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Unlabelled: Myocardial infarction causes remodeling of the tissue structure and the density and kinetics of several ion channels in the cell membrane. Heterogeneities in refractory period (ERP) have been shown to occur in the infarct border zone and have been proposed to lead to initiation of arrhythmias. The purpose of this study is to quantify the window of vulnerability (WV) to block and initiation of reentrant impulses in myocardium with ERP heterogeneities using computer simulations. We found that ERP transitions at the border between normal ventricular cells (NZ) with different ERPs are smooth, whereas ERP transitions between NZ and infarct border zone cells (IZ) are abrupt. The profile of the ERP transitions is a combination of electrotonic interaction between NZ and IZ cells and the characteristic post-repolarization refractoriness (PRR) of IZ cells. ERP heterogeneities between NZ and IZ cells are more vulnerable to block and initiation of reentrant impulses than ERP heterogeneities between NZ cells. The relationship between coupling intervals of premature impulses (V1V2) and coupling intervals between premature and first reentrant impulses (V2T1) at NZ/NZ and NZ/IZ borders is inverse (i.e. the longer the coupling intervals of premature impulses the shorter the coupling interval between the premature and first reentrant impulses); this is in contrast with the reported V1V2/V2T1 relationship measured during initiation of reentrant impulses in canine infarcted hearts which is direct., In Conclusion: (1) ERP transitions at the NZ-IZ border are abrupt as a consequence of PRR; (2) PRR increases the vulnerability to block and initiation of reentrant impulses in heterogeneous myocardium; (3) V1V2/V2T1 relationships measured at ERP heterogeneities in the computer model and in experimental canine infarcts are not consistent. Therefore, it is likely that other mechanisms like micro and/or macro structural heterogeneities also contribute to initiation of reentrant impulses in infarcted hearts., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Aims: Nitric oxide (NO) is synthesized from L-arginine (L-Arg) by three different isoforms of NO synthase (NOS), i.e. the constitutive neuronal and endothelial NOS (nNOS and eNOS) and the inducible NOS (iNOS). NO has been involved in the pathophysiology of epilepsy, but available data are conflicting and the actual role of NO in epilepsy still remains to be clarified. In this study we investigated the basal and post-seizure levels of constitutive NOS (cNOS) activity as well as the expression of the cNOS isoforms across brain regions in a novel model of epilepsy., Main Methods: cNOS activity was assessed in various brain areas along the rostro-caudal axis in control wild type hamsters, unstimulated generalized audiogenic seizure prone hamsters, Salamanca strain, GASH:Sal and GASH:Sal after 10 sound-induced epileptic seizures. Additionally, Western blot experiments for nNOS and eNOS were performed in those areas where relevant changes in cNOS activity were found., Key Findings: In the GASH:Sal, cNOS activity increased in the mesencephalic areas studied while cNOS activity decreased in both the striatum and cerebral cortex after 10 sound-induced epileptic seizures. nNOS (but not eNOS) expression paralleled the variations in cNOS activity. The same sound stimulation had no effect on control hamsters., Significance: These results suggest a different NOS response in the regions close to the original epileptic focus (caudal, in our auditory model) versus the remote areas (rostral) possibly recruited at later stages or after repeated crises. These findings may account for some of the discrepancies found regarding the role of NO in epilepsy., (Copyright © 2012 Elsevier Inc. All rights reserved.)

These studies investigated whether endogenous activation of CCK(A) receptors mediates the expression of amphetamine (AMP)-induced locomotor activity. In Experiment 1, locomotor activity was assessed in rats pretreated with the CCK(A) antagonist devazepide (0.001, 0.01, and 0.1 mg/kg) and subsequently injected with AMP (1.5 mg/kg). In Experiment 2, rats were administered AMP (1.5 mg/kg) once daily for 7 days. Following a 10-day withdrawal, locomotor activity was assessed following treatment with devazepide (0.001, 0.01, and 0.1 mg/kg) and AMP (0.75 mg/kg). In both studies, rats were classified as low (LR) or high (HR) responders based upon a median split of their locomotor response to a novel environment. Results from Experiment 1 showed that AMP potentiated the expression of locomotor activity, and this effect was most pronounced in HR rats. However, devazepide did not affect AMP-induced locomotion. Results from Experiment 2 demonstrated that chronic AMP pretreatment augmented the locomotor response to subsequent AMP challenge, and this effect was most pronounced in the HR group. Further, this augmented response was blocked by devazepide in HR rats. These findings constitute the first demonstration that endogenous CCK(A) receptor activation is an important substrate mediating AMP-induced locomotor activity in animals with a previous history of AMP treatment.

We have previously shown that individual differences in oral sucrose consumption are predictive of behavioral reactivity of rats in the elevated plus-maze (EPM). The present experiments were designed to replicate the EPM results and to extend them to another animal model of anxiety, the acoustic startle reflex (ASR) paradigm. In two experiments, sucrose consumption was assessed in separate groups of rats across eight daily 1-h feeding sessions. Animals were designated as either low (LSF) or high sucrose feeders (HSF) based on a median split of their sucrose intake on the final test day. Following this assay, animals were tested in the EPM in Experiment 1, and in the ASR paradigm in Experiment 2. Results from Experiment 1 replicated our previous findings and showed that the percentage of time spent on, and entries into, open arms was significantly lower in LSF than HSF. Further, results from Experiment 2 revealed a significantly augmented startle response to acoustic stimuli (94-108 dB SPL) in LSF compared to HSF. These data provide converging evidence to support the notion that individual differences in baseline levels of oral sucrose consumption are predictive of anxious behaviors in rats.

Cardiac arrhythmias are caused by alterations in the electrophysiologic properties of the cardiac cells, which affect the characteristics of the transmembrane potentials. The electrophysiologic properties that cause arrhythmias are automaticity, triggered activity, and reentrant excitation. Each of these mechanisms is described in terms of the characteristics of the transmembrane potentials and how these influence the appearance of the arrhythmia on the electrocardiogram.

The possible influence of weaning on the development of different neural mechanisms involved in stress-induced antinociception (SIA) was studied. Male Wistar albino rats were used for studies on adult and pre- and postweanling rats of 20 and 25 days of age, respectively. Animals were stressed by warm-water (20C) swimming for 3-min periods. Antinociception was assessed by the tail electric stimulation test. The thresholds for the motor response (tail withdrawal) (TW), vocalization during stimulus (V), and vocalization after discharge (VAD) were recorded. These responses are considered to be integrated at spinal, medulla oblongata, and diencephalon-rhinencephalon levels, respectively. In 20-day-old neonates, swimming stress only induced significant increases in the VAD thresholds that were not significantly reversed by naloxone (NAL) (1 mg/kg). Twenty-five-day-old rats showed increased threshold for the three nociceptive responses after stress, the effects on TW and V being antagonized by NAL. Adult rats subjected to stress showed increased threshold for the three responses, an effect that was antagonized by NAL in all cases. These results suggest that the weaning period might be critical for the development of the mechanisms mediating SIA. Besides, a different involvement of opioid systems throughout development, particularly in relation to the affective/emotional component of pain, is also suggested.