The influence of pressure overload left ventricular hypertrophy on diastolic properties during hypoxia in isovolumically contracting rat hearts.

Lorell, Beverly H.; Wexler, Laura; Momomura, Shin‐ichi; Weinberg, Ellen O.; Apstein, Carl S.

doi:10.1161/01.res.58.5.653

Cited by 56 publications

(14 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In fact, it should be noted that creatine rephosphorylation rate, which is an in vivo assessment of mitochondrial function after ischemia (62), was superior in Myc-activated hearts. This is in contrast to previous studies wherein hypertrophied hearts were more sensitive to ischemic injury and more dependent on glycolytic substrates than nonhypertrophied hearts (63)(64)(65)(66)(67). The cellular mechanisms responsible for the observed cardioprotective effect in Myc-activated hearts are speculative; however, Myc's ability to induce mitochondrial biogenesis with normally functioning mitochondria in the setting of increased glucose metabolism might explain this effect.…”

Section: Figurecontrasting

confidence: 82%

Myc controls transcriptional regulation of cardiac metabolism and mitochondrial biogenesis in response to pathological stress in mice

et al. 2010

View full text Add to dashboard Cite

In the adult heart, regulation of fatty acid oxidation and mitochondrial genes is controlled by the PPARγ coactivator-1 (PGC-1) family of transcriptional coactivators. However, in response to pathological stressors such as hemodynamic load or ischemia, cardiac myocytes downregulate PGC-1 activity and fatty acid oxidation genes in preference for glucose metabolism pathways. Interestingly, despite the reduced PGC-1 activity, these pathological stressors are associated with mitochondrial biogenesis, at least initially. The transcription factors that regulate these changes in the setting of reduced PGC-1 are unknown, but Myc can regulate glucose metabolism and mitochondrial biogenesis during cell proliferation and tumorigenesis in cancer cells. Here we have demonstrated that Myc activation in the myocardium of adult mice increases glucose uptake and utilization, downregulates fatty acid oxidation by reducing PGC-1α levels, and induces mitochondrial biogenesis. Inactivation of Myc in the adult myocardium attenuated hypertrophic growth and decreased the expression of glycolytic and mitochondrial biogenesis genes in response to hemodynamic load. Surprisingly, the Myc-orchestrated metabolic alterations were associated with preserved cardiac function and improved recovery from ischemia. Our data suggest that Myc directly regulates glucose metabolism and mitochondrial biogenesis in cardiac myocytes and is an important regulator of energy metabolism in the heart in response to pathologic stress.

show abstract

Section: Figurecontrasting

confidence: 82%

Myc controls transcriptional regulation of cardiac metabolism and mitochondrial biogenesis in response to pathological stress in mice

et al. 2010

View full text Add to dashboard Cite

show abstract

“…The isolated isovolumic working rat heart preparation has previously been described in detail (23). Rats were injected intraperitoneally with 1.0-1.5 ml sodium pentobarbital ( (25) to be required for accurate measurement ofleft ventricular pressure and its first derivative.…”

Section: Methodsmentioning

confidence: 99%

Increased rat cardiac angiotensin converting enzyme activity and mRNA expression in pressure overload left ventricular hypertrophy. Effects on coronary resistance, contractility, and relaxation.

Schunkert¹,

Dzau²,

Tang³

et al. 1990

J. Clin. Invest.

Self Cite

589

239

View full text Add to dashboard Cite

We compared the activity and physiologic effects of cardiac angiotensin converting enzyme (ACE) using isovolumic hearts from male Wistar rats with left ventricular hypertrophy due to chronic experimental aortic stenosis and from control rats. In response to the infusion of 3.5 X 10-8 M angiotensin I in the isolated buffer perfused beating hearts, the intracardiac fractional conversion to angiotensin II was higher in the hypertrophied hearts compared with the controls (17.3±4.1% vs 6.8±1.3%, P < 0.01). ACE activity was also significantly increased in the free wall, septum, and apex of the hypertrophied left ventricle, whereas ACE activity from the nonhypertrophied right ventricle of the aortic stenosis rats was not different from that of the control rats. Northern blot analyses of poly(A)+ purified RNA demonstrated the expression of ACE mRNA, which was increased fourfold in left ventricular tissue obtained from the hearts with left ventricular hypertrophy compared with the controls. In both groups, the intracardiac conversion of angiotensin I to angiotensin II caused a comparable dose-dependent increase in coronary resistance. In the control hearts, angiotensin II activation had no significant effect on systolic or diastolic function; however, it was associated with a dose-dependent depression of left ventricular diastolic relaxation in the hypertrophied hearts. These novel observations suggest that cardiac ACE is induced in hearts with left ventricular hypertrophy, and that the resultant intracardiac activation of angiotensin II may have differential effects on myocardial relaxation in hypertrophied hearts relative to controls. (J. Clin.

show abstract

“…The heart was quickly excised and soaked in KrebsÐHenseleit solution at 4°C. Coronary perfusion was initiated through a short cannula in the aortic root and maintained at a constant pressure of 90 mmHg in a non-recirculating way by the Langendorff technique as described by Lorell et al (1986). Perfusion pressure was measured by a P23Db transducer (Bentley Trantec) connected to the aortic infusion cannula.…”

Section: Perfusion Of Isolated Rat Heartsmentioning

confidence: 99%

“…This model consists in treating rats every two days for 11 days with anthracyclines, at the dose of 3 mg kg Ð1 per day (18 mg kg Ð1 cumulative dose), intraperitonealy (i.p.). The myocardial functional performances are studied on the 12th day by perfusion of the isolated hearts and measure of the pressure developed in the left ventricle, according to Langendorff (Lorell et al, 1986).…”

mentioning

confidence: 99%

Preclinical evaluation of the cardiac toxicity of HMR-1826, a novel prodrug of doxorubicin

Platel

Bonoron‐Adèle

Dix³

et al. 1999

Br J Cancer

View full text Add to dashboard Cite

Cardiotoxicity represents the major side-effect limiting the clinical use of anthracyclines, especially doxorubicin, in cancer chemotherapy. The use of non-toxic prodrugs, or of liposome-encapsulated drugs, allows a better targeting of the tumours and may, therefore, improve the tolerance to the treatment. Using the model of isolated perfused rat heart, we have evaluated the cardiotoxicity of a novel prodrug of doxorubicin, HMR-1826, which consists of the association of doxorubicin to glucuronic acid. We have compared the cardiac effects (developed pressure, contractility and relaxation of the left ventricle) induced by HMR-1826 to those induced by doxorubicin and Doxil, a liposomal form of doxorubicin. HMR-1826 was administered intravenously every other day for 11 days at doses of 50–200 mg kg −1 per injection while doxorubicin was administered according to the same protocol at doses of 1–3 mg kg −1 per injection. Doxorubicin strongly decreased the cardiac functional parameters at the doses of 2.5 and 3 mg kg −1 per injection. Doxil (3 mg kg −1 ) and HMR-1826 (50–150 mg kg −1 ) were largely devoid of cardiotoxicity. HMR-1826 only induced significant alterations of the cardiac function at the highest dose used (200 mg kg −1 per injection). These alterations were much lower than those of doxorubicin at 2.5 mg kg −1 per injection, despite similar general toxicity symptoms (weight loss, nose bleeding and diarrhoea) at these respective doses. Thus, HMR-1826 appeared about 100-fold less cardiotoxic than doxorubicin. © 1999 Cancer Research Campaign

show abstract

The influence of pressure overload left ventricular hypertrophy on diastolic properties during hypoxia in isovolumically contracting rat hearts.

Cited by 56 publications

References 61 publications

Myc controls transcriptional regulation of cardiac metabolism and mitochondrial biogenesis in response to pathological stress in mice

Myc controls transcriptional regulation of cardiac metabolism and mitochondrial biogenesis in response to pathological stress in mice

Increased rat cardiac angiotensin converting enzyme activity and mRNA expression in pressure overload left ventricular hypertrophy. Effects on coronary resistance, contractility, and relaxation.

Preclinical evaluation of the cardiac toxicity of HMR-1826, a novel prodrug of doxorubicin

Contact Info

Product

Resources

About