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Ward 2015 Abstract IOC106

From Bioblast
Power A, Crossman D, Hickey AJ, Ward M (2015) Investigating mitochondrial function in a rat model of right ventricular hypertrophy. Mitochondr Physiol Network 20.10.

Link:

Power A, Crossman D, Hickey AJ, Ward M (2015)

Event: IOC106 Schroecken

Background: The heart is a highly aerobic organ with more than 90% of ATP regenerated by oxidative phosphorylation (OXPHOS) in the mitochondria. Mitochondrial dysfunction has been identified as a hallmark in the transition of compensatory hypertrophy to heart failure. However, the contribution of mitochondrial dysfunction to the contractile deficit is debated.

Objectives: To determine if mitochondrial energy supply compromises contractile function in right ventricular (RV) hypertrophy.

Methods: Rats were injected with monocrotaline (MCT) to induce pulmonary artery hypertension and RV hypertrophy, or saline (CON) for age-matched controls. Four weeks post-injection, multicellular cardiac trabeculae (length 2-3 mm, diameter 150-250 ยตm) were micro-dissected from the RV and mounted on an inverted microscope between a force transducer and a length changer. Steady-state force and intracellular Ca2+ transients were measured prior to saponin "skinning" of the sarcolemma to allow buffer access to the cytosol without damaging organelle membranes. Contraction and relaxation of the trabeculae was then assessed using buffered Ca2+ solutions, with and without exogenous ATP added to the superfusate.

Results: MCT trabeculae produced similar force to CON despite having lower Ca2+ transients. Following skinning, CON trabeculae showed no change in the maximum Ca2+-activated force when exogenous ATP was removed from superfusate, while MCT trabeculae showed smaller contractures without exogenous ATP when stimulated with saturating Ca2+.

Discussion: In this MCT model of compensated right ventricular hypertrophy there appears to be only a small contribution of mitochondrial dysfunction to contraction/relaxation when intracellular Ca2+ is controlled. This protocol can be used to further examine energy specific deficits in the failing heart, and to investigate the effects of drugs that modulate mitochondrial energy supply on contractile function.


โ€ข O2k-Network Lab: NZ Auckland Hickey AJ


Labels: Pathology: Cardiovascular 

Organism: Rat  Tissue;cell: Heart 





Affiliations

Dept Physiology and School of Biol Sc, Univ Auckland, New Zealand