Increase In Total Peripheral Resistance Research Articles

Breathing 5% carbon dioxide for 1 minute increases cerebral blood flow during lower body negative pressure

Objective: Lower body negative pressure (LBNP) is an established surrogate of hypergravity to investigate responses to central hypovolemia, including the reduction in cerebral blood flow. Increased inspired carbon dioxide (CO2) causes cerebrovascular dilation and increases cerebral blood flow. We aimed to determine whether breathing 5% CO2 for 1 minute increased cerebral blood flow during LBNP. We hypothesized 5% inspired CO2 would increase cerebral blood flow during LBNP. Methods: We collected data from 15 (9 M/6 F, 31±8 yr, 25.6±3.2 kg/m2) healthy individuals. Subjects breathed room air or a mix of 5% CO2, 21% oxygen, balance nitrogen gas for 1 minute prior to initiation of 2 minutes of -60 mmHg LBNP and throughout the duration of LBNP. We allowed a 2-minute wash-out between trials. We measured middle cerebral artery velocity (MCAv) with transcranial Doppler ultrasound and continuous, non-invasive blood pressure (MAP) with a finger plethysmograph. We corrected MCAv for MAP and present it as cerebrovascular conductance index (CVCi). We also measure ventilation and gas exchange with a pneumotachometer and gas analyzer. Results: All measured variables were similar prior to the initiation of room air and 5% CO2 prebreathe ( p > 0.05). Inspired (1±1 vs. 36±1 mmHg) and end-tidal (38±4 vs. 47±3 mmHg) CO2 were greater during the 5% inspired CO2 trial ( p < 0.05, main effect of gas). LBNP caused an increase in heart rate, decrease in stroke volume, decrease in cardiac output, and an increase in total peripheral resistance ( p < 0.05, main effect of LBNP). These variables were similar regardless of inspiratory gas. MCAv (40±16 vs. 53±19 cm/s), MAP (94±10 vs. 99±11 mmHg), and CVCi (0.46±0.22 vs 0.56±0.24 cm/s/mmHg) were all greater during the 5% inspired CO2 trials ( p < 0.05, main effect of gas). Discussion: Breathing a mixture of 5% CO2 for 1 minute increased cerebral blood flow and blood pressure during a mimic of hypergravity stress. Despite technical challenges of integration into high-performance aircraft, increasing inspired CO2 could contribute to better tolerance to hypergravity stress. Funding was provided by the Air Force Offce of Scientific Research and King’s College London. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Adrenoceptors and Hypertension.

Hypertension is a very prevalent condition associated with high mortality and morbidity, secondary to changes resulting in blood vessels and resultant end-organ damage. Haemodynamic changes, including an initial rise in cardiac output followed by an increase in total peripheral resistance, denote the early changes associated with borderline or stage 1 hypertension, especially in young men. Increased sodium reabsorption leading to kidney damage is another mechanism proposed as one of the initial triggers for essential hypertension. The underlying pathophysiological mechanisms include catecholamine-induced α1- and ß1-adrenoceptor stimulation, and renin-angiotensin-aldosterone system activation leading to endothelial dysfunction which is believed to lead to persistent blood pressure elevation.α1 blockers, α2 agonists, and ß blockers were among the first oral anti-hypertensives. They are no longer first-line therapy after outcome trials did not demonstrate any benefits over and above other agents, despite similar blood pressure reductions. Angiotensin-converting enzyme inhibitors(or angiotensin receptor blockers), calcium channel blockers, and thiazide-like diuretics are now considered the first line of therapy, although adrenoceptor agents still have a role as second- or third-line therapy. The chapter also highlights hypertension in specific medical conditions such as pregnancy, phaeochromocytoma, hyperthyroidism, portal hypertension, pulmonary arterial hypertension, and ocular hypertension, to provide an overview for clinicians and researchers interested in the role of adrenoceptors in the pathophysiology and management of hypertension.

Changes in Cardiac Structure and Function Following Fistula Ligation in Kidney Transplant Recipients (Cohort Study)

Purpose: International guidelines recommend that haemodialysis access is provided by an arteriovenous fistula (AVF), which enables frequent, reliable access to the circulation, but there are no guidelines to suggest whether these AVFs need to be ligated after kidney transplantation. Cardiovascular morbidity and mortality remain high in recipients of a kidney transplant, the persistence of a patent arteriovenous fistula (AVF) after transplantation may contribute to ongoing maladaptive cardiovascular remodelling. The ability to reverse this maladaptive remodelling by ligation of this AVF is unknown. We conducted this trial to evaluate the effect of AVF ligation on cardiac structure and function in stable kidney transplant recipients. Also we studied the ability of preoperative echocardiographic and non-invasive hemodynamic measurements, including the effects of acute temporary occlusion of the fistula, to predict postoperative left ventricular diameter and mass reduction, by the closure of the fistula.
 Materials and Methods: Nonrandomized controlled trial. kidney transplant recipients (>12 months after transplantation with stable graft function) were divided into 2 groups. The first referred for surgical arteriovenous fistula closure. The second group didn’t receive Fistula closure (control). Standard echocardiographic parameters, heart rate, and blood pressure were assessed preoperatively (fistula closure) at baseline. These measurements were repeated 6 months after surgical closure.
 Findings: Seventeen kidney transplant patients were prospectively studied with 11 case and 6 controls with no fistula closure. Surgical fistula closure decreased left ventricular end-diastolic diameter and mass indexes (29.9_2.4to 27.4_2.1 mm/m2, P<0.001, and 141_37 to 132_39 g/m2, P<0.05, respectively), whereas no changes were seen in controls after a similar delay. Postoperative left ventricular end-diastolic diameter and mass reductions correlated best with the increases in total peripheral resistance (r_0.85, P<0.0001) and mean arterial blood pressure (r_0.64, P_0.006), respectively.
 Conclusions. Surgical closure of arteriovenous fistula reduces left ventricular diameter and mass in kidney transplant recipients. The best predictors of those morphological changes are the rise in blood pressure and total peripheral resistance induced by temporary occlusion of the fistula.
 Implications to Theory, Practice and Policy: Surgical closure of persistent AV fistula after renal transplantation to correct LV geometry and improve symptoms in terms of exertional dyspnea and palpitations.

Cardiovascular disorders in children with COVID-19

Background. The purpose of the work is to study the prevalence of cardiac disorders in hospitalized children with coronavirus disease (COVID-19). Materials and methods. A retrospective, cohort, monocenter study of the medical records of children who underwent inpatient treatment between September and December 2021 at the Kyiv City Children’s Clinical Infectious Disease Hospital was conducted. For our study, we selected the medical records of patients with polymerase chain reaction-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the presence of at least one result of cardiac activity examination by electrocardiography (ECG) and/or echocardiography. The first study of cardiac activity by ECG and/or echocardiography was carried out in the first three days of inpatient treatment. Standard methods of descriptive statistics were used for data processing. Non-parametric statistical methods (Mann-Whitney test, chi-square, Pearson’s exact test) were used for mathematical analysis. The research was carried out in accordance with the Declaration of Helsinki principles. The study was approved by the bioethics committee of the hospital. Results. Among 305 children hospitalized with a diagnosis of U07.1 (2019-nCoV acute respiratory disease), there were selected 195 medical histories of patients aged 15 days to 18 years (median of 5.37 years), who were examined for cardiac activity by ECG and/or echocardiography. The most common changes were rhythm disturbances in the form of sinus tachycardia (20.8 %), bradycardia (11.9 %) and sinus arrhythmia (7.9 %), ventricular conduction disorders (25.7 %), deviation of the electrical axis of the heart (10.9 %) and repolarization disorders (31.7 %). During echocardiographic examination, structural abnormalities in the form of myocardial hypertrophy were detected in 3.1 % of patients, dilated heart chambers in 2 %, and pericardial effusion in 9.2 %. Among the functional changes, we observed: a decrease in left ventricular contractility in 4.1 % of cases, in cardiac output in 28.6 %, and an increase in total peripheral resistance in 41.8 %. Heart rhythm disturbances in the form of sinus tachycardia, deviation of the electrical axis of the heart, a decrease in the amplitude of the ECG waves, repolarization disorders, and pericardial effusion were associated with an increased risk of death in children with COVID-19. Clinical cases of cardiovascular complications in the form of jugular vein thrombosis and infectious endocarditis illustrate the role of the cardiovascular system in the pathogenesis of coronavirus disease. Conclusions. SARS-CoV-2 infection is often associated with damage to the cardiovascular system. In most pediatric patients, this occurs in the form of subclinical changes registered during laboratory or instrumental studies, but the development of manifest forms such as myocarditis, endocarditis, pericarditis, heart attack, coronary disease, thrombotic complications, and heart failure is possible. Using simple non-invasive methods (ECG and echocardiography) during screening, it is possible to diagnose damage to the cardiovascular system, as well as to detect changes in the cardiovascular system, which are subclinical, but can have an important prognostic value regarding the adverse course of the disease in children, which are hospitalized with SARS-CoV-2 infection.

Splenic contraction and cardiovascular responses are augmented during apnea compared to rebreathing in humans.

The spleen contracts during apnea, releasing stored erythrocytes, thereby increasing systemic hemoglobin concentration (Hb). We compared apnea and rebreathing periods, of equal sub-maximal duration (mean 137s; SD 30), in eighteen subjects to evaluate whether respiratory arrest or hypoxic and hypercapnic chemoreceptor stimulation is the primary elicitor of splenic contraction and cardiovascular responses during apnea. Spleen volume, Hb, cardiovascular variables, arterial (SaO2), cerebral (ScO2), and deltoid muscle oxygen saturations (SmO2) were recorded during the trials and end-tidal partial pressure of oxygen (PETO2) and carbon dioxide (PETCO2) were measured before and after maneuvers. The spleen volume was smaller after apnea, 213 (89)mL, than after rebreathing, 239 (95)mL, corresponding to relative reductions from control by 20.8 (17.8) % and 11.6 (8.0) %, respectively. The Hb increased 2.4 (2.0) % during apnea, while there was no significant change with rebreathing. The cardiovascular responses, including bradycardia, decrease in cardiac output, and increase in total peripheral resistance, were augmented during apnea compared to during rebreathing. The PETO2 was higher, and the PETCO2 was lower, after apnea compared to after rebreathing. The ScO2 was maintained during maneuvers. The SaO2 decreased 3.8 (3.1) % during apnea, and even more, 5.4 (4.4) %, during rebreathing, while the SmO2 decreased less during rebreathing, 2.2 (2.8) %, than during apnea, 8.3 (6.2) %. We conclude that respiratory arrest per se is an important stimulus for splenic contraction and Hb increase during apnea, as well as an important initiating factor for the apnea-associated cardiovascular responses and their oxygen-conserving effects.

Augmented Ouabain-Induced Vascular Response Reduces Cardiac Efficiency in Mice with Migraine-Associated Mutation in the Na+, K+-ATPase α2-Isoform

Heterozygous mice (α2+/G301R mice) for the migraine-associated mutation (G301R) in the Na+,K+-ATPase α2-isoform have decreased expression of cardiovascular α2-isoform. The α2+/G301R mice exhibit a pro-contractile vascular phenotype associated with decreased left ventricular ejection fraction. However, the integrated functional cardiovascular consequences of this phenotype remain to be addressed in vivo. We hypothesized that the vascular response to α2-isoform-specific inhibition of the Na+,K+-ATPase by ouabain is augmented in α2+/G301R mice leading to reduced cardiac efficiency. Thus, we aimed to assess the functional contribution of the α2-isoform to in vivo cardiovascular function of wild-type (WT) and α2+/G301R mice. Blood pressure, stroke volume, heart rate, total peripheral resistance, arterial dP/dt, and systolic time intervals were assessed in anesthetized WT and α2+/G301R mice. To address rate-dependent cardiac changes, cardiovascular variables were compared before and after intraperitoneal injection of ouabain (1.5 mg/kg) or vehicle during atrial pacing. The α2+/G301R mice showed an enhanced ouabain-induced increase in total peripheral resistance associated with reduced efficiency of systolic development compared to WT. When the hearts were paced, ouabain reduced stroke volume in α2+/G301R mice. In conclusion, the ouabain-induced vascular response was augmented in α2+/G301R mice with consequent suppression of cardiac function.

Adverse childhood experiences are associated with altered cardiovascular reactivity to head-up tilt in young adults.

Adverse childhood experiences (ACEs) are associated with greater prevalence of cardiovascular disease and altered acute stress reactivity. The current study investigated the effect of ACEs on hemodynamic and autonomic responses to orthostatic stress imposed by 60° head-up tilt (HUT) in young adults. Two-hundred twenty-six healthy young adults (age = 22.6 ± 1.5 yr; n = 116 females) without cardiovascular disease participated and had complete data. Participants underwent supine blood pressure (BP), R-R interval (RRI), cardiac output (CO), total peripheral resistance (TPR), and cardiovagal baroreflex sensitivity (cvBRS) testing followed by a transition to 60° HUT where measures were reassessed. Childhood adversity exposures were assessed based on categorical exposure and nonexposure to childhood household dysfunction and maltreatment, and <4 and ≥4 types of ACEs. Significantly greater increases in SBP (P < 0.05), DBP, MAP, and TPR (P < 0.01; all) following 60° HUT were observed in individuals with ≥4 compared with those with <4 types of ACEs. Attenuated decreases in RRI and cvBRS were observed in those with ≥4 types of ACEs (P < 0.05). Experiencing ≥4 types of ACEs was associated with augmented BP and TPR reactivity and a blunted decrease in cvBRS in response to 60° HUT in young adults. Results suggest that a reduced vagal response to orthostatic stress is present in those who have experienced ≥4 types of ACEs that may promote autonomic dysfunction. Future research examining the sympathetic and vagal baroreflex branches is warranted.

Effects of lung volume and trigeminal nerve stimulation on diving response in breath-hold divers and non-divers

PurposeThis study investigated the effects of lung volume and trigeminal nerve stimulation (TS) on diving responses in breath-hold divers (BHDs) and non-divers (NDs). MethodsEight BHDs and nine NDs performed four breath-hold trials at different lung volumes, with or without TS, and one trial of TS. Haemodynamic parameters and electrocardiograms were measured for each trial. ResultsDuring the TS trial, the total peripheral resistance increased more in BHDs. Breath-hold performed at total lung capacity showed a more pronounced decrease in stroke volume and cardiac output in BHDs. The decrease in heart rate and increase in total peripheral resistance were more pronounced in BHDs when breath-holding was performed with TS. ConclusionThe more pronounced diving response in BHDs was attributed to the greater increase in total peripheral resistance caused by TS. Furthermore, the lower stroke volume and cardiac output in BH performed at total lung capacity could also cause a more pronounced diving response in BHDs.

Microcirculation and Macrocirculation in Hypertension: A Dangerous Cross-Link?

Microcirculation and macrocirculation are tightly interconnected into a dangerous cross-link in hypertension. Small artery damage includes functional (vasoconstriction, impaired vasodilatation) and structural abnormalities (mostly inward eutrophic remodeling). These abnormalities are major determinants of the increase in total peripheral resistance and mean blood pressure (BP) in primary hypertension, which in the long term induces large artery stiffening. In turn, large artery stiffening increases central systolic and pulse pressures, which are further augmented by wave reflection in response to the structural alterations in small resistance arteries. Finally, transmission of high BP and flow pulsatility to small resistance arteries further induces functional and structural abnormalities, thus leading to increased total peripheral resistance and mean BP, thus perpetuating the vicious circle. Hyperpulsatility, in addition to higher mean BP, exaggerates cardiac, brain, and kidney damages and leads to cardiovascular, cerebral, and renal complications. The dangerous cross-link between micro and macrocirculation can be reversed into a virtuous one by ACE (angiotensin-converting enzyme) inhibitors, sartans, and calcium channel blockers. These three pharmacological classes are more potent than β-blockers and diuretics for reducing arterial stiffness and small artery remodeling. The same ranking was observed for their effectiveness at reducing left ventricular hypertrophy, preserving glomerular filtration rate, and preventing dementia, suggesting that they can act beyond brachial BP reduction, by breaking the micro/macrocirculation vicious circle.

Зміни центральної гемодинаміки у період раннього відновлення після різних режимів фізичного навантаження

We studied the changes in central hemodynamics in the early recovery period after physical load in 28 young men. Dynamic loading was induced using a modified Martine functional test, static loading - by maintaining on the standing dynamometer DS-200 muscle effort in the amount of 50% of maximum standing force. The change in central hemodynamic para- meters was recorded by tetrapolar thoracic impedance rheo- plethysmogram using a computerized diagnostic complex «Cardio +». Dynamic exercise during early recovery did not lead to a significant increase in heart rate, however, it caused a decrease in the resistance of resistive blood vessels and an increase in pulse blood pressure. The increase in minute blood volume in our study is mainly due to an increase in stroke volume, pointing for high functional reserves of the heart. In the case of static physical activity, the adaptive reactions of central hemodynamics and the course of the processes of early recovery of the circulatory system are radically different from similar indicators during dynamic physical activity. In subjects with a normodynamic type of response of the cardiovascular system to dynamic load, no significant changes in the minute volume of blood flow were registered at a similar volume of active muscle mass static load. In subjects with a normodynamic type of cardiovascular response to dynamic load, no significant changes in cardiac output were observed at a similar static load in terms of active muscle mass. However, during early recovery period, the total peripheral vascular resistance and systolic arterial pressure were increased. The increase in total peripheral resistance may be due to reactive hyperemia in ischemic skeletal muscle caused by increased blood flow to the capillaries after muscle relaxation and delayed outflow into the veins. The significant increase in systolic blood pressure can be explained by the mechanical obstruction of blood flow in the muscle capillaries during prolonged static contraction.

Comparison of the sit-up test and head-up tilt test for assessing blood pressure and hemodynamic responses in healthy young individuals.

The sit-up test is used to assess orthostatic hypotension, without the use of a tilt table, in populations who are unable to stand. The primary objective of this study was to determine the differences in blood pressure and hemodynamic responses between the sit-up and head-up tilt tests. The secondary objective was to determine the hemodynamic responses related to changes in blood pressure during each test. Nineteen healthy volunteers (nine males, aged 24.3 ± 2.4 years) underwent the sit-up and head-up tilt tests. Systolic and diastolic blood pressure, heart rate, stroke volume, cardiac output, and total peripheral resistance were measured. The increase in systolic blood pressure (15 ± 9 vs. 8 ± 8 mmHg) was greater, while the increase in heart rate (8 ± 5 vs. 12 ± 8 bpm) and reduction in stroke volume (-17 ± 10 vs. -21 ± 10 ml) were smaller during the sit-up test than during the head-up tilt test (P < 0.05). Additionally, the increases in blood pressure variables were significantly associated with the increase in total peripheral resistance (P < 0.05), but not with changes in other hemodynamic variables in both tests. Although the magnitudes of changes in systolic blood pressure, heart rate, and stroke volume differed between the tests, the hemodynamic variable related to changes in blood pressure was the same for both tests. These results may contribute to the clinical application of the sit-up test for identifying the presence and hemodynamic mechanisms of orthostatic hypotension.

Evidence that Young Normotensive South Asians Show Early Signs of Disturbed Arterial Blood Pressure (ABP) Regulation of in Acute Mental Stress Relative to White Europeans

The risk of cardiovascular disease (CVD) including hypertension is higher in South Asians (SAs) than White Europeans (WEs). But, whether disturbances in autonomic control of the cardiovascular system are present in early adulthood in SAs has not been tested. Thus, we performed studies on young 20 WEs and 21 SAs aged (21.9±0.36, 20.7±0.41 respectively, equal numbers of men and women in each group) in whom arterial blood pressure (ABP), electrocardiogram (ECG), heart rate (HR) and respiration were recorded at rest, during mental stress (3 min Colour Stroop test) and during 5 min slow breathing (6 breaths/min). Stroke volume (SV), cardiac output (CO), and total peripheral resistance (TPR) were computed from the pulse contour. Baroreflex sensitivity (BRS) was calculated by the sequence method as change in R-R interval evoked by spontaneous up and down sequences in systolic pressure (SP) at rest and during mental stress and as the relationship between R-R interval and the fall in SP evoked by standing from a squat before and at 0, 3, 6 min following the stress test. HRV was computed in time-domain during mental stress and slow breathing. Comparisons within and between WEs and SAs were done by paired and un-paired t-tests respectively. At rest, WEs and SAs had similar mean ABP (mABP, 86.9±1.42 vs 87.1±1.77mmHg), HR (71.1±2.45 vs 76.2±3.56 beats/min), CO (4.8±0.21 vs 5.2±0.21L/min), SV (76.5±3.86 vs 81.5±2.97ml), TPR (1.14±0.06 vs 1.01±0.04 resistance units), and BRS (up-sequence: 1.2±0.05, down-sequence: 1.2±0.05 vs 1.0±0.09 and 1.2±0.09ms/mmHg). Further, mental stress evoked similar increases in mABP and HR in WEs and SAs but was accompanied by an increase CO in WEs and by an increase in TPR in SAs. Concomitantly, vagal indices of HRV were depressed during mental stress in SAs only (RMSSD: 66.2±7.8 to56.2±11.4 and 67.6±8.7 to 50.0±6.5*ms, *: P<0.05 within WE or SAs). Further during up-sequences in SP, BRS was depressed in both SAs and WEs during mental stress, but during down-sequences, BRS was depressed in WE only (to 0.59±0.10 vs 0.96±0.08*ms/mmHg). Also, following mental stress, BRS during squat to stand, an index of vagosympathetic activity, was depressed in WEs only (0.5±0.04 at rest to 0.3±0.04* vs 0.5±0.06 to 0.5±0.06ms/mmHg). On the other hand, slow breathing, tended to decrease ABP in both WEs and SAs (82.1±1.8 to 79.2±2.1mmHg: P<0.05; 79.4±2.0 to 77.4±2.0mmHg: P=0.09 respectively) and increased vagal indices of HRV in both WEs and SAs (66.3±8.6 to 86.0±13.2*ms; 67.6±8.7 to 86.48.8*ms). These results suggest that during and after mental stress, young normotensive SAs show greater sympathetic vasoconstriction than WEs, and attenuated respiratory modulation of HR, while their ability to evoke baroreflex tachycardia by vagal inhibition and sympathetic activation is preserved relative to young WEs. Such disturbances in would be expected to increase the risk of future CVD and hypertension in SAs, particularly in those with high levels of daily stress. The finding that slow breathing increased vagal activity in young SAs raises the possibility that regular slow breathing may help to normalize autonomic regulation of ABP in SAs and limit future CVD.

Impact of mild hypothermia therapy on hemodynamics during the induction stage in neonates with moderate to severe hypoxic-ischemic encephalopathy

Objective To study the changes in hemodynamics during the induction stage of systemic mild hypothermia therapy in neonates with moderate to severe hypoxic-ischemic encephalopathy (HIE). Methods A total of 21 neonates with HIE who underwent systemic mild hypothermia therapy in the Department of Neonatology, Dongguan Children's Hospital Affiliated to Guangdong Medical University, from July 2017 to April 2020 were enrolled. The rectal temperature of the neonates was lowered to 34℃ after 1-2 hours of induction and maintained at this level for 72 hours using a hypothermia blanket. The impedance method was used for noninvasive hemodynamic monitoring, and the changes in heart rate (HR), mean arterial pressure (MAP), stroke volume (SV), cardiac output (CO), cardiac index (CI), and total peripheral resistance (TPR) from the start of hypothermia induction to the achievement of target rectal temperature (34℃). Blood lactic acid (LAC) and resistance index (RI) of the middle cerebral artery were recorded simultaneously. Results The 21 neonates with HIE had a mean gestational age of (39.6±1.1) weeks, a mean birth weight of (3 439±517) g, and a mean 5-minute Apgar score of 6.8±2.0. From the start of hypothermia induction to the achievement of target rectal temperature (34℃), there were significant reductions in HR, CO, and CI (P 0.05). There was a significant increase in TPR (P 0.05). Conclusions The systemic mild hypothermia therapy may have a significant impact on hemodynamics in neonates with moderate to severe HIE, and continuous hemodynamic monitoring is required during the treatment.

Factors mediating the pressor response to isometric muscle contraction: An experimental study in healthy volunteers during lower body negative pressure.

Whilst both cardiac output (CO) and total peripheral resistance (TPR) determine mean arterial blood pressure (MAP), their relative importance in the pressor response to isometric exercise remains unclear. This study aimed to elucidate the relative importance of these two different factors by examining pressor responses during cardiopulmonary unloading leading to step-wise reductions in CO. Hemodynamics were investigated in 11 healthy individuals before, during and after two-minute isometric exercise during lower body negative pressure (LBNP; -20mmHg and -40mmHg). The blood pressure response to isometric exercise was similar during normal and reduced preload, despite a step-wise reduction in CO during LBNP (-20mmHg and -40mmHg). During -20mmHg LBNP, the decreased stroke volume, and consequently CO, was counteracted by an increased TPR, while heart rate (HR) was unaffected. HR was increased during -40 mmHg LBNP, although insufficient to maintain CO; the drop in CO was perfectly compensated by an increased TPR to maintain MAP. Likewise, transient application of LBNP (-20mmHg and -40mmHg) resulted in a short transient drop in MAP, caused by a decrease in CO, which was compensated by an increase in TPR. This study suggests that, in case of reductions of CO, changes in TPR are primarily responsible for maintaining the pressor response during isometric exercise. This highlights the relative importance of TPR compared to CO in mediating the pressor response during isometric exercise.

The influence of aircraft noise exposure on the systemic and renal haemodynamics.

Epidemiological studies found a link between aircraft noise exposure and increased incidence of arterial hypertension and cardiovascular disease, but the underlying pathophysiological mechanisms are not fully understood. Clinical studies have shown that mental stress affects the systemic and renal haemodynamic, but no such study was performed with noise exposure as stress factor. We analysed systemic and renal effects of 25 min standardized aircraft noise in a sham controlled clinical study including 80 healthy men and 34 male patients with hypertension. Systemic haemodynamic parameters were measured using electrocardiography and impedance cardiography. The renal haemodynamic was assessed using steady state input clearance with infusion of para-aminohippuric acid and inulin for glomerular filtration rate and renal plasma flow, respectively. In the systemic circulation of hypertensive patients, there was an increase in total peripheral resistance (TPR) (1420 ± 387 vs. 1640 ± 516 dyn·s·cm-5, P = 0.001) and a decrease in cardiac index (CI) (2.9 ± 0.8 vs. 2.6 ± 0.8 L/(min·m2, P < 0.001) 25 min after the start of noise exposure, which was not present during sham procedure (P = 0.10, P = 0.86). In healthy individuals a procedure induced increase in TPR and decrease in CI was present after noise (TPR: 995 ± 239 vs. 1106 ± 308 dyn·s·cm-5, P = 0.001, CI: 3.6 ± 0.7 vs. 3.3 ± 0.9 L/(min·m2, P < 0.001) and sham application (TPR: P = 0.002, CI: P < 0.001). However, in healthy individuals changes in TPR (P = 0.450) and CI (P = 0.605) from baseline until 25 min after the start of the intervention did not differ between noise and sham exposure. In the renal circulation of hypertensive patients and healthy individuals the response did not differ between noise and sham procedure. In hypertensive but not healthy men we observed a systemic vasoconstrictive response after aircraft noise exposure accompanied by a decrease in CI. No significant changes were observed in the renal circulation. Our results suggest that male hypertensive patients are more susceptible for noise-induced changes of vascular resistance in the systemic circulation.

Impact of Graded Passive Cycling on Hemodynamics, Cerebral Blood Flow, and Cardiac Function in Septic ICU Patients.

Background: In-bed passive cycling is considered a safe and feasible early mobilization technique in intensive care unit (ICU) patients who are unable to exercise actively. However, the impact of varying intensity of passive cycling on perfusion and function of ischemia-prone organs is unknown. In this study, we assessed the impact of a graded passive cycling protocol on hemodynamics, cerebral blood flow, and cardiac function in a cohort of septic ICU patients.Methods: In consecutive patients presenting with sepsis, we measured global hemodynamic indices, middle cerebral artery velocity (MCAv), and cardiac function in response to a graded increase in passive cycling cadence. Using 5-min stages, we increased cadence from 5 to 55 RPM in increments of 10 RPM, preceded and followed by 5 min baseline and recovery periods at 0 RPM. The mean values obtained during the last 2 min of each stage were compared within and between subjects for all metrics using repeated-measures ANOVA.Results: Ten septic patients (six males) completed the protocol. Across patients, there was a 5.2% reduction in MCAv from baseline at cycling cadences of 25–45 RPM with a dose-dependent decrease of MCAv of > 10% in four of the 10 patients enrolled. There was a 16% increase in total peripheral resistance from baseline at peak cadence of 55 RPMs and no changes in any other measured hemodynamic parameters. Patient responses to passive cycling varied between patients in terms of magnitude, direction of change, and the cycling cadence at which these changes occurred.Conclusions: In septic patients, graded passive cycling is associated with dose-dependent decreases in cerebral blood flow, increases in total peripheral resistance, and either improvement or worsening of left ventricular function. The magnitude and cadence threshold of these responses vary between patients. Future studies should establish whether these changes are associated with clinical outcomes, including cognitive impairment, vasopressor use, and functional outcomes.

Aerobic fitness and sympathetic responses to spontaneous muscle sympathetic nerve activity in young males

Lower aerobic fitness increases the risk of developing hypertension. Muscle sympathetic nerve activity (MSNA) is important for the beat-by-beat regulation of blood pressure. Whether the cardiovascular consequences of lower aerobic fitness are due to augmented transduction of MSNA into vascular responses is unclear. We tested the hypothesis that aerobic fitness is inversely related to peak increases in total peripheral resistance (TPR) and mean arterial pressure (MAP) in response to spontaneous MSNA bursts in young males. Relative peak oxygen consumption (VO2peak, indirect calorimetry) was assessed in 18 young males (23 ± 3years; 41 ± 8ml/kg/min). MSNA (microneurography), cardiac intervals (electrocardiogram) and arterial pressure (finger photoplethysmography) were recorded continuously during supine rest. Stroke volume and cardiac output (CO) were estimated via the ModelFlow method. TPR was calculated as MAP/CO. Changes in TPR and MAP were tracked for 12 cardiac cycles following heartbeats associated with or without spontaneous bursts of MSNA. Overall, aerobic fitness was inversely correlated to the peak ΔTPR (0.8 ± 0.7mmHg/l/min; R = -0.61, P = 0.007) and ΔMAP (2.3 ± 0.8mmHg; R = -0.69, P < 0.001), but not with the peak ΔCO (0.2 ± 0.1l/min; P = 0.50), MSNA burst frequency (14 ± 5 bursts/min; P = 0.43) or MSNA relative burst amplitude (65 ± 12%; P = 0.13). Heartbeats without an associated burst of MSNA did not increase TPR, MAP or CO. Although unrelated to traditional MSNA characteristics, aerobic fitness was inversely associated with spontaneous sympathetic neurovascular transduction in young males. This may be a potential mechanism by which aerobic fitness modulates the regulation of arterial blood pressure through the sympathetic nervous system.

Systemic and regional hemodynamic response to activation of the exercise pressor reflex in patients with peripheral artery disease.

Patients with peripheral artery disease (PAD) have an accentuated exercise pressor reflex (EPR) during exercise of the affected limb. The underlying hemodynamic changes responsible for this, and its effect on blood flow to the exercising extremity, are unclear. We tested the hypothesis that the exaggerated EPR in PAD is mediated by an increase in total peripheral resistance (TPR), which augments redistribution of blood flow to the exercising limb. Twelve patients with PAD and 12 age- and sex-matched subjects without PAD performed dynamic plantar flexion (PF) using the most symptomatic leg at progressive workloads of 2-12 kg (increased by 1 kg/min until onset of fatigue). We measured heart rate, beat-by-beat blood pressure, femoral blood flow velocity (FBV), and muscle oxygen saturation () continuously during the exercise. Femoral blood flow (FBF) was calculated from FBV and baseline femoral artery diameter. Stroke volume (SV), cardiac output (CO), and TPR were derived from the blood pressure tracings. Mean arterial blood pressure and TPR were significantly augmented in PAD compared with control during PF. FBF increased during exercise to an equal extent in both groups. However, of the exercising limb remained significantly lower in PAD compared with control. We conclude that the exaggerated pressor response in PAD is mediated by an abnormal TPR response, which augments redistribution of blood flow to the exercising extremity, leading to an equal rise in FBF compared with controls. However, this increase in FBF is not sufficient to normalize the SmO2 response during exercise in patients with PAD.NEW & NOTEWORTHY In this study, peripheral artery disease (PAD) patients and healthy control subjects performed graded, dynamic plantar flexion exercise. Data from this study suggest that previously reported exaggerated exercise pressor reflex in patients with PAD is driven by greater vasoconstriction in nonexercising vascular territories which also results in a redistribution of blood flow to the exercising extremity. However, this rise in femoral blood flow does not fully correct the oxygen deficit due to changes in other mechanisms that require further investigation.

Changes of endothelial function and intracardiac hemodynamics during implantation of different types of pacemakers

Aim. To determine the dynamics of endothelial function and intracardiac hemodynamics during implantation of different types of pacemakers. Material and methods. The study involved 61 patients, 29 of them were implanted with single-chamber pacemaker (the first group), 32 — two-chamber pacemaker (second group) with sick sinus syndrome (SSS), as well as patients with 2-3 degrees AV conduction disorder. Test with endothelium-dependent vasodilation of the brachial artery was performed using the standard technique and the velocity parameters of blood flow were determined. Parameters of intracardiac hemodynamics and left atrial (LA) function were determined. These studies were conducted in patients initially upon admission to the hospital and 2 months later implantation of pacemaker. Results. Endothelium-dependent vasodilation significantly deteriorated in patients with single-chamber pacemaker which initially was 6,1 [2,74;9,815]% and in 2 months decreased to 5,4 [2,37;7,55]% (p=0,05). There was a tendency to deterioration of left ventricular (LV) contractile function accompanied by a decrease in ejection fraction (EF) to 55,04 [49,04;68,72]%, and decrease emptying fraction of LA to 37,36 [31,67;52,85]%. There was a tendency to increase the volume index of LA which indicates an increasing overload of the volume and pressure of LA. There was a significant increase in the degree of endothelium-dependent vasodilation in patients of the second group initially compiling a 3,25 [2,15;6,61]% and then reaches 6,15 [2,75;8,97]% 2 months after surgery (p <0,04). There was no overload in the volume and pressure of LA and improved indirect signs of LV compliance parameters (growth of end-systolic dimension and volume) and decreased LV EF to 53,23 [44,1;69,95]%. In patients in the first group there was a tendency to increase peripheral resistance to 1227 [1065;1318] dyne x cm -5 x sec, accompanied by a significant decrease in blood flow rate. In the second group there was a tendency to reduce peripheral resistance to 1215 [1136;1391] dyne x cm -5 x sec and a significant increase in blood flow rate. There was a significant correlation between the systole LA dimension and total peripheral resistance in patients with VVI stimulation (r=0,78, p=0,0022), which indicates an increase in total peripheral resistance with a change in blood flow from LA to LV and a decrease in cardiac output. Conclusion. Endothelial function deteriorates with single-chamber stimulation and improves with two-chamber stimulation. These changes are based on shear stress and nitric oxide endothelium secretion the changes of which depend on the characteristics of central and peripheral hemodynamics.

Sex differences in blood pressure regulation during ischemic isometric exercise: the role of the β-adrenergic receptors.

We sought to investigate whether the β-adrenergic receptors play a pivotal role in sex-related differences in arterial blood pressure (BP) regulation during isometric exercise. Sixteen volunteers (8 women) performed 2 min of ischemic isometric handgrip exercise (IHE) and 2 min of postexercise circulatory occlusion (PECO). Heart rate (HR) and beat-to-beat arterial BP were continuously measured. Beat-to-beat estimates of stroke volume (ModelFlow) were obtained and matched with HR to calculate cardiac output (Q̇) and total peripheral resistance (TPR). Two trials were randomly conducted between placebo and nonselective β-adrenergic blockade (40 mg propranolol). Under the placebo condition, the magnitude of the BP response in IHE was lower in women compared with men. During PECO, the BP remained elevated and the sex differences persisted. The β-blockade attenuated the BP response during IHE in men (∆57 ± 4 vs. ∆45 ± 7 mmHg, P = 0.025) due to a reduction in Q̇ (∆3.7 ± 0.5 vs. ∆1.8 ± 0.2 L/min, P = 0.012) while TPR was not affected. In women, however, the BP response during IHE was unchanged (∆27 ± 3 vs. ∆28 ± 3 mmHg, P = 0.889), despite attenuated Q̇ (∆2.7 ± 0.4 vs. ∆1.3 ± 0.2 L/min, P = 0.012). These responses were mediated by a robust increase in TPR under β-blockade (∆-0.2 ± 0.4 vs. ∆2.2 ± 0.7 mmHg·L-1·min, P = 0.012). These findings demonstrate that the sex differences in arterial BP regulation during ischemic IHE are mediated by β-adrenergic receptors.NEW & NOTEWORTHY We found that the blood pressure response during isometric exercise in women is mediated by increases in cardiac output, whereas in men it is mediated by increases in both cardiac output and total peripheral resistance. In addition, women showed a robust increase in total peripheral resistance under β-blockade during isometric exercise and muscle metaboreflex activation. These findings demonstrate that sex differences in blood pressure regulation during isometric exercise are mediated by β-adrenergic receptors.