Research Papers

Cryotherapy-Induced Persistent Vasoconstriction After Cutaneous Cooling: Hysteresis Between Skin Temperature and Blood Perfusion

[+] Author and Article Information
Sepideh Khoshnevis

Bioheat Transfer Laboratory,
Biomedical Engineering Department,
The University of Texas at Austin,
Austin, TX 78712
e-mail: Sepideh@utexas.edu

Natalie K. Craik, Kenneth R. Diller

Bioheat Transfer Laboratory,
Biomedical Engineering Department,
The University of Texas at Austin,
Austin, TX 78712

R. Matthew Brothers

Environmental and Autonomic
Physiology Laboratory,
Department of Kinesiology and
Health Education,
The University of Texas at Austin,
Austin, TX 78712

1Corresponding author.

2Current affiliation: Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030.

3Current affiliation: Associate Professor, Department of Kinesiology, University of Texas at Arlington, 701 S Nedderman Dr, Arlington, TX 76019.

Manuscript received September 2, 2015; final manuscript received November 20, 2015; published online January 29, 2016. Assoc. Editor: Ram Devireddy.

J Biomech Eng 138(3), 031004 (Jan 29, 2016) (8 pages) Paper No: BIO-15-1438; doi: 10.1115/1.4032126 History: Received September 02, 2015; Revised November 20, 2015

The goal of this study was to investigate the persistence of cold-induced vasoconstriction following cessation of active skin-surface cooling. This study demonstrates a hysteresis effect that develops between skin temperature and blood perfusion during the cooling and subsequent rewarming period. An Arctic Ice cryotherapy unit (CTU) was applied to the knee region of six healthy subjects for 60 min of active cooling followed by 120 min of passive rewarming. Multiple laser Doppler flowmetry perfusion probes were used to measure skin blood flow (expressed as cutaneous vascular conductance (CVC)). Skin surface cooling produced a significant reduction in CVC (P < 0.001) that persisted throughout the duration of the rewarming period. In addition, there was a hysteresis effect between CVC and skin temperature during the cooling and subsequent rewarming cycle (P < 0.01). Mixed model regression (MMR) showed a significant difference in the slopes of the CVC–skin temperature curves during cooling and rewarming (P < 0.001). Piecewise regression was used to investigate the temperature thresholds for acceleration of CVC during the cooling and rewarming periods. The two thresholds were shown to be significantly different (P = 0.003). The results show that localized cooling causes significant vasoconstriction that continues beyond the active cooling period despite skin temperatures returning toward baseline values. The significant and persistent reduction in skin perfusion may contribute to nonfreezing cold injury (NFCI) associated with cryotherapy.

Copyright © 2016 by ASME
Your Session has timed out. Please sign back in to continue.


Knight, K. L. , 1995, Cryotherapy in Sport Injury Management, Human Kinetics, Champaign, IL.
Swenson, C. , Swärd, L. , and Karlsson, J. , 1996, “ Cryotherapy in Sports Medicine,” Scand. J. Med. Sci. Sports, 6(4), pp. 193–200. [CrossRef] [PubMed]
MacAuley, D. , 2001, “ Do Textbooks Agree on Their Advice on Ice?” Clin. J. Sport Med., 11(2), pp. 67–72. [CrossRef] [PubMed]
Francis, T. J. , and Golden, F. S. , 1985, “ Non-Freezing Cold Injury: The Pathogenesis,” J. R. Nav. Med. Serv., 71(1), pp. 3–8. [PubMed]
Francis, T. J. , 1984, “ Non Freezing Cold Injury: A Historical Review,” J. R. Nav. Med. Serv., 70(3), pp. 134–139. [PubMed]
Thomas, J. R. , and Oakley, E. H. N. , 2002, “ Nonfreezing Cold Injury,” Textbooks of Military Medicine: Medical Aspects of Harsh Environments, Office of the Surgeon General, U. S. Army, Falls Church, VA.
Jia, J. , and Pollock, M. , 1999, “ Cold Nerve Injury is Enhanced by Intermittent Cooling,” Muscle Nerve, 22(12), pp. 1644–1652. [CrossRef] [PubMed]
Selfe, J. , Hardaker, N. , Whitaker, J. , and Hayes, C. , 2007, “ Thermal Imaging of an Ice Burn Over the Patella Following Clinically Relevant Cryotherapy Application During a Clinical Research Study,” Phys. Ther. Sport, 8(3), pp. 153–158. [CrossRef]
Brown, W. C. , and Hahn, D. B. , 2009, “ Frostbite of the Feet After Cryotherapy: A Report of Two Cases,” J. Foot Ankle Surg., 48(5), pp. 577–580. [CrossRef] [PubMed]
Lee, C. K. , Pardun, J. , Buntic, R. , Kiehn, M. , Brooks, D. , and Buncke, H. J. , 2007, “ Severe Frostbite of the Knees After Cryotherapy,” Orthopedics, 30(1), pp. 63–64. [PubMed]
Babwah, T. , 2011, “ Common Peroneal Neuropathy Related to Cryotherapy and Compression in a Footballer,” Res. Sports Med., 19(1), pp. 66–71. [CrossRef] [PubMed]
Bassett, F. H. , Kirkpatrick, J. S. , Engelhardt, D. L. , and Malone, T. R. , 1992, “ Cryotherapy-Induced Nerve Injury,” Am. J. Sports Med., 20(5), pp. 516–518. [CrossRef] [PubMed]
Moeller, J. L. , Monroe, J. , and McKeag, D. B. , 1997, “ Cryotherapy-Induced Common Peroneal Nerve Palsy,” Clin. J. Sport Med., 7(3), pp. 212–216. [CrossRef] [PubMed]
Hodges, G. J. , Zhao, K. , Kosiba, W. A. , and Johnson, J. M. , 2006, “ The Involvement of Nitric Oxide in the Cutaneous Vasoconstrictor Response to Local Cooling in Humans,” J. Physiol., 574(3), pp. 849–857. [CrossRef] [PubMed]
Johnson, J. M. , and Kellogg, D. L. , 2010, “ Local Thermal Control of the Human Cutaneous Circulation,” J. Appl. Physiol., 109(4), pp. 1229–1238. [CrossRef] [PubMed]
Johnson, J. M. , 2006, “ Mechanisms of Vasoconstriction With Direct Skin Cooling in Humans,” AJP Heart Circ. Physiol., 292(4), pp. H1690–H1691. [CrossRef]
Minson, C. T. , 2010, “ Thermal Provocation to Evaluate Microvascular Reactivity in Human Skin,” J. Appl. Physiol., 109(4), pp. 1239–1246. [CrossRef] [PubMed]
Thompson-Torgerson, C. S. , Holowatz, L. A. , Flavahan, N. A. , and Kenney, W. L. , 2006, “ Cold-Induced Cutaneous Vasoconstriction is Mediated by Rho Kinase In Vivo in Human Skin,” AJP Heart Circ. Physiol., 292(4), pp. H1700–H1705. [CrossRef]
Brown, F. T. , 2006, Engineering System Dynamics: A Unified Graph-Centered Approach, CRC Press, Boca Raton, FL.
Noori, H. R. , 2014, Hysteresis Phenomena in Biology, Springer, Heidelberg, Germany.
Clough, G. , Chipperfield, A. , Byrne, C. , de Mul, F. , and Gush, R. , 2009, “ Evaluation of a New High Power, Wide Separation Laser Doppler Probe: Potential Measurement of Deeper Tissue Blood Flow,” Microvasc. Res., 78(2), pp. 155–161. [CrossRef] [PubMed]
Khoshnevis, S. , Craik, N. K. , and Diller, K. R. , 2015, “ Cold-Induced Vasoconstriction May Persist Long After Cooling Ends: An Evaluation of Multiple Cryotherapy Units,” Knee Surg. Sports Traumatol. Arthrosc., 23(9), pp. 2475–2483. [CrossRef] [PubMed]
Khoshnevis, S. , Nordhauser, J. , Craik, N. , and Diller, K. R. , 2014, “ Quantitative Evaluation of the Thermal Heterogeneity on the Surface of Cryotherapy Cooling Pads,” ASME J. Biomech. Eng., 136(7), p. 074503. [CrossRef]
Ramanathan, N. L. , 1964, “ A New Weighting System for Mean Surface Temperature of the Human Body,” J. Appl. Physiol., 19(3), pp. 531–533. [PubMed]
Bissonnette, B. , Sessler, D. I. , and LaFlamme, P. , 1989, “ Intraoperative Temperature Monitoring Sites in Infants and Children and the Effect of Inspired Gas Warming on Esophageal Temperature,” Anesth. Analg., 69(2), pp. 192–196. [CrossRef] [PubMed]
Brinnel, H. , and Cabanac, M. , 1989, “ Tympanic Temperature is a Core Temperature in Humans,” J. Therm. Biol., 14(1), pp. 47–53. [CrossRef]
Gagnon, D. , Lemire, B. B. , Jay, O. , and Kenny, G. P. , 2010, “ Aural Canal, Esophageal, and Rectal Temperatures During Exertional Heat Stress and the Subsequent Recovery Period,” J. Athl. Train., 45(2), pp. 157–163. [CrossRef] [PubMed]
NIST, 2014, NIST/SEMATECH e-Handbook of Statistical Methods, National Institute of Standards and Technology (NIST), Gaithersburg, MD.
Pokala, N. , 2012, “ Dunnett Test for Multiple Comparisons,” MATLAB Central File Exchange, accessed 26 Oct., 2013, http://www.mathworks.com/matlabcentral/fileexchange/38157-dunnett-m
Faul, F. , Erdfelder, E. , Lang, A.-G. , and Buchner, A. , 2007, “ G* Power 3: A Flexible Statistical Power Analysis Program for the Social, Behavioral, and Biomedical Sciences,” Behav. Res. Methods, 39(2), pp. 175–191. [CrossRef] [PubMed]
Faul, F. , Erdfelder, E. , Buchner, A. , and Lang, A.-G. , 2009, “ Statistical Power Analyses Using G* Power 3.1: Tests for Correlation and Regression Analyses,” Behav. Res. Methods, 41(4), pp. 1149–1160. [CrossRef] [PubMed]
Holmes, K. R. , 1998, “ Thermal Conductivity of Selected Tissues,” Biotransport: Heat and Mass Transfer in Living Systems, K. R. Diller , ed., New York Academy of Sciences, New York.
Fiala, D. , Lomas, K. J. , and Stohrer, M. , 1999, “ A Computer Model of Human Thermoregulation for a Wide Range of Environmental Conditions: The Passive System,” J. Appl. Physiol., 87(5), pp. 1957–1972. [PubMed]
Roselli, R. J. , and Diller, K. R. , 2011, Biotransport: Principles and Applications, Springer, New York.
Pennes, H. H. , 1948, “ Analysis of Tissue and Arterial Blood Temperatures in the Resting Human Forearm,” J. Appl. Physiol., 1(2), pp. 93–122. [PubMed]
Hegarty, T. W. , 1973, “ Temperature Coefficient (Q10), Seed Germination and Other Biological Processes,” Nature, 243(5405), pp. 305–306. [CrossRef]
Dennis, B. H. , Eberhart, R. C. , Dulikravich, G. S. , and Radons, S. W. , 2003, “ Finite-Element Simulation of Cooling of Realistic 3-D Human Head and Neck,” ASME J. Biomech. Eng., 125(6), pp. 832–840. [CrossRef]
Razali, N. M. , and Wah, Y. B. , 2011, “ Power Comparisons of Shapiro–Wilk, Kolmogorov–Smirnov, Lilliefors and Anderson–Darling Tests,” J. Stat. Model. Anal., 2(1), pp. 21–33.
Taber, C. , Contryman, K. , Fahrenbruch, J. , LaCount, K. , and Cornwall, M. W. , 1992, “ Measurement of Reactive Vasodilation During Cold Gel Pack Application to Nontraumatized Ankles,” Phys. Ther., 72(4), pp. 294–299. [PubMed]
Ho, S. S. W. , Illgen, R. L. , Meyer, R. W. , Torok, P. J. , Cooper, M. D. , and Reider, B. , 1995, “ Comparison of Various Icing Times in Decreasing Bone Metabolism and Blood Flow in the Knee,” Am. J. Sports Med., 23(1), pp. 74–76. [CrossRef] [PubMed]
Curl, W. W. , Smith, B. P. , Marr, A. , Rosencrance, E. , Holden, M. , and Smith, T. L. , 1997, “ The Effect of Contusion and Cryotherapy on Skeletal Muscle Microcirculation,” J. Sports Med. Phys. Fitness, 37(4), pp. 279–286. [PubMed]
Sendowski, I. , Savourey, G. , Besnard, Y. , and Bittel, J. , 1997, “ Cold Induced Vasodilatation and Cardiovascular Responses in Humans During Cold Water Immersion of Various Upper Limb Areas,” Eur. J. Appl. Physiol., 75(6), pp. 471–477. [CrossRef]
Karunakara, R. G. , Lephart, S. M. , and Pincivero, D. M. , 1999, “ Changes in Forearm Blood Flow During Single and Intermittent Cold Application,” J. Orthop. Sports Phys. Ther., 29(3), pp. 177–180. [CrossRef] [PubMed]
Knobloch, K. , Kraemer, R. , Lichtenberg, A. , Jagodzinski, M. , Gosling, T. , Richter, M. , and Krettek, C. , 2006, “ Microcirculation of the Ankle After Cryo/Cuff Application in Healthy Volunteers,” Int. J. Sports Med., 27(3), pp. 250–255. [CrossRef] [PubMed]
Knobloch, K. , Grasemann, R. , Spies, M. , and Vogt, P. M. , 2008, “ Midportion Achilles Tendon Microcirculation After Intermittent Combined Cryotherapy and Compression Compared With Cryotherapy Alone: A Randomized Trial,” Am. J. Sports Med., 36(11), pp. 2128–2138. [CrossRef] [PubMed]
Yanagisawa, O. , Homma, T. , Okuwaki, T. , Shimao, D. , and Takahashi, H. , 2007, “ Effects of Cooling on Human Skin and Skeletal Muscle,” Eur. J. Appl. Physiol., 100(6), pp. 737–745. [CrossRef] [PubMed]
Hodges, G. J. , Traeger, J. A., 3rd , Tang, T. , Kosiba, W. A. , Zhao, K. , and Johnson, J. M. , 2007, “ Role of Sensory Nerves in the Cutaneous Vasoconstrictor Response to Local Cooling in Humans,” Am. J. Physiol. Heart Circ. Physiol., 293(1), pp. H784–H789. [CrossRef] [PubMed]
Johnson, J. M. , Yen, T. C. , Zhao, K. , and Kosiba, W. A. , 2005, “ Sympathetic, Sensory, and Nonneuronal Contributions to the Cutaneous Vasoconstrictor Response to Local Cooling,” Am. J. Physiol. Heart Circ. Physiol., 288(4), pp. H1573–H1579. [CrossRef] [PubMed]
Ross, D. C. , and Diller, K. R. , 1978, “ The Therapeutic Effects of Postburn Cooling,” ASME J. Biomech. Eng., 100(3), pp. 149–152. [CrossRef]
Vuksanović, V. , Sheppard, L. W. , and Stefanovska, A. , 2008, “ Nonlinear Relationship Between Level of Blood Flow and Skin Temperature for Different Dynamics of Temperature Change,” Biophys. J., 94(10), pp. L78–L80. [CrossRef] [PubMed]
Kozelek, P. , Holcik, J. , and Sedlinska, M. , 2007, “ Statistical Analysis of QT/RR Hysteresis in Healthy Horses,” 29th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBS 2007), Lyon, France, Aug. 22–26, pp. 5319–5322.
Merrick, M. A. , Knight, K. L. , Ingersoll, C. D. , and Potteiger, J. A. , 1993, “ The Effects of Ice and Compression Wraps on Intramuscular Temperatures at Various Depths,” J. Athl. Train., 28(3), pp. 236–245. [PubMed]
Myrer, J. , Measom, G. , and Fellingham, G. , 1998, “ Temperature Changes in the Human Leg During and After Two Methods of Cryotherapy,” J. Athl. Train., 33(1), pp. 25–29. [PubMed]
Warren, T. A. , 2004, “ Intra-Articular Knee Temperature Changes: Ice Versus Cryotherapy Device,” Am. J. Sports Med., 32(2), pp. 441–445. [CrossRef] [PubMed]
Holwerda, S. W. , Trowbridge, C. A. , Womochel, K. S. , and Keller, D. M. , 2013, “ Effects of Cold Modality Application With Static and Intermittent Pneumatic Compression on Tissue Temperature and Systemic Cardiovascular Responses,” Sports Health, 5(1), pp. 27–33. [CrossRef] [PubMed]
Diller, K. R. , 2015, “ Heat Transfer in Health and Healing,” ASME J. Heat Transfer, 137(10), p. 103001. [CrossRef]
Goudkamp, J. E. , Seebacher, F. , Ahern, M. , and Franklin, C. E. , 2004, “ Physiological Thermoregulation in a Crustacean? Heart Rate Hysteresis in the Freshwater Crayfish Cherax Destructor,” Comp. Biochem. Physiol. A, 138(3), pp. 399–403. [CrossRef]
Zachariassen, K. E. , 1985, “ Physiology of Cold Tolerance in Insects,” Physiol. Rev., 65(4), pp. 799–832. [PubMed]
George, N. T. , Irving, T. C. , Williams, C. D. , and Daniel, T. L. , 2013, “ The Cross-Bridge Spring: Can Cool Muscles Store Elastic Energy?” Science, 340(6137), pp. 1217–1220. [CrossRef] [PubMed]
Inoue, I. , Kobatake, Y. , and Tasaki, I. , 1973, “ Excitability, Instability and Phase Transitions in Squid Axon Membrane Under Internal Perfusion With Dilute Salt Solutions,” Biochim. Biophys. Acta, 307(3), pp. 471–477. [CrossRef] [PubMed]


Grahic Jump Location
Fig. 1

Application of instrumentation at a measurement site. P1, P2, and P3 are the three perfusion probes. T shows the locations of thermocouples. This site will be covered with the cooling pad.

Grahic Jump Location
Fig. 2

(a) Percent change compared to baseline values for CVC (top panel) and skin temperature (bottom panel) for a sample experiment. The protocol followed 30 min of baseline, 60 min of active cooling, and 2 hrs of passive rewarming. (b) Percent change in CVC from baseline from a control experiment. The duration of active water flow through the cooling pad is marked on the plot.

Grahic Jump Location
Fig. 3

Temperature (top panel) and absolute CVC (bottom panel) values during the last 5 min of baseline and cooling (marked as B and C, respectively) and at the end of 10-min intervals during rewarming period. The values are average measurements from six different experiments. Error bars show the standard errors of the mean. The cooling process lasted for 60 min.

Grahic Jump Location
Fig. 4

Skin perfusion as a function of skin temperature during cooling (stars) and passive rewarming (dots). The arrows show the process direction. Each two subsequent data points are separated by 1 min. (a) Hysteresis plot from a single experiment. (b) The hysteresis plot based on the average measurements from six experiments.

Grahic Jump Location
Fig. 5

Simulation of transient temperature at incremental tissue depths during cooling and rewarming. The dark solid graph depicts the applied surface skin temperature (Ts). The initial spatial temperature gradient was calculated for steady-state conditions prior to the start of cooling.



Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging and repositioning the boxes below.

Related Journal Articles
Related eBook Content
Topic Collections

Sorry! You do not have access to this content. For assistance or to subscribe, please contact us:

  • TELEPHONE: 1-800-843-2763 (Toll-free in the USA)
  • EMAIL: asmedigitalcollection@asme.org
Sign In