What is it about?

Chronic heart failure develops when heart muscle cells have to continuously work harder than sustainable, for instance due to high blood pressure. Millions of patients are affected worldwide. Heart muscle cells can adapt to increased workload. However, limits to adaptation exist, beyond which pump work of the heart decreases. These limits have not yet been precisely determined. Heart muscle cells need energy. The cells release energy by oxidation of fat and glucose in the mitochondria. The oxidation uses oxygen, produces waste products - carbon dioxide and heat - and resynthezises the cellular energy carrier ATP, which is used to produce force, shortening as well as relaxation. We have developed techniques to test the possibility that energy release processes in overloaded muscle cells fail. Heart muscle preparations from rats with right-sided heart failure due to high blood pressure in the pulmonary artery have been used. Work, oxygen consumption, several key molecules of the energy release processes and enzyme activities were measured in small heart muscle preparations (volume smaller than 1 mm3). The development of right-sided chronic heart failure is multifactorial. Energy use redistributes in the muscle cells: work per unit of oxygen consumed is reduced with increasing cell size, activation processes require more oxygen, the rate of antioxidant production increases, and the energy release mechanisms in the mitochondria fail at several sites, indicating that ATP produced/oxygen consumed is reduced. Oxygen consumption for activation processes of the failing heart muscle cells is larger than expected on the basis of previous heat experiments by Pham and coworkers. This discrepancy suggests that overloaded heart muscle cells may excrete hydrogen peroxide.

Featured Image

Why is it important?

Identifying the causes of chronic heart failure is important for prevention and treatment. The results indicate that mitochondrial damage occurs early in the development of chronic heart failure. Mitochondrial damage reduces ATP production and likely induces a vicious cycle of further damage, also elsewhere in and outside the muscle cells. The results warrant further research on mitochondrial function and mitochondrial repair in chronic heart failure.


I hope this work stimulates continued research in myocardial energetics.

Willem J. van der Laarse

Read the Original

This page is a summary of: Work and oxygen consumption of isolated right ventricular papillary muscle in experimental pulmonary hypertension, The Journal of Physiology, September 2022, Wiley, DOI: 10.1113/jp282991.
You can read the full text:



The following have contributed to this page