Scheiber 2019 Exp Mol Med
Scheiber D, Jelenik T, Zweck E, Horn P, Schultheiss HP, Lassner D, Boeken U, Saeed D, Kelm M, Roden M, Westenfeld R, Szendroedi J (2019) High-resolution respirometry in human endomyocardial biopsies shows reduced ventricular oxidative capacity related to heart failure. Exp Mol Med 51:16. |
Scheiber D, Jelenik T, Zweck E, Horn P, Schultheiss HP, Lassner D, Boeken U, Saeed D, Kelm M, Roden M, Westenfeld R, Szendroedi J (2019) Exp Mol Med
Abstract: The lifetime risk of developing heart failure is approximately 20%, and survival rates remain poor. Myocardial mitochondrial function has been suggested to play a pivotal role in heart failure pathophysiology. Human studies on ex vivo mitochondrial function have mostly been limited to atrial tissue obtained during open heart surgery and have provided contradictory results. This study aimed at measuring myocardial mitochondrial function in transcatheter ventricular endomyocardial biopsies and assessing the relationship between oxidative capacity and heart function. We enrolled 40 heart failure patients undergoing ventricular assist device surgery or heart transplantation (34 males, age 57βΒ±β11 years, body mass index 26.6βΒ±β4.8βkg/m2) and 29 heart transplant recipients of comparable age and body mass index with normal left ventricular function undergoing surveillance biopsies (23 males, 57βΒ±β12 years, body mass index 26.2βΒ±β4.1βkg/m2). High-resolution respirometry was established in the myocardium to measure oxidative capacity ex vivo. The mitochondrial oxidative capacity was 90% higher in ventricular compared to atrial tissues (nβ=β11, pβ<β0.01) of explanted hearts. Respiration rates were comparable in ventricular samples of heart failure patients obtained during open heart surgery by standard tissue preparation or ex vivo endomyocardial biopsy (rβ=β0.9988, pβ<β0.0001, nβ=β8), and the mitochondrial oxidative capacity in samples from these patients remained stable for 8βh when stored in either of two common preservation buffers. The oxidative capacity was 44% lower in heart failure than in transplant recipients (67βΒ±β3 vs. 97βΒ±β5 pmol/[sβmg], pβ<β0.0001) and correlated positively with heart function (rβ=β0.49, pβ<β0.01). High-resolution respirometry of ventricular tissue is feasible in transcatheter biopsies, facilitating clinical studies on myocardial mitochondrial function in patients not undergoing heart surgery. β’ Keywords: Amplex Red in muscle fibers β’ Bioblast editor: Plangger M β’ O2k-Network Lab: DE Duesseldorf Roden M
Labels: MiParea: Respiration, Patients
Pathology: Cardiovascular
Organism: Human Tissue;cell: Heart Preparation: Permeabilized tissue, Isolated mitochondria
Coupling state: LEAK, OXPHOS, ET
Pathway: F, N, NS
HRR: Oxygraph-2k, O2k-Fluorometer
2019-02, AmR