Key points
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The influence of normative ageing on cerebral perfusion, oxygenation and metabolism during exercise is not well known.
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This study assessed cerebral perfusion and concentration ...differences for oxygen, glucose and lactate across the brain, in young and elderly individuals at rest and during incremental exercise to exhaustion.
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We observed that during submaximal exercise (at matched relative intensities) and during maximal exercise, cerebral perfusion was reduced in older individuals compared with young individuals, while the cerebral metabolic rate for oxygen and uptake of glucose and lactate were similar.
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The results indicate that the age‐related reduction in cerebral perfusion during exercise does not affect brain uptake of lactate and glucose.
We evaluated cerebral perfusion, oxygenation and metabolism in 11 young (22 ± 1 years) and nine older (66 ± 2 years) individuals at rest and during cycling exercise at low (25%Wmax), moderate (50%Wmax), high (75%Wmax) and exhaustive (100%Wmax) workloads. Mean middle cerebral artery blood velocity (MCA Vmean), mean arterial pressure (MAP), cardiac output (CO) and partial pressure of arterial carbon dioxide () were measured. Blood samples were obtained from the right internal jugular vein and brachial artery to determine concentration differences for oxygen (O2), glucose and lactate across the brain. The molar ratio between cerebral uptake of O2 versus carbohydrate (O2–carbohydrate index; O2/glucose +1/2 lactate; OCI), the cerebral metabolic rate of O2 (CMRO2) and changes in mitochondrial O2 tension () were calculated. 100%Wmax was ∼33% lower in the older group. Exercise increased MAP and CO in both groups (P < 0.05 vs. rest), but at each intensity MAP was higher and CO lower in the older group (P < 0.05). MCA Vmean, and cerebral vascular conductance index (MCA Vmean/MAP) were lower in the older group at each exercise intensity (P < 0.05). In contrast, young and older individuals exhibited similar increases in CMRO2 (by ∼30 μmol (100 g−1) min−1), and decreases in OCI (by ∼1.5) and (by ∼10 mmHg) during exercise at ≥75%Wmax. Thus, despite the older group having reduced cerebral perfusion and maximal exercise capacity, cerebral oxygenation and uptake of lactate and glucose are similar during exercise in young and older individuals.
Pulse (PPV) and systolic pressure variation (SPV) quantify variations in arterial pressure related to heart-lung interactions and have been introduced as biomarkers of preload dependency to guide ...fluid treatment in mechanically ventilated patients. However, respiratory intra-thoracic pressure changes during spontaneous breathing are considered too small to affect preload and stroke volume sufficiently for the detection by PPV and/or SPV. This study addressed the effects of paced breathing and/or an external respiratory resistance on PPV and SPV in detecting preload dependency in spontaneously breathing subjects.
In 10 healthy subjects, hemodynamic and respiratory parameters were evaluated during progressive central hypovolemia (head-up tilt). Breathing conditions were varied by manipulating breathing frequency and respiratory resistance. Subjects responding with a reduction in stroke volume index ≥15% were classified as having developed preload dependency. The ability for PPV and SPV to predict preload dependency was expressed by the area under the ROC curve (AUC).
A breathing frequency at 6/min increased the PPV (16±5% vs. 10±3%, p<0.001) and SPV (9±3% vs. 5±2%, p<0.001) which was further enhanced by an expiratory resistance (PPV: 19±3%, p = 0.025 and SPV: 10±2%, p = 0.047). These respiratory modifications, compared to free breathing, enhanced the predictive value of PPV with higher accuracy (AUC: 0.92 vs. 0.46).
Under conditions of progressive central hypovolemia, the application of an external respiratory resistance at a breathing frequency of 6/min enhanced PPV and SPV and is worth further study for detection of preload dependency from arterial pressure variations in non-ventilated subjects.
Type 2 diabetes is associated with an increased risk of endothelial dysfunction and microvascular complications with impaired autoregulation of tissue perfusion. Both microvascular disease and ...cardiovascular autonomic neuropathy may affect cerebral autoregulation. In the present study, we tested the hypothesis that, in the absence of cardiovascular autonomic neuropathy, cerebral autoregulation is impaired in subjects with DM+ (Type 2 diabetes with microvascular complications) but intact in subjects with DM- (Type 2 diabetes without microvascular complications). Dynamic cerebral autoregulation and the steady-state cerebrovascular response to postural change were studied in subjects with DM+ and DM-, in the absence of cardiovascular autonomic neuropathy, and in CTRL (healthy control) subjects. The relationship between spontaneous changes in MCA V(mean) (middle cerebral artery mean blood velocity) and MAP (mean arterial pressure) was evaluated using frequency domain analysis. In the low-frequency region (0.07-0.15 Hz), the phase lead of the MAP-to-MCA V(mean) transfer function was 52+/-10 degrees in CTRL subjects, reduced in subjects with DM- (40+/-6 degrees ; P<0.01 compared with CTRL subjects) and impaired in subjects with DM+ (30+/-5 degrees ; P<0.01 compared with subjects with DM-), indicating less dampening of blood pressure oscillations by affected dynamic cerebral autoregulation. The steady-state response of MCA V(mean) to postural change was comparable for all groups (-12+/-6% in CTRL subjects, -15+/-6% in subjects with DM- and -15+/-7% in subjects with DM+). HbA(1c) (glycated haemoglobin) and the duration of diabetes, but not blood pressure, were determinants of transfer function phase. In conclusion, dysfunction of dynamic cerebral autoregulation in subjects with Type 2 diabetes appears to be an early manifestation of microvascular disease prior to the clinical expression of diabetic nephropathy, retinopathy or cardiovascular autonomic neuropathy.
Endothelial vascular function and capacity to increase cardiac output during exercise are impaired in patients with type 2 diabetes (T2DM). We tested the hypothesis that the increase in cerebral ...blood flow (CBF) during exercise is also blunted and, therefore, that cerebral oxygenation becomes affected and perceived exertion increased in T2DM patients. We quantified cerebrovascular besides systemic hemodynamic responses to incremental ergometer cycling exercise in eight male T2DM and seven control subjects. CBF was assessed from the Fick equation and by transcranial Doppler‐determined middle cerebral artery blood flow velocity. Cerebral oxygenation and metabolism were evaluated from the arterial‐to‐venous differences for oxygen, glucose, and lactate. Blood pressure was comparable during exercise between the two groups. However, the partial pressure of arterial carbon dioxide was lower at higher workloads in T2DM patients and their work capacity and increase in cardiac output were only ~80% of that established in the control subjects. CBF and cerebral oxygenation were reduced during exercise in T2DM patients (P < 0.05), and they expressed a higher rating of perceived exertion (P < 0.05). In contrast, CBF increased ~20% during exercise in the control group while the brain uptake of lactate and glucose was similar in the two groups. In conclusion, these results suggest that impaired CBF and oxygenation responses to exercise in T2DM patients may relate to limited ability to increase cardiac output and to reduced vasodilatory capacity and could contribute to their high perceived exertion.
We tested the hypothesis that in type 2 diabetes (T2DM) patients the increase in cerebral blood flow (CBF) during exercise is blunted and, therefore, that cerebral oxygenation becomes affected and perceived exertion increased. Male T2DM patients with T2DM exhibited reduced cerebral perfusion and oxygenation during incremental exercise associated with attenuated increase in cerebral and systemic vascular conductance. An impaired CBF and oxygenation response to exercise may relate to a limited ability to increase cardiac output contributing to increased perceived exertion in T2DM patients
The first step to exercise is preceded by the required assumption of the upright body position, which itself involves physical activity. The gravitational displacement of blood from the chest to the ...lower parts of the body elicits a fall in central blood volume (CBV), which corresponds to the fraction of thoracic blood volume directly available to the left ventricle. The reduction in CBV and stroke volume (SV) in response to postural stress, post-exercise, or to blood loss results in reduced left ventricular filling, which may manifest as orthostatic intolerance. When termination of exercise removes the leg muscle pump function, CBV is no longer maintained. The resulting imbalance between a reduced cardiac output (CO) and a still enhanced peripheral vascular conductance may provoke post-exercise hypotension (PEH). Instruments that quantify CBV are not readily available and to express which magnitude of the CBV in a healthy subject should remains difficult. In the physiological laboratory, the CBV can be modified by making use of postural stressors, such as lower body "negative" or sub-atmospheric pressure (LBNP) or passive head-up tilt (HUT), while quantifying relevant biomedical parameters of blood flow and oxygenation. Several approaches, such as wearable sensors and advanced machine-learning techniques, have been followed in an attempt to improve methodologies for better prediction of outcomes and to guide treatment in civil patients and on the battlefield. In the recent decade, efforts have been made to develop algorithms and apply artificial intelligence (AI) in the field of hemodynamic monitoring. Advances in quantifying and monitoring CBV during environmental stress from exercise to hemorrhage and understanding the analogy between postural stress and central hypovolemia during anesthesia offer great relevance for healthy subjects and clinical populations.
Brain function requires oxygen and maintenance of brain capillary oxygenation is important. We evaluated how faithfully frontal lobe near-infrared spectroscopy (NIRS) follows haemoglobin saturation ...(SCap) and how calculated mitochondrial oxygen tension (PMitoO2) influences motor performance. Twelve healthy subjects (20 to 29 years), supine and seated, inhaled O2 air-mixtures (10% to 100%) with and without added 5% carbon dioxide and during hyperventilation. Two measures of frontal lobe oxygenation by NIRS (NIRO-200 and INVOS) were compared with capillary oxygen saturation (SCap) as calculated from the O2 content of brachial arterial and right internal jugular venous blood. At control SCap (78% ± 4%; mean ± s.d.) was halfway between the arterial (98% ± 1%) and jugular venous oxygenation (SVO2; 61% ± 6%). Both NIRS devices monitored SCap (P < 0.001) within ~5% as SvO2 increased from 39% ± 5% to 79% ± 7% with an increase in the transcranial ultrasound Doppler determined middle cerebral artery flow velocity from 29 ± 8 to 65 ± 15 cm/sec. When SCap fell below ~70% with reduced flow and inspired oxygen tension, PMitoO2 decreased (P < 0.001) and brain lactate release increased concomitantly (P < 0.001). Handgrip strength correlated with the measured (NIRS) and calculated capillary oxygenation values as well as with PMitoO2 (r > 0.74; P < 0.05). These results show that NIRS is an adequate cerebral capillaryoxygenation-level-dependent (COLD) measure during manipulation of cerebral blood flow or inspired oxygen tension, or both, and suggest that motor performance correlates with the frontal lobe COLD signal.
Lower-body negative pressure (LBNP) has been proposed as a MRI-compatible surrogate for orthostatic stress. Although the effects of LBNP on cerebral hemodynamic behavior have been considered to ...reflect those of orthostatic stress, a direct comparison with actual orthostasis is lacking. We assessed the effects of LBNP (-50 mmHg) vs. head-up tilt (HUT; at 70°) in 10 healthy subjects (5 female) on transcranial Doppler-determined cerebral blood flow velocity (CBF
) in the middle cerebral artery and cerebral perfusion pressure (CPP) as estimated from the blood pressure signal (finger plethysmography). CPP was maintained during LBNP but decreased after 2 min in response to HUT, leading to an ~15% difference in CPP between LBNP and HUT (
≤ 0.020). Mean CBF
initially decreased similarly in response to LBNP and for HUT, but, from minute 3 on, the decline became ~50% smaller (
≤ 0.029) during LBNP. The reduction in end-tidal Pco
partial pressure (Pet
) was comparable but with an earlier return toward baseline values in response to LBNP but not during HUT (
= 0.008). We consider the larger decrease in CBF
during HUT vs. LBNP attributable to the pronounced reduction in Pet
and to gravitational influences on CPP, and this should be taken into account when applying LBNP as an MRI-compatible orthostatic stress modality.
Lower-body negative pressure (LBNP) has the potential to serve as a MRI-compatible surrogate of orthostatic stress but a comparison with actual orthostasis was lacking. This study showed that the pronounced reduction in end-tidal Pco
together with gravitational effects on the brain circulation lead to a larger decline in cerebral blood flow velocity in response to head-up tilt than during lower-body negative pressure. This should be taken into account when employing lower-body negative pressure as MRI-compatible alternative to orthostatic stress.
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