Electrical Remodeling of the Ventricular Myocardium in Myocarditis

Saito, Junko; Niwano, Shinichi; Niwano, Hiroe; Inomata, Takayuki; Yumoto, Yoshihiro; Ikeda, Kazuko; Inuo, Kimiatsu; Kojima, Jisho; Horie, Minoru; Izumi, Tohru

doi:10.1253/circj.66.97

Cited by 42 publications

(37 citation statements)

References 24 publications

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“…The MAP trace in the sham rats exhibited a relatively short MAPD, but it was prolonged in the control EAM rats as a result of a "dome" like prolongation in phase 2 of the action potential as previously described. 14) We expected that the MAPD would be shortened by the administration of Nic or Mex because of their opening effect on sarcolemmal K-ATP channels, however, the administration of Nic did not result in any significant shortening of the MAPD even with a higher dose (ie, 10 mg/kg/day in this study). As a result, the treatment with a higher dose of Mex (ie, 25 mg/kg/day in this study) caused a significant shortening of the MAPD in comparison with the control EAM.…”

Section: Hemodynamic and Echocardiographical Findingsmentioning

confidence: 63%

“…13,14) The sham rats received injections of the same amount of saline (0.25 mL) in the same manner (n = 20). EAM was induced in all 110 rats immunized, however, 7 rats died during the acute phase so 103 of 110 were used in the experiments.…”

Section: Methodsmentioning

confidence: 99%

“…For the hemodynamic parameters, the left ventricular systolic pressure (LVSP) and left ventricular end-diastolic pressure (LVEDP) were monitored by a needle tip micromanometer (SPR477, Millar, USA) as previously described. 13,14) For the electrophysiological evaluation, a pair of platinum needle electrodes (φ 0.1 mm) was directly inserted into the left ventricular free wall, and used for electrical stimulation and recording. The analogue signals were converted into digital signals at a sampling frequency of 1000 Hz (Power Lab 8sp, Bio Research, Tokyo) and stored on a computer hard disk.…”

Section: Methodsmentioning

confidence: 99%

“…The MAP duration (MAPD) was determined as the interval from the onset of the MAP to 20% of the repolarization time (MAPD 20 ) or to its 90% (MAPD 90 ). 13,14) Heart weight and histology: After the electrophysiological measurements, the heart was totally excised and the weight of the whole heart was measured to calculate the ratio of the heart to body weight (Hw/Bw). The heart was fixed with 10% formalin and embedded in paraffin.…”

Section: Methodsmentioning

confidence: 99%

“…11) This prolongation of the action potential duration may increase transient calcium and may exaggerate intracellular calcium overload, resulting in the deterioration of myocardial dysfunction. 12) We documented that this electrophysiological change can also be observed in acute inflammatory conditions in an experimental autoimmune myocarditis (EAM) model in rats, 13,14) which is a model showing acute myocarditis in the acute phase followed by dilated cardiomyopathy in the chronic phase. In the acute phase of this model, there would be a worsening cycle between the intracellular calcium overload and prolonged action potential duration as a result of the myocardial injury, which may also adversely affect mitochondrial function.…”

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confidence: 96%

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Cardioprotective Effects of Sarcolemmal and Mitochondrial K-ATP Channel Openers in an Experimental Model of Autoimmune Myocarditis

et al. 2012

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SummaryIt has been reported that K-ATP channel openers have a cardioprotective effect in acute ischemia as a pharmacological preconditioning effect. In the present study, the chronic effects of clinical K-ATP channel openers, ie, nicorandil (Nic) and mexiletine (Mex), on cardiac function were evaluated in a rat model of experimental autoimmune myocarditis (EAM). Nicorandil (3 or 10 mg/kg/day) or Mex (10 or 25 mg/kg/day) was administered to the EAM rats, and the effects were compared with those in untreated EAM rats (control EAM) and sham rats without EAM on day 21 (acute phase) or day 60 (chronic phase). In the acute phase, the control EAM rats exhibited a reduced left ventricular ejection fraction (LVEF) and prolonged monophasic action potential duration (MAPD). Neither drug had an affect on the LVEF or degree of myocarditis, but Mex 25 mg suppressed the MAPD prolongation. In the chronic phase, EAM+Nic and EAM+Mex 25 mg exhibited a higher LVEF than the control EAM. Although the control EAM exhibited sustained MAPD prolongation, the other groups showed recovery of the MAPD in the chronic phase. The mitochondorial redox state was lower in the control EAM than in the sham, and EAM+Nic exhibited a similar level of the redox state as the sham in the chronic phase. Nicorandil exhibited a cardioprotective effect through the protection of mitochondrial function. Mexiletine exhibited a cardioprotective effect possibly through a reduction in the calcium overload by shortening the MAPD in the acute phase. (Int Heart J 2012; 53: 139-145)

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Section: Hemodynamic and Echocardiographical Findingsmentioning

confidence: 63%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 96%

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