Tracing cardiac metabolism in vivo: one substrate at a time

Abstract

In the myocardial cell, a series of enzyme-catalyzed reactions results in the efficient transfer of chemical energy into mechanical energy. The goals of this article are to emphasize the ability of noninvasive imaging techniques using isotopic tracers to detect the metabolic footprints of heart disease and to propose that cardiac metabolic imaging is more than a useful adjunct to current myocardial perfusion imaging studies. A strength of metabolic imaging is in the assessment of regional myocardial differences in metabolic activity, probing for 1 substrate at a time. We hope that new and developing methods of cardiac imaging will lead to the earlier detection of heart disease and improve the management and quality of life for patients afflicted with ischemic and nonischemic heart muscle disorders.

Figure 1

The transfer of energy from the coronary circulation to the contractile elements (crossbridges) moves through a series of moiety-conserved cycles. Substrates and metabolites can be traced by non-invasive methods. See text for further detail.

Figure 2

Substrate metabolism in the heart can be divided into substrate uptake and metabolism [1], oxidation [2], and ATP production [3]. Each state can be traced. See text for further detail.

Figure 3

Positron labeled tracer analogs for either fatty acids or glucose are transported into the heart muscle cell and retained, while positron labeled tracer substrates (¹¹C-compounds and ¹⁵O₂) are taken up, metabolized and released (as either ¹¹CO₂ or H₂¹⁵O). See text for further details.

Figure 4

Progressive accumulation of the glucose tracer analog 18F-2-deoxyglucose by an isolated working rat heart perfused with Krebs-Henseleit bicarbonate saline containing glucose (5mM) as substrate. The input function (radioactivity in the perfusate) was stable (lower curve). At time 60 min perfusate was switched to the same saline without the tracer analog (lower curve). The tissue retention of the tracer analog was stable (upper curve). Cardiac work was the same throughout the experiment. See text for further detail. (Adapted from (42)).

Figure 5

Adaptive and maladaptive stress responses of the myocardium. The adaptive response of myocardial hibernation has distinctly different features from the maladaptive response of myocardial lipotoxicity. Both processes can be traced by non-invasive methods. See text for further detail. (Adapted from (64)).