Luke Wilson

Human cardiorespiratory and cerebrovascular function during severe passive hyperthermia: effects of mild hypohydration

The influence of severe passive heat stress and hypohydration (Hypo) on cardiorespiratory and cerebrovascular function is not known. We hypothesized that 1) heating-induced hypocapnia and peripheral redistribution of cardiac output (Q) would compromise blood flow velocity in the middle cerebral artery (MCAv) and cerebral oxygenation; 2) Hypo would exacerbate the hyperthermic-induced hypocapnia, further decreasing MCAv; and 3) heating would reduce MCAv-CO2 reactivity, thereby altering ventilation. Ten men, resting supine in a water-perfused suit, underwent progressive hyperthermia [0.5 degrees C increments in core (esophageal) temperature (TC) to +2 degrees C] while euhydrated (Euh) or Hypo by 1.5% body mass (attained previous evening). Time-control (i.e., non-heat stressed) data were obtained on six of these subjects. Cerebral oxygenation (near-infrared spectroscopy), MCAv, end-tidal carbon dioxide (PetCO2) and arterial blood pressure, Q (flow model), and brachial and carotid blood flows (CCA) were measured continuously each 0.5 degrees C change in TC. At each level, hypercapnia was achieved through 3-min administrations of 5% CO2, and hypocapnia was achieved with controlled hyperventilation. At baseline in Hypo, heart rate, MCAv and CCA were elevated (P<0.05 vs. Euh). MCAv-CO2 reactivity was unchanged in both groups at all TC levels. Independent of hydration, hyperthermic-induced hyperventilation caused a severe drop in PetCO2 (-8+/-1 mmHg/ degrees C), which was related to lower MCAv (-15+/-3%/ degrees C; R2=0.98; P<0.001). Elevations in Q were related to increases in brachial blood flow (R2=0.65; P<0.01) and reductions in MCAv (R2=0.70; P<0.01), reflecting peripheral distribution of Q. Cerebral oxygenation was maintained, presumably via enhanced O2-extraction or regional differences in cerebral perfusion.

Cerebrovascular and corticomotor function during progressive passive hyperthermia in humans

The present study examined the integrative effects of passive heating on cerebral perfusion and alterations in central motor drive. Eight participants underwent passive hyperthermia [0.5°C increments in core temperature (Tc) from normothermia (37 ± 0.3°C) to their limit of thermal tolerance (T-LIM; 39.0 ± 0.4°C)]. Blood flow velocity in the middle cerebral artery (CBFv) and respiratory responses were measured continuously. Arterial blood gases and blood pressure were obtained intermittently. At baseline and each Tc level, supramaximal femoral nerve stimulation and transcranial magnetic stimulation (TMS) were performed to assess neuromuscular and cortical function, respectively. At T-LIM, measures were (in a randomized order) also made during a period of breathing 5% CO(2) gas to restore eucapnia (+5% CO(2)). Mean heating time was 179 ± 51 min, with each 0.5°C increment in Tc taking 40 ± 10 min. CBFv was reduced by ∼20% below baseline from +0.5°C until T-LIM. Maximal voluntary contraction (MVC) of the knee extensors was decreased at T-LIM (-9 ± 10%; P < 0.05), and cortical voluntary activation (VA), assessed by TMS, was decreased at +1.5°C and T-LIM by 11 ± 8 and 22 ± 23%, respectively (P < 0.05). Corticospinal excitability (measured as the EMG response produced by TMS) was unaltered. Reductions in cortical VA were related to changes in ventilation (Ve; R(2) = 0.76; P < 0.05) and partial pressure of end-tidal CO(2) (Pet(CO(2)); R(2) = 0.63; P < 0.05) and to changes in CBFv (R(2) = 0.61; P = 0.067). Interestingly, although CBFv was not fully restored, MVC and cortical VA were restored towards baseline values during inhalation of 5% CO(2). These results indicate that descending voluntary drive becomes progressively impaired as Tc is increased, presumably due, in part, to reductions in CBFv and to hyperthermia-induced hyperventilation and subsequent hypocapnia.

Mechanisms of orthostatic intolerance following very prolonged exercise

Nine men completed a 24-h exercise trial, with physiological testing sessions before (T1, approximately 0630), during (T2, approximately 1640; T3, approximately 0045; T4, approximately 0630), and 48-h afterwards (T5, approximately 0650). Participants cycled and ran/trekked continuously between test sessions. A 24-h sedentary control trial was undertaken in crossover order. Within testing sessions, participants lay supine and then stood for 6 min, while heart rate variability (spectral analysis of ECG), middle cerebral artery perfusion velocity (MCAv), mean arterial pressure (MAP; Finometer), and end-tidal Pco(2) (Pet(CO(2))) were measured, and venous blood was sampled for cardiac troponin I. During the exercise trial: 1) two, six, and four participants were orthostatically intolerant at T2, T3, and T4, respectively; 2) changes in heart rate variability were only observed at T2; 3) supine MAP (baseline = 81 +/- 6 mmHg) was lower (P < 0.05) by 14% at T3 and 8% at T4, whereas standing MAP (75 +/- 7 mmHg) was lower by 16% at T2, 37% at T3, and 15% at T4; 4) Pet(CO(2)) was reduced (P < 0.05) at all times while supine (-3-4 Torr) and standing (-4-5 Torr) during exercise trial; 5) standing MCAv was reduced (P < 0.05) by 23% at T3 and 30% at T4 during the exercise trial; 6) changes in MCAv with standing always correlated (P < 0.01) with changes in Pet(CO(2)) (r = 0.78-0.93), but only with changes in MAP at T1, T2, and T3 (P < 0.05; r = 0.62-0.84); and 7) only two individuals showed minor elevations in cardiac troponin I. Recovery was complete within 48 h. During prolonged exercise, postural-induced hypotension and hypocapnia exacerbate cerebral hypoperfusion and facilitate syncope.

Influence of age on syncope following prolonged exercise: differential responses but similar orthostatic intolerance

Orthostatic tolerance is reduced with increasing age and following prolonged exercise. The aim of this study was to determine the effect of age on cardiovascular and cerebrovascular responses to orthostatic stress following prolonged exercise. Measurements were obtained before, and within 45 min after, 4 h of continuous running at 70–80% of maximal heart rate in nine young (Y; 27 ± 4 years; 59 ± 10 ml kg−1 min−1) and twelve older (O; 65 ± 5 years; 46 ± 8 ml kg−1 min−1) athletes. Middle cerebral artery blood flow velocity (MCAv; transcranial Doppler ultrasound), blood pressure (BP; Finometer) and stroke volume (SV) were measured continuously whilst supine and during 60 deg head‐up tilt for 15 min or to pre‐syncope. Orthostatic tolerance was reduced post‐exercise (tilt completed (min:s, mean ±s.d.): Pre, 14:39 ± 0:55; Post, 5:59 ± 4:53; P < 0.05), but did not differ with age (P > 0.05). Despite a 25% higher supine MCAv in the young, MCAv at syncope was the same in both groups (Y: 34 ± 10 cm s−1; O: 32 ± 13; P > 0.05). Although the hypotensive response to syncope did not differ with age, the components of BP did; SV was lowered more in the young (Y: –57 ± 16%; O: –34 ± 13%; P < 0.05); and total peripheral resistance was lowered in the older athletes but was unchanged in the young (Y: +8 ± 10%; O: –21 ± 12%; (at 10 s pre‐syncope) P < 0.05). Despite a lower MCAv in the older athletes, time to syncope was similar between groups; however, the integrative mechanisms responsible for syncope did differ with age. The similar MCAv at pre‐syncope indicates there is an age‐independent critical cerebral blood flow threshold at which syncope occurs.

Cerebrovascular reactivity and dynamic autoregulation in tetraplegia

Humans with spinal cord injury have impaired cardiovascular function proportional to the level and completeness of the lesion. The effect on cerebrovascular function is unclear, especially for high-level lesions. The purpose of this study was to evaluate the integrity of dynamic cerebral autoregulation (CA) and the cerebrovascular reactivity in chronic tetraplegia (Tetra). After baseline, steady-state hypercapnia (5% CO(2)) and hypocapnia (controlled hyperventilation) were used to assess cerebrovascular reactivity in 6 men with Tetra (C5-C7 lesion) and 14 men without [able-bodied (AB)]. Middle cerebral artery blood flow velocity (MCAv), cerebral oxygenation, arterial blood pressure (BP), heart rate (HR), cardiac output (Q; model flow), partial pressure of end-tidal CO(2) (Pet(CO(2))), and plasma catecholamines were measured. Dynamic CA was assessed by transfer function analysis of spontaneous fluctuations in BP and MCAv. MCAv pulsatility index (MCAv PI) was calculated as (MCAv(systolic) - MCAv(diastolic))/MCAv(mean) and standardized by dividing by mean arterial pressure (MAP). Resting BP, total peripheral resistance, and catecholamines were lower in Tetra (P < 0.05), and standardized MCAv PI was approximately 36% higher in Tetra (P = 0.003). Resting MCAv, cerebral oxygenation, HR, and Pet(CO(2)) were similar between groups (P > 0.05). Although phase and transfer function gain relationships in dynamic CA were maintained with Tetra (P > 0.05), coherence in the very low-frequency range (0.02-0.07 Hz) was approximately 21% lower in Tetra (P = 0.006). Full (hypo- and hypercapnic) cerebrovascular reactivity to CO(2) was unchanged with Tetra (P > 0.05). During hypercapnia, standardized MCAv PI reactivity was enhanced by approximately 78% in Tetra (P = 0.016). Despite impaired cardiovascular function, chronic Tetra involves subtle changes in dynamic CA and cerebrovascular reactivity to CO(2). Changes are evident in coherence at baseline and MCAv PI during baseline and hypercapnic states in chronic Tetra, which may be indicative of cerebrovascular adaptation.

The Type 2 Diabetic Heart: Its Role in Exercise Intolerance and the Challenge to Find Effective Exercise Interventions

The metabolic and microvascular benefits of regular exercise for people with diabetes are unequivocal. However, cardiovascular disease, which disproportionately affects people with diabetes, is not reduced by regular exercise, and heart disease remains the leading cause of death for people with type 2 diabetes. ‘Subclinical’ changes in the function of the diabetic left ventricle are common and reduce cardiac reserve and exercise capacity. This review describes the changes in resting and exercising left ventricular function, and the possible causes of these changes, and introduces the possibility that more vigorous exercise may be needed to improve left ventricular function and reduce rates of cardiovascular disease in people with type 2 diabetes.

Cardiorespiratory and cerebrovascular responses to head-up tilt II: influence of age, training status and acute exercise.

The purpose of this study was to examine the combined cardiorespiratory and cerebrovascular responses to head-up tilt (HUT) in young and older trained and untrained humans following moderate-duration exercise. Middle cerebral artery blood flow velocity (MCAv; transcranial Doppler ultrasound), blood pressure (BP; Finometer), and stroke volume (SV) were measured continuously whilst supine and during 60° HUT for 15 min or to pre-syncope in 41 participants [nine young trained; eleven young untrained; twelve older trained; nine older untrained] prior to and following 30 min of treadmill exercise at 70-80% maximal HR. Orthostatic tolerance was not reduced following exercise [Mean (all groups) 14:45 ± 1:19, vs. 14:47 ± 0:43 min:s (before exercise); P = 0.73], and did not differ with age or fitness. Mean MCAv was elevated [~5 ± 11%] whilst supine after exercise in the older participants but reduced [~-4 ± 12%] in the young [P = 0.03]. The postural reductions in MCAv [~-22% vs. -17%; P = 0.02], MAP [~-8% vs. -3%; P = 0.04] and SV [~-28% vs. -23%; P = 0.03] were increased after exercise (vs. pre-exercise). Orthostatic tolerance was not reduced following 30 min of exercise, and did not differ with age or fitness, despite more pronounced post-exercise reductions in MCAv, MAP and SV with postural change.

Alterations in left ventricular function and cardiac biomarkers as a consequence of repetitive endurance cycling

Abstract The aim of this study was to assess left ventricular (LV) function and cardiac biomarkers in response to repetitive endurance cycling over 22 days. Ten trained male cyclists (mean±s: age 40±5 years, VO2max 56±4 ml · kg−1 · min−1) completed the 2007 Tour de France route. Before, during, and 2 days after the Tour, all participants underwent an echocardiographic examination to determine ejection fraction, as well as systolic (S′), early diastolic (E′), and late diastolic (A′) myocardial tissue velocities, together with the E′:A′ ratio. Venous blood samples were collected and analysed for cardiac troponin I (cTnI) and B-type-natriuretic peptide. Repeated-measures analysis of variance was used to investigate the cumulative effects of prolonged exercise bouts on LV function and cardiac biomarkers. Alpha was set at 0.05. Although both the ejection fraction (71±2% vs. 59±4%; P<0.05) and the E′:A′ ratio (1.60±0.15 vs. 1.09±0.12; P<0.05) were reduced at post-stage assessments, there was limited evidence of a progressive decline in either variable over the 22 days. Although post-tour ejection fraction was not different to baseline (68±3%; P>0.05), the E′:A′ ratio remained depressed (1.37±0.26; P<0.05) following 2 days of recovery. No cTnI was detectable at baseline and B-type-natriuretic peptide was within normal ranges (24±7 pg · ml−1). Cardiac troponin I was detectable in at least one cyclist at every assessment, with 60% being positive after stage 15 (range 0.02–0.09 µg · ml−1). B-type-natriuretic peptide peaked following stage 17 (240±145 pg · ml−1). In conclusion, repetitive endurance cycling resulted in an acute reduction in LV function and the sporadic appearance of cardiac biomarkers following each day of exercise. Despite this there was no cumulative effect of repetitive exercise. Minor changes in diastolic function persisted up to 48 h of recovery.

Resting heart rate variability and exercise capacity in Type 1 diabetes

People with type 1 diabetes (T1D) have lower exercise capacity (V̇O2max) than their age‐matched nondiabetic counterparts (CON), which might be related to cardiac autonomic dysfunction. We examined whether Heart Rate Variability (HRV; indicator of cardiac autonomic modulation) was associated with exercise capacity in those with and without T1D. Twenty‐three participants with uncomplicated T1D and 17 matched CON were recruited. Heart rate (HR; ECG), blood pressure (BP; finger photo‐plethysmography), and respiratory rate (respiratory belt) were measured during baseline, paced‐breathing and clinical autonomic reflex tests (CARTs); deep breathing, lying‐to‐stand, and Valsalva maneuver. Baseline and paced‐breathing ECG were analyzed for HRV (frequency‐domain). Exercise capacity was determined during an incremental cycle ergometer test while V̇O2, 12‐lead ECG, and BP were measured. In uncomplicated T1D, resting HR was elevated and resting HRV metrics were reduced, indicative of altered cardiac parasympathetic modulation; this was generally undetected by the CARTs. However, BP and plasma catecholamines were not different between groups. In T1D, V̇O2max tended to be lower (P = 0.07) and HR reserve was lower (P < 0.01). Resting Total Power (TP) had stronger positive associations with V̇O2max (R2 ≥ 0.3) than all other traditional indicators such as age, resting HR, and self‐reported exercise (R2 = 0.042–0.3) in both T1D and CON. Alterations in cardiac autonomic modulation are an early manifestation of uncomplicated T1D. Total Power was associated with reduced exercise capacity regardless of group, and these associations were generally stronger than traditional indicators.

Cardiorespiratory and cerebrovascular responses to head-up tilt I: influence of age and training status.

The purpose of this study was to examine the combined cardiorespiratory and cerebrovascular responses to head-up tilt (HUT) in young (27 ± 4 years) and older (65 ± 5 years) trained and untrained humans. Middle cerebral artery blood velocity (MCAv; transcranial Doppler ultrasound), blood pressure (BP; Finometer) and cardiac output (Q) were measured continuously whilst supine and during 60° HUT for 15 min or to pre-syncope in 41 participants [nine young trained; eleven young untrained; twelve older trained; nine older untrained]. Thirty seven of forty one participants completed 15 min HUT, and orthostatic tolerance did not differ with age or fitness (P = 0.66). Supine MCAv was 30% lower in the older participants but the HUT-induced drop in MCAv was not altered by age [-18% (young) vs. -17% (older)], or fitness. Mean arterial BP was maintained during HUT and not altered by age or fitness. In the untrained, peripheral resistance was elevated [11% vs. -2% (trained); P = 0.01], and Q was reduced [-10% vs. -5% (trained); P = 0.04] with HUT. Despite these age- and fitness-associated differences in some cardiovascular responses to HUT, orthostatic tolerance was similar across groups. Thus, at least in this healthy population, neither age nor fitness impacts on the ability to adapt to postural change.