Effect of substrate on mitochondrial NADH, cytosolic redox state, and phosphorylated compounds in isolated hearts

Scholz, Thomas; Laughlin, Maren R.; Balaban, Robert S.; Kupriyanov, V.V.; Heineman, F. W.

doi:10.1152/ajpheart.1995.268.1.h82

Cited by 62 publications

(77 citation statements)

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“…It has been found in isolated mitochondria [218], in single cells [101], and in perfused whole-hearts [219]. The positive inotropic actions of pyruvate have also been noticed many times in vivo [219][220][221] and, more recently, in isolated myocytes [222]. In Table 3b, we document the increased work output per beat achieved when pyruvate replaces glucose or when it is present together with glucose.…”

Section: Modifiers Of Basal Metabolismmentioning

confidence: 57%

Cardiac Basal Metabolism.

Gibbs

Loiselle²

2001

JJP

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The cardiac basal metabolism is the rate of energy expenditure of the quiescent myocardium. It is also called the resting metabolism or the arrested heart metabolism. It has been measured in numerous ways, and in vivo there is good evidence that it accounts for about 1/5 to 1/3 of the total energy flux. The difficulty arises, however, when the heart is stopped because the magnitude of the basal metabolism depends, as blood viscosity, on how and under what physiological condition it is measured. It is possible for the in vivo basal value to fall to less than 1/5 of its original value without cellular damage or to increase to values 5 times greater than its probable in vivo magnitude (i.e., to rise to values in excess of the energy flux of the normally beating heart) by altering the composition of the perfusion medium. We have written on this subject several times [1][2][3], but believe that developments in knowledge now make it possible for us to speculate in a more informed manner. Since several million openheart operations are performed on arrested hearts worldwide each year, it would seem imperative that we understand the cellular mechanisms that can change the magnitude of basal metabolism.A. V. Hill [4] has pointed out that in examining physiological activities, it is necessary to assume a baseline from which some quantity or rate can be measured. If the energy flux produced by the beating heart were very large compared with the energy flux of the arrested heart, baseline ambiguity would be relatively unimportant. But this is not so in regard to the heart; its basal metabolism is high. Within a species, the basal metabolism of cardiac tissue is several-fold higher than the resting metabolism of skeletal muscle and is an order of magnitude greater than the resting metabolism of amphibian skeletal muscle.Species differences are clearly evident in the magnitude of cardiac basal metabolism, and we believe that the major reason for these differences relates to the leakiness of cell membranes, such as those of the sarcolemma and sarcoplasmic reticulum and those of Japanese Journal of Physiology, 51, 399-426, 2001 Key words: whole hearts, isolated preparations, biochemical contributors, modifiers, species difference, temperature, substrate, hypoxia. Abstract:We endeavor to show that the metabolism of the nonbeating heart can vary over an extreme range: from values approximating those measured in the beating heart to values of only a small fraction of normal-perhaps mimicking the situation of nonflow arrest during cardiac bypass surgery. We discuss some of the technical issues that make it difficult to establish the magnitude of basal metabolism in vivo. We consider some of the likely contributors to its magnitude and point out that the biochemical reasons for a sizable fraction of the heart's basal ATP usage remain unresolved. We consider many of the physiological factors that can alter the basal metabolic rate, stressing the importance of substrate supply. We point out that the protective effect of hypothermia ...

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Section: Modifiers Of Basal Metabolismmentioning

confidence: 57%

Cardiac Basal Metabolism.

Gibbs

Loiselle²

2001

JJP

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“…Later, Scholz et al used a spectrograph and photodiode array to measure average fNADH from a large area of the LV. This approach reduced the effects of epicardial fluorescence heterogeneities and local variations in circulation while revealing macroscopic work-related variations of fNADH 31 . This approach is similar to computing average fNADH levels for a region of interest across all frames of an fNADH imaging dataset, as illustrated in Figure 2.…”

Section: Discussionmentioning

confidence: 99%

NADH Fluorescence Imaging of Isolated Biventricular Working Rabbit Hearts

Asfour

Wengrowski

Jaimes

et al. 2012

JoVE

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Since its inception by Langendorff 1 , the isolated perfused heart remains a prominent tool for studying cardiac physiology 2 . However, it is not well-suited for studies of cardiac metabolism, which require the heart to perform work within the context of physiologic preload and afterload pressures. Neely introduced modifications to the Langendorff technique to establish appropriate left ventricular (LV) preload and afterload pressures 3 . The model is known as the isolated LV working heart model and has been used extensively to study LV performance and metabolism [4][5][6] . This model, however, does not provide a properly loaded right ventricle (RV). Demmy et al. first reported a biventricular model as a modification of the LV working heart model 7,8 . They found that stroke volume, cardiac output, and pressure development improved in hearts converted from working LV mode to biventricular working mode 8 . A properly loaded RV also diminishes abnormal pressure gradients across the septum to improve septal function. Biventricular working hearts have been shown to maintain aortic output, pulmonary flow, mean aortic pressure, heart rate, and myocardial ATP levels for up to 3 hours 8 .When studying the metabolic effects of myocardial injury, such as ischemia, it is often necessary to identify the location of the affected tissue. This can be done by imaging the fluorescence of NADH (the reduced form of nicotinamide adenine dinucleotide) [9][10][11] , a coenzyme found in large quantities in the mitochondria. NADH fluorescence (fNADH) displays a near linearly inverse relationship with local oxygen concentration 12 and provides a measure of mitochondrial redox state 13. fNADH imaging during hypoxic and ischemic conditions has been used as a dye-free method to identify hypoxic regions 14,15 and to monitor the progression of hypoxic conditions over time 10.The objective of the method is to monitor the mitochondrial redox state of biventricular working hearts during protocols that alter the rate of myocyte metabolism or induce hypoxia or create a combination of the two. Hearts from New Zealand white rabbits were connected to a biventricular working heart system (Hugo Sachs Elektronik) and perfused with modified Krebs-Henseleit solution 16 at 37 °C. Aortic, LV, pulmonary artery, and left & right atrial pressures were recorded. Electrical activity was measured using a monophasic action potential electrode. To image fNADH, light from a mercury lamp was filtered (350±25 nm) and used to illuminate the epicardium. Emitted light was filtered (460±20 nm) and imaged using a CCD camera. Changes in the epicardial fNADH of biventricular working hearts during different pacing rates are presented. The combination of the heart model and fNADH imaging provides a new and valuable experimental tool for studying acute cardiac pathologies within the context of realistic physiological conditions. Video LinkThe video component of this article can be found at https://www. 10.0 glucose, 2.00 NaPyruvate, and 20.0 mg/L albumin). The soluti...

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“…Both sites, especially complex III, are potential sources of electron leakage with formation of free radicals in the presence of O 2 (38). NADH (and FADH 2 ) are products of the tricarboxylic acid (TCA) cycle and the ␤-oxidation of fatty acids (36). Dehydrogenases generate NADH from NAD ϩ during glycolysis.…”

Section: Discussionmentioning

confidence: 99%

Altered NADH and improved function by anesthetic and ischemic preconditioning in guinea pig intact hearts

Riess¹,

Camara²,

Chen³

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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NADH increases during ischemia because O2 shortage limits NADH oxidation at the electron transport chain. Ischemic (IPC) and anesthetic preconditioning (APC) attenuate cardiac reperfusion injury. We examined whether IPC and APC similarly alter NADH, i.e., mitochondrial metabolism. NADH fluorescence was measured at the left ventricular wall of 40 Langendorff-prepared guinea pig hearts. IPC was achieved by two 5-min periods of ischemia and APC by exposure to 0.5 or 1.3 mM sevoflurane for 15 min, each ending 30 min before 30 min of global ischemia. During ischemia, NADH initially increased in nonpreconditioned control hearts and then gradually declined below baseline levels. This increase in NADH was lower after APC but not after IPC. The subsequent decline was slower after IPC and APC. On reperfusion, NADH was less decreased after IPC or APC, mechanical and metabolic functions were improved, and infarct size was lower compared with controls. Our results indicate that IPC and APC cause distinctive changes in mitochondrial metabolism during ischemia and thus lead to improved function and tissue viability on reperfusion.experimental; infarction; sevoflurane; dose dependency; mitochondrial function EXPERIMENTS IN ISOLATED MYOCYTES, intact hearts, and whole animal models have shown that cardiac cell injury and mechanical dysfunction are caused by reperfusion after prolonged ischemia. Depending on the duration and magnitude of the ischemia, the injury can be reversible (stunning) or irreversible (infarction) (20). Several interrelated mechanisms are responsible:

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Effect of substrate on mitochondrial NADH, cytosolic redox state, and phosphorylated compounds in isolated hearts

Cited by 62 publications

References 0 publications

Cardiac Basal Metabolism.

Cardiac Basal Metabolism.

NADH Fluorescence Imaging of Isolated Biventricular Working Rabbit Hearts

Altered NADH and improved function by anesthetic and ischemic preconditioning in guinea pig intact hearts

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