The Neuroprotective Effects of Administration of Methylprednisolone in Cardiopulmonary Resuscitation in Experimental Cardiac Arrest Model.

Although advances in diagnosis and treatment of cardiac arrest (CA) could improve neurological outcomes after cardiopulmonary resuscitation (CPR), survival rate and neurological outcome after CA and CPR remain poor. This study aimed to investigate the effect of epinephrine (EP) alone and EP in combination with methylprednisolone (MP) (EP + MP) on some the apoptotic and anti-apoptotic genes and proteins levels expression of the cerebral cortex as well as neuronal death in a CA rat model. Forty-five male Sprague Dawley rats were randomly divided into three groups including the hypoxic CA + EP, hypoxic CA + EP + MP, and sham groups using a simple randomization procedure. In both hypoxic CA groups, CA was induced by asphyxia and immediately after confirmation of CA, the treatment strategies including chest compression or cardiac massage simultaneously with ventilation, and administration of EP alone (20 mg/kg, every 3 min) and EP (20 mg/kg, every 3 min) + 30 (mg/kg) of MP were done. The sham group only received anesthetic drugs without CA. Some neurological outcomes were investigated using histopathological, immunohistochemical, molecular, and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) assays at 5 and 48 h post-CPR. The data obtained showed the highest up-regulation of apoptotic genes and proteins expression, the lowest expression of anti-apoptotic gene and protein expression, the most DNA fragmentation and histopathological changes belonged to the EP group on 48 h post-CPR. While mild and intermediate histopathological changes, DNA fragmentation and apoptotic activity was detected in theEP alone and EP + MP groups at 5 h and 48 h post-CPR, respectively. As a novel finding, the present study showed that EP + MP protects neurons from death provoked/induced by hypoxia and reperfusion injury in an experimental model of CA through up and down-regulation of pro- (caspases 3 and 8) and anti-apoptotic (BCL2) molecules, respectively.

Comparative evaluation of adolescent repeated psychological or physical stress effects on adult cognitive performance, oxidative stress, and heart rate in female rats.

Multiple adult health problems are associated with adolescent stress. As the brain discriminates physical and psychological stressors by activation of different neural networks, we hypothesized that behavioral and physiological performance would be modulated differently based on the nature of the stressors. Thus, we studied the comparative effects of adolescent repeated physical and psychological stresses on adult cognitive performance, pro-oxidant-antioxidant balance (PAB) and heart rate in female rats. The aim was to differentiate disparate potency of chronic psychological and physical stresses leading to long-term behavioral and physiological alterations. Twenty-one female rats were divided randomly into three groups of seven rats each; control, physical, and psychological stress. Experimental rats were exposed to the stressors for five consecutive days (10 min daily) via a two-communication box. After verifying stress induction by serum corticosterone measurement, the rats were returned to their home cage for 6 weeks, until adulthood, elevated plus maze (EPM), forced swimming test (FST), Y-maze, object recognition task (ORT), and passive avoidance test (PAT) were used as five different behavioral tests to evaluate cognitive performance of each group. Serum PAB and heart rate were measured to assess long-term stress-induced physiological disorders. The results showed exposure to adolescent psychological stress resulted in a larger set of significant changes (in behavioral variation, oxidative stress, and elevated heart rate) 6 weeks post-stress compared to adolescent physical stress. Hence, mental health care in adolescence and therapies targeting PAB and heart rate could be prevention and treatment approaches to confront persistent adolescent stress-induced disorders. Lay summaryThe aim of our study on female laboratory rats was to differentiate disparate potency of chronic psychological and physical stresses in adolescence leading to long-term behavioral and physiological alterations. The results suggest that psychological stresses result in a greater extent of changes compared to physical stress. Adolescent chronic psychological stress may reveal itself in the form of certain behavioral and physiological variations in adulthood. Therefore, mental health care in adolescence could be a valuable prevention approach to confront a variety of adult stress-induced disorders.

Decrease in VEGF-Induced Pericardial Adhesion Formation Using Bevacizumab After Surgery.

OBJECTIVES: Some degrees of postoperative cardiac adhesions occur in response to the first cardiac surgery in patients that may limit surgeons for subsequent operations and increase the risk of heart injury. In this article, we established a model of postoperative pericardial adhesions, and because vascular endothelial growth factor (VEGF) seems to initiate adhesion formation through inflammatory responses, we used an anti-VEGF antibody, that is, bevacizumab, to examine its effects on postoperative adhesion formation. METHODS: Twenty Wistar rats were divided in 2 groups: control and bevacizumab. After chest opening, pericardial sac was opened and the heart was fully exposed. In the bevacizumab group, bevacizumab (2.5 mg/kg) was applied locally on the heart and then the chest was closed. The control group received saline solution as placebo. After 42 days, high-sensitivity C-reactive protein in peripheral blood was measured, and re-sternotomy was performed to measure severity of pericardial adhesions. Then, the hearts were collected from all rats to evaluate percentage of CD-31-positive cells (as a marker of angiogenesis) using immunohistochemical staining. RESULTS: When the bevacizumab group was compared with the control group, we found that the mean score of adhesion (0.89 ± 0.38 vs 2.56 ± 0.41) and CD-31 expression (27.45 ± 3.75% vs 56.26 ± 1.98%) was decreased significantly after bevacizumab administration. However, we did not find any difference in high-sensitivity C-reactive protein levels of control and bevacizumab animals. CONCLUSION: In the current study, bevacizumab administration could effectively reduce adhesion formation after first sternotomy by preventing VEGF-induced angiogenesis through CD-31 downregulation.

Acute sleep deprivation induces cardioprotection against ischemia/ reperfusion injury through reducing inflammatory responses: the role of central GABA-A receptors.

Sleep is considered as a physiological regulator in the body. Gamma-aminobutyric acid (GABA) is a neurotransmitter that modulates sleep and affects cardiac functions. We evaluated effects of acute sleep deprivation (SD) on cardiac hemodynamic parameters, expression of pro-inflammatory cytokines, and Heat shock protein (Hsp70), serum level of lactate dehydrogenase (LDH) and prooxidant/antioxidant balance (PAB). Male Wistar rats were bilaterally cannulated in the central nucleus of amygdala (CeA) and saline or bicuculline was injected 24 hours prior to induction of 30 minute ischemia following 120 minute reperfusion. Forty-eight animals were randomly divided into four groups: Control (CONT), bicuculline (BIC), acute SD and bicuculline + acute sleep deprivation (BIC+SD). Animals in SD and BIC+SD groups were put in an aquarium for inducing sleep deprivation. SD attenuated LDH, pro-inflammatory cytokines and PAB; improved cardiac hemodynamic parameters and increased Hsp70 in non-infarcted area as compared to CONT. Administration of bicuculline increased LDH, pro-inflammatory cytokines and PAB, reduced cardiac hemodynamic parameters and Hsp70 as compared to CONT. Furthermore, bicuculline administration prior to acute sleep induction decreased SD effects on LDH, PAB, Hsp70, cardiac hemodynamic parameters and pro-inflammatory cytokines. Induction of SD prior to ischemia/reperfusion induces cardioprotection through suppressing inflammatory responses.

Upregulated Hsp27 expression in the cardioprotection induced by acute stress and oxytocin in ischemic reperfused hearts of the rat.

In view of the cardioprotective effect of oxytocin (OT) released in response to stress, the aim of this study was to evaluate the role of heat shock proteins Hsps 70, 27 and 20 in stress-induced cardioprotection in isolated, perfused rat hearts. Rats were divided in two main groups: unstressed and stressed rats, and all of them were subjected to i.c.v. infusion of vehicle or drugs: unstressed rats [control: vehicle, OT (100 ng/5 µl), atosiban (ATO; 4.3 µg/5 µl) as OT antagonist, ATO+OT], and stressed rats [St: stress, OT+St, ATO+St]. After anesthesia, hearts were isolated and subjected to 30 min regional ischemia and 60 min subsequent reperfusion (IR). Acute stress protocol included swimming for 10 min before anesthesia. Malondialdehyde in coronary effluent was measured and the expression of Hsp 70, 27 and 20 was measured in myocardium using real-time reverse transcriptase polymerase chain reaction (RT-PCR). The malondialdehyde levels, which decreased in the St and OT groups, increased by the administration of atosiban as an OT antagonist. The expression of Hsp27 increased 4 to 5 folds by stress induction and i.c.v. infusion of OT. Central administration of atosiban prior to both stress and OT decreased Hsp27 mRNA levels. These findings suggest that endogenous OT may participate in stress-induced cardioprotection via Hsp27 over-expression as an early response.

Acute sleep deprivation (ASD) and cardioprotection: Impact of ASD on oxytocin-mediated sympathetic nervous activation preceding myocardial infarction.

INTRODUCTION: This study explored how acute sleep deprivation (ASD) before myocardial ischemia influences oxytocin release from paraventricular (PVN) neurons and its correlation with sympathetic nervous system (SNS) activity post-acute sleep loss, impacting subsequent left ventricular (LV) remodeling following myocardial infarction (MI). METHODS: The study was conducted in two phases: induction of ASD, inducing MI, blood sampling, euthanizing animals and collecting their heart and brain for histological and gene expression evaluations. The animals in first and second phase were euthanized 24 h and 14 days after MI, respectively. RESULTS: Pre-MI ASD, accompanied by increased serum epinephrine levels within 24 h of MI, upregulated oxytocin and cFos expression in the PVN. Also, pre-MI ASD resulted in decreased serum PAB levels 14 days post-MI (P < 0.001). While notable echocardiographic changes were seen in MI versus sham groups, ASD demonstrated protective effects. This was evidenced by reduced infarct size, elevated TIMP1, MMP2, and MMP9 in the LV of SD + MI animals versus MI alone (P < 0.05). Additionally, histological analysis showed reduced LV fibrosis in pre-MI ASD subjects (P < 0.05). CONCLUSION: Our study supports the notion that activation of oxytocin neurons within the PVN subsequent to ASD interacts with autonomic centers in the central nervous system. This enhanced sympathetic outflow to the heart prior to MI triggers a preconditioning response, thereby mediating cardioprotection through decreased oxidative stress biomarkers and regulated extracellular matrix (ECM) turnover.

Unfavorable left ventricular remodeling due to experience of chronic sleep restriction after myocardial infarction: The role of matrix metalloproteinases & oxidative stress.

Disturbed sleep or sleep loss due to vocational or lifestyle changes following MI is a common problem that may affect many physiological processes involved in left ventricle (LV) remodeling. Herein, we proposed that experience of sleep disruption and/or restriction after myocardial infarction (MI) may aggravate cardiac extracellular matrix remodeling and induce apoptosis in the cardiomyocytes. MI was induced in adult male rats by permanent ligation of the left anterior descending coronary artery. Twenty-four hours after surgery, some animals experienced chronic sleep restriction (CSR) for 6 days. Serum levels of CK-MB, PAB, and TNF-α were evaluated at days 1, 8, and 21 postsurgery. Twenty-one days after surgery, hemodynamic parameters and expression of MMP-2, MMP-9, TIMP-1, and TNF-α, as well as myocardial fibrosis and apoptosis in the noninfarcted area of the LV were assessed. Our results showed a clear decrease in serum concentrations of CK-MB, PAB and TNF-α at day 21 postsurgery in the MI group as compared to MI+SR animals in which these markers remained at high levels. CSR following MI deteriorated LV hemodynamic indexes and also impaired the balance between MMPs and TIMP-1. Further, it yielded an increase in oxidant and inflammatory state which caused deleterious fibrotic and apoptotic effects on cardiomycytes. Our data suggest post-MI sleep loss may cause adverse LV remodeling due to increased inflammatory reactions as well as oxidative burden and/or anti-oxidative insufficiency that in turn impede the balance between MMPs and their inhibitors.

Comparable assessment of adolescent repeated physical or psychological stress effects on adult cardiac performance in female rats.

Extensive evidence highlights a robust connection between various forms of chronic stress and cardiovascular disease (CVD). In today's fast-paced world, with chronic stressors abound, CVD has emerged as a leading global cause of mortality. The intricate interplay of physical and psychological stressors triggers distinct neural networks within the brain, culminating in diverse health challenges. This study aims to discern the unique impacts of chronic physical and psychological stress on the cardiovascular system, unveiling their varying potencies in precipitating CVD. Twenty-one adolescent female rats were methodically assigned to three groups: (1) control (n = 7), (2) physical stress (n = 7), and (3) psychological stress (n = 7). Employing a two-compartment enclosure, stressors were administered to the experimental rats over five consecutive days, each session lasting 10 min. After a 1.5-month recovery period post-stress exposure, a trio of complementary techniques characterized by high specificity or high sensitivity were employed to meticulously evaluate CVD. Echocardiography and single-photon emission computed tomography (SPECT) were harnessed to scrutinize left ventricular architecture and myocardial viability, respectively. Subsequently, the rats were ethically sacrificed to facilitate heart removal, followed by immunohistochemistry staining targeting glial fibrillary acidic protein (GFAP). Rats subjected to psychological stress showed a wider range of significant cardiac issues compared to control rats. This included left ventricular hypertrophy [IVSd: 0.1968 ± 0.0163 vs. 0.1520 ± 0.0076, P < 0.05; LVPWd: 0.2877 ± 0.0333 vs. 0.1689 ± 0.0057, P < 0.01; LVPWs: 0.3180 ± 0.0382 vs. 0.2226 ± 0.0121, P < 0.05; LV-mass: 1.283 ± 0.0836 vs. 1.000 ± 0.0241, P < 0.01], myocardial ischemia [21.30% vs. 32.97%, P < 0.001], and neuroinflammation. This outcome underscores the imperative of prioritizing psychological well-being during adolescence, presenting a compelling avenue to curtail the prevalence of CVD in adulthood. Furthermore, extending such considerations to individuals grappling with CVD might prospectively enhance their overall quality of life.

The effect of acute stress exposure on ischemia and reperfusion injury in rat heart: role of oxytocin.

Previous studies showed the protective effects of oxytocin (OT) on myocardial injury in ischemic and reperfused rat heart. Moreover, exposure to various stressors not only evokes sudden cardiovascular effects but also triggers the release of OT in the rat. The present study was aimed to evaluate the possible cardioprotective effects of endogenous OT released in response to stress (St), and effects of administration of exogenous OT on the ischemic-reperfused isolated heart of rats previously exposed to St. Wistar rats were divided into six groups: ischemia/reperfusion (IR); St: rats exposed to swim St for 10 min before anesthesia; St+atosiban (ATO): an OT receptor antagonist, was administered (1.5 mg/kg i.p.) prior to St; St+OT: OT was administered (0.03 mg/kg i.p.) prior to St; OT: OT was administrated prior to anesthesia; ATO was given prior to anesthesia. Isolated hearts were perfused with Krebs buffer solution by the Langendorff method and subjected to 30 min of regional ischemia followed by 60 min of reperfusion. The infarct size (IS) and creatine kinase MB isoenzyme (CK-MB) and lactate dehydrogenase (LDH) in coronary effluent were measured. Hemodynamic parameters were recorded throughout the experiment. The plasma concentrations of OT and corticosterone were significantly increased by St. Unexpectedly St decreased IR injury compared with the IR alone group. OT administration significantly inhibited myocardial injury, and administration of ATO with St abolished recovery of the rate pressure product, and increased IS and levels of CK-MB and LDH. These findings indicate that activation of cardiac OT receptors by OT released in response to St may participate in cardioprotection and inhibition of myocardial IR injury.

The role of nitric oxide on the antiarrhythmic effects of ketamine/xylazine in a rat model of acute cardiac ischemia-reperfusion.

The prevalence of ventricular arrhythmias during general anesthesia is about 70%. In experimental studies on the antiarrhythmic effects of different agents, using anesthetic drugs that do not have any protective properties are preferable. The present study was conducted to investigate molecular mechanisms involved in the antiarrhythmic effects of ketamine/xylazine (K/X). Sixty male rats were assigned to eight groups: K/X, L -NAME (25-35 mg/kg) with thiopental (TP), L-NAME (25-35 mg/kg) with ketamine/xylazine, L arginine (100 mg/kg) with thiopental, L-arginine (100 mg/kg) with ketamine/xylazine. After anesthetic induction using TP or K/X, the animals were subjected to 30 min of ischemia. Hemodynamic parameters, ventricular arrhythmias during ischemia, the incidence of ventricular tachycardia (VT), and ventricular fibrillation (VF) were measured. Additionally, in order to assess nitrite/nitrate ratio and LDH after ischemia, serum samples were collected and used. Our results showed that in the K/X group, the number of VT and VF, duration of VT (p = 0.006), the severity of arrhythmias (p = 0.0179). There was no VF incidence in this group. These protective effects were faded by administration of L-NAME with K/X. The combination of L- Arginine in the TP group decreased the number and duration of VT (p < 0.001, p = 0.0013) with no incidence of VF in comparison with TP. L-arginine with K/X groups increased the number and duration of VT (p < 0.0001, p < 0.001) compared to K/X and VF was seen (100%). However, there was no significant difference between TP and K/X groups in terms of this nitrite/nitrate ratio. These findings suggest that the antiarrhythmic effects of ketamine/xylazine might be partially relative to the nitric oxide synthesis pathway.

Effects of Acute Potassium Chloride Administration on Ventricular Dysrhythmias after Myocardial Infarction in a Rat Model of Ischemia/Reperfusion.

Background: Acute myocardial infarction is an important cause of morbidity. This study aimed to investigate the effects of the administration of potassium chloride (KCl) on reperfusion-induced injuries in a rat model of myocardial ischemia/reperfusion. Methods: Thirty-six male Wistar rats, weighing 200 to 250 g, were randomly assigned to 3 experimental groups: control, K1 (10 µg/kg of KCl), and K2 (20 µg/kg of KCl). Twenty minutes before ischemia, a single dose of 10 and 20 µg/kg of KCl was intraperitoneally administered in the K1 and K2 groups, respectively. The coronary artery was occluded for 30 minutes (ischemia); thereafter, it was opened for 60 minutes (reperfusion) to measure hemodynamic parameters and ventricular arrhythmias. Blood sampling was performed after the reperfusion period to determine the serum levels of lactate dehydrogenase, troponin I, creatine kinase (CK)-MB, malondialdehyde, and pro-oxidant-antioxidant balance. Results: Serological parameters significantly decreased in the potassium groups compared with the control group. In particular, the decline was more pronounced for the serum levels of lactate dehydrogenase (1180.25±69.48 vs 1556.67±77.02 U/L; P=0.011), troponin I (21.98±0.61 vs 28.76±1.65 ng/mL; P=0.020), and pro-oxidant-antioxidant balance (15.51±0.72 vs 20.63±1.42 HK; P=0.041) in the K2 group compared with the K1 group. Moreover, the administration of 20 µg/kg of KCl significantly decreased the incidence of ventricular tachycardias and fibrillations compared with the control group (P=0.002). Additionally, no considerable differences were observed between the control group and the groups with 10 µg/kg and 20 µg/kg of KCl regarding the number of ventricular ectopic beats. Conclusion: The administration of KCl before ischemia could reduce ventricular arrhythmias and reperfusion-induced injuries by reducing oxidative stress.

Noradrenaline protects in vivo rat heart against infarction and ventricular arrhythmias via nitric oxide and reactive oxygen species.

BACKGROUND: Our previous study showed that pretreatment with noradrenaline via opening of the mitochondrial ATP-sensitive potassium channel protects myocardium against ischemia/reperfusion injuries. We have hypothesized that production of nitric oxide (NO) and generation of reactive oxygen species (ROS) are involved in noradrenaline-induced cardioprotection in rat heart. METHODS: All anesthetized rats underwent 25 min of regional ischemia followed by 120 min of reperfusion. Animals were randomized to receive one of the following treatment: saline, noradrenaline (2 µg/kg, i.v.), noradrenaline plus prazosin (an α(1)-adrenoceptor blocker, 0.5mg/kg, i.v.), noradrenaline plus L-NAME (a nonspecific NOS inhibitor, 10mg/kg, i.v.), noradrenaline plus tempol (a membrane-permeable radical scavenger, 30 mg/kg, i.v.), Prazosin alone, only L-NAME and tempol alone. RESULTS: Infarct size (% of risk area) was reduced from 49.6 ± 2.4 in saline-control group to 18.2 ± 1.5 in noradrenaline preconditioned group. Administration of prazosin, L-NAME, or tempol prior to noradrenaline injection abolished the observed cardioprotection of noradrenaline (45.5 ± 3, 41.7 ± 4.5 and 38.7 ± 5.4, respectively) and restored infarct size to saline-control rats' level. Incidences and severity of ventricular arrhythmia during ischemia and early reperfusion significantly decreased in noradrenaline preconditioned group compared with saline-control group. This cardioprotective effect of noradrenaline against ventricular arrhythmia was abrogated by administration of prazosin, L-NAME, or tempol. CONCLUSION: Cardioprotection effect of the α(1)-adrenoceptor stimulation by noradrenaline was inhibited by L-NAME or tempol in anesthetized rat heart.

Cardioprotective effects of acute sleep deprivation on ischemia/reperfusion injury.

OBJECTIVES: Modulation of sympathetic activity during acute sleep deprivation can produce various effects on body functions. We studied the effects of acute sleep deprivation before ischemia/reperfusion on myocardial injury in isolated rat hearts, and the role of sympathetic nervous system that may mediate these sleep deprivation induced effects. METHODS: The animals were randomized into four groups (n = 11 per group): Ischemia- Reperfusion group (IR), Acute sleep deprivation group (SD), Control group for sleep deprivation (CON-SD) and Sympathectomy + ASD group (SYM-SD). In SD group, sleep deprivation paradigm was used 24 h prior to induction of ischemia/reperfusion. In SYM-SD group, the animals were chemically sympathectomized using 6-hydroxydopamine, 24 h before sleep deprivation. Then, the hearts of animals were perfused using Langendorff setup and were subjected to 30 min regional ischemia followed by 60 min of reperfusion. Throughout the experiment, the hearts were allowed to beat spontaneously and left ventricular developed pressure (LVDP) and rate pressure product (RPP) were recorded. At the end of study, infarct size and percentage of the area at risk were determined. RESULTS: We found that SD increased LVDP and RPP, while reducing the myocardial infarct size. Moreover, sympathectomy reversed SD induced reduction in infarct size and showed no differences as compared to IR. CONCLUSION: This study shows cardioprotective effects of acute sleep deprivation, which can be abolished by chemical sympathectomy in isolated hearts of rats.

Phenylephrine induces early and late cardioprotection through mitochondrial permeability transition pore in the isolated rat heart.

BACKGROUND: The aim of this study was to investigate the role of mitochondrial permeability transition pore (mPTP) in cardioprotection afforded by phenylephrine pretreatment in early and late phases. METHODS: Rat hearts were isolated and perfused with Krebs buffer in Langendorff preparation and subjected to 30 min regional ischemia followed by 60 min of reperfusion. Phenylephrine as a selective α1-adrenoceptor agonist and atractyloside as a specific opener of the mPTP were used. Seven groups (n = 6) of rats were randomly studied: (I) control: surgical procedure was performed with no ischemia/reperfusion, (II) ischemia/reperfusion: hearts underwent regional ischemia/reperfusion, (III) early phenylephrine: phenylephrine (50 µM) was perfused for 5 min prior to ischemia/reperfusion, (IV) late phenylephrine: rats were treated with phenylephrine (10 mg/kg, i.p) 24 h prior to ischemia/reperfusion, (V) early phenylephrine+atractyloside: hearts were perfused with phenylephrine as in group III and then atractyloside (20 mM) 5 min before reperfusion for 20 min, (VI) late phenylephrine+atractyloside: hearts were treated with phenylephrine as in group IV and then received atractyloside (20 mM), 5 min before reperfusion for 20 min, (VII) atractyloside-IR group: hearts were perfused with atractyloside (20 mM) 5 min before reperfusion for 20 min. RESULTS: Compared with ischemia/reperfusion group, perfusion of phenylephrine in early and late phases decreased myocardial infarct size (% of ischemia zone), reduced creatine kinase-MB (CK-MB) in the coronary effluent, and improved cardiac function. Administration of atractyloside abolished cardioprotective effects of phenylephrine in both early and late phases and returned infarct size, CK-MB and cardiac function to levels as seen in ischemia/reperfusion group. CONCLUSION: These results suggest that administration of atractyloside as a specific opener of the mPTP abolishes phenylephrine-induced early and late cardioprotection in the isolated rat hearts.

Post-infarct morphine treatment reduces apoptosis and myofibroblast density in a rat model of cardiac ischemia-reperfusion.

Following myocardial ischemia, the cardiac tissue undergoes both, physiological and pathological changes to compensate the initial loss of function. Long-term continuous adjustments often take a drastic picture indicated by deteriorated ventricular function. Morphine is commonly used for rescuing patients suffering a heart attack. Recent results from our laboratory showed the anti-remodeling potential of morphine. Here, we explored the effect of morphine treatment on gelatinolytic activity, apoptosis and myofibroblast density. The male Sprague - Dawley rats underwent ischemia via ligation of left anterior descending coronary artery and received morphine (3 mg/kg; i.p.) for five consecutive days. Seven days post-MI, morphine led to significant reduction in MMP - 2 activity, apoptotic cell death and fibroblast density. Morphine also reduced MI-induced rise in serum pro-oxidant antioxidant balance and nitrite levels on day 28th following the surgery. These results provide mechanistic insight for morphine - induced anti-remodeling effects.

Detection and Molecular Characterization of Babesia canis vogeli and Theileria annulata in Free-Ranging Dogs and Ticks from Shahriar County, Tehran Province, Iran.

BACKGROUND: We aimed to detect and characterize vector-borne parasites of Babesia and Theileria in dog and ticks by PCR assay. Canine babesiosis is a significant tick-borne disease caused by different Babesia species. As the infection has not been reported in Shahriar region Tehran, Iran, molecular techniques allowed us to identify tick-borne parasites in asymptomatic dogs. METHODS: The number of 40 dog peripheral blood samples and 27 skin attached ticks were analyzed by molecular PCR assay. The specific primers were used for detecting Babesia canis, B. gibsoni and T. annulata. RESULTS: B. c. vogeli was detected in 10 dog blood samples (25%). Additionally, T. annulata infection was identified in 13 dog blood samples (32.5%) and 18 isolated tick DNAs (66.7%). The results of PCR were confirmed by 18S rRNA and Tams1 gene sequence analyzing and have been registered in GenBank under following accession numbers for B. c. vogeli (MH793502) and T. annulata (MK105284). Conclusion: The verification of T. annulata infection in free-ranging dogs and ticks shows dogs might be considered as important natural carriers/reservoirs for T. annulata in enzootic region for bovine theileriosis. The obtained data may be useful for veterinary practitioners and dog owners to aware of Babesia and Theileria infection in dog and tick to establish the effective preventive measures.

Semiconductor laser phase-noise cancellation using an electrical feed-forward scheme.

We demonstrate the reduction of semiconductor laser phase noise by using an electrical feed-forward scheme. We have carried out proof-of-concept experiments on a commercially available distributed-feedback laser emitting at the 1550 nm communication band. The preliminary results show more than 20 times reduction in the phase-noise power spectrum. The feed-forward scheme does not have the limited bandwidth, stability, and speed issues that are common in feedback systems. Moreover, in the absence of electronic noise, feed-forward can completely cancel the close-in phase noise. In this scheme, the ultimate achievable phase noise will be limited by the electronics noise. Using the proposed feed-forward approach, the linewidth of semiconductor lasers can be reduced by 3-4 orders of magnitude in a monolithic approach using today's low-noise scaled transistors with terahertz gain-bandwidth product.

Effect of different doses of noradrenaline against ischemia-induced ventricular arrhythmias in rat heart in vivo.

BACKGROUND: The present study was designed to evaluate the preconditioning effect of different doses of noradrenaline on ischemia-induced ventricular arrhythmias in open chest anesthetized rats. METHODS: The anaesthetized rats were subjected to 25 min of regional ischemia by left descending coronary artery (LAD) occlusion. In sham group, surgical procedures were done but ischemia was not applied. In control rats, saline was injected prior to ischemia. In noradrenaline groups, rats pretreated with three different doses of noradrenaline (respectively, 0.5, 1 and 2 microg/kg, IV). RESULTS: In control rats, induction of ischemia shortened the QTc (corrected QT) interval (ms) and led to occurrence of ventricular arrhythmias. Administration of low-dose of noradrenaline prevented shortening of the QTc interval during ischemia but could not significantly attenuate severity and incidences of arrhythmias. Injection of mid-dose of noradrenaline stabilized the QTc during ischemia and reduced severity of arrhythmias. Pretreatment with high-dose of noradrenaline significantly prolonged the QTc interval and declined severity and incidence of arrhythmias. CONCLUSIONS: Noradrenaline dose-dependently attenuated ischemia-induced ventricular arrhythmias.

Correlation between adolescent chronic emotional stress and incidence of adult cardiovascular disease in female rats.

OBJECTIVES: Association of adolescent emotional stress (ES) with the incidence of cardiovascular disease (CVD) at older age was investigated. MATERIALS AND METHODS: 21 female rats were divided into three groups of 7 each; ES, foot-shock, and control. Chronic ES was induced by exposing the rats to witness foot-shock of their neighboring counterparts in the stress-box system in 5 successive days. 6 weeks after the last stress exposure, M-Mode echocardiographic assessment, qRT-PCR, and western blotting were performed in adult rats to determine the persistent effect of adolescent ES on cardiac performance and gene/protein expression levels of cardiac natriuretic peptide receptor 3 (NPR3) as a biomarker of CVD. RESULTS: Interventricular septum thicknesses in diastole (IVSd) increased from 0.152±0.007 cm to 0.197±0.016 cm (P<0.05), left ventricular posterior wall thickness in diastole (LVPWd) significantly enlarged from 0.169±0.006 cm to 0.288±0.033 cm (P<0.01), left ventricular posterior wall thickness in systole (LVPWs) enlarged from 0.223±0.012 cm to 0.318±0.038 cm (P<0.05), left ventricular mass increased from 1.000±0.024 g to 1.283±0.084 g (P<0.01), and mean heart rate elevated from 229.42±6.57 bpm to 280.29±10.45 bpm (P<0.01). Moreover, ES significantly upregulated the expression levels of cardiac NPR3 gene (P<0.01) and protein (P<0.01). CONCLUSION: The incidence of adult CVD seemed to be increased under the influence of adolescent ES. Consequently, we suggest that mental healthcare during adolescence would be a critical factor for adult CVD prevention.

Acute Physical Stress Preconditions the Heart Against Ischemia/Reperfusion Injury Through Activation of Sympathetic Nervous System.

BACKGROUND: Stress is defined as a complicated state that related to homeostasis disturbances, over-activity of the sympathetic nervous system and hypothalamus-pituitary-adrenal axis responses. Cardiac preconditioning reduces myocardial damages. OBJECTIVE: This study was designed to assess the cardioprotective effects of acute physical stress against ischemia/reperfusion (I/R) injury through the activation of the sympathetic nervous system. METHODS: Thirty-two male Wistar rats were divided into four groups; (1) IR (n = 8): rats underwent I/R, (2) Acute stress (St+IR) (n = 8): physical stress induced 1-hour before I/R, (3) Sympathectomy (Symp+IR) (n = 8): chemical sympathectomy was done 24-hours before I/R and (4) Sympathectomy- physical stress (Symp+St+IR) (n = 8): chemical sympathectomy induced before physical stress and I/R. Chemical sympathectomy was performed using 6-hydroxydopamine (100 mg/kg, sc). Then, the hearts isolated and located in the Langendorff apparatus to induce 30 minutes ischemia followed by 120 minutes reperfusion. The coronary flows, hemodynamic parameters, infarct size, corticosterone level in serum were investigated. P < 0.05 demonstrated significance. RESULTS: Physical stress prior to I/R could improve left ventricular developed pressure (LVDP) and rate product pressure (RPP) of the heart respectively, (63 ± 2 versus 42 ± 1.2, p < 0.05, 70 ± 2 versus 43 ± 2.6, p < 0.05) and reduces infarct size (22.16 ± 1.3 versus 32 ± 1.4, p < 0.05) when compared with the I/R alone. Chemical sympathectomy before physical stress eliminated the protective effect of physical stress on I/R-induced cardiac damages (RPP: 21 ± 6.6 versus 63 ± 2, p < 0.01) (LVDP: 38 ± 4.5 versus 43 ± 2.6, p < 0.01) (infarct size: 35 ± 3.1 versus 22.16 ± 1.3, p < 0.01). CONCLUSION: Findings indicate that acute physical stress can act as a preconditional stimulator and probably, the presence of sympathetic nervous system is necessary.