The Acute Phase of Experimental Subarachnoid Hemorrhage: Intracranial Pressure Dynamics and Their Effect on Cerebral Blood Flow and Autoregulation
- 138 Downloads
Clinical presentation and neurological outcome in subarachnoid hemorrhage (SAH) is highly variable. Aneurysmal SAH (aSAH) is hallmarked by sudden increase of intracranial pressure (ICP) and acute hypoperfusion contributing to early brain injury (EBI) and worse outcome, while milder or non-aneurysmal SAH with comparable amount of blood are associated with better neurological outcome, possibly due to less dramatic changes in ICP. Acute pressure dynamics may therefore be an important pathophysiological aspect determining neurological complications and outcome. We investigated the influence of ICP variability on acute changes after SAH by modulating injection velocity and composition in an experimental model of SAH. Five hundred microliters of arterial blood (AB) or normal saline (NS) were injected intracisternally over 1 (AB1, NS1), 10 (AB10, NS10), or 30 min (AB30) with monitoring for 6 h (n = 68). Rapid blood injection resulted in highest ICP peaks (AB1 median 142.7 mmHg [1.Q 116.7–3.Q 230.6], AB30 33.42 mmHg [18.8–38.3], p < 0.001) and most severe hypoperfusion (AB1 16.6% [11.3–30.6], AB30 44.2% [34.8–59.8]; p < 0.05). However, after 30 min, all blood groups showed comparable ICP elevation and prolonged hypoperfusion. Cerebral autoregulation was disrupted initially due to the immediate ICP increase in all groups except NS10; only AB1, however, resulted in sustained impairment of autoregulation, as well as early neuronal cell loss. Rapidity and composition of hemorrhage resulted in characteristic hyperacute hemodynamic changes, with comparable hypoperfusion despite different ICP ranges. Only rapid ICP increase was associated with pronounced and early, but sustained disruption of cerebral autoregulation, possibly contributing to EBI.
KeywordsExperimental subarachnoid hemorrhage Acute phase Cerebral autoregulation Early brain injury (EBI) Intracranial pressure (ICP) Cerebral hypoperfusion
We cordially thank Ekaterina Harder, Jörn Iwertowski (Translational Neurosurgery and Neurobiology) and Birgit Nellessen (Dept. of Anesthesiology, RWTH Aachen University) for technical assistance. Further technical support was provided by the Immunohistochemistry Facility, a core facility of the Interdisciplinary Center for Clinical Research (IZKF) Aachen within the Faculty of Medicine at RWTH Aachen University.
Conceived and designed the experiments and the study protocol: CC, GAS, UL. Performed the experiments: CC, KB. Analyzed the data: CC, UL, GAS, WA. Interpretation of the data: CC, GAS, UL. Designed and performed immunohistochemistry: CC, AB, KB. Blinded cell counting: NL. Blinded analysis of successful SAH: MW. Contributed reagents/materials/analysis tools: AS, WA, CC, UL, HC, GAS, SP, MW, KB. Wrote the paper: CC, KB, GAS. Critical review of the manuscript: UL, HC, MW, AS, WA, AB, KB.
This study was supported by grants from DFG (FOR 2591) and by grants from the Foundation of Neurosurgical Research (German Society of Neurosurgery, 2016).
Compliance with Ethical Standards
All applicable international, national, and institutional guidelines for the care and use of animals were followed. All experimental protocols were approved by the responsible state authorities in line with the EU Directive 2010/63/EU on the protection of animals used for scientific purposes (Landesamt für Natur, Umwelt und Verbraucherschutz (LANUV) Nordrhein – Westfalen, Recklinghausen, Germany; AZ 84-02.04.2015.A412) and were performed in accordance with the ARRIVE Guidelines .
The authors declare that there is no conflict of interest.
- 2.Vergouwen MD, Vermeulen M, van Gijn J, Rinkel GJ, Wijdicks EF, Muizelaar JP, et al. Definition of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage as an outcome event in clinical trials and observational studies: proposal of a multidisciplinary research group. Stroke. 2010;41(10):2391–5.CrossRefGoogle Scholar
- 4.Schubert GA, Seiz M, Hegewald AA, Manville J, Thome C. Hypoperfusion in the acute phase of subarachnoid hemorrhage. Acta Neurochir Suppl. 2011;110(Pt 1):35–8.Google Scholar
- 36.Ebel H, Rust DS, Leschinger A, Ehresmann N, Kranz A, Hoffmann O, et al. Vasomotion, regional cerebral blood flow and intracranial pressure after induced subarachnoid haemorrhage in rats. Zentralblatt fur Neurochirurgie. 1996;57(3):150–5.Google Scholar
- 42.Boedtkjer E. Acid-base regulation and sensing: accelerators and brakes in metabolic regulation of cerebrovascular tone. J Cereb Blood Flow Metab. 2017:271678X17733868.Google Scholar
- 44.Balbi M, Koide M, Schwarzmaier SM, Wellman GC, Plesnila N. Acute changes in neurovascular reactivity after subarachnoid hemorrhage in vivo. J Cereb Blood Flow Metab. 2015;16.Google Scholar
- 45.Balbi M, Koide M, Wellman GC, Plesnila N. Inversion of neurovascular coupling after subarachnoid hemorrhage in vivo. J Cereb Blood Flow Metab. 2017:271678X16686595.Google Scholar
- 47.Yamamoto S, Nishizawa S, Tsukada H, Kakiuchi T, Yokoyama T, Ryu H, et al. Cerebral blood flow autoregulation following subarachnoid hemorrhage in rats: chronic vasospasm shifts the upper and lower limits of the autoregulatory range toward higher blood pressures. Brain Res. 1998;782(1–2):194–201.CrossRefGoogle Scholar
- 49.Hollig A, Weinandy A, Nolte K, Clusmann H, Rossaint R, Coburn M. Experimental subarachnoid hemorrhage in rats: comparison of two endovascular perforation techniques with respect to success rate, confounding pathologies and early hippocampal tissue lesion pattern. PLoS One. 2015;10(4):e0123398.CrossRefGoogle Scholar
- 54.Prunell GF, Mathiesen T, Diemer NH, Svendgaard NA. Experimental subarachnoid hemorrhage: subarachnoid blood volume, mortality rate, neuronal death, cerebral blood flow, and perfusion pressure in three different rat models. Neurosurgery. 2003;52(1):165–75 discussion 75-6.Google Scholar