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BACKGROUND Chronic, excessive ethanol intake has been linked with various electrical instabilities, conduction disturbances, and even sudden cardiac death, but the underlying cause for the latter is insufficiently delineated. METHODS We studied surface electrocardiography (ECG) in a community-dwelling cohort with moderate-to-heavy daily alcohol intake (grouped as >90g/day, ≤90g/day, and nonintake). RESULTS Compared with nonintake, heavier alcohol users showed markedly widened QRS duration and higher prevalence of QRS fragmentation (64.3%, 50.9%, and 33.7%, respectively, χ2 12.0, both p

Diabetic cardiomyopathy is a well-recognized complication of diabetes, but its pathophysiology is unclear. We aimed to investigate the mechanisms underlying cardiac dysfunction in an elderly type 2 diabetic (T2DM) mouse model, using membrane proteomic analyses. Elderly mice were fed a high fat diet for 12 weeks to induce T2DM, and myocardial structure and function were assessed by echocardiography. Cardiomyocytes were isolated by Langendorff perfusion and subjected to iTRAQ-based quantitative membrane proteomic profiling, immunoblotting, and real-time quantitative reverse-transcriptase polymerase chain reaction. Compared to controls, elderly T2DM mice showed worse systolic function, more myocardial fibrosis and up-regulation of several heart failure markers (all p0.05). Cardiomyocyte membrane proteomic profiling revealed that 417 proteins had differential expressions related to perturbations in several biological processes in T2DM mice compared with the control. The most up-regulated proteins were involved in oxidative phosphorylation, whereas many down-regulated proteins were involved in cytoskeletal regulation. Differential protein expression correlated with myocardial systolic velocity by tissue Doppler. In addition, cardiomyocyte immunofluorescence staining showed greater disorganization of thick/parallel F-actin stress fibers and marked reduction in F-to-G-actin ratio in T2DM vs control (p0.05), which paralleled worsened myocardial systolic velocity. We concluded that cardiac contractile dysfunction in elderly T2DM mice was associated with impaired energetics and cytoskeletal disorganization.

Aims Excessive consumption of alcoholic beverages is associated with cardiac remodeling and cardiomyopathy. We examined the possible association of alcohol use, common Asian genetic variants in genes involved in alcohol metabolism, and cardiac structures/functions alterations. Methods A prospective, community-dwelling survey among individuals with available complete echocardiography examined the associations of alcohol use, cardiac structure/functions, and three common alcohol metabolizing genetic variants, including aldehyde dehydrogenase 2 (ALDH2), alcohol dehydrogenase 1B (ADH1B) and cytochrome P450 (CYP) isoform 2E1 (CYP2E1). Results Among 1577 participants (mean age: 53 ± 9, 59.7% female), we observed that in subjects with more frequent weekly ethanol intake showed greater left ventricle (LV) mass, more impaired diastolic functions, and reduced global longitudinal strain (GLS), systolic (SRs) and early diastolic strain rates (SRe) (P Conclusions Among East Asians, even moderate alcohol consumption can confer subclinical adverse effects on cardiac systolic functions, which was most pronounced in subjects carrying common variants in alcohol metabolizing genes. These findings challenge the notion of beneficial influences of less heavy ethanol consumption on the heart, especially among East Asians. Short summary This study evaluated the association of level of alcohol consumption and genetic variants in genes involved in alcohol metabolism with changes in cardiac function in East Asians. Even moderate alcohol use conferred subclinical adverse effects on cardiac systolic functions, which were most pronounced in subjects carrying common alcohol metabolizing genes.

In this study, the (Fe,Cr)7C3 particles strengthened gradient composite was produced by in situ synthesis process with subsequent heat treatment from gray cast iron (HT300) and high purity chrome plate. The microstructure, phase composition and wear resistance of the composite were studied by scanning electron microscopy (SEM), X-ray diffraction (XRD) and scratch tester. The results showed that the thickness of the gradient layer was about 758 μm after heat treatment at 900 °Cfor 4 h. And it can be divided into three areas depending on microstructure. The outermost layer which was ~60 μm of thickness, was the dense ceramic layer with high volume fraction of (Fe,Cr)7C3 ~90%. No obvious grain boundaries were observed. The subsurface layer was the particles dispersed layer, which was ~525 μm of thickness, with the volume fraction of (Fe,Cr)7C3 decreased to 70%. The lowermost layer was ferrite, with about 173 μm thickness. A good metallurgical bond generated between the composite layer and matrix. The depth and the width of surface scratch increased with the raising loads from 0 to 100 N, and the cracks mainly included micro-crack, tiny dens crack, mixture crack and through-wall crack. The (Fe,Cr)7C3 particles were broken and scraped when the load exceeded 80 N.

Summary 1. Heart failure (HF) predisposes to atrial fibrillation (AF) as a result of substrate remodelling. The present study aimed to investigate the impact of HF on the electrical remodelling of the pulmonary veins (PV) and left atrium (LA). 2. The electrical activity was recorded in LA and PV from control rabbits and rabbits with rapid ventricular pacing-induced HF, using a multi-electrode array system and conventional microelectrodes. 3. Compared with the control-PV (n = 21), the HF-PV (n = 13) had a higher incidence and frequency of rapid pacing-induced spontaneous activity (85 vs 29%, P = 0.005; 3.5 ± 0.2 vs 1.7 ± 0.1 Hz, P

Diabetes mellitus may result in impaired cardiac contractility, but the underlying mechanisms remain unclear. We aimed to investigate the temporal alterations in cardiac force- and flow-generation capacity and loading conditions as well as mechanical efficiency in the evolution of systolic dysfunction in streptozotocin (STZ)-induced diabetic rats. Adult male Wistar rats were randomized into control and STZ-induced diabetic groups. Invasive hemodynamic studies were done at 8, 16, and 22 wk post-STZ injection. Maximal systolic elastance (Emax) and maximum theoretical flow (Qmax) were assessed by curve-fitting techniques, and ventriculoarterial coupling and mechanical efficiency were assessed by a single-beat estimation technique. In contrast to early occurring and persistently depressed Emax, Qmax progressively increased with time but was decreased at 22 wk post-STZ injection, which temporally correlated with the changes in cardiac output. The favorable loading conditions enhanced stroke volume and Qmax, whereas ventriculoarterial uncoupling attenuated the cardiac mechanical efficiency in diabetic animals. The changes in Emax and Qmax are discordant during the progression of contractile dysfunction in the diabetic heart. In conclusion, our study showed that depressed Qmax and cardiac mechanical efficiency, occurring preceding overt systolic heart failure, are two major determinants of deteriorating cardiac performance in diabetic rats.

Acupuncture is a practice that has existed in Chinese society for thousands of years. Today, it is gaining greater acceptance and integration into medical practices of the western world. Its mechanism, however, remains elusive. Our study shows that only specific stimulation frequencies at specific acupoints will induce dopamine release in the corpus striatum, as demonstrated by in vivo microdialysis performed on Sprague-Dawley rats. In the first trial, electroacupuncture (EA) stimulation at 15 Hz and 15 mA was conducted at six different points on the upper limbs of the experimental rats. These points mimic acupoints along six different meridians in the human body. Only Point 2 (corresponding to Pericardium 7) induced a response. In the second trial, EA stimulation at varying frequencies of 3, 6, 9, 12, 15, 18, 21, 24, 27 and 30 Hz, and 15 mA were conducted through Point 2. Stimulation at 6 and 15 Hz induced an immediate response; 21 Hz induced a response only after the ceasing of stimulation. All other frequencies failed to induce a response. The data point to the importance of frequency-specific stimulation at specific acupoints for the release of neurotransmitters in the brain. We speculate that each meridian entails a stimulus of a specific frequency and intensity, which induces the release of its associated neurotransmitters or cytokines. This is a concept with far-reaching clinical implications for acupuncture therapy, including the treatment of dopamine-related disorders.

We studied the response of the superior vena cava (SVC) myocardial sleeve to atrial fibrillation (AF). We examined adult male dogs without pacing (N=6) and after rapid atrial pacing (600 bpm) for 2 weeks (P2w; N=5) and 6–8 weeks (P6–8w; N=5). After pacing, the sleeve was increased in thickness (non-paced vs. either paced group, both P

SUMMARY We investigated the phenotypic features of cardiomyocytes, including the gap junctions, in the myocardial sleeve of thoracic veins. Single cardiomyocytes, isolated from the canine pulmonary veins (PV) and superior vena cava (SVC) using digestive enzymes, were examined by immunoconfocal microscopy using antisera against connexin43 (Cx43), Cx40, and other cell markers. The results showed that isolated cardiomyocytes displayed rod shapes of various sizes, ranging from � 50 � m to � 200 � m in length, and all the cells expressed � -actinin and vinculin. Gap junctions made of various amounts of Cx43 and Cx40 were found at the cell borders. These two connexins were extensively co-localized. Comparison between the thoracic veins showed that cells of the SVC contained more Cx43 gap junctions (total Cx43 gap junctions area per cell surface area, 4.0 � 0.2% vs 1.5 � 0.2%; p � 0.01). In addition, for single-nucleus cells, those from the PV were longer (103.7 � 3.6 vs 85.0 � 3.1 � m; p � 0.01) but narrower (14.4 � 0.5 vs 16.9 � 0.9 � m; p � 0.01). In conclusion, canine thoracic veins contain cardiomyocytes with differences in shape and gap junctions, suggesting that the electrical conduction properties may be different between the thoracic veins. (J Histochem Cytochem 51:259–266, 2003)

Background The effects of light to moderate alcohol consumption on cardiac mechanics remain poorly understood. The aim of this study was to investigate the dose-response relationship between alcohol consumption and left ventricular (LV) and left atrial (LA) function using myocardial deformation. Methods In total 3,946 asymptomatic participants (mean age, 49.7 ± 10.7 years; 65% men) were consecutively studied using comprehensive echocardiography and two-dimensional speckle-tracking in a cross-sectional, retrospective manner. Global LV longitudinal and circumferential strain and LA strain were assessed and related to habitual alcohol consumption pattern (fewer than one, one to six, or more than six drinks per week) before and after propensity matching. Results With increasing weekly alcohol consumption, participants displayed greater LV eccentric remodeling, impaired diastolic function, and more attenuated global longitudinal strain, LA strain (adjusted coefficients, −1.07 [95% CI, −1.95 to −0.19] and −3.73 [95% CI, −5.36 to −2.11]), and early diastolic strain rates (adjusted coefficients, 0.07 [95% CI, 0.03–0.11] and 0.33 [95% CI, 0.24–0.42]) for one to six and more than six drinks per week, respectively ( P n = 1,140), participants currently consuming more than one drink per week continued to have significantly attenuated global longitudinal strain and all LA mechanics compared with those consuming fewer than one drink per week ( P Conclusions Habitual alcohol consumption, even at light to moderate doses, is associated with both reduced LV and LA mechanics in a dose-dependent manner. Whether such observations are reversible or related to future atrial fibrillation deserves further study.

The zero-net flux microdialysis method was used to determine (1) the basal concentration of dopamine (DA) in the extracellular space, and (2) the in vivo recovery of DA in the striatum and the medial prefrontal cortex by using three different kinds of perfusion medium. They were, (a) commercial Ringer's solution, (b) low Ca 2+ Ringer's solution, and (c) artificial cerebrospinal fluid (aCSF). Our results not only support previous findings that the high Ca 2+ concentration in the perfusion medium could increase the baseline concentration of DA in the dialysate, which was collected from extracellular space through dialysis probe; but also provides evidence that this baseline increase was primarily due to an increase of basal DA concentration, and not from the increase of the in vivo recovery. Additionally, there was no significant difference in the basal DA concentration by using either commercial Ringer's solution or aCSF. This indicates that both commercial Ringer's solution and aCSF are suitable as good perfusion medium to determine the basal DA in the rat's brain.

Geranylgeranylacetone (GGA) has been reported up-regulating heat shock protein (HSP) expression, and protecting against atrial remodeling. This study aimed to investigate the effects of GGA on atrial electrophysiology and inducibility of atrial fibrillation (AF) in heart failure (HF) model.HF rabbits were created 4 weeks after coronary artery ligation. Monophasic action potential recordings and multielectrode array were used to record the electrophysiological characteristics of left atrium (LA) in normal, or HF rabbits with (HF-GGA) and without (HF-control) oral administration of GGA (200 mg/kg, 24 h before experiments). The mRNA and protein expressions of ionic channels were measured by Western blot and PCR. HF-GGA LA (n = 10), similar to normal LA (n = 10) had a shorter action potential duration (APD) and effective refractory period than HF-control LA (n = 10). HF-GGA LA had less triggered activity and APD alternans (20% vs. 100%, P = 0.001), lower maxima slope of restitution curve of APD (0.94 ± 0.04 vs.1.69 ± 0.04, P0.001), and less inducibility of AF (50% vs. 100%, P = 0.033) than HF-control LA. HF-GGA LA had a shorter activation time and higher conduction velocity than HF-control LA. HF-GGA LA had a higher mRNA expression of Cav1.2, Nav1.5, Kir2.1, Kv1.4, Kv7.1, Kv11.1, sarcoplasmic reticulum Ca(2+)-ATPase, and higher phosphorylation of phospholamban than HF-control LA.GGA decreases triggered activity, dispersion of APD and inducibility of AF in failing heart through induction of HSP, and modulation of ionic channels and calcium homeostasis.

We evaluated the effects of two anesthetics on the cocaine-induced electroencephalographic (EEG) desynchronization in male, Sprague-Dawley rats. One group was anesthetized with chloral hydrate (400 mg/kg, i.p., 80 mg/kg/h i.v. supplement; group A). The other group was anesthetized with pentobarbital sodium (50 mg/kg, i.p., 10 mg/kg/h i.v. supplement; group B). The degree of EEG desynchronization after cocaine administration (1.5 mg/kg, i.v.) was expressed as an increase in the mean power frequency (MPF) and a decrease in the root mean square (RMS). These maximal increases and decreases were observed to be larger in group A (MPF: 43.3 +/- 7.0% increase; RMS: 47.4 +/- 5.0% decrease) than in group B (MPF: 17.8 +/- 3.6% increase; RMS: 19.2 +/- 2.5% decrease). Our laboratory previously proved that dopaminergic neurotransmission at the medial prefrontal cortex (mPFC) participated in the cocaine-induced EEG desynchronization and that both D-1 and D-2 receptors were involved in the process. Therefore, in vivo microdialysis coupled with high performance liquid chromatography was used to quantify the changes of extracellular dopamine (DA) concentrations at the mPFC for 90 minutes at 10 minute intervals after 1.5 mg/kg cocaine i.v. injection. The extracellular DA increases in both groups was rapid and reached the maximal peak within 10 min. There was no significant difference in the maximal increase of DA between groups (group A: 375.2 +/- 35.77% versus group B: 332.2 +/- 16.69% over basal value). These results suggest that different anesthetics may differentially affect cocaine-induced EEG desynchronization and this difference has no bearing on the DA response in the mPFC.

1. Heart failure (HF) predisposes to atrial fibrillation (AF) as a result of substrate remodelling. The present study aimed to investigate the impact of HF on the electrical remodelling of the pulmonary veins (PV) and left atrium (LA). 2. The electrical activity was recorded in LA and PV from control rabbits and rabbits with rapid ventricular pacing-induced HF, using a multi-electrode array system and conventional microelectrodes. 3. Compared with the control-PV (n = 21), the HF-PV (n = 13) had a higher incidence and frequency of rapid pacing-induced spontaneous activity (85 vs 29%, P = 0.005; 3.5 ± 0.2 vs 1.7 ± 0.1 Hz, P0.001) and high-frequency irregular electrical activity (92 vs 38%, P = 0.01; 23 ± 1 vs 19 ± 1 Hz, P = 0.003), greater depolarized resting membrane potential (-59 ± 1 vs -70 ± 2 mV, P0.001), higher incidence of early afterdepolarizations (EAD; 69 vs 6%, P = 0.001) and delayed afterdepolarizations (DAD; 92 vs 25%, P = 0.001), and slower conduction velocity (38 ± 2 vs 63 ± 2 cm/s, P0.05). In comparison to the HF-LA, the HF-PV had a higher incidence of spontaneous activity and high-frequency irregular electrical activity (85 vs 39%, P = 0.04; 92 vs 46%, P = 0.03), and higher incidence of EAD and DAD, and those differences were not found between the control-LA and control-PV. The control-PV with high-frequency irregular electrical activity had a higher incidence of DAD and spontaneous activity as compared with those without it. 4. HF contributed to an increased automaticity, triggered activity and conduction disturbance in the PV. The PV possessed more arrhythmogenic properties, which might play an important role in the genesis of AF in HF.

We have previously shown that left atrial-pulmonary vein tissue (LA-PV) can generate reentrant arrhythmias (atrial fibrillation, AF) in wild-type (mXinalpha+/+) but not in mXinalpha-null (mXinalpha-/-) mice. With the present experiments, we investigated the arrhythmogenic activity and the underlying mechanisms in mXinalpha+/+ vs. mXinalpha-/- LA-PV. Electrical activity and conduction velocity (CV) were recorded in LA-PV by means of a MED64 system. CV was significantly faster in mXinalpha+/+ than in mXinalpha-/- LA-PV and it was increased by 1 muM isoproterenol (ISO). AF could be induced by fast pacing in the mXinalpha+/+ but not in mXinalpha-/- LA-PV where automatic rhythms could occur. ISO increased the incidence of AF in Xinalpha+/+ whereas it increased that of automatic rhythms in mXinalpha-/- LA-PV. In LA-PV with the right atrium attached (RA-LA-PV), automatic rhythms occurred in all preparations. In mXinalpha+/+ RA-LA-PV simultaneously treated with ISO, strophanthidin and atropine, the incidence of the automatic rhythm was about the same, but AF increased significantly. In contrast, in mXinalpha-/- RA-LA-PV under the same condition, the automatic rhythm was markedly enhanced, but still no AF occurred. Conventional microelectrode techniques showed a longer APD(90) and a less negative maximum diastolic potential (MDP) in mXinalpha-/- than mXinalpha+/+ LA-PV tissues. Whole-cell current clamp experiments also showed a less negative MDP in mXinalpha-/- vs. mXinalpha+/+ LA-PV cardiomyocytes. The fact that AF could be induced by fast pacing under several conditions in mXinalpha+/+ but not in mXinalpha-/- LA-PV preparations appears to be due to a slower CV, a prolonged APD(90), a less negative MDP and possibly larger areas of conduction block in mXinalpha-/- myocardial cells. In contrast, the non-impairment of automatic and triggered rhythms in mXinalpha-/- preparations may be due to the fact that the mechanisms underlying these rhythms do not involve cell-to-cell conduction.

Objectives: We examined the role of atrial gap junctions, NF-κB and fibrosis in the occurrence of postoperative atrial fibrillation (AF) in patients undergoing coronary artery bypass graft (CABG) surgery. Methods: Forty-five patients with sinus rhythm were randomly assigned to the beating heart (n = 22) or cardioplegic cardiac arrest (n = 23) technique for surgery. Of them, 14 patients experienced post-CABG AF. Atrial samples taken before and after CABG surgery were analyzed. Results: During surgery, Cx43 and Cx40 proteins were significantly reduced (both p < 0.05) in the arrested heart group, but only mildly decreased in the beating heart group. However, the change of either connexin was not associated with AF. In contrast, patients with AF had a higher baseline expression of NF-κB and more fibrosis compared to those without AF (both p < 0.05). Conclusions: CABG surgery with the beating heart technique attenuated the reduction of atrial Cx43 and Cx40 compared to the cardioplegic cardiac arrest technique. Atrial inflammation and fibrosis status before surgery, but not the changes of connexins during surgery, were associated with the occurrence of post-CABG AF.

mXin alpha, a downstream target gene of Nkx2.5 transcription factor, was shown to encode a proline-rich and Xin repeats-containing protein which localizes to the intercalated disc of adult hearts. Our previous voltage-clamp studies have shown that the ventricular myocytes of mXin alpha -deficient mice exhibited a significant reduction in K+ currents (Ito and IK1), L-type Ca2+ currents, and maximum diastolic potential, leading to the development of early afterdepolarization (EAD) and arrhythmias. However, changes in cationic inward currents could also contribute to the genesis of EAD and arrhythmias in mXin alpha -deficient mice.The present study aims to characterize changes in Na+ currents on depolarization and transient inward currents (Iti) on repolarization. Conduction velocity (CV) on the frontal surface of ventricles were also measured and compared.Results of optical mapping on the Langendorff-perfused hearts at 37oC revealed a 36% reduction of CV in mXin alpha -/- ventricle. Pacing (3 Hz)-induced tachyarrhythmias were more frequently found and ventricular fibrillation (VF, 21 Hz for 5 min) occurred in one out of 8 mXin alpha-/- heart. When perfused at 30 degrees C, no VF was observed in both types of preparations. Voltage-clamp study on isolated ventricular myocytes at 37 degrees C shows increase in INa and Iti in mXin alpha -/- cardiomyocytes thus could explain the occurrence of re-entrant triggered arrhythmias.The present results revealed that the CV was slower, but INa and Iti were increased in mXin alpha -/-cardiomyocytes thus were prone to reentrant triggered arrhythmias. Hypothermia could reduce the occurrence of arrhythmias.

The purpose of this research was to study the propagation of the excitation wave along epicardium in the area of the pulmonary veins ostia in rabbit in normal conditions and while cooling.The excitation wave spreading along epicardium in the area of pulmonary veins ostia in the left atrium at 36-37 degrees C and when cooling to 32 degrees C was studied by the method of electrocardiochronotopography in rabbit of Chinchilla species, five months age. The size of the registering surface of the electrode was 1.08 x 1.08 cm.The time of depolarization when cooling from 36 degrees C to 32 degrees C changes unevenly in various zones of pulmonary veins. On the epicardium of pulmonary veins area at temperature reduction from 36 degrees C to 33 degrees C, change in the direction of excitation and essential reduction of depolarization time, and its significant increase under further cooling to 32 degrees C were observed. In the middle part of the left atrium at temperature reduction, change in the main direction of the excitation wave propagation, shift of the location of the areas of the latest depolarization were revealed and the front become more homogeneous.In the area of the left atrium base the heterogeneity of the front of depolarization at temperature reduction was revealed.

Background Gabapentin, a gamma-aminobutyric acid analog anticonvulsant, has been shown to possess antinociceptive effects in animal models and clinical trials. An endogenous binding site of [3H]gabapentin has been revealed to be the alpha(2)delta subunit of voltage-dependent Ca2+ channels. Magnesium chloride, ruthenium red, and spermine have been shown to modulate [3H]gabapentin binding to this binding site in vitro. In this study, the authors examined whether intrathecal magnesium chloride, ruthenium red, or spermine could affect the antiallodynic effect of intrathecal gabapentin in a rat model of postoperative pain. Methods Under isoflurane anesthesia, male Sprague-Dawley rats received an incision over the plantar surface of the right hind paw to produce punctate mechanical allodynia. Withdrawal thresholds to von Frey filament stimulation near the incision site were measured before incision, 2 h after incision, and every 30 min after intrathecal coadministration of gabapentin with normal saline or different doses of magnesium chloride, ruthenium red, or spermine for 2 h. Results Intrathecal gabapentin (30, 100, 200 microg) dose-dependently reduced incision-induced allodynia. Hexahydrated magnesium chloride (5, 10, 20 microg) and ruthenium red (0.2, 2, 20 ng) noncompetitively inhibited the antiallodynic effect of gabapentin. Spermine at doses not inducing motor weakness (30, 60 microg) did not affect the antiallodynic effect of gabapentin. The antiallodynic effect of intrathecal morphine (1.5 microg) was not affected by hexahydrated magnesium chloride (20 microg), ruthenium red (20 ng), or spermine (60 microg). Conclusions These results provide behavioral evidence to support that the alpha(2)delta subunit of Ca2+ channels may be involved in the antiallodynic action of intrathecal gabapentin in the postoperative pain model.

Abstract —Endothelial cells form gap junctions that, according to vessel type, may be composed of up to 3 types of connexin, connexin37, connexin40, and connexin43. Although changes in connexin expression have been linked to growth and injury in cultured endothelial cells, information on connexin expression in regenerating endothelium in situ is lacking. We investigated gap junction distribution and expression of all 3 endothelial connexins during healing in rat carotid artery after denudation injury. En face viewing of the vascular luminal surface by means of immunoconfocal microscopy was used to examine the spatial and temporal expression pattern of the endothelial connexins. Gap junction spots labeled by specific antisera against connexin37, connexin40, and connexin43 were quantified 7, 14, and 28 days after injury, and the relations among the connexins were examined by using colocalization analysis. Complementary electron microscopy was also conducted. After injury, the regenerating endothelium initially expressed small, sparse gap junctions, the numbers of which progressively increased to values equivalent to those of controls. Although connexin40 gap-junctional spot size and area returned to uninjured levels by 28 days after injury, connexin37 and connexin43 spot size and area exceeded those of the uninjured artery ( P 80% in the intact artery at postinjury day 28 and P

There are many evidences suggest that ascorbate in the extracellular space can affect glutamate concentration in the rat's brain. In this report, we studied how ascorbate in microdialysis perfusion medium affected glutamate level at the striatum in freely-moving rats. Three perfusion mediums were used: 0, 250, and 400 microM of ascorbate in perfusion medium. The extracellular basal concentrations of glutamate were determined to be 1.29+/-0.52 microM for the no ascorbate group, 0.86+/-0.35 microM for the low ascorbate group and 4.76+/-1.48 microM for the high ascorbate group. By using 400 microM of ascorbate in a perfusion medium, we found that the extracellular basal concentration of glutamate significantly increased and its in vivo recovery significantly decreased. This indicated that ascorbate concentration in a perfusion medium was important and must be carefully considered while using microdialysis technique to monitor glutamate concentration in vivo.

Background: Alcohol-induced cardiac remodeling has been well documented. However, data regarding the dose-related ventricular electrical disturbances and the exact pathophysiologic mechanisms remained largely unknown. Methods: We examined in a community-dwelling cohort the cardiac electromechanical dysfunction among 260 participants (mean age: 64.9 years, 57.5% female) who had habitual alcohol consumption. In parallel, adult male C57BL/6 mice were fed a liquid diet containing 4% or 6% alcohol, or a normal diet (Ctrl) for 14 weeks followed by electrophysiological (whole heart optical mapping and single cardiomyocyte patch clamp technique) examination and analysis of sodium channel (INaV 1.5), gap junctions, and fibrosis. Results: When categorized by daily alcohol consumption (heavy group: >90 gm/day), the heavy alcohol consumption group demonstrated larger mass (trend p 30% decrement, both p

We evaluated the effects of chloral hydrate and pentobarbital sodium on the basal extracellular concentrations of dopamine (DA) and norepinephrine (NA) as well as their in vivo extraction fraction (relative recovery) at the medial prefrontal cortex (mPFC) in rats by using zero-net flux microdialysis method. Adult, male Sprague-Dawley rats anesthetized with either chloral hydrate (400 mg/kg, i.p., with 80 mg/kg i.v. supplements) or pentobarbital sodium (50 mg/kg, i.p., with 10 mg/kg i.v. supplements) were used as treatment groups. Conscious rats were used as a control group. The basal extracellular concentration and in vivo recovery of DA in the conscious group were 2.38 ± 0.70 nM and 41 ± 6%. In comparison with the chloral hydrate group (1.51 ± 0.55 nM and 41 ± 9%) and the pentobarbital sodium group (2.81 ± 1.20 nM and 42 ± 4%), there were no significant effects of anesthesia on the basal extracellular concentration and the in vivo recovery of DA at the mPFC. Additionally, the basal extracellular concentration and the in vivo recovery of NA in the conscious group were 1.59 ± 0.37 nM and 51 ± 8%. There also were no significant differences of the basal extracellular concentration of NA among these three groups (chloral hydrate group: 4.38 ± 1.39 nM; pentobarbital group: 3.67 ± 0.90 nM). However, the conscious group had a higher in vivo recovery than the two anesthetized groups (chloral hydrate group: 16 ± 2%; pentobarbital group: 27 ± 5%). Based on these findings, we then concluded that pentobarbital sodium and chloral hydrate selectively suppressed NA's active processes (such as release, reuptake, and metabolism) but not DA's yet do not affect the basal extracellular concentrations of NA and DA at the mPFC. Therefore, anesthesia was accompanied by a selective change of the active processes of certain types of neurons but not by altering their basal extracellular concentrations. However, more studies are necessary to draw a relationship between these findings and the action of general anesthesia. © 1995 Wiley-Liss, Inc.

Adult male Sprague-Dawley rats anesthetized with chloral hydrate and pentobarbital sodium were used as two different treatment groups. Conscious rats were used as a control group. By using baseline (precocaine) concentration as 100%, after cocaine administration (3.0 mg/kg i.v.), the maximal dopamine (DA) increase occurring at the first microdialysis collection period (20 min) in the medial prefrontal cortex was 299 +/- 46% for the chloral hydrate group, 168 +/- 12% for the pentobarbital sodium group, and 325 +/- 23% for the conscious group. At the same time, norepinephrine (NA) increases reached a maximum and were 162 +/- 20%, 100 +/- 5%, and 141 +/- 17%, respectively. The maximal changes of DA and NA in the chloral hydrate group and in the control group were both significantly higher than that in the pentobarbital sodium group. Meanwhile, the cocaine concentration was higher over a 100-min period of time in the chloral hydrate group when compared with the pentobarbital group and the control group. The peak cocaine concentration in dialysate occurred in the same time slot of maximal DA and NA responses, which were 0.65 +/- 0.08, 0.30 +/- 0.02, and 0.41 +/- 0.05 microM, respectively. Anesthetics suppress the pharmacologic response of neurons, which may explain the difference in catecholamine response between the pentobarbital sodium and the conscious groups. Conversely, because there was no significant difference in DA and NA response between the chloral hydrate group and the conscious group, it may possible be due to the balancing effect between the higher existing cocaine concentration and the anesthetic suppression on pharmacological response of neurons in the chloral hydrate group. The effect of guide cannula implantation on the cocaine-induced catecholamine response was also evaluated.

Background Long-term heavy alcohol drinkers are prone to the development of cardiac arrhythmia. To understand the mechanisms, we evaluated the cardiac structural and electrophysiological changes in mice chronically drinking excessive alcohol. Results Male C57BL/6J mice were given 36% alcohol in the drinking water. Those given blank water were used as control. Twelve weeks later, the phenotypic characteristics of the heart, including gap junctions and electrical properties were examined. In the alcohol group the ventricles contained a smaller size of cardiomyocytes and a higher density of capillary networks, compared to the control. Western blots showed that, after drinking alcohol, the content of connexin43 (Cx43) protein in the left ventricle was increased by 18% (p < 0.05). Consistently, immunoconfocal microscopy demonstrated that Cx43 gap junctions were up-regulated in the alcohol group with a disorganized distribution, compared to the control. Optical mapping showed that the alcohol group had a reduced conduction velocity (40 ± 18 vs 60 ± 7 cm/sec, p < 0.05) and a higher incidence of ventricular tachyarrhythmia (62% vs 30%, p < 0.05). Conclusion Long-term excessive alcohol intake resulted in extensive cardiac remodeling, including changes in expression and distribution of gap junctions, growth of capillary network, reduction of cardiomyocyte size, and decrease of myocardial conduction.