Pravastatin Reduces Myocardial Infarct Size Via Increasing Protein Kinase C-Dependent Nitric Oxide, Decreasing Oxyradicals and Opening the Mitochondrial Adenosine Triphosphate-Sensitive Potassium Channels in Rabbits

Bao, Narentuoya; Minatoguchi, Shinya; Kobayashi, Hiroyuki; Yasuda, Shinji; Kawamura, Itta; Iwasa, Motoh; Yamaki, Takashi; Sumi, Syohei; Yu, Ming; Arai, M.; Nishigaki, Kazuhiko; Takemura, Genzou; Fujiwara, Takako; Fujiwara, Hisayoshi

doi:10.1253/circj.71.1622

Cited by 32 publications

(27 citation statements)

References 33 publications

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“…During the following 19 min, further increase was detected in all hearts; however, it was statistically significant only for rats and rabbits. These values are comparable with results of Bao et al (2007) who reported that in rabbits the production of 2.5-DHBA measured by microdialysis technique reached during 30 min of ischemia was in tens of nmol/l.…”

Section: Discussionsupporting

confidence: 91%

Hydroxyl radicals’ production and ECG parameters during ischemia and reperfusion in rat, guinea pig and rabbit isolated heart

Paulová¹,

Stračina²,

Jarkovský³

et al. 2013

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Abstract. Ischemic and reperfusion injury is a serious condition related to numerous biochemical and electrical abnormalities of the myocardium. It has been repeatedly studied in various animal models. In this study, the production of hydroxyl radicals and electrophysiological parameters were compared in three species. Rat, guinea pig and rabbit isolated hearts were perfused according to Langendorff under strictly identical conditions. The heart rate and arrhythmia were monitored during ischemia and reperfusion periods at defined time intervals; the production of hydroxyl radical was determined by HPLC as 2.5-dihydroxybenzoic acid (2.5-DHBA) formed by salicylic acid hydroxylation. Relationship between arrhythmias and production of 2.5-DHBA was studied. The inter-species differences were observed in timing of arrhythmias onset and their severity, and in the production of 2.5-DHBA in both ischemia and reperfusion. The most considerable changes were observed in rats, where arrhythmias appeared early and with highest severity during ischemia on one side and the regular rhythm was restored early and completely during reperfusion. The corresponding changes in the production of 2.5-DHBA were observed. It can be concluded that rat isolated heart is the most suitable model for evaluation of ischemia/reperfusion injury under given experimental conditions.

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Section: Discussionsupporting

confidence: 91%

Hydroxyl radicals’ production and ECG parameters during ischemia and reperfusion in rat, guinea pig and rabbit isolated heart

Paulová¹,

Stračina²,

Jarkovský³

et al. 2013

gpb

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show abstract

“…In rabbits undergoing myocardial infarction through reversible coronary artery occlusion, preischemic but not prereperfusion treatment with pravastatin reduced the myocardial infarct size. 19 However, it is well recognized that the cardioprotection window during reperfusion starts within seconds of the reperfusion and lasts a few minutes. Thus, it has been reported that pravastatin administered at the beginning of the reoxygenation period conferred cardioprotection in neonatal rat cardiomyocytes 20 and isolated human cardiomyocytes obtained from children undergoing elective surgery for congenital heart disease.…”

Section: Discussionmentioning

confidence: 99%

Mechanisms Involved in Cardioprotective Effects of Pravastatin Administered during Reoxygenation in Human Myocardium In Vitro

Lemoine¹,

Allouche

Coulbault

et al. 2012

Anesthesiology

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Background:The authors investigated the effect of pravastatin during reoxygenation after myocardial hypoxia and examined the involvement of nitric oxide synthase, mitochondrial permeability transition pore, and expression of markers of apoptosis in human myocardium in vitro. Methods: Human atrial trabeculae were exposed to hypoxia for 30 min and reoxygenation for 60 min (control group; n ϭ 10). Pravastatin (5, 10, 50, 75 M; n ϭ 6 in each group) was administered throughout the reoxygenation. In separate groups (n ϭ 6 in each group), pravastatin 50 M was administered in the presence of 200 M L-NG-nitroarginine methyl ester, a nitric oxide synthase inhibitor, and 50 M atractyloside, the mitochondrial permeability transition pore

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“…Although statins have also been proposed as a postconditioning treatment for the heart, their ability to limit infarction when given at reperfusion in the isolated heart 28 has not been replicated in the in-situ heart. 29 These interventions have only recently been identified, and as a result their clinical testing is still in its infancy. Two small trials of cyclosporin 30 and ischemic postconditioning 31 are very encouraging, but of course need to be confirmed in much larger studies.…”

Section: Have We Been Testing the Wrong Drugs?mentioning

confidence: 99%

Why Do We Still Not Have Cardioprotective Drugs?

Downey

Cohen

2009

Circ J

125

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Despite thousands of publications describing agents that limit infarct size in animals, all we have available today is reperfusion therapy. In this review, we examine why these drugs have not been translated into clinical practice.Many of the first interventions tested in clinical trials were very controversial in animal trials and their actual efficacy is still in question. Interventions based on the preconditioning mechanism have been very reproducible in animals, but clinical testing of them has just begun. Only approximately 25% of reperfused patients have infarcts large enough to put them at risk of heart failure and would require additional treatment. Inclusion of the 75% of patients with small infarcts in treatment groups has greatly diluted the significance of data in past clinical trials. Size of the risk zone has emerged as a reliable way to identify the vulnerable 25%. Recent small-scale clinical trials using risk stratification algorithms have shown clear infarct size limitation using ischemic and pharmacological postconditioning, confirming that the human heart responds like hearts of animal models. Most cardioprotectants have been studied in healthy animals, but recent studies indicate that aging and diabetes, common in coronary patients, do interfere with preconditioning-based interventions in animals. Clearly more study is needed to identify which interventions are adversely affected by comorbidities. (Circ J 2009; 73: 1171 -1177

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Pravastatin Reduces Myocardial Infarct Size Via Increasing Protein Kinase C-Dependent Nitric Oxide, Decreasing Oxyradicals and Opening the Mitochondrial Adenosine Triphosphate-Sensitive Potassium Channels in Rabbits

Cited by 32 publications

References 33 publications

Hydroxyl radicals’ production and ECG parameters during ischemia and reperfusion in rat, guinea pig and rabbit isolated heart

Hydroxyl radicals’ production and ECG parameters during ischemia and reperfusion in rat, guinea pig and rabbit isolated heart

Mechanisms Involved in Cardioprotective Effects of Pravastatin Administered during Reoxygenation in Human Myocardium In Vitro

Why Do We Still Not Have Cardioprotective Drugs?

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