Aggravation of left ventricular dilatation and reduction of survival by a calcium channel blocker in rats with chronic myocardial infarction

Gaudron, Peter; Blumrich, Monika; Ertl, Georg

doi:10.1016/0002-8703(93)90989-m

Cited by 17 publications

(9 citation statements)

References 32 publications

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“…A recent study by Sanbe et al (29) examined high-energy phosphate stores in residual intact myocardium of rat hearts with infarct sizes similar to our work using a columnfreezing method. In agreement with our results, these authors found significant reductions of CP and creatine [1][2][3][4][5][6][7][8][9][10][11][12] wk after MI. In contrast, however, they also found significant reductions of ATP and of Pi.…”

Section: Discussionsupporting

confidence: 92%

“…Infarcts or sham operations were carried out in 12-wk-old Wistar rats, kept in a 12-h light-dark cycle. Left anterior descending coronary artery (LAD) ligation was performed by a previously described technique (1,11). Briefly, a left thoracotomy was performed under ether anesthesia and positive pressure ventilation.…”

Section: Methodsmentioning

confidence: 99%

“…Thereafter, a set of 6 3`P-NMR magnetization transfer spectra was recorded in 32 min. After a final one-pulse spectrum, hearts were fixed in formalin for determination of infarct size (1,11). Hearts were perfused with oxygenated KrebsHenseleit buffer throughout this protocol.…”

Section: Methodsmentioning

confidence: 99%

“…Infarct size was determined by a previously described technique ( 1,11). The left ventricle was embedded in paraffin, and 20-jm sections were cut serialy from apex to base of the heart.…”

Section: Methodsmentioning

confidence: 99%

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Impairment of energy metabolism in intact residual myocardium of rat hearts with chronic myocardial infarction.

Neubauer

Horn²,

Naumann³

et al. 1995

J. Clin. Invest.

212

129

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IntroductionThe purpose of this study was to test the hypothesis that energy metabolism is impaired in residual intact myocardium of chronically infarcted rat heart, contributing to contractile dysfunction. Myocardial infarction (MI) was induced in rats by coronary artery ligation. (6), aortic stenosis (7), dilated cardiomyopathy in the Syrian hamster (8), uninephrectomy plus steroid treatment (9), or the spontaneously hypertensive rat (10). The purpose of the present work was, therefore, to define performance, oxygen consumption, and parameters of energy reserve, i.e., tissue contents of ATP and creatine phosphate (CP), creatine kinase (CK) activity and isoenzyme distribution, and phosphoryl transfer rates via CK (using 3P-magnetization transfer), in normal rat heart and in residual intact myocardium after MI. Using these measurements, we directly tested whether changes in energy metabolism can contribute to contractile dysfunction in post-MI heart. MethodsAnimals and experimental MI. Infarcts or sham operations were carried out in 12-wk-old Wistar rats, kept in a 12-h light-dark cycle. Left anterior descending coronary artery (LAD) ligation was performed by a previously described technique (1, 11). Briefly, a left thoracotomy was performed under ether anesthesia and positive pressure ventilation. The heart was rapidly exteriorized by applying gentle pressure on both sides of the thorax. The LAD was ligated between the pulmonary outflow tract and the left atrium. The heart was then replaced into the thorax, lungs were inflated by increasing positive end-expiratory pressure, and the wound was closed immediately. Sham operation was performed using an identical procedure except that the suture was passed under the coronary artery without ligation. Mortality rate of infarcted rats for the first 24 h after the operation was 40-50%. Surviving rats were kept on commercial rat chow and water ad libitum. All procedures conformed to the guiding principles of the American Physiological Society. Isolated rat heart preparation. 8 wk after LAD ligation or sham operation, rats were anesthetized by injecting 20 mg pentobarbital sodium intraperitoneally. After thoracotomy, the heart was rapidly excised and immersed in ice-cold buffer. The aorta was dissected free and mounted onto a cannula attached to a perfusion apparatus, as described previously (12). Retrograde perfusion of the heart was started in the 1092Neubauer et al.J. Clin. Invest.C) The

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Section: Discussionsupporting

confidence: 92%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…Infarct size was determined by a previously described technique ( 1,11). The left ventricle was embedded in paraffin, and 20-jm sections were cut serialy from apex to base of the heart.…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Impairment of energy metabolism in intact residual myocardium of rat hearts with chronic myocardial infarction.

Neubauer

Horn²,

Naumann³

et al. 1995

J. Clin. Invest.

212

129

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“…15 Furthermore, in residual intact myocardium, PCr levels are reduced by up to 30% 15 and Flux CK up to 50%, 15 but ATP and P i levels remain constant. This HF model is well suited to study the effects of pharmacological intervention: eg, ACE inhibitors 18,22 and ␤-receptor blockers 22 have been found to preserve cardiac structure, function, and energetics, whereas the Ca 2ϩ channel blocker anipamil 23 exerted detrimental effects in this model.…”

Section: Definition Of the Modelmentioning

confidence: 99%

Chronic Phosphocreatine Depletion by the Creatine Analogue β-Guanidinopropionate Is Associated With Increased Mortality and Loss of ATP in Rats After Myocardial Infarction

et al. 2001

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Background-The failing myocardium is characterized by reductions of phosphocreatine (PCr) and free creatine content and by decreases of energy reserve via creatine kinase (CK), ie, CK reaction velocity (Flux CK ). It has remained unclear whether these changes contribute directly to contractile dysfunction. In the present study, myocardial PCr stores in a heart failure model were further depleted by feeding of the PCr analogue ␤-guanidinopropionate (GP). Functional and metabolic consequences were studied. Methods and Results-Rats were subjected to sham operation or left coronary artery ligation (MI). Surviving rats were assigned to 4 groups and fed with 0% (nϭ7, Sham; nϭ5, MI) or 1% (nϭ7 ShamϩGP, nϭ8 MIϩGP) GP. Two additional groups were fed GP for 2 or 4 weeks before MI. After 8 weeks, hearts were isolated and perfused, and left ventricular pressure-volume curves were obtained. High-energy phosphate metabolism was determined with 31 P NMR spectroscopy. After GP feeding or MI, left ventricular pressure-volume curves were depressed by 33% and 32%, respectively, but GP feeding in MI hearts did not further impair mechanical function. Both MI and GP feeding reduced PCr content and Flux CK , but here, effects were additive. In MIϩGP rats, PCr levels and Flux CK were reduced by 87% and 94%, respectively. Although ATP levels were maintained in the GP and MI groups, ATP content was reduced by 18% in MIϩGP hearts. Furthermore, 24-hour mortality in GP-prefed rats was 100%. Conclusions-Rats with an 87% predepletion of myocardial PCr content cannot survive an acute MI. Chronically infarcted hearts subjected to additional PCr depletion cannot maintain ATP homeostasis.

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Three‐dimensional ³¹P magnetic resonance spectroscopic imaging of regional high‐energy phosphate metabolism in injured rat heart

Kienlin

Rösch

Fur

et al. 1998

Magnetic Resonance in Med

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The purpose of this study was to measure the spatially varying 31P MR signals in global and regional ischemic injury in the isolated, perfused rat heart. Chronic myocardial infarcts were induced by occluding the left anterior descending coronary artery eight weeks before the MR examination. The effects of acute global low-flow ischemia were observed by reducing the perfusate flow. Chemical shift imaging (CSI) with three spatial dimensions was used to obtain 31P spectra in 54-microl voxels. Multislice 1H imaging with magnetization transfer contrast enhancement provided anatomical information. In normal hearts (n = 8), a homogeneous distribution of high-energy phosphate metabolites (HEP) was found. In chronic myocardial infarction (n = 6), scar tissue contained negligible amounts of HEP, but their distribution in residual myocardium was uniform. The size of the infarcted area could be measured from the metabolic images; the correlation of infarct sizes determined by histology and 31P MR CSI was excellent (P < 0.006). In global low-flow ischemia (n = 8), changes of HEP showed substantial regional heterogeneity. Three-dimensional 31P MR CSI should yield new insights into the regionally distinct metabolic consequences of various forms of myocardial injury.

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Aggravation of left ventricular dilatation and reduction of survival by a calcium channel blocker in rats with chronic myocardial infarction

Cited by 17 publications

References 32 publications

Impairment of energy metabolism in intact residual myocardium of rat hearts with chronic myocardial infarction.

Impairment of energy metabolism in intact residual myocardium of rat hearts with chronic myocardial infarction.

Chronic Phosphocreatine Depletion by the Creatine Analogue β-Guanidinopropionate Is Associated With Increased Mortality and Loss of ATP in Rats After Myocardial Infarction

Three‐dimensional ³¹P magnetic resonance spectroscopic imaging of regional high‐energy phosphate metabolism in injured rat heart

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Aggravation of left ventricular dilatation and reduction of survival by a calcium channel blocker in rats with chronic myocardial infarction

Cited by 17 publications

References 32 publications

Impairment of energy metabolism in intact residual myocardium of rat hearts with chronic myocardial infarction.

Impairment of energy metabolism in intact residual myocardium of rat hearts with chronic myocardial infarction.

Chronic Phosphocreatine Depletion by the Creatine Analogue β-Guanidinopropionate Is Associated With Increased Mortality and Loss of ATP in Rats After Myocardial Infarction

Three‐dimensional 31P magnetic resonance spectroscopic imaging of regional high‐energy phosphate metabolism in injured rat heart

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Three‐dimensional ³¹P magnetic resonance spectroscopic imaging of regional high‐energy phosphate metabolism in injured rat heart