Skin Microcirculatory Parameters as Diagnostic Markers of Central and Cerebral Circulatory Disorders in Hemorrhagic Shock
https://doi.org/10.15360/1813-9779-2025-3-2559
Abstract
The aim of the study was to evaluate the relationship between skin microcirculatory parameters and central and cerebral hemodynamic parameters during progressive blood loss.
Materials and Methods. A randomized, prospective, controlled in vivo experimental study was performed using male Wistar rats (250–350 g, N=23) divided into two groups: «hemorrhagic shock» (HS, N=13), with blood loss of 15% and subsequently 35% of estimated circulating blood volume (CBV), and «sham-operated» controls (SO, N=10). After combined anesthesia, femoral artery catheterization, and craniotomy, the following were measured at baseline (stage 1): mean arterial pressure (MAP), cortical cerebral perfusion (LSCIbrain), and skin perfusion in the hindlimb (LSCIskin) using laser speckle contrast imaging (LSCI). These measurements were repeated after 15% CBV loss (stage 2) and 35% CBV loss (stage 3). Cerebral (CVCbrain=LSCIbrain/MAP) and cutaneous (CVCskin=LSCIskin/MAP) vascular conductance indices were calculated. At stage 3, parameters of post-occlusive reactive hyperemia (PORH) in hindlimb skin were additionally assessed. Statistical analysis was performed using STATISTICA 13.0 with non-parametric methods. Spearman's correlation coefficient (R) was used to assess associations between circulatory parameters.
Results. A 15% CBV loss led to a 26% reduction in LSCIskin (P=0.003 vs SO), with no significant change in LSCIbrain. With further blood loss and a 43% reduction in LSCIskin (P<0.001 vs SO), LSCIbrain decreased by 14% (P0.001 vs SO). These changes were accompanied by a sustained increase in CVCbrain (P0.001 vs SO at stage 3), while CVCskin remained unchanged throughout the experiment. In the HS group, blood loss led to a significant decrease in PORH amplitude (P=0.003 vs SO), while microvascular flow reserve increased (P=0.036 vs SO). Before blood loss, moderate positive correlations were found between LSCIskin, CVCskin, and CVCbrain. In HS, LSCIbrain correlated with the degree of LSCIskin reduction (R=0.57, P=0.041), and skin microvascular flow reserve showed a strong positive correlation with arterial blood pH and base excess (BE) (R=0.84, P=0.001). The correlation between LSCIskin and MAP shifted from a moderate negative correlation at stage 1 to a strong positive correlation at stage 3.
Conclusion. Skin microcirculation parameters (LSCIskin, CVCskin, and PORH), as assessed by laser speckle contrast imaging, are promising diagnostic markers of central and cerebral hemodynamic impairment during progressive blood loss and warrant further validation.
About the Authors
I. A. RyzhkovRussian Federation
Ivan A. Ryzhkov
25 Petrovka Str., Bldg. 2, 107031 Moscow
AuthorID (РИНЦ): 781730
N. V. Golubova
Russian Federation
Nadezhda V. Golubova
25 Petrovka Str., Bldg. 2, 107031 Moscow
95 Komsomolskaya Str., 302026 Orel
AuthorID (РИНЦ): 1144542
K. N. Lapin
Russian Federation
Konstantin N. Lapin
25 Petrovka Str., Bldg. 2, 107031 Moscow
AuthorID (РИНЦ): 1061143
S. N. Kalabushev
Russian Federation
Sergey N. Kalabushev
25 Petrovka Str., Bldg. 2, 107031 Moscow
AuthorID (РИНЦ): 992594
V. V. Dremin
Russian Federation
Viktor V. Dremin
95 Komsomolskaya Str., 302026 Orel
AuthorID (РИНЦ): 787806
E. V. Potapova
Russian Federation
Elena V. Potapova
95 Komsomolskaya Str., 302026 Orel
AuthorID (РИНЦ): 240669
A. V. Dunaev
Russian Federation
Andrey V. Dunaev
95 Komsomolskaya Str., 302026 Orel
AuthorID (РИНЦ): 212404
V. T. Dolgikh
Russian Federation
Vladimir T. Dolgikh
25 Petrovka Str., Bldg. 2, 107031 Moscow
AuthorID (РИНЦ): 540900
V. V. Moroz
Russian Federation
Viktor V. Moroz
25 Petrovka Str., Bldg. 2, 107031 Moscow
AuthorID (РИНЦ): 168246
References
1. Cannon J. W. Hemorrhagic shock. N Engl J Med. 2018; 378 (19): 1852–1853. DOI: 10.1056/NEJMc1802361. PMID: 29742379
2. Moroz V. V., Ryzhkov I. A. Acute blood loss: regional blood flow and microcirculation (Review, Part II). General Reanimatology = Obshchaya Reanimatologiya 2016; 12 (5): 65–94. (in Russ.&Eng.). DOI: 10.15360/1813-9779-2016-5-65-94.
3. Grigoriev E. V., Lebedinsky K. M., Shchegolev A. V., Bobovnik S. V., Bulanov A. Yu., Zabolotskikh I. B., Sinkov S. V., et al. Resuscitation and intensive care in acute massive blood loss in adults (clinical guidelines). Russian Journal of Anaesthesiology and Reanimatology = Anesteziologiya i Reanimatologiya. 2020; (1): 5–24. (in Russ.). DOI: 10.17116/anaesthesiology20200115.
4. Filho I. T. Hemorrhagic shock and the microvasculature. Compr Physiol. 2017; 8 (1): 61–101. DOI: 10.1002/cphy.c170006. PMID: 29357125.
5. Harrois A., Tanaka S., Duranteau J. The microcirculation in hemorrhagic shock. Annual Update in Intensive Care and Emergency Medicine. 2013: 277–289. DOI: 10.1007/978-3-642-35109-9_22.
6. Moroz V. V., Ryzhkov I. A. Acute blood loss: regional blood flow and microcirculation (Review, Part I). General Reanimatology = Obshchaya Reanimatologiya 2016; 12 (2): 66–89. (in Russ.&Eng.). DOI: 10.15360/1813-9779-2016-2-66-89.
7. Wan Z., Sun S., Ristagno G., Weil M. H., Tang W. The cerebral microcirculation is protected during experimental hemorrhagic shock. Crit Care Med. 2010; 38 (3): 928–932. DOI: 10.1097/CCM.0b013e3181cd100c. PMID: 20068466.
8. Cavus E., Meybohm P., Doerges V., Hugo H. H., Steinfath M., Nordstroem J., Scholz J., et al. Cerebral effects of three resuscitation protocols in uncontrolled haemorrhagic shock: a randomised controlled experimental study. Resuscitation. 2009; 80 (5): 567–572. DOI: 10.1016/j.resuscitation.2009.01.013. PMID: 19217706.
9. Reva V. A., Samakaeva A. R., Shelukhin D. A., Orlov S. V., Potemkin V. D., Bulgin D. V., Gracheva G. Y., et al. Emergency ultra-deep hypothermia in cardiac arrest induced by blood loss (experimental study on nonhuman primates). General Reanimatology = Obshchaya Reanimatologiya. 2025; 21 (1): 62–74. (in Russ.&Eng.). DOI: 10.15360/1813-9779-2025-1-62-74.
10. Rickards C. A. Cerebral blood‐flow regulation during hemorrhage. Compr Physiol. 2015; 5 (4): 1585–1621. DOI: 10.1002/cphy.c140058. PMID: 26426461.
11. Tonnesen.J, Pryds A., Larsen E. H., Paulson O. B., Hauerberg J., Knudsen G. M. Laser doppler flowmetry is valid for measurement of cerebral blood flow autoregulation lower limit in rats. Exp Physiol. 2005; 90 (3): 349–355. DOI: 10.1113/expphysiol.2004.029512. PMID: 15653714.
12. Ryzhkov I. A., Zarzhetsky Yu. V., Novoderzhkina I. S. Comparative aspects of the regulation of cutaneous and cerebral microcirculation during acute blood loss. General Reanimatology = Obshchaya Reanimatologiya. 2017; 13 (6): 18–27. (in Russ.&Eng.). DOI: 10.15360/1813-9779-2017-6-18-27.
13. Cracowski J., Roustit M. Current methods to assess human cutaneous blood flow: an updated focus on laser‐based‐techniques. Microcirculation. 2016; 23 (5): 337–44. DOI: 10.1111/micc.12257. PMID: 26607042.
14. Potapova E. V., Mikhailova M. A., Koroleva A. K., Stavtsev D. D., Dremin B. B., Dunaev A. V., Yakushkina N. Y., et al. A multiparametric approach to assessing skin microcirculation in dermatological patients (using psoriasis as an example). Human physiology = Physiologiya Cheloveka. 2021; 47 (6): 33–42. (in Russ.). DOI: 10.31857/S013116462105009X.
15. Holowatz L. A., Thompson-Torgerson C. S., Kenney W. L. The human cutaneous circulation as a model of generalized microvascular function. J Appl Physiol (1985). 2008; 105 (1): 370–372. DOI: 10.1152/japplphysiol.00858.2007. PMID: 17932300.
16. Urakov A. L., Kasatkin A. A., Urakova N. A., Dement’ev V. B. Infrared thermography of human fingers as a method for assessing regional circulation adaptation to blood loss. Regional Blood Circulation and Microcirculation = Regionarnoye Krovoobrashcheniye i Mikrocirkulyatsiya. 2016; 15 (3): 24–29. (in Russ.). DOI: 10.24884/1682-6655-2016-15-3-24-29.
17. Tankanag A. V. Wavelet analysis methods in the comprehensive study approach of skin microhemodynamics as a cardiovascular unit. Regional Blood Circulation and Microcirculation = Regionarnoye Krovoobrashcheniye i Mikrocirkulyatsiya. 2018; 17 (3): 33–41. (in Russ.). DOI: 10.24884/1682-6655-2018-17-3-33-41.
18. Ostapchenko D. A., Gutnikov A. I., Davydova L. A. Current approaches to the treatment of traumatic shock (review). General Reanimatology = Obshchaya Reanimatologiya. 2021; 17 (4): 65–76. (in Russ.&Eng.). DOI: 10.15360/1813-9779-2021-4-65-76.
19. Kerger H., Waschke K. F., Ackern K. V., Tsai A. G., Intaglietta M. Systemic and microcirculatory effects of autologous whole blood resuscitation in severe hemorrhagic shock. Am J Physiol. 1999; 276 (6): H2035–43. DOI: 10.1152/ajpheart.1999.276.6.H2035. PMID: 10362685.
20. González R., Urbano J., López J., Solana M. J., Botrán M., García A., Fernández S. N., et al. Microcirculatory alterations during haemorrhagic shock and after resuscitation in a paediatric animal model. Injury. 2016; 47 (2): 335–341. DOI: 10.1016/j.injury.2015.10.075. PMID: 26612478.
21. Tachon G., Harrois A., Tanaka S., Kato H., Huet O., Pottecher J., Vicaut E., et al. Microcirculatory alterations in traumatic hemorrhagic shock. Crit Care Med. 2014; 42 (6): 1433–1441. DOI: 10.1097/CCM.0000000000000223. PMID: 24561562.
22. Krupatkin A. I., Sidorov V. V. Functional diagnostics of microcirculatory and tissue systems: Fluctuations, information, non-linearity (A manual for doctors). Moscow: LIBRIKOM Book House; 2013. 496. (in Russ.).
23. Dunn A. K. Laser speckle contrast imaging of cerebral blood flow. Ann Biomed Eng. 2012; 40 (2): 367–377. DOI: 10.1007/s10439-011-0469-0. PMID: 22109805.
24. Piavchenko G., Kozlov I., Dremin V., Stavtsev D., Seryogina E., Kandurova K., Shupletsov V., et al. Impairments of cerebral blood flow microcirculation in rats brought on by cardiac cessation and respiratory arrest. J Biophotonics. 2021; 14 (12): e202100216. DOI: 10.1002/jbio.202100216. PMID: 34534405.
25. Golubova N., Potapova E., Seryogina E., Dremin V. Time–frequency analysis of laser speckle contrast for transcranial assessment of cerebral blood flow. Biomedical Signal Processing and Control. 2023; 85: 104969. DOI: 10.1016/j.bspc.2023.104969.
26. Ziebart A., Möllmann C., Garcia-Bardon A., Kamuf J., Schäfer M., Thomas R., Hartmann E. K. Effect of gelatin-polysuccinat on cerebral oxygenation and microcirculation in a porcine haemorrhagic shock model. Scand J Trauma Resusc Emerg Med. 2018; 26 (1): 15. DOI: 10.1186/s13049-018-0477-2. PMID: 29426
27. Golubova N., Ryzhkov I., Lapin K., Seryogina E., Dunaev A., Dremin V., Potapova E. Effect of thinned-skull cranial window on monitoring cerebral blood flow using laser speckle contrast imaging. IEEE J Select Topics Quantum Electron. 2025; 31 (4): 1–8. DOI: 10.1109/JSTQE.2025.3533950
28. Vishwanathan K., Chhajwani S., Gupta A., Vaishya R. Evaluation and management of haemorrhagic shock in polytrauma: clinical practice guidelines. J Clin Orthop Trauma. 2020; 13: 106–15. DOI: 10.1016/j.jcot.2020.12.003. PMID: 33680808.
29. Secher N. H., Van Lieshout J. J. Heart rate during haemorrhage: time for reappraisal. J Physiol. 2010; 588 (Pt 1): 19. DOI: 10.1113/jphysiol.2009.184499. PMID: 20045902.
30. Tew G. A., Klonizakis M., Crank H., Briers J. D., Hodges G. J. Comparison of laser speckle contrast imaging with laser Doppler for assessing microvascular function. Microvasc Res. 2011; 82 (3): 326–32. DOI: 10.1016/j.mvr.2011.07.007. PMID: 21803051.
31. Schadt J. C., Ludbrook J. Hemodynamic and neurohumoral responses to acute hypovolemia in conscious mammals. Am J Physiol. 1991; 260 (2 Pt 2): H305–18. DOI: 10.1152/ajpheart.1991.260.2.H305.PMID: 1671735.
32. Dubensky A., Ryzhkov I., Tsokolaeva Z;, Lapin K., Kalabushev S., Varnakova L., Dolgikh V. Post-occlusive reactive hyperemia variables can be used to diagnose vascular dysfunction in hemorrhagic shock. Microvasc Res. 2024; 152: 104647. DOI: 10.1016/j.mvr.2023.104647. PMID: 38092223.
Supplementary files
Review
For citations:
Ryzhkov I.A., Golubova N.V., Lapin K.N., Kalabushev S.N., Dremin V.V., Potapova E.V., Dunaev A.V., Dolgikh V.T., Moroz V.V. Skin Microcirculatory Parameters as Diagnostic Markers of Central and Cerebral Circulatory Disorders in Hemorrhagic Shock. General Reanimatology. 2025;21(3):11-25. (In Russ.) https://doi.org/10.15360/1813-9779-2025-3-2559