The network for cardiac fuel metabolism contains intricate sets of interacting pathways that result in both ATP-producing and non-ATP-producing end points for each class of energy substrates. The most salient feature of the network is the metabolic flexibility demonstrated in response to various stimuli, including developmental changes and nutritional status. The heart is also capable of remodeling the metabolic pathways in chronic pathophysiological conditions, which results in modulations of myocardial energetics and contractile function. In a quest to understand the complexity of the cardiac metabolic network, pharmacological and genetic tools have been engaged to manipulate cardiac metabolism in a variety of research models. In concert, a host of therapeutic interventions have been tested clinically to target substrate preference, insulin sensitivity, and mitochondrial function. In addition, the contribution of cellular metabolism to growth, survival, and other signaling pathways through the production of metabolic intermediates has been increasingly noted. In this review, we provide an overview of the cardiac metabolic network and highlight alterations observed in cardiac pathologies as well as strategies used as metabolic therapies in heart failure. Lastly, the ability of metabolic derivatives to intersect growth and survival are also discussed.

Cardiac Metabolism and its Interactions With Contraction, Growth, and Survival of Cardiomyocytes

Heart failure (HF) is a syndrome resulting from the inability of the cardiac pump to meet the energy requirements of the body. Despite intensive work, the pathogenesis of the cardiac intracellular abnormalities that result from HF remains incompletely understood. Factors that lead to abnormal contraction and relaxation in the failing heart include metabolic pathway abnormalities that result in decreased energy production, energy transfer and energy utilization. Heart failure also affects the periphery. Patients suffering from heart failure always complain of early muscular fatigue and exercise intolerance. This is linked in part to intrinsic alterations of skeletal muscle, among which decreases in the mitochondrial ATP production and in the transfer of energy through the phosphotransfer kinases play an important role. Alterations in energy metabolism that affect both cardiac and skeletal muscles argue for a generalized metabolic myopathy in heart failure. Recent evidence shows that decreased expression of mitochondrial transcription factors and mitochondrial proteins are involved in mechanisms causing the energy starvation in heart failure. This review will focus on energy metabolism alterations in long-term chronic heart failure with only a few references to compensated hypertrophy when necessary. It will briefly describe the energy metabolism of normal heart and skeletal muscles and their alterations in chronic heart failure. It is beyond the scope of this review to address the metabolic switches occurring in compensated hypertrophy; readers could refer to well-documented reviews on this subject.

https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1113/jphysiol.2003.055095

Energy metabolism in heart failure

VI. VOLTAGE GA'r~D Ca\" + C ~ , lc, 1. Effects of O-Stimulation on Ic, 2. Regulation of Ca \"÷ Channel Properties by Narepinephrine and cAMP 3. Relationship Between Inactivation and Availability 4. Purification of Ca\" + Channels and their Phosphorylation 5. Effects of ACh on Control Ic. 6. Effects of ACh on [3-Stimulated Ic. 7. Possible Role of cGMP in Regulating Ic. 8. Direct Effects of G-Proteins 9. ,,-Adrenergic Regulation of Ic,

Regulation of cardiac ion channels by catecholamines, acetylcholine and second messenger systems.

The transverse tubules (t-tubules) of mammalian cardiac ventricular myocytes are invaginations of the surface membrane. Recent studies have suggested that the structure and function of the t-tubules are more complex than previously believed; in particular, many of the proteins involved in cellular Ca2+ cycling appear to be concentrated at the t-tubule. Thus, the t-tubules are an important determinant of cardiac cell function, especially as the main site of excitation-contraction coupling, ensuring spatially and temporally synchronous Ca2+ release throughout the cell. Changes in t-tubule structure and protein expression occur during development and in heart failure, so that changes in the t-tubules may contribute to the functional changes observed in these conditions. The purpose of this review is to provide an overview of recent studies of t-tubule structure and function in cardiac myocytes.

T-Tubule Function in Mammalian Cardiac Myocytes

In 1923, Nobel Laureate A.V. Hill proposed that maximal exercise performance is limited by the development of anaerobiosis in the exercising skeletal muscles. Variants of this theory have dominated teaching in the exercise sciences ever since, but 90 years later there is little biological evidence to support Hill’s belief, and much that disproves it. The cardinal weakness of the Hill model is that it allows no role for the brain in the regulation of exercise performance. As a result, it is unable to explain at least 6 common phenomena, including (i) differential pacing strategies for different exercise durations; (ii) the end spurt; (iii) the presence of fatigue even though homeostasis is maintained; (iv) fewer than 100% of the muscle fibers have been recruited in the exercising limbs; (v) the evidence that a range of interventions that act exclusively on the brain can modify exercise performance; and (vi) the finding that the rating of perceived exertion is a function of the relative exercise duration ra...

/pdf/time-to-move-beyond-a-brainless-exercise-physiology-the-3mv6g5vl0f.pdf

Time to move beyond a brainless exercise physiology: the evidence for complex regulation of human exercise performance.

In the single authored, expert voice that is this book's unique strength, Arnold Katz provides a comprehensive overview of the physiological and biophysical basis of cardiac function, beginning with structure and proceeding to biochemistry, biophysics, and pathophysiology in arrhythmias, ischemia, and heart failure. Emphasis is on the interrelationships of basic processes among the cell, cardiac muscle function, and the biophysics of contractile and electrical behavior. This edition includes new material on cell signaling and molecular biology.

Ulrich J

Papers

Physiology of the heart