Mechanistic Model of Myocardial Energy Metabolism Under Normal and Ischemic Conditions

Model Status

This CellML model has been recoded to remove the reaction element. The model runs in both COR and PCEnv and we believe it is close to recreating the original published results. The units have been checked and they are consistent.

Model Structure

In myocardial ischemia, or the reduction of blood flow to the heart, myocardial oxygen consumption and pyruvate oxidation decreases, glycolysis becomes accelerated, and lactate accumulates. To better understand myocardial metabolism under ischemic conditions, Jennifer Salem et al. developed a quantitative mechanistic model in their 2002 paper (see the figure below). They modelled a 60% reduction of coronary blood flow and found that at the onset of ischemia, the concentration of lactate in myocytes increased, and the myocardium switched from a net consumer of lactate to a net producer. After sixty minutes of ischemia, the glycogen concentration was reduced by 60%, phosphocreatine by 75%, and ATP by 50%. Furthermore, their model predicts a rapid 13-fold increase in the ratio of NADH to NAD⁺, but only a twofold increase in the ratio of acetyl-CoA to free-CoA. These predictions are consistent with the idea that pyruvate oxidation is inhibited during ischemia partially by the rise in NADH/NAD⁺.

The complete original paper reference is cited below:

Mechanistic Model of Myocardial Energy Metabolism Under Normal and Ischemic Conditions, Jennifer E. Salem, Gerald M. Saidel, William C. Stanley, and Marco E. Cabrera, 2002, Annals of Biomedical Engineering , 30, 202-216. (A PDF of the article is available to subscribers on the Annals of Biomedical Engineering website.) PubMed ID: 11962772

The reaction pathway of the Salem et al. model. Glucose (through the GLUT transporters), lactate, CO2, O2, and palmitate (fatty acids) are the only species in this model considered to transfer between the blood and myocytes.