support the contention that neither beta adrenergic receptor density or affinity changes with age in the ventricles of the rat heart.

Adrenergic beta-Antagonists↗

PubMed1986

The effect of acute and chronic administration of timolol on cardiac sympathetic neural discharge, arrhythmia, and beta adrenergic receptor density associated with coronary occlusion in the cat.

The effect of timolol (5 mg/kg, p.o., b.i.d. 7 or 14 days) on cardiac beta adrenergic receptor density, the times to arrhythmia (AR) and death (D), heart rate, mean arterial blood pressure, and postganglionic cardiac sympathetic neural discharge after acute coronary occlusion in cats was examined. In the control animals, receptor densities in the left and right atria did not differ, but were lower than the right ventricle. Left ventricle and septum receptor densities were higher, with the left ventricle the highest. The importance of the gradation of beta receptors with increasing density from base to apex appears to be its relation to cardiac contractile function. Occlusion in cats not treated with timolol did not alter the cardiac beta receptor densities. After timolol for 7 or 14 days, no occlusion, receptor density increased in left ventricle and septum although the increase was only significant after 14 days. A comparison of the beta adrenergic receptor densities in cats pretreated with timolol for 7 or 14 days with or without occlusion revealed that, in general, a decrease (p greater than 0.05) occurred for the occlusion group. Timolol decreased heart rate and blood pressure prior to occlusion. The mean times to AR and D were not significantly increased by either dosing regimen of timolol, although the trend was for an increase in the time to D after 7 days of timolol and an increase in the time to AR and D after 14 days of timolol. When compared with data obtained in saline cats, chronic timolol produced minimal changes in postganglionic cardiac sympathetic neural discharge. Timolol given chronically (p.o.) or acutely (5 mg/kg, i.v. given 15 min prior to occlusion) also did not prevent the cardiac sympathetic discharge associated with the development of AR. The time to AR and D in the acutely treated cats was increased but not significantly. Since cardiac sympathetic neural discharge increased as blood pressure fell in the control period but did not increase after occlusion in the timolol treated animals, the combination of timolol and occlusion may have modified neural discharge via an action on the baroreceptor mechanism. That chronic administration of timolol produces an effect not present in cats in which only occlusion was done is supported by the observation that chronic treatment produced an occlusion-induced decrease in beta adrenergic receptor density.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

PubMed1985

Comparison of intraosseous, central, and peripheral routes of sodium bicarbonate administration during CPR in pigs.

Obtaining venous access continues to be one of the most difficult problems faced by a physician caring for the pediatric patient in cardiac arrest. Our study examined the use of the intraosseous route (through the bone) to obtain venous access for sodium bicarbonate administration in a cardiac arrest model. Ventricular fibrillation was induced in 23 domestic swine. Cardiopulmonary resuscitation was performed for five minutes and sodium bicarbonate (1 mEq/kg) was administered through a peripheral IV line (n = 6), a central IV line (n = 5), or intraosseously (n = 6). Controls (n = 6) did not receive bicarbonate. Blood pH was sampled every two minutes for 30 minutes from the right ventricle, left ventricle, and femoral artery. An analysis of variance revealed that the central and intraosseous routes were significantly different (P less than .05) from the peripheral group, and that all three groups were significantly different (P less than .05) from the control. Pathology studies revealed only minor damage to bone when sodium bicarbonate was administered intraosseously. These data demonstrate that the intraosseous route is a rapid and effective alternative for venous access in a cardiac arrest model.

Animals↗

PubMedDate not supplied

Anticonvulsant and antiarrhythmic actions of the beta blocking agent timolol.

Cats were anesthetized with alpha-chloralose and pentylenetetrazol, 10 and/or 20 mg were administered intracerebroventricularly (i.c.v.) to elicit epileptiform activity, including both interictal and ictal discharges. Timolol, 10, 100, 500 micrograms/kg i.c.v. and 1, 5, 10 and/or 20 mg/kg i.v., was administered at 5 min intervals to determine whether it suppressed the epileptiform activity. Mean arterial blood pressure and heart rate increased after the administration of pentylenetetrazol; these increases were associated with the development of epileptiform activity and cardiac arrhythmias. All doses of timolol caused a decrease in the blood pressure and heart rate elevated by pentylenetetrazol and suppressed the epileptiform activity. Similar findings were obtained in cats that received the same doses of timolol administered at different time intervals. The data indicate that the central administration of timolol reverses the epileptiform activity of pentylenetetrazol in the brain and suppresses the associated increases in blood pressure, heart rate and cardiac arrhythmias.

Adrenergic beta-Antagonists↗