In cholesterol-fed rabbits the extent of monocyte involvement in atherogenesis may be influenced by the level of circulating leukocytes during hypercholesterolemia. We characterized the leukocytosis in rabbits fed either a 0.25% or a 0.1% cholesterol-enriched diet (0.25% or 0.1% rabbits, respectively). Circulating leukocytes were elevated by 1 week of feeding, and the elevation was sustained for at least 30 weeks. Differential counts were unchanged. Immature leukocytes were not seen, indicating that the leukocytosis was not due to premature release of bone marrow cells. Animals were free of bacterial or parasitic disease; selected rabbits with leukocytosis had normal body temperatures. Spleen weights averaged at least 100% higher in 0.25% rabbits but did not show histological evidence for hematopoiesis that could account for the leukocytosis. At approximately 22 weeks there was a second rise in leukocytosis in bilirubinemic 0.25% rabbits, suggesting that in the late stages of hypercholesterolemia, leukocytosis is related to liver failure. Cholesterol-fed rabbits also showed thrombocytosis. Existing leukocytosis and hypercholesterolemia were reversed to pretreatment levels by switching the rabbits to chow diets. In bone marrow from 0.25% rabbits, the mean number of cells per gram was greater (p<0.05) than that from normocholesterolemic rabbits. In 0.25% rabbits, the fraction of blood mononuclear cells showing phagocytosis of immunoglobulin G-coated red blood cells did not differ from that of controls, suggesting an unchanged population of these cells with regard to Fc and phagocytic function during hypercholesterolemia. These data suggest an effect (direct or indirect) of hypercholesterolemia on the production of leukocytes in the bone marrow and/or on the circulation kinetics of leukocytes in the blood. (Arteriosclerosis and Thrombosis 1991;ll:985-994)

Hypokalemia prolongs the QRS and QT intervals, deteriorates intercellular coupling, and increases the risk for arrhythmia. Melatonin preserves gap junctions and shortens action potential as potential antiarrhythmic mechanisms, but its properties under hypokalemia remain unknown. We hypothesized that melatonin protects against low potassium-induced arrhythmias through the activation of its receptors, resulting in action potential shortening and connexin-43 preservation. After stabilization in Krebs-Henseleit solution (4.5 mEq/L K + ), isolated hearts from Wistar rats underwent perfusion with low-potassium (1 mEq/L) solution and melatonin (100 μmol/L), a melatonin receptor blocker (luzindole, 5 μmol/L), melatonin + luzindole or vehicle. The primary endpoint of the study was the prevention of ventricular fibrillation.Electrocardiography was used, and epicardial action potentials and heart function were measured and analyzed. The ventricular expression, dephosphorylation, and distribution of connexin-43 were examined. Melatonin reduced the incidence of low potassium-induced ventricular fibrillation from 100% to 59%, delayed the occurrence of ventricular fibrillation and induced a faster recovery of sinus rhythm during potassium restitution. Melatonin prevented QRS widening, action potential activation delay, and the prolongation of action potential duration at 50% of repolarization. Other ECG and action potential parameters, the left ventricular developed pressure, and nonsustained ventricular arrhythmias did not differ among groups. Melatonin prevented connexin-43 dephosphorylation and its abnormal topology (lateralization). Luzindole abrogated the protective effects of melatonin on electrophysiological properties and connexin-43 misdistribution. Our results indicate that melatonin receptor activation protects against low potassium-induced ventricular fibrillation, shortens action potential duration, preserves ventricular electrical activation, and prevents acute changes in connexin-43 distribution. All of these properties make melatonin a remarkable antifibrillatory agent. K E Y W O R D Saction potential, arrhythmias, connexin-43, hypokalemia, melatonin, QRS

People with metabolic syndrome have higher risk of cardiovascular diseases then those without. The aim of the work was to investigate whether high fat diet administered to Prague hereditary hypertriglyceridemic (HTG) rats can induce signs of metabolic syndrome (MetS). Our results showed that HTG rats fed high fat diet (HTGch) had disturbed glucose metabolism and also lipid metabolism – increased serum triacylglycerols (TAG), total cholesterol (Ch), low-density lipoprotein-Ch (LDL-Ch), and decreased high-density lipoprotein-Ch (HDL-Ch). Their livers proved markers of developing steatosis. Moreover, HTGch had increased blood pressure, yet the vascular endothelium was not significantly damaged. All these changes were accompanied with oxidative stress and tissue damage identified as increased liver concentrations of thiobarbituric acid reactive substances (TBARS) and activity of the lysosomal enzyme N-acetyl-D-glucosaminidase (NAGA). We assume that the model used may be suitable for the study of MetS with no evidence of obesity. Prolongation of the high fat diet duration might have a major impact on all parameters tested, especially on vascular endothelial function.

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Fat-rich diet (FRD) triggers health complications like hypertension, dyslipidemia, hyperglycemia, insulin resistance and non-alcoholic fatty liver disease, known as the risk factors of metabolic syndrome (MetS), which may result in neurological deficits. The impact of MetS on neuronal functions and brain morphology are poorly understood. We induced MetS-like conditions by exposing hypertriacylglycerolemic (HTG) rats to FRD for eight weeks with the aim to study possible neurological dysfunctions. HTG-FRD rats were compared to HTG rats and Wistar rats on standard diet. The physiological status of the animals was monitored by body, liver and kidney weight (wt). Morphology of the liver, vessel wall and hippocampus were investigated. Basal neurotransmission and synaptic plasticity were measured in the hippocampus ex-vivo. A marked increase of liver weight with marks of steatosis was found in the HTG-FRD group. FRD induced an increase of aortic intima-media thickness. Extracellular recording revealed FRD-induced impairment of long-term potentiation (LTP) at Cornu Ammonis (CA)3-CA1 synapse, contrary to increased presynaptic fiber volley (pV). Reduced thickness of pyramidal cell layer at the CA1 area was found morphometrically. LTP was directly associated with kidney weight and inversely associated with liver weight, pV directly correlated with liver weight, liver wt/body wt ratio and aortic intima-media thickness. Our results suggest correlations between altered physiological status due to MetS-like conditions and neurological deficits, which may be related with consecutive development of socalled metabolic cognitive syndrome.

Handling is a form of experience which can result in physiological changes depending on the period of postnatal age when performed. There is a lot of evidence about the positive effect of neonatal handling, but a lack dealing with handling of adult rats. Behavioral changes and memory deficits are present in dementia-like disorders. In the present work, we tested whether 6 weeks lasting handling of young adult rats could revert memory impairment induced by trimethyltin (TMT) (7.5 mg/kg, intraperitoneally). Testing rats in Morris water maze revealed significant effect of TMT as well significant effect of handling. We observed improvement of spatial memory also between healthy, non-degenerated rats as well as degenerated rats, represented by shorter latency onto the platform. In our paper, we report beneficial effect of handling on spatial memory that is in compliance with published works about beneficial effect of cognitive therapy and training in patients with early stage of Alzheimer΄s disease and dementia.

OBJECTIVES: Metabolic disturbances are considered to condition the occurrence of malignant heart arrhythmias and negatively infl uence the chances of a patient to survive. To test this assumption, a model of metabolic syndrome was selected in which rats were receiving a diet resembling that of the westernized population. BACKGROUND: Metabolic syndrome is a comorbidity of major cardiovascular risk factors (dyslipidemia, hypertension, impaired glucose tolerance or insulin resistance, diabetes mellitus, and obesity), all facilitating cardiovascular complications leading to morbidity and mortality of patients. METHODS: Hearts were isolated and perfused according to Langendorff. Global ischemia was induced in the hearts and arrhythmia occurrence in reperfusion was monitored. All hearts were stimulated with the electrocardio-stimulator to test the electrical inducibility of heart arrhythmia. RESULTS: Isolated hearts from rats with the metabolic syndrome were more susceptible to ventricular arrhythmias. The high-fat diet increased the occurrence of malignant heart arrhythmias in rats with metabolic syndrome to an even greater extent. All subjects with metabolic syndrome were sensitive to ventricular tachyarrhythmia with signifi cantly decreased threshold to its induction in cardio-stimulation. CONCLUSIONS: These results indicate that metabolic syndrome patients may be more sensitive to the occurrence of malignant heart arrhythmias following myocardial infarction or other heart diseases (Tab. 1, Fig. 2

The aim of the work was to find an experimental model suitable for the study of endothelial dysfunction induced by MS. We used hypertriglyceridemic rats (HTG) that were fed a hypercholesterolemic diet of different composition and duration: a 6-week administration of standard diet with an addition of cholesterol and fat (HTGChol) and a three-month administration of the same diet with an addition of fructose (HTGCholF). We investigated the effect of different diets on aortic endothelial function. The standard diet fed Wistar (W) and HTG rats served as controls. Decision for addition of fructose to HTGChol was done based on in vitro experiments evaluating the effect of high concentration of saccharide in the incubation solution on aortic endothelial function. This intervention caused significant deterioration of relaxation induced by acetylcholine (ACh). While in HTGChol, we did not find significant differences in the function of the aorta compared to W or HTG rats, adding of fructose to high fat diet and prolonging its administration resulted in significantly impaired endothelium-dependent relaxation. It seems that such a model is suitable for the study of endothelial dysfunction in MS and the effect of substances that may protect the endothelium.