Search PubMed⌕ Search

Biomedical subjects

N Westerhof

Publications and source records attributed to N Westerhof.

At least 91 records · Page 5Linked to original sources

Systemic autoregulation counteracts the carotid baroreflex.

The interaction between autoregulation and baroregulation and its effect on the gains of the short-term pressure regulatory system was studied by performing both open- and closed-loop experiments in the same five anesthetized, vagotomized dogs, and by analyzing the data making use of a new model. With carotid pressure constant (no baroregulation) the pressure-flow data were convex to the flow axis, thus indicating the presence of autoregulation. When baroregulation was present the data were convex to the pressure axis. Our model was able to fit the data as measured in both cases. From the fitting procedure the zero-flow pressure intercept Pzf, the autoregulation resistance gain Gra, and the baroregulation resistance gain Grb were estimated. Pzf was about 20 mmHg in three dogs and about zero in the other two. Average values of Gra and Grb were 13.0 +/- 3.5 mmHg min2/L2 and 0.83 +/- 0.25 min/L, respectively. The two curves which fitted the data points collected in the presence and in the absence of baroreflex intersected at a point (Qo, Po) generally different from the control point. We determined the open-loop gain, Goc = GrbQo, about the point (Qo, Po). The averaged value was 2.23 +/- 0.84. When autoregulation was neglected, the resistance gain Grb and the open-loop gain Goc obtained from the same closed-loop method were underestimated (0.32 +/- 0.15 min/L and 0.88 +/- 0.48, respectively). In the open-loop preparation the carotid sinuses were isolated and the aortic (P) versus carotid (Pca) pressure data were collected. A third-order polynomial was fitted to these data.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Response time of cardiac mitochondrial oxygen consumption to heart rate steps.

We investigated the time course of cardiac mitochondrial O2 consumption following steps in heart rate in 16 isolated rabbit hearts perfused with Tyrode solution. The time course was characterized by the mean response time, i.e., the first statistical moment (mean time) of the impulse response function. Like the mean transit time for an indicator, it provides an important characteristic of the response time course. The venous O2 content transients during steps in heart rate were measured and corrected for O2 diffusion and vascular transport using a mathematical model with experimental information derived from O2 washout following steps in arterial O2 concentration or perfusion flow. We deduce from these washout experiments that the effective O2 solubility in heart tissue is 86 +/- 13% (mean +/- SE) of solubility in water. The measured venous mean response time following a step in heart rate at 37 degrees C was 17.6 +/- 1.1 s. The mean response time of cardiac mitochondrial O2 consumption to changes in heart rate after correction for O2 transport was 7.7 +/- 0.7 s.

Animals↗

Normalized input impedance and arterial decay time over heart period are independent of animal size.

The arterial system of mammals in the weight range from 0.6 to 70 kg is characterized by the three-element windkessel, a succinct representation of the arterial tree consisting of the parameters peripheral resistance (Rp), total arterial compliance (C), and aortic characteristic impedance (Zc). The values of these parameters in resting conditions are related to body mass (M). The time constant, or decay time (tau), of the arterial system (defining rate of decay of aortic pressure in diastole), the product of Rp and C, is also evaluated. The dependencies of the heart period (T, inverse of heart rate), and durations of ejection (Ts) and of diastole (Td) in resting conditions are also determined as a function of M. It is found that Rp = Rp0M-0.93; Zc = Zc0M-0.97; and C = C0M+1.23, where Rp0, Zc0, and C0 are proportionality constants. Zc is thus a constant fraction of Rp in all mammals. tau is related to M as tau = tau 0M+0.29; T and Td are related to M as T = T0M+0.27 and Td = Td0M+0.30, where tau 0, T0, and Td0 are proportionality constants. The duration of diastole is thus a constant fraction of T, and the ratios T/tau and Td/tau are independent of M. The findings indicate that arterial input impedance, normalized to aortic Zc and plotted as a function of frequency normalized to heart rate, is similar for all mammals. The finding that the ratio Td/tau is the same in mammals (and Ts/T and stroke volume/M are constant) explains the constancy of pulse pressure (systolic minus diastolic pressure).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Matching between ventricle and arterial load. An evolutionary process.

The hemodynamic properties of the ventricle are related to those of the arterial load. However, the precise nature of this relation is not known. At least three different matching criteria have been described in the literature: optimization of heart rate, of power output, and of external efficiency. Although these suggestions are based on experimental findings, there is little understanding of the underlying principles. We now suggest that the balance between the ventricle and its load is a result of the evolutionary process. To support our view, three simple assumptions are proposed regarding the evolutionary determinants underlying the relation between ventricle and arterial load: 1) Arterial pressure and flow to be generated by the ventricular pump under normal (control) conditions are set by the demands of the body. 2) Mechanical properties of contractile machinery and arterial wall material are given. 3) The heart and arterial system should have minimum size. On the basis thereof, we argue that heart rate is related to maintenance of diastolic pressure and show that the ventricle operates close to optimum power and efficiency to attain minimum size.

Animals↗

Heart rate and cardiac energetics.

The heart and arterial system are matched in the sense that the heart pumps at maximal external power. Why external power is optimized and what regulatory mechanisms are responsible for this optimization are not known. In the present report we will suggest a mechanism of matching on the basis of the following arguments. 1) Mean aortic pressure, the perfusion pressure for most organs, most notably the cerebral circulation, is similar in mammals. 2) Heart period (T), a cardiac parameter, is related to body mass in a similar way as the decay time (tau = RpC, where R is peripheral resistance and C is total arterial compliance) of aortic pressure in diastole, a vascular parameter. In other words, the ratio of T/tau is similar in all mammals and assures a similar aortic pressure in diastole so that coronary perfusion, which mainly takes place in diastole, is guaranteed. 3) Assuming given mechanical properties of mammalian cardiac muscle, optimal power delivery relates to a minimal cardiac size; in other words, during evolution total cardiac volume was minimized, resulting in a heart that pumps at maximal power.

Animals↗

Arteriolar and venular reactivity to superfusate pO2 in tissues with different metabolic capacity. A study in skeletal muscle and mesentery of the rat.

In skeletal muscle (extensor hallucis proprius) and mesentery of anesthetised (pentobarbital 30 mg/kg) female rats (200 g) we have compared reactivity to O2 of arterioles and venules with their response to a vasoconstrictor (epinephrine 5.5 x 10(-7) M) and a vasodilator (adenosine 10(-4) M). Muscle arterioles fully constricted with O2 and epinephrine and dilated with adenosine (22%). Muscle venules did not respond to changes in superfusate pO2, constricted 18% with epinephrine and dilated 10% with adenosine. In the mesentery changes in superfusate pO2 had no effect on diameters of arterioles or venules but epinephrine fully constricted arterioles and constricted venules by 19%, while adenosine dilated arterioles (6%) but not venules. When we set arteriolar and venular diameters during adenosine superfusion at 100%, muscle arterioles appeared to operate at 63% and mesenterial arterioles at 84% of maximal diameter at normal tissue pO2. For venules these percentages were 91 and 97%, respectively. Arterioles and venules in muscle thus have higher tone and muscle arterioles are greatly sensitive to changes in tissue pO2 while in our preparation mesenterial arterioles are not.

Adenosine↗

Geometry and pump function in cardiac ventricular hypertrophy.

Ventricular pump function can be quantified by the inverse relation between pressure and output, i.e., the pump function graph, which is obtained by varying arterial load without changing end-diastolic volume, inotropic state and heart rate. The ratio of pressure and output, i.e., the peripheral resistance, can be represented in the same graph by a line through the origin. The 2 pressure-output relations intersect in the working point, i.e., the pressure and flow at the prevailing steady state. In normal, anesthetized cats the ventricle appears to be matched to the arterial load in the sense that the working point is found at the optimal power, i.e., the optimal value of the product of pressure and output along the pump function graph. To maintain this matching criterion during pressure overload, the ventricular volume has to remain the same while thickening of the wall takes place: concentric hypertrophy. With volume overload, matching would be preserved with eccentric hypertrophy. Because volume and pressure overloads typically lead to eccentric and concentric hypertrophy, respectively, the matching criterion may be a valuable predictor of the geometric changes found with changes in load. This idea was further investigated experimentally by determining the position of the working point in the perinephritic cat that had 1 kidney removed and the other wrapped in cellophane for 15 to 26 weeks. The working point was no longer found at the optimal power, indicating that either matching was permanently comprised or that the ventricle was still trying to restore matching.

Animals↗

Response time of mitochondrial oxygen consumption following stepwise changes in cardiac energy demand.

We determined the speed with which mitochondrial oxygen consumption and therefore the mitochondrial ATP-synthesis adapted to changes in metabolic demand in the rabbit heart. This was done by measuring the oxygen uptake of the whole heart during a stepwise change in heart rate and correcting for the time taken by diffusion and by convective transport in the blood vessels. Data for the correction for transport time were obtained from the response of venous oxygen concentration to a stepwise change of arterial oxygen concentration. The time constant of the response of mitochondrial oxygen consumption to a step change in heart rate was found to be 4-8 s.

Adenosine Triphosphate↗

Isolated aorta setup for hemodynamic studies.

A setup consisting of a high-performance hydraulic pump connected to the ascending part of an isolated aorta, including all major distal branches, each loaded with calibrated artificial resistors, was developed. The system was used to study total aortic compliance of the baboon as a function of mean aortic pressure (n = 5). The aorta loaded with the resistors was mounted in a custom-designed sink table, such that it was submersed in physiological saline maintained at 37 degrees C. Mean distending pressure in the entire aorta could be varied. The three-element Windkessel model was used to estimate total aortic compliance from pressure and flow waves generated by the pump. Total aortic compliance as a function of mean pressure was fitted with a logarithmic function: Ln(Compliance) = A + B * P. The value of A (+/- SE) was: 1.565 +/- 0.319 and B: -0.020 +/- 0.003 (P less than 0.001). The results were compared with previously published results (also using the same three-element Windkessel fit) obtained in three of the same animals in vivo. The in vivo data were A: 1.095 +/- 0.235 and B: B: -0.019 +/- 0.003. In vitro data had a significantly higher value of A than in vivo (P = 0.017), implying a significantly higher aortic compliance in vitro than in vivo. Occlusion of the proximal descending aorta was performed at a low distending pressure (55 mm Hg) to determine the proximal compliance. It was found (n = 4) that 46 +/- 11% (SD) of the total arterial compliance is to be attributed to the ascending and proximal descending aorta.

Animals↗

Accurate measurement of intraarterial pressure through radial artery catheters in neonates.

A technique is described for accurate measurement of intraarterial pressure through radial artery catheters in neonates. The technique, which can be used for short-term monitoring, uses cannulation of the radial artery with a 24-gauge Teflon catheter, connected by a Luer-Lok fitting to a three-way stopcock and a high-fidelity tip transducer. In vitro studies showed that the system is linear and the frequency response is flat (+/- 3 dB) up to 50 Hz. The technique permits gathering of high-quality pressure data and can be used in the area of neonatal clinical research for short-term monitoring. It needs to be developed further before routine application in clinical practice can be recommended.

Arteries↗

Short-term systemic autoregulation.

We studied total systemic autoregulation in closed-chest, chloralose-anesthetized dogs. Cardiac out-put (previously implanted electromagnetic flow probe on ascending aorta) and aortic pressure were varied by reducing venous return using a balloon catheter in the vena cava. Compensatory action of the baroreflex was prevented by bilateral vagotomy and isolation of both carotid sinuses. To avoid high vessel tone carotid sinus pressure was set at the original baseline value using a pressurized blood reservoir. With each balloon inflation aortic flow and aortic pressure decreased and stabilized in about 1 min. Pressure and flow were allowed to return to base-line values after each balloon inflation in an attempt to minimize the activation of slower regulatory mechanisms. The steady-state pressure-flow relations could be fitted with a sigmoidal curve. The mean quality (0 less than Q less than 1) of autoregulation in eight dogs was 0.41 +/- 0.08 (SD). Autoregulation was found in the pressure range from 42 to 140 mmHg. The early appearance of total systemic autoregulation suggests that, in the intact animal, it may counteract baroreflex control.

Animals↗

Two zero-flow pressure intercepts exist in autoregulating isolated skeletal muscle.

The autoregulating vascular bed of the isolated canine extensor digitorum longus muscle was investigated for the possible existence of two positive zero-flow pressure axis intercepts, a tone-dependent one and a tone-independent one. An isolated preparation, perfused with autologous blood, was used to exclude effects of collateral flow and nervous and humoral regulation while autoregulation was left intact [mean autoregulatory gain 0.50 +/- 0.24 (SD)]. In a first series of experiments, the steady-state (zero flow) pressure axis intercept [mean 8.9 +/- 2.6 (SD) mmHg, tone independent] and the instantaneous (zero flow) pressure axis intercept [mean 28.5 +/- 9.9 (SD) mmHg, tone dependent] were determined as a function of venous pressure (range: 0-45 mmHg) and were independent of venous pressure until the venous pressure exceeded their respective values. Beyond this point the relations between the venous pressure and the steady-state and instantaneous pressure axis intercept followed the line of identity. The findings agree with the predictions of the vascular waterfall model. In a second series it was shown by means of administration of vasoactive drugs that the instantaneous pressure axis intercept is tone dependent, whereas the steady-state pressure axis intercept is not. It is concluded that there is a (proximal) tone-dependent zero-flow pressure at the arteriolar level and a (distal) tone-independent zero-flow pressure at the venous level.

Animals↗

Pulmonary arterial compliance at rest and exercise in normal humans.

We evaluated the feasibility of determining pulmonary arterial compliance (Cp) by a parameter estimation procedure based on the three-element windkessel model. Eight normal patients studied with multisensor micromanometry technology had simultaneous rest and exercise pulmonary artery pressures (PAP) and flows recorded. These were submitted to the model and independent methods to determine Cp, pulmonary characteristic impedance (Zc), and pulmonary vascular resistance (PVR). Significant changes in heart rate, PAP, and stroke volume (P less than 0.05) occurred with exercise. In comparing rest and exercise Zc and PVR values determined by the model and independent methods, and in comparing each method for these values, there was no significant difference. Model-derived and independently derived estimates of Cp were significantly different at rest (P less than 0.04) and exercise (P less than 0.001). There was no significant difference between rest and exercise values of Cp by either method. The model estimates of PVR at rest (64 +/- 11 dyn.s.cm-5) and exercise (41 +/- 7 dyn.s.cm-5) (P = 0.06) and the model Zc value at rest (22 +/- 3 dyn.s.cm5) were appropriate. The model Cp values at rest (0.22 +/- 0.05 ml.mmHg-1.kg-1) correlated with previously reported normalized values in other species. This study reports the successful use of a parameter estimation procedure based on the three-element windkessel model to describe pulmonary artery compliance in normal humans.

Adult↗

Coronary oscillatory flow amplitude is more affected by perfusion pressure than ventricular pressure.

In this study on the isolated, maximally vasodilated, blood-perfused cat heart we investigated the relation between left ventricular developed pressure (delta Piv) and coronary oscillatory flow amplitude (diastolic minus systolic flow, delta F) at different levels of constant perfusion pressure (Pp). We hypothesized that the effect of cardiac contraction on the phasic flow results from the changing elastic properties of cardiac muscle. The coronary vessel compartment can, as can the left ventricular lumen compartment, be described by a time-varying elastance. This concept predicts that the effect of left ventricular pressure on delta F is small, whereas the effect of Pp is considerable. Both the waterfall model and the intramyocardial pump model predict the inverse. The relation between delta Piv and delta F at a Pp of 10 kPa is delta F = (4.71 +/- 3.08).delta Piv + 337 +/- 75 (slope in ml.min-1.100 g-1.kPa-1 and intercept in ml.min-1.100 g-1; n = 7); the relation between (constant levels of) Pp and delta F at a constant delta Piv of 10 kPa is delta F = 51.Pp + 211 (slope in ml.min-1.100 g-1.kPa-1 and intercept in ml.min-1.100 g-1; n = 6). The differences in slope are best predicted by the time-varying elastance concept.

Animals↗

Coronary resistance increase by nondefatted albumin in saline-perfused rabbit hearts.

In isolated hearts perfused with salt solutions, albumin is often added in low concentrations for preservation of endothelial function. Albumin in low concentrations is also sometimes used as an intravascular indicator in such preparations. We perfused isolated rabbit hearts according to Langendorff with a constant flow of Tyrode solution. Despite maximal vasodilation with 10 microM adenosine, coronary vascular resistance increased by 14% after 0.3 g/100 ml nondefatted bovine serum albumin (Sigma A-9647) was added to the perfusate compared with the control resistance with no albumin present. The 50% response time for the vasoconstrictive response to the step change in albumin concentration was 20 +/- 13 s (mean +/- SD). When 0.3 g/100 ml of defatted albumin (Sigma A-6003) was added, the resistance increase was only 1.4% and is explained by increased viscosity. Vasoconstrictive effects of certain nondefatted albumin preparations must be taken into account by investigators who perfuse organs with albumin-containing solutions.

Animals↗

Oxygen uptake in saline-perfused rabbit heart is decreased to a similar extent during reductions in flow and in arterial oxygen concentration.

In experiments reported in the literature, oxygen uptake in saline-perfused heart decreased after small reductions in arterial O2 concentration (CaO2) at constant perfusion flow. This may have resulted from the decrease in O2 supply, but may also have been due to decreased O2 demand caused by reduced perfusion pressure following hypoxic vasodilation (garden hose effect). We tested both possibilities in 8 isolated rabbit hearts, perfused with Tyrode solution at 37 degrees C, perfusion pressure 94 +/- 4 mm Hg (mean +/- SD). Vasodilation with 10 microM adenosine in the perfusate prevented changes in perfusion pressure during hypoxia. Oxygen uptake decreased significantly by 5.8 +/- 2.1% for a 10% decrease in CaO2 at constant flow, and by 4.4 +/- 1.8% per 10% decrease in flow at constant CaO2. In both cases a 10% reduction in oxygen supply was applied and the decrease in oxygen uptake was not significantly different. The decrease in perfusion pressure during flow reduction did therefore not cause a detectable decrease in oxygen consumption via the garden hose effect in addition to the decrease caused by reduced oxygen supply. The data show that oxygen uptake in saline-perfused rabbit heart, at 37 degrees C, is limited by O2 supply.

Animals↗

A dynamic nonlinear lumped parameter model for skeletal muscle circulation.

A dynamic nonlinear lumped parameter model of the circulation of skeletal muscle for constant vasoactive state is presented. This model consists of four compartments that represent the large arteries, the arterioles, the capillaries and venules, and the veins, respectively. The first compartment consists of a linear compliance (C1) and resistance (R1). The third compartment possesses no compliance and is represented by a linear resistance (R3). The second and fourth compartments each consist of a nonlinear pressure-volume relation, resulting in a pressure dependent compliance (C2, C4, respectively) and nonlinear resistance (R2, R4, respectively). The eleven model parameters were collected in a complementary way: they were partly obtained from a priori knowledge including information at the microscopic level, and partly determined by means of an estimation algorithm. Estimated values of the compliances (in cm3.kPa-1.100 g-1, 1 kPa = 7.5 mmHg) and resistances (in kPa.s.cm-3.100 g) at an (arterial) inflow pressure of 10 kPa and a (venous) outflow pressure of 0 kPa were: C1: 0.014; R1: 6.6; C2: 0.565; R2: 84.6; R3: 37.9; C4: 1.044; R4: 24.5. The model (with the nonlinear pressure-volume relations) is able to predict the static and dynamic instantaneous (i.e., for constant vasomotor tone) pressure-flow relation and the instantaneous zero flow pressure intercept. These phenomena are therefore not necessarily the result of the rheological properties of blood. The secondary or delayed dilatation upon a positive inflow pressure step (or negative step in venous pressure) is predicted by the model implying that delayed dilatation is not necessarily related to changes in vasomotor tone. Venous outflow delay, upon a positive inflow pressure step (starting from zero flow), is also predicted by the model.

Algorithms↗

Mechanics of a thin walled collapsible microtube.

The purpose of this study is to measure the transmural pressure-cross sectional area relation of micro tubes (240 microns diameter) and to compare the measured perfusion pressure-flow relation with the pressure-flow relation calculated from the experimental pressure-cross sectional area relation. The microtubes are made by dipping a glass mould in a latex solution and glueing their outside ends to the inside of glass pipettes. The pressure-cross sectional area relation is determined both with a microplethysmograph (pressure-volume relation) and the microscope (pressure-diameter relations). Heparinized blood is used to include the rheological properties of blood as a perfusion medium. Static pressure-flow relations are obtained with a constant velocity piston pump for two values of external pressure (0 and 10 kPa) and with two downstream resistor settings (0 and 380 kPa cm-3 sec). The calculated pressure-flow relations using length and the experimental pressure-cross sectional area relation, Poiseuille's law, and accounting for the diameter- and shear-dependent viscosity compared well with the relations obtained from the experiments. It is also found that the pressure-flow relation shows an apparent zero flow pressure axis intercept (the extrapolation of the pressure-flow relation to the pressure axis), which can therefore be explained on the basis of the shape of the pressure-area relations.

Hemodynamics↗