Visual Evoked Potentials Change as Heart Rate and Carotid Pressure Change

The relationship between cardiovascular activity and the brain was explored by recording visual evoked potentials from the occipital regions of the scalp during systolic and diastolic pressure (Experiment I) and during fast and slow heartbeats at systolic and diastolic pressure (Experiment II). Visual evoked potentials changed significantly as heart rate and carotid pressure fluctuated normally, and these changes were markedly different in the right and left cerebral hemispheres. Evoked potentials recorded from the right hemisphere during various cardiac events differed significantly, whereas those recorded from the left did not. In both experiments, differences in the right hemisphere were due primarily to the P1 component, which was larger at diastolic than at systolic pressure. The present findings are consistent with formulations from behavioral studies suggesting that baroreceptor activity can influence sensory intake, and suggest that hemispheric specialization may play an important role in the relationship between cardiac events, the brain and behavior.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73146/1/j.1469-8986.1982.tb02579.x.pd

Therapeutic efficacy of TBC3711 in monocrotaline-induced pulmonary hypertension

Background: Endothelin-1 signalling plays an important role in pathogenesis of pulmonary hypertension. Although different endothelin-A receptor antagonists are developed, a novel therapeutic option to cure the disease is still needed. This study aims to investigate the therapeutic efficacy of the selective endothelin-A receptor antagonist TBC3711 in monocrotaline-induced pulmonary hypertension in rats. Methods: Monocrotaline-injected male Sprague-Dawley rats were randomized and treated orally from day 21 to 35 either with TBC3711 (Dose: 30 mg/kg body weight/day) or placebo. Echocardiographic measurements of different hemodynamic and right-heart hypertrophy parameters were performed. After day 35, rats were sacrificed for invasive hemodynamic and right-heart hypertrophy measurements. Additionally, histologic assessment of pulmonary vascular and right-heart remodelling was performed. Results: The novel endothelin-A receptor antagonist TBC3711 significantly attenuated monocrotaline-induced pulmonary hypertension, as evident from improved hemodynamics and right-heart hypertrophy in comparison with placebo group. In addition, muscularization and medial wall thickness of distal pulmonary vessels were ameliorated. The histologic evaluation of the right ventricle showed a significant reduction in fibrosis and cardiomyocyte size, suggesting an improvement in right-heart remodelling. Conclusion: The results of this study suggest that the selective endothelin-A receptor antagonist TBC3711 demonstrates therapeutic benefit in rats with established pulmonary hypertension, thus representing a useful therapeutic approach for treatment of pulmonary hypertension

Effects of aging on the cardiac remodeling induced by chronic high-altitude hypoxia in rat

Effects of chronic high-altitude hypoxia on the remodeling of right ventricle were examined in three age groups of rats: 2, 6, and 18 mo. The extent of right ventricular (RV) hypertrophy (RVH) showed an age-associated diminution. RV cell size and pericellular fibrosis showed a significant increase in the 2- and 6-mo-old exposed rats but not in the 18-mo-old exposed rats compared with control. A hyperplasic response was underscored in the three exposed age groups but appeared less pronounced in the 18-mo-old rats. A significant decrease in the transient outward potassium current (Ito) density was observed in RV cell only in the 2-mo-old exposed group compared with the control group. In the control group, there was a clear tendency for Ito density to decrease as a function of age. The sustained outward current density was modified neither by the hypoxia condition nor by the age. Neither the cytochrome c oxidase activity nor the heat shock protein 72 content in the RV was altered after hypoxic exposure regardless of age. The norepinephrine content in the RV was significantly decreased in each age group exposed to hypoxia when compared with their age-matched control group. Our findings indicate that the remodeling (at morphological and electrophysiological levels) induced by chronic hypoxia in the RV can be decreased by the natural aging process

Electrophysiological characterization of left ventricular myocytes from obese Sprague-Dawley rat

OBJECTIVE: Obesity is a complex multifactorial disease that is often associated with cardiac arrhythmias. Various animal models have been used extensively to study the effects of obesity on physiological functions, but, to our knowledge, no study related to ionic membrane currents has been performed on isolated cardiac myocytes. Therefore, we examined the electrophysiological characteristics of four ionic currents from isolated left ventricular myocytes of a high-energy (HE)-induced obesity rat model. RESEARCH METHODS AND PROCEDURES: Male Sprague-Dawley rats were fed with either a control diet or a diet containing 33% kcal as fat (HE) for 14 weeks starting at 6 weeks of age. Voltage-clamp experiments were performed on ventricular myocytes. Leptin receptor (ObR) expression was measured using ObR enzyme-linked immunosorbent assay. RESULTS: In the HE group, rats designated as obese did not develop a cardiac hypertrophy, either at the organ level or at the cellular level. Densities and kinetics of the L-type calcium current, the transient outward potassium current, the delayed rectifier potassium current, and the sodium-calcium exchange current (I(NCX)) were not significantly different between control and obese rats. A down-regulation of ObR expression was evidenced in the heart of obese rats compared with controls. Acute exposure (5 minutes) of leptin (100 nM) did not induce a significant modification in the current densities either in control or in obese rats, except for I(NCX) density measured in control rats. DISCUSSION: The absence of effect of leptin on I(NCX) in obese rats could be a potential arrhythmogenic substrate in obesity

In vitro and in vivo reversal of cancer cell multidrug resistance by the semi-synthetic antibiotic tiamulin.

International audienceA large number of multidrug resistance (MDR) modulators, termed chemosensitizers, have been identified from a variety of chemicals, but most have been proven to be clinically toxic. Low concentrations of the pleuromutilin-derived semi-synthetic antibiotic tiamulin (0.1 to 10 microM) sensitized the three highly resistant P-glycoprotein (Pgp)-overexpressing tumor cell lines P388 (murine lymphoid leukemia), AS30-D (rat hepatoma), CEM (human lymphoblastic leukemia), and the barely resistant AS30-D/S cell lines to several MDR-related anticancer drugs. Flow cytometric analysis showed that tiamulin significantly increased the intracellular accumulation of daunomycin. When compared to reference modulating agents such as verapamil and cyclosporin A, tiamulin proved to be 1.1 to 8.3 times more efficient in sensitizing the resistant cell lines. Moreover, when given i.p. (1.6 microg/mg body weight), tiamulin increased the survival rate of adriamycin-treated mice bearing the P388/ADR25 tumor line by 29%. In the presence of an anticancer drug, tiamulin inhibited both ATPase and drug transport activities of Pgp in plasma membranes from tumor cells. Tiamulin is thus a potent chemosensitizer that antagonizes the Pgp-mediated chemoresistance in many tumor cell lines expressing the MDR phenotype at different levels and displays no toxic effects on contractile tissues at active doses, therefore providing the promise for potential clinical applications.A large number of multidrug resistance (MDR) modulators, termed chemosensitizers, have been identified from a variety of chemicals, but most have been proven to be clinically toxic. Low concentrations of the pleuromutilin-derived semi-synthetic antibiotic tiamulin (0.1 to 10 microM) sensitized the three highly resistant P-glycoprotein (Pgp)-overexpressing tumor cell lines P388 (murine lymphoid leukemia), AS30-D (rat hepatoma), CEM (human lymphoblastic leukemia), and the barely resistant AS30-D/S cell lines to several MDR-related anticancer drugs. Flow cytometric analysis showed that tiamulin significantly increased the intracellular accumulation of daunomycin. When compared to reference modulating agents such as verapamil and cyclosporin A, tiamulin proved to be 1.1 to 8.3 times more efficient in sensitizing the resistant cell lines. Moreover, when given i.p. (1.6 microg/mg body weight), tiamulin increased the survival rate of adriamycin-treated mice bearing the P388/ADR25 tumor line by 29%. In the presence of an anticancer drug, tiamulin inhibited both ATPase and drug transport activities of Pgp in plasma membranes from tumor cells. Tiamulin is thus a potent chemosensitizer that antagonizes the Pgp-mediated chemoresistance in many tumor cell lines expressing the MDR phenotype at different levels and displays no toxic effects on contractile tissues at active doses, therefore providing the promise for potential clinical applications

Improved Functionality and Control in the Isomerization of a Calix[4]Arene-Capped Azobenzene

An improved azobenzene core capped by two calix[4]arene units isomerizes readily between trans and cis configurations via photochemical and/or thermal means. In addition, the presence of acid (particularly HCl) increases the rate of thermal cis→trans conversion. These enhancements to the functional response, control, and understanding of calixarene-capped azobenzene isomerization are important for future application in the dynamic encapsulation of small chemical species. © 2011 Elsevier Ltd. All rights reserved