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1.
Hill C  Dunbar JC 《Peptides》2002,23(9):1625-1630
Alpha melanocyte stimulating hormone (alphaMSH) has been demonstrated to have regulatory functions in the periphery and central nervous system (CNS). alphaMSH plays a central role in the regulation of metabolic balance such as decreasing food intake, increasing sympathetic outflow and hypothalamic/pituitary function. Our laboratory has investigated the actions of alphaMSH on sympathetic and cardiovascular dynamics using anesthetized animals. In this study we determined both the acute and chronic effects of alphaMSH on cardiovascular and metabolic dynamics in conscious unrestrained rats. Animals were each implanted with a radio-telemetry transmitter for recording of cardiovascular parameters and subsequently instrumented with intracerebroventricular (ICV) cannulas. The acute ICV administration of alphaMSH significantly increased the mean arterial pressure (MAP) and heart rate (HR) when compared to artificial cerebrospinal fluid (ACSF) controls. On the other hand chronic alphaMSH infusion resulted in an initial increase in MAP and HR lasting for 2 days followed by a decrease in MAP. Chronic alphaMSH administration decreased physical activity and food intake but not weight gain. We conclude that in the conscious unrestrained animal the acute administration of alphaMSH increased MAP and HR, however, chronic infusion is associated with decreased MAP, physical activity and food intake.  相似文献   

2.
The possible effects of cervical lymphatic blockade (CLB) on a series of parameters in conscious freely moving rats were analysed. Blood pressure (BP) and heart rate (HR) for conscious male Sprague-Dawley rats at 1, 3, 7, 11, 15 and 21 days after a CLB or a sham operation were monitored continuously for 24 hours with a computerized recording system. Since BP and HR were subjected to spontaneous variations, blood pressure variability (BPV) and heart rate variability (HRV) were expressed as the standard deviation of beat-to-beat BP and HR values. The baroreflex sensitivities (BRS) were determined by measuring the heart period (HP = 60,000/HR) prolongation in response to the elevation in BP induced by an intravenous administration of phenylephrine at 1, 7, 15 and 21 days after the CLB or sham operation. Compared with those in sham-operated rats, the values of systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (MAP), HR and BRS in CLB rats were significantly lower, whereas the values of BPV and HRV were markedly raised in CLB rats at different time points. Furthermore, the impaired ultrastructure in the dorsomedial nucleus of the solitary tract (dmNTS) including degeneration, apoptosis and necrosis in neurons and gliacytes, were apparent from the 1st to 15th day but the changes were most significant at 7th day after CLB operation. Structural changes appeared to be closely related to functional changes of the dmNTS at each time point. Thus, in CLB conscious rats, a significant decline in blood pressure accompanied by dysfunction in its regulation might be due to the impaired structure in the dmNTS.  相似文献   

3.
A simple and reliable means for accurate, chronic measurement of pulsatile blood pressure (BP) from conscious, freely moving laboratory mice was developed and validated. The newly developed device consists of a small (1.9 ml, 3.4 g), fully implantable radiotelemetry transmitter. Initial frequency response tests showed an adequate dynamic response; the average -3-dB point found in five transmitters was 145 +/- 14 (SD) Hz. BP, heart rate, and locomotor activity were recorded from 16 chronically (30-150 days) implanted mice. Mean arterial and pulse pressure, checked at regular intervals, ranged from 90-140 mmHg and from 30-50 mmHg, respectively, throughout the study. Transmitter BP measurements were validated against a Millar 1.4-Fr. transducer-tipped catheter. The mean error of the transmitters for diastolic pressures was +1.1 +/- 6.9 mmHg (n = 7). The error for systolic pressures was, on average, 2.7 +/- 3.9 mmHg larger. This new device accurately monitors BP, heart rate, and locomotor activity in conscious, untethered, freely moving mice living in their home cages for periods of at least 150 days.  相似文献   

4.
A radio-telemetry recording system is presented which is applied to stimulate specific brain areas and record neuronal activity in a free-roaming rat.The system consists of two major parts:stationary section and mobile section.The stationary section contains a laptop,a Micro Control Unit (MCU),an FM transmitter and a receiver.The mobile section is composed of the headstage and the backpack (which includes the mainboard,FM transmitter,and receiver),which can generate biphasic microcurrent pulses and simultaneously acquire neuronal activity.Prior to performing experiments,electrodes are implanted in the Ventral Posterolateral (VPL) thalamic nucleus,primary motor area (M 1) and Medial Forebrain Bundle (MFB) of the rat.The stationary section modulates commands from the laptop for stimulation and demodulates signals for neuronal activity recording.The backpack is strapped on the back of the rat and executes commands from the stationary section,acquires neuronal activity,and transmits the neuronal activity singles of the waking rat to the stationary section.All components in the proposed system are commercially available and are fabricated from Surface Mount Devices (SMD) in order to reduce the size (25 mm × 15 mm × 2 mm) and weight (10 g with battery).During actual experiments,the backpack,which is powered by a rechargeable Lithium battery (4 g),can generate biphasic microcurrent pulse stimuli and can also record neuronal activity via the FM link with a maximum transmission rate of 1 kbps for more than one hour within a 200 m range in an open field or in a neighboring chamber.The test results show that the system is able to remotely navigate and control the rat without any prior training,and acquire neuronal activity with desirable features such as small size,low power consumption and high precision when compared with a commercial 4-channel bio-signal acquisition and processing system.  相似文献   

5.
The purpose of this study was to compare the cardiovascular responses to electrical stimulation of different supramedullary brain regions. Arterial blood pressure (BP) and heart rate (HR) effects were elicited by electrical stimulation of the lateral hypothalamus (LH), mamillary bodies (Mm), substantia nigra (SN), globus pallidus (GP), and the subthalamic nucleus (Sub) in conscious, freely moving cats. Pressor responses were obtained from all of these regions. The higher intensity of stimulation the higher increase in BP and HR was obtained. However, clear-cut differences occurred in the effects both during and after the termination of stimulations. Namely, a continuous increase in BP and HR was obtained from the LH and SN. In contrast, the initial increase in BP and HR was followed by a reduction compared to the peak value of the effects of stimulation in the GP and the Sub. However, the BP and HR never reduced to the pre-stimulaion level during the stimulation. Also the changes following the cessation of stimulation at the different brain loci were dissimilar. The BP and HR either returned gradually to the pre-stimulation level, or long-lasting oscillation occurred. The electrical activity of the nucleus of the solitary tract (NTS) and the vagus nerve co-varied with the changes in BP and HR. It is concluded that the supramedullary stimulations produce differential cardiovascular effects, and these effects are modified by the baroreflexes that are activated by the electrically elicited rise in blood pressure.  相似文献   

6.
Radiotelemetry provides an alternative means of obtaining physiological measurements from conscious and freely moving animals, without introducing stress artefacts. A surgical procedure is described for implanting radiotelemetry transmitters to monitor the electrocardiogram (ECG), heart rate (HR) and body temperature (BT) in small goldfish (Carassius auratus; 50-100 g) and Prussian carp (Carassius auratus gibelio; 100 g). This type of transmitter is commonly implanted in freely moving mice. After surgery and a recovery period of 24 h, the ECG, HR and BT were recorded in freely swimming fish within the limitations of the aquarium.  相似文献   

7.
Exposure to microgravity induces cardiovascular deconditioning characterized by orthostatic hypotension when astronauts return to the earth. In order to understand the mechanism of cardiovascular deconditioning, it is necessary to clarify the changes in hemodynamics and the cardiovascular regulation system over the period of space flight. The telemetry system applied to freely moving animals will be a useful and appropriate technique for this kind of long term study of the cardiovascular system in the conscious animal during space flight. The purpose of the present study is twofold: firstly, to observe the detailed changes of arterial pressure and heart rate (HR) during microgravity elicited by the parabolic flight in order to study the acute effect of microgravity exposure on the cardiovascular system; and secondly, to test the feasibility of the telemetry system for recording blood pressure, HR and autonomic nervous activities continuously during space flight.  相似文献   

8.
In this study, the investigation of the intraoperative effects of dipyrone (metamizol) on heart rate (HR), mean arterial pressure (MAP) and analgesic efficacy in rabbits is described for the first time. This was carried out to evaluate the cardiovascular stability achieved using dipyrone compared with fentanyl. In this prospective study, 17 female New Zealand White rabbits were randomly allocated to either one of two groups: dipyrone/propofol (DP) or fentanyl/propofol (FP). Anaesthesia was induced in both groups using propofol to effect (4.0-8.0 mg/kg intravenously) until the swallowing reflex was lost for intubation. After induction, anaesthesia was maintained with continuous infusion of propofol 1.5-1.7 mg/kg/min intravenously. Analgesics were then injected in defined boluses of either dipyrone 65 mg/kg or fentanyl 0.0053 mg/kg. After surgical tolerance, defined as loss of the ear pinch reflex and loss of the anterior and posterior pedal withdrawal reflex, was achieved, two surgical procedures were performed. The surgical procedures (implantation of either a pacemaker or an electrocardiogram transmitter), both require a comparable level of analgesic depth. During and after surgery, clinical variables, such as MAP, HR, peripheral arterial oxygen saturation (SpO?) and end-tidal CO? (P(E')CO?) were recorded simultaneously every 2 min. Eight time points were chosen for comparison: baseline, surgical tolerance (ST), values at 10, 20 and 30 min after reaching ST, values at the end of propofol infusion (EI) and data at 10 and 20 min after EI. Both FP and DP combinations provided effective anaesthesia and analgesia in rabbits. In both groups a significant decrease of HR and MAP was measured. The results of this study indicate that the non-opioid drug dipyrone produces similar analgesic and even better cardiovascular effects by trend in rabbits. Therefore we conclude that dipyrone in combination with propofol can be used as an alternative to FP for intraoperative analgesia.  相似文献   

9.
在麻醉大鼠观察了向延髓腹外侧区微量注射NO合成酶抑制剂N-硝基左旋精氨酸(LNNA)和硝普钢(SNP)对血压、心率和肾交感神经活动的影响,旨在探讨中枢左旋精氨酸-NO通路在动脉血压调节中的作用及其机制。实验结果如下:(1)向延髓腹外侧头端区(RVLM)注射L-NNA后,平均动脉压(MAP)升高,肾交感神经活动(RSNA)增强;心率(HR)减慢,但无统计学意义。MAP和RSNA的变化持续30min以上;此效应可被预先静注左旋精氨酸所逆转。(2)向RVLM微量注射SNP,MAP降低,RSNA减弱;但HR的变化无统计学意义。(3)向延髓腹外侧尾端区(CVLM)注射L-NNA,MAP降低,HR减慢,RSNA减弱。(4)向CVLM微量注射SNP,MAP升高,RSNA增强,而心率无明显变化。以上结果表明,中枢左旋精氨酸-NO通路对延髓腹外侧部的神经元活动有调变作用。  相似文献   

10.
The aim of the study was to compare an often-used method to measure blood pressure (BP) using a tail-cuff (TC) device, with radiotelemetry (RT) which allows to sample data on heart rate (HR) and BP in freely moving rodents without any restraint in behaviour. Data were collected in male normotensive Wistar-Kyoto rats and in spontaneously hypertensive rats. Experiments were performed under 12:12 h light–dark conditions (lights on at 07:00 h) with simulated dawn and dusk for 45 min. Experiments were performed at 08:00–10:00 h (rest phase) and at 20:00–22:00 h (activity phase) under control conditions and after treatment with the beta-adrenoceptor blocker metoprolol (8 mg/kg). For TC, the Harvard BP Monitoring System (Edenbrigde, England) and for RT radio transmitters (Dataquest IV system, TA11PA-C40, DSI, St. Paul, Minnesota, USA) were used. Rats bearing the TC device were also monitored under RT. The experiments show that TC significantly increased HR and both systolic and diastolic BP in both strains and both at L and D. Metoprolol reduced TC-induced HR but left BP increase uneffected. The study shows that RT is the method of choice to monitor BP and HR in rodents, TC is not suitable.  相似文献   

11.
It has been speculated that if baroafferent signals are only related to the negative feedback control of arterial pressure (AP), then physical activity would increase the range of AP fluctuation in baroafferent-denervated animals. Mean AP (MAP), heart rate (HR), and cardiac output (CO) were measured for 24 h in free-moving conscious rabbits. On the basis of hydrostatic pressure and electromyogram, MAP data taken during periods of physical activity and rest were selected from the overall 24-h MAP data and then converted into histograms. During physical activity, the mode of MAP histogram increased in intact rabbits and was unchanged in sinoaortic-denervated (SAD) rabbits. Movement increased the mode of total peripheral resistance (TPR) but did not significantly change CO in intact rabbits. Conversely in SAD rabbits, movement slightly decreased TPR and slightly increased CO. These findings indicate that arterial baroafferent signals are required to shift MAP to a higher pressure level by an increase in TPR but not in CO during a moving phase. These results suggest that baroafferent signals may not only minimize the fluctuating range of MAP through negative feedback control but also be involved in actively resetting MAP toward a higher pressure level during daily physical activity.  相似文献   

12.
There is continuing discussion on the effect of music (“Mozart effect”) on numerous functions in man and experimental animals. Radiotelemetry now allows one to monitor cardiovascular functions in freely‐moving unrestrained experimental animals. Radiotelemetry was used to monitor systolic and diastolic blood pressure (SBP, DBP), heart rate (HR), and motor activity (MA) in male normotensive WKY and hypertensive SHR animals. Rats were synchronized to a 12 h light (L): 12 h dark (D) regimen in an isolated, ventilated, light‐controlled, sound‐isolated animal container. Music (Mozart, Symphony # 40; Ligeti, String Quartet # 2) were played for 2 h at 75 dB in the animal cabin starting at the onset of L or D in a cross‐over design. Data were collected every 5 min for 24 h under control conditions and during and after music. In addition, plasma concentrations of norepinephrine (NE) were determined in unrestrained animals at 3 h intervals over 24 h. In both WKY and SHR, highly significant circadian rhythms were obtained in SBP, DBP, HR, and MA under control conditions; HR was lower and BP higher in SHR than in WKY. NE was circadian rhythmic in both strains with higher values in D; the increase in NE with immobilization was much more pronounced in SHR than in WKY. The music of Mozart had no effect on either parameter in WKY, neither in L nor in D. In contrast, in SHR, the music of Mozart presented in L significantly decreased HR and left BP unaffected, leading to a small decrease in cardiac output. The music of Ligeti significantly increased BP both in L and in D and reflexively reduced HR in L, the effects being long‐lasting over 24 h. Interestingly, white noise at 75 dB had no effect at all on either function in both strains. The effects of both Mozart and Ligeti cannot be attributed to a stress reaction, as stress due to cage switch increased HR and BP both in WKY and SHR. The study clearly demonstrates that music of different character (tempo, rhythm, pitch, tonality) can modify cardiovascular functions in freely‐moving rats, with SHR being more sensitive than normotensive animals. The relative contribution of the characteristics of the two pieces of music, however, needs further evaluation.  相似文献   

13.
G E Sander  T D Giles  J C Rice 《Peptides》1985,6(1):133-137
Interactions between the undecapeptide Substance P (SP) and the pentapeptide methionine-enkephalin (Met5-ENK) have been described in isolated organ systems and in baroreceptor reflex mechanisms. Previous studies in our laboratory have demonstrated that systemically injected Met5-ENK simultaneously increases mean systemic arterial pressure (MAP) and heart rate (HR) in the conscious, chronically instrumented dog. We have now evaluated cardiovascular interactions between SP and Met5-ENK. In this model, SP injected intravenously produces a rapid and transient decrease in MAP and increase in HR over the dose range from 1.0 to 10.0 ng/kg. SP does not appear to appreciably alter subsequent responses to Met5-ENK. At SP doses of 1.0 ng/kg, the peak hemodynamic response to SP and Met5-ENK (35 micrograms/kg) given together appears to represent a simple summation effect of both drugs on HR and MAP. However, at higher SP doses (5.0 ng/kg), the SP response predominates and is little altered by the presence of Met5-ENK. Thus, Met5-ENK does appear capable of modulating the hemodynamic responses to SP over certain dose ranges.  相似文献   

14.
We have previously demonstrated that leptin-mediated activation of the central nervous system (CNS) melanocortin system reduces appetite and increases sympathetic activity and blood pressure (BP). In the present study we examined whether endogenous melanocortin system activation, independent of leptin's actions, contributes to the regulation of BP and metabolic functions in obese Zucker rats, which have mutated leptin receptors. The long-term cardiovascular and metabolic effects of central melanocortin-3/4 receptor (MC3/4R) antagonism with SHU-9119 were assessed in lean (n = 6) and obese (n = 8) Zucker rats. BP and heart rate (HR) were measured 24-h/day by telemetry and an intracerebroventricular cannula was placed in the brain lateral ventricle. After stable control measurements, SHU-9119 was infused intracerebroventricularlly (1 nmol/h) for 10 days followed by a 10-day recovery period. Chronic CNS MC3/4R antagonism significantly increased food intake and body weight in lean (20 ± 1 to 45 ± 2 g and 373 ± 11 to 432 ± 14 g) and obese (25 ± 2 to 35 ± 2 g and 547 ± 10 to 604 ± 11 g) rats. No significant changes were observed in plasma glucose levels in lean or obese rats, whereas plasma leptin and insulin levels markedly increased in lean Zucker rats during CNS MC3/4R antagonism. Chronic SHU-9119 infusion in obese Zucker rats reduced mean arterial pressure (MAP) and HR by 6 ± 1 mmHg and 24 ± 5 beats/min, whereas in lean rats SHU-9119 infusion reduced HR by 31 ± 9 beats/min while causing only a transient decrease in MAP. These results suggest that in obese Zucker rats the CNS melanocortin system contributes to elevated BP independent of leptin receptor activation.  相似文献   

15.
The cardiovascular effects of i.v. treatment with 1,8-cineole, a monoterpenic oxide present in many plant essential oils, were investigated in normotensive rats. This study examined (i) whether the autonomic nervous system is involved in the mediation of 1,8-cineole-induced changes in mean aortic pressure (MAP) and heart rate (HR) and (ii) whether the hypotensive effects of 1,8-cineole could result from its vasodilatory effects directly upon vascular smooth muscle. In both pentobarbital-anesthetized and conscious, freely moving rats, bolus injections of 1,8-cineole (0.3-10 mg/kg, i.v.) elicited similar and dose-dependent decreases in MAP. Concomitantly, 1,8-cineole significantly decreased HR only at the highest dose (10 mg/kg). Pretreatment of anesthetized rats with bilateral vagotomy significantly reduced the bradycardic responses to 1,8-cineole (10 mg/kg) without affecting hypotension. In conscious rats, i.v. pretreatment with methylatropine (1 mg/kg), atenolol (1.5 mg/kg), or hexamethonium (30 mg/kg) had no significant effects on the 1,8-cineole-induced hypotension, while bradycardic responses to 1,8-cineole (10 mg/kg) were significantly reduced by methylatropine. In rat isolated thoracic aorta preparations, 1,8-cineole (0.006-2.6 mM) induced a concentration-dependent reduction of the contraction induced by potassium (60 mM). This is the first physiological evidence that i.v. treatment with 1,8-cineole in either anesthetized or conscious rats elicits hypotension; this effect seems related to an active vascular relaxation rather than withdrawal of sympathetic tone.  相似文献   

16.
A design for an inexpensive and reliable subminiature microdrive for recording single neurons in the freely moving animal is presented. The Scribe microdrive is small and lightweight and has been used successfully to record in freely moving rats and pigeons. It would also be suitable for recording in mice. The device is simple and inexpensive yet allows for stable and precise manipulation of the recording electrodes. As a result it supports stable recordings conducted over long periods. Because the Scribe microdrive is a small-diameter device it is also suitable for multisite, multielectrode applications. Here we discuss the construction of the device and comment on its use in recording from freely moving rats and pigeons.  相似文献   

17.
Gao XY  Wang HJ  Zhang Y  Lu ZH  Wang W  Zhu GQ 《Life sciences》2006,78(10):1129-1134
A closed-loop implanted chip system was designed to control blood pressure without using drugs. The chip system instantaneously reset blood pressure by stimulating the left aortic depressor nerve according to the feedback signals of arterial blood pressure. The relationship between pressure signals and frequency of stimulation was identified in vitro and in vivo, and the efficiency of the chip system was evaluated in normal anesthetized Wistar rats. To determine whether the depressor effect of the chip was primarily independent on the bradycardia induced by the resetting, the effects of methyl atropine (1.5 g/kg, iv.) and bilateral vagotomy on depressor effect induced by the chip system were determined, respectively. The results indicated that the chip system worked well. The frequency of stimulus linearly increased following the elevation of pressure from 70 to 160 mm Hg. The frequency of the stimulus reached its maximum (100 Hz) when pressure exceeded 160 mm Hg, and the stimulation stopped when MAP was below 70 mm Hg. There were significant decreases in mean arterial pressure (MAP, -20.0+/-4.4 mm Hg) and heart rate (HR, -43.0+/-10.5 bpm) during the resetting in rats. After resetting, both MAP and HR recovered in a minute without any significant rebound. Pretreatment with either methyl atropine or bilateral vagotomy abolished the bradycardia effect but produced no significant effect on hypotension. The results demonstrated that the chip system successfully reset blood pressure in rats, and that the hypotension induced by the chip system was primarily independent on the bradycardia effect.  相似文献   

18.
Radiokinetocardiogram (RKCG) recorded with the aid of telemetric system and electromagnetic kinetotransducer was sufficiently differentiated and was of the shape identical to the directly recorded kinetogram. A possibility of reliable recording of the RKCG in a freely moving man (during a micropause in the process of movement) was demonstrated under laboratory and natural working conditions.  相似文献   

19.
This study dealt with the long-term effects of hypertension on circadian rhythms of hemodynamic and cardiovascular autonomic functions in radiotelemetered rats. Blood pressure (BP), heart rate (HR), spontaneous locomotor activity, and respiration.were monitored in spontaneously hypertensive rats (SHRs), a model of human hypertension, from 14 to 27 weeks of age and in Wistar-Kyoto rats (WKY) as controls. Cardiovascular autonomic changes were determined by time-domain analysis of the variability of BP (standard deviation of mean arterial pressure, SDMAP) and HR (standard deviation of R-R intervals, SDRR, and the root mean square of successive differences in R-R intervals, rMSSD). Compared with WKY rats, the 24-hr MAP and SDMAP were higher at week 14 in SHRs and showed stepwise increases over the study duration, suggesting progressive increases in vasomotor sympathetic activity in hypertensive rats. Also, higher SDRR, rMSSD, and activity and lower HR and respiration were demonstrated in SHRs. Normal circadian rhythms (higher dark-time values) of MAP, HR, SDMAP, and SDRR were evident in WKY rats at week 20 and continued thereafter. Compared with WKY rats, the circadian BP and HR patterns were abolished and inverted, respectively, in SHRs. Lower dark-time, compared with light-time, SDMAP values were observed in SHRs that were associated with temporal increases in HR variability indices. These findings demonstrate that hypertension elicits significant alterations in circadian autonomic and hemodynamic profiles. Further, the steady increases in BP, average level and oscillations, in SHRs may explain the reported progressive age-related vascular and cardiac hypertrophy in these rats.  相似文献   

20.
The objective of this study was to determine systolic, diastolic, and mean arterial blood pressure (SBP, DBP, and MAP), heart rate (HR), double-product (DP: SBP x HR), and activity levels and their 24h pattern in liver glycogen storage disease (LGSD) patients. A case series of 12 (11 pediatric and one adult) diurnally active LGSD (seven type I, three type III, and two type IX) subjects were simultaneously assessed by 24h ambulatory blood pressure monitoring and wrist actigraphy. Nine subjects were judged to be hypertensive based on the criterion of an elevated 24h mean SBP and/or DBP being elevated beyond reference standards or the SBP and/or DBP load (percentage of time BP exceeds normal values) being greater than 25%. Two of the three other subjects, not viewed as hypertensive based on their 24h average SBP or DBP, exhibited daytime or nighttime SBP and/or DBP load hypertension. Each study variables displayed statistically significant (p < 0.001) group circadian rhythmicity. The SBP, DBP, and MAP displayed comparable 24h patterns of appreciable amplitude (total peak-trough variation equal to 17.7, 23.6, and 19.6%, respectively, of the 24h mean) with highest values (orthophase) occurring approximately 11 h after the commencement of daytime activity. The sleep-time trough (bathyphase) occurred approximately 4.5 h before morning awakening. The statistically significant (p < 0.006) circadian rhythms of HR (amplitude equal to 33.2% of the 24h mean) and DP (amplitude equal to 49.4% of the 24h mean) peaked earlier, approximately 7.4 h into the daytime activity span. The sleep-time trough occurred approximately 3 h before morning awakening. The 24h pattern in the cardiovascular variables was correlated with the 24h pattern of activity, with r ranging from 0.50 for DBP to 0.39 for HR.  相似文献   

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