Effect of Carotid Sinus Stimulation on Cardiac Output and Peripheral Vascular Resistance during Changes in Blood Volume Distribution in Man

In ten healthy subjects (mean age 29.6 years) the hemodynamic response to carotid sinus stimulation (neck suction - 40 mmHg) was studied under control conditions and during peripheral pooling of blood (lower body negative pressure). Heart rate, arterial and central venous pressure, cardiac output and forearm blood flow were measured. The time sequence of the heart rate response was studied separately in six healthy subjects. During control conditions, carotid sinus stimulation induced a significant decrease in arterial pressure and heart rate. The blood pressure decrease mainly reflected a reduction in cardiac output, total peripheral vascular resistance being essentially unchanged. However, in the skeletal muscle, represented by a forearm segment, vascular resistance decreased significantly. During lower body negative pressure (LBNP) the same stimulation of the carotid sinus induced a significantly greater fall in mean arterial pressure even though the reduction in cardiac output was slightly smaller on the average than in the control condition. The heart rate increased, probably secondary to a time dependent increase in heart rate elicited by the continuous LBNP stimulus. Total peripheral vascular resistance decreased significantly during LBNP, the reaction likewise differing significantly from that in the control condition. Thus the augmented blood pressure response was due to a more pronounced vasodilatation when the carotid sinus was stimulated during lower body negative pressure. The results indicate that the hemodynamic changes elicited by carotid sinus stimulation are modified by changes in the distribution of blood volume and in the tone of resistance vessels.     

Cardiovascular Responses to Changes in Carotid Sinus Transmural Pressure in Man

To study the relative importance of cardiac and peripheral effector mechanisms in the carotid sinus baroreflex in man cardiovascular responses to equal changes of the carotid sinus transmural pressure (Ptm) in either direction of the normal were recorded and compared in eight physically well-trained young male volunteers. In both the supine and the 70d? head-up position, a decrease in Ptm produced a more potent reflex response of the systemic arterial pressure than did a similar increase in Ptm. Whereas the arterial pressure response to increased Ptm was due solely to a reduction in vascular resistance, a significant increase in cardiac output contributed to the more potent pressor response to a decrease in Ptm and thus to the predominantly antihypotensive properties that characterize the carotid sinus baroreceptor control system in man. However, since combined beta-adrenergic and parasympathetic blockade abolished the effect of reduced Ptm on cardiac output without greatly impairing the blood pressure response, it is concluded that adjustments in cardiac output are not of critical importance in the buffering function of the carotid sinus baroreceptors. Autonomic cardiac blockade exaggerated the fall in cardiac output on head-up tilt, the arterial pressure remaining unaffected due to a compensatory increase in systemic vascular resistance.     

Extent of Engagement of Various Cardiovascular Effectors to Alterations of Carotid Sinus Pressure

Reflex adjustments of blood pressure, heart rate, skeletal muscle and renal resistance vessels to changes in intrasinusal pressure were recorded and the respective sinus pressure—reflex response curves plotted. In this way one could evaluate whether the various individual reflex arcs, which together constitute the baroreceptor reflex control of the circulation, display “threshold” response and maximal sensitivities, respectively, at identical sinus pressures.—The curves describing the blood pressure, muscle and renal resistance vessel responses were found to follow identical courses, while the heart rate response curve was displaced to the right of the others. This discrepancy is, however, in all probability a mere consequence of the peculiar neuro-effector characteristics in the heart. The individual components of the baroreceptor reflex, therefore seem to be recruited simultaneously when the sinus pressure is increased, and there is thus nothing to indicate that afferents from low and high “threshold” baroreceptors, respectively, are preferentially distributed to different neuron pools in the bulbar cardiovascular centres.—A displacement of the response curves to the right was observed when a) non-pulsating sinus pressures were used instead of pulsating, b) sinus pressures alterations were induced by lowering the pressure from higher levels instead of elevating it, c) arterial PCO₂ was increased.     

Blood Pressure and Heart Rate Regulating Capacity of the Carotid Sinus during Changes in Blood Volume Distribution in Man

The influence of changes in blood volume distribution on the carotid baroreflex was studied in 18 subjects. Blood volume distribution was changed by varying the pressure around the lower body above and below ambient, thereby varying the amount of blood pooled in this region and exerting a secondary influence on the central blood volume. The carotid arterial stretch receptors were stimulated by varying the pressure in an air-tight box enclosing the neck. To obtain a standardized carotid sinus stimulus (SCS) the pressure in the box was varied sinusoidally between -10 and ? 40 mmHg with a fixed frequency of 0.03 Hz. The effects on heart rate and blood pressure were assessed by harmonic analysis performed off-line on a digital computer. During lower body negative pressure of –40 mmHg (LBNP - 40), i.e. during a procedure known to reduce the central blood volume, SCS induced an augmented effect on the blood pressure regulating capacity but not on the heart rate response. Expressing the blood pressure regulating capacity as peak-to-peak changes in systolic arterial pressure, the response during LBNP 40 mmHg was almost twice the control value. The opposite stimulus–lower body positive pressure–influenced the SCS-induced effects only slightly but on the average a minor reduction in both blood pressure and heart rate regulating capacity was found compared with the control condition, though the difference did not reach significant levels. The results support the hypothesis that changes in blood volume distribution modify the function of the carotid baroreflex, possibly via intrathoracic receptors sensitive to changes in central blood volume and/or central venous pressure.     

Intra-Arterial Blood Pressure Response in Hypertensive Subjects during Low- and High-Intensity Resistance Exercise

OBJECTIVE:

The aim of this study was to describe blood pressure responses during resistance exercise in hypertensive subjects and to determine whether an exercise protocol alters these responses.

INTRODUCTION:

Resistance exercise has been recommended as a complement for aerobic exercise for hypertensive patients. However, blood pressure changes during this kind of exercise have been poorly investigated in hypertensives, despite multiple studies of normotensives demonstrating significant increases in blood pressure.

METHODS:

Ten hypertensive and ten normotensive subjects performed, in random order, two different exercise protocols, composed by three sets of the knee extension exercise conducted to exhaustion: 40% of the 1-repetition maximum (1RM) with a 45-s rest between sets, and 80% of 1RM with a 90-s rest between sets. Radial intra-arterial blood pressure was measured before and throughout each protocol.

RESULTS:

Compared with normotensives, hypertensives displayed greater increases in systolic BP during exercise at 80% (+80±3 vs. +62±2 mmHg, P<0.05) and at 40% of 1RM (+75±3 vs. +67±3 mmHg, P<0.05). In both exercise protocols, systolic blood pressure returned to baseline during the rest periods between sets in the normotensives; however, in the hypertensives, BP remained slightly elevated at 40% of 1RM. During rest periods, diastolic blood pressure returned to baseline in hypertensives and dropped below baseline in normotensives.

CONCLUSION:

Resistance exercise increased systolic blood pressure considerably more in hypertensives than in normotensives, and this increase was greater when lower-intensity exercise was performed to the point of exhaustion.     

Attention and Vigilance: Performance and Skin Conductance Response Changes

The skin conductance response component of the orienting reflex was used to measure changes in attention during vigilance performance in order to test several hypotheses which have related aspects of vigilance performance to the occurrence and habituation of orienting or observing responses. Subjects detected irregularly presented visual signals among similar visual events during two 30-min tasks. Skin conductance responses were analyzed in epochs of time immediately preceding and following signals and in nonsignal-related time epochs. Magnitudes of skin conductance responses declined in both signal-related epochs (pre and post), but this decrement was correlated with performance changes only in the post-signal epoch. There was no decrement in SCR magnitudes during the nonsignal-related epochs. Skin conductance response magnitudes were significantly larger both before and after detected signals compared to misses. The data support the hypothesis that changes in vigilance performance over time are related to habituation of the orienting reflex evoked by signals. They also suggest that attentional processes preceding signals are related to successful detections.     

The Respiratory Response to Carbon Dioxide in Humans with Unilateral and Bilateral Resections of the Carotid Bodies

The acute hypercapnic ventilatory response (AHCVR) arises from both peripheral and central chemoreflexes. In humans, one technique for identifying the separate contributions of these chemoreflexes to AHCVR has been to associate the rapid component of AHCVR with the peripheral chemoreflex and the slow component with the central chemoreflex. Our first aim was to validate this technique further by determining whether a single slow component was sufficient to describe AHCVR in patients with bilateral carotid body resections (BR) for glomus cell tumours. Our second aim was to determine whether the slow component of AHCVR was diminished following carotid body resection as has been suggested by studies in experimental animals. Seven BR subjects were studied together with seven subjects with unilateral resections (UR) and seven healthy controls. A multifrequency binary sequence in end-tidal P _CO2 was employed to stimulate ventilation dynamically under conditions of both euoxia and mild hypoxia. Both two- and one-compartment models of AHCVR were fitted to the data. For BR subjects, the two-compartment model fitted significantly better on 1 out of 13 occasions compared with 22 out of 28 occasions for the other subjects. Average values for the chemoreflex sensitivity of the slow component of AHCVR differed significantly (   P < 0.05  ) between the groups and were 0.95, 1.38 and 1.50 l min⁻¹ Torr⁻¹ for BR, UR and control subjects, respectively. We conclude that, without the peripheral chemoreflex, AHCVR is adequately described by a single slow component and that BR subjects have sensitivities for the slow component that are lower than those of control subjects.     

Rate-dependent Myogenic Response of Vascular Smooth Muscle during Imposed Changes in Length and Force

A recent study of electrical and mechanical responses to stretch in isolated vascular smooth muscle revealed a clear-cut and graded influence of the rate of change in length, dL/dt (Johansson and Mellander, 1975). This myogenic “dynamic” response at high rates of stretch was much more pronounced than the “static” response to constant, increased (+ 40%) length. In this previous study the mechanical responses were recorded as active force. In view of the fact that myogenic reactions in vivo must be associated with changes in vessel caliber, it was considered of interest to investigate the responses to stretch also in smooth muscle undergoing active shortening. In the present study, as in the one referred to above, electrical and mechanical activity in the isolated rat portal vein was studied by the sucrose gap method. However, in the present experiments the mechanical responses were recorded not only as active force but also as active shortening, making possible a comparison of the myogenic responses under these two types of smooth muscle contraction. Dynamic passive stretch was found to be associated with marked increases in spike discharge and mechanical activity under both these experimental conditions and the quantitative relation between spike discharge and rate of passive stretch (or shortening) was similar. Thus, active shortening of the smooth muscle did not interfere with the ability of the vessel to respond myogenically to passive stretch. A further analysis of the results suggested that, for the preparations as a whole, the dynamic excitatory response was more closely related to the rate of change of passive force, dP/dt, than to dL/dt.     

Leptospiral Proteins Recognized during the Humoral Immune Response to Leptospirosis in Humans

Leptospirosis is an emerging zoonosis caused by pathogenic spirochetes belonging to the genus Leptospira. An understanding of leptospiral protein expression regulation is needed to develop new immunoprotective and serodiagnostic strategies. We used the humoral immune response during human leptospirosis as a reporter of protein antigens expressed during infection. Qualitative and quantitative immunoblot analysis was performed using sera from 105 patients from Brazil and Barbados. Sera from patients with other diseases and healthy individuals were evaluated as controls. Seven proteins, p76, p62, p48, p45, p41, p37, and p32, were identified as targets of the humoral response during natural infection. In both acute and convalescent phases of illness, antibodies to lipopolysaccharide were predominantly immunoglobulin M (IgM) while antibodies to proteins were exclusively IgG. Anti-p32 reactivity had the greatest sensitivity and specificity: positive reactions were observed in 37 and 84% of acute- and convalescent-phase sera, respectively, while only 5% of community control individuals demonstrated positive reactions. Six immunodominant antigens were expressed by all pathogenic leptospiral strains tested; only p37 was inconsistently expressed. Two-dimensional immunoblots identified four of the seven infection-associated antigens as being previously characterized proteins: LipL32 (the major outer membrane lipoprotein), LipL41 (a surface-exposed outer membrane lipoprotein), and heat shock proteins GroEL and DnaK. Fractionation studies demonstrated LipL32 and LipL41 reactivity in the outer membrane fraction and GroEL and DnaK in the cytoplasmic fraction, while p37 appeared to be a soluble periplasmic protein. Most of the other immunodominant proteins, including p48 and p45, were localized to the inner membrane. These findings indicate that leptospiral proteins recognized during natural infection are potentially useful for serodiagnosis and may serve as targets for vaccine design.     

Secretory Immune Response to Membrane Antigens during Giardia lamblia Infection in Humans

The secretory immune response in humans infected with Giardia lamblia was studied by using saliva samples and a membrane-rich protein fraction. The membrane fraction, studied by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, showed 24 antigen bands, ranging from 170 to 14 kDa. Saliva samples from giardiasis patients showed a heterogeneous response against the membrane fraction when they were assayed by immunoblotting. Among the antigens recognized by patient saliva samples, those of 170, 105, 92, 66, 32, 29, and 14 kDa stood out. These antigens were not recognized by saliva samples from healthy individuals. They may be of importance in future studies of protection from or diagnosis of G. lamblia infections.     

Denervation of Carotid Baro- and Chemoreceptors in Humans

Experimental denervation in animals has shown that carotid baro- and chemoreceptors play an eminent role in maintaining blood pressure and blood gas homeostasis. Denervation of carotid sinus baro- and chemoreceptors in humans may occur as a complication of invasive interventions on the neck or after experimental surgical treatment in asthma. In this topical review, the short- and long-term effects of carotid baro- and chemoreceptor denervation on the control of circulation and ventilation in humans are discussed. Carotid baroreceptor denervation in humans causes a persistent decrease in vagal and sympathetic baroreflex sensitivity and an increase in blood pressure variability; however, carotid denervation does not lead to chronic hypertension. Therefore, although carotid baroreceptors contribute to short-term blood pressure control, other receptors are able to maintain normal chronic blood pressure levels in the absence of carotid baroreceptors. Conversely, carotid chemoreceptor denervation leads to permanent abolition of normocapnic ventilatory responses to hypoxia and reduced ventilatory responses to hypercapnia.     

Acute Inflammatory Response to Endotoxin in Mice and Humans

Endotoxin injection has been widely used to study the acute inflammatory response. In this study, we directly compared the inflammatory responses to endotoxin in mice and humans. Escherichia coli type O113 endotoxin was prepared under identical conditions, verified to be of equal biological potency, and used for both mice and humans. The dose of endotoxin needed to induce an interleukin-6 (IL-6) concentration in plasma of ~1,000 pg/ml 2 h after injection was 2 ng/kg of body weight in humans and 500 ng/kg in mice. Healthy adult volunteers were injected intravenously with endotoxin, and male C57BL/6 mice (n = 4 to 12) were injected intraperitoneally with endotoxin. Physiological, hematological, and cytokine responses were determined. Endotoxin induced a rapid physiological response in humans (fever, tachycardia, and slight hypotension) but not in mice. Both mice and humans exhibited lymphopenia with a nadir at 4 h and recovery by 24 h. The levels of tumor necrosis factor (TNF) and IL-6 in plasma peaked at 2 h and returned to baseline levels by 4 to 6 h. IL-1 receptor antagonist RA and TNF soluble receptor I were upregulated in both mice and humans but were upregulated more strongly in humans. Mice produced greater levels of CXC chemokines, and both mice and humans exhibited peak production at 2 h. These studies demonstrate that although differences exist and a higher endotoxin challenge is necessary in mice, there are several similarities in the inflammatory response to endotoxin in mice and humans.     

颈总动脉末段、颈动脉窦处动脉粥样硬化和血栓的研究现状

目的：探讨颈动脉末段、颈动脉窦处的粥样硬化和血栓的研究现状。方法：系统回顾近年来对颈动脉粥样硬化病变的研究,在诱因及病因、危害、诊治几个方面作分析讨论。结果：颈动脉粥样硬化的发生、发展受血流动力学、血管病变、血液成份三个因素影响;病因与自身生活饮食习惯、多种疾病密切相关;颈动脉粥样硬化、血栓可引起脑缺血、脑卒中等严重损害;诊断一般采用影像学技术,治疗方法有药物及手术两种。结论：颈动脉粥样硬化及血栓可引起脑缺血、脑中卒等脑血管疾病,应尽可能采取早期预防、早期诊断,以避免脑血管疾病的发生。     

Effect of BMI on the Thermogenic Response to Cold Exposure and Associated Changes in Metabolism and Browning Markers in Adult Humans

IntroductionBrown adipose tissue (BAT) serves to produce heat by nonshivering thermogenesis. Activation of BAT increases energy expenditure and is seen as a putative strategy to treat obesity. There are conflicting data on the capacity for cold-induced thermogenesis in individuals with higher BMI.MethodsTo investigate the effect of BMI on cold-induced stimulation of energy expenditure, changes in the metabolic profile, and the expression of browning markers in subcutaneous white adipose tissue (scWAT), healthy adults (N = 173, 50.9% females) with a median age of 26.0 (interquartile range [IQR]: 23.0; 28.0) years and a median body mass index (BMI) of 23.6 [IQR: 21.9; 26.6] kg/m² were exposed to short-term mild cold exposure (CE). Resting energy expenditure (REE) was measured by indirect calorimetry and blood sampling was conducted at baseline and after CE. In a subgroup of participants with obesity, subcutaneous abdominal fat biopsies were taken before and after CE.ResultsThe cold-induced median increase in REE was 74 (IQR: −28; 241) kcal/day (p < 0.001). This increase negatively correlated with BMI (p < 0.001). Participants with BMI 18.5–24.9 kg/m² displayed a significant median increase of 103 kcal/day (p < 0.001), participants with overweight or obesity were not able to increase REE (23, p = 0.468 or −30 kcal/day, p = 0.917, respectively). In participants with obesity, expression of cell death activator in scWAT after CE was upregulated in females (p = 0.034).ConclusionsPersons with overweight and obesity do not increase REE in response to CE, presumably reflecting lower BAT activity. Likewise, the metabolic response to cold is diminished in participants with elevated BMI.     

Influence of Changes in Intrathoracic and Central Venous Pressure on Cardiac Filling Dynamics

Changes in the ratio between intrathoracic and central venous pressure were studied in narcotized cats under conditions of constant positive or negative pressure ventilation. Transformation of elastic characteristics in the respiratory system caused by changes in intrathoracic pressure led to inversion of the ratio between transpulmonary intrathoracic and central venous pressure determining right atrial filling pressure.