Respiratory Physiology & Neurobiology 233 (2016) 60–65 Contents lists available at ScienceDirect Respiratory Physiology & Neurobiology journal h om epa ge: www.elsevier.com/locate/resphysiol Cerebral microvascular blood flow and CO 2 reactivity in pulmonary arterial hypertension  Erika Treptow a,b , Mayron F. Oliveira a , Aline Soares a , Roberta P. Ramos a,b , Luiz Medina a , Rita Lima a , Maria Clara Alencar a , Eloara Vieira Ferreira a,b , Jaquelina S. Ota-Arakaki b , Sergio Tufik c , Luiz E. Nery a , Lia Rita Bittencourt c , J. Alberto Neder (MD PhD) a,b,d,∗ a Pulmonary Function and Clinical Exercise Physiology Unit (SEFICE), Respiratory Division, Department of Medicine, Federal University of São Paulo, Paulista School of Medicine (UNIFESP-EPM), Brazil b Division of Respiratory Diseases, Department of Medicine, Federal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil c Departamento de Psicobiologia da Universidade Federal de São Paulo (UNIFESP), Brazil d Laboratory of Clinical Exercise Physiology (LACEP), Division of Respiratory and Critical Care Medicine, Department of Medicine, Queen’s University, Kingston, Canada a r t i c l e i n f o Article history: Received 6 April 2016 Received in revised form 8 August 2016 Accepted 10 August 2016 Available online 10 August 2016 Keywords: Cerebral blood flow Carbon dioxide Pulmonary hypertension Ventilation Near-infrared spectroscopy a b s t r a c t Hypocapnia and endothelial dysfunction might impair microvascular cerebral blood flow (CBF micr ) and cerebrovascular reactivity to CO 2 (CVR CO2 ). Pulmonary arterial hypertension (PAH) is characteristically associated with chronic alveolar hyperventilation and microvascular endothelial dysfunction. We there- fore determined CBF micr (pre-frontal blood flow index (BFI) by the indocyanine green-near infrared spectroscopy methodology) during hypocapnia and hypercapnia in 25 PAH patients and 10 gender- and age-matched controls. Cerebral BFI was lower in patients than controls at similar transcutaneous PCO 2 (PtcCO 2 ) levels in both testing conditions. In fact, while BFI increased from hypocapnia to hypercapnia in all controls, it failed to increase in 17/25 (68%) patients. Thus, BFI increased to a lesser extent from hypo to hypercapnia (“”) in patients, i.e., they showed lower  BFI/ PtcCO 2 ratios than controls. In conclusion, CBF micr and CVR CO2 are lessened in clinically stable, mildly-impaired patients with PAH. These abnor- malities might be associated with relevant clinical outcomes (hyperventilation and dyspnea, cognition, cerebrovascular disease) being potentially amenable to pharmacological treatment. © 2016 Elsevier B.V. All rights reserved. 1. Introduction The precise regulation of blood flow through the small brain vessels (i.e. pre-capillary arterioles, capillary and glial vessels) is paramount to nutrient and oxygen supply to neurons with impor- tant implications for motor-sensory function, neuro-vegetative control and cognition (Ainslie and Duffin, 2009). Owing to anatomic and physiological peculiarities however, cerebral microvascular blood flow (CBF micr ) might differ from that observed in large con- duit arteries (Zirak et al., 2014). Interrogation of the human cerebral microvasculature may therefore provide a more accurate assess-  Funded by: Fundacao de Amparo a Pesquisa de Sao Paulo (FAPESP), Brazil (Grant # 11/52102-6). ∗ Corresponding author at: Division of Respiratory and Critical Care Medicine Queen’s University and Kingston General Hospital Richardson House, 102 Stuart Street Kingston, K7L 2V6 ON, Canada. E-mail address: nederalb@gmail.com (J.A. Neder). ment of actual tissue perfusion than macrovascular hemodynamic measurements (Kuebler et al., 1998; Gora et al., 2002). The regulation of CBF micr is a sophisticated physiological process that integrates intracranial mediators of cerebral vessel resistance (e.g., cerebral metabolism and auto-regulation) to cardiovascular (e.g., mean blood pressure and cardiac output) and pulmonary gas exchange function (Jordan et al., 2000; Ainslie and Duffin, 2009; Goadsby, 2013). The arterial partial pressure for carbon dioxide (PaCO 2 ) stands out as a key “humoral” regulator of cerebral tissue perfusion as CBF micr increases 3–6% and decreases 1–3% for each mmHg change in CO 2 above and below eupnoeic PaCO 2 . (Ainslie and Duffin, 2009) Thus, the cerebro(micro)vascular reactivity to CO 2 (CVR CO2 ) can be measured by relating simultaneous varia- tions in PaCO 2 and CBF micr . (Zirak et al., 2014) Of note, endothelial vasodilatory prostanoids, nitric oxide (NO) and the system of phos- phodiesterases constitute important mediators of both CBF micr and CVR CO2 (Diomedi et al., 2005; Brenner, 2006; Fathi et al., 2011; Pretnar-Oblak, 2014). It is therefore conceivable that those measurements would hold particular relevance to disease condi- http://dx.doi.org/10.1016/j.resp.2016.08.001 1569-9048/© 2016 Elsevier B.V. All rights reserved.