| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
INVITED EDITORIALS
Bispebjerg Hospital, Copenhagen, Denmark
IN A WARM ENVIRONMENT, humans may experience neurological impairment such as dizziness, cognitive decline, and fatigue. These symptoms may reflect a mismatch of increased cerebral metabolic activity and impaired nutritive supply (8). Hyperthermia challenges cerebral circulation by inducing hyperventilation, and in turn hypocapnia, the strongest cerebrovascular constrictor. For thermoregulatory purposes, a significant proportion of cardiac output is diverted to the skin. Under these circumstances a number of studies have examined the cerebral hemodynamic response to exercise and orthostasis, and it is a general finding that indexes of cerebral blood flow (CBF) decrease (1, 5, 13).
In a study in the Journal of Applied Physiology, Fan et al. (4) demonstrate an impressive data set that indicates a heat-stress induced reduction in CBF in the resting supine human. The authors carefully investigated not only the effect of increasing core temperature but also examined the influence of two major components for determination of cerebrovascular resistance: the carbon dioxide tension and cardiac output.
CBF is modulated by its perfusion pressure, i.e., the difference between mean arterial pressure and the venous and intracranial pressures, and by changes in cerebral vascular resistance (CVR). For the brain as a whole, CVR is modified by cerebral autoregulation to maintain CBF stable within a wide range of perfusion pressures and may be modified by the arterial carbon dioxide tension, cardiac output, and/or sympathetic neural stimulation. On a local level, the brain cell's metabolic demand regulates CVR, increasing regional blood flow with neuronal activation.
With increasing core temperature, ventilation increases and, in turn, the end-tidal CO2 concentration declines. It is noteworthy that the authors (4) determined the individual CO2 reactivity at each level of core temperature. The slopes of the relationship between middle cerebral artery blood flow velocity (MCAv) and the partial pressure of end-tidal CO2 (PETCO2) were similar throughout the range of elevations in core temperatures from 0.5 to 2°C, regardless of whether the evaluation was during a hypocapnic or hypercapnic challenge. Interestingly, the CO2 reactivity of MCAv appeared to be unaffected by mild dehydration. At 2°C elevation in core temperature, MCAv decreased 
32%, with a decline in PETCO2 by 17 mmHg. Since CO2 reactivity was 2.5%/mmHg, the marked decline in MCAv could be fully accounted for by heat-induced hyperventilation. Such reductions in MCAv are aggravated further when exercise is performed in a hot environment since CO2 reactivity increases compared with resting normothermic conditions (9).
Do other factors contribute to the decline in cerebral perfusion in the heat? Mean arterial pressure is slightly reduced during heat stress conditions but remains well within the range of perfusion pressure governed by cerebral autoregulation, thus making it an unlikely cause for the reduction in MCAv during heat stress. Cardiac output has the potential of changing cerebral vascular conductance and, in turn, CBF, independent of changes in its perfusion pressure (12). In the present study the authors (4) suggest a role of cardiac output redistribution for the decline in MCAv. When core temperature increased by 2°C, cardiac output increased only 30% while flow to the brachial artery rose 8-fold, reflecting an elevation in muscle sympathetic nerve activity >90% and a 3- to 6-fold increase in skin sympathetic nerve activity (2). With whole body heat stress, a rise in sympathetic neural outflow is, presumably, responsible for reduction in splanchnic and renal blood flow. It is not known whether passive heating increases sympathetic influence on the cerebral vasculature, an effect that is evident when cardiac output is challenged as during exercise with beta-blockade (7). It is tempting to speculate that hyperthermia induces a cerebral steal phenomenon similar to that reported for other vascular beds. Thus, during exercise, blood flow to the legs may decrease when arm exercise is added to leg exercise (10), and also respiratory muscles may "steal" flow from the exercising legs (11). However, in face of the formerly described CO2 effect that fully explains the drop in velocity, it appears speculative whether a steal from the brain exists during heat stress in resting supine humans.
It is a surprising finding that at baseline, mild hypohydration increased MCAv and also the common carotid artery blood flow in 8 of 10 subjects. The authors (4) do not provide an explanation for these findings. Although not reported, it is likely that the dehydrated subjects felt thirsty. In subjects experiencing severe thirst following infusion of hypertonic saline (to a plasma osmolality similar to that of the dehydrated subjects), positron-emission tomography and functional magnetic resonance imaging detect local activation in several cortical and subcortical areas (3). It remains to be evaluated whether thirst-related regional elevations in flow are large enough to be detected by MCAv. Another potential mechanism that could support MCAv during dehydration includes an elevated cardiac output (in 8 of 10 subjects; P = 0.1). It should also be noted that subjects were supine and not physically active. Both an orthostatic challenge and muscular exercise are expected to unmask the negative circulatory effects of dehydration (1, 5).
The authors (4) report a drop by as much as 30% in MCAv, to a level that lies somewhat between the physiological reduction, e.g., when standing up (15%) and loss of consciousness (50%). At the same time, and although several subjects had presyncopal symptoms, near-infrared spectroscopy (NIRS)-determined cerebral oxygenation remained unchanged. The authors' suggestion of a higher cerebral O2 extraction needs further evaluation. The applied so-called tissue oxygenation index, which reflects changes in oxyhemoglobin-to-total hemoglobin ratio, provides an index of tissue oxygen saturation. While it is acknowledged that the spatially resolved NIRS technique emphasizes changes in oxygenation in deeper structures and minimizes the contribution of oxygenation changes in extracerebral tissues, the NIRS signal may be influenced by a marked heat-induced increase in flow to the cranial skin that is obvious by reddening of the face in a warm environment and also reflected in a fourfold elevation in external carotid blood flow (6).
The stable NIRS oxygenation is an unexpected finding since presyncopal symptoms are usually accompanied by a reduction of NIRS oxygenation of >10% (12). NIRS reflects mainly the venous saturation, and a stable cerebral tissue oxygenation at a reduced flow would therefore be indicative of decreases rather than increased O2 extraction. In the present study, NIRS reflects oxygenation of frontal cortical tissue, while MCAv reflects blood flow to predominantly the temporal part of the cortex, and heat stress may induce differences in regional blood flow (8). Thus, while the observed stable NIRS signal does not exclude compromised oxygenation at the cellular level in some areas, it may be enhanced in others. Therefore, under the conditions of severe heat stress, NIRS oxygenation data should be interpreted with care and not be taken to reflect overall cerebral oxygenation.
In the supine resting human, passive heat stress leads to hyperventilation and, in turn, a reduction in cerebral blood supply that is fully explained by maintained CO2 reactivity. The finding of an increase in flow to the brain with dehydration and the issue of whether oxygenation to the brain is maintained during supine heat stress need further study, preferably applying techniques that allow for imaging of regional changes in flow and metabolism.
FOOTNOTES
Address for reprint requests and other correspondence: F. C. Pott, Brovænget 15, 2830 Virum, Denmark (e-mail: frank.pott{at}gmail.com)
REFERENCES
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
