Human cardiac metabolism

Abstract

The heart is the most metabolically active organ in the human body, and cardiac metabolism has been studied for decades. However, the bulk of studies have focused on animal models. The objective of this review is to summarize specifically what is known about cardiac metabolism in humans. Techniques available to study human cardiac metabolism are first discussed, followed by a review of human cardiac metabolism in health and in heart failure. Mechanistic insights, where available, are reviewed, and the evidence for the contribution of metabolic insufficiency to heart failure, as well as past and current attempts at metabolism-based therapies, is also discussed.

Keywords: 11C-palmitate; FDG; PCr/ATP; cardiac; coronary sinus; heart failure; metabolism.

Figure 1:

Methodologies for evaluation of human cardiac metabolism. A: arterio-venous sampling. B: FDG-PET scanning. Inset shows typical short axis FDG-PET image. Below: spontaneous decay of FDG to glucose. C: 4-compartment model of ¹¹C-palmitate uptake and oxidation. D: ³¹P-MRS. Inset shows typical resonance pattern at 3 and 7 tesla (T), revealing prominent peaks for high-energy phosphates PCr, ATP, and 2,3 DPG. Below: PCr shuttle; see text for details. Image created with Biorender.

Figure 2:

Fuel uptake, cycling through intracellular pools, and simultaneous lactate uptake and secretion. A: rates of uptake and oxidation of carbohydrates (glucose and lactate) and of glucose cycling through the glycogen pool, in fasting young healthy male volunteers. Adapted from data in Wisneski et al. 1985. Note that one glucose molecule yields 2 molecules of pyruvate. B: rates of uptake and oxidation of fatty acids from albumin-carried FFA and lipoprotein-carried TG pools, of FA cycling through the intracellular TG pool, and of ketones, in fasting young healthy male volunteers. Adapted from data in Wisneski et al. 1987. All values are micromoles/min/g. Image created with Biorender.

Figure 3:

Estimated fuel contribution to the generation of cardiac ATP in fasting individuals, compared to fed and fasted mice. Left: healthy 18-year-old male in 1950’s, BMI 25. Middle: average 60-year-old American in 2020, BMI 30. Right: average American in 2020 with HFrEF. Data collated from Bing et al. 1954, Most et al. 1969, Wisneski et al. 1985, Murashige et al. 2020, Hui et al. 2020. Image created with Biorender.

Figure 4:

Comparing pre-clinical and human alterations of fuel use and mitochondrial function in heart failure. See Lopaschuk et al. 2021 for pre-clinical details. G6P: glucose-6-phosphate. PDH: pyruvate dehydrogenase. FAO: fatty acid oxidation. TCA: tricarboxylic acid. Image created with Biorender.