Effects of ischemia on function and metabolism of the isolated working rat heart

Neely,; Rovetto, MJ; Jt, Whitmer; He, Meian

doi:10.1152/ajplegacy.1973.225.3.651

Cited by 326 publications

(106 citation statements)

References 17 publications

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“…Similarly, ischemia induced GLUT4 translocation in isolated cardiac myocytes (31). On the other hand, three decades ago Finck et al (32) had shown an ischemia-induced reduction of glucose uptake, a finding that was supported by a recent study that found no increase in glucose uptake despite AMPK activation in ischemic isolated working hearts (33). Similarly, the data regarding ACC are not entirely consistent.…”

Section: Discussionmentioning

confidence: 86%

Metabolic Switch and Hypertrophy of Cardiomyocytes following Treatment with Angiotensin II Are Prevented by AMP-activated Protein Kinase

Stuck¹,

Lenski²,

Böhm

et al. 2008

Journal of Biological Chemistry

107

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Left ventricular (LV)3 hypertrophy is a major independent risk factor for premature death (1). Myocardial hypertrophy is a response to hemodynamic overload such as hypertension or aortic valve stenosis. A fundamental mechanism leading to both hypertrophy and subsequent heart failure is activation of the renin-angiotensin-aldosteron system. All components of the system are expressed at the mRNA and protein levels in the heart (2), circulating plasma concentrations of angiotensin II (Ang II) correlate to the extend of LV hypertrophy (3) and the progression to heart failure (4), and the increase in left ventricular mass can be prevented with an angiotensin converting enzyme inhibitor or angiotensin receptor blocker (5).Molecular mechanisms by which the renin-angiotensin-aldosteron system evokes cardiac hypertrophy are activation of protein kinase cascades, initiation of a fetal-like gene program, impaired calcium handling, and increased production of reactive oxygen species (6). Changes in substrate utilization occurring during cardiomyocyte hypertrophy are not well known, and their consequences on cardiomyocyte metabolism and energy supply are not completely understood. A shift in the substrate pattern from fatty acid oxidation to glucose utilization appears to occur in different forms of LV hypertrophy (7), but whether metabolic changes precede hypertrophy or result from it and which pathways are involved is unknown.A key metabolic regulator is AMP-activated protein kinase (AMPK), a heterotrimeric protein that is centrally involved in controlling cellular energy homeostasis. Its activation through metabolic stress stimulates energy-generating processes and has been shown to regulate hypertrophy-regulating genes in several models (8). When AMPK binds AMP the ␣-subunit gets sensitized to phosphorylation by upstream kinases and increases kinase activity. Upon activation AMPK increases fatty acid oxidation by phosphorylating ACC, in turn decreasing malonyl-CoA content and activating carnitine palmitoyltransferase-I. In several tissues AMPK has been shown to also regulate glucose metabolism (9) and translocation of glucose transporter 4 (GLUT4) to the plasma membrane (10). Activated AMPK mediates changes in protein expression through regu-

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Section: Discussionmentioning

confidence: 86%

Metabolic Switch and Hypertrophy of Cardiomyocytes following Treatment with Angiotensin II Are Prevented by AMP-activated Protein Kinase

Stuck¹,

Lenski²,

Böhm

et al. 2008

Journal of Biological Chemistry

107

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“…Alterations in mechanical and metabolic functions of myocardial cells are generally reversible up to 20 minutes following restriction of coronary blood flow, but irreversible damage and cell death occur between 20 and 60 minutes (2)(3)(4)(5)(6)(7). The time of onset of cell death may be directly proportional to the restriction in coronary blood flow.…”

mentioning

confidence: 99%

Effect of coronary blood flow on glycolytic flux and intracellular pH in isolated rat hearts.

Neely¹,

Whitmer²,

Rovetto³

1975

Circulation Research

197

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The rate of coronary blood flow was varied in isolated working rat heart preparations to determine its influence on the rate of glucose utilization, tissue high-energy phosphates, and intracellular pH. A 60% reduction in coronary blood flow resulted in a 30% reduction in oxygen consumption, an accelerated rate of glucose utilization, lower tissue levels of high-energy phosphates, and higher tissue levels of lactate and H + . Ventricular performance deteriorated as reflected by a decrease in heart rate and peak systolic pressure. Further reductions in coronary blood flow resulted in inhibition of glycolysis, a greater decrease in tissue levels of high-energy phosphates, and higher tissue levels of both lactate and H + . These changes in glycolytic flux, tissue metabolites, and ventricular performance were proportional to the degree of restriction in coronary blood flow. The importance of coronary blood flow and washout of the interstitial space in the maintenance of accelerated glycolytic flux in oxygen-deficient hearts is emphasized. It is concluded that acceleration of ATP production from glycolysis can occur only in the marginally ischemic tissue in the peripheral area of tissue supplied by an occluded artery. The central area of tissue which receives a low rate of coronary blood flow will have a reduced rate of ATP production due to both a lack of oxygen and an inhibition of glycolysis.

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“…Perfüze edilen sıvı kanüle edilen sol atriyumdan kalbe girer, sol ventrikülden geçerek aorttan çıkar. 78 …”

Section: çAlışan Kalp Modeliunclassified

Myocardial and Renal Ischemia/Reperfusion Injury and Experimental Models: Review

Şenol¹,

Tunçtan²

2016

Turkiye Klinikleri J Pharm Sci

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Ö ÖZ ZE ET T Doku iskemisi, miyokard infarktüsü ve inme gibi klinik durumlarda ya da damar cerrahisi ve organ transplantasyonunda komplikasyon olarak ortaya çıkabilen bir durumdur. Reperfüzyon, iskemiye maruz kalan dokunun yeniden kanlanarak oksijenlenmesidir. İskemi/reperfüzyon (İ/R) zedelenmesi, kan akışının yeniden düzenlenmesiyle gelişen inflamatuar tepkilerin bir sonucudur. Erken evrede glikoliz yoluyla laktat üretimi sonucu hücre içi pH değeri düşer. Hücreleri nekroza karşı koruyan bu düşüş, reperfüzyon sıra-sında normal pH değerine yükseldiğinde iskemik hücrelerin ölümünü hızlandırır. Orta evre ise oksidatif stres ile belirgindir. Oksidatif stres belli bir eşiği aşarsa hücresel işlev bozukluğu, geri döndürülemez zedelenme ve hücre ölümü gerçekleşir. Geç evrede, inflamatuar hücreler ve adezyon molekülleri baskındır. Birçok inflamatuar molekül tarafından uyarılan nötrofil etkinliği İ/R süreci boyunca görülür. Miyokardiyal İ/R zedelenmesi miyokardiyal sersemleme (stunning), reperfüzyon aritmileri, miyositlerde nekroz ile koroner endotelyal ve mikrovasküler işlev bozukluğu gibi istenmeyen durumların ortaya çıkmasına yol açabilir. Deneysel olarak çalışılan konular miyokardiyal sersemleme, hibernasyon, reperfüzyon aritmileri ve ön koşul-lamadır. Akut renal yetmezlik (ARY) insanlarda yüksek mortalite ile ilişkili majör bir böbrek hastalığıdır. Kalp debisinin azalması, renal vasküler oklüzyon veya obstrüksiyon ile renal transplantasyon gibi durumların neden olduğu iskemi, ARY gelişmesine neden olabilir. Deneysel olarak çift taraflı (bilateral) ve tek taraflı (unilateral) renal İ/R zedelenmesi oluşturulabilmektedir. Çift taraflı iskemik ARY modeli insandaki patolojik duruma çok daha uygun olmasından dolayı yaygın olarak kullanılmaktadır. Bu çalışmada, ilaçla-rın miyokardiyal veya renal İ/R zedelenmesine bağlı olarak gelişen fizyopatolojik değişiklikler üzerindeki etkilerinin araştırılması amacıyla kullanılan deneysel modeller üzerinde durulmuştur.A An na ah h t ta ar r K Ke e l li i m me e l le er r: : İskemi; reperfüzyon hasarı; oksidatif stres; inflamasyon; miyokardiyal reperfüzyon hasarı; akut böbrek hasarı A AB BS S T TR RA AC CT T Tissue ischemia is a condition that can occur with clinical conditions like myocardial infarction and stroke or as a complication of vascular surgery and organ transplantation. Reperfusion is reoxygenation of tissue exposed to ischemia by restoration of blood flow. Ischemia/reperfusion (I/R) injury is a consequence of inflammatory reaction induced by modulating blood flow. Intracellular pH falls as a result of lactate production through glycolysis at early stage. The decrease protecting cells against necrosis accelerates ischemic cell death at normal pH value during reperfusion. Intermediate phase is characterized by oxidative stress. If oxidative stress exceeds a certain threshold, cellular dysfunction, irreversible injury, and cell death occurs. At the late stage, inflammatory cells and adhesion molecules are dominant. Neutrophil activity stimulated by many inflammatory molecules ...

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Effects of ischemia on function and metabolism of the isolated working rat heart

Cited by 326 publications

References 17 publications

Metabolic Switch and Hypertrophy of Cardiomyocytes following Treatment with Angiotensin II Are Prevented by AMP-activated Protein Kinase

Metabolic Switch and Hypertrophy of Cardiomyocytes following Treatment with Angiotensin II Are Prevented by AMP-activated Protein Kinase

Effect of coronary blood flow on glycolytic flux and intracellular pH in isolated rat hearts.

Myocardial and Renal Ischemia/Reperfusion Injury and Experimental Models: Review

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