scholarly journals Reproducibility of Whole‐Body Cooling Response Using Laser Doppler Flowmetry

2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Kelsey S. Schwartz ◽  
Behnia R. Shirazi ◽  
James A. Lang
2007 ◽  
Vol 293 (5) ◽  
pp. H3187-H3192 ◽  
Author(s):  
Gary J. Hodges ◽  
Wojciech A. Kosiba ◽  
Kun Zhao ◽  
Guy E. Alvarez ◽  
John M. Johnson

Previous work showed that local cooling (LC) attenuates the vasoconstrictor response to whole body cooling (WBC). We tested the extent to which this attenuation was due to the decreased baseline skin blood flow following LC. In eight subjects, skin blood flow was assessed using laser-Doppler flowmetry (LDF). Cutaneous vascular conductance (CVC) was expressed as LDF divided by blood pressure. Subjects were dressed in water-perfused suits to control WBC. Four forearm sites were prepared with microdialysis fibers, local heating/cooling probe holders, and laser-Doppler probes. Three sites were locally cooled from 34 to 28°C, reducing CVC to 45.9 ± 3.9, 42 ± 3.9, and 44.5 ± 4.8% of baseline ( P < 0.05 vs. baseline; P > 0.05 among sites). At two sites, CVC was restored to precooling baseline levels with sodium nitroprusside (SNP) or isoproterenol (Iso), increasing CVC to 106.4 ± 12.4 and 98.9 ± 10.1% of baseline, respectively ( P > 0.05 vs. precooling). Whole body skin temperature, apart from the area of blood flow measurement, was reduced from 34 to 31°C. Relative to the original baseline, CVC decreased ( P < 0.05) by 44.9 ± 2.8 (control), 11.3 ± 2.4 (LC only), 29 ± 3.7 (SNP), and 45.8 ± 8.7% (Iso). The reductions at LC only and SNP sites were less than at control or Iso sites ( P < 0.05); the responses at those latter sites were not different ( P > 0.05), suggesting that the baseline change in CVC with LC is important in the attenuation of reflex vasoconstrictor responses to WBC.


2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Mohamed R. Gemae ◽  
Ashley P. Akerman ◽  
Greg W. McGarr ◽  
Madison D. Schmidt ◽  
Robert D. Meade ◽  
...  

2013 ◽  
Vol 115 (7) ◽  
pp. 1025-1031 ◽  
Author(s):  
Anna E. Stanhewicz ◽  
Lacy M. Alexander ◽  
W. Larry Kenney

Reflex vasoconstriction is attenuated in aged skin due to a functional loss of adrenergic vasoconstriction. Bioavailability of tetrahydrobiopterin (BH4), an essential cofactor for catecholamine synthesis, is reduced with aging. Locally administered BH4 increases vasoconstriction through adrenergic mechanisms in aged human skin. We hypothesized that oral sapropterin (Kuvan, a pharmaceutical BH4) would augment vasoconstriction elicited by whole-body cooling and tyramine perfusion in aged skin. Ten healthy subjects (age 75 ± 2 yr) ingested sapropterin (10 mg/kg) or placebo in a randomized, double-blind crossover design. Venous blood samples were collected prior to, and 3 h following ingestion. Three intradermal microdialysis fibers were placed in the forearm skin for local delivery of 1) lactated Ringer, 2) 5 mM BH4, and 3) 5 mM yohimbine + 1 mM propranolol (Y+P; to inhibit adrenergic vasoconstriction). Red cell flux was measured at each site by laser-Doppler flowmetry (LDF) as reflex vasoconstriction was induced by lowering and then clamping whole-body skin temperature ( T̄sk) using a water-perfused suit. Following whole-body cooling, subjects were rewarmed and 1 mM tyramine was perfused at each site to elicit endogenous norepinephrine release from the perivascular nerve terminal. Cutaneous vascular conductance was calculated as CVC = LDF/mean arterial pressure and expressed as change from baseline (ΔCVC). Plasma BH4 was elevated 3 h after ingestion of sapropterin (43.8 ± 3 vs. 19.1 ± 2 pmol/ml; P < 0.001). Sapropterin increased reflex vasoconstriction at the Ringer site at T̄sk ≤ 32.5°C ( P < 0.05). Local BH4 perfusion augmented reflex vasoconstriction at T̄sk ≤ 31.5°C with placebo treatment only ( P < 0.05). There was no treatment effect on reflex vasoconstriction at the BH4-perfused or Y+P-perfused sites. Sapropterin increased pharmacologically induced vasoconstriction at the Ringer site (−0.19 ± 0.03 vs. −0.08 ± 0.02 ΔCVC; P = 0.01). There was no difference in pharmacologically induced vasoconstriction between treatments at the BH4-perfused site (−0.16 ± 0.04 vs. −0.14 ± 0.03 ΔCVC; P = 0.60) or the Y+P-perfused site (−0.05 ± 0.02 vs.−0.06 ± 0.02 ΔCVC; P = 0.79). Sapropterin increases both reflex (cold-induced) and pharmacologically induced vasoconstriction through adrenergic mechanisms and may be a viable intervention to improve reflex vasoconstriction in aged humans.


2007 ◽  
Vol 292 (4) ◽  
pp. H1700-H1705 ◽  
Author(s):  
Caitlin S. Thompson-Torgerson ◽  
Lacy A. Holowatz ◽  
Nicholas A. Flavahan ◽  
W. Larry Kenney

Cutaneous vasoconstriction (VC) is the initial thermoregulatory response to cold exposure and can be elicited through either whole body or localized skin cooling. However, the mechanisms governing local cold-induced VC are not well understood. We tested the hypothesis that Rho kinase participates in local cold-induced cutaneous VC. In seven men and women (20–27 yr of age), up to four ventral forearm skin sites were instrumented with intradermal microdialysis fibers for localized drug delivery during cooling. Skin blood flow was monitored at each site with laser-Doppler flowmetry while local skin temperature was decreased and maintained at 24°C for 40 min. Cutaneous vascular conductance (CVC; laser-Doppler flowmetry/mean arterial pressure) was expressed as percent change from 34°C baseline. During the first 5 min of cooling, CVC decreased at control sites (lactated Ringer solution) to −45 ± 6% ( P < 0.001), increased at adrenoceptor-antagonized sites (yohimbine + propranolol) to 15 ± 14% ( P = 0.002), and remained unchanged at both Rho kinase-inhibited (fasudil) and adrenoceptor-antagonized + Rho kinase-inhibited sites (yohimbine + propranolol + fasudil) (−9 ± 1%, P = 0.4 and −6 ± 2%, P = 0.4, respectively). During the last 5 min of cooling, CVC further decreased at all sites when compared with baseline values (control, −77 ± 4%, P < 0.001; adrenoceptor antagonized, −61 ± 3%, P < 0.001; Rho kinase inhibited, −34 ± 7%, P < 0.001; and adrenoceptor antagonized + Rho kinase inhibited sites, −35 ± 3%, P < 0.001). Rho kinase-inhibited and combined treatment sites were significantly attenuated when compared with both adrenoceptor-antagonized ( P < 0.01) and control sites ( P < 0.0001). Rho kinase mediates both early- and late-phase cold-induced VC, supporting in vitro findings and providing a putative mechanism through which both adrenergic and nonadrenergic cold-induced VC occurs in an in vivo human thermoregulatory model.


2012 ◽  
Vol 113 (10) ◽  
pp. 1512-1518 ◽  
Author(s):  
Dean L. Kellogg ◽  
Joan L. Zhao ◽  
Yubo Wu ◽  
John M. Johnson

VPAC2 receptors sensitive to vasoactive intestinal polypeptide (VIP) and pituitary adenylyl cyclase activating polypeptide (PACAP), PAC1 receptors sensitive to PACAP, and nitric oxide (NO) generation by NO synthase (NOS) are all implicated in cutaneous active vasodilation (AVD) through incompletely defined mechanisms. We hypothesized that VPAC2/PAC1 receptor activation and NO are synergistic and interdependent in AVD and tested our hypothesis by examining the effects of VPAC2/PAC1 receptor blockade with and without NOS inhibition during heat stress. The VPAC2/PAC1 antagonist, pituitary adenylate cyclase activating peptide 6–38 (PACAP6–38) and the NOS inhibitor, NG-nitro-l-arginine methyl ester (l-NAME) were administered by intradermal microdialysis. PACAP6–38, l-NAME, a combination of PACAP6–38 and l-NAME, or Ringer's solution alone were perfused at four separate sites. Skin blood flow was monitored by laser-Doppler flowmetry at each site. Body temperature was controlled with water-perfused suits. Blood pressure was monitored by Finapres, and cutaneous vascular conductance (CVC) calculated (CVC = laser-Doppler flowmetry/mean arterial pressure). The protocol began with a 5- to 10-min baseline period without antagonist perfusion, followed by perfusion of PACAP6–38, l-NAME, or combined PACAP6–38 and l-NAME at the different sites in normothermia (45 min), followed by 3 min of whole body cooling. Whole body heating was then performed to induce heat stress and activate AVD. Finally, 58 mM sodium nitroprusside were perfused at all sites to effect maximal vasodilation for normalization of blood flow data. No significant differences in CVC (normalized to maximum) were found among Ringer's PACAP6–38, l-NAME, or combined antagonist sites during normothermia ( P > 0.05 among sites) or cold stress ( P > 0.05 among sites). CVC responses at all treated sites were attenuated during AVD ( P < 0.05 vs. Ringer's). Attenuation was greater at l-NAME and combined PACAP6–38- and l-NAME-treated sites than at PACAP6–38 sites ( P > 0.05). Because responses did not differ between l-NAME and combined treatment sites ( P > 0.05), we conclude that VPAC2/PAC1 receptors require NO in series to effect AVD.


2006 ◽  
Vol 100 (6) ◽  
pp. 2083-2088 ◽  
Author(s):  
Guy E. Alvarez ◽  
Kun Zhao ◽  
Wojciech A. Kosiba ◽  
John M. Johnson

The reduction in skin blood flow (SkBF) with cold exposure is partly due to the reflex vasoconstrictor response from whole body cooling (WBC) and partly to the direct effects of local cooling (LC). Although these have been examined independently, little is known regarding their roles when acting together, as occurs in environmental cooling. We tested the hypothesis that the vasoconstrictor response to combined LC and WBC would be additive, i.e., would equal the sum of their independent effects. We further hypothesized that LC would attenuate the reflex vasoconstrictor response to WBC. We studied 16 (7 women, 9 men) young (30.5 ± 2 yr) healthy volunteers. LC and WBC were accomplished with metal Peltier cooler-heater probe holders and water-perfused suits, respectively. Forearm SkBF was monitored by laser-Doppler flowmetry (LDF). Cutaneous vascular conductance (CVC) was calculated as LDF/blood pressure. Subjects underwent 15 min of LC alone or 15 min of WBC with and without simultaneous LC, either at equal levels (34–31°C) or as equipotent stimuli (34–28°C LC; 34–31°C WBC). The fall in CVC with combined WBC and LC was greater ( P < 0.05) than for either alone (57.0 ± 5% combined vs. 39.2 ± 6% WBC; 34.4 ± 4% LC) with equipotent cooling, but it was only significantly greater than for LC alone with equal levels of cooling (51.3 ± 8% combined vs. 29.5 ± 4% LC). The sum of the independent effects of WBC and LC was greater than their combined effects (74.9 ± 4 vs. 51.3 ± 8% equal and 73.6 ± 7 vs. 57.0 ± 5% equipotent; P < 0.05). The fall in CVC with WBC at LC sites was reduced compared with control sites (17.6 ± 2 vs. 42.4 ± 8%; P < 0.05). Hence, LC contributes importantly to the reduction in SkBF with body cooling, but also suppresses the reflex response, resulting in a nonadditive effect of these two components.


2009 ◽  
Vol 297 (5) ◽  
pp. H1792-H1797 ◽  
Author(s):  
James A. Lang ◽  
John D. Jennings ◽  
Lacy A. Holowatz ◽  
W. Larry Kenney

Primary human aging may be associated with augmented Rho kinase (ROCK)-mediated contraction of vascular smooth muscle and ROCK-mediated inhibition of nitric oxide synthase (NOS). We hypothesized that the contribution of ROCK to reflex vasoconstriction (VC) is greater in aged skin. Cutaneous VC was elicited by 1) whole body cooling [mean skin temperature (Tsk) = 30.5°C] and 2) local norepinephrine (NE) infusion (1 × 10−6 M). Four microdialysis fibers were placed in the forearm skin of eight young (Y) and eight older (O) subjects for infusion of 1) Ringer solution (control), 2) 3 mM fasudil (ROCK inhibition), 3) 20 mM NG-nitro-l-arginine methyl ester (NOS inhibition), and 4) both ROCK + NOS inhibitors. Red cell flux was measured by laser-Doppler flowmetry over each site. Cutaneous vascular conductance (CVC) was calculated as flux/mean arterial pressure and normalized to baseline CVC (%ΔCVCbaseline). VC was reduced at the control site in O during cooling (Y, −34 ± 3; and O, −18 ± 3%ΔCVCbaseline; P < 0.001) and NE infusion (Y, −53 ± 4, and O, −41 ± 9%ΔCVCbaseline; P = 0.006). Fasudil attenuated VC in both age groups during mild cooling; however, this reduction remained only in O but not in Y skin during moderate cooling (Y, −30 ± 5; and O, −7 ± 1%ΔCVCbaseline; P = 0.016) and was not altered by NOS inhibition. Fasudil blunted NE-mediated VC in both age groups (Y, −23 ± 4; and O, −7 ± 3%ΔCVCbaseline; P < 0.01). Cumulatively, these data indicate that reflex VC is more reliant on ROCK in aged skin such that approximately half of the total VC response to whole body cooling is ROCK dependent.


2006 ◽  
Vol 291 (5) ◽  
pp. E1025-E1030 ◽  
Author(s):  
P. Wellhöner ◽  
D. Rolle ◽  
P. Lönnroth ◽  
L. Strindberg ◽  
M. Elam ◽  
...  

The present study aimed to evaluate adipose tissue blood flow (ATBF) by means of laser-Doppler flowmetry (LDF) in humans. Lower body negative pressure (LBNP) and straining known to affect epidermal blood flow through the autonomic nervous system were performed in 11 lean and 11 obese female volunteers. ATBF changes were compared between both groups and also discriminated from skin blood flow (SBF) responses of the immediate vicinity. Additionally, LDF measurements were compared with flow measurements using 133xenon washout in 10 lean subjects during whole body cooling. LDF estimations of SBF and ATBF showed a positive correlation to 133Xe during cooling. SBF and ATBF were reduced to the same extent in both lean and obese subjects during LBNP. Straining induced divergent changes in SBF and ATBF: initially SBF decreased while ATBF increased, but toward the end of straining SBF increased above baseline and ATBF returned down to baseline level. Those changes were similar in both weight groups. Interestingly, only in obese subjects, both LBNP and straining were followed by ATBF augmentation, while SBF levels remained stable. In conclusion, LDF compares with 133Xe washout in monitoring ATBF during tonic perfusion changes. Its strength, however, lies in the detection of rapid flow alterations within the subcutaneous tissue, allowing the evaluation of reflex responses of the subcutaneous microcirculation. Interestingly, those rapid changes in SBF and ATBF can be both concordant and discordant. With regard to ATBF, vasoconstrictor components of the reflex responses were similar in lean and obese subjects, whereas vasodilatory responses were more pronounced in obese volunteers.


2004 ◽  
Vol 287 (3) ◽  
pp. H1404-H1409 ◽  
Author(s):  
Dan P. Stephens ◽  
Adham R. Saad ◽  
Lee Ann T. Bennett ◽  
Wojciech A. Kosiba ◽  
John M. Johnson

Previous studies have provided evidence of a non-noradrenergic contributor to reflex cutaneous vasoconstriction in humans but did not identify the transmitter responsible. To test whether neuropeptide Y (NPY) has a role, in two series of experiments we slowly reduced whole body skin temperature (TSK) from 34.5 to 31.7°C. In protocol 1, Ringer solution and the NPY receptor antagonist BIBP-3226 alone were delivered intradermally via microdialysis. In protocol 2, yohimbine plus propranolol (Yoh + Pro), Yoh + Pro in combination with BIBP-3226, and Ringer solution were delivered to antagonize locally the vasomotor effects of NPY and norepinephrine. Blood flow was measured by laser Doppler flowmetry (LDF). Mean arterial blood pressure (MAP) was monitored at the finger (Finapres). In protocol 1, cutaneous vascular conductance (CVC) fell by 45%, to 55.1 ± 5.6% of baseline at control sites ( P < 0.05). At BIBP-3226-treated sites, CVC fell by 34.1% to 65.9 ± 5.0% ( P < 0.05; P < 0.05 between sites). In protocol 2, during body cooling, CVC at control sites fell by 32.6%, to 67.4 ± 4.3% of baseline; at sites treated with Yoh + Pro, CVC fell by 18.7%, to 81.3 ± 4.4% of baseline ( P < 0.05 vs. baseline; P < 0.05 vs. control) and did not fall significantly at sites treated with BIBP-3226 + Yoh + Pro ( P > 0.05; P < 0.05 vs. other sites). After cooling, exogenous norepinephrine induced vasoconstriction at control sites ( P < 0.05) but not at sites treated with Yoh + Pro + BIBP-3226 ( P > 0.05). These results indicate that NPY participates in sympathetically mediated cutaneous vasoconstriction in humans during whole body cooling.


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