Studies Of Cardiovascular Function Research Articles

Abstract P203: Time-restricted Feeding Attenuates Hypertension In Mice

Hypertension is associated with inflammation and decreased kidney function. Studies of cardiovascular function have observed that time-restricted feeding (TRF), a form of intermittent fasting, is associated with decreased blood pressure, decreased inflammation, and improved kidney function. We hypothesized that implementation of a time-restricted feeding protocol in hypertensive mice would decrease systolic blood pressure and increase kidney function. C57BL6/J mice were randomly assigned to either an L-arginine methyl ester hydrochloride (LNAME)-induced hypertension (LHTN) model, where they received LNAME in their drinking water, or a salt-sensitive hypertension (SSHTN) model, where they received a 4% high salt diet following LNAME priming and a washout period. Two days following introduction of LNAME or the high salt diet, mice were either provided food ad libitum or placed on a 12-hour TRF protocol, where they were only allowed to eat from 8PM to 8AM. Hypertensive mice receiving TRF treatment displayed a significantly decreased systolic blood pressure (SBP) after 4 weeks when compared to the control hypertensive groups (LHTN SBP: 164±1 vs. 149±2 mmHg, p<0.001; SSHTN SBP: 139±1 vs. 130±1 mmHg, p<0.001). When kidney function was examined in the LHTN group, TRF mice had decreased serum creatinine (Sc) levels along with decreased fractional excretion of sodium (FENa) when compared to their respective control mice (Sc: 0.19±0.01 vs. 0.13±0.01 mg/dL, p=0.007; FENa: 0.59±0.05 vs. 0.32±0.05 %, p=0.009). Glomerular filtration rate was significantly increased in TRF treated LHTN mice. Overall, these data indicate that TRF treatment reduces blood pressure in hypertensive mice, which is associated with an improvement in renal function. These findings could establish TRF as a potential therapeutic option for hypertensive patients.

A transient decrease in heart rate with unilateral and bilateral galvanic vestibular stimulation in healthy humans.

The study of cardiovascular function with galvanic vestibular stimulation has provided evidence on the neural structures that are involved in the vestibulo-autonomic reflex. This study determined if the effect on heart rate using galvanic vestibular stimulation persists after provoking a sympathetic response and if this response differs when using unilateral or transmastoid (bilateral) stimulation. We analysed heart rate and heart rate variability using unilateral and transmastoid galvanic vestibular stimulation combined with cardiovascular reflex evoked by postural change in 24 healthy human subjects. Three electrode configurations were selected for unilateral stimulation considering the anatomical location of each semicircular canal. We compared recordings performed in seated and standing positions, and with unilateral and transmastoid stimulation. With subjects seated, a significant transient decrease in heart rate was observed with unilateral stimulation. With transmastoid stimulation, heart rate decreased in both seated and standing positions. Average intervals between normal heartbeats recorded with stimulation resemble parasympathetic cardiac function induced by auricular vagal nerve stimulation. Our results indicate that unilateral stimulation does not eliminate the natural heart rate increase caused by orthostatic hypotension. In contrast, transmastoid stimulation provoked a transient reduction in heart rate, even when subjects were standing. These responses should be considered while performing experiments with galvanic vestibular stimulation and subsequent effects in cardiac regulation mechanisms.

Wavelet Analysis of Microcirculatory Flowmotion Reveals Cardiovascular Regulatory Mechanisms–Data from a Beta-Blocker

A variety of animal models exist for the study of cardiovascular function using many approaches from surgically induced ischemia to genetic manipulation. A murine physiological model was recently proposed for the non-invasive study of peripheral circulation and was strengthened by the wavelet transform analysis (WA) of laser Doppler flowmetry (LDF) signals. WA allows the extraction of cardiac, respiratory, sympathetic, endothelial, and myogenic components from the raw LDF signal. The present study was designed to evaluate the discernment capacity of the model through an analysis of the short-term effects of the well-known hypotensive cardiovascular drug, atenolol. Six male C57/BL6 mice (16 weeks old) were included in the study, with each animal serving as its own control. Following anesthesia with ketamine-xylazine, skin perfusions were continuously assessed in both hindlimbs by LDF during baseline and after two sequential atenolol administrations (2.5 and 5.0 mg/kg, as commonly prescribed). Expected atenolol-induced hypotension was present, associated with a significantly increased heart rate and peripheral perfusion with both dosages. Through the application of WA to the LDF signal, we could detail the mechanisms of the atenolol-induced peripheral perfusion modulation: an immediate amplitude decrease of the cardiac LDF spectrum with an amplitude increase of the sympathetic component (p < 0.05) and the endothelial and myogenic components (non-significant). These data suggested a regulatory crosstalk between the peripheral (baroreceptors) and the microcirculatory units, which ultimately resulted in hypotension, inotropic reduction, and tachycardia. In conclusion, WA offered insight that simply could not be seen with only the perfusion curve and, thus, was an effective tool to investigate this cardiovascular mechanism of regulation.

Study of cardiovascular function using a coupled left ventricle and systemic circulation model

To gain insight into cardio-arterial interactions, a coupled left ventricle-systemic artery (LV–SA) model is developed that incorporates a three-dimensional finite-strain left ventricle (LV), and a physiologically-based one-dimensional model for the systemic arteries (SA). The coupling of the LV model and the SA model is achieved by matching the pressure and the flow rate at the aortic root, i.e. the SA model feeds back the pressure as a boundary condition to the LV model, and the aortic flow rate from the LV model is used as the input for the SA model. The governing equations of the coupled system are solved using a combined immersed-boundary finite-element (IB/FE) method and a Lax–Wendroff scheme. A baseline case using physiological measurements of healthy subjects, and four exemplar cases based on different physiological and pathological scenarios are studied using the LV–SA model. The results of the baseline case agree well with published experimental data. The four exemplar cases predict varied pathological responses of the cardiovascular system, which are also supported by clinical observations. The new model can be used to gain insight into cardio-arterial interactions across a range of clinical applications.

A study of cardiovascular function under controlled and spontaneous ventilation in isoflurane–medetomidine anaesthetized horses

ObjectiveTo determine, in mildly hypercapnic horses under isoflurane–medetomidine balanced anaesthesia, whether there is a difference in cardiovascular function between spontaneous ventilation (SV) and intermittent positive pressure ventilation (IPPV). Study designProspective randomized clinical study. AnimalsSixty horses, undergoing elective surgical procedures under general anaesthesia: ASA classification I or II. MethodsHorses were sedated with medetomidine and anaesthesia was induced with ketamine and diazepam. Anaesthesia was maintained with isoflurane and a constant rate infusion of medetomidine. Horses were assigned to either SV or IPPV for the duration of anaesthesia. Horses in group IPPV were maintained mildly hypercapnic (arterial partial pressure of carbon dioxide (PaCO2) 50–60 mmHg, 6.7–8 kPa). Mean arterial blood pressure (MAP) was maintained above 70 mmHg by an infusion of dobutamine administered to effect. Heart rate (HR), respiratory rate (fR), arterial blood pressure and inspiratory and expiratory gases were monitored continuously. A bolus of ketamine was administered when horses showed nystagmus. Cardiac output was measured using lithium dilution. Arterial blood-gas analysis was performed regularly. Recovery time was noted and recovery quality scored. ResultsThere were no differences between groups concerning age, weight, body position during anaesthesia and anaesthetic duration. Respiratory rate was significantly higher in group IPPV. Significantly more horses in group IPPV received supplemental ketamine. There were no other significant differences between groups. All horses recovered from anaesthesia without complications. ConclusionsThere was no difference in cardiovascular function in horses undergoing elective surgery during isoflurane–medetomidine anaesthesia with SV in comparison with IPPV, provided the horses are maintained slightly hypercapnic. Clinical relevanceIn horses with health status ASA I and II, cardiovascular function under general anaesthesia is equal with or without IPPV if the PaCO2 is maintained at 50–60 mmHg.

Cardiovascular function in pregnant women with polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is associated with a range of cardiovascular abnormalities including decreased vascular resistance and arterial compliance and increased intima media thickness in the carotid circulation. There is also some evidence that blood pressure is higher in these women. In pregnancy it is associated with diabetes and possibly also with pre-eclampsia. There are however no studies of cardiovascular function in pregnant women with the Syndrome. This study was designed to compare blood pressure and arterial properties in pregnant PCOS women and healthy controls.

Daily variability in resting levels of cardiovascular variables in normal subjects and those with homozygous sickle cell disease

Measurements were made of cardiovascular variables and oral temperature in 16 male subjects with homozygous sickle cell disease (SS) and in 17 matched controls (AA) at 10.00 a.m., 1.00 p.m. and 4.00 p.m. All subjects were in a rested state throughout. At 10.00 a.m., mean arterial pressure was lower, while heart rate, total forearm blood flow and cutaneous red cell flux in the forearm were higher in SS than AA. Vascular resistance in total forearm and forearm skin, calculated by dividing arterial pressure by blood flow or red cell flux, were lower in SS but hand cutaneous red cell flux and vascular resistance were not significantly different in SS and AA. In both SS and AA, there were parallel increases over the three sessions, in mean arterial pressure (by approximately 12 and 10%, respectively) forearm vascular resistance (by approximately 17 and 27%) and hand cutaneous vascular resistance and hand cutaneous resistance (by approximately 2240 and 350%) whereas forearm blood flow and hand cutaneous red cell flux fell. By contrast, forearm cutaneous resistance showed no change during the day in SS, but increased progressively in AA (by approximately 75%). These results indicate that, during the day, there is progressive vasoconstriction in forearm muscle and hand skin in SS and AA and also in forearm skin of AA that contributes to a progressive rise in the resting level of mean arterial pressure. We suggest this daily variability should be considered in studies of cardiovascular function: within a given study they should be performed at the same time of day.

Engineering and physiological approaches to the study of cardiovascular function

Engineering and physiological approaches to the study of cardiovascular function

Engineering and physiological approaches to the study of cardiovascular function: alternative or complementary?

Engineering and physiological approaches to the study of cardiovascular function: alternative or complementary?

Engineering and physiological approaches to the study of cardiovascular function: science and pseudoscience?

Engineering and physiological approaches to the study of cardiovascular function: science and pseudoscience?

Radionuclide Studies of Cardiovascular Function in Normal Subjects and Relationship to Age

Radionuclide Studies of Cardiovascular Function in Normal Subjects and Relationship to Age

Assessment of emetine cardiotoxicity in a subacute toxicity experiment in rats.

We explored the usefulness of cardiovascular function studies for the detection and characterization of emetine cardiotoxicity in a subacute toxicity experiment. Rats received 1 mg/kg, s.c., emetine five times weekly for up to 7 weeks. In unanesthetized animals, statistically significant changes of the electrocardiogram (EKG) appeared in the following sequence: prolongation of QRS interval (5th day), flattening of T wave (beginning of 4th week), and prolongation of PR interval (end of 4th week). Terminal cardiovascular studies were conducted under urethane anesthesia. EKG changes were comparable to those recorded in conscious rats, but no decrease in T wave voltage occurred. Blood pressure and heart rate remained unchanged. Cardiac output was decreased after 5 and 7 weeks of treatment, when heart weights were also significantly reduced. The response of cardiac output and mean arterial blood pressure to intravenously injected norepinephrine and epinephrine remained unchanged. Catecholamine-induced arrhythmias occurred less frequently in emetine-treated animals than in controls. No significant structural lesions of the heart muscle were detected by light microscopy. The cardiotoxic effects observed in rats were similar to those reported in humans receiving the usual therapeutic dose of approximately 1 mg/kg/day. We conclude that cardiovascular function studies can make an important contribution to the predictive value of animal toxicity experiments.

Special instrumentation problems encountered in physiological research concerning the heart and circulation in man.

T HE FUNCTION OF THE HEART is to maintain an adequate flow of blood through the lungs and to the body. A quantitative study of this function therefore requires physical measurements of such variables as pressure, volume, velocity of flow, volume of flow, and others. For the most part, measurement of physiologic variables concerned in the heart and circulation of man requires that these determinations be carried out on intact unanesthetized human beings. Therefore, direct measurements of many of the variables must commonly be made through small needles or long, narrowbore, flexible tubes. Since variables such as blood pressure have both static and dynamic components, their high-fidelity recording under such circumstances requires close attention to the frequency and damping characteristics of the instruments used. Adequate instrumentation must be capable of faithful reproduction of both the static component and all dynamic components of a magnitude to be of practical importance. The highest frequencies of the dynamic components of practically important magnitudes in a complex wave form, such as an arterial pressure pulse or the action potential complex of the heart muscle (electrocardiogram), are not accurately known. It is generally considered, however, that instruments with a uniform dynamic sensitivity to the tenth harmonic of the fundamental frequency of such complex wave forms are suitable for high-fidelity recording of the wave concerned. By this criterion, since the heart rate of human beings seldom exceeds 240 beats per minute, an instrument with a uniform sensitivity from 0 to 40 cycles per second should be adequate for the recording of arterial blood pressure and most other physiologic variables associated with the cardiovascular system. Recent direct evidence (22) indicates that manometer systems with a uniform dynamic response to 10 cycles per second will record peripheral arterial pressure in man without significant amplitude distortion. It is of interest also that the sensitivity 'Abstract of paper presented at Gordon Research Conference on Instrumentation, August 4, 1950. of the majority of clinically acceptable electrocardiographs is diminished by more than 20 per cent at a frequency of 40 cycles per second. In the functioning cardiovascular system, the various factors of pressure, flow, velocity, rate, and so forth are all mutually interrelated and continuously varying. Therefore, accurate studies of the over-all function of the circulatory system require continuous recording of multiple variables. The desirability of recording multiple physiologic variables in studies of cardiovascular function is well illustrated by the results of studies concerning the nature of the blackout and unconsciousness sometimes experienced by pilots as a result of exposure to positive acceleration or centrifugal force (12, 16, 26). Sudden exposure of a fighter pilot to a commonly experienced positive acceleration of five times the force of gravity (5g) will, because of the effective increase in the weight of the blood, reduce arterial pressure at head level to zero. Studies of the physiologic effects of this type of stress in human beings are carried out under controlled laboratory conditions by means of human centrifuges (26), perhaps the largest type of physiologic instrument designed for the study of the circulation (1) (Fig. 1). Physiologic recordings taken during exposure of a normal subject to positive acceleration on the human centrifuge are shown in Fig. 2. The left panel shows the changes produced by an exposure to 4.6g when the subject was unprotected. The increase in weight of the blood associated with this acceleration reduced arterial blood pressure temporarily to zero at head level, and a temporary loss of vision resulted. The reflex compensatory increases in blood pressure at heart level induced by the lowered blood pressure in the head region (carotid sinus) are evident during the latter portion of this exposure. The center panel illustrates the increase in arterial pressure produced by inflation of a pneumatic antiblackout suit. The panel on the right was recorded from the same subject during exposure to 5.5g while protected by the antiblackout suit. Protecticn is afforded by the increase in blood pressure at heart level produced by inflation of the suit.