Change in Cerebrovascular Resistance as Diagnostic Index of Cerebral Hemodynamics in Patients with Severe Combined Traumatic Brain Injury

The aim of the investigation was to evaluate changes in cerebrovascular resistance (CVR) in severe combined traumatic brain injury (CTBI) against the background of intracranial hematoma development and its role in diagnosing the state of cerebral hemodynamics.

Materials and Methods. Treatment outcomes in 70 patients with severe CTBI (42 males and 28 females) were studied. Mean age was 35.5±14.8 years (from 15 to 73 years). Depending on the presence of intracranial hemorrhage, the patients were divided into two groups: group 1 — without hematomas, group 2 — with hematomas. The severity of condition according to the Glasgow Coma Scale in group 1 averaged 10.4±2.6 scores, in group 2 it was 10.6±2.8. The severity of injuries according to ISS scale was 32±8 and 31±11 scores, respectively. Epidural hematomas in group 2 were revealed in 6 persons, subdural ones were found in 26, there were multiple hematomas in 4 patients. All the sufferers underwent surgery within the first three days, 30 patients (83.3%) were operated on for hematomas during the first day.

All the patients underwent perfusion CT examination of the brain, transcranial Doppler of both middle cerebral arteries, their mean arterial pressure was measured. Relying on these data, cerebral perfusion pressure and CVR (cerebrovascular resistance) were calculated.

Results. The mean CVR values in each group (both with and without hematomas) appeared to be statistically significantly higher than the mean normal value of this parameter. Intergroup comparison of CVR values showed statistically significant increase in the CVR level in group 2 on the side of removed hematoma (р=0.037). Cerebrovascular resistance in the perifocal zone of removed hematoma remained significantly higher compared to the symmetrical zone in the contralateral hemisphere (p=0.0009).

Conclusion. Cerebrovascular resistance in patients with combined traumatic brain injury is significantly increased compared to the normal value and remains significantly elevated after evacuation of hematoma in the perifocal zone compared to the symmetrical zone in the contralateral hemisphere. This is indicative of certain correlation between the mechanisms of cerebral blood flow autoregulation and maintaining CVR.

1. Oshorov A.V., Savin I.A., Goryachev A.S., Popugaev K.A., Polupan A.A., Sychev A.A., Gavrilov A.G., Kravchuk A.D., Zakharova N.E., Danilov G.V., Potapov A.A. ICP plateau waves in patients with severe traumatic brain injury. Anesteziologiya i reanimatologiya 2013; 4: 44–50.
2. Furuya Y., Hlatky R., Valadka A., Diaz P., Robertson C.S. Comparison of cerebral blood flow in computed tomographic hypodense areas of the brain in head-injured patients. Neurosurgery 2003; 52(2): 340–346, http://dx.doi.org/10.1227/01.neu.0000043931.83041.aa.
3. Potapov A.A., Zakharova N.E., Pronin I.N., Kornienko V.N., Gavrilov A.G., Kravchuk A.D., Oshorov A.V., Sychev A.A., Zaĭtsev O.S., Fadeeva L.M., Takush S.V. Prognostic value of ICP, CPP and regional blood flow monitoring in diffuse and focal traumatic cerebral lesions. Voprosy neyrokhirurgii im. N.N. Burdenko 2011; 75(3): 3–18.
4. Etminan N., Hänggi D. Perfusion CT imaging as a radiological surrogate for early brain injury — summary of current data on aneurysmal subarachnoid hemorrhage (Part А). In: Brain Edema 2014. The 16th International Conference on Brain Edema and Cellular Injury. The 3rd International Conference on Preconditioning for Neurological Disorders. Huntington Beach, California; September 27–30, 2014. URL: http://brainedema2014.com/program_outline.html.
5. Hattingen E., Blasel S., Dumesnil R., Vatter H., Zanella F.E., Weidauer S. MR angiography in patients with subarachnoid hemorrhage: adequate to evaluate vasospasm-induced vascular narrowing? Neurosurg Rev 2010; 33(4): 431–439, http://dx.doi.org/10.1007/s10143-010-0267-4.
6. Ursino M., Lodi C.A. A simple mathematical model of the interaction between intracranial pressure and cerebral hemodynamics. J Appl Physiol 1997; 82(4): 1256–1269.
7. Westermaier T., Pham M., Stetter C., Willner N., Solymosi L., Ernestus R.I., Vince G.H., Kunze E. Value of transcranial Doppler, perfusion-CT and neurological evaluation to forecast secondary ischemia after aneurysmal SAH. Neurocrit Care 2014; 20(3): 406–412, http://dx.doi.org/10.1007/s12028-013-9896-0.
8. Aries M. Cerebral hemodynamics in stroke and traumatic brain injury: the interplay between blood pressure, cerebral perfusion, body position and autoregulation. Doctoral Dissertation. Gröningen, The Netherlands; 2012.
9. Avezaat C.J.J., Eijndhoven J.H.M. Cerebrospinal fluid pulse pressure and craniospatial dynamics. A theoretical, clinical and experimental study. Erasmus University, Rotterdam; 1984.
10. Rhee C., Kibler K., Easley R., Andropulos D., Czosnyka M., Smielewski P., Vorsos G., Brady K., Rusin C., Kaiser J. The ontogeny of cerebral blood flow autoregulation and critical closing pressure. In: The 15th International Conference on Intracranial Pressure and Brain Monitoring. Singapore; November 6–10, 2013; p. 66.
11. Heldt T., Noraky J., Verghese G. Noninvasive intracranial pressure determination in patients with subarachnoid hemorrhage. In: The 15th International Conference on Intracranial Pressure and Brain Monitoring. Singapore; November 6–10, 2013; p. 40.
12. Kapinos G., Sadoughi A., Narayan R. Intracranial pressure treatment tailored to transcranial Doppler-derived compliance and perfusion. In: The 15th International Conference on Intracranial Pressure and Brain Monitoring. Singapore; November 6–10, 2013; p. 44.
13. Dewey R., Pierer H., Hunt W. Experimental cerebral hemodynamics. Vasomotor tone, critical closing pressure, and vascular bed resistance. J Neurosurg 1974; 41(5): 597–606, http://dx.doi.org/10.3171/jns.1974.41.5.0597.
14. Kasprowicz M. Badania hemodynamiki mózgowej na podstawie analizy pulsacji ciśnienia wewnątrzczaszkowego, ciśnienia tętniczego i przepływu krwi mózgowej [Assessment of cerebral hemodynamics based on pulse waveform analysis of intracranial pressure, arterial blood pressure and cerebral blood flow]. Oficyna Wydawnicza Politechniki Wrocławskiej. Wrocław; 2012.
15. Kasprowicz M., Diedler J., Reinhard M., Carrera E., Steiner L.A., Smielewski P., Budohoski K.P., Haubrich C., Pickard J.D., Czosnyka M. Time constant of the cerebral arterial bed in normal subjects. Ultrasound Med Biol 2012; 38(7): 1129–1137, http://dx.doi.org/10.1016/j.ultrasmedbio.2012.02.014.
16. Laan ter Mark. Neuromodulation of cerebral blood flow. PhD Dissertation. Gröningen, The Netherlands; 2014.
17. Narayanan N., Leffler C.W., Czosnyka M., Daley M.L. Assessment of cerebrovascular resistance with model of cerebrovascular pressure transmission. Acta Neurochir Suppl 2008; 102: 37–41, http://dx.doi.org/10.1016/j.medengphy.2008.07.002.
18. Sharples P.M., Matthews D.S., Eyre J.A. Cerebral blood flow and metabolism in children with severe head injuries. Part 2: cerebrovascular resistance and its determinants. J Neurol Neurosurg Psychiatry 1995; 58(2): 153–159, http://dx.doi.org/10.1136/jnnp.58.2.153.
19. Daley M., Narayanan N., Leffler C. Model-derived assessment of cerebrovascular resistance and cerebral blood flow following traumatic brain injury. Exp Biol Med (Maywood) 2010; 235(4): 539–545, http://dx.doi.org/10.1258/ebm.2010.009253.
20. Smirl J.D., Tzeng Y.C., Monteleone B.J., Ainslie P.N. Influence of cerebrovascular resistance on the dynamic relationship between blood pressure and cerebral blood flow in humans. J Appl Physiol 2014; 116(12): 1614–1622, http://dx.doi.org/10.1152/japplphysiol.01266.2013.
21. Bragin D.E., Bush R.C., Müller W.S., Nemoto E.M. High intracranial pressure effects on cerebral cortical microvascular flow in rats. J Neurotrauma 2011; 28(5): 775–785, http://dx.doi.org/10.1089/neu.2010.1692.
22. Muizelaar J.P., Marmarou A., DeSalles A.A., Ward J.D., Zimmerman R.S., Li Z., Choi S.C., Young H.F. Cerebral blood flow and metabolism in severely head-injured children. Part 1: relationship with GCS score, outcome, ICP, and PVI. J Neurosurg 1989; 71(1): 63–71, http://dx.doi.org/10.3171/jns.1989.71.1.0063.
23. Pluta R.M. Delayed cerebral vasospasm and nitric oxide: review, new hypothesis, and proposed treatment. Pharmacol Ther 2005; 105(1): 23–56, http://dx.doi.org/10.1016/j.pharmthera.2004.10.002.
24. Siemkowicz E. Cerebrovascular resistance in ischemia. Pflügers Archiv 1980; 388(3); 243–247, http://dx.doi.org/10.1007/bf00658489.
25. Potapov A.A., Zakharova N.E., Kornienko V.N., Pronin I.N., Aleksandrova E.V., Zaĭtsev O.S., Likhterman L.B., Gavrilov A.G., Danilov G.V., Oshorov A.V., Sychev A.A., Polupan A.A. Neuroanatomical basis for traumatic coma: clinical and magnetic resonance correlates. Voprosy neyrokhirurgii im. N.N. Burdenko 2014; 78(1): 4–13.
26. Czosnyka M., Smielewski P., Kirkpatrick P., Laing R.J., Menon D., Pickard J.D. Continuous assessment of the cerebral vasomotor reactivity in head injury. Neurosurgery 1997; 41(1): 11–19, http://dx.doi.org/10.1097/00006123-199707000-00005.
27. Scheinberg P., Stead E. The cerebral blood flow in male subjects as measured by the nitrous oxide technique. Normal values for blood flow, oxygen utilization, glucose utilization, and peripheral resistance, with observations on the effect of tilting and anxiety. J Clin Invest 1949; 28(5): 1163-1171, http://dx.doi.org/10.1172/jci102150.
28. Lassen N.A. Autoregulation of cerebral blood flow. Circ Res 1964; 15(Suppl): 201–204.
29. Marmarou A. A review of progress in understanding the pathophysiology and treatment of brain edema. Neurosurg Focus 2007; 22(5): E1, http://dx.doi.org/10.3171/foc.2007.22.5.2.
30. Cernak I., Vink R., Zapple D.N., Cruz M.I., Ahmed F., Chang T., Fricke S.T., Faden A.I. The pathobiology of moderate diffuse traumatic brain injury as identified using a new experimental model of injury in rats. Neurobiol Dis 2004; 17(1): 29–43, http://dx.doi.org/10.1016/j.nbd.2004.05.011.
31. Rey F.E., Li X.C., Carretero O.A., Garvin J.L., Pagano P.J. Perivascular superoxide anion contributes to impairment of endothelium-dependent relaxation: role of gp91(phox). Circulation 2002; 106(19): 2497–2502, http://dx.doi.org/10.1161/01.cir.0000038108.71560.70.
32. Østergaard L., Engedal T.S., Aamand R., Mikkelsen R., Iversen N.K., Anzabi M., Næss-Schmidt E.T., Drasbek K.R., Bay V., Blicher J.U., Tietze A., Mikkelsen I.K., Hansen B., Jespersen S.N., Juul N., Sørensen J.C., Rasmussen M. Capillary transit time heterogeneity and flow-metabolism coupling after traumatic brain injury. J Cereb Blood Flow Metab 2014; 34(10): 1585–1598, http://dx.doi.org/10.1038/jcbfm.2014.131.
33. Bullock R., Maxwell W.L., Graham D.I., Teasdale G.M., Adams J.H. Glial swelling following human cerebral contusion: an ultrastructural study. J Neurol Neurosurg Psychiatry 1991; 54(5): 427–434, http://dx.doi.org/10.1136/jnnp.54.5.427.
34. Armulik A., Genové G., Mäe M., Nisancioglu M.H., Wallgard E., Niaudet C., He L., Norlin J., Lindblom P., Strittmatter K., Johansson B.R., Betsholtz C. Pericytes regulate the blood-brain barrier. Nature 2010; 468(7323): 557–561, http://dx.doi.org/10.1038/nature09522.
35. Dore-Duffy P., Wang S., Mehedi A., Katyshev V., Cleary K., Tapper A., Reynolds C., Ding Y., Zhan P., Rafols J., Kreipke C.W. Pericyte-mediated vasoconstriction underlies TBI-induced hypoperfusion. Neurol Res 2011; 33(2): 176–186, http://dx.doi.org/10.1179/016164111x12881719352372.
36. Hall C.N., Reynell C., Gesslein B., Hamilton N.B., Mishra A., Sutherland B.A., O’Farrell F.M., Buchan A.M., Lauritzen M., Attwell D. Capillary pericytes regulate cerebral blood flow in health and disease. Nature 2014; 508(7494): 55–60, http://dx.doi.org/10.1038/nature13165.
37. Kreipke C.W., Schafer P.C., Rossi N.F., Rafols .A. Differential effects of endothelin receptor A and B antagonism on cerebral hypoperfusion following traumatic brain injury. Neurol Res 2010; 32(2): 209–214, http://dx.doi.org/10.1179/174313209x414515.
38. Yemisci M., Gursoy-Ozdemir Y., Vural A., Can A., Topalkara K., Dalkara T. Pericyte contraction induced by oxidative-nitrative stress impairs capillary reflow despite successful opening of an occluded cerebral artery. Nat Med 2009; 15(9): 1031–1037, http://dx.doi.org/10.1038/nm.2022.
39. Vollmar B., Westermann S., Menger M.D. Microvascular response to compartment syndrome-like external pressure elevation: an in vivo fluorescence microscopic study in the hamster striated muscle. J Trauma 1999; 46(1): 91–96, http://dx.doi.org/10.1097/00005373-199901000-00015.
40. Вragin D., Bush R., Nemoto E. Effect of cerebral perfusion pressure on cerebral cortical microvascular shunting at high intracranial pressure in rats. Stroke 2013; 44(1): 177–181, http://dx.doi.org/10.1161/STROKEAHA.112.668293.

Trofimov A.O., Kalentiev G.V., Voennov O.V., Martynov D.S., Agarkova D.I., Grigorieva V.N. Change in Cerebrovascular Resistance as Diagnostic Index of Cerebral Hemodynamics in Patients with Severe Combined Traumatic Brain Injury. Sovremennye tehnologii v medicine 2016; 8(3): 105, https://doi.org/10.17691/stm2016.8.3.12