Evidence of functional deficits at the single muscle fiber level in experimentally-induced renal insufficiency
2019
Chronic kidney disease patients present with metabolic and functional muscle
abnormalities, called uremic myopathy, whose mechanisms have not yet been fully
elucidated. We investigated whether chronic renal insufficiency (CRI) affects skeletal
muscle contractile properties at the cellular level. CRI was induced surgically in New
Zealand rabbits (UREM), with sham-operation for controls (CON), and samples were
collected at 3 months post-surgery, following euthanasia. All protocols had University
Ethics approval following national and European guidelines. Sample treatments and
evaluations were blinded. Maximal isometric force was assessed in 382 permeabilized
psoas fibers (CON, n=142, UREM, n=240) initially at pH7, 10oC (‘standard’
conditions), in subsets of fibers in acidic conditions (pH6.2, 10oC) but also at near
physiological temperature (pH7, 30oC and pH6.2, 30oC). CRI resulted in significant
smaller average CSA (~11%) for UREM muscle fibers (vs CON, P<0.01). At
standard conditions, UREM fibers produced lower absolute and specific forces (i.e.
normalized force per fiber CSA) (vs CON, P<0.01); force increased in 30oC for both
groups (P<0.01), but the disparity between UREM and CON remained significant.
Acidosis significantly reduced force (vs pH7, 10oC P<0.01), similarly in both groups
(in UREM by -48% and in CON by -43%, P>0.05). For the first time, we give
evidence that CRI can induce significant impairments in single psoas muscle fibers
force generation, only partially explained by fiber atrophy, thus affecting muscle
mechanics at the cellular level.
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