L.J. Norcliffe

Water Drinking Acutely Improves Orthostatic Tolerance in Healthy Subjects

Background—Orthostatic symptoms and syncope are common, even in apparently healthy subjects. In patients with severe autonomic dysfunction, water drinking elicits an acute pressor response and improves orthostatic hypotension. We tested the hypothesis that water drinking also improves orthostatic tolerance in healthy subjects. Methods and Results—In a randomized, controlled, crossover fashion, 13 healthy subjects (9 men, 4 women, 31±2 years) ingested 500 mL and 50 mL of mineral water 15 minutes before head-up tilt on two separate days. Finger blood pressure, brachial blood pressure, heart rate, thoracic impedance, and blood flow velocity in the brachial artery and the middle cerebral artery were measured. Orthostatic tolerance was determined as the time to presyncope during a combined protocol of 20 minutes of 60° head-up tilt alone, followed by additional increasing steps of lower body negative pressure (−20, −40, and −60 mm Hg for 10 minutes each or until presyncope). Drinking 500 mL of water improved orthostatic tolerance by 5±1 minute (range, −1 to +11 minutes, P <0.001). After drinking 500 mL of water, supine mean blood pressure increased slightly (P <0.01) as the result of increased peripheral resistance (P <0.01). It also blunted both the increase in heart rate and the decrease in stroke volume with head-up tilt. Cerebral blood flow regulation improved after water drinking. Conclusions—Water drinking elicits an acute hemodynamic response and changes in cerebrovascular regulation in healthy subjects. These effects are associated with a marked improvement in orthostatic tolerance.

Water drinking improves orthostatic tolerance in patients with posturally related syncope

Water drinking improves OT (orthostatic tolerance) in healthy volunteers; however, responses to water in patients with PRS (posturally related syncope) are unknown. Therefore the aim of the present study was to examine whether water would improve OT in patients with PRS. In a randomized controlled cross-over fashion, nine patients with PRS ingested 500 ml and 50 ml (control) of water 15 min before tilting on two separate days. OT was determined using a combined test of head-up tilting and lower body suction and expressed as the time required to induce presyncope. We measured blood pressure and heart rate (using Portapres) and middle cerebral artery velocity (using transcranial Doppler). SV (stroke volume) and TPR (total peripheral resistance) were calculated using the Modelflow method. OT was significantly (P<0.02) greater after drinking 500 ml of water than after 50 ml (25.4+/-1.5 compared with 19.8+/-2.3 min respectively). After ingestion of 500 ml of water, blood pressure during tilting was higher, the tiltinduced reduction in SV was smaller and the increase in TPR was greater (all P<0.05). The correlation coefficient of the relationship between cerebral blood flow velocity and pressure was lower after 500 ml of water (0.43+/-0.1 compared with 0.73+/-0.1; P<0.05), indicating better autoregulation. In conclusion, drinking 500 ml of water increased OT and improved cardiovascular and cerebrovascular control during orthostasis. Patients with PRS should be encouraged to drink water before situations likely to precipitate a syncopal attack.

Cerebrovascular responses to hypoxia and hypocapnia in high-altitude dwellers

Cerebral blood flow is known to increase in response to hypoxia and to decrease with hypocapnia. It is not known, however, whether these responses are altered in high‐altitude dwellers who are not only chronically hypoxic and hypocapnic, but also polycythaemic. Here we examined cerebral blood flow responses to hypoxia and hypocapnia, separately and together, in Andean high‐altitude dwellers, including some with chronic mountain sickness (CMS), which is characterized by excessive polycythaemia. Studies were carried out at high altitude (Cerro de Pasco (CP), Peru; barometric pressure (PB) 450 mmHg) and repeated, following relief of the hypoxia, on the day following arrival at sea level (Lima, Peru; PB 755 mmHg). We compared these results with those from eight sea‐level residents studied at sea level. In nine high‐altitude normal subjects (HA) and nine CMS patients, we recorded middle cerebral artery mean blood flow velocity (MCAVm) using transcranial Doppler ultrasonography, and expressed responses as changes from baseline. MCAVm responses to hypoxia were determined by changing end‐tidal partial pressure of oxygen (PET,O2) from 100 to 50 mmHg, with end‐tidal partial pressure of carbon dioxide clamped. MCAVm responses to hypocapnia were studied by voluntary hyperventilation with (PET,O2) clamped at 100 and 50 mmHg. There were no significant differences between the cerebrovascular responses of the two groups to any of the interventions at either location. In both groups, the MCAVm responses to hypoxia were significantly greater at Lima than at CP (HA, 12.1 ± 1.3 and 6.1 ± 1.0%; CMS, 12.5 ± 0.8 and 5.6 ± 1.2%; P < 0.01 both groups). The responses at Lima were similar to those in the sea‐level subjects (13.6 ± 2.3%). The responses to normoxic hypocapnia in the altitude subjects were also similar at both locations and greater than those in sea‐level residents. During hypoxia, both high‐altitude groups showed responses to hypocapnia that were significantly smaller at Lima than at CP (HA, 2.17 ± 0.23 and 3.29 ± 0.34% mmHg−1, P < 0.05; CMS, 1.87 ± 0.16 and 3.23 ± 0.24% mmHg−1; P < 0.01). The similarity of the results from the two groups of altitude dwellers suggests that haematocrit is unlikely to greatly affect cerebrovascular reactivity to hypoxia and hypocapnia. The smaller vasodilatation to hypoxia and larger vasoconstriction to hypoxic hypocapnia at high altitude suggest that cerebrovascular responses may be impaired at the high altitude, i.e. a maladaptation. The changes in the responses within less than 24 h at sea level indicate that this impairment is rapidly reversible.

Orthostatic tolerance and blood volumes in Andean high altitude dwellers

Orthostatic tolerance is a measure of the ability to prevent hypotension during gravitational stress. It is known to be dependent on the degree of vasoconstriction and the magnitude of plasma volume, but the possible influence of packed cell volume (PCV) is unknown. High altitude residents have high haematocrits and probably high packed cell volumes. However, it is not known whether plasma volume and blood volume are affected, or whether their orthostatic tolerance is different from low altitude residents. In this study we determined plasma volume, PCV and orthostatic tolerance in a group of high altitude dwellers (HA), including a subgroup of highland dwellers with chronic mountain sickness (CMS) and extreme polycythaemia. Plasma volume and PCV were determined using Evans Blue dye dilution and peripheral haematocrit. Orthostatic tolerance was assessed as the time to presyncope in a test of head‐up tilting and lower body suction. All studies were performed at 4338 m. Results showed that plasma volumes were not significantly different between CMS and HA, or in highland dwellers compared to those seen previously in lowlanders. PCV and haematocrit were greater in CMS than in HA. Orthostatic tolerance was high in both CMS and HA, although the heart rate responses to orthostasis were smaller in CMS than HA. Orthostatic tolerance was correlated with haematocrit (r= 0.57, P < 0.01) and PCV (r= 0.54, P < 0.01). This investigation has shown that although high altitude residents have large PCV, their plasma volumes were similar to lowland dwellers. The group with CMS have a particularly large PCV and also have a very high orthostatic tolerance, despite smaller heart rate responses. These results are compatible with the view that PCV is of importance in determining orthostatic tolerance.

Cardiovascular responses to orthostatic stress in healthy altitude dwellers, and altitude residents with chronic mountain sickness

High altitude (HA) dwellers have an exceptionally high tolerance to orthostatic stress, and this may partly be related to their high packed cell and blood volumes. However, it is not known whether their orthostatic tolerance would be changed after relief of the altitude‐related hypoxia. Furthermore, orthostatic tolerance is known also to be influenced by the efficiency of the control of peripheral vascular resistance and by the effectiveness of cerebral autoregulation and these have not been reported in HA dwellers. In this study we examined plasma volume, orthostatic tolerance and peripheral vascular and cerebrovascular responses to orthostatic stress in HA dwellers, including some with chronic mountain sickness (CMS) in whom packed cell and blood volumes are particularly large. Eleven HA control subjects and 11 CMS patients underwent orthostatic stress testing, comprising head‐up tilting with lower body suction, at their resident altitude (4338 m) and at sea level. Blood pressure (Portapres), heart rate (ECG), brachial and middle cerebral artery blood velocities (Doppler) were recorded during the test. Plasma volumes were found to be similar in both groups and at both locations. Packed cell and blood volumes were higher in CMS patients than controls. All subjects had very good orthostatic tolerances at both locations, compared to previously published data in lowland dwellers. In CMS patients responses of forearm vascular resistance to the orthostatic stress, at sea level, were smaller than controls (P < 0.05). Cerebral blood velocity was less in CMS than in controls (P < 0.01) and, at sea level, it decreased more than the controls in response to head‐up tilting (P < 0.02). Cerebral autoregulation, assessed from the relationship between cerebral pressure and velocity, was also impaired in CMS patients compared to HA controls, when examined at sea level (P < 0.02). These results have shown that the good orthostatic tolerance seen in high altitude dwellers at altitude is also seen at sea level. There was no difference in orthostatic tolerance between CMS patients, with their exceptionally large blood volumes, and the HA controls. This may be because peripheral vascular and cerebrovascular responses (at least at sea level) are impaired in the CMS patients relative to HA controls. Thus, the advantage of the large blood volume may be offset by the smaller vascular responses.

Carotid baroreflex regulation of vascular resistance in high‐altitude Andean natives with and without chronic mountain sickness

We investigated carotid baroreflex control of vascular resistance in two groups of high‐altitude natives: healthy subjects (HA) and a group with chronic mountain sickness (CMS), a maladaptation condition characterized by high haematocrit values and symptoms attributable to chronic hypoxia. Eleven HA controls and 11 CMS patients underwent baroreflex testing, using the neck collar method in which the pressure distending the carotid baroreceptors was changed by applying pressures of −40 to +60 mmHg to the chamber. Responses of forearm vascular resistance were assessed from changes in the quotient of blood pressure divided by brachial artery blood velocity. Stimulus–response curves were defined at high altitude (4338 m) and within 1 day of descent to sea level. We applied a sigmoid function or third‐order polynomial to the curves and determined the maximal slope (equivalent to peak gain) and the corresponding carotid pressure (equivalent to ‘set point’). The results showed that the peak gains of the reflex were similar in both groups and at both locations. The ‘set point’ of the reflex, however, was significantly higher in the CMS patients compared to HA controls, indicating that the reflex operates over higher pressures in the patients (94.4 ± 3.0 versus 79.6 ± 4.1 mmHg; P < 0.01). This, however, was seen only when subjects were studied at altitude; after descent to sea level the curve reset to a lower pressure with no significant difference between HA and CMS subjects. These results indicate that carotid baroreceptor control of vascular resistance may be abnormal in CMS patients but that descent to sea level rapidly normalizes it. We speculate that this may be explained by CMS patients having greater vasoconstrictor activity at altitude owing to greater hypoxic stimulation of chemoreceptors.