Head down tilt 15° to preserve salvageable brain tissue in acute ischemic stroke: A pre‐clinical pooled analysis, with focus on cerebral hemodynamics

• Published in: The European journal of neuroscience 2023-06, Vol.57 (12), p.2149-2159
• Main Authors: Diamanti, Susanna, Mariani, Jacopo, Versace, Alessandro, Riva, Matteo, Cuccione, Elisa, Cai, Ruiyao, Monza, Laura, Viganò, Martina, Bolbos, Radu, Chauveau, Fabien, Cho, Tae‐Hee, Carone, Davide, Ferrarese, Carlo, Beretta, Simone
• Format: Article
• Language: English
• Subjects: acute ischemic stroke; Animals; Brain; Brain Ischemia; Cerebral blood flow; cerebral perfusion; Food and Nutrition; head down tilt 15; Head-Down Tilt; Hemodynamics; Humans; Infarction, Middle Cerebral Artery; Ischemia; Ischemic Stroke; Life Sciences; middle cerebral artery occlusion; Perfusion; Population studies; positional therapy; Rats; Stroke
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1111/ejn.15852

Neurological outcome after ischemic stroke depends on residual salvageable brain tissue at the time of recanalization. Head down tilt 15° (HDT15) was proven effective in reducing infarct size and improving functional outcome in rats with transient middle cerebral artery occlusion (t‐MCAO) by increasing cerebral perfusion within the ischemic penumbra. In this pooled analysis, individual animal‐level data from three experimental series were combined in a study population of 104 t‐MCAO rats (45 in HDT15 group and 59 in flat position group). Co‐primary outcomes were infarct size and functional outcome at 24 h in both groups. The secondary outcome was hemodynamic change induced by HDT15 in ischemic and non‐ischemic hemispheres in a subgroup of animals. Infarct size at 24 h was smaller in HDT15 group than in flat position group (absolute mean difference 31.69 mm3, 95% CI 9.1–54.2, Cohen's d 0.56, p = 0.006). Functional outcome at 24 h was better in HDT15 group than in flat position group (median [IQR]: 13[10–16] vs. 11), with a shift in the distribution of the neurobehavioural scores in favour of HDT15. Mean cerebral perfusion in the ischemic hemisphere was higher during HDT15 than before its application (Perfusion Unit [P.U.], mean ± SD: 52.5 ± 19.52 P.U. vs. 41.25 ± 14.54 P.U., mean of differences 13.36, 95% CI 7.5–19.18, p = 0.0002). Mean cerebral perfusion in the non‐ischemic hemisphere before and during HDT15 was unchanged (P.U., mean ± SD: 94.1 ± 33.8 P.U. vs. 100.25 ± 25.34 P.U., mean of differences 3.95, 95%, CI −1.9 to 9.6, p = 0.1576). This study confirmed that HDT15 improves the outcome in t‐MCAO rats by promoting cerebral perfusion in the ischemic territory, without disrupting hemodynamics in non‐ischemic areas. In this pre‐clinical study, Head down tilt 15° was applied for 60 min during a transient right middle cerebral artery occlusion (t‐MCAO) in rats. HDT15 effectively improved functional outcome and reduced infarct size at 24 h. Bi‐hemispheric Laser Doppler monitoring of cerebral perfusion showed that HDT15 increases cerebral perfusion in the ischemic territory, without disrupting hemodynamics in non‐ischemic areas.