Increase In Total Peripheral Resistance Research Articles

De novo expression of Kv6.3 contributes to changes in vascular smooth muscle cell excitability in a hypertensive mice strain

Essential hypertension involves a gradual and sustained increase in total peripheral resistance, reflecting an increased vascular tone. This change associates with a depolarization of vascular myocytes, and relies on a change in the expression profile of voltage-dependent ion channels (mainly Ca(2+) and K(+) channels) that promotes arterial contraction. However, changes in expression and/or modulation of voltage-dependent K(+) channels (Kv channels) are poorly defined, due to their large molecular diversity and their vascular bed-specific expression. Here we endeavor to characterize the molecular and functional expression of Kv channels in vascular smooth muscle cells (VSMCs) and their regulation in essential hypertension, by using VSMCs from resistance (mesenteric) or conduit (aortic) arteries obtained from a hypertensive inbred mice strain, BPH, and the corresponding normotensive strain, BPN. Real-time PCR reveals a differential distribution of Kv channel subunits in the different vascular beds as well as arterial bed-specific changes under hypertension. In mesenteric arteries, the most conspicuous change was the de novo expression of Kv6.3 (Kcng3) mRNA in hypertensive animals. The functional relevance of this change was studied by using patch-clamp techniques. VSMCs from BPH arteries were more depolarized than BPN ones, and showed significantly larger capacitance values. Moreover, Kv current density in BPH VSMCs is decreased mainly due to the diminished contribution of the Kv2 component. The kinetic and pharmacological profile of Kv2 currents suggests that the expression of Kv6.3 could contribute to the natural development of hypertension.

2種類の暗算課題遂行時における心血管反応

Eighteen young females performed two kinds of mental tasks, an Internally-Generated Mental Arithmetic task (IGMA: serial subtraction) and an Externally-Presented Mental Arithmetic task (EPMA: continual subtraction). Both tasks were equal in establishing active coping, but EPMA made participants attend more to an external stimulus. The expected reaction patterns were vascular-dominant (blood pressure elevation mainly due to an increase in total peripheral resistance) for only EPMA, or cardiac-dominant (mainly due to an increase in cardiac output) for both IGMA and EPMA. The results showed that vascular-dominant patterns were evoked during EPMA, while mixed (moderate increases in both cardiac output and total peripheral resistance) reaction patterns were evoked during IGMA. Post-task questionnaires confirmed that attention to an external stimulus was required much more in EPMA than in IGMA. These results indicate that the vascular-dominant reaction pattern was evoked in the state where attention to an external stimulus was heightened. The implications of the present findings are discussed in term of how to interpret the hemodynamic reaction patterns during mental stress.

Influence of the 6‑month anemia therapy with erythropoietin on renal function and some hemodynamic parameters in predialysis patients

The aim of this study was to evaluate the influence of a 6-month anemia therapy with recombinant human erythropoietin (rHuEpo) on glomerular filtration rate (GFR) and renal blood flow related to hemoglobin (Hb) concentration, changes in heart function and total peripheral resistance in patients with chronic kidney disease (CKD) treated conservatively. We evaluated 13 patients (9 women and 4 men) aged 64.8 +/- 8.9 years with serum creatinine of 3.82 +/- 1.30 mg/dl and Hb concentration of 10.02 +/- 0.45 g/dl. rHuEpo was given in the mean dose of 2296 +/- 673 U/week s.c. to achieve Hb 12 g/dl. At baseline and after 6 months of rHuEpo therapy echocardiography and renoscintigraphy were performed. After 6 months' therapy Hb increased significantly, while blood pressure did not change significantly. Renal anemia correction led to a decrease in left ventricular end-diastolic dimension index, left ventricular end-diastolic volume index, stroke volume index and cardiac index. Total peripheral vascular resistance index increased significantly. At the same time a significantly reduced left ventricular mass index was observed. Correction of renal anemia and changes in systemic hemodynamics did not exert unfavorable effect on renal hemodynamic parameters. GFR index, blood flow rate index, renal vascular resistance index and filtration fraction remained unchanged. During rHuEpo therapy decline in renal function expressed as 1/serum creatinine did not differ compared with a 6-month period before initiating rHuEpo therapy. Therapy with rHuEpo in patients with stage 3 and 4 CKD with correct blood pressure control does not result in worsening of renal function despite changes in left ventricular function and increase of total peripheral resistance.

Sodium, hypertension, and an explanation of the “lag phenomenon” in hemodialysis patients

Sodium balance is precisely regulated by intake and output. The kidneys are responsible for adjusting sodium excretion to maintain balance at varying intakes. Our distant ancestors were herbivores. Their diet contained little sodium, so they developed powerful mechanisms for conserving sodium and achieving low urinary excretion. About 10,000 years ago, early humans became villagers and discovered that food could be preserved in brine. This led to increased consumption of salt. High salt intake increases extracellular volume (ECV), blood volume, and cardiac output resulting in elevation of blood pressure. High ECV induces release of a digitalis-like immunoreactive substance and other inhibitors of Na(+)-K(+)-ATPase. As a consequence, intracellular sodium and calcium concentrations increase in vascular smooth muscles predisposing them to contraction. Moreover, high ECV increases synthesis and decreases clearance of asymmetrical dimethyl-l-arginine leading to inhibition of nitric oxide (NO) synthase. High concentration of sodium and calcium in vascular smooth muscles, and decreased synthesis of NO lead to an increase in total peripheral resistance. Restoration of normal ECV and blood pressure are attained by increased glomerular filtration and decreased sodium reabsorption. In some individuals, the kidneys have difficulty in excreting sodium, so the equilibrium is achieved at the expense of elevated blood pressure. There is some lag time between reduction of ECV and normalization of blood pressure because the normal levels of Na(+)-K(+)-ATPase inhibitors and asymmetrical dimethyl-l-arginine are restored slowly. In dialysis patients, all mechanisms intended to increase renal sodium removal are futile but they still operate and elevate blood pressure. The sodium balance must be achieved via dialysis and ultrafiltration. Blood pressure is normalized a few weeks after ECV is returned to normal, i.e., when the patient reaches dry body weight. This is called the "lag phenomenon."

Attenuated peripheral vasoconstriction during an orthostatic challenge in older men

orthostatic hypotension is common in older men and associated with morbidity and mortality. During orthostatic challenges, older men maintain their blood pressure by an augmented increase in total peripheral resistance. Changes in the leg vascular bed contribute importantly to blood pressure regulation during orthostatic challenges, partly because of blood pooling in the legs. Little is known about the contribution of the leg vascular bed to the augmented increase in total peripheral resistance. to examine tilt-induced peripheral vasoconstriction in the leg vascular bed of young and older men. we measured forearm and calf blood flow in 12 young and 12 older men, using venous occlusion plethysmography during 30 degrees head-up tilt (HUT). Forearm and calf vascular resistance were calculated as mean arterial blood pressure divided by blood flow. during HUT, calf and forearm vascular resistance increased in older and young men. The increase in forearm vascular resistance was similar between older (40 +/- 6%) and young men (51 +/- 12%). However, the increase in calf vascular resistance was lower in older (96 +/- 15%) than in young men (175 +/- 30%). advancing age leads to an attenuated tilt-induced increase in calf vascular resistance, which may contribute to age-related orthostatic hypotension.

Ethanol lowers blood pressure in conscious female rats via enhancing the phosphorylation of myocardial neuronal nitric oxide synthase

Intragastric (i.g.) ethanol lowers blood pressure (BP) in female rats via a reduction in cardiac output (CO) and stroke volume (SV). We tested the hypothesis that enhancement of myocardial nNOS and/or eNOS activity constitutes a cellular mechanism for ethanol‐evoked reductions in CO and BP. We investigated the effect of inhibition of nNOS (Nω‐propyl‐L‐arginine, NPLA) or eNOS [N5‐(1‐iminoethyl)‐L‐ornithine, L‐NIO] on hemodynamic, biochemical (nitrate/nitrite levels, NOx), and myocardial nNOS/eNOS phosphorylation elicited by ethanol (1 g/kg i.g.) in proestrus female rats. In saline‐pretreated rats, the hemodynamic effects of ethanol (reductions in BP, CO, and SV) were coupled with increases in plasma NOx and myocardial p‐nNOS, but not p‐eNOS, expression. nNOS inhibition by NPLA attenuated the hemodynamic effects of ethanol and associated increases in plasma NOx and cardiac p‐nNOS. eNOS inhibition by L‐NIO attenuated ethanol hypotension, but not concomitant CO/SV reductions. L‐NIO uncovered a dramatic increase in total peripheral resistance (TPR) in response to ethanol, which appeared to have offset the reduction in CO. These findings highlight: (i) myocardial nNOS as the cellular mechanism that underlies, in part, reductions in BP and CO caused by ethanol in female rats, and (ii) vascular eNOS‐NO signaling counterbalances ethanol‐induced increases in TPR.Supported by Grant R01 AA014441 from NIAAA.

Orthostatic hypotension: a new classification system

Orthostatic hypotension (OH) is a common condition, which is defined as a reduction in systolic blood pressure of >or=20 mmHg or diastolic blood pressure of >or=10 mmHg within 3 min of orthostatic stress. Utilizing total peripheral resistance (TPR) and cardiac output (CO) measurements during tilt-table testing (Modelflow method), we classified OH into three categories, namely arteriolar, venular, and mixed. The principle defect in arteriolar OH is impaired vasoconstriction after orthostatic stress, reflected by absence of the compensatory increase in TPR. In venular OH, the predominant defect is excessive reduction in venous return, reflected by a large drop in CO after orthostatic stress with marked tachycardia. Mixed OH is due to a combination of both these mechanisms. We analysed haemodynamic parameters of 110 patients with OH and categorized them as arteriolar, venular, or mixed. Significant differences between the groups were found for the magnitude and time to reach nadir of the systolic blood pressure drop post-head-up tilt. The mixed OH category had the largest systolic blood pressure reduction (42.5, 31.9, 53.3 mmHg, P < 0.001) and the longest nadir time (18.6, 20, 30.7 s, P = 0.002). This is a practical classification tool and when validated physiologically, this system could be useful in directing treatment of OH.

On the Cardiovascular Effects of Whole‐Body Vibration Part II. Lateral Effects: Statistical Analysis

Lateral vibrations of vessels generate relative lateral motions between red blood cells and plasma. These relative motions would cause additional transport of longitudinal momentum between different layers and therefore would increase the viscosity. Particularly for arterioles, which play the major role for the total peripheral resistance (TPR), the lateral vibration would destroy the cell‐free plasma layer near the wall if the local lateral amplitude of vibration were larger than 40 μm. Thus, if the local vibration gets stronger, one would expect TPR to increase if the vessels were not dilated. In order to test the possible dilations of vessels, a special design was made as follows. Three male subjects participated in this study. Each of them carried out a series of vibration tests on each of three vibrating devices. Accelerations at three locations on the body and various cardiovascular parameters were measured simultaneously. Each vibration test was divided into two or three parts with different body modes in a way that each change of body mode would increase the transmissibility and the local amplitudes. For the majority of changes of body mode, a decrease instead of an increase of TPR was observed. Statistical analysis (ANOVA Within Within) confirmed that the observed reduction of TPR during the changes of body mode was significant (p= 0.0235). This gives indirect but clear evidences for the dilation of vessels, particularly the dilation of arterioles. Since the dilation of vessels, particularly of arterioles, is an important ability of human body to prevent the blood pressure from getting too high during strong exercises, competitions and heavy physical work, the present study suggests a potential benefit, among others, of vibration training to improve this ability.

Hypnosis Prevents the Cardiovascular Response to Cold Pressor Test

To highlight the effects of hypnotic focused analgesia (HFA), 20 healthy participants underwent a cold pressor test (CPT) in waking basal conditions (WBC) by keeping the right hand in icy water until tolerable (pain tolerance); subjective pain was quantified by visual scale immediately before extracting the hand from water. The test was then repeated while the participants were under hypnosis and underwent HFA suggestions. Cardiovascular parameters were continuously monitored. Pain tolerance was 121.5±96.1 sec in WBC and 411.0 ± 186.7 sec during HFA (p < 0.0001), and visual rating score 7.75 ± 2.29 and 2.45 ± 2.98 (p < 0.0001), respectively. CPT-induced increase of total peripheral resistance was non significant during HFA and +21% (p < 0.01) in WBC. HFA therefore reduced both perception and the reflex cardiovascular consequences of pain as well. This indicates that hypnotic analgesia implies a decrease of sensitivity and/or a block of transmission of painful stimuli, with depression of the nervous reflex arc.

Sympathetic activation in rats with L-NAME-induced hypertension

We evaluated the hemodynamic pattern and the contribution of the sympathetic nervous system in conscious and anesthetized (1.4 g/kg urethane, iv) Wistar rats with L-NAME-induced hypertension (20 mg/kg daily). The basal hemodynamic profile was similar for hypertensive animals, conscious (N = 12) or anesthetized (N = 12) treated with L-NAME for 2 or 7 days: increase of total peripheral resistance associated with a decrease of cardiac output (CO) compared to normotensive animals, conscious (N = 14) or anesthetized (N = 14). Sympathetic blockade with hexamethonium essentially caused a decrease in total peripheral resistance in hypertensive animals (conscious, 2 days: from (means +/- SEM) 2.47 +/- 0.08 to 2.14 +/- 0.07; conscious, 7 days: from 2.85 +/- 0.13 to 2.07 +/- 0.33; anesthetized, 2 days: from 3.00 +/- 0.09 to 1.83 +/- 0.25 and anesthetized, 7 days: from 3.56 +/- 0.11 to 1.53 +/- 0.10 mmHg mL-1 min-1) with no change in CO in either group. However, in the normotensive group a fall in CO (conscious: from 125 +/- 4.5 to 96 +/- 4; anesthetized: from 118 +/- 1.5 to 104 +/- 5.5 mL/min) was observed. The responses after hexamethonium were more prominent in the hypertensive anesthetized group. However, no difference was observed between conscious and anesthetized normotensive rats in response to sympathetic blockade. The present study shows that the vasoconstriction in response to L-NAME was mediated by the sympathetic drive. The sympathetic tone plays an important role in the initiation and maintenance of hypertension.

Sympathetic activation in rats with L-NAME-induced hypertension

We evaluated the hemodynamic pattern and the contribution of the sympathetic nervous system in conscious and anesthetized (1.4 g/kg urethane, iv) Wistar rats with L-NAME-induced hypertension (20 mg/kg daily). The basal hemodynamic profile was similar for hypertensive animals, conscious (N = 12) or anesthetized (N = 12) treated with L-NAME for 2 or 7 days: increase of total peripheral resistance associated with a decrease of cardiac output (CO) compared to normotensive animals, conscious (N = 14) or anesthetized (N = 14). Sympathetic blockade with hexamethonium essentially caused a decrease in total peripheral resistance in hypertensive animals (conscious, 2 days: from (means ± SEM) 2.47 ± 0.08 to 2.14 ± 0.07; conscious, 7 days: from 2.85 ± 0.13 to 2.07 ± 0.33; anesthetized, 2 days: from 3.00 ± 0.09 to 1.83 ± 0.25 and anesthetized, 7 days: from 3.56 ± 0.11 to 1.53 ± 0.10 mmHg mL-1 min-1) with no change in CO in either group. However, in the normotensive group a fall in CO (conscious: from 125 ± 4.5 to 96 ± 4; anesthetized: from 118 ± 1.5 to 104 ± 5.5 mL/min) was observed. The responses after hexamethonium were more prominent in the hypertensive anesthetized group. However, no difference was observed between conscious and anesthetized normotensive rats in response to sympathetic blockade. The present study shows that the vasoconstriction in response to L-NAME was mediated by the sympathetic drive. The sympathetic tone plays an important role in the initiation and maintenance of hypertension.

Antihypertensive Efficacy and Safety of Manidipine versus Amlodipine in Elderly Subjects with Isolated Systolic Hypertension

Isolated systolic hypertension (ISH) affects 10-20% of the elderly population and is strongly related to the risk of cardiovascular events. Elevated systolic BP values are primarily caused by reduced large vessel compliance with a consequent increase in total peripheral resistance. Vasodilating drugs, such as calcium channel antagonists, have proven to be effective in controlling ISH in elderly patients. This study set out to compare the antihypertensive efficacy and safety of two different calcium channel antagonists, manidipine and amlodipine, administered once daily in elderly subjects with ISH. In a European, randomised, double-blind, multicentre, parallel-group study, after a 2-week placebo run-in period, 195 patients aged >or=60 years with ISH received manidipine 10-20 mg once daily or amlodipine 5-10 mg once daily. Chlortalidone 25mg once daily could be added to the high dose of test drug in the event of insufficient antihypertensive control. The primary efficacy parameter was the proportion of patients with a reduction in office sitting systolic BP (SBP) >or=15 mm Hg, measured at trough, at the final visit. Secondary efficacy parameters included: the proportion of patients with a normal sitting SBP value (<140 mm Hg) at the final visit; a change from baseline to the final visit in mean office trough sitting SBP; a change from baseline to the final visit in the cardiovascular risk score as measured by the INDANA (INdividual Data ANalysis of Antihypertensive intervention trials) project score; the proportion of patients with at least a two-point reduction in the cardiovascular risk score; the percentage of patients requiring upward dose titration and diuretic add-on treatment and the investigator's final judgement. Safety and tolerability evaluations were based on adverse events, ECG and laboratory tests, and clinically relevant reports of abnormalities. In the intention-to-treat population (n = 189), 76% and 72% of patients in the manidipine and amlodipine groups, respectively, had a reduction in sitting SBP of >or=15 mm Hg (p-value not significant for between-group comparison). The percentage of patients with a normal sitting SBP value was 52% in the manidipine group and 51% in the amlodipine group (p-value not significant for between-group comparison). Sitting SBP reductions at the end of treatment were -19.5 +/- 11.8 mm Hg in patients receiving manidipine and -18.4 +/- 11.1 mm Hg in patients receiving amlodipine. Both treatments induced a small reduction in cardiovascular risk score, with 45% of patients in both treatment groups having a two-point reduction in the final score. At the final visit, approximately half of the patients in both treatment groups were still being treated with the low dose of one of the test drugs (manidipine 10mg or amlodipine 5mg). Chlortalidone was added to the high dose of test drugs in 7% and 11% of patients in the amlodipine and manidipine groups, respectively. Both drugs were well tolerated, with a higher incidence of oedema in the amlodipine group (9% vs 4%). No clinically relevant changes in heart rate were induced by either treatment. In elderly patients with ISH, treatment with manidipine for 12 weeks was well tolerated and effective and the antihypertensive effects obtained with manidipine were the same as those obtained with amlodipine.

Comparison of Stress Responses between Mental Tasks and White Noise Exposure

The purpose of this study was to compare the cardiovascular responses to different types of mental stress. Ten healthy males performed a mental arithmetic task (MA) on one day and were exposed to white noise (WN, 80dB) on another day. Both the MA and the WN were composed of four 5-min consecutive periods with a 3-min rest between them. On each day, the systolic and diastolic blood pressure (SBP and DBP), mean arterial pressure (MAP), cardiac output (CO), and total peripheral resistance (TPR) were measured continually during the entire experimental period. The changes from the baseline (Delta) in all periods were calculated for both mental stresses. As for the results, the DeltaMAP, DeltaCO, DeltaHR, and DeltaTPR in the MA did not significantly change during the task periods. However, in the WN, the DeltaMAP and DeltaTPR showed significant increases over the time of the consecutive periods. In addition, we discuss the response patterns for the two mental stresses. We examine three hemodynamic reactivity patterns: a cardiac pattern characterized by increased CO and decreased TPR, a mixed pattern characterized by a moderate increase in both CO and TPR, and a vascular pattern characterized by increased TPR and decreased CO. The results show that throughout all task/exposure periods, the response pattern remained the same for six subjects in each stress. Furthermore, of these six subjects, half showed the same response pattern in both the MA and the WN. In conclusion, compared to the MA task, consecutive WN exposure showed an accumulation of stress responses. A change in TPR contributed to a gradual increase in MAP in the WN. It is also possible that among the subjects there were different types of response to the MA and WN.

Orthostatic Hypotension and Autonomic Pathways after Spinal Cord Injury

Individuals with spinal cord injury (SCI) are prone to orthostatic hypotension (OH). We aimed to develop a simple bedside test to evaluate autonomic control following chronic SCI, and to identify those most at risk of OH and cardiovascular dysfunction. We studied 14 subjects with cervical SCI, 11 with thoracic SCI, and 17 able-bodied controls. We continuously recorded heart rate (HR; ECG) and beat-to-beat systolic (SAP), diastolic (DAP) and mean (MAP) arterial pressures (Finometer) while supine, and following the passive assumption of an upright seated position. Stroke volume (SV), cardiac output (CO), and total peripheral resistance (TPR) were calculated. Plasma catecholamines were determined. Motor and sensory loss was assessed using the American Spinal Injury Association (ASIA) impairment scale. Autonomic pathways were assessed from sympathetic skin responses (SSR). Cervical SCI subjects had lower supine HR, SAP, and noradrenaline levels than thoracic SCI and controls (p < 0.05), and lower DAP and MAP than controls (p < 0.05). When upright, HR increased in all groups (p < 0.05); SAP, DAP, and MAP increased (p < 0.01) in thoracic SCI and controls, but not in cervical SCI. Cervical SCI had larger postural falls in SV (p < 0.05) and CO, with smaller increases in TPR than the other two groups. Upright catecholamine levels were lower in cervical SCI (p < 0.05) than thoracic SCI and controls. Completeness of SCI assessed by ASIA scale did not necessarily correlate with autonomic completeness assessed by SSR. Cardiovascular control during orthostasis was impaired and OH was common in cervical SCI, but not thoracic SCI. SSR may identify those at greatest risk of orthostatic hypotension and impaired cardiovascular control. We advocate that assessments of autonomic function be included in the neurological evaluation of SCI, in addition to the ASIA assessment.

Proteasomal Regulation of Cardiac Hypertrophy

Left ventricular hypertrophy (LVH) is a common adaptive response of the heart to the increased workload associated with hypertension.1 Essential hypertension is characterized by an increase in total peripheral resistance.2 Mechanical modeling of the cardiovascular system suggests that a necessary consequence of increased downstream resistance to flow is increased pressure to maintain end organ perfusion. Energetically, increased pressure generation requires greater work to be performed by the existing cardiac mass or an increase in cardiac mass to normalize workload per unit of mass. The result of LVH is to normalize wall tension and workload. According to the law of Laplace, increased wall tension is induced by the increased pressure and may also be induced by an increase in the fluid-containing volume of the left ventricle because of the partially elastic expansion of the ventricle under greater pressure loads.3 Without hypertrophy, increased workload by the existing cardiac mass would require greater perfusion of the myocardium or decreased cardiac reserve. Increased wall tension has the potential to decrease myocardial compliance, thereby limiting myocardial perfusion. In this scenario, it is not surprising that inhibition of cardiac hypertrophy in response to increased peripheral resistance is detrimental. Indeed, Meguro et al4 found that inhibition of LVH due to pressure overload in mice resulted in an increase in death due to heart failure. Inhibition of postinfarction cardiac hypertrophy has also been shown to cause left ventricular dilation and diminishment of cardiac function.5 This topic is well reviewed by Morisco et al.6 Article p 1821 Empirical evidence is beginning to mount, however, that indicates cardiac hypertrophy may be maladaptive. LVH in the human population is poorly explained by blood pressure alone. Ambulatory blood pressure appears to be a better predictor of the …

Cardiovascular responses to oxygen inhalation after hemorrhage in anesthetized rats: hyperoxic vasoconstriction

Oxygen inhalation is recommended for the initial care of trauma victims. The improved survival seen in early hemorrhage is normally associated with an increase in blood pressure. Although clinical use of oxygen can occur late after hemorrhage, the effects of late administration have not been specifically examined. Anesthetized rats were studied using an isobaric hemorrhage model with target pressures of either 70 or 40 mmHg. At various times after hemorrhage, the feedback control of the blood pressure was stopped and the inspired gas was changed from room air to 100% oxygen. The results show that shortly after hemorrhage to 70 mmHg, oxygen inhalation results in an increase in mean arterial blood pressure of 60 +/- 3 mmHg, which is associated with a large increase in total peripheral resistance from 0.89 +/- 0.05 to 1.25 +/- 0.1 peripheral resistance units. The blood pressure response is essentially unchanged with time, and it is not altered by a 10-min exposure to N(G)-nitro-l-arginine methyl ester. At a target pressure of 40 mmHg, the initial blood pressure response to oxygen is the same, but it gradually decreases as the animal develops a lactic acidosis. We conclude that the therapeutic value of oxygen needs to be separately evaluated for late hemorrhage.

Increased impedance to inspiration ameliorates hemodynamic changes associated with movement to upright posture in orthostatic hypotension: A randomized blinded pilot study

Movement to upright posture may result in marked drop of blood pressure with susceptibility to injury from syncope and falls in patients with orthostatic hypotension. The purpose of this study was to determine if increasing negative intrathoracic pressure by using an inspiratory impedance threshold device before change of posture diminishes blood pressure fall by enhancing venous return. Eighteen healthy subjects and 22 orthostatic hypotension patients were randomized to either an active (impedance 7 cmH2O) or sham (no inspiratory impedance) impedance threshold device. Arterial blood pressure, heart rate, and estimated stroke volume and total peripheral resistance were recorded in the supine and upright postures using a noninvasive finger arterial blood pressure monitor. After a rest period, the alternate impedance threshold device (sham or active) was tested in each individual. Compared with the sham impedance threshold device test, the active impedance threshold device resulted in significant reduction in the magnitude of upright posture-induced fall in blood pressure and a greater increase of total peripheral resistance after standing in both healthy subjects and orthostatic hypotension patients. Stroke volume was not measurably altered. Among all subjects who exhibited a postural blood pressure drop >10 mmHg on the day of study, active impedance threshold device treatment consistently blunted blood pressure fall during the initial 100 seconds after standing (<0.04). Induced orthostatic symptoms were less severe with the active impedance threshold device both at onset of upright posture and during 30 seconds of standing. Enhancing impedance to inspiration may prove useful as adjunctive therapy for diminishing symptoms associated with movement to upright posture in individuals with orthostatic hypotension.

Changes in regional blood volume and blood flow during static handgrip

Increased blood pressure (BP) and heart rate during exercise characterizes the exercise pressor reflex. When evoked by static handgrip, mechanoreceptors and metaboreceptors produce regional changes in blood volume and blood flow, which are incompletely characterized in humans. We studied 16 healthy subjects aged 20-27 yr using segmental impedance plethysmography validated against dye dilution and venous occlusion plethysmography to noninvasively measure changes in regional blood volumes and blood flows. Static handgrip while in supine position was performed for 2 min without postexercise ischemia. Measurements of heart rate and BP variability and coherence analyses were used to examine baroreflex-mediated autonomic effects. During handgrip exercise, systolic BP increased from 120 +/- 10 to 148 +/- 14 mmHg, whereas heart rate increased from 60 +/- 8 to 82 +/- 12 beats/min. Heart rate variability decreased, whereas BP variability increased, and transfer function amplitude was reduced from 18 +/- 2 to 8 +/- 2 ms/mmHg at low frequencies of approximately 0.1 Hz. This was associated with marked reduction of coherence between BP and heart rate (from 0.76 +/- 0.10 to 0.26 +/- 0.05) indicative of uncoupling of heart rate regulation by the baroreflex. Cardiac output increased by approximately 18% with a 4.5% increase in central blood volume and an 8.5% increase in total peripheral resistance, suggesting increased cardiac preload and contractility. Splanchnic blood volume decreased reciprocally with smaller decreases in pelvic and leg volumes, increased splanchnic, pelvic and calf peripheral resistance, and evidence for splanchnic venoconstriction. We conclude that the exercise pressor reflex is associated with reduced baroreflex cardiovagal regulation and driven by increased cardiac output related to enhanced preload, cardiac contractility, and splanchnic blood mobilization.

The venous system is the main determinant of hypotension in patients with vasovagal syncope

In patients with vasovagal syncope (VVS), a neural reflex appears the main determinant of hypotension leading to loss of consciousness; whether hypotension is mainly due to involvement of the arterial system or the venous system remains a debated issue. The aim of the present study was to assess which of these two systems is responsible for the fall in blood pressure (BP) in patients with VVS; to this end, a haemodynamic study was carried out not only before and during loss of consciousness but also during the recovery phase. Beat-to-beat recordings of heart rate (HR), BP (volume-clamp method) and stroke volume (SV) (modelflow method), cardiac output (CO), and total peripheral resistance (TPR) were made at rest, during unmedicated tilt testing (TT) and recovery from loss of consciousness in 18 patients with a history of syncope (age 45+/-23 years) and positive response to TT. Blood pressure showed a significant fall during prodromal symptoms and a further fall at the beginning of loss of consciousness, together with a fall in SV, CO, and HR, and a slight, but significant, increase in TPR. At the beginning of recovery, BP showed a significant increase and a further increase 5 min later, together with an increase in SV, CO, and HR without significant changes in TPR. These results suggest that in VVS the fall in BP is mainly caused by reduced venous return to the heart. The arterial system does not appear to be the main determinant of the fall of BP; however, the system appears unable to make the appropriate compensatory changes.

WISE‐2005: Drug‐induced changes in compliance affect model flow calculation of stroke volume

Model flow (MF) estimates of cardiac stroke volume (SV) from the finger pressure wave form (Finometer) have been compared to SV estimates from pulsed Doppler ultrasound (DU) of the ascending aorta. Data were collected at rest and during the administration of 0.005 and 0.01 ug/kg/min isoproterenol (Iso), 10 and 50 ng/kg/min norepinephrine (NE) by intravenous infusion, and 0.3 mg nitroglycerin (NG) by sublingual spray. Data are from 12 women participating in the WISE bed rest study in the pre-bed rest condition. There was no significant difference between SV recorded with DU (68.3±10.2 ml, mean±SD) and MF (70.7±11.5 ml) at baseline (p=0.22). However, estimates of SV differed (p<0.01) between DU and MF during 0.01 ug/kg/min Iso (DU +57±20%, MF +21±21%), 50 ng/kg/min NE (DU −14±12%, MF +7±7%), and NG (DU +7±12 %, MF −8±11%). The model flow method uses assumed values for aortic compliance and peripheral vascular resistance. In this investigation total peripheral resistance (TPR) was significantly increased from baseline (1.3 PRU) during 50 ng/kg/min NE (1.7 PRU, p<0.01) and reduced during 0.01 ug/kg/min Iso (0.6 PRU, p<0.01) and 0.3 mg NG (1.1 PRU, p=0.04). Hence, with reduced TPR MF underestimated SV while an increase in TPR resulted in an overestimation. We have shown that SV values determined by MF should be interpreted with caution when measured during drug administration. Supported by Canadian Space Agency, NASA, ESA, CNES