Dynamic time course of hemodynamic responses after passive head-up tilt and tilt back to supine position.

Mechanisms involved in the control of arterial pressure during postural changes were studied by analysis of the dynamic time course of cardiovascular changes during head-up tilt (HUT) and tilt back to supine position (TB). Beat-to-beat values of cardiovascular variables were recorded continuously before, during, and after passive HUT to 30 degrees in seven healthy humans. Left cardiac stroke volume (SV, Doppler ultrasound), mean arterial blood pressure (MAP), heart rate (HR), cardiac output (CO), and total peripheral conductance (TPC) were recorded. During HUT, MAP at the level of the carotid baroreceptors decreased by approximately 5 mmHg. There was a striking asymmetry between the time courses of cardiovascular changes on HUT and on TB. Adjustments generally took up to 30 s after HUT, whereas most changes were completed during the first 10 s after TB. Cardiovascular reflex adjustments of HR and TPC were more symmetrical. After HUT, SV was maintained during the first 4-6 s and then decreased steadily during the next 30 s to a stable level approximately 25% below its pretilt value. However, after TB, SV increased rapidly to its pretilt value in <10 s. This asymmetry in SV dynamics may be explained in part by a more rapid change in left cardiac filling after TB than after HUT. On TB, there must be a rapid inflow of stagnant blood from the legs, whereas venous valves will impede backward filling of veins in the lower body on HUT. In conclusion, we have revealed a characteristic asymmetry in cardiovascular responses to inverse variations in gravity forces in humans. This asymmetry can be explained in part by nonlinear, hydrodynamic factors, such as the one-way effect of venous valves in the lower part of the body.     

Balancing tissue perfusion demands: cardiovascular dynamics of Cancer magister during exposure to low salinity and hypoxia

Decapod crustaceans inhabit aquatic environments that are frequently subjected to changes in salinity and oxygen content. The physiological responses of decapod crustaceans to either salinity or hypoxia are well documented; however, there are many fewer reports on the physiological responses during exposure to these parameters in combination. We investigated the effects of simultaneous and sequential combinations of low salinity and hypoxia on the cardiovascular physiology of the Dungeness crab, Cancer magister. Heart rate, as well as haemolymph flow rates through the anterolateral, hepatic, sternal and posterior arteries were measured using a pulsed-Doppler flowmeter. Summation of flows allowed calculation of cardiac output and division of this by heart rate yielded stroke volume. When hypoxia and low salinity were encountered simultaneously, the observed changes in cardiac properties tended to be a mix of both factors. Hypoxia caused a bradycardia, whereas exposure to low salinity was associated with a tachycardia. However, the hypoxic conditions had the dominant effect on heart rate. Although hypoxia caused an increase in stroke volume of the heart, the low salinity had a more pronounced effect, causing an overall decrease in stroke volume. The patterns of haemolymph flow through the arterial system also varied when hypoxia and low salinity were offered together. The resulting responses were a mix of those resulting from exposure to either parameter alone. When low salinity and hypoxia were offered sequentially, the parameter experienced first tended to have the dominant effect on cardiac function and haemolymph flows. Low salinity exposure was associated with an increase in heart rate, a decrease in stroke volume and cardiac output, and a concomitant decrease in haemolymph flow rates. Subsequent exposure to hypoxic conditions caused a slight decrease in rate, but other cardiovascular variables were largely unaffected. In contrast, when low salinity followed acclimation to hypoxic conditions, apart from an increased heart rate, there were no other cardiovascular changes associated with the low salinity episode. The implications of these changes in cardiovascular dynamics are discussed in relation to physiological mechanisms and the ecology of decapod crustaceans, in hypoxic or low salinity environments.     

Development of the adrenergic innervation in the myocardium and coronary arteries of the dog

The development of the adrenergic cardiac innervation was studied in premature dog fetuses, puppies and adult dogs by means of the formalin-induced fluorescence technique. A point-counting technique was used to evaluate the density of innervation. Two types of fluorescent profiles can be observed in the heart during development: (1) sprouting axons, and (2) beaded terminals. The axonal fluorescence disappears in adult neurons. A different morphology and a different time course of development enable to study separately the innervation of the myocardium (cardiomotor innervation) and that of the vessels (vasomotor innervation). The late prenatal innervation is very poor (0.1 hit). The first but very scant cardiomotor terminals appear in this period. A mature cardiomotor innervation is found in 4-month-old puppies [1.5 +/- 0.3 (SD) hits]. The vasomotor innervation is shifted to the right. The development of beaded vascular terminals begins and matures 1-2 weeks later. The growing fluorescent axons reveal that the myocardium is supplied by axons of the cardiac plexus and of the perivascular nerves; the vascular wall, on the other hand, is supplied by the perivascular nerves only. The developmental, spatial and morphological differences in innervation suggest that two different types of neurons exist in the sympathetic ganglia: (1) neurons innervating the vessels (coronaromotor neurons), and (2) neurons innervating the myocardium (cardiomotor neurons).     

Development of cardiac form and function in ectothermic sauropsids

Evolutionary morphologists and physiologists have long recognized the phylogenetic significance of the ectothermic sauropsids. Sauropids have been classically considered to bridge between early tetrapods, ectotherms, and the evolution of endotherms. This transition has been associated with many modifications in cardiovascular form and function, which have changed dramatically during the course of vertebrate evolution. Most cardiovascular studies have focused upon adults, leaving the development of this critical system largely unexplored. In this essay, we attempt a synthesis of sauropsid cardiovascular development based on the limited literature and indicate fertile regions for future studies. Early morphological cardiovascular development, i.e., the basic formation of the tube heart and the major pulmonary and systemic vessels, is similar across tetrapods. Subsequent cardiac chamber development, however, varies considerably between developing chelonians, squamates, crocodilians, and birds, reflected in the diversity of adult ventricular structure across these taxa. The details of how these differences in morphology develop, including the molecular regulation of cardiac and vascular growth and differentiation, are still poorly understood. In terms of the functional maturation of the cardiovascular system, reflected in physiological mechanisms for regulating heart rate and cardiac output, recent work has illustrated that changes during ontogeny in parameters such as heart rate and arterial blood pressure are somewhat species‐dependent. However, there are commonalities, such as a β‐adrenergic receptor tone on the embryonic heart appearing prior to 60% of development. Differential gross morphological responses to environmental stressors (oxygen, hydration, temperature) have been investigated interspecifically, revealing that cardiac development is relatively plastic, especially, with respect to change in heart growth. Collectively, the data assembled here reflects the current limited morphological and physiological understanding of cardiovascular development in sauropsids and identifies key areas for future studies of this diverse vertebrate lineage. J. Morphol., 2009. © 2009 Wiley‐Liss, Inc.     

Extrinsic regulation of cardiomyocyte differentiation of embryonic stem cells

Cardiovascular disease is one of leading causes of death throughout the U.S. and the world. The damage of cardiomyocytes resulting from ischemic injury is irreversible and leads to the development of progressive heart failure, which is characterized by the loss of functional cardiomyocytes. Because cardiomyocytes are unable to regenerate in the adult heart, cell-based therapy of transplantation provides a potential alternative approach to replace damaged myocardial tissue and restore cardiac function. A major roadblock toward this goal is the lack of donor cells; therefore, it is urgent to identify the cardiovascular cells that are necessary for achieving cardiac muscle regeneration. Pluripotent embryonic stem (ES) cells have enormous potential as a source of therapeutic tissues, including cardiovascular cells; however, the regulatory elements mediating ES cell differentiation to cardiomyocytes are largely unknown. In this review, we will focus on extrinsic factors that play a role in regulating different stages of cardiomyocyte differentiation of ES cells.     

Hippo信号通路与心血管发育及疾病调控

心血管疾病已成为中国乃至全球首位死亡原因,探索心血管系统发育及调控异常的原因及相关机制可以为心血管疾病的预防和治疗提供重要的科学依据。Hippo信号通路是新近发现的在调节器官大小、细胞增殖及凋亡、干细胞命运等方面具有重要功能的一条信号通路。Hippo信号通路的不同成分参与心脏血管的发育和心血管细胞增殖、分化等功能调控,影响损伤后修复及再生等过程,该通路调节异常可引起心血管疾病,如心梗、心肌肥大、血管内膜增生、动脉硬化等。本文综述了Hippo信号通路对心血管系统发育和疾病调控的相关研究及最新进展,以期为Hippo通路在心血管疾病的发病机制及临床转化研究提供潜在的理论基础。     

Circulating leptin and stress-induced cardiovascular activity in humans

Obesity is associated with an elevated risk of hypertension and cardiovascular disease. The adipocyte hormone leptin, which stimulates energy expenditure in animals by activating the sympathetic nervous system (SNS), is believed to play a role in this association. However, evidence in humans remains sparse. We investigated the relationship between circulating leptin and cardiovascular and inflammatory responses to acute psychological stress in humans. Participants were 32 men and 62 women aged 18-25 years. Cardiovascular activity was assessed using impedance cardiography at baseline, during acute laboratory stress, and during a 45-min recovery period. Plasma cytokines were measured in blood drawn at baseline and 45-min poststress. In women only, baseline plasma leptin was significantly associated with stress-induced changes in heart rate (beta = 0.53, P = 0.006), heart rate variability (HRV) (beta = -0.44, P = 0.015), and cardiac preejection period (PEP) (beta = -0.51, P = 0.004), independent of age, adiposity, and smoking. Women's plasma leptin levels also correlated with stress-induced elevations in the proinflammatory cytokine interleukin-6 (IL-6) (beta = 0.35, P = 0.042). Circulating leptin is an independent predictor of sympathetic cardiovascular activity, parasympathetic withdrawal, and inflammatory responses to stress in women. Because cardiovascular and inflammatory stress responses are predictive of future cardiovascular disease, leptin may be a mechanism mediating the adverse effects of stress and obesity on women's cardiovascular health.     

低氧对斑马鱼胚胎心脏和血管发育及相关基因表达的影响

研究以斑马鱼(Danio rerio)为研究模型,选择心脏和血管荧光标记的2个品系斑马鱼为实验材料,设定低氧和常氧2种水体溶氧条件,用荧光显微镜检测低氧胁迫对胚胎形态结构、心脏和血管外部形态、心率、胚胎躯干部主要血管形成的影响.研究发现低氧导致胚胎存活率低于常氧.低氧不仅滞后胚胎发育,而且造成胚胎形态异常.低氧胁迫后斑...     

NO as a mediator during the early development of the cardiovascular system in the zebrafish

As a general pattern innervation of the cardiovascular system appears late during development in vertebrate embryos, and cardiovascular control may be achieved by hormonal activity in early stages. However, very little is known about the onset of NO-responsiveness during development, which in adult vertebrates is known to play a key function in many physiological processes such as control of vascular tone, neurotransmission, macrophage activity, and angiogenesis. Analysis of the effect of NO on the cardiovascular system in zebrafish (Danio rerio) embryos and larvae revealed almost no effect on cardiac activity during chronic exposure to NO-producing chemicals, whereas vascular reactivity was observed in veins and arteries of the zebrafish in early developmental stages (5-6 days post fertilization). Chronic exposure also modified the development of the vascular system. The presence of an NO donor (sodium nitroprusside) did not change the patterning of the vascular bed, but it induced an earlier appearance of some blood vessels in the trunk region of the zebrafish larvae. The data reveal that NO plays an important role in the development of the cardiovascular system and in the ontogeny of the cardiovascular control system in fish.     

Detrimental effect of hypothermia during acute normovolaemic haemodilution in anaesthetized cats

 Haemodynamic responses to hypothermia were studied at normal haematocrit and following the induction of acute normovolaemic haemodilution. Experiments were performed on 20 cats anaesthetized with a mixture of chloralose and urethane in two groups. In one group (n=10) the effects of hypothermia on various haemodynamic variables were studied at normal haematocrit (41.0±1.7%) and in the second group of cats (n=10) the effects of hypothermia on various haemodynamic variables were studied after the induction of acute normovolaemic haemodilution (14.0±1.0%). The haemodynamic variables left ventricular pressure, left ventricular contractility, arterial blood pressure, heart rate and right atrial pressure were recorded on a polygraph. Cardiac output was measured using a cardiac output computer. In both groups hypothermia was induced by surface cooling with the help of ice. Cardiovascular variables were recorded at each 1° C fall in body temperature. Hypothermia produced a significant (P<0.05) drop in heart rate, cardiac output, arterial blood pressure and left ventricular contractility in both groups. However, the percentage decrease in these variables in response to hypothermia was significantly (P<0.05) higher in cats with low haematocrit than in those with normal haematocrit. The severity of hypothermia – induced cardiovascular effects is evident from the drastic decrease in heart rate, cardiac output, arterial blood pressure and myocardial contractility in cats with low haematocrit, indicating a higher risk of circulatory failure under anaemic conditions at low temperatures. Received: 21 October 1996 / Revised: 20 April 1997 / Accepted 21 May 1997     

Level of ventilation influences the cardiovascular response to hypoxemia in lambs

Newborn animals of a number of species display a brisk increase in ventilation followed by a gradual drop toward or below baseline within minutes of exposure to acute hypoxemia. Heart rate and cardiac output (a determinant of systemic oxygen transport along with the arterial oxygen content) appear to follow a similar pattern, but whether or not the cardiovascular response is influenced by the respiratory response is unknown. We therefore carried out experiments in which the level of ventilation was controlled during normoxemia and hypoxemia to test the hypothesis that the level of ventilation influences the cardiovascular response to acute hypoxemia. Six lambs ranging in age from 17 to 22 days were anesthetized, tracheostomized, and instrumented for measurement of cardiovascular variables. A recovery period of at least 3 days was allowed before the study when each lamb was artificially ventilated with a mixture of 70% nitrous oxide and 30% oxygen in nitrogen. A control respiratory frequency (f) of 30 breaths per min was set and a control tidal volume (VT) was chosen to achieve normocapnia. Cardiovascular measurements were made during normoxemia and hypoxemia (FIO2 0.10) 5 min after f or VT was changed to simulate a decrease, no change, or an increase in ventilation. During normoxemia, the level of ventilation had little effect on the measured cardiovascular variables. At control levels of ventilation, hypoxemia caused an increase in cardiac output that was due solely to an increase in stroke volume as heart rate decreased; blood pressure was unchanged. Increasing ventilation during hypoxemia did not augment cardiac output or alter blood pressure as compared with that observed at control levels of ventilation. Decreasing ventilation during hypoxemia, however, decreased cardiac output due to a profound bradycardia; blood pressure increased significantly. Our data provide evidence that the level of ventilation significantly influences the cardiovascular response to hypoxemia in young lambs.     

Existence of very weak level of residual multiple innervation of Purkinje cells through climbing fibers in the cerebellum of the normal adult rat

Extra- or intracellular unit responses of Purkinje cells to the activation of climbing fibres were recorded in the cerebellum of adult rats. Out of 1.719 cels studied, only 4 were found to be innervated by more than one climbing fibre. This very small rate of residual multiple innervation in the normal adult illustrates the accuracy of the synaptic elimination process which leads to the innervation of each Purkinje cell through only one climbing fibre during normal development in the rat.     

Naloxone does not influence cardiovascular responses to mild mental stress in postmenopausal women

The interaction between central opioid activity, sex hormones, and the cardiovascular reactivity to stress is unknown. Twenty-eight healthy postmenopausal women, 16 without, and 12 with hormone replacement therapy (HRT) participated in this randomized, double-blind, cross-over study. The opioid receptor antagonist naloxone or placebo was administered intravenously on 2 different days and mild mental stress was induced by the Stroop Color-Word Test. Cardiovascular responses were assessed noninvasively by impedance cardiography. Stress significantly increased stroke volume, cardiac output, blood pressure, and heart rate, which was not influenced by opioid receptor blockade. Whereas naloxone increased cortisol plasma concentrations irrespective of HRT status, luteinizing hormone concentrations, which were higher in non-HRT compared with HRT women, were increased by naloxone in women with HRT only. These data suggest that the opioidergic tone of the hypothalamus-pituitary-adrenal axis persists in postmenopausal women, irrespective of HRT use, while the opioidergic tone on the hypothalamus-pituitary-gonadal axis seems to depend on an estrogenic milieu. Naloxone does not alter cardiovascular mental stress reactions in postmenopausal women independent of their hormone substitution status.     

Effect of cardiac denervation on cardiorespiratory responses to exercise in goats

The purpose of this study was to determine whether intact cardiac innervation and a normal cardiovascular (CV) response are required for a normal ventilatory (VE) response to mild and moderate treadmill exercise in awake goats. Accordingly, we measured CV and respiratory responses to two levels of exercise in seven normal (N) and six cardiac-denervated (CD) goats. Evidence of surgical CD included 1) absence of a cardiac response during surgery when the left thoracic cardiac nerves, thoracic vagi, and right and left stellate ganglia were electrically stimulated, 2) total and 80% attenuation of baroreflex changes in heart rate (HR) when arterial blood pressure was raised or lowered, respectively, by infusion of vasoactive agents in awake goats, and 3) attenuation of the CV responses to exercise. At each level of exercise in the CD goats, the HR response was significantly reduced relative to the response observed before CD (P less than 0.05) and the recovery HR response was delayed. Cardiac index increased in a work rate-dependent manner in N and CD goats but was significantly lower in the CD animals (P less than 0.05). Hypotension was consistently observed during exercise following CD. There was no effect of CD on steady-state VE at any metabolic rate or on the VE-O2 uptake relationship (P greater than 0.05). The rest-to-work and work-to-work transition responses of arterial PCO2 were similar between N and CD goats, but there was a tendency toward greater hypocapnia at the exercise onset in CD goats at the highest work rate.(ABSTRACT TRUNCATED AT 250 WORDS)     

Age dependency of cardiovascular autonomic responses to head-up tilt in healthy subjects.

In elderly subjects, heart rate responses to postural change are attenuated, whereas their vascular responses are augmented. Altered strategy in maintaining blood pressure homeostasis during upright position may result from various cardiovascular changes, including age-related cardiovascular autonomic dysfunction. This exploratory study was conducted to evaluate impact of age on cardiovascular autonomic responses to head-up tilt (HUT) in healthy subjects covering a wide age range. The study population consisted of 63 healthy, normal-weight, nonsmoking subjects aged 23-77 yr. Five-minute electrocardiogram and finger blood pressure recordings were performed in the supine position and in the upright position 5 min after 70 degrees HUT. Stroke volume was assessed from noninvasive blood pressure signals by the arterial pulse contour method. Heart rate variability (HRV) and systolic blood pressure variability (SBPV) were analyzed by using spectral analysis, and baroreflex sensitivity (BRS) was assessed by using sequence and cross-spectral methods. Cardiovascular autonomic activation during HUT consisted of decreases in HRV and BRS and an increase in SBPV. These changes became attenuated with aging. Age correlated significantly with amplitude of HUT-stimulated response of the high-frequency component (r = -0.61, P < 0.001) and the ratio of low-frequency to high-frequency power of HRV (r = -0.31, P < 0.05) and indexes of BRS (local BRS: r = -0.62, P < 0.001; cross-spectral baroreflex sensitivity in the low-frequency range: r = -0.38, P < 0.01). Blood pressure in the upright position was maintained well irrespective of age. However, the HUT-induced increase in heart rate was more pronounced in the younger subjects, whereas the increase in peripheral resistance was predominantly observed in the older subjects. Thus it is likely that whereas the dynamic capacity of cardiac autonomic regulation decreases, vascular responses related to vasoactive mechanisms and vascular sympathetic regulation become augmented with increasing age.     

Role of the neuropeptide CCAP in Drosophila cardiac function

The heartbeat of adult Drosophila melanogaster displays two cardiac phases, the anterograde and retrograde beat, which occur in cyclic alternation. Previous work demonstrated that the abdominal heart becomes segmentally innervated during metamorphosis by peripheral neurons that express crustacean cardioactive peptide (CCAP). CCAP has a cardioacceleratory effect when it is applied in vitro. The role of CCAP in adult cardiac function was studied in intact adult flies using targeted cell ablation and RNA interference (RNAi). Optical detection of heart activity showed that targeted ablation of CCAP neurons selectively altered the anterograde beat, without apparently altering the cyclic cardiac reversal. Normal development of the abdominal heart and of the remainder of cardiac innervation in flies lacking CCAP neurons was confirmed by immunocytochemistry. Thus, in addition to its important role in ecdysis behavior (the behavior used by insects to shed the remains of the old cuticle at the end of the molt), CCAP may control the level of activity of the anterograde cardiac pacemaker in the adult fly. Expression of double stranded CCAP RNA in the CCAP neurons (targeted CCAP RNAi) caused a significant reduction in CCAP expression. However, this reduction was not sufficient to compromise CCAP's function in ecdysis behavior and heartbeat regulation.