Novel Insights into Pathophysiology of Delayed Cerebral Ischemia: Effects of Current Rescue Therapy on Microvascular Perfusion Heterogeneity

Björn B Hofmann; Cihat Karadag; Christian Rubbert; Simon Schieferdecker; Milad Neyazi; Yousef Abusabha; Igor Fischer; Hieronymus D Boogaarts; Sajjad Muhammad; Kerim Beseoglu; Daniel Hänggi; Bernd Turowski; Marcel A Kamp; Jan F Cornelius

doi:10.3390/biomedicines11102624

Novel Insights into Pathophysiology of Delayed Cerebral Ischemia: Effects of Current Rescue Therapy on Microvascular Perfusion Heterogeneity

Biomedicines. 2023 Sep 24;11(10):2624. doi: 10.3390/biomedicines11102624.

Authors

Affiliations

¹ Department of Neurosurgery, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, 40225 Düsseldorf, Germany.
² Department of Diagnostic and Interventional Radiology, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, 40225 Düsseldorf, Germany.
³ Department of Neurosurgery, Medical Faculty, Radboud University Nijmegen, 6525 GA Nijmegen, The Netherlands.
⁴ Department of Neurosurgery, International Neuroscience Institute, 30625 Hannover, Germany.
⁵ Centre for Palliative and Neuropalliative Care, Brandenburg Medical School Theodor Fontane, Campus Rüdersdorf, 15562 Rüdersdorf bei Berlin, Germany.
⁶ Faculty of Health Sciences Brandenburg, Brandenburg Medical School Theodor Fontane, 16816 Neuruppin, Germany.

Abstract

General microvascular perfusion and its heterogeneity are pathophysiological features of delayed cerebral ischemia (DCI) that are gaining increasing attention. Recently, CT perfusion (CTP) imaging has made it possible to evaluate them radiologically using mean transit time (MTT) and its heterogeneity (measured by cvMTT). This study evaluates the effect of multimodal rescue therapy (intra-arterial nimodipine administration and elevation of blood pressure) on MTT and cvMTT during DCI in aneurysmal subarachnoid haemorrhage (aSAH) patients. A total of seventy-nine aSAH patients who underwent multimodal rescue therapy between May 2012 and December 2019 were retrospectively included in this study. CTP-based perfusion impairment (MTT and cvMTT) on the day of DCI diagnosis was compared with follow-up CTP after initiation of combined multimodal therapy. The mean MTT was significantly reduced in the follow-up CTP compared to the first CTP (3.7 ± 0.7 s vs. 3.3 ± 0.6 s; p < 0.0001). However, no significant reduction of cvMTT was observed (0.16 ± 0.06 vs. 0.15 ± 0.06; p = 0.44). Mean arterial pressure was significantly increased between follow-up and first CTP (98 ± 17 mmHg vs. 104 ± 15 mmHg; p < 0.0001). The combined multimodal rescue therapy was effective in addressing the general microvascular perfusion impairment but did not affect the mechanisms underlying microvascular perfusion heterogeneity. This highlights the need for research into new therapeutic approaches that also target these pathophysiological mechanisms of DCI.

Keywords: aneurysmal subarachnoid haemorrhage; delayed cerebral ischemia; intra-arterial nimodipine; microvascular perfusion heterogeneity; rescue therapy; spasmolysis.

Grants and funding

This work was supported by the James and Elisabeth Cloppenburg, Peek and Cloppenburg Düsseldorf Stiftung. The APC was funded by the open access fund of the Heinrich-Heine University Düsseldorf, Germany and the Medical Faculty of the Heinrich-Heine University Düsseldorf, Germany.