Antiarrhythmic effects of KLN-93, dicaine, and lidocaine in neurogenic atrial fibrillation

Antiarrhythmic activities of KLN-93 (crystallographically homogeneous paraaminobenzoic acid ester derivative), dicaine, and lidocaine in cats with neurogenic atrial fibrillation rank in the order in which these agents are named and depend on their vagolytic but not cardiotropic effect whose intensity decreases in the following series: dicaine>lidocaine>KLN-93. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 124, No. 7, pp. 77–80, July, 1997     

Comparison of antiarrhythmic activities of befol,lidocaine, and bonnecor

The antiarrhythmic activity of befol (an isotoxic dose) is higher than (or comparable to) that of lidocaine and bonnecor in atrial and ventricular arrhythmias induced by acute ischemia, reperfusion, myocardial infarction, or ouabain treatment. In epinephrine-induced arrhythmia, befol is inferior to these drugs (except lidocaine) in activity and range of therapeutic action. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 122, No. 12, pp. 665–668, December, 1996     

Effect of adaptation to moderate physical loads on the increased resistance of the isolated heart to ischemia and reperfusion

Adaptation to physical loads elicits pronounced anti-ischemic and antireperfusion effects on the isolated heart. By the 20th min of total ischemia contracture in the hearts of adapted animals is much less than that in the control group. During reperfusion of hearts from adapted animals the degree of restoration of the contractile force was 6-fold higher, contracture was lesser, and the total period of tachycardia and fibrillation were 3-fold shorter than in the control. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 119, N ^o 1, pp. 25–27, January, 1995 Presented by S. S. Debov, Member of the Russian Academy of Medical Sciences     

Delta sleep-inducing peptide and flunitrazepam acting jointly increase cardiac electrical stability

In experiments on rabbits under Nembutal anesthesia, intravenous injection of flunitrazepam in a single dose of 0.125 mg/kg in combination with delta sleep-inducing peptide in a single dose of 60 nmol/kg raised the threshold of ventricular fibrillation to a level that was significantly higher than that after injection of flunitrazepam alone in the same dose and comparable to that after injection of this benzodiazepine alone in twice as high a dose (0.25 mg/kg), but without the side effects (persistent hypotension and transient bradycardia) produced by the latter dose. It is concluded that the ability of jointly acting delta sleep-inducing peptide and flunitrazepam to increase the electrical stability of the heart may have practical relevance to the prevention of ventricular arrhythmias occurring under conditions of emotional stress and myocardial ischemia. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 119, N ^o 4, pp. 342–345, April, 1995 Presented by K. V. Sudakov, Member of the Russian Academy of Medical Sciences     

Psychotropic activity of cholecystokinine tetrapeptide analogs

Psychotropic activity of two cholecystokinin analogs Trp-R₁-Asp-Phe-NH₂ and R₂-Trp-R₃-Asp-Phe-NH₂ is studied using behavioral tests. Both analogs have no effect on motor activity. Trp-R₁-Asp-Phe-NH₂ in doses of 0.1 and 0.3 mg/kg exhibits anxiogenic activity and impairs learning (only in a dose of 0.1 mg/kg) of experimental animals. R₂-Trp-R₃-Asp-Phe-NH₂ possesses no anxiogenic activity and in doses of 0.1 and 0.3 mg/kg promotes learning, which attests to its nootropic activity. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 125, No. 6, pp. 647–650, June, 1998     

Tolerance to the bronchoprotective effect of β2 -agonists: Comparison of the enantiomers of salbutamol with racemic salbutamol and placebo

Background: Regular use of racemic salbutamol results in the partial loss of its bronchoprotective effect. The 2 enantiomers of salbutamol, the bronchodilator R-salbutamol and nonbronchodilator S-salbutamol, are now available. Objective: We sought to compare the effect of regular use of S-salbutamol, R-salbutamol, racemic salbutamol, and placebo on the bronchoprotective effect of a single dose of racemic salbutamol against methacholine-induced bronchoconstriction. Methods: Eleven of 13 well-controlled β₂ -agonist–free asthmatic subjects completed a double-blind, randomized study comparing racemic salbutamol 2.5 mg, S-salbutamol 1.25 mg, R-salbutamol 1.25 mg, and diluent placebo nebulized and inhaled 3 times daily for 6 days (≥6-day washout period). Ten to 12 hours after the last dose, the subjects performed measurement of FEV₁ , methacholine PC₂₀ , and a repeat methacholine PC₂₀ done 1 hour after the first methacholine test and 10 minutes after 2 puffs (200 μg) of racemic salbutamol administered from a metered-dose inhaler. The primary endpoint was the methacholine PC₂₀ dose shift (Δlog PC₂₀ ÷ log 2) from before to after administration of 200 μg of racemic salbutamol. Results: The methacholine dose shift was 3.2 doubling doses (9-fold increase in methacholine PC₂₀ after 200 μg of racemic salbutamol) during the placebo treatment and was unaltered (3.2) after administration of S-salbutamol. The dose shift was significantly lower after both the R-salbutamol and racemic salbutamol treatments (2.2 and 2.6 doubling doses, respectively); there was no significant difference between R-salbutamol and racemic salbutamol. There was no treatment effect on baseline FEV₁ , baseline methacholine PC₂₀ , or bronchodilation. Conclusion: Regular treatment with racemic salbutamol or R-salbutamol, but not S-salbutamol, results in a partial loss of bronchoprotection, without loss of bronchodilation, compared with placebo. (J Allergy Clin Immunol 1999;103:1049-53.)     

Adaptation to physical load increases the activity of prostaglandins E and I2 and reduces stress reaction

Adaptation to physical load protects against stress and other damage. It is suggested that this protection is associated with activation of prostaglandins E (PGE) and I₂ (PGI₂). Plasma contents of PGE₂, PGI₂, and thromboxane A₂ (TxA₂) and the severity of stress reaction are measured in male Wistar rats adapted to swimming. Training increases the concentrations of these prostaglandins and the prostaglandin/TxA₂ ratio, reduces almost 2-fold the severity of stress reaction as assessed by the plasma corticosterone concentration and corticosterone/insulin ratio. After stress, the PGI₂ and PGI₂/TxA₂ in adapted rats were, respectively, 33 and 31% higher than in unadapted. These findings suggest that prostaglandins are involved in the reduction of stress reaction. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 122, No. 12, pp. 622–624, December, 1996     

Norbornane-induced changes in the density of chloride-ion channels in the brain of rodents

In this study on rats and mice, the clinical course of poisoning in rats injected with norbornane [2,2-di-(trifluoromethyl)-3,3-dicyano-5,6-dichloronorbornene] in a dose equal to 2 LD₅₀ was characterized by slow progression of the convulsive syndrome. Radioligand analysis revealed reduced densities of chloride-ion channels in the striatum and cerebellum of rats and in the whole brain of mice after norbornane administration. Picrotoxin in equitoxic doses did not alter the density of these channels. It is concluded that norbornane causes irreversible inhibition of chloride-ion channels. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 122, No. 7, pp. 14–16, July, 1996     

The role of neurotropic component in therapeutic effect of antiarrhythmic drugs

Acute experiments on anesthetized cats with neurogenic atrial fibrillation showed that the antifibrillatory effect of procainamide, lidocaine, and ethacizin correlated with their vagolytic rather than with cardiotropic activity. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 127, No. 3, pp. 353–356, March 1999     

Effect of NO-synthase inhibitor L-NAME on occlusion and reperfusion arrhythmias in cats

On the model of occlusion/reperfusion arrhythmia in cats it was shown that repeated injections of the NO-synthase inhibitor L-NAME decreased the incidence of occlusion arrhythmias (to 40%), eliminated reperfusion-induced ventricular fibrillation, and drastically reduced the latency of occlusion arrhythmias. A single injection of L-NAME (20 mg/kg) immediately before ligation of the coronary artery did not decrease the incidence of occlusion and reperfusion arrhythmias. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 127, No. 5, pp. 509–511, May, 1999     

Stimulation of the DNA replication and murine bone marrow cell proliferation with exogenous zinc-metallothionein

It is shown that zinc-metallothionein from rat liver increases 1.5-fold thein vitro incorporation of³H-thymidine in murine bone marrow cells. The same concentrations of zinc chloride and a mixture imitating zinc-metallothionein (zinc, cysteine, and albumin) inhibit DNA synthesis. In mice receiving an intraperitoneal injection of zinc-metallothionein 10–15 min before γ-irradiation, the incorporation of³H-thymidine and the content of nucleated cells in the bone marrow is 1.5- to 2-fold higher than those in unprotected animals, the number of endogenous splenic colonies in pretreated mice being 2.7-fold higher. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 122, No. 11, pp. 505–508, November, 1996     

Saponin in thein vitro phosphorylation system

The possibility of the use of saponin for permeabilization of synaptic vesicles from P₂ fraction is explored. This fraction is isolated from rat brain cortex. Phosphorylation of membrane-bound proteins is performedin vitro. At the saponin:protein ratio 1:10 (w/w) phosphorylation of these proteins increases 2-fold due to increased membrane permeability for ATP and cAMP. Treatment of synaptic vesicles with saponin at the same ratio leads to the loss of cytosolic but not membrane-bound protein. This concentration of saponin can be used for permeabilization of other membranes, providing that the protein:cholesterol ratio is taken into consideration. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 122, No. 10, pp. 453–456, October, 1996     

Effect of irradiation on vitamin status and spermatogenesis in rats

It is shown that in rats exposed to single external irradiation in a dose of 0.5 Gy the concentration of spermatozoa surpasses that of nonirradiated controls. The level of vitamin B₂ increases in the liver and testes of irradiated animals. For the given dose of ionizing radiation, the participation of angiotensin-converting enzyme in cell maturation during spermatogenesis is not observed. Various changes in the content of antioxidant vitamins at different stages of the experiment are described. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 123, No. 5, pp. 524–527, May, 1997     

Structural alterations of rat erythrocytes induced by phosphacol poisoning

Nembutal-anesthetized rats under conditions of artificial respiration received intramuscular injections of phosphacol in doses equal to 0.5, 5, and 50 LD₅₀. The lung ventilation per se induced blood changes typical of hyperventilation alkalosis. Poisoned animals showed the development of dose-dependent tissue acidosis. At a later stage of poisoning (2 hours) a high phosphacol dose induced decompensated acidosis, which caused the death of some animals. Electron microscopy revealed that the previously described rat erythrocyte deformation coincides in time with the changes of cytoskeleton content and depends on the dose of phosphacol but not on the blood pH. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 119, N ^o 5, pp. 517–520, May, 1995 Presented by S. N. Golikov, Member of the Russian Academy of Medical Sciences     

Role of cholinergic regulation of the heart in the protective antiarrhythmic effect of adaptation to continuous moderate stress

Rats were adapted to the continuous action of moderate immobilization stress for 1, 5, and 15 days. Thereafter the threshold of ventricular fibrillation and the heart rate were compared with biochemical indexes of adrenergic and cholinergic regulation of the heart, namely, catecholamine, cAMP, and cGMP content, acetylcholinesterase and choline acetyltransferase activity, the number and affinity of cardiac muscarinic receptors, and the catecholamine content in the adrenals. The threshold of ventricular fibrillation fell on the 1st day due to a predominance of the adrenergic regulatory effect over the cholinergic. Adaptation for 5 days is attended by a rise of the threshold of ventricular fibrillation to the norm and by marked bradycardia, both these shifts being abolished by atropine. Elevation of the heart's resistance to arrhythmias stems from the prevalence of cholinergic regulation. Equilibrium between the cholinergic and adrenergic effects on the heart was found as a results of 15-day adaptation. The normal threshold of ventricular fibrillation and the increased cardiac resistance to arrhythmia were preserved and dictated largely by adaptive changes at the cardiomycyte level. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120. N ^o 7, pp. 36–39, July, 1995 Presented by G. N. Kryzhanovskii, Member of the Russian Academy of Medical Sciences     

Effect of befol on the electric threshold of ventricular fibrillation

Befol (20 mg/kg) rises electric threshold of ventricular fibrillation in cats. This effect is most pronounced in ischemized myocardium. It is shown that not only tricyclic but also monocyclic antidepressants exhibit antifibrillatory activity. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 123, No. 3, pp. 305–307, March, 1997     

Effect of sarcolemmal anion transport system blockers on the development of ischemia-induced myocardial edema and recovery of contractile function during reperfusion

Subtotal 30-min ischemia leads to myoglobin release and increases water content in the heart. Reperfusion partially restores the developed pressure. Addition of furosemide (a Na⁺, K⁺, 2Cl⁻-sumport blocker) or NMA (inhibitor of Na⁺/H⁺-exchange) to perfusate decreases myocardial water content, reduces myoglobin loss, and completely restores myocardial contractile function. The low-rate perfusion of isolated heart and its reperfusion with solutions containing DIOA (inhibitor of K⁺, Cl⁻-co-transport) or IAA-94 (Cl⁻ channel blocker) increases water accumulation and myoglobin release from the myocardium, and deteriorated its contractile function during reperfusion. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 127, No. 4, pp. 400–403, April, 1999     

Melatonin and ulceration in rat stomach in acute emotional stress

Formation of peptic ulcers under conditions of acute emotional stress was studied in rats injected with different doses of melatonin (0.5, 1, and 2 mg/kg). The number of total length of peptic ulcers increases under conditions of stress. In unstressed rats melatonin induces ulceration of gastric mucosa. In a dose of 1 mg/kg melatonin exerts protective effect on gastric mucosa. No significant changes in the number and total length of peptic ulcers are noted with 0.5 and 2 mg/kg melatonin. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 125, No. 1, pp. 12–14, January, 1998     

Enhancement of the anti-ischemic kidney resistance by adaptive hypoxic preconditioning and drug therapy

Hypoxic preconditioning and pretreatment with pentoxifylline, α-tocopherol, or their combination promotes stabilization of Po₂ in rabbit kidney cortex in the early reperfusion period (in experiments with α-tocopherol at a significantly lower level), while after 30-min reperfusion, the protective effect of α-tocopherol (especially in combination with pentoxifylline) markedly surpasses that of pentoxifylline and hypoxic preconditioning. α-Tocopherol sharply inhibits LPO in the reperfusion period, while pentoxifylline exhibits only weak antioxidant activity and hypoxic preconditioning was ineffective. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 127, No. 3, pp. 278–281, March, 1999     

Inhalation challenge testing of latex-sensitive health care workers and the effectiveness of laminar flow HEPA–filtered helmets in reducing rhinoconjunctival and asthmatic reactions

Background: There are few data relating latex aeroallergen concentrations to biologic responses in latex-sensitized persons. Objectives: We sought to investigate acceptable latex aeroallergen concentrations below which latex-sensitive health care workers do not experience symptoms and to study the effect of high-efficiency particle arrest (HEPA)–filtered laminar flow helmets in preventing latex-induced symptoms. Methods: Under challenge chamber conditions, latex-sensitive health care workers underwent 7 sequential inhalation challenge tests by donning and discarding either vinyl gloves (challenge 1), low latex–allergen powder-free gloves (challenge 2), or high latex–allergen powdered gloves (challenges 3 to 7) for up to 1 hour. Volunteers wore a laminar flow helmet during all challenges; HEPA filters in the helmet were in place only during challenges 3 and 4. Flow-volume loops, symptom scores, and latex aeroallergen concentrations were measured before and during each test. Results: At 60 minutes, latex aeroallergen concentrations during challenges 3 to 7 (mean, 7600 ng/m³ ; range, 93 to 54,000 ng/m³ ) were significantly higher than during challenges 1 or 2 (mean, 65 ng/m³ ; range, nondetectable to 100 ng/m³ ) (P < .001). During challenges 5 and 6, mean maximum percent falls in FEV₁ (–16% and –11%, respectively) were significantly greater compared with those measured during challenges 3 and 4 (–3% and –1%, respectively) (P = .03). Mean maximum change from baseline symptom scores during challenges 5 and 6 was significantly higher than that during challenges 3 and 4 (P = .006). During challenges with high latex–allergen gloves, 4 volunteers had reproducible FEV₁ falls of 20% or greater at cumulative inhaled latex aeroallergen doses ranging from less than 100 ng to 1500 ng. Conclusion: The laminar flow helmets were effective in reducing latex-induced symptoms. Only 1 volunteer exhibited a fall in FEV₁ of 20% or greater after a cumulative inhaled latex aeroallergen dose of less than 100 ng, and no volunteer showed a decline in FEV₁ after exposure to powder-free low allergen gloves. (J Allergy Clin Immunol 1998;102:998-1004.)