Reperfusion In Rat Hearts Research Articles

Attenuation of Inflammatory Response and Reduction in Infarct Size by Postconditioning Are Associated with down-regulation of Early Growth Response-1 during Reperfusion in Rat Heart: Erratum.

Attenuation of Inflammatory Response and Reduction in Infarct Size by Postconditioning Are Associated with down-regulation of Early Growth Response-1 during Reperfusion in Rat Heart: Erratum.

Cardioprotective effects of Prolame and SNAP are related with nitric oxide production and with diminution of caspases and calpain-1 activities in reperfused rat hearts.

Cardiac tissue undergoes changes during ischemia-reperfusion (I-R) that compromise its normal function. Cell death is one of the consequences of such damage, as well as diminution in nitric oxide (NO) content. This signaling molecule regulates the function of the cardiovascular system through dependent and independent effects of cyclic guanosine monophosphate (cGMP). The independent cGMP pathway involves post-translational modification of proteins by S-nitrosylation. Studies in vitro have shown that NO inhibits the activity of caspases and calpains through S-nitrosylation of a cysteine located in their catalytic site, so we propose to elucidate if the regulatory mechanisms of NO are related with changes in S-nitrosylation of cell death proteins in the ischemic-reperfused myocardium. We used two compounds that increase the levels of NO by different mechanisms: Prolame, an amino-estrogenic compound with antiplatelet and anticoagulant effects that induces the increase of NO levels in vivo by activating the endothelial nitric oxide synthase (eNOS) and that has not been tested as a potential inhibitor of apoptosis. On the other hand, S-Nitroso-N-acetylpenicillamine (SNAP), a synthetic NO donor that has been shown to decrease cell death after inducing hypoxia-reoxygenation in cell cultures. Main experimental groups were Control, I-R, I-R+Prolame and I-R+SNAP. Additional groups were used to evaluate the NO action pathways. Contractile function represented as heart rate and ventricular pressure was evaluated in a Langendorff system. Infarct size was measured with 2,3,5-triphenyltetrazolium chloride stain. NO content was determined indirectly by measuring nitrite levels with the Griess reaction and cGMP content was measured by Enzyme-Linked ImmunoSorbent Assay. DNA integrity was evaluated by DNA laddering visualized on an agarose gel and by Terminal deoxynucleotidyl transferase dUTP Nick-End Labeling assay. Activities of caspase-3, caspase-8, caspase-9 and calpain-1 were evaluated spectrophotometrically and the content of caspase-3 and calpain-1 by western blot. S-nitrosylation of caspase-3 and calpain-1 was evaluated by labeling S-nitrosylated cysteines. Our results show that both Prolame and SNAP increased NO content and improved functional recovery in post-ischemic hearts. cGMP-dependent and S-nitrosylation pathways were activated in both groups, but the cGMP-independent pathway was preferentially activated by SNAP, which induced higher levels of NO than Prolame. Although SNAP effectively diminished the activity of all the proteases, a correlative link between the activity of these proteases and S-nitrosylation was not fully established.

68 - Mitochondrial STAT3 serine phosphorylation by zinc reduces ROS generation at reperfusion in rat hearts

STAT3 plays a role in the regulation of mitochondrial respiration. This study tested if STAT3 serine phosphorylation by zinc could alter mitochondrial ROS generation in the setting of ischemia/reperfusion in the heart. Under normoxic conditions, treatment of isolated rat hearts with ZnCl2 increased mitochondrial STAT3 phosphorylation at Ser727. In isolated rat hearts subjected to ischemia followed by reperfusion, ZnCl2 increased mitochondrial phospho-STAT3. Moreover, ZnCl2 prevented mitochondrial ROS generation and dissipation of mitochondrial membrane potential (ΔΨm) at reoxygenation through Ser727 phosphorylation. Finally, ZnCl2 suppression of succinate dehydrogenase (SDH) activity upon the onset of reperfusion was nullified by the Ser727 mutation. In conclusion, zinc inhibits mitochondrial ROS generation at reperfusion by increasing mitochondrial STAT3 phosphorylation at Ser727. The inhibition of SDH activity may account for the role of STAT3 in the inhibitory action of zinc on ROS generation at reperfusion.

Lasalocid immediately and completely prevents the myocardial damage caused by coronary ischemia reperfusion in rat heart

Lasalocid, a specific mobile membrane ionophore for calcium, dopamine and norepinephrine was assayed in its capacity to reduce or maintain unaltered the cardiovascular function in conditions of imminent myocardial injury. In experiments of coronary blockade and reperfusion carried out in rat heart, it was found that when administered from 5 to 30 minutes prior to the induction of coronary blockade, at a concentration of 2 mg/kg of body weight, the ionophore immediately, simultaneously, and completely interrupts the blood pressure decay, cardiac frequency increase, electrical ventricular tachycardia and fibrillation, as well as the fall of mitochondrial oxidative phosphorylation and decay of mitochondrial oxygen uptake provoked by the induced myocardial injury. It appears that the molecular mode of action of the lasalocid is associated with its unique ability to transport both calcium and the catecholamines, dopamine and norepinephrine, across mitochondrial and bimolecular lipid membranes, as well as through synaptic cell membrane terminals from rat heart, myocardial fibers of the heart and heart chromaffin membrane vesicles. It is suggested that for the potential medical use of lasalocid to detain incoming ischemic myocardial damage, there exists a need to develop a personal electronic device able to simultaneously monitor, detect, and inform on the very early and simultaneous signs of cardiac alterations of electrical, mechano-chemical, metabolic and hydraulic nature, all which precede heart failure and to administer the lasalocid.

Low-flow ischaemia and reperfusion in rat hearts: energetic of stunning and cardioprotection of genistein.

Low-flow ischemia (LFI) is consequent to coronary disease and produces cardiac stunning during reperfusion (R). Energetic performance and mechanisms of Ca2+ handling during LFI/R are not known. Moreover, cardioprotection of the phytoestrogen genistein (Gen) remains to be demonstrated in LFI/R. The aim was to study the mechanisms of the stunning consequent to LFI/R and the effects of Gen on both sexes. Rat ventricles were perfused inside a calorimeter to measure maximal pressure development (P) and total heat rate (Ht) before and during exposition to LFI/R. The mechanisms of stunning were evaluated with selective drugs. Female hearts (FH) developed higher postischemic contractile recovery (PICR) and muscle economy (P/Ht) than males (MH). Cardioprotection was sensitive to blockade of mKATP channels, UCam and NOS. Perfusion of 20μmol/l Gen reduced PICR and P/Ht during LFI/R in FH, and dysfunction was increased by mNCX blockade with mPTP opening. However, intraperitoneal 5mg/kg Gen (Gen-ip) was cardioprotective in both sexes, and the beneficial effect of Gen-ip was blocked by 100μmol/l 5-HD. FH are more protected than MH against the LFI/R dysfunction, which involves mitochondrial Ca2+ loss; Gen-ip was more cardioprotective in MH than in FH, mainly by activation of the mKATP channels.

Real-Time Fluorescence Measurements of ROS and [Ca2+] in Ischemic / Reperfused Rat Hearts: Detectable Increases Occur only after Mitochondrial Pore Opening and Are Attenuated by Ischemic Preconditioning.

Mitochondrial permeability transition pore (mPTP) opening is critical for ischemia / reperfusion (I/R) injury and is associated with increased [Ca2+] and reactive oxygen species (ROS). Here we employ surface fluorescence to establish the temporal sequence of these events in beating perfused hearts subject to global I/R. A bespoke fluorimeter was used to synchronously monitor surface fluorescence and reflectance of Langendorff-perfused rat hearts at multiple wavelengths, with simultaneous measurements of hemodynamic function. Potential interference by motion artefacts and internal filtering was assessed and minimised. Re-oxidation of NAD(P)H and flavoproteins on reperfusion (detected using autofluorescence) was rapid (t0.5 < 15 s) and significantly slower following ischemic preconditioning (IP). This argues against superoxide production from reduced Complex 1 being a critical mediator of initial mPTP opening during early reperfusion. Furthermore, MitoPY1 (a mitochondria-targeted H2O2-sensitive fluorescent probe) and aconitase activity measurements failed to detect matrix ROS increases during early reperfusion. However, two different fluorescent cytosolic ROS probes did detect ROS increases after 2–3 min of reperfusion, which was shown to be after initiation of mPTP opening. Cyclosporin A (CsA) and IP attenuated these responses and reduced infarct size. [Ca2+]i (monitored with Indo-1) increased progressively during ischemia, but dropped rapidly within 90 s of reperfusion when total mitochondrial [Ca2+] was shown to be increased. These early changes in [Ca2+] were not attenuated by IP, but substantial [Ca2+] increases were observed after 2–3 min reperfusion and these were prevented by both IP and CsA. Our data suggest that the major increases in ROS and [Ca2+] detected later in reperfusion are secondary to mPTP opening. If earlier IP-sensitive changes occur that might trigger initial mPTP opening they are below our limit of detection. Rather, we suggest that IP may inhibit initial mPTP opening by alternative mechanisms such as prevention of hexokinase 2 dissociation from mitochondria during ischemia.

Valsartan-induced cardioprotection involves angiotensin II type 2 receptor upregulation in isolated ischaemia and reperfused rat hearts

The angiotensin II type 1 receptor (AT1R) antagonist protects the heart against acute ischaemia-reperfusion injury. The underlying mechanism is unclear. To determine the eff ects of angiotensin II type 1 receptor blockade, valsartan on AT1 and AT2 receptor during ischaemia reperfusion in isolated rat, the hearts of 24 SD rats were isolated, linked to Langendorff perfusion apparatus, and exposed to ischaemia for 30 min. The l eft ventricular systolic pressure, maximal uprising velocity of left ventricular pressure (+dp/dtmax), maximal decreasing velocity of left ventricular pressure (-dp/dtmax) and coronary fl ow were measured after stabilization of the perfusion. The isoenzyme of creatine kinase in the effl uent liquid from the heart, AT1and AT2 receptor mRNA and protein expression were measured after stabilization of the perfusion. The results showed that ischaemia-reperfusion induced a marked decrease in left ventricular systolic pressure, +dp/dtmax and -dp/dtmax, indicating severe cardiac dysfunction and decreased coronary effl uence. Concurrently, myocardial AT1 and AT 2 receptor mRNA and protein expression were increased with valsartan. However, AT2 receptor mRNA and protein expression decreased during ischaemia-reperfusion. The creatine kinase levels at diff erent time points of the valsartan group were signifi cantly lower. The results suggested that valsartan improved left ventricular function and increased coronary effl uence because the angiotensin receptor blocker valsartan induced cardioprotection associated with upregulating AT2 receptor protein and mRNA expression after ischaemia-reperfusion in isolated rats.

Apocynum venetum leaf attenuates myocardial ischemia/reperfusion injury by inhibiting oxidative stress.

Apocynum venetum, a Chinese medicinal herb, is reported to be neuroprotective. However, whether Apocynum venetum leaf extract (AVLE) protects against ischemic myocardium remains elusive. Our present study was aimed to observe the effects of AVLE preconditioning on myocardial ischemia/reperfusion (MI/R) injury and to investigate the possible mechanisms. Rats were treated with AVLE (500 mg/kg/d, o.g.) or distilled water once daily for one week. Afterward, all the animals were subjected to 30 min of myocardial ischemia followed by 4 h of reperfusion. AVLE preconditioning for one week significantly improved cardiac function following MI/R. Meanwhile, AVLE reduced infarct size, plasma creatine kinase (CK)/lactate dehydrogenase (LDH) activities and myocardial apoptosis at the end of reperfusion in rat hearts. Moreover, AVLE preconditioning significantly inhibited superoxide generation, gp91(phox) expression, malonaldialdehyde formation and enhanced superoxide dismutase (SOD) activity in I/R hearts. Furthermore, AVLE treatment increased Akt and extracellular regulated protein kinases 1/2 (ERK1/2) phosphorylations in I/R rat heart. Either the Phosphatidylinositide 3-kinase (PI3K) inhibitor wortmannin or the ERK1/2 inhibitor PD98059 blocked AVLE-stimulated anti-oxidative effects and cardioprotection. Our study demonstrated for the first time that AVLE reduces oxidative stress and exerts cardioprotection against MI/R injury in rats.

Glycyrrhetinic Acid Protects the Heart from Ischemia/Reperfusion Injury by Attenuating the Susceptibility and Incidence of Fatal Ventricular Arrhythmia During the Reperfusion Period in the Rat Hearts

Background/Aims: Licorice has been used to treat many diseases, including palpitations, in both Eastern and Western societies for thousands of years. It has been reported that glycyrrhetinic acid (GA), an aglycone saponin extracted from licorice root, exerts protective effects on the cardiovascular system, limits infarct sizes and protects against the development of arrhythmia. However, the mechanisms underlying the effects of glycyrrhetinic acid on the cardiovascular system remain poorly understood. This study aimed to determine the mechanisms underlying the protective effects of GA against lethal cardiac arrhythmias induced via ischemia-reperfusion in rat hearts, and to examine its electropharmacological properties. Materials and Methods: Anesthetized rats were divided into control (CTL), GA5, GA10, and GA20 groups. GA was administered intravenously 15 min before the occlusion of the left anterior descending coronary artery, at dosages of 5, 10 and 20 mg/kg, respectively. Single ventricular myocytes were isolated using enzymolysis. The whole-cell patch clamp technique was utilized to record Ica, L, Ito and action potentials (APs). Results: During reperfusion, the incidence of ventricular fibrillation (VF) was decreased in each of the groups compared with the CTL group (p<0.05). The ventricular tachycardia (VT)/VF score was significantly decreased in the GA20 group. Action potential durations (APDs) were prolonged by GA; both L-type calcium current (Ica-L) and transient outward potassium current (Ito) were blocked in a concentration-dependent manner by GA. Conclusion: These results suggest that GA attenuates both the susceptibility to and the incidence of fatal ventricular arrhythmia during reperfusion in rat hearts via the prolongation of the APD and the inhibition of both Ica-L and Ito. GA appears to be a promising antiarrhythmic agent in the setting of ischemia/reperfusion.

Biochemical and Physiological Studies of Ischemia-Reperfusion in (Doca)-Salt Hypertensive Rat Heart

Abstract Using a (DOCA)-salt arterial hypertension rat model we aimed to test on isolated, ischemised and reperfused rat heart, physiological parameters as well as biochemical markers, both in myocardium and in plasma, in order to characterize modifications induced by DOCA-salt treatment. In our study we used 20 rats of 10 months old divided into two groups of 10 rats each: control and treated. The treated group has received for 4 weeks 2 subcutaneous injections/week with DOCA (20 mg/b.w. in solution of 0.9% NaCl+0.2% KCl) according to the protocol, and 10-14 days since the last dose of treatment, the animals have been sacrificed. Coronary flow (CF), heart rate (HR) and left ventricle developed pressure (LVDP) have been measured on isolated and perfused Langendorff heart system at a constant pressure and total lipids, cholesterol, HDL and LDL, lipid peroxides as well as GGT, LDH, CK have been assessed using standard biochemical methods and Randox and Sigma kits. As results, there was an increase in C.F, H.R. and LVPD in DOCA-salt treated hearts, accounting for an intense mechanic cardiac activity generated by the hypertension following DOCA-salt treatment, accompanied by an increase in lipid peroxide, in CK and LDH as markers of myocardial lesion and a reduction of GGT activity in myocardial tissue probably due to hypoxia generated by the cardiac insufficiency following the increase in arterial blood pressure and a decrease in antioxidant potential . DOCA-salt hypertension is associated with rapid development of high blood pressure, vascular growth, vascular stiffening, and cardiac hypertrophy with increasing in mechanical activity of the heart, and a decrease in GGT activity and in antioxidant potential.

P165Magnesium orotate in high concentration elicits cardioprotection via modulation of mitochondrial functions

Modulation of mitochondrial function in the settings of ischemia/reperfusion (I/R) injury represents a major therapeutic target of pharmacological agents able to reduce the cell death at reperfusion. The aim of this study was to compare the effects of acute administration of magnesium orotate (MO), MgCl2, orotic acid (OA) with those elicited by the classic mitochondrial permeability transition pore (mPTP) desensitizer, cyclosporine A (CsA) in two experimental settings. The pharmacological agents were administered: i) at reoxygenation in neonatal cardiomyocytes subjected to 4 hours simulated ischemia followed by 2 hours reoxygenation with the assessment of cell viability and reactive oxygen species (ROS) generation, and ii) at reperfusion in isolated rat hearts subjected to 30 min of global ischemia and 120 min of reperfusion. In the latter model myocardial functional recovery (at 30 min of reperfusion) and infarct size (at 120 min of reperfusion) were assessed. In a separate group of animals, mitochondria were isolated at 15 min of reperfusion after global ischemia, and mitochondrial respiration, ROS production (Amplex Red) and calcium retention capacity were assessed. Acute administration of 5 mM MO, MgCl2, OA or 1 μM CsA in neonatal cardiomyocytes subjected to simulated ischemia/reoxygenation enhanced cell survival; these protective effects were not associated with changes in ROS production during reoxygenation. During the postischemic reperfusion in rat hearts and isolated mitochondria, respectively, MO, MgCl2 (5 mM both) and CsA (0.2 μmol/L), but not OA: (i) induced an important recovery of left ventricular end-diastolic pressure (LVDP), and decreased infarct size vs. controls, and (ii) protected against loss of outer mitochondrial membrane integrity and subsequent deficits in electron transport and also inhibited the calcium triggered-mPTP opening. In particular, the effects of MO were comparable to the ones elicited by CsA. In conclusion, acute administration of magnesium orotate in high concentration during the postischemic reperfusion is associated with cardioprotective effects via modulation of mitochondria functions.

Attenuation of Inflammatory Response and Reduction in Infarct Size by Postconditioning Are Associated With Downregulation of Early Growth Response 1 During Reperfusion in Rat Heart

Early growth response 1 (EGR-1) works as a master regulator that plays a key role in triggering inflammation-induced tissue injury after ischemia and reperfusion. This study tested the hypothesis that postconditioning (Postcon) or anti-inflammatory compound, curcumin, ameliorates inflammatory responses and further reduces infarct size by normalizing EGR-1 expression during reperfusion. In the control group, male Sprague-Dawley rats were subjected to 30-min ischemia and 180-min reperfusion. Postcon with four cycles of 10-s/10-s reperfusion/ischemia was applied at the onset of reperfusion. Curcumin (150 mg/kg per day) was fed 5 days before ischemia. Relative to the control, Postcon reduced expression of EGR-1 mRNA and protein, as further identified by less EGR-1 immunoreactivity in myocardial nuclei and microvessels during reperfusion. Along with EGR-1 downregulation, levels of plasma and myocardial tumor necrosis factor α and interleukin 6 (IL-6) were significantly decreased. Upregulated P-selectin and intercellular adhesion molecule 1 mRNA and protein as well as their immunoreactivity at area at risk myocardium were significantly attenuated. Neutrophil extravasation identified by myeloperoxidase immunohistochemical staining was inhibited. Infarct size, determined with triphenyltetrazolium chloride staining, was smaller in the Postcon group than that in the control. The protection achieved with pretreatment with curcumin was comparable to the benefits gained by Postcon in all end points measured. In H9C2 rat cardiomyoblast cell line, EGR-1 siRNA downregulated hydrogen peroxide-induced EGR-1 mRNA expression and subsequently reduced tumor necrosis factor α mRNA level. These results suggest that EGR-1 seems to play a critical role in myocardial reperfusion injury because downregulation of EGR-1 either by Postcon or the use of pharmacological intervention reduces infarct size, most likely through an inhibition of inflammation-mediated processes.

Achyranthes bidentata Polypeptides Reduces Oxidative Stress and Exerts Protective Effects against Myocardial Ischemic/Reperfusion Injury in Rats

Achyranthes bidentata, a Chinese medicinal herb, is reported to be neuroprotective. However, its role in cardioprotection remains largely unknown. Our present study aimed to investigate the effects of Achyranthes bidentata polypeptides (ABPP) preconditioning on myocardial ischemia/reperfusion (MI/R) injury and to test the possible mechanisms. Rats were treated with ABPP (10 mg/kg/d, i.p.) or saline once daily for one week. Afterward, all the animals were subjected to 30 min of myocardial ischemia followed by 4 h of reperfusion. ABPP preconditioning for one week significantly improved cardiac function following MI/R. Meanwhile, ABPP reduced infarct size, plasma creatine kinase (CK)/lactate dehydrogenase (LDH) activities and myocardial apoptosis at the end of reperfusion in rat hearts. Moreover, ABPP preconditioning significantly inhibited superoxide generation, gp91phox expression, malonaldialdehyde formation and enhanced superoxide dismutase activity in I/R hearts. Furthermore, ABPP treatment inhibited PTEN expression and increased Akt phosphorylation in I/R rat heart. PI3K inhibitor wortmannin blocked Akt activation, and abolished ABPP-stimulated anti-oxidant effect and cardioprotection. Our study demonstrated for the first time that ABPP reduces oxidative stress and exerts cardioprotection against MI/R injury in rats. Inhibition of PTEN and activation of Akt may contribute to the anti-oxidant capacity and cardioprotection of ABPP.

研究 灌流液H+緩衝能増強による虚血後再灌流時の心機能回復の改善

研究 灌流液H+緩衝能増強による虚血後再灌流時の心機能回復の改善

Low-dose bisphenol A and estrogen increase ventricular arrhythmias following ischemia–reperfusion in female rat hearts

Bisphenol A (BPA) is an environmental estrogenic endocrine disruptor that may have adverse health impacts on a range of tissue/systems. In previous studies, we reported that BPA rapidly promoted arrhythmias in female rodent hearts through alteration of myocyte calcium handling. In the present study we investigated the acute effects of BPA on ventricular arrhythmias and infarction following ischemia-reperfusion in rat hearts. Rat hearts were subjected to 20 min of global ischemia followed by reperfusion. In female, but not male hearts, acute exposure to 1 nM BPA, either alone or combined with 1 nM 17β-estradiol (E2), during reperfusion resulted in a marked increase in the duration of sustained ventricular arrhythmias. BPA plus E2 increased the duration ventricular fibrillation, and the duration of VF as a fraction of total duration of sustained ventricular arrhythmia. The pro-arrhythmic effects of estrogens were abolished by MPP combined with PHTPP, suggesting the involvements of both ERα and ERβ signaling. In contrast to their pro-arrhythmic effects, BPA and E2 reduced infarction size, agreeing with previously described protective effect of estrogen against cardiac infarction. In conclusion, rapid exposure to low dose BPA, particularly when combined with E2, exacerbates ventricular arrhythmia following IR injury in female rat hearts.

A proteolytic cleavage to separate the sarcolemma/T‐tubule from the sarcoplasmic reticulum

A proteolytic cleavage to separate the sarcolemma/T‐tubule from the sarcoplasmic reticulum

Hypoxic Preconditioning Prevents Induction and Activation of 5-Lipoxygenase during Ischemia and Reperfusion of Rat Heart

Hypoxic Preconditioning Prevents Induction and Activation of 5-Lipoxygenase during Ischemia and Reperfusion of Rat Heart

IS ZINC CRITICAL FOR MYOCARDIAL REPERFUSION INJURY?

ObjectivesThe purpose of this study was to investigate the role intracellular free zinc in myocardial reperfusion injury.MethodsIsolated perfused rat hearts were subjected to 30 min ischaemia followed by 2 h...

Oxytocin protects cardiomyocytes from apoptosis induced by ischemia–reperfusion in rat heart: Role of mitochondrial ATP-dependent potassium channel and permeability transition pore

The current study examines the protective effect of oxytocin (OT) on cardiomyocyte apoptosis modulated by mitochondrial ATP-dependent potassium (mitoKATP) channel and permeability transition pore (mPTP) in the preconditioned myocardium of anesthetized rats. Eighty rats were equally divided into eight groups. The hearts of all animals except for the sham group were subjected to 25min ischemia and 120min reperfusion. Oxytocin, 5-hydroxydeconoate (5-HD), a specific inhibitor of the mitoKATP channel, and atractyloside (ATRC), an mPTP opener, were used prior to ischemia. Hemodynamic parameters were recorded throughout the experiment. Evaluations were made by infarct size, plasma lactate dehydrogenase level (LDH), transmission electron microscopy (TEM) and immunohistochemistry studies. OT prevented mean arterial pressure drop during early phase of ischemia and reperfusion. Treatment with OT before IR induction normalizes cardiomyocytes both in light microscopy and TEM observations. In addition, OT significantly reduced TUNEL- and increased Bcl-2-labeled positive cell number relative to IR (p<0.05). However, 5HD or ATRC inhibited the protective effects of OT on cardiomyocytes damaged by IR (p<0.05). Ultrastructural changes including extensive myofibril loss, sarcolemmal disruption and mitochondrial swelling due to amorphous dens bodies indicate necrosis induction in 5HD and ATRC as well as in IR groups. Restoration of immunohistochemistry parameters and protection against IR-induced ultrastructural changes confirm OT cardioprotective effects via mitoKATP channel and mPTP modulation in apoptosis induced by ischemia–reperfusion.

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.