Frisbee, Jefferson C., Goodwill, Adam G., Frisbee, Stephanie J., Butcher, Joshua T., Wu, Fan and Chantler, Paul D. (2014) Skeletal muscle microvasculopathy in the metabolic syndrome: What is the fundamental problem contributing to increased muscle fatigue. Journal of Physiology.

Abstract

Over the course of the last 20 years, the OZR model of the metabolic syndrome has proven to be an exceptionally useful model for interrogating health outcomes associated with a constellation of elevated cardiovascular disease risk factors. While impairments to the integrated patterns of vascular reactivity have been extremely well established, simply assigning translational relevance to these measurements as being directly associated with impaired perfusion and, by extension, muscle performance, does not appear to be well justified. While the impairments to vascular reactivity are widely distributed, their functional consequences are not as tightly correlated to their severity as has generally been assumed. As such, simply correcting vascular dysfunction does not necessarily improve muscle perfusion and performance outcomes. More detailed investigation has determined that the importance of the alterations to vascular reactivity is that it engenders a shift in hemodynamic behavior at arteriolar bifurcations, leading to an increasingly heterogeneous distribution of blood flow at each successive bifurcation , with the end result being an extremely heterogeneous distribution of perfusion at the pre-capillary level. Further, this increasingly heterogeneous distribution of perfusion becomes increasingly stable, such that the flexibility within the microvascular networks of OZR is severely attenuated and the ability of the networks to adapt their perfusion patterns to imposed challenges becomes increasingly abrogated. Ultimately, the functional consequences of this accumulating error at successive bifurcations leads to a microvascular hematocrit that is somewhat lower in OZR than LZR, but exceptionally variable and stable. When combined with the significant rarefaction of the microvascular networks of skeletal muscle in OZR, this represents a series of significant contributing impairments to the ability of skeletal muscle to maintain performance with elevated metabolic demand; a defining feature of peripheral vascular disease in afflicted patients. Future experimentation and development of clinical therapeutic efforts could do well to focus on interventions that target the restoration of normal patterns of microvascular perfusion in human subjects suffering from the metabolic syndrome.

Item Type:	Article
Keywords:	Microcirculation, metabolism syndrome,
Date Deposited:	13 Oct 2015 13:12
Last Modified:	13 Oct 2015 13:12
URI:	https://oak.novartis.com/id/eprint/23493