Abstract
Caffeine is one of the most widely consumed psycho-stimulants in the world, yet little is known about its effects on brain oxygenation and metabolism. Using a double-blind, placebo-controlled, randomized cross-over study design, we combined transcranial Doppler ultrasound (TCD) and near-infrared spectroscopy (NIRS) to study caffeine's effect on middle cerebral artery peak blood flow velocity (Vp), brain tissue oxygenation (StO2), total hemoglobin (tHb), and cerebral oxygen metabolism (CMRO2) in five subjects. Hyperventilation-induced hypocapnia served as a control to verify the sensitivity of our measurements. During hypocapnia (∼16 mmHg below resting values), Vp decreased by 40.0 ± 2.4% (95% CI, P < 0.001), while StO2 and tHb decreased by 2.9 ± 0.3% and 2.6 ± 0.4%, respectively (P = 0.003 and P = 0.002, respectively). CMRO2, calculated using the Fick equation, was reduced by 29.3 ± 9% compared to the isocapnic-euoxia baseline (P < 0.001). In the pharmacological experiments, there was a significant decrease in Vp, StO2, and tHb after ingestion of 200 mg of caffeine compared with placebo. There was no significant difference in CMRO2 between caffeine and placebo. Both showed a CMRO2 decline compared to baseline showing the importance of a placebo control. In conclusion, this study showed that profound hypocapnia impairs cerebral oxidative metabolism. We provide new insight into the effects of caffeine on cerebral hemodynamics. Moreover, this study showed that multimodal NIRS/TCD is an excellent tool for studying brain hemodynamic responses to pharmacological interventions and physiological challenges.
Highlights
Cerebral hemodynamics are important brain physiological parameters that can change in response physiological challenge or drug ingestions (Blaha et al 2007; Chen and Parrish 2009; Bain et al 2013)
We used noninvasive multimodal transcranial Doppler ultrasound (TCD) and near-infrared spectroscopy (NIRS) imaging to carry out a randomized double-blind, placebo-controlled, cross-over study to investigate the effect of caffeine on cerebral hemodynamics
We demonstrated that a combined NIRS and TCD approach is sensitive at detecting physiologically and pharmacologically induced hemodynamic changes and so could be useful at individualizing drug responses
Summary
Cerebral hemodynamics (blood flow, metabolic rate, oxygenation) are important brain physiological parameters that can change in response physiological challenge or drug ingestions (Blaha et al 2007; Chen and Parrish 2009; Bain et al 2013). Caffeine is known to significantly decrease cerebral blood flow (CBF) (Perthen et al 2008; Chen and Parrish 2009; Vidyasagar et al 2013). This appears paradoxical to its stimulating effects, as a decrease in CBF is usually associated with a decrease in CMRO2 (Buxton et al 1998; Kida et al 2007)
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