Examination of the Changes in Calcium Homeostasis in the Delayed Antiarrhythmic Effect of Sodium Nitrite

We have evidence that the intravenous infusion of sodium nitrite (NaNO2) results in an antiarrhythmic effect when given 24 h prior to an ischemia and reperfusion (I/R) insult in anaesthetized dogs. This protection was associated with the reduction of reactive oxygen species resulting from I/R through the attenuation of mitochondrial respiration. Here, we examined whether the changes in calcium, which also contributes to arrhythmia generation, play a role in the NaNO2-induced effect. On the first day, 30 anaesthetized dogs were treated either with saline or NaNO2 (0.2 µmol/kg/min) for 20 min. Some animals were subjected to a 25 min LAD (anterior descending branch of the left coronary artery) occlusion and 2 min reperfusion (I/R = 4; NaNO2-I/R = 6), or the heart was removed 24 h later. We have shown that nitrite prevented the I/R-induced increase in cellular and mitochondrial calcium deposits. During simulated I/R, the amplitude of the calcium transient and the diastolic calcium level were significantly lower in the nitrite-treated hearts and the ERP (effective refractory period) fraction of the action potential was significantly increased. Furthermore, nitrite also enhanced the mitochondrial respiratory response and prevented the MPTPT opening during calcium overload. These results suggest that nitrite can reduce the harmful consequences of calcium overload, perhaps directly by modulating ion channels or indirectly by reducing the mitochondrial ROS (reactive oxygen species) production.

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The role of reactive oxygen species in the infarct-limiting effect of hypoxic preconditioning

Regional blood circulation and microcirculation ◽

10.24884/1682-6655-2021-20-2-87-91 ◽

2021 ◽

Vol 20 (2) ◽

pp. 87-91

Author(s):

A. S. Sementsov ◽

N. V. Naryzhnaya ◽

M. A. Sirotina ◽

L. N. Maslov

Keyword(s):

Reactive Oxygen Species ◽

Coronary Artery ◽

Ischemia Reperfusion ◽

Reactive Oxygen ◽

Coronary Artery Occlusion ◽

Artery Occlusion ◽

Hypoxic Preconditioning ◽

Male Rats ◽

Oxygen Species ◽

Infarct Size Reduction

Introduction. Increased resistance of the heart to ischemia/reperfusion (I/R) is an urgent aim of physiology, pharmacology, and cardiac surgery, since I/R injury of the heart is often the cause of cardiogenic shock and subsequent death of patients in the postoperative period. Materials and methods. The study was carried out in male rats which were subjected to coronary artery occlusion (45 min) and reperfusion (2 h). Before coronary occlusion, early hypoxic preconditioning (HP) was modeled. The rats were subjected to six sessions of hypoxia (8 % O2, 10 min) and reoxygenation (21 % O2, 10 min) 30 min before coronary artery occlusion. The rats were injected with the following drugs: 1,3-dimethylthiourea (DMTM), 2-mercaptopropionyl glycine (2-MPG), deferoxamine. Results. It was found that HP contributes to infarct size reduction by 30 %. Preliminary administration of DMTM, 2-MPG, deferoxamine eliminated the infarct-reducing effect of HP. Conclisuon. The obtained data indicate that reactive oxygen species are involved in the cardioprotective effect of HP.

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Reactive oxygen species are critical mediators of coronary collateral development in a canine model

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00318.2003 ◽

2003 ◽

Vol 285 (4) ◽

pp. H1582-H1589 ◽

Cited By ~ 34

Author(s):

Weidong Gu ◽

Dorothee Weihrauch ◽

Katsuya Tanaka ◽

John P. Tessmer ◽

Paul S. Pagel ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Blood Flow ◽

Coronary Artery ◽

Reactive Oxygen ◽

Coronary Artery Occlusion ◽

Artery Occlusion ◽

Oxygen Species ◽

Collateral Blood Flow ◽

Collateral Development ◽

Coronary Collateral

Recent evidence suggests that reactive oxygen species (ROS) promote proliferation and migration of vascular smooth muscle (VSMC) and endothelial cells (EC). We tested the hypothesis that ROS serve as crucial messengers during coronary collateral development. Dogs were subjected to brief (2 min), repetitive coronary artery occlusions (1/h, 8/day, 21 day duration) in the absence (occlusion, n = 8) or presence of N-acetylcysteine (NAC) (occlusion + NAC, n = 8). A sham group ( n = 8) was instrumented identically but received no occlusions. In separate experiments, ROS generation after a single 2-min coronary artery occlusion was assessed with dihydroethidium fluorescence. Coronary collateral blood flow (expressed as a percentage of normal zone flow) was significantly increased (71 ± 7%) in occlusion dogs after 21 days but remained unchanged (13 ± 3%) in sham dogs. Treatment with NAC attenuated increases in collateral blood flow (28 ± 8%). Brief coronary artery occlusion and reperfusion caused ROS production (256 ± 33% of baseline values), which was abolished with NAC (104 ± 12%). Myocardial interstitial fluid produced tube formation and proliferation of VSMC and EC in occlusion but not in NAC-treated or sham dogs. The results indicate that ROS are critical for the development of the coronary collateral circulation.

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N -Acetylcysteine Restores Isoflurane-induced Preconditioning against Myocardial Infarction during Hyperglycemia

Anesthesiology ◽

10.1097/00000542-200306000-00013 ◽

2003 ◽

Vol 98 (6) ◽

pp. 1384-1390 ◽

Cited By ~ 23

Author(s):

Franz Kehl ◽

John G. Krolikowski ◽

Dorothee Weihrauch ◽

Paul S. Pagel ◽

David C. Warltier ◽

...

Keyword(s):

Myocardial Infarction ◽

Reactive Oxygen Species ◽

Infarct Size ◽

Myocardial Infarct ◽

Reactive Oxygen ◽

Coronary Artery Occlusion ◽

Artery Occlusion ◽

Myocardial Infarct Size ◽

Oxygen Species ◽

Blood Glucose Concentrations

Background Hyperglycemia generates reactive oxygen species and prevents isoflurane-induced preconditioning. The authors tested the hypothesis that scavenging reactive oxygen species with N-acetylcysteine will restore protection against myocardial infarction produced by isoflurane in vivo. Methods Barbiturate-anesthetized dogs (n = 45) were instrumented for measurement of systemic hemodynamics. Myocardial infarct size and coronary collateral blood flow were measured with triphenyltetrazolium staining and radioactive microspheres, respectively. All dogs were subjected to a 60-min left anterior descending coronary artery occlusion followed by 3 h of reperfusion. Dogs were randomly assigned to receive an infusion of 0.9% saline or 15% dextrose in water to increase blood glucose concentrations to 600 mg/dl (hyperglycemia) in the absence or presence of isoflurane (1.0 minimum alveolar concentration) with or without pretreatment with N-acetylcysteine (150 mg/kg i.v.) in six experimental groups. Isoflurane was discontinued, and blood glucose concentrations were allowed to return to baseline values before left anterior descending coronary artery occlusion. Results Myocardial infarct size was 27 +/- 2% (n = 8) of the left ventricular area at risk in control experiments. Isoflurane significantly (P < 0.05) decreased infarct size (13 +/- 2%; n = 7). Hyperglycemia alone did not alter infarct size (29 +/- 3%; n = 7) but abolished the protective effect of isoflurane (25 +/- 2%; n = 8). N-Acetylcysteine alone did not affect infarct size (28 +/- 2%; n = 8) but restored isoflurane-induced cardioprotection during hyperglycemia (10 +/- 1%; n = 7). Conclusions Acute hyperglycemia abolishes reductions in myocardial infarct size produced by isoflurane, but N-acetylcysteine restores these beneficial effects. The results suggest that excessive quantities of reactive oxygen species generated during hyperglycemia impair isoflurane-induced preconditioning in dogs.

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