Cerebral hemodynamic response to maximal exercise

The response of central and cerebral hemodynamics to a stepwise increase in dynamic exercise until failure was studied in healthy young men. Each subject was examined using Doppler ultrasound assessment of blood flow in the middle cerebral artery (MCA), Doppler echocardiography, and spiroergometry. Hemodynamic parameters were recorded before the study and during the last several seconds of each step of the dynamic exercise. The central hemodynamic and energy exchange parameters exhibited typical changes with increasing exercise intensity. The peak systolic blood flow velocity in the MCA increased only in response to exercise of a moderate intensity (1 W/kg body weight, 45% of the maximal oxygen uptake); the further increase in exercise intensity did not affect the blood flow velocity. The cerebral vascular resistance index at the last step of the exercise was 24% higher than at rest. The increase in the MCA resistance index during the exercise was moderately correlated with the increase in the pulse pressure and systolic blood pressure, whereas the increase in blood pressure was not related to the increase in the peak systolic blood flow velocity in the MCA in response to an exercise intensity at which the oxygen uptake was higher than 45% of its maximal value. The differences between the responses of central and cerebral hemodynamics to the stepwise increase in exercise intensity reflect the phenomenon of cerebral hemodynamic autoregulation.     

Functional characteristics of hemodynamics in adolescents under the conditions of different motor activities

The formation of functional systems in correspondence with the conditions of natural activity is the most important issue of developmental physiology. In this study, data on the assessment of the state of central and cerebral hemodynamics, as well as indices of spectral analysis of the heart rate’s variability (HRV) in adolescents depending on the level of motor activity has been collected and systematized. The possibility of integration of methods of rheoencephallography and cardiorythmography for the assessment of the characteristics of the ontogenetic formation of the cardiovascular system has been studied. Analysis of the formation of indices of hemodynamics during an academic year and the training cycle in swimmers and healthy adolescents who do not enroll in sports classes has been made. Changes in, and correlations between, the parameters of central hemodynamics and cerebral circulation, as well as parameters of HRV, have been detected. Analysis of the changes in the statistical indices of the cardiac rhythm in adolescents during an academic year on the basis of the qualitative and quantitative characteristics of the state of regulatory systems, as well as the determination of the direction of the response to the combination of academic loads and the factor of physical training, permitted a detailed study of changes that take place in some hemodynamic parameters in athletes and students, which is of particular importance for the diagnosis of their functional state.     

Characteristics of ventilatory control during exercise in coronary heart disease patients

The relationship between the carbon dioxide ventilatory equivalent and hemodynamic parameters during exercise was studied in healthy subjects and coronary heart disease (CHD) patients. Gas exchange, ventilatory control, and central hemodynamics during graded exercise were analyzed in 85 subjects, including 32 healthy subjects and 53 CHD patients. Twenty-seven CHD patients had coronary insufficiency but not heart failure and had a left ventricle ejection fraction of ≥50%; 26 patients had chronic heart failure and an ejection fraction of <40%. A high carbon dioxide ventilatory equivalent and its disturbed response (a decrease below 20%) with an increase in physical load, which reflects an imbalance of ventilatory control with decreased parameters of maximum oxygen consumption and hemodynamics, allows the ventilatory equivalent to be used as a marker for stratifying CHD patients with chronic heart failure.     

Cerebral hemodynamics response to low intensity physical exercise

The aim of this research was to study the cerebral hemodynamics reaction to step increase of physical exercises intensity during bicycle ergometer test in young healthy male subjects. Hemodynamics parameters were registered with the transcranial Doppler ultrasonography of middle cerebral artery (MCA) prior to the study and during the last seconds of every step of physical exercise. Cerebral hemodynamics response to physical exercise was characterized by a significant increase of peak systolic blood velocity in the MCA up to 0.25 W/kg of the body weight (90 rpm with regard to 0 W/kg) without further increase of blood velocity in the same physical exercise becoming more intensive up to 0.5 W/kg of the body weight. The stabilization mechanism of blood velocity in cerebral arteries in case of physical exercise increase and, hence, the autoregulation mechanism of cerebral circulation means that the increase of regional cerebral vascular resistance depends on the value of arterial pressure. The autoregulation mechanism of cerebral circulation starts working with he exercise intensity of 0.25 W/kg and the value of systolic blood pressure about 140-145 mm Hg.     

New approaches to an understanding of hemodynamic norms]

Tetrapolar rheography was used to investigate central hemodynamics parameters in a group of 80 healthy subjects aged 25-68. Hyperkinetic, eukinetic and hypokinetic types of circulation were determined by interval distribution according to cardiac index. The proportion of the examinees by their hemodynamic type was: 16.3:63.7:20.0%. In hyperkinetic type the optimal level of average blood pressure was provided by a relatively high cardiac output (CO) and low total and specific peripheral resistance (TPR, SPR). The hypokinetic type of hemodynamics was characterized by a low level of CO and a high value of TPR and SPR. Subjects with eukinetic hemodynamic type were in an intermediate position. It is suggested to take into consideration the hemodynamic type in hypertensive subjects for drug selection and treatment control.     

Hemodynamic and renal effects of low-dose brain natriuretic peptide infusion in humans: a randomized,placebo-controlled crossover study

Brain natriuretic peptide (BNP) is a cardiac hormone with natriuretic activity. The aim of this study was to investigate the cardiovascular effects of pathophysiological levels of BNP on central hemodynamics, cardiac function, renal hemodynamics and function, and microvascular hemodynamics in healthy subjects. In this double-blind, placebo-controlled crossover study, we intravenously infused BNP (4 pmol. kg-1. min-1) or placebo for 1 h on two separate days in 12 healthy subjects (mean age, 60 +/- 5 yr). Nailfold and conjunctival capillary density, finger-skin (thermoregulatory) microvascular blood flow, and cardiac output were studied before and after infusion using intravital videomicroscopy, laser-Doppler fluxmetry, and echocardiography, respectively. Furthermore, during infusion, we measured the effective renal plasma flow and glomerular filtration rate using p-aminohippurate and inulin clearances. Blood pressure and heart rate were monitored for all measurements. Compared with placebo, BNP significantly decreased stroke volume with a tendency to decrease cardiac output. With subjects in the sitting position, mean arterial pressure decreased and heart rate increased after BNP infusion, whereas with subjects in the supine position, these variables remained unchanged. BNP increased natriuresis, diuresis, glomerular filtration rate, filtration fraction, and filtered load of Na+ compared with placebo, whereas effective renal plasma flow did not change. BNP did not affect the microvascular capillary density of conjunctiva and skin, microvascular blood flow, total skin oxygen capacity, and postocclusive recruitment. These results suggest that BNP has predominantly central and renal hemodynamic effects; however, it does not influence peripheral microcirculation in skin and conjunctiva.     

Relationships of Oxygen Consumption, Hemodynamics, and Heart Rate Variability with the Functional Class of Coronary Artery Disease Patients

The functional classes (FCs) established according to the criteria of the New York Heart Association were tested for association with oxygen consumption, the state of central hemodynamics, and heart rate (HR) variability in coronary artery disease (CAD) patients. Oxygen consumption, central hemodynamics, and HR variability at rest and during exercise were assayed in 146 CAD patients and 30 healthy individuals (the control group). It was established that the peak oxygen consumption (VO_2max), anaerobic threshold, pulmonary ventilation, systolic and minute blood volume at the threshold load (TL), and HR variability in a supine position significantly decrease and the total vascular peripheral resistance at rest and during exercise increases with increasing FC in CAD patients. The closest correlation of FC was revealed with physical working capacity, anaerobic threshold, age, and peak oxygen consumption. Moderate correlations were established with the chronotropic function of the heart at the threshold load, HR variability, the high- and low-frequency components of the cardiac rhythm at TL, pulmonary ventilation, stroke volume at rest and at TL, and the carbon dioxide ventilation equivalent at TL. In healthy individuals, the peak oxygen consumption closely correlated with the HR variability, the very low frequency component at TL, and physical capacity. With an increase in FC in CAD patients, peak oxygen consumption became more tightly associated with the chronotropic function and the hemodynamic components at TL than with the HR variability in a supine position or at TL.     

Inhibition of nitric oxide synthase does not alter dynamic cerebral autoregulation in humans

The aim of this study was to determine whether inhibition of nitric oxide synthase (NOS) alters dynamic cerebral autoregulation in humans. Beat-to-beat blood pressure (BP) and cerebral blood flow (CBF) velocity (transcranial Doppler) were measured in eight healthy subjects in the supine position and during 60 degrees head-up tilt (HUT). NOS was inhibited by intravenous NG-monomethyl-L-arginine (L-NMMA) infusion. Dynamic cerebral autoregulation was quantified by transfer function analysis of beat-to-beat changes in BP and CBF velocity. Pressor effects of L-NMMA on cerebral hemodynamics were compared with those of phenylephrine infusion. In the supine position, L-NMMA increased mean BP from 83+/-3 to 94+/-3 mmHg (P < 0.01). However, CBF velocity remained unchanged. Consequently, cerebrovascular resistance index (CVRI) increased by 15% (P < 0.05). BP and CBF velocity variability and transfer function gain at the low frequencies of 0.07-0.20 Hz did not change with L-NMMA infusion. Similar changes in mean BP, CBF velocity, and CVRI were observed after phenylephrine infusion, suggesting that increase in CVRI after L-NMMA was mediated myogenically by increase in arterial pressure rather than a direct effect of cerebrovascular NOS inhibition. During baseline tilt without L-NMMA, steady-state BP increased and CBF velocity decreased. BP and CBF velocity variability at low frequencies increased in parallel by 277% and 217%, respectively (P < 0.05). However, transfer function gain remained unchanged. During tilt with L-NMMA, changes in steady-state hemodynamics and BP and CBF velocity variability as well as transfer gain and phase were similar to those without L-NMMA. These data suggest that inhibition of tonic production of NO does not appear to alter dynamic cerebral autoregulation in humans.     

Relationships between Cerebral Blood Flow Dynamics and Bioelectric Activity of the Human Brain in Experimental Acute Hypoxia

The relationships between the parameters of oxygen content in the body (hemoglobin saturation with oxygen and trancutaneous oxygen tension), central hemodynamics (cardiac output), and cerebral hemodynamics (cerebral blood flow rate) were studied during a hypoxic test (inhalation of an oxygen–nitrogen mixture containing 8% oxygen for 15 min). Special attention was paid to the relationships between the dynamics of cerebral blood flow and cerebral bioelectric activity measured by EEG parameters. It was demonstrated that the trancutaneous oxygen tension decreased to a greater extent than the hemoglobin saturation with oxygen and the cerebral blood flow increased to a greater extent than the cardiac output. The increase in cerebral blood flow and the increase in the indices and power of and EEG waves in the course of hypoxia were strongly positively correlated with each other in most subjects. However, if these parameters were considered in the series of subjects, the degree of the increase in the indices and power of and waves in different subjects was negatively correlated with the increase in the cerebral blood flow. The results are explained in terms of redistribution of blood flow in the body to provide a better oxygen supply to the brain and optimization of the ratios between the cerebral oxygen consumption and the functional load on the system of oxygen supply.     

The dynamic of breathing biomechanics and intrathoracic hemodynamics parameters during microgravity modeling

In ground-based model of the hemodynamics effects of weightlessness, the intersystem relation of breathing and circulation was investigated during inspiration and expiration separately in anesthetized catz. It's shown that the dynamics of central venous pressure, esophageal pressure and filling pressure of the heart during inspiration in supine and head-down tilt position has obvious similarity to those which hypothetically can be present in microgravity. The results suggest that intrathoracic hemodynamics during inspiration in supine and head-down position may be an adequate ground model for investigation of weightlessness influences on intrathoracic circulation.     

The effect of intravenous PACAP38 on cerebral hemodynamics in healthy volunteers

PACAP38 is an endogenous peptide located in trigeminal perivascular nerve fibers in the brain. It reduces neuronal loss and infarct size in animal stroke models and has been proposed a candidate substance for human clinical studies of stroke. The effect on systemic hemodynamics and regional cerebral blood flow (rCBF) is not well understood. We here present the first study of the effect of PACAP38 on cerebral hemodynamics in humans.

PACAP (10 pmol kg^− 1 min^− 1) or placebo (0.9% saline) was infused for 20 min into 12 healthy young volunteers in a cross over, double blind study. rCBF was measured with SPECT and ¹³³Xe inhalation and mean blood flow velocity in the middle cerebral artery was measured with transcranial Doppler ultrasonography. End tidal partial pressure of CO₂ (P_etCO₂) and vital parameters were recorded throughout the 2 hour study period.

PACAP38 decreased rCBF in all regions of interest (ROIs) by  3–10%, though not uniformly significant. P_etCO₂ decreased significantly during PACAP38 infusion compared to placebo (P = 0.032), peak decrease was 8.9 ± 3.8%. After correction for P_etCO₂, rCBF remained unchanged in most ROIs. Heart rate increased 61.9 ± 22.4% (P < 0.0001 vs. placebo).

These findings suggest that PACAP38 has no major direct effect on rCBF in healthy volunteers. The marked increase in heart rate and the reduction in rCBF caused by decreased P_etCO₂ are important dose-limiting factors to consider in future clinical studies.     

Syncope, cerebral perfusion, and oxygenation.

During standing, both the position of the cerebral circulation and the reductions in mean arterial pressure (MAP) and cardiac output challenge cerebral autoregulatory (CA) mechanisms. Syncope is most often associated with the upright position and can be provoked by any condition that jeopardizes cerebral blood flow (CBF) and regional cerebral tissue oxygenation (cO(2)Hb). Reflex (vasovagal) responses, cardiac arrhythmias, and autonomic failure are common causes. An important defense against a critical reduction in the central blood volume is that of muscle activity ("the muscle pump"), and if it is not applied even normal humans faint. Continuous tracking of CBF by transcranial Doppler-determined cerebral blood velocity (V(mean)) and near-infrared spectroscopy-determined cO(2)Hb contribute to understanding the cerebrovascular adjustments to postural stress; e.g., MAP does not necessarily reflect the cerebrovascular phenomena associated with (pre)syncope. CA may be interpreted as a frequency-dependent phenomenon with attenuated transfer of oscillations in MAP to V(mean) at low frequencies. The clinical implication is that CA does not respond to rapid changes in MAP; e.g., there is a transient fall in V(mean) on standing up and therefore a feeling of lightheadedness that even healthy humans sometimes experience. In subjects with recurrent vasovagal syncope, dynamic CA seems not different from that of healthy controls even during the last minutes before the syncope. Redistribution of cardiac output may affect cerebral perfusion by increased cerebral vascular resistance, supporting the view that cerebral perfusion depends on arterial inflow pressure provided that there is a sufficient cardiac output.     

Dynamic cardiorespiratory interaction during head-up tilt-mediated presyncope

In 28 healthy adults, we compared the dynamic interaction between respiration and cerebral autoregulation in 2 groups of subjects: those who did and did not develop presyncopal symptoms during 70 degrees passive head-up tilt (HUT), i.e., nonpresyncopal (23 subjects) and presyncopal (5 subjects). Airflow, CO2, cerebral blood flow velocity (CBF), ECG, and blood pressure (BP) were recorded. To determine whether influences of mean BP (MBP) and systolic SP (SBP) on CBF were altered in presyncopal subjects, coherencies and transfer functions between these variables and mean and peak CBF (CBFm and CBFp) were estimated. To determine the influence of end-tidal CO2 (ETco2) on CBF, the relative CO2 reactivity (%change in CBFm per mmHg change in ETco2) was calculated. We found that in presyncopal subjects before symptoms during HUT, coherence between SBP and CBFp was higher (P=0.02) and gains of transfer functions between BP (MBP and SBP) and CBFm were larger (MBP, P=0.01; SBP, P=0.01) in the respiratory frequency region. In the last 3 min before presyncope, presyncopals had a reduced relative CO2 reactivity (P=0.005), likely a consequence of the larger decrease in ETco2. We hypothesize that the CO2-mediated increase in resistance attenuates autoregulation such that the relationship between systemic and cerebral hemodynamics is enhanced. Our results suggest that an altered cardiorespiratory interaction involving cerebral hemodynamics may contribute in the cascade of events during tilt that culminate in unexplained syncope.     

Slow Rhythmic Oscillations within the Human Cranium: Phenomenology, Origin, and Informational Significance

Slow rhythmic oscillations in the human cranial cavity were studied using two noninvasive methods: the bioimpedance method (volume ratios between liquid media in the cranial cavity) and transcranial ultrasound Doppler echography (variation in the blood flow in the middle cerebral artery). The combination of these methods made it possible to estimate the intracranial hemodynamics. Simultaneous recording of these parameters and their spectral analysis were carried out in healthy subjects and patients with intracranial hypertension syndrome and disturbed cerebrospinal fluid (CSF) flow. The parameters were recorded at rest and immediately after manual (osteopathic) correction. The recording and analysis were performed using a Macintosh-IIsi PC and the Chart-3.52, Cricket Graph-3.32, and Canvas-3.5 software. It was found that slow oscillations of the bioimpedance (BIM) in the frequency range 0.08–0.2 Hz were of intracranial origin and were related to the mechanisms of regulation of the blood supply to and oxygen consumption by cerebral tissue, as well as with the dynamics of the CSF circulation.     

Prediction of human orthostatic tolerance by changes in arterial and venous hemodynamics in the microgravity environment

In this article, we intentionally present exclusively the results of our recent studies of arterial and venous hemodynamics as predictors of human orthostatic tolerance during space flight and after the return to Earth. The possibility of in-flight orthostatic tolerance prediction by arterial hemodynamic responses to the lower body negative pressure (LBNP) and venous hemodynamic changes in response to occlusion of the lower extremities is demonstrated. For the first time, three levels of cerebral blood flow deficits during the determination of orthostatic tolerance in the course of the LBNP test performed in microgravity. We offer quantitative arguments for the dependence of the cerebral blood flow deficit on the degree of tolerance of the LBNP test. Patterns of arterial hemodynamics during LBNP were successfully used to diagnose the actual orthostatic tolerance and to follow its trend during flight, which testifies to the possibility of predicting orthostatic tolerance changes in an individual cosmonaut during space flight. Occlusion plethysmography of the legs revealed three levels of response of the most informative venous parameters (capacity, distensibility, and rate of filling) of the lower extremities correlated to the severity of decrease in orthostatic tolerance.     

Effects of leg venous hemodynamics on cardiovascular responses to lower body negative pressure and aging

In aged people, decreases in stroke volume and cardiac output during orthostatic challenge are less. It is suggested that the stiffness of blood vessels is greater in the elderly, blunting leg venous pooling and drop in central blood volume in an upright position. Leg venous hemodynamics plays an important role in human cardiovascular homeostasis against gravitational stress. This study aimed to clarify how aging influences the leg venous hemodynamics and its contribution to cardiovascular homeostasis during lower body negative pressure (LBNP) in humans.     

Central hemodynamics of dogs in the early postresuscitation period and the outcome of resuscitation

Variations in central hemodynamics of dogs were compared with the outcome of resuscitation of 18 dogs subjected to 12-minute reversible circulatory arrest because of ventricular fibrillation. Nine survived dogs with completely recovered neurological status during the first 10 minutes after resuscitation had moderate hypertension, the mean arterial pressure (MAP) being 175.0 + 8.9 mm Hg. In the dogs who died within 24-48 hours after resuscitation, the MAP did not rise during this period as compared to the initial level; 2 dogs developed excessive hypertension (MAP about 200 mm Hg). There were also found certain differences in other parameters of central hemodynamics. Moderate hypertension in the first 10 minutes of the postresuscitation period leads to rapid restoration of the adequate level of peripheral blood flow in organs and tissues, thus favouring survival of animals subjected to a long circulatory arrest.     

Cyclic Alternating Pattern Is Associated with Cerebral Hemodynamic Variation: A Near-Infrared Spectroscopy Study of Sleep in Healthy Humans

The cyclic alternating pattern (CAP), that is, cyclic variation of brain activity within non-REM sleep stages, is related to sleep instability and preservation, as well as consolidation of learning. Unlike the well-known electrical activity of CAP, its cerebral hemodynamic counterpart has not been assessed in healthy subjects so far. We recorded scalp and cortical hemodynamics with near-infrared spectroscopy on the forehead and systemic hemodynamics (heart rate and amplitude of the photoplethysmograph) with a finger pulse oximeter during 23 nights in 11 subjects. Electrical CAP activity was recorded with a polysomnogram. CAP was related to changes in scalp, cortical, and systemic hemodynamic signals that resembled the ones seen in arousal. Due to their repetitive nature, CAP sequences manifested as low- and very-low-frequency oscillations in the hemodynamic signals. The subtype A3+B showed the strongest hemodynamic changes. A transient hypoxia occurred during CAP cycles, suggesting that an increased CAP rate, especially with the subtype A3+B, which may result from diseases or fragmented sleep, might have an adverse effect on the cerebral vasculature.     

The effect of dim light at night on cerebral hemodynamic oscillations during sleep: A near-infrared spectroscopy study

Recent studies have reported that dim light at night (dLAN) is associated with risks of cardiovascular complications, such as hypertension and carotid atherosclerosis; however, little is known about the underlying mechanism. Here, we evaluated the effect of dLAN on the cerebrovascular system by analyzing cerebral hemodynamic oscillations using near-infrared spectroscopy (NIRS). Fourteen healthy male subjects underwent polysomnography coupled with cerebral NIRS. The data collected during sleep with dim light (10 lux) were compared with those collected during sleep under the control dark conditions for the sleep structure, cerebral hemodynamic oscillations, heart rate variability (HRV), and their electroencephalographic (EEG) power spectrum. Power spectral analysis was applied to oxy-hemoglobin concentrations calculated from the NIRS signal. Spectral densities over endothelial very-low-frequency oscillations (VLFOs) (0.003–0.02 Hz), neurogenic VLFOs (0.02–0.04 Hz), myogenic low-frequency oscillations (LFOs) (0.04–0.15 Hz), and total LFOs (0.003–0.15 Hz) were obtained for each sleep stage. The polysomnographic data revealed an increase in the N2 stage under the dLAN conditions. The spectral analysis of cerebral hemodynamics showed that the total LFOs increased significantly during slow-wave sleep (SWS) and decreased during rapid eye movement (REM) sleep. Specifically, endothelial (median of normalized value, 0.46 vs. 0.72, p = 0.019) and neurogenic (median, 0.58 vs. 0.84, p = 0.019) VLFOs were enhanced during SWS, whereas endothelial VLFOs (median, 1.93 vs. 1.47, p = 0.030) were attenuated during REM sleep. HRV analysis exhibited altered spectral densities during SWS induced by dLAN, including an increase in very-low-frequency and decreases in low-frequency and high-frequency ranges. In the EEG power spectral analysis, no significant difference was detected between the control and dLAN conditions. In conclusion, dLAN can disturb cerebral hemodynamics via the endothelial and autonomic systems without cortical involvement, predominantly during SWS, which might represent an underlying mechanism of the increased cerebrovascular risk associated with light exposure during sleep.