Browsing by Author "Rasmussen, Mads"

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    Impact of intravenous antihypertensive therapy on cerebral blood flow and neurocognition: a systematic review and meta-analysis
    (Elsevier, 2025) Meacham, Kylie S.; Schmidt, Jacob D.; Sun, Yanhua; Rasmussen, Mads; Liu, Ziyue; Adams, David C.; Backfish-White, Kevin M.; Meng, Lingzhong; Anesthesia, School of Medicine
    Background: Intravenous antihypertensivedrugs are commonly used in acute care settings, yet their impact on cerebral blood flow (CBF) remains uncertain. Methods: A systematic review and meta-analysis of 50 studies evaluated the effects of commonly used i.v. antihypertensive agents on CBF in normotensive, hypertensive, and intracranial pathology populations. Meta-analyses used standardised mean differences (SMD), stratified by population type, consciousness state, antihypertensive agent, and CBF measurement method. Results: Intravenous antihypertensivedrug therapy significantly reduced CBF in normotensive individuals without intracranial pathology (SMD -0.31, 95% confidence interval -0.51 to -0.11), primarily driven by nitroprusside and nitroglycerin in awake subjects (SMD -0.80, 95% confidence interval -1.15 to -0.46), with a median CBF decrease of 14% (interquartile range 13-16%) and a median mean arterial pressure reduction of 17% (interquartile range 9-22%). Other antihypertensives showed no significant effects on CBF in normotensive individuals, nor were changes observed in hypertensive patients or those with intracranial pathology when the median mean arterial pressure reduction was ∼20%. No correlation was found between mean arterial pressure reduction and CBF change, supporting intact cerebral autoregulation. Historical data revealed neurocognitive changes when CBF fell to ∼30 ml 100 g-1 min-1, associated with a 58% mean arterial pressure reduction and a 38% CBF reduction. Conclusions: Most i.v. antihypertensive agents do not significantly affect CBF in clinical dose ranges; however, nitroprusside and nitroglycerin can reduce CBF under specific clinical conditions. The certainty of evidence remains low. Neurocognitive changes appear to depend on the magnitude of blood pressure and CBF reductions.
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    Integrated Feedforward and Feedback Mechanisms in Neurovascular Coupling
    (Wolters Kluwer, 2024-12) Meng, Lingzhong; Rasmussen, Mads; Meng, Deyi M.; White, Fletcher A.; Wu, Long-Jun; Anesthesia, School of Medicine
    Neurovascular coupling (NVC) is the mechanism that drives the neurovascular response to neural activation, and NVC dysfunction has been implicated in various neurologic diseases. NVC is driven by (1) nonmetabolic feedforward mechanisms that are mediated by various signaling pathways and (2) metabolic feedback mechanisms that involve metabolic factors. However, the interplay between these feedback and feedforward mechanisms remains unresolved. We propose that feedforward mechanisms normally drive a swift, neural activation–induced regional cerebral blood flow (rCBF) overshoot, which floods the tissue beds, leading to local hypocapnia and hyperoxia. The feedback mechanisms are triggered by the resultant hypocapnia (not hyperoxia), which causes cerebral vasoconstriction in the neurovascular unit that counterbalances the rCBF overshoot and returns rCBF to a level that matches the metabolic activity. If feedforward mechanisms function improperly (eg, in a disease state), the rCBF overshoot, tissue-bed flooding, and local hypocapnia fail to occur or occur on a smaller scale. Consequently, the neural activation–related increase in metabolic activity results in local hypercapnia and hypoxia, both of which drive cerebral vasodilation and increase rCBF. Thus, feedback mechanisms ensure the brain milieu’s stability when feedforward mechanisms are impaired. Our proposal integrates the feedforward and feedback mechanisms underlying NVC and suggests that these 2 mechanisms work like a fail-safe system, to a certain degree. We also discussed the difference between NVC and cerebral metabolic rate-CBF coupling and the clinical implications of our proposed framework.