جستجوی مقالات مرتبط با کلیدواژه "cardioprotection" در نشریات گروه "پزشکی"

Lethal ventricular arrhythmias are a significant clinical concern following reperfusion therapies in elderly patients with myocardial infarction. The combination of multi-target therapies to achieve optimal anti-arrhythmogenesis and improve the chances of successful translation for patient benefit has prompted considerable interest. This study examined the anti-arrhythmic effect of nicotinamide mononucleotide (NMN)/ubiquinol combination treatment following myocardial ischemia/reperfusion (IR) injury in aged rats, with an emphasis on the role of oxidative stress and nitric oxide (NO).

Male Wistar rats (n=30, 22-24 months old, 400-450 g) were randomized into five groups with or without IR and/or NMN and ubiquinol, either alone or in combination. NMN (100 mg/kg/48 hours) was administered intraperitoneally for 28 days before IR, and ubiquinol (30 mg/kg) was injected intravenously at early reperfusion. Electrocardiographic signals were recorded during the ischemia and the first 30 minutes of reperfusion. Two hours after reperfusion, myocardial hemodynamic and LDH release were measured, and the left ventricle samples were obtained to evaluate oxidative stress markers and NO levels.

NMN/ubiquinol combination treatment significantly minimized the occurrence and severity of IR-induced arrhythmias, improved myocardial function, and reduced LDH release (P<0.05). It also decreased MDA content, increased superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT) activities, and enhanced NO formation (P<0.05). This combined treatment showed greater efficacy than the single treatments.

This study revealed the anti-arrhythmic effect of NMN/ubiquinol combination treatment in IR-treated aged rats, which may be associated with reduced oxidative stress and increased NO formation. This combinational approach deserves more investigation due to its potential to confer better anti-arrhythmic effect during aging.

Myocardial arrhythmia is a major complication of ischemia-reperfusion (I/R) injury in patients with diabetes. Irisin has significant cardioprotective effects, while its role in the pathophysiology of I/R injury-induced myocardial arrhythmia in the presence of diabetes is not well identified. Here, we aimed to investigate the potential antiarrhythmic impacts and mechanisms (mitochondrial biogenesis, endoplasmic reticulum (ER) stress, and pyroptosis) by which irisin reduces I/R injury-induced myocardial arrhythmia in diabetic rats.

Thirty high-fat diet-induced diabetic rats were subjected to I/R injury and myocardial arrhythmia. Irisin (0.5 μg/kg/day) was injected intraperitoneally before induction of I/R injury. Electrocardiography was used to measure the incidence and severity of ventricular arrhythmias. ELISA and western blotting analyses were employed to quantify the expression of mitochondrial biogenesis, ER stress, and pyroptosis-related proteins in ischemic myocardium.

Irisin treatment in diabetic rats significantly decreased the lactate dehydrogenase level and the number and severity of arrhythmia induced by I/R injury. Irisin up-regulated the expression of mitochondrial biogenesis-related proteins while down-regulating the expression of ER stress and pyroptosis-related proteins. Furthermore, the inhibition of mitochondrial quality control by mdivi-1 significantly abolished the cardioprotective effect of irisin.

Our findings suggest that irisin reduced myocardial arrhythmia induced by I/R injury in diabetic rats by modulating the interaction of mitochondrial biogenesis and ER stress proteins and inhibiting the pyroptosis pathway. These findings provide a promising strategy for managing myocardial arrhythmia in diabetic patients, but supplementary studies are needed to confirm the clinical efficacy of irisin in these patients.

Background:

 Plant secondary metabolites have been reported to offer a wide variety of medicinal purposes, including protection against heavy metal toxicity.

Objectives: 

This study aimed to investigate the potentiality of naringenin a flavonoid in ameliorating the antioxidant defense system of neural and cardiac cells against aluminum chloride (AlCl3 ) toxicity in rats.

Methods: 

The rats were divided into control (group 1), AlCl3 -treated (2), AlCl3+Naringenin-treated (3), and Naringenin-treated (4) groups. During experimentation, group 2 received an oral dose of 100 mg/kg/BW of AlCl3 , and group 3 received 100 mg/kg/BW of AlCl3 and 50 mg/ kg/BW of naringenin. In addition, group 4 received 50 mg/kg/BW of naringenin each day, while group 1 and all groups received a normal diet and water ad libitum for 30 days. The animals were sacrificed, and then blood, brain, and heart tissues were collected for biochemical and histological studies.

Results: 

The results revealed that naringenin administration ameliorates the antioxidant defense system (catalase [CAT], superoxide dismutase [SOD], glutathione peroxidase [GPx], and glutathione transferase) in AlCl3 toxicity in neural and cardiac tissues. AlCl3 caused oxidative tissue damage, showing a significant increase in malondialdehyde (MDA) (P<0.05) in both tissues. The levels of neurotransmitter acetylcholine esterase, nitric oxide, and lactate dehydrogenase (LDH) in the rats of group 3 were significantly (P<0.05) higher compared with AlCl3 -intoxicated rats. Furthermore, the AlCl3 -administered group had significantly (P<0.05) elevated levels of total cholesterol (TC), triglycerides, and low-density lipoprotein-cholesterol, with reduced high-density lipoprotein-cholesterol levels in comparison to the naringenin-treated and control groups. Naringenin treatment normalized the lipid profile. Histological analysis using the hematoxylin and eosin staining method revealed that AlCl3 caused degenerative changes in the cerebellum and cardiac tissues, which were ameliorated by co-treatment with naringenin.

Conclusion: 

Naringenin has the potential to mitigate AlCl3 -induced oxidative stress (OS) in the neural and cardiac tissues of rats by enhancing the antioxidant defense system and reversing tissue injuries in the brain and heart.

Ischemia is a common condition in the population and has become one of the leading causes of mortality in recent years. It occurs due to a shortage of oxygen in the cell caused by inadequate blood flow, leading to the formation of free radicals. These free radicals can bind to the phospholipids in the cell membrane, resulting in proxy radicals and lipid hydroperoxidation. Malondialdehyde (MDA) is a cytotoxic byproduct of lipid peroxidation that causes cell damage and necrosis by rupturing the cell membrane. Subsequently, mitochondrial dysfunction related to fatty acid oxidation can develop, further exacerbating the damage caused by ischemia. Reactive oxygen species (ROS) produced in mitochondria have been shown to elevate oxidative phosphorylation disorder and disrupt the functioning of complexes I and IV. These enzyme activities can be restored to normal levels by activating antioxidant enzymes such as superoxide dismutase (Mn-SOD) and catalase, thereby strengthening the antioxidant defense system. Various antioxidants have been found to have protective effects. In this review, we compare the antioxidant effects of various plants and tannins that have been studied up to this point on myocardial ischemia. We also explain some of the cellular and molecular pathways that have been investigated to protect the myocardium against ischemia-reperfusion injury.

 Atherosclerosis is a complicated cascade of inflammatory processes, oxidative stress, and apoptosis, making it the most prevalent cardiovascular disease. The onset and progression of cardiovascular diseases are greatly influenced by oxidative stress. Targeting oxidative stress is an effective strategy for treating such diseases. Marrubiin is a bioactive furan labdane diterpenoid acts as a strong antioxidant to protect against oxidative damage. This study aimed to investigate the protective effects of marrubiin against oxidative stress and apoptosis in a cellular model of the vascular system.

 Human umbilical vein endothelial cells were treated with varying concentration of marrubiin and its IC50 value was determined. The antioxidant potential of marrubiin was assessed by measuring the intracellular level of glutathione (GSH) using a colorimetric technique. Since apoptosis plays a significant role in the plaque rupture, the study also evaluated the protective effects of marrubiin on the expression of key genes involved in apoptotic pathways.

 Cells treated with marrubiin showed increased GSH levels compared to cell therapy control cells, indicating marrubiin’s ability to counteract the effects of TNF-α’s on GSH levels. Furthermore real-time PCR analysis demonstrated that marrubiin upregulated Bcl-xl while downregulating caspase3 and Nox4 in treated cells. These findings suggest that marrubiin protects against apoptosis and oxidative stress.

 Based on our findings, marrubiin is recommended as a preventive/therapeutic treatment for diseases caused by elevated intracellular reactive oxygen species levels in cardiovascular diseases.

A major clinical challenge in ischemic heart disease is the prevention of myocardial injury following ischemia/reperfusion (I/R). Application of natural pharmaceuticals seems to be clinically interesting due to their multiplex activities. Protective effects of troxerutin (TXR) in myocardial I/R injury have been ever demonstrated, nevertheless, the purpose of this study is to explore the role of mitochondrial adenosine triphosphate -sensitive potassium (mitoKATP) channels and toll-like receptor 4 (TLR4)-nuclear factor kappa B (NF-κB) pathway in cardioprotective effects of TXR against I/R injury in rats. Male Wistarrats (n=72, 250–300 g, 12 weeks old) were randomized into groups with/without I/R and/or TXR and 5-hydroxydecanoate(5-HD), alone or in combination. To induce I/Rmodel, the langendorff-perfused hearts were subjected to left anterior descending coronary artery (LAD) ligation and re-opening. TXR (150mg/kg/day) was administered for 4 weeks before I/R. Moreover, 5-HD (100 μM) was added to the perfusion solution before the ischemia. Finally, myocardial infarct size, LDH release, protein expression levels of TLR4 and NF-κB, and the levels of pro-inflammatory cytokines (TNF-α and IL-1β) were assessed. TXR preconditioning significantly reduced IS and LDH release (P<0.05). Furthermore, it decreased the expression of TLR4 and NF-κB and the levelof pro-inflammatory cytokines (P<0.05 to P<0.01). Inhibition of mitoKATPchannels by 5-HD significantly reversed the cardioprotective effects of TXR. This work shed some light on the knowledge about the mechanisms involved in the anti-inflammatory effect of TXR preconditioning in myocardial I/R injury. This effect may be partly mediated through mitoKATPchannels opening and subsequent suppression of the TLR4/NF-κB pathway.

Myocardial infarction (MI) is the leading cause of death among cardiovascular diseases. Reperfusion, the most harmful phase, is accompanied byinflammatory, oxidative, andapoptotic cascades in cardiomyocytes, impairing thehemodynamic and histologic status of the cardiac tissue. The Scrophularia genus is well known for the cardioprotective effects of its species, showing beneficial impacts on blood pressure and arrhythmias in previous studies.

Regarding the mechanisms involved in MI and the cardioprotective effects of the Scrophularia genus, in this study, we evaluated the cardioprotective effects of Scrophularia atropatana on MI.

Isoproterenol (ISO) injections (100 mg/kg, sc, 24-hour intervals) were used to induce MI in rats. In intervention groups, two hours after the first ISO injection, 5, 10, and 20 mg/kg S. atropatana extract was administered by gavage (24-hour intervals) for three days. Cardiac hemodynamic parameters were measured by placing a catheter into the right carotid artery and the left ventricle. Total antioxidant status (TAS), malondialdehyde (MDA) and lactate levels, and histopathologic changes were evaluated.

Induction of MI was accompanied by declined median arterial pressure (MAP), left ventricular systolic pressure (LVSP), and total antioxidant status (TAS) levels. In contrast, the heart rate, left ventricle end-diastolic pressure (LVEDP), malondialdehyde (MDA), and lactate levels were elevated in the MI group. Scrophularia atropatana treatment increased the MAP, LVSP, and TAS levels and significantly reduced the heart rate, LVEDP, MDA, and lactate levels. Also, S. atropatana treatment prevented histopathologic changes post-MI.

The improving effects of S. atropatana on MI injuries suggest its potential as a complementary cardioprotective medication.

The present study examined the effects of a 10-week preconditioning with moderate-intensity aerobic exercise and curcumin supplementation before ischemia-reperfusion (IR) to investigate if this method contributes to the protection of cardiac myocardium against IR-induced injury and left ventricular dysfunction in rat.

Male Wistar rats (6-8 weeks old) were randomly assigned to the 5 groups (each with 10 rats), sedentary-control (Sed-CON), sedentary ischemia-reperfusion (Sed-IR), exercise with IR (Ex-IR), curcumin with IR (Cu-IR), and both exercise and curcumin with IR (Ex-Cu-IR). Exercise intervention performed five times a week for 10 weeks. After the training period, arrhythmias and electrocardiogram parameters, factors involved in cardiac structure and function, and infarct size of myocardium were investigated.

We observed that a 10-week moderate-intensity aerobic exercise (15-45 min at 12-24 m/min) five sessions a week as well as curcumin supplementation (50 mg/kg) over the mentioned period, in advance to IR, significantly decreased IR-induced infarct size in Ex-IR, Cu-IR, and Ex-Cu-IR groups compared to Sed-IR (P = 0.0001), alleviated arrhythmia by reduction in ventricular ectopic beats episodes in Ex-IR, Cu-IR, and Ex-Cu-IR groups compared to Sed-IR (P = 0.001), decreased ventricular tachycardia episods in Ex-IR, Cu-IR, and Ex-Cu-IR groups in comparison to that of Sed-IR group (P = 0.001) and improved cardiac function (P = 0.001).

According to our findings, exercise has superior cardioprotective effects than curcumin. The combination of curcumin and exercise has no preference on exercise or curcumin alone. Hence both long-term aerobic exercise and curcumin supplementation are effective cardioprotectors against IR-induced injury.

Literature has shown the effects of intravenous/intracoronary nicorandil on increased myocardial salvage in patients with ST-segment elevation myocardial infarction (STEMI) treated with mechanical reperfusion. However, the possible cardioprotective effect of oral nicorandil on the clinical outcome prior to primary coronary angioplasty is not well documented. Our aim was to assess the effect of oral nicorandil on primary percutaneous coronary intervention (PPCI).

A total of 240 patients with acute STEMI undergoing PPCI were randomly assigned to oral nicorandil (Intervention, n=116) and placebo (Control, n=124) groups. The intervention group received 20 mg oral nicorandil at the emergency department and another 20 mg oral nicorandil in the catheterization laboratory just before the procedure. The control group received matched placebo. Our primary outcome was ST-segment resolution ≥50% one hour after primary angioplasty. Secondary outcome was in-hospital major adverse cardiovascular events (MACE), defined as a composite of death, ventricular arrhythmia, heart failure and stroke.

In the patients of intervention and control groups, the occurrence of ST-segment resolution ≥ 50% were 68.1% and 62.9% respectively, (P=0.27). In-hospital MACE occurred less frequently in the intervention group, compared to placebo group (11.2% vs. 22.5%, P=0.012).

Although the administration of oral nicorandil before primary coronary angioplasty did not improve ST-segment resolution in patients with acute STEMI, its promoting effects was remarkable on in-hospital clinical outcomes.

To study the effect of acute and repeated stress on cardioprotection-induced by remote ischemic preconditioning (RIPC). RIPC was induced by giving 4 short cycles of ischemia and reperfusion, each consisting of five min. The Langendorff’s apparatus was used to perfuse the isolated rat hearts by subjecting the hearts to global ischemia of 30 min and reperfusion of 120 min. The coronary effluent was collected to measure the levels of lactate dehydrogenase (LDH) and creatine kinase (CK) for the assessment of injury to the myocardium. Myocardial infarct size was measured by the use of triphenyl tetrazolium chloride. Acute stress was induced by subjecting the animals to cold immersion stress for 5 min. However, in the case of stress adaptation, rats were exposed to a homotypic stressor (cold-water immersion stress) each of 5 min duration for five consecutive days. RIPC demonstrated a significant decrease in ischemia-reperfusion-induced myocardial injury in terms of decrease in LDH, CK, and infarct size. However, acute stress for five minutes prior to RIPC significantly abolished its cardioprotective effects. Exogenous administration of adenosine restored RIPC-induced cardioprotective effects in the presence of acute stress. On repeated stress exposure for 5 days, stress adaptation was noted, and there was no effect of repeated stress exposure on RIPC-induced cardioprotection. However, the cardioprotective effects of adenosine were absent in the case of rats subjected to repeated episodes of stress. Acute stress, but not repeated stress exposure, may alter the release of adenosine during RIPC, which may be manifested in the form of reduced cardioprotection during ischemic-reperfusion injury.

This study explored the inter-relationship among nitric oxide, opioids, and KATP channels in the signaling pathway underlying remote ischemic preconditioning (RIPC) conferred cardioprotection. Blood pressure cuff was placed around the hind limb of the animal and RIPC was performed by 4 cycles of inflation (5 min) followed by deflation (5 min). An ex vivo Langendorff’s isolated rat heart model was used to induce ischemia (of 30 min duration)-reperfusion (of 120 min duration) injury. RIPC significantly decreased ischemia-reperfusion associated injury assessed by decrease in myocardial infarct, LDH and CK release, improvement in postischemic left ventricular function, LVDP, dp/dtmax, and dp/dtmin. Pretreatment with L-NAME and naloxone abolished RIPC-induced cardioprotection. Moreover, preconditioning with sodium nitroprusside (SNP) and morphine produced a cardioprotective effect in a similar manner to RIPC. L-NAME, but not naloxone, attenuated RIPC and SNP preconditioning-induced increase in serum nitrite levels. Morphine preconditioning did not increase the NO levels, probably suggesting that opioids may be the downstream mediators of NO. Furthermore, glibenclamide and naloxone blocked cardioprotection conferred by morphine and SNP, respectively. It may be proposed that the actions of NO, opioids, and KATP channels are interlinked. It is possible to suggest that RIPC may induce the release of NO from endothelium, which may trigger the synthesis of endogenous opioids, which in turn may activate heart localized KATP channels to induce cardioprotection.

Dietary n-3 polyunsaturated fatty acids have positive effects on the heart. The present study investigated the effects of pretreatment with fish oil (FO) and flaxseed oil (FLO) on the heart of the rat, which is associated with the isoprenaline (ISO)-induced myocardial injury. The study was conducted on 40 male Wistar rats which were included in control, ISO, FO + ISO, and FLO + ISO groups (each containing 10 rats). In ISO rats, acute myocardial ischemia was induced by ISO while in FO + ISO group, the rats were pretreated with FO orally for 4 weeks. Finally, rats in the FLO + ISO group received pretreatment with FO and flaxseed oil orally for 4 weeks. Eventually, the histopathological examinations of the cardiac tissues and serum activity of creatine kinase-MB (CK-MB) were assessed. Moreover, mitochondria were isolated to examine the mitochondrial swelling. Based on the results, ISO administration significantly increased the serum CK-MB activity compared to the control group. In addition, severe muscular damage to the heart was observed in more than 70% of the rats in ISO group. However, a remarkable decrease in the intensity of heart tissue destruction, as well as the serum levels of CKMB was found in the FO + ISO group compared to the ISO group. Conversely, there was no significant decrease in the serum level of CKMB in FLO + ISO group compared to the ISO group. In general, pretreatment with FLO significantly suppressed the intensity of heart tissue destruction compared to the myocardial ischemic group. FO and FLO led to a decrease in CaCl2-induced swelling in the mitochondria. Therefore, FO and FLO result in protecting against ischemia/reperfusion injury through inhibiting the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.

Treatment-induced cardiotoxicity is one of the major side effects of trastuzumab treatment in patients with breast cancer. Left ventricular (LV) dysfunction is the leading cause of treatment-induced cardiotoxicity. The development of treatment-induced cardiotoxicity during cancer treatment may force patients to modify or quit the treatment. In this trial, we evaluated the prophylactic effects of carvedilol on LV dysfunction in patients with breast cancer receiving trastuzumab using 2D speckle-tracking echocardiography (2DSTE). We conducted an open-label randomized clinical trial and enrolled 71 non-metastatic HER-2 positive patients with breast cancer candidated to receive trastuzumab. Carvedilol was administered concomitantly with the trastuzumab standard regimen at a dosage of 6.25 mg twice a day and up-titrated to the maximum tolerated dosage. The 2DSTE parameters to evaluate the LV systolic and diastolic functions were evaluated initially and 3 months thereafter. Thirty-six patients were randomly assigned to the carvedilol group and 35 patients to the control group. The mean left ventricular ejection fraction (LVEF) was not significantly different either in both groups or between the 2 groups (P=.61) during the follow-up. In contrast, the global longitudinal strain of the LV (GLS) (P=.000) and the strain rate of the LV systolic function (SRS) (P=.004) as markers of the LV systolic function were reduced in the control group. Furthermore, the LV strain rate of the early (SRE) and late (SRA) diastolic functions were preserved in the patients who received prophylactic carvedilol (P=.000 and P=.005, respectively). Concomitant carvedilol treatment with a maximum tolerable dose in patients with non- metastatic HER2-positive breast cancer under treatment with trastuzumab might be effective on the reduction of systolic and diastolic echocardiographic findings other than the LVEF in patients with weak markers of heart failure.

Ischemia-Reperfusion (IR) injury is one of the most common cardiac disorders leading to irreversible heart damage. Many underlying mechanisms seem to be involved, among which disruption of cellular autophagy balance. Since physical training has a beneficial effect on the improvement of autophagy balance, it may have a cardioprotective effect against IR injury. This study investigates the protective role of aerobic training from cardiac IR injury and the autophagy process as a possible mechanism. Thirty-two male Wistar rats (8 weeks old) were divided into control, sham, control plus IR, and training plus IR groups (8 rats each). The training group was exercised aerobically on a treadmill for 8 weeks (5 d/wk). After 8 weeks, the anesthetized rats underwent left thoracotomy (sham, control plus IR, and training plus IR groups) to access the left anterior descending coronary artery, which was occluded by a silk suture for 30 min and then released for 90 min of reperfusion (IR groups). Triphenyltetrazolium chloride staining was used to determine the infarct size. The gene expression of Beclin-1 was evaluated by real-time polymerase chain reaction. One-way ANOVA was used for statistical analysis with the significance level set at P≤0.05. The cardiac infarct size was smaller in training plus IR (20.24±5.7%) group compared to that in the control plus IR (35.9±2.3%) group (P≤0.05). On the other hand, IR operation significantly increased the gene expression of Beclin-1, while exercise training prevented expression of the mentioned gene in training plus IR group (P≤0.05). Aerobic training can protect the heart against Ischemia-Reperfusion injury. It seems that improvement of autophagy balance during IR injury may be involved in exercise-induced cardioprotection against Ischemia-Reperfusion.

Diabetes mellitus as a main risk-factor of ischemic heart disease may interfere with postconditioning’scardioprotective effects. This study aimed to investigate the involvement of glycogen synthase kinase-3β (GSK-3β) and oxidation status in chronic diabetes-induced loss of cardioprotective effect of ischemic-postconditioning (IPostC) in Wistar rats. After 8 weeks of induction of diabetes by streptozotocin (50mg/kg), hearts of control and diabetic rats were isolated and mounted on a constant-pressure Langendorff system. All hearts were subjected to 30min regional ischemia followed by 60min reperfusion (by occluding and re-opening of left anterior descending coronary artery, respectively). IPostC was applied immediately at the onset of reperfusion. At the end of reperfusion, the infarct size of myocardium was measured via computerized planimetry. Myocardial contents of malondealdehyde and glutathione as indices of oxidative status were assayed spectrophotometrically and the total and phosphorylated forms of myocardial GSK- 3β were quantified through western blotting. IPostC reduced the infarct size of control hearts from 41±2.9% to 28±1.9% (P<0.05), whereas it could not induce significant changes in infarct size of diabetic animals (35±1.8% vs. 39±3.1%). IPostC-induced reduction in malondealdehyde and elevation in glutathione contents were significant only in control not in diabetic hearts. The total forms of GSK-3β were similar in all groups; however, the phosphorylation of GSK-3β (at Ser9) by IPostC was greater in control hearts than diabetics (P<0.01). The failure of cardioprotection by IPostC in diabetic hearts may be attributed to the loss of phosphorylation of GSK-3β and thereby increase in oxidative stress in diabetic states.

The aim of this study was to investigate the effects of High-Intensity Interval Training (HIIT) on nitric oxide metabolites (NO2-, NO3-) and myocardial infarct size after Ischemia/Reperfusion (I/R) injury in healthy male rats. A total of 44 Wistar rats were randomly divided into 4 groups including HIIT (n=8), HIIT + IR protocol (n=14), control (n=8), and control + IR (n=14). Each training session of HIIT consisted of 1 hour of exercise in three stages: 6-minute running at 50-60% VO2max for warm-up; 7 intervals of 7-minute running on treadmill with a slope of 50 to 20° (4 minutes with an intensity of 80-100% VO2max and 3 minutes at 50-60% VO2max); and 5-minute running at 50-60% VO2max for cool-down. The control group did not participate in any exercise program. Nitric Oxide (NO) and its metabolites were measured by using Griess reaction test. The results showed that eight weeks of exercise training exerted a significantly increasing effect on nitrite (8.55 µmol per liter, equivalent to 34.79%), nitrate (62.02 µmol per liter, equivalent to 149.48%), and NOx (66 µmol per liter, equivalent to 98.11%) in the HIIT group compared with the control group. The results showed myocardial infract size (IS) was significantly smaller (23.2%, P<0.001) in the exercise training group compared with the control group. Incremental changes in NO-NO3-, NO2- axis are one of mechanisms through which HIIT program can protect the heart from I/R injury and decrease myocardial infarction.

Cardiovascular diseases are still the main cause of mortality around the world. Therefore, it is essential to develop practical means to reduce their burden. A wealth of evidence supports the role of physical exercise in attenuating many of the risk factors of cardiovascular diseases. Moreover, endurance training warrants protection against myocardial infarction. Exercise, even if performed only in a few days, can protect the heart against ischemia-reperfusion (IR) injury, and this protection will be even more in longer exercises. It is yet to be clarified how exercise maneuvers provide protection against IR. However, it is suggested that some molecular and cellular mechanisms in addition to metabolic and hormonal alterations are seemingly involved in exercise-induced cardioprotection (EICP), such as increased capacity of antioxidant system, higher expression of heat shock proteins, improvement in ATP-sensitive potassium channels, change in nitric oxide production, and adaptive cardiac mitochondrial modulations. This paper discusses the current data on molecular and cellular mechanisms of EICP. Understanding the molecular basis of EICP against IR injury will provide us with the required knowledge for development of preventive and therapeutic approaches. In addition, exercise characteristics leading to more pronounced cardioprotection will be concisely addressed.