Cardiovascular manifestations of acute nitrite intoxication in laboratory rats

The systemic and peripheral hemodynamics was studied in male white rats under conditions of acute nitrite hypoxia (subcutaneous administration of sodium nitrite at doses of 1, 3, and 5 mg/100 g body mass). By the electrocardiographic, rheographic, and other methods there were recorded the heart rate (HR), minute circulation volume (MCV), cardiac output (CO), skeletal muscle circulation (SMC), brain circulation (BC), and systemic arterial pressure (AP). Nitrite was shown to produce a fast, dose-dependent AP fall accompanied by a decrease of MCV due to development of bradycardia and a fall of CO. At the phase of the steady hypotension, MCV increased due to a significant rise of CO on the background of the continuing bradycardia. The systemic circulatory effects of NaNO₂ were found to be accompanied by a redistribution of peripheral circulation in the form of a dose-dependent increase of BC and a sharp fall of MCV. It was shown that 1–1.5 h after the nitrite injection the parameters of systemic and peripheral hemodynamics approached the initial levels. Possible triggering mechanisms of the initial stage of the rat cardiovascular adaptation to conditions of acute nitrite hypoxia are discussed.     

Peculiarities of myocardial electrogenesis in laboratory rats under conditions of acute nitrite intoxication

In anesthetized male rats the arterial blood pressure in femoral artery and electrocardiogram in standard leads were recorded uninterruptedly for 1–1.5 h under conditions of acute nitrite intoxication produced by a subcutaneous injection of water solution of sodium nitrite (donor of nitric oxide) at concentrations of 10, 30, and 50 mg/kg body mass. Results of the study have shown dose-dependent changes of arterial pressure as well as of time and amplitude characteristics of electrocardiogram under effect of NaNO₂. At the threshold hypoxic dose, an increase of amplitude of R and S waves was observed by the 30–45th min, while at the maximal NaNO₂ dose, amplitude of all waves rose by the 15th min of intoxication. High nitrite doses often caused an elevation of the ST segment above the isoelectric line and a rise of the amplitude of the T wave, on which a notch appeared in some cases. The change of the ECG time parameters was expressed in the dose-dependent development of bradycardia for the first 4–7 min; its level correlated with the progressively decreasing arterial pressure in the beginning (the 2–4th min) of nitrite intoxication. Variation analysis of the heart rate spectral characteristics by Baevskii’s method has revealed a rise of the total spectral power of pulse oscillations. Under effect of nitrite, in the specter of cardiointervals, the slower oscillations have been revealed with frequency of 0.15–0.2 Hz in the LF diapason with subsequent recovery of the normal ECG specter at the end of the experimental period. The maximal nitrite dose produced more pronounced shifts of the heart rate specter towards the LF and VLF diapasons that were not restored for 1 h of experiment. Transitory processes of readjustment of the cardiac rhythm had discrete character. The nitrite dose of 100 mg/kg body mass increased the RR-interval after 4–7 min with amplitude steps of 3–5 imp/s and the time constant of 20–40 s. The revealed ECG changes had the reflex (enhancement of parasympathetic tonus) and metabolic (the hypoxic and histotoxic damage of myocardium) nature.     

Protective effect of activators of biological oxidation in nitrite intoxication in rats]

The purpose of the study was to asses the effect of mexidol, cudesan, hypoxen and essenciale on the functions of the immune system, liver and muscular tissue in nitrite intoxication. The investigation was carried out on Wistar rats exposed to sodium nitrite. Administration of mexidol, cudesan or hypoxen to the animals did not affect the indices characterizing the functional activity of immunocytes, hepatocytes and myocytes. Mexidol in combination with cudesan reduced the intensity of the decrease of the functional metabolic activity of leukocytes and the development of the humoral immune response. Mexidol in combination with hypoxen increased the physical working cepacity of the animals. Both the combinations increased the rate of the drug biotransformation in the liver. The use of essenciale in combination with mexidol resulted in normalization of the metabolic functions of the liver. Essenciale in combination with cudesan normalized the majority of the immunity functions. The combination of essenciale with hypoxen recovered the lowered physical working capacity in the animals.     

Treatment of acute cobalt intoxication in rats with L-methionine

The antidotal action of L-methionine in acute cobalt (II) chloride intoxication given orally or intraperitoneally to rats has been investigated in this paper. The doses of CoCl2 (2.73 mmole/kg oral, 0.21 mmole/kg i.p.) are always above their LD50 for both means of administration, reaching during oral administration values above its LD95 (4.20 mmole/kg). The doses of L-methionine varied from 0.63 mmole/kg (i.p.) to 8.19 mmole/kg (orally). L-methionine did not show a significant antidotal action (mortality rates) against the other sulphurous aminoacid: L-cysteine, which is considered an effective antidote. The administration of Co2+-methionine chelates prepared in vitro, showed rates of 10% mortality when given orally and 30% when given intraperitoneally, against Co2+-cysteine and co2+-N-acetylcysteine chelates with rates of 0% mortality. No significant functional changes were observed in the survivors killed seven days after administration in groups receiving L-methionine. Although L-methionine cannot be considered an effective antidote, it is likely to reduce partially the toxic effects of cobalt.     

Severe acute respiratory syndrome: clinical and laboratory manifestations

Severe acute respiratory syndrome (SARS) is a recently emerged infectious disease with significant morbidity and mortality. An epidemic in 2003 affected 8,098 patients in 29 countries with 774 deaths. The aetiological agent is a new coronavirus spread by droplet transmission. Clinical and general laboratory manifestations included fever, chills, rigor, myalgia, malaise, diarrhoea, cough, dyspnoea, pneumonia, lymphopenia, neutrophilia, thrombocytopenia, and elevated serum lactate dehydrogenase (LD), alanine aminotransferase (ALT) and creatine kinase (CK) activities. Treatment has been empirical; initial potent antibiotic cover, followed by simultaneous ribavirin and corticosteroids, with or without pulse high-dose methylprednisolone, have been used. The postulated disease progression comprises (1) active viral infection, (2) hyperactive immune response, and (3) recovery or pulmonary destruction and death. We investigated serum LD isoenzymes and blood lymphocyte subsets of SARS patients, and found LD1 activity as the best biochemical prognostic indicator for death, while CD3+, CD4+, CD8+ and natural killer cell counts were promising predictors for intensive care unit (ICU) admission. Plasma cytokine and chemokine profiles showed markedly elevated Th1 cytokine interferon (IFN)-gamma, inflammatory cytokines interleukin (IL)-1beta, IL-6 and IL-12, neutrophil chemokine IL-8, monocyte chemoattractant protein-1 (MCP-1), and Th1 chemokine IFN-gamma-inducible protein-10 (IP-10) for at least two weeks after disease onset, but there was no significant elevation of inflammatory cytokine tumor necrosis factor (TNF)-alpha and anti-inflammatory cytokine IL-10. Corticosteroid reduced IL-8, MCP-1 and IP-10 concentrations from 5-8 days after treatment. Measurement of biochemical markers of bone metabolism demonstrated significant but transient increase in bone resorption from Day 28-44 after onset of fever, when pulse steroid was most frequently given. With tapering down of steroid therapy, there was a decrease in bone resorption marker together with an increase in bone formation markers round Day 50, suggesting that some of the bone loss might be reversed. Our research studies on the chemical pathology and clinical immunology of SARS should have implications for the pathophysiology and therapy of this potentially lethal infection.     

Lesions of skeletal muscles in rats with acute alcoholic intoxication

Histological and histochemical studies of the rat skeletal muscles in acute alcohol intoxication have revealed metabolic disturbances, characterized by a decreased glycogen level, small-drop fatty infiltration, decreased activity of aerobic and enhanced activity of anaerobic enzyme glycolysis, dystrophic and focal necrotic myocyte changes. Acute alcohol intoxication in fasting animals is accompanied by more pronounced dystrophic and necrotic myocyte changes, decreased glycogen and lipid content.     

Comparative-physiological study of leukocyte participation in initiation of lipid peroxidation during nitrite intoxication in rats and muskrats

The study is carried out on Wistar white rats non-adapted to oxygen deficit and on semiaquatic rodents muskrats adapted to periodic arrest of respiration during diving under conditions of Nembutal narcosis. It has been revealed that 1 h after a subcutaneous injection of sodium nitrite (3 mg/100 g body mass), intensification of lipid peroxidation (LPO) in the muskrat brain is absent, the activity of the antioxidant enzyme catalase increasing 16 times (p < 0.01) as compared with control injected with equivalent saline volume. In heart and liver, there was a statistically significant decrease of the content of LPO products active in the test with 2-thiobarbituric acid; in the femoral muscle tissue, the LPO intensity did not change. In rats, unlike muskrats, after injection of sodium nitrite, an increase of LPO is recorded in brain, while a decrease of the LPO product content in the femoral muscle; in liver the LPO intensity did not change. In muskrats, the sodium nitrite administration led to a decrease of the leukocyte spontaneous mobility, of lymphocyte cytokine-producing activity, and of neutrophil bactericidal activity (by the content of cationic proteins in neutrophilic phagocytes), whereas in rats the leukocyte mobility did not change, only the blood neutrophil bactericidal activity decreased. The ability of neutrophils to produce the superoxide anion during the nitrite intoxication did not change both in rats and in muskrats. The obtained data allow concluding that under conditions of Nembutal narcosis the leukocyte functional activity on the background of nitrite intoxication is suppressed to the greater degree in the muskrats genotypically adapted to oxygen deficit than in immunocompetent cells of the rodents not adapted to hypoxia.     

Cardiovascular manifestations of ankylosing spondylitis

The incidence of cardiovascular lesions in 97 patients with ankylosing spondylitis (AS) was found to be 14%; 8 patients had isolated aortic insufficiency (AI), 3 had isolated heart block, 2 had combined AI and heart block, and 1 had mitral insufficiency. In comparison with control groups of 81 patients with rheumatoid arthritis and 99 random hospital patients there was no increased incidence of isolated heart block in patients with AS. Clinical and postmortem findings indicated that the cardiovascular lesions of some patients with AS may antedate articular disease and may regress spontaneously. In addition, the unusual occurrence of AI in two patients with psoriatic spondylitis and in one with AS and regional enteritis is documented.     

Granulocyte and plasma cytokine activity in acute cadmium intoxication in rats.

Changes in the number and ex vivo function of peripheral blood neutrophils were investigated following intraperitoneal administration of cadmium-chloride in rats. Besides a dose-dependent increase in the number of peripheral blood neutrophils, changes were found in the functional state of isolated polymorphonuclear leukocytes (PMNs). Increased spontaneous adhesion and activation, and TNF activity in a conditioned medium were observed in cultures of granulocytes in comparison to granulocytes from control (saline-treated) animals. Increased levels of plasma activity of inflammatory cytokines, tumor necrosis factor (TNF) and interleukin-6 (IL-6) were noted following cadmium administration. Cytological signs of pulmonary inflammation were revealed histologically and the majority of neutrophils recovered from the lungs by enzyme digestion exhibited a capacity of nitroblue tetrazolium (NBT) reduction. Our data demonstrate that acute cadmium intoxication leads to a systemic inflammatory response characterized by numerical and functional changes in the granulocyte compartment and to increased levels of inflammation-related cytokine activity in the circulation. Correlations between the increased number of peripheral blood neutrophils and IL-6 plasma activity (r=0.776, p<0.00001) and the number of neutrophils recovered from the lung tissue (r=0.893, p<0.00001) suggested that systemic cadmium-induced inflammation might be involved in the pulmonary toxicity of cadmium.     

Regulation of peripheral and systemic blood circulation in rats in conditions of acute nitrite hypoxia

Regulation of the systemic and peripheral hemodynamics in the conditions of acute nitrite hypoxia (doses of NaNO₂ 10, 30, and 50 mg/kg of the body mass) were studied on white male rats. It was shown that NaNO₂ causes a quick dose-dependent decrease in the blood pressure with an intensification of the parasympathetic tonus and development of bradycardia. The hemodynamics was restored as the oxygen capacity of the blood decreased with an increase in the sympathetic tonus and development of tachycardia. The role of intracardial metasympathetic structures and the renin-angiotensin system in cardiovascular adaptation to hypoxia was established. Adaptation to nitrite hypoxia is accomplished by a coordinated interaction of neurogenic and humoral factors. A combination of pharmacological agents, which include separate links of regulator systems of the organism, leads to failure of the adaptation process.     

Effects of the addition of carbon dioxide on manifestations of acute hypoxia in rats

In pentobarbitalized rats, hypoxia induced by inhalation of O2 8%-N2 92%, produces a transient hyperventilation which is followed by a respiratory depression and an apnea. A cardiovascular collapse is then observed. Correction of the hypocapnia depending on the initial hyperventilation, by inhalation of a gas mixture containing 4% CO2 maintains the hyperventilation and suppresses the cardiovascular collapse. Carbon dioxide activity is both a direct one by stimulation of respiratory centers and an indirect one by increasing the sensitivity of the peripheral arterial chemoreceptors to hypoxia. Four percent carbon dioxide just compensating hypocapnia are sufficient to prevent apnea and vascular collapse. The increase of this concentration up to hypercapnia complicates the interpretation of the results by addition of hypoxic and hypercapnic effects.     

Psychopathological and hormonal manifestations of alcoholic intoxication and emotional stress in monkeys

Ethological approach to studying mature P. hamadryas and M. mulatta males has revealed a wide spectrum of changes in individual and zoosocial behaviour in response to the administration of different alcohol doses and stress stimuli. It has been established that neuroendocrine basis for the depression of psychic and locomotor activities developing in conditions of alcohol intoxication and emotional stress is an extremely high release of catecholamines and the increase of glucocorticoid secretion accompanied by a sharp decrease in androgen products. It should be noted that the exposure to stress stimuli during consumption of small alcohol doses intensifies depression-like stress-induced behaviour of monkeys.     

Lysosomal damage under nitrite intoxication in rainbow trout (Salmo gairdneri Rich.)

1. In Salmo gairdneri specimens exposed to 450 micrograms/l NO2-N (nearly 36 hr LC50) for various exposure times (12-72 hr) some parameters of liver lysosomal function were examined. 2. In vivo both total proteolytic activity and single protease activities were inhibited, the inhibition increasing with the lengthening of exposure time. In vitro no analogous effect was observed. 3. Lysosomal membranes showed an increased fragility correlated with the physiological conditions of treated animals. 4. Data were considered as the results of a nitrite mediated effect on functional and structural proteins.     

Characteristics of creatine kinase isoenzyme spectrum in the blood of rats in aging and acute alcoholic intoxication

The study of creatine kinase (CK) activity in biological liquids of rats of different age has shown that CK blood activity is decreased in aged rats. Acute alcohol intoxication leads to significant increase of CK blood activity.     

Lung function in acute paraquat intoxication.

Functional and morphological examination of the lungs was performed in rats 48 hours after intratracheal injection of 0.5 mg/kg of the herbicide paraquat. Pronounced tachypnoea was observed (235+/-20 c/min), which also persisted under urethane anaesthesia (210+/-18 c/min). In control rats the mean breathing rate was 115+/-11 and 90+/-9 c/min in wake and anaesthetized rats respectively. The rate of breathing decreased to comparable values in experimental and control rats after bilateral cervical vagotomy. The functional residual lung capacity was significantly increased in experimental rats. After vagotomy also this increase of functional residual capacity became normalized. Histologically the disease was characterized by focal formation of hyaline membranes and oedema with occasional haemorrhages and signs of inflammation. The significant role fo vagal function in lung pathology is demonstrated.