Blunted temporal activity of microvascular perfusion heterogeneity in metabolic syndrome: a new attractor for peripheral vascular disease?

Abstract

Butcher JT, Goodwill AG, Stanley SC, Frisbee JC. Blunted temporal activity of microvascular perfusion heterogeneity in metabolic syndrome: a new attractor for peripheral vascular disease? Am J Physiol Heart Circ Physiol 304: H547-H558, 2013. First published December 21, 2012 doi:10.1152/ajpheart.00805.2012.-A key clinical outcome for peripheral vascular disease (PVD) in patients is a progressive decay in skeletal muscle performance and its ability to resist fatigue with elevated metabolic demand. We have demonstrated that PVD in obese Zucker rats (OZR) is partially due to increased perfusion distribution heterogeneity at successive microvascular bifurcations within skeletal muscle. As this increased heterogeneity (␥) is longitudinally present in the network, its cumulative impact is a more heterogeneous distribution of perfusion between terminal arterioles than normal, causing greater regional tissue ischemia. To minimize this negative outcome, a likely compensatory mechanism against an increased ␥ should be an increased temporal switching at arteriolar bifurcations to minimize downstream perfusion deficits. Using in situ cremaster muscle, we determined that temporal activity (the cumulative sum of absolute differences between successive values of ␥, taken every 20 s) was lower in OZR than in control animals, and this difference was present in both proximal (1A-2A) and distal (3A-4A) arteriolar bifurcations. Although adrenoreceptor blockade (phentolamine) improved temporal activity in 1A-2A arteriolar bifurcations in OZR, this was without impact in the distal microcirculation, where only interventions against oxidant stress (Tempol) and thromboxane A2 activity (SQ-29548) were effective. Analysis of the attractor for ␥ indicated that it was not only elevated in OZR but also exhibited severe reductions in range, suggesting that the ability of the microcirculation to respond to any challenge is highly restricted and may represent the major contributor to the manifestation of poor muscle performance at this age in OZR. rodent models of obesity; microcirculation; skeletal muscle blood flow regulation; models of peripheral vascular disease; blood flow heterogeneity; vascular dysfunction WITH ONGOING STUDY, THERE is increasing appreciation that the transition from healthy physiology to disease states represents a change in the overall system of control from an existing normal structure (46). It is also generally unclear whether this transition represents a failure of the healthy system or evolving compensations to attempt to optimize the most critical biological outcomes despite progression of a challenged environment (38, 57). For this reason, a detailed understanding of which major contributing processes to an outcome are altered with pathology and the extent for which these are compensated is critical for developing appropriate therapeutic interventions. Failure to elucidate both the key sites of impairment and the compensatory mechanisms, as well as how these impact functional outcomes, has resulted in poorly targ...

Increased peripheral vascular disease risk progressively constrains perfusion adaptability in the skeletal muscle microcirculation

“…Going forward, recent studies have shed new light on microvascular dysfunction itself that may represent a more accurate predictor of poor outcomes in OZR than has been available previously. Specifically, previous studies have identified an attractor that integrates vascular hemodynamics and reactivity at successive arteriolar bifurcations to create a condition in which terminal arteriolar perfusion becomes both increasingly heterogeneous and less responsive to changes in the local environment (5,21).…”

Peripheral Blood Flow Regulation in Human Obesity and Metabolic Syndrome

“…Therefore, not only does sympathetic inhibition improve total flow, it also improves blood flow distribution. However, this is only true in the proximal circulation [at the level of 1A-2A arterioles, (4, 14)] (Figure 4A and B). …”

β2-Adrenoreceptor blockade improves early posttrauma hyperglycemia and pulmonary injury in obese rats

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