Cardiovascular measurements relevant to heart size in copper-deficient rats.

Dietary copper deficiency in animals is often associated with cardiac enlargement and anemia. In this study we examined the hypothesis that anemia leads to a high cardiac output state that results in work-induced (physiological) cardiac hypertrophy. Blood pressure was measured by carotid cannulation and cardiac output was measured by aortic flow probe in anesthetized, open-chested rats that had been subjected to various degrees of dietary copper deficiency for five weeks. Cardiac output was unaffected by dietary copper deficiency. However, the components of cardiac output were found to vary reciprocally, heart rate decreasing and stroke volume increasing with copper deficiency. Further, total peripheral resistance, calculated as the ratio of mean arterial blood pressure and cardiac output, was depressed by dietary copper deficiency. These findings suggest that bradycardia and depression of vascular resistance induced by copper deficiency contribute to increased venous filling and a resultant increase in stroke volume; these factors may lead to cardiac hypertrophy. A significant correlation between stroke volume and heart weight in rats of varying copper status supports this conclusion.

Comparison of rat aortic, carotid & femoral artery viscoelastic properties using harmonic analysis.

Viscoelastic properties of rat (Wistar Kyota) large (6 aorta), medium (12 carotid) and small (8 femoral) in vitro artery segments, were contrasted over a wide range of static and dynamic pressures. Relationship of change in static pressure (delta dyne/mm2) to diameter (delta mm) was used to estimate a segment's incremental elasticity (KD) at each pressure level. Dynamic intravascular pressure response (Po) was recorded during swept frequency pressure (2-200 Hz; +/- 10 mm Hg) inputs as superimposed on mean pressure steps of 40, 80, 120, 160 and 200 mm Hg (P(i)). Analysis of dynamic data included Fast Fouier Transform of Po/P(i) with FANSIM (TUTSIM Products) curve fit to Bode plots. Curve fit coefficients were used to estimate properties of natural frequency (omega n) damping, viscosity and inertia. Statistical analysis employed ANOVA and SNK multiple comparison procedures. Results indicated that as step-pressure was increased diameter, KD and omega n increased proportionately in all segments. Values of KD and omega n were always highest in femoral and lowest in aortic segments. In all segments damping decreased inversely with increasing pressure while, viscosity and inertia were lowest between 80 and 160 mm Hg. These results documented distinct viscoelastic properties for the three arteries as well as, differences in their response characteristics.

Transfer function comparisons of rat aortic wall image and intravascular pressure harmonic responses.

This study examined the relationship between rat (mature Sprague-Dawley males) thoracic aortic wall and intraluminal pressure responses to a dynamic pressure input. High speed video image (Do) of outer wall area and intravascular pressure (Po) responses of the in vitro aorta were digitized and computer recorded during swept frequency pressure input (2-200 Hz; +/- 10 mm Hg) that was superimposed on static pressures from 20 to 200 mm Hg (Pi). Analysis included Fast Fourier transform (FFT) for Do/Pi and Po/Pi transfer functions and focused on comparison of coefficients from FANSIM (TUTSIM Products) polynomial equation fit to Bode plots for mean data of multiple aortas. The working hypothesis was that Do/Pi = Po/Pi. In FANSIM division by B0 of the general transfer function equality (A1s + A0)/(B2s2 + B1s + B0) yields (a1s + a0)/(b2s2 + b1s + 1); which was the form analyzed. Graphic and statistical comparisons indicated no difference for coefficients a1, a0, b2, and b1 between Do/Pi and Po/Pi. Coefficients b2, and b1 varied with change in level of static pressure. Values for a1 for both Do/Pi and Pi/Po remained relatively constant and appeared independent of static pressure. These results indicated appropriateness of the transfer function form and suggested that: b2, represented inertia of wall and intraluminal fluid mass; b1, represented wall and fluid viscosity influence; a1, represented influence of fluid viscosity and a0, represented influence of wall elasticity.

The mobility analog for modeling the intra-arterial pressure wave parameters.

To assist in the identification of physical/physiological parameters obtained from in vivo rat aortic artery dynamic pressure data, the natural (mobility) mechanical circuit model was constructed. The direct electrical analog of the model thus obtained was then analyzed using SPICE. The experimental data were obtained using a Multifunction Pressure Generator (MPG), appropriate pressure probes, and a high-speed video camera. Two 486 computers were used for system control and data recording and computation. Transfer functions in rational form of the ratio of the MPG input pressure (Pi) to the intra-arterial pressure (Po) were then generated in the s-domain. The mechanical circuit described by these rational functions was then constructed and transformed into its equivalent electrical model for analysis. On this basis, physiological pressures are represented by electrical currents, and volume flow rates by electrical voltages. The results obtained through steady-state (Bode plot) and transient analysis of the model developed suggest a compartmental model that explains the experimental observations. The mobility model is an improvement over previous models in that the mass element is referred to a single frame of reference, which agrees with the physical property that mass is a one-terminal device.

Harmonic analysis of intravascular pressure response as an index of arterial wall mechanical properties.

The ability to routinely assess mechanical properties of large blood vessels, like the aorta, before an aneurysm or rupture occurs, could benefit diagnostic and therapeutic procedures and save lives. In this study, images of the wall area and intravascular pressure (IP) responses of in vitro rat aorta were recorded during swept frequency pressure input (2-200 Hz; +/- 10 mm Hg) superimposed on mean pressures from 20 to 160 mm Hg. Data analysis included Fast Fourier transform (FFT) of input and responses. Wall and IP responses were underdamped with respective resonance frequencies (Wn) that varied as a function of mean input pressure and the nonlinear nature of wall elasticity. Results indicated closely coupled wall and IP responses and suggested that the IP response may be an adequate index of wall elasticity without need of a direct measure of wall displacement. We considered results to be a key step towards development of a clinical tool which would facilitate analysis of mechanical properties of in vivo conducting vessels.

Synchronizing blood vessel response CCD imagery to swept frequency dynamic pressure signals.

Harmonic analysis of the pressure and wall responses of a blood vessel exposed to a dynamic pressure input signal required the development of a software application which could properly synchronize the data gathered by two separate microcomputers. In order to accomplish this task, the Pressure-Image Editor was developed. The first computer is used to generate a swept frequency sinusoidal dynamic pressure input signal while at the same time monitoring the resulting response pressures. The second computer is used to record the physical (visual) response of the artery to the pressure signal via a high speed CCD camera and video digitizer. Using the Pressure-Image Editor, 256 animated images along with 65,536 pressure points can be combined and synchronized based on the camera frame rate, input trigger frequency, and any internal timing delays. The Pressure-Image Editor is a object-oriented application written in C++ and includes a window based graphical user interface.

Virtual instrumentation for frequency analysis of carotid sinus responses.

An advanced microcomputer based process control and instrumentation system was developed for real time frequency analysis of the viscoelastic relationships between the carotid sinus wall and indwelling baroreceptors. A 486 based AT bus microprocessor running data acquisition and visualization software was customized providing a virtual instrument for data collection, display, and recording. A full complement of signal processing algorithms was developed for the collection of large time sampled data sets and their conversion to the frequency domain for analysis. Polynomial curve fitting procedures were used for transfer function estimation of wall viscoelastic properties. Simulated in situ sinus data was collected and analysis was used to test the methodology.

Endothelial vasoactive influence simulated by exponential feedback.

We hypothesized that results from rabbit carotid sinus wall and baroreceptors could be simulated using exponential feedback in a viscoelastic model. Wall and baroreceptor were each modeled by second order differential equations. Coefficients for viscosity, elasticity and feedback were estimated from experimental data. Feedback of model wall distension (y1) on viscosity (C) was expressed by the transfer function: C/y1 = RW/(s tau W + 1). With gain (RW) = 52.5E6 N(s)/m2 and tau W = 34 sec, this feedback resulted in simulation of wall response for sinuses with intact endothelium. Model receptor required no (or negative gain) feedback to simulate baroreceptors.

Model inferences on baroreceptor & sinus wall responses.

Mechanical associations between sinus wall elements and those between wall and baroreceptor were modeled with differential equations. Viscoelastic relationships were tested using frequency domain analysis (TUTSIM, FANSIM). Two wall models were examined. The first had a single degree of freedom (df) and the second was a cascade system with two df. Component of the cascade model represented adventitia and media layers of the wall. This wall model had little deviation in gain between 0.1 and 10 Hz; regardless of a 100 fold difference in component damping. Properties of a wall-receptor model were in part estimated from myelinated baroreceptor responses (Brown et al., Circ. Res. 42:694-702, 1978). The wall-receptor model was designed with a natural frequency (omega b) of 12.7 Hz and damping ratio (zeta b) of 0.2 for the receptor and omega w of 50 Hz and zeta w of 1.2 for the wall component. Analysis of receptor responses, with respect to input forcing function, resulted in a omega b of 12.6 Hz. Analysis of responses with respect to those of the wall, resulted in a omega b of 16.0 Hz. These results are indicative of the complexity involved with interactive systems. If frequency analysis is used to estimate mechanical associations between sinus wall elements and baroreceptors, modeling can provide comparative data for interpretation of experimental responses.

Frequency analysis instrumentation for sinus wall and baroreceptor responses.

Blood pressure regulation involves feedback signals from baroreceptors detecting wall strain of arterial sinuses. A research goal is identification of wall viscoelastic properties and associations between elements and baroreceptors. This report presents development of computer-based procedures for control of pressure inputs and recording responses of an in situ carotid sinus. Features include a hydraulic system to generate swept-frequency sinusoidal pressure inputs (0.2 to 200 Hz); measurements of: (i) sinus wall area and vectors of strain using a fiber optic sensor system, (ii) intrasinus pressure using solid state probes, (iii) baroreceptor fiber activity using a unipolar electrode and (iv) algorithms for data archival, frequency domain analysis and transfer function determinations. Data analysis will focus on estimates of wall properties of elasticity (K), viscosity (C), natural frequency (omega w), damping ratio (zeta w), reactive mass (Mw) and relationships to similar properties at tissue-baroreceptor junctions. Computer-based procedures are exemplified with data detailing mechanical properties of the hydraulic system; which is an important prerequisite to analysis of sinus viscoelastic properties.

Cardiovascular responses to unilateral and bilateral stimulation of rabbit aortic nerves.

Reflex heart and mean arterial pressure (MAP) responses during unilateral and bilateral electrical stimulation of the central end of the cut aortic nerves were studied in 14 anesthetized closed-thorax rabbits. During control of carotid intrasinus pressure (ISP), with ISP = MAP, heart rate was 248 +/- 12 beats/min and fell -79 +/- 14, -61 +/- 16, and -117 +/- 16 beats/min during left (LAN), right (RAN), and bilateral (BAN) nerve stimulation. MAP was 79 +/- 5 mmHg and fell -57 +/- 4 (LAN), -46 +/- 6 (RAN), and -65 +/- 4 mmHg (BAN). Responses were also determined following blockade of cardiac vagal efferents (atropine) and then vagotomy (n = 4) or vagotomy alone (n = 10). Results indicated that cardiac parasympathetic effects of LAN and RAN stimulation were additive, whereas the respective summation of cardiac and arterial vascular sympathetic effects were mutually inhibitory. BAN stimulation at low (25 mmHg) and high (greater than or equal to 125 mmHg) ISP levels resulted in different magnitudes of MAP and heart rate responses before and after vagotomy and beta-receptor blockade. These results indicated that summation was mutually inhibitory for cardiac and vasomotor sympathetics when maximal stimulation of opposite influence was applied to aortic and carotid afferents. However, arterial baroreceptor afferents may summate differently at more normal blood pressure conditions.

Modulation of rabbit carotid baroreflex during positive end-expiratory pressure.

Modification of carotid baroreflex heart and vascular responses during increased lung positive end-expiratory pressure (PEEP) were measured anesthetized aortic-denervated rabbits. Static carotid intrasinus pressure (ISP) was varied in increments of 12.5 mmHg over 25-140 mmHg during lung inflation conditions ranging from spontaneous breathing (SB) to positive-pressure respiration at 0.0-7.5 cmH2O PEEP. To distinguish cardiopulmonary vagally and nonvagally mediated influences, heart rate (HR), mean arterial pressure (MAP), cardiac output (CO), and total peripheral resistance (TPR) were measured and compared before and after sequential vagotomy and beta- and alpha-receptor blockade. When compared with responses of SB animals the HR-ISP relationship was not significantly altered during controlled respiration (CR) with PEEP before or after vagotomy. With CR and then PEEP, MAP-ISP relationship curves and linear slope values (ISP range 62-113 mmHg) were significantly depressed when compared with those of SB rabbits. Before vagotomy slope values were -1.61 (SB), -1.22 (CR + 0.0 cmH2O PEEP), and -0.82 (CR + 7.5 cmH2O PEEP); respective values after vagotomy were -2.26, -0.96, and -0.64. Results of CO and TPR responses during low ISP and PEEP demonstrated components of both vagally and nonvagally mediated influences from inflation sensitive cardiopulmonary receptors.U

Rabbit carotid baroreflexes after carotid sympathectomy, vagotomy, and beta blockade.

Factors that modify carotid vascular baroreflexes were studied in anesthetized rabbits after section of the cervical aortic nerves. We recorded steady-state reflex responses of heart rate (HR) and mean arterial pressure (MAP) to changes in isolated nonpulsatile carotid intrasinus pressures (ISP) over a wide range. These measurements and the procedures were repeated 1) after sympathetic denervation of the carotid sinuses by section of the cervical sympathetic nerve below the superior cervical ganglia; 2) after cervical vagotomy; and 3) after beta-receptor blockade by propranolol administration. The linearity of the MAP-ISP relation curve slope was determined between ISP levels of 63 and 100 mmHg. Comparison of results before and after sympathetic denervation of the sinuses indicated that the denervation significantly lowered the position of the MAP-ISP relation curve over a mid-ISP range. Subsequent vagotomy significantly elevated both HR-ISP relation curve and MAP-ISP relation curve. AFter beta-receptor blockade HR remained constant, whereas the slope of the MAP-ISP relation curve decreased to -1.34 from the slope of -2.26 before blockade. Comparison of results before and after beta blockade in the vagotomized animals suggested a substantial cardiac influence on carotid reflex control of MAP.

Altered cardiovascular reflex responses during positive pressure breathing.

Cardiovascular responses during hyperinflation produced by positive end-expiratory pressure (PEEP) are considered to be reflexly influenced by pulmonary mechanoreceptors. Numerous studies have indicated heart and vascular effects attributed to mechanical events and cardiopulmonary mechanoreflexes. Yet interactions of these modalities with the systemic baroreflexes are not clear. We examined aspects of these modulatory interactions by distinguishing changes in pulmonary, heart, and vascular responses during PEEP-hyperinflation before and after progressive elimination of chemo-, mechano-, and baroreflex influences in the closed-chest anesthetized rabbit. During respiratory alkalosis PEEP was imposed in increments of 2.5 cm H2O (range 0.0 to 7.5 cm H2O) before and during control of carotid intrasinus pressure and following aortic denervation and vagotomy. Heart rate responses during PEEP increased prior to aortic denervation, decreased following elimination of baroreflexes, and were abolished after vagotomy. The fall in mean arterial pressure (MAP) during PEEP was accentuated during elimination of the baroreflexes and ameliorated following vagotomy. Mean right atrial (MRAP), intrapleural (MIP), and right atrial transmural pressure increased during PEEP prior to vagotomy. Regression analyses of MAP versus MRAP and MAP versus MIP suggest that vagally receptors reflexly influence venous as well as systemic arterial vascular pressure. Conclusion indicate that when superimposed on mechanical events, cardiopulmonary mechanoreceptors and arterial baroreceptors effect conflicting facilitory reflex influences on heart and vascular responses during PEEP-hyperinflation.

Rabbit cardiovascular responses to aortic nerve stimulation at fixed carotid pressure.

In pentobarbital-anesthetized rabbits with aortic nerves cut, reflex heart rate and mean arterial pressure (MAP) changes were quantified in response to maximal central stimulation of the left aortic nerve (LANS) before and during steady-state changes in isolated carotid intrasinus pressure (ISP). To distinguish possible vagally mediated cardiopulmonary influences, responses were measured before and after vagotomy. Changes in MAP observed by altering ISP within +/- 15 mmHg of the equilibrium pressure (EP) were linear and inversely correlated to changes in ISP, with a slope of approximately 3 both before and after vagotomy (r greater than or equal to 0.929, P less than 0.05). The peak fall in MAP during LANS was dependent upon ISP. The change in the MAP responses to LANS for each mmHg change in ISP ranged from 1.7 with vagi intact to 1.3 after vagotomy. Heart rate was unaltered by isolation of the carotid sinus and was independent of the small changes in ISP between +/- 15 mmHg of EP. These results indicate that blood pressure changes elicited by the aortic baroreflex are extremely sensitive to the degree of carotid sinus compensation. Thus, to assess the sensitivity of any arterial reflex area, the existing level of compensation by other barosensitive areas must be known.

Fluid and electrolyte shifts in women during +Gz acceleration after 15 days' bed rest.

Twelve women (23-34 yr), comprising a bed-rest (BR) group of eight subjects and an ambulatory (AMB) group of four subjects, were centrifuged after 14 days of ambulatory control (C),after 15 days of a 17-day BR period, and on the third day of recovery (R). Venous blood was taken before and after the third +3.0 G acceleration run (1.8 G/min). Relative to (C), the +Gz tolerance after BR was reduced -49.0% (P less than 0.05) in the BR group and -38.7% (NS) in the AMB group; during (R) the BR group regained up to 89.4% and the AMB group up to 87.1% of their (C) tolerances. In each of the three test periods, the shifts in plasma Na, Cl, PO4, and osmotic contents, which accompanied +Gz, followed the outward shift of plasma volume (PV). The correlation of the shift of PV during acceleration with the +Gz tolerance was 0.72 (P less than 0.01). During acceleration, the PV and electrolyte loss for both groups after BR was about half the loss of (C) and (R). Compared with (C) and (R) values, potassium shifts were variable but the mean corpuscular volume and mean corpuscular Hb contents and concentrations were unchanged during all +Gz runs; The results indicate that: 1) the higher the (C) + Gz tolerance, the greater the tolerance decline due to BR; 2) relative confinement and reduced activity contribute as much to the reduction in tolerance as does the horizontal body position during BR; 3) bed-rest deconditioning has no effect on the erythrocyte volume during +3.0 Gz; and 4) about one-half the loss in tolerance after BR can be attributed to PV and electrolyte shifts.