Capillary hemodynamics and contracting skeletal muscle oxygen pressures in male rats with heart failure: Impact of soluble guanylyl cyclase activator.
Capillary hemodynamics and contracting skeletal muscle oxygen pressures in male rats with heart failure: Impact of soluble guanylyl cyclase activator.
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DOI：
10.1016/j.niox.2021.12.001
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发表时间：
2022-02-01
影响因子：
3.9
通讯作者：
Poole, David C.
中科院分区：
文献类型：
--
作者：
Weber, Ramona E.;Schulze, Kiana M.;Colburn, Trenton D.;Horn, Andrew G.;Hageman, K. Sue;Ade, Carl J.;Hall, Stephanie E.;Sandner, Peter;Musch, Timothy I.;Poole, David C.
In heart failure with reduced ejection fraction (HFrEF), nitric oxide-soluble guanylyl cyclase (sGC) pathway dysfunction impairs skeletal muscle arteriolar vasodilation and thus capillary hemodynamics, contributing to impaired oxygen uptake kinetics. Targeting this pathway with sGC activators offers a new treatment approach to HFrEF. We tested the hypotheses that sGC activator administration would increase the O2 delivery ratio in the skeletal muscle interstitial space (PO2is) of HFrEF rats during twitch contractions due, in part, to increases in red blood cell (RBC) flux (fRBC), velocity (VRBC), and capillary hematocrit (Hctcap). HFrEF was induced in male Sprague-Dawley rats via myocardial infarction. After 3 weeks, rats were treated with 0.3 mg/kg of the sGC activator BAY 60–2770 (HFrEF + BAY; n = 11) or solvent (HFrEF; n = 9) via gavage b.i.d for 5 days prior to phosphorescence quenching (PO2is, in contracting muscle) and intravital microscopy (resting) measurements in the spinotrapezius muscle. Intravital microscopy revealed higher fRBC (70 ± 9 vs 25 ± 8 RBC/s), VRBC (490 ± 43 vs 226 ± 35 μm/s), Hctcap (16 ± 1 vs 10 ± 1%) and a greater number of capillaries supporting flow (91 ± 3 vs 82 ± 3%) in HFrEF + BAY vs HFrEF (all P < 0.05). Additionally, PO2is was especially higher during 12–34s of contractions in HFrEF + BAY vs HFrEF (P < 0.05). Our findings suggest that sGC activators improved resting via increased fRBC, VRBC, and Hctcap allowing for better matching during the rest-contraction transient, supporting sGC activators as a potential therapeutic to target skeletal muscle vasomotor dysfunction in HFrEF.
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影响因子：
3.3
作者：
Delp, MD;Duan, CP;Musch, TI
通讯作者：
Musch, TI
DOI：
10.1113/jp279608
发表时间：
2020-08
期刊：
The Journal of physiology
影响因子：
--
作者：
Colburn TD;Hirai DM;Craig JC;Ferguson SK;Weber RE;Schulze KM;Behnke BJ;Musch TI;Poole DC
通讯作者：
Poole DC
DOI：
10.1249/01.mss.0000177466.01232.7e
发表时间：
2005-09-01
期刊：
MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
影响因子：
--
作者：
Jones, AM;Poole, DC
通讯作者：
Poole, DC
影响因子：
18.2
作者：
Crespo-Leiro, Maria G.;Metra, Marco;Ruschitzka, Frank
通讯作者：
Ruschitzka, Frank
影响因子：
3.3
作者：
Ferguson, Scott K.;Holdsworth, Clark T.;Poole, David C.
通讯作者：
Poole, David C.