Cardioprotective effects of nitric oxide-aspirin in myocardial ischemia-reperfused rats

Fu, Yi Long; Wang, Zhong Jing; Chen, Woei Lee; Moore, Philip K.; Zhu, Yi‐Zhun

doi:10.1152/ajpheart.00064.2007

Cited by 25 publications

(14 citation statements)

References 55 publications

(57 reference statements)

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“…First, naproxcinod and NCX‐4016 were shown to reduce blood pressure in hypertensive rats, while no alteration of blood pressure in normotensive animals was reported for aspirin and flurbiprofen prodrugs . Second, naproxcinod and NCX‐4016 were able to reduce myocardial damage induced by ischemia/reperfusion in animal experiments . Third, NCX‐4016 has exhibited antiatherosclerotic actions in rodent studies .…”

Section: Association Of Nsaids With Protective Mediatorsmentioning

confidence: 99%

Nonsteroidal Anti‐Inflammatory Therapy: A Journey Toward Safety

Pereira-Leite

Nunes

Jamal

et al. 2016

Medicinal Research Reviews

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The efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) against inflammation, pain, and fever has been supporting their worldwide use in the treatment of painful conditions and chronic inflammatory diseases until today. However, the long-term therapy with NSAIDs was soon associated with high incidences of adverse events in the gastrointestinal tract. Therefore, the search for novel drugs with improved safety has begun with COX-2 selective inhibitors (coxibs) being straightaway developed and commercialized. Nevertheless, the excitement has fast turned to disappointment when diverse coxibs were withdrawn from the market due to cardiovascular toxicity. Such events have once again triggered the emergence of different strategies to overcome NSAIDs toxicity. Here, an integrative review is provided to address the breakthroughs of two main approaches: (i) the association of NSAIDs with protective mediators and (ii) the design of novel compounds to target downstream and/or multiple enzymes of the arachidonic acid cascade. To date, just one phosphatidylcholine-associated NSAID has already been approved for commercialization. Nevertheless, the preclinical and clinical data obtained so far indicate that both strategies may improve the safety of nonsteroidal anti-inflammatory therapy.

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Section: Association Of Nsaids With Protective Mediatorsmentioning

confidence: 99%

Nonsteroidal Anti‐Inflammatory Therapy: A Journey Toward Safety

Pereira-Leite

Nunes

Jamal

et al. 2016

Medicinal Research Reviews

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“…The coronary artery ligation model was used as a model for AMI as we reported previously (15,42). Within each treatment group, rats were randomly subdivided to a coronary artery ligation operation or a sham operation group.…”

Section: Experimental Induction Of Acute Myocardial Infarctionmentioning

confidence: 99%

S-allylcysteine mediates cardioprotection in an acute myocardial infarction rat model via a hydrogen sulfide-mediated pathway

Chuah¹,

Moore²,

Zhu³

2007

American Journal of Physiology-Heart and Circulatory Physiology

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138

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Chuah SC, Moore PK, Zhu YZ. S-allylcysteine mediates cardioprotection in an acute myocardial infarction rat model via a hydrogen sulfide mediated pathway. Am J Physiol Heart Circ Physiol 293: H2693-H2701, 2007. First published August 31, 2007; doi:10.1152 doi:10. /ajpheart.00853.2007 is an organosulfur-containing compound derived from garlic. Studies have shown that garlic is beneficial in the treatment of cardiovascular diseases. This study aims to elucidate if SAC is responsible for this cardioprotection using acute myocardial infarction (AMI) rat models. In addition, we hypothesized that SAC may mediate cardioprotection via a hydrogen sulfide (H2S)-related pathway. Rats were pretreated with saline, SAC (50 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 ), SAC ϩ propagylglycine (PAG; 50 mg ϩ 10 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 ) or PAG (10 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 ) for 7 days before AMI induction and killed 48 h after. Our results showed that SAC significantly lowered mortality (12.5% vs. 33.3%, P Ͻ 0.05) and reduced infarct size. SAC ϩ PAG-and PAG-treated rats had larger infarct sizes than controls (60.9 Ϯ 0.01 and 62.0 Ϯ 0.03%, respectively, vs. 50.0 Ϯ 0.03%; P Ͻ 0.05). Pretreatment with SAC did not affect BP, but BP was significantly elevated in SAC ϩ PAG and PAG-treated groups (P Ͻ 0.05). In addition, plasma H2S levels and left ventricular cystathionine-␥-lyase (CSE) activities were analyzed to investigate the involvement of H2S. CSE is the enzyme responsible for H2S production in the heart. SAC increased left ventricular CSE activity in AMI rats (2.75 Ϯ 0.34 vs. 1.23 Ϯ 0.16 mol ⅐ g protein Ϫ1 ⅐ h Ϫ1 ; P Ͻ 0.01). SAC ϩ PAG-treated rats had significantly lower CSE activity compared with the SAC-treated group (1.22 Ϯ 0.27 vs. 2.75 Ϯ 0.34 mol ⅐ g protein Ϫ1 ⅐ h Ϫ1 ; P Ͻ 0.05). Similarly, SAC-treated rats had higher plasma H2S concentration compared with controls and the SAC ϩ PAG-treated group. Protein expression studies revealed that SAC upregulated CSE expression (1.1-fold of control; P Ͻ 0.05), whereas SAC ϩ PAG and PAG downregulated its expression (0.88-fold of control in both groups; P Ͻ 0.005). In conclusion, our study provides novel evidence that SAC is protective in myocardial infarction via an H2S-related pathway.

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“…For open-chest models, examples of mortality rates range from 35 % [15] to 65 % [16]. A significant reduction of overall mortality could be expected, as in the closed-chest model the I/R experiments are performed when the animals have recovered from the impact of the thoracotomy and thus are in a much more stable condition.…”

Section: Discussionmentioning

confidence: 99%

Closed-chest small animal model to study myocardial infarction in an MRI environment in real time

h-Icí

Jeuthe

Dietrich

et al. 2014

Int J Cardiovasc Imaging

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Current models for real time study of the effects of myocardial ischemia/reperfusion have major limitations and confounders. Confounders include the surgical stresses of a thoracotomy and abnormal physiology of an open chest. The need to reposition the animal interferes with the study of the early changes associated with ischemia. Direct comparison of pre-ischemia and post-ischemia images is then difficult. We developed a novel "closed chest" model of ischemia/reperfusion to overcome these issues. Following thoracotomy, we sutured a balloon occluder to the left coronary artery of male Sprague-Dawley rats. We used both visual inspection and ECG to assess for successful occlusion and reperfusion of the coronary artery at the time of operation by brief inflation and deflation of the balloon. The tubing was then placed under the skin and the incision closed. Following a recovery period (5-10 days), the animals underwent MRI. We performed baseline assessment of left ventricle function, and repeated LV measurement during a 15-min coronary occlusion and again during a 60-min reperfusion period following reopening of the coronary artery. The occluder was successfully placed in 40 of 44 animals. Four developed intraoperative complications; two large myocardial infarction, two terminal bleeding. Six died in the week following surgery, [four sudden deaths (presumed arrhythmic), one anterior infarction, one sepsis]. Cine-MRI demonstrated localised hypokinesia in 31 of the remaining 34 animals. LV ejection fraction (EF) was reduced from 63 ± 7 % at baseline, to 49 ± 9 % during coronary occlusion. LV EF recovered to 61 ± 2 %. The area at risk on staining of the heart was 41.9 ± 15.8 %. This method allows the effects of ischemia/reperfusion to be studied before, during, and after coronary occlusion. Ischemia can be caused while the animal is in the MRI. This new and clinically relevant small animal model is a valuable tool to study the effects of single or repeated coronary occlusion/reperfusion in real-time.

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Cardioprotective effects of nitric oxide-aspirin in myocardial ischemia-reperfused rats

Cited by 25 publications

References 55 publications

Nonsteroidal Anti‐Inflammatory Therapy: A Journey Toward Safety

Nonsteroidal Anti‐Inflammatory Therapy: A Journey Toward Safety

S-allylcysteine mediates cardioprotection in an acute myocardial infarction rat model via a hydrogen sulfide-mediated pathway

Closed-chest small animal model to study myocardial infarction in an MRI environment in real time

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