Non-technical summary Heat stress reduces brain blood flow and impairs orthostatic tolerance. Brain blood flow is largely controlled by the partial pressure of arterial P CO 2 . Indeed, hyperthermia-induced over-breathing and related reductions in arterial P CO 2 account for ∼50% of the reduction in brain blood flow. This investigation tested the unique hypothesis that the distribution of cardiac output during heat stress (challenged by thermoregulatory increases in skin blood flow and sweat loss) contributes to the remaining 50%. We show that cardiac output is not related to brain blood flow, but rather arterial P CO 2 plays a much larger role than previously suggested. These findings help us understand the mechanisms relating heat stress with an increased likelihood of fainting, and are also relevant to pathological conditions that are accompanied by elevations in body temperature.Abstract Cerebral blood flow (CBF) is reduced during passive heat stress, with 50% of this reduction associated with hyperventilatory-induced hypocapnia and subsequent cerebral vasoconstriction. It remains unknown, however, what other factors may contribute to the remaining 50%. We tested the hypothesis that the distribution of cardiac output plays an important role in maintaining cerebral perfusion during mild and severe heat stress. Middle cerebral artery and posterior cerebral artery blood flow velocity (MCAv and PCAv; transcranial Doppler) and left ventricular end-diastolic and end-systolic volumes (2-D echocardiography) were measured under conditions of normothermia and mild and severe passive heat stress (core temperature +0.8 ± 0.1• C (Protocol I; n = 10) and 1.8 ± 0.1 • C (Protocol II; n = 8) above baseline). Venous return was manipulated by passive tilt table positioning (30 deg head-down tilt (HDT) and 30 deg head-up tilt (HUT)). Measurements were made under poikilocapnic and isocapnic conditions. Protocol I consisted of mild heat stress which resulted in small reductions in end-tidal CO 2 (−5.6 ± 3.5%), MCAv/PCAv (−7.3 ± 2.3% and −10.3 ± 2.9%, respectively) and stroke volume (−8.5 ± 4.2%); while end-diastolic volume was significantly reduced (−16.9 ± 4.0%) and cardiac output augmented (17.2 ± 7.4%). During mild heat stress, CBF was related to left ventricular end-diastolic volume (MCAv, r 2 = 0.81; PCAv, r 2 = 0.83; P < 0.05) and stroke volume (MCAv, r 2 = 0.38; PCAv, r 2 = 0.43), but not with cardiac output. Protocol II consisted of severe heat stress which resulted in much greater reductions in end-tidal CO 2 (−87.5 ± 31.5%) and CBF (MCAv, −36.4 ± 6.1%; PCAv, −30.1 ± 4.8%; P < 0.01 for all variables), while end-diastolic volume and stroke volume decreased to a similar extent as for mild heat stress. Importantly, isocapnia restored MCAv and PCAv back to normothermic baseline. This investigation therefore produced two novel findings: first, that venous return and stroke volume are related to CBF during mild heat stress; and second, that hyperventilatory hypocapnia has a major influence on CBF during severe passive heat str...

Cerebral blood flow (CBF) increases from rest to ∼60% of peak oxygen uptake (VO 2peak ) and thereafter decreases towards baseline due to hyperventilation-induced hypocapnia and subsequent cerebral vasoconstriction. It is unknown what happens to CBF in older adults (OA), who experience a decline in CBF at rest coupled with a blunted ventilatory response during VO 2peak . In 14 OA (71±10 year) and 21 young controls (YA; 23±4 years), we hypothesized that OA would experience less hyperventilationinduced cerebral vasoconstriction and therefore an attenuated reduction in CBF at VO 2peak . Incremental exercise was performed on a cycle ergometer, whilst bilateral middle cerebral artery blood flow velocity (MCA V mean ; transcranial Doppler ultrasound), heart rate (HR; ECG) and end-tidal PCO 2 (P ET CO 2 ) were monitored continuously. Blood pressure (BP) was monitored intermittently. From rest to 50% of VO 2peak , despite greater elevations in BP in OA, the change in MCA V mean was greater in YA compared to OA (28% vs. 15%, respectively; P<0.0005). In the YA, at intensities >70% of VO 2peak , the hyperventilationinduced declines in both P ET CO 2 (14 mmHg (YA) vs. 4 mmHg (OA); P<0.05) and MCA V mean (−21% (YA) vs. −7% (OA); P<0.0005) were greater in YA compared to OA. Our findings show (1), from rest-tomild intensity exercise (50% VO 2peak ), elevations in CBF are reduced in OA and (2) age-related declines in hyperventilation during maximal exercise result in less hypocapnic-induced cerebral vasoconstriction.

BackgroundAssess process, uptake, validity and resource needs for return of actionable research findings to biobank participants.MethodsParticipants were prospectively enrolled in a multicenter biorepository of childhood onset heart disease. Clinically actionable research findings were reviewed by a Return of Research Results Committee (RRR) and returned to the physician or disclosed directly to the participant through a research genetic counselor. Action taken following receipt of this information was reviewed.ResultsGenetic data was generated in 1963 of 7408 participants. Fifty-nine new findings were presented to the RRR committee; 20 (34%) were deemed reportable. Twelve were returned to the physician, of which 7 were disclosed to participants (median time to disclosure, 192 days). Seven findings were returned to the research genetic counselor; all have been disclosed (median time to disclosure, 19 days). Twelve families (86%) opted for referral to clinical genetics after disclosure of findings; 7 results have been validated, 5 results are pending. Average cost of return and disclosure per reportable finding incurred by the research program was $750 when utilizing a research genetic counselor; clinical costs associated with return were not included.ConclusionsReturn of actionable research findings was faster if disclosed directly to the participant by a research genetic counselor. There was a high acceptability amongst participants for receiving the findings, for referral to clinical genetics, and for clinical validation of research findings, with all referred cases being clinically confirmed.

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