Cerebrovascular response to the cold pressor test – the critical role of carbon dioxide

Abstract

What is the central question of this study? What is the role of carbon dioxide in the cerebral blood flow (CBF) response to the cold pressor test (CPT)? What is the main finding and its importance? The CBF response was elevated during the isocapnic (controlled CO ) CPT in the middle cerebral artery and the internal carotid artery compared with the poikilocapnic (uncontrolled CO ) CPT, owing to ventilation-associated reductions in end-tidal CO . Furthermore, the common carotid artery vasodilated to a greater extent during the isocapnic compared with the poikilocapnic CPT, whereas the internal carotid artery vasoconstricted during both CPTs. Our data highlight the importance of CO control when investigating the CBF response to the CPT. In addition to increasing sympathetic nervous activity, blood pressure and cerebral blood flow (CBF), the cold pressor test (CPT) stimulates pain receptors, which may increase ventilation above metabolic demand; this response is likely to reduce the partial pressure of end-tidal carbon dioxide (P ET ,CO2) and will attenuate elevations in CBF. Our hypotheses were as follows: (i) the CPT will elicit hyperventilation, effectively lowering P ET ,CO2; (ii) the CBF response will be elevated during an isocapnic (controlled P ET ,CO2) compared with a poikilocapnic CPT (uncontrolled P ET ,CO2); and (iii) in response to the CPT, the common carotid artery (CCA) will vasodilate, while the internal carotid artery (ICA) will remain unchanged to help regulate CBF. Using a new, randomized experimental design, we measured the cerebrovascular response in the middle cerebral artery (MCA), CCA and internal carotid artery (ICA), during an isocapnic and poikilocapnic CPT in 15 participants. Blood pressure and cardiac output (finger photoplethysmography), heart rate (ECG), MCA mean velocity (transcranial Doppler ultrasound) and CCA and ICA CBF (Duplex ultrasound) were recorded during both CPT trials. Our findings were as follows: (i) ventilation increased, which reduced P ET ,CO2 (-5.3 ± 6.4 mmHg) during the poikilocapnic compared with the isocapnic CPT; (ii) the CBF response was elevated during the isocapnic compared with the poikilocapnic CPT in the MCA and ICA, but not in the CCA; and (iii) the CCA dilated to a greater extent during the isocapnic compared with the poikilocapnic CPT, and the ICA vasoconstricted during both trials. Our data emphasize the importance of P ET ,CO2 control in the CBF response to the CPT and in the differential vasomotor regulation between the CCA and ICA.

Human cerebrovascular responses to diving are not related to facial cooling

“… controlled at +1 mmHg baseline) MCA v mean increased during CPT (Protocol 2). Such findings agree with those of Tymko, Kerstens, Wildfong, and Ainslie (2017) and highlight the importance of nociceptor‐mediated alterations in ventilation, and thus , on blunting the cerebral perfusion response to the CPT. A striking example of the balance between the effects of ventilation, and thus , on cerebral perfusion in the cold has been provided by Datta and Tipton (2006).…”

Sex differences in the circulatory responses to an isocapnic cold pressor test

“…We controlled for both and during the CPT protocol in order to remove the influence of arterial blood gases on changes in cerebral blood flow (Sato et al., ; Willie et al., ). A recent study performed by our research group demonstrated that during a 0–1°C, 3 min CPT, was elevated in both males and females, resulting in a reduction in and the diameter response of the CCA (Tymko et al., ). Unfortunately, we were unsuccessful at maintaining isocapnia throughout the entire CPT, because was reduced at CPT2 compared with baseline values; however, the observed reduction was on average <1 mmHg, and importantly, no interaction effect was present between males and females.…”

“…Two female participants were excluded from data analyses owing to failure to complete the experimental protocol. The data collected and analysed in the present study includes data from 15 participants (five females) from a previous publication (Tymko et al., ). To extend these findings and in order to compare the sex‐specific response to the CPT adequately, five additional age‐matched female participants were recruited; therefore, the present study was designed to answer this a priori research question.…”

“…The and the partial pressure of end‐tidal O 2 () were controlled by a portable dynamic end‐tidal forcing system as previously described in detail elsewhere (Tymko et al., ; Tymko, Ainslie, MacLeod, Willie, & Foster, ). This system has been used to control end‐tidal gases during several different physiological stressors, such as heat stress (Bain et al., ), exercise (Smith et al., ), lower‐body negative pressure (Lewis et al., ; van Mil et al., ) and a CPT (Tymko et al., ; van Mil et al., ).…”

“…An important methodological consideration regarding these previous investigations is that they did not control for ventilation‐related changes in the partial pressure of end‐tidal CO 2 () during the CPT, which may be influenced by changes in autonomic activity (Heistad, Abboud, Mark, & Schmid, ). This consideration is important for a more precise control, measurement and standardization of the physiological responses to the CPT (Tymko, Kerstens, Wildfong, & Ainslie, ).…”