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. 2014 Nov;21(8):677-87.
doi: 10.1111/micc.12146.

Impact of increased intramuscular perfusion heterogeneity on skeletal muscle microvascular hematocrit in the metabolic syndrome

Joshua T Butcher  1 , Shyla C Stanley, Steven D Brooks, Paul D Chantler, Fan Wu, Jefferson C Frisbee
Affiliations

Impact of increased intramuscular perfusion heterogeneity on skeletal muscle microvascular hematocrit in the metabolic syndrome

Joshua T Butcher et al. Microcirculation. 2014 Nov.

Abstract

Objective: To determine HMV and PS in skeletal muscle of OZR and evaluate the impact of increased microvascular perfusion heterogeneity on mass transport/exchange.

Methods: The in situ gastrocnemius muscle from OZR and LZR was examined under control conditions and following pretreatment with TEMPOL (antioxidant)/SQ-29548 (PGH2 /TxA2 receptor antagonist), phentolamine (adrenergic antagonist), or all agents combined. A spike input of a labeled blood tracer cocktail was injected into the perfusing artery. Tracer washout was analyzed using models for HMV and PS. HT was determined in in situ cremaster muscle of OZR and LZR using videomicroscopy.

Results: HMV was decreased in OZR versus LZR. While TEMPOL/SQ-29548 or phentolamine had minor effects, treatment with all three agents improved HMV in OZR. HT was not different between strains, although variability was increased in OZR, and normalized following treatment with all three agents. PS was reduced in OZR and was not impacted by intervention.

Conclusions: Increased microvascular perfusion heterogeneity in OZR reduces HMV in muscle vascular networks and increases its variability, potentially contributing to premature muscle fatigue. While targeted interventions can ameliorate this, the reduced microvascular surface area is not acutely reversible.

Keywords: microcirculation; microvascular hemodynamics; peripheral vascular disease; regulation of skeletal muscle blood flow; rodent models of metabolic syndrome.

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Figures

Figure 1
Figure 1
Representative tracer washout curves following bolus intra-arterial injection proximal to the in situ gastrocnemius muscle from LZR and OZR under the conditions of the present study. Data are presented for LZR – Control (Panel A), and OZR – Control (Panel B) and following pre-treatment of OZR with phentolamine (Panel C), TEMPOL and SQ-29548 (Panel D) and all three agents (Panel E). Please see text for details.
Figure 2
Figure 2
Calculated hematocrit reduction ratio (%; Panel A) and aggregate microvascular hematocrit (%, Panel B) in the in situ gastrocnemius muscle of LZR and OZR under the conditions of the current study. Calculations are based on the analyses of the tracer washout curves, representative washout curves are presented in Figure 1. Data are presented as mean±SE, * p<0.05 versus LZR-Control, † p<0.05 versus OZR-Control. For LZR, n=6 for Control, n=3 for Phentolamine, n=3 for TEMPOL/SQ-29548 and n=6 for all. For OZR, n=17 for Control, n=8 for Phentolamine, n=9 for TEMPOL/SQ-29548 and n=17 for all. Please see text for details.
Figure 3
Figure 3
Capillary tube hematocrit in microvessels from LZR and OZR under the conditions of the present study. Calculations are made from individual microvessels from a trans-illuminated in situ cremaster muscle from LZR and OZR. Data are presented as mean±SE. Panel A presents aggregate for HT, while Panel B presents the data as a ‘box-and-whisker’ plot, where The bottom boundary of the box indicates the 25th percentile, a central line within the box marks the median, and the upper boundary of the box indicates the 75th percentile. Whiskers are represented as the error bars above and below the box and represent the 90th and 10th percentiles. HT values in Panel A are based on 10 measurements/animal, with n=6 for LZR and 8-10 for OZR. Please see text for details.
Figure 4
Figure 4
Data describing the calculated extraction (Panel A) and permeability-surface area product (PS; Panel B) across the in situ gastrocnemius muscle of LZR and OZR under the conditions of the current study. Calculations are based on the analyses of the tracer washout curves, representative washout curves are presented in Figure 1. Data are presented as mean±SE, * p<0.05 versus LZR-Control. For LZR, n=6 for Control, n=3 for Phentolamine, n=3 for TEMPOL/SQ-29548 and n=6 for all. For OZR, n=17 for Control, n=8 for Phentolamine, n=9 for TEMPOL/SQ-29548 and n=17 for all. Please see text for details.
Figure 5
Figure 5
Data describing perfusive oxygen flux (QO2; Panel A), diffusive oxygen flux (JO2; Panel B) and the correlation between JO2 and PS Product (Panel C) under the conditions of the present study. In Panel C, the equation for the relationship in LZR is:y = 0.0377 + 0.0165χ; r2=0.819, while for OZR this relationship is: y = 0.0162 + 0.0248χ; r2=0.721. * p<0.05 vs. LZR Control, † p<0.05 vs. OZR Control.
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