Biomedical subjects

N Westerhof

Publications and source records attributed to N Westerhof.

At least 19 recordsLinked to original sources

PubMed1992

Modeling the circulation with three-terminal electrical networks containing special nonlinear capacitors.

Development, first of analog and later of digital computers, as well as algorithms for analysis of electrical circuits, stimulated the use of electrical circuits for modeling the circulation. The networks used as building blocks for electrical models can provide accurate representation of the hydrodynamic equations relating the inflow and outflow of individual segments of the circulation. These networks, however, can contain connections in which voltages and currents have no analogues in the circulation. Problems arise because (a) electrical current must flow in closed loops, whereas no such constraints exist for hydraulic models; and (b) electrical capacitors have a number of characteristics that are not analogous to those of hydraulic compliant chambers. Disregarding these differences can lead to erroneous results and misinterpretation of phenomena. To ensure against these errors, we introduce an imaginary electrical element, the nonlinear residual-charge capacitor (NRCC), with characteristics equivalent to those of a compliant chamber. If one uses appropriate circuit connections and incorporates the residual-charge capacitor, then all voltages and currents in the model are proper analogues of pressures and flows in the circulation. It is shown that the capacitive current represents the rate of change of volume of blood inside the vessel, as well as the rate of the corresponding displacement of volume of the surrounding tissue.

Blood Circulation↗

PubMed1992

A new mounting technique for perfusion of isolated small arteries: the effects of flow and oxygen on diameter.

There is at present no suitable technique available for performing pressure-flow studies in isolated small arteries (i.e., less than 500 microns), in which the effects of flow and pressure on artery dimensions can be studied independently. A new mounting technique is presented in which the ends of a vessel segment are cemented to the inner surface of two cannulae, with a tip diameter slightly larger than the outer diameter of the vessel, using two-component human fibrin glue. By means of this technique the pressure drop over the cannulae can be made small. First the effect of the glue on constrictive properties is studied. The glue used has no significant influence on the norepinephrine dose-response relation or on the relaxation in response to 1.0 microM acetylcholine. Small mesenteric arteries of the rabbit with outer passive diameters (at zero pressure) of 315 microns (+/- 22 microns SEM) are studied with this method. The effects of flow (shear stress) and oxygen are investigated (vessels are preconstricted (30%) with norepinephrine (1-2 microM)). The flow range used resulted in shear stresses between 0 and 290 dyn.cm-2, a range including values found in vivo. There is a significant (P less than 0.001) decrease in diameter when flow is increased, and hypoxia (pO2 less than 30 mm Hg) augmented the preconstriction with norepinephrine (P = 0.002). The flow effect and the oxygen influence are independent of each other. These results are similar to our previous findings in the femoral artery of the rabbit (diameter about 1200 microns).

Adhesives↗

PubMed1992

Coronary flow and left ventricular pressure during diastole in the anaesthetized dog.

There is controversy about the effect of left ventricular pressure on resistance of the intramyocardial coronary vessels. In anaesthetized dogs the effect of left ventricular pressure on coronary flow during diastole was studied using an extracorporeal circulation and allowing the heart to contract and relax isovolumically. At constant coronary perfusion pressure of about 45 mmHg with maximal coronary vasodilatation, produced by dipyridamole, increases in diastolic left ventricular pressure to 22 mmHg, producing a volume of 50 ml, did not affect diastolic coronary flow. It is suggested that in the intact animal over the physiological range of left ventricular diastolic pressure the resistance in the coronary vessels is not affected.

Anesthesia↗

PubMed1992

Influence of temperature on the response time of mitochondrial oxygen consumption in isolated rabbit heart.

1. In this study we determined the temperature dependence of the mean response time of cardiac mitochondrial oxygen consumption following steps in metabolic demand. Metabolic demand was altered by stepwise changes in heart rate or in left ventricular volume at 20 and 28 degrees C. 2. Ten isolated rabbit hearts were perfused with Tyrode solution at constant oxygen tension and constant arterial flow. A balloon was inserted in the left ventricle and developed pressure was measured. Coronary venous oxygen tension was measured continuously with a Clark-type oxygen electrode. 3. The mean response time of mitochondrial oxygen consumption is defined as the first statistical moment of the impulse response function. This mean response time of mitochondrial oxygen consumption, following the change in metabolic demand, is calculated from the measured mean response time for the change in coronary venous oxygen tension by subtracting the transport time resulting from diffusion and convective transport in the blood vessels. The transport time is obtained from a model for oxygen transport developed previously. Experimental data, necessary for the model calculation, were obtained from measurement of the coronary venous oxygen tension transients following stepwise changes either in arterial oxygen tension or perfusion flow. 4. The calculated mean response times of mitochondrial oxygen consumption were 26.9 +/- 3.0 s (mean +/- S.E.M.) at 20 degrees C and 14.9 +/- 1.0 s at 28 degrees C. The mean response times of mitochondrial oxygen consumption did not differ significantly for steps in heart rate and in left ventricular volume and between upward and downward steps. 5. We suggest that intracellular calcium concentration is not the sole regulator of mitochondrial oxygen consumption in the isolated rabbit heart, since steps in heart rate and in left ventricular volume showed the same time course of oxygen uptake. 6. The mean response time of mitochondrial oxygen consumption obtained in the isolated rabbit heart at 20 degrees C did not differ significantly from the mean response time of mitochondrial oxygen consumption of isolated rabbit papillary muscle. After combining our data with previously published data on empty beating hearts at 37 degrees C, a Q10, which is the factor by which the mean response time of mitochondrial oxygen consumption increases per 10 degrees C decrease in temperature, of 2.1 was calculated.

Animals↗

PubMed1992

Effect of perfusion pressure on force of contraction in thin papillary muscles and trabeculae from rat heart.

1. Increased coronary perfusion leads to increased myocardial contraction and oxygen consumption (Gregg's phenomenon) even when oxygen supply is presumably sufficient. Previous studies concerned whole hearts, however, in which local hypoxia may play a role. We developed techniques for internal perfusion of thin papillary muscles from rat heart. The influence of perfusion pressure on muscle contraction was studied. We investigated whether Gregg's phenomenon is due to (a) hypoxia, (b) stretch of the muscle fibres, or (c) increased contractility. 2. The effectiveness of the perfusion technique was demonstrated in four ways: (a) the diameter of the capillaries increased with perfusion pressure; (b) 14 +/- 4% (mean +/- S.D., n = 11) increase in muscle diameter was observed on a change of perfusion pressure from 0 to 50 cmH2O; (c) addition of India ink to the perfusate caused rapid staining of the entire muscle; (d) during internal perfusion and external superfusion peak force was mainly determined by the [Ca2+] in the internal perfusate. 3. An increase of perfusion pressure from 0 to 70 cmH2O induced 74 +/- 20% (mean +/- S.D., n = 11) increase in peak force of contraction. In the absence of internal perfusion peak force was not affected by approximately 50% reduction of the PO2 in the bathing solution (from 700 to 350 mmHg). Hence, oxygen supply was not a limiting factor, i.e. the effect of internal perfusion on force was not related to hypoxia. 4. Segment length was measured with markers attached to the surface of the muscle. Perfusion-induced changes in segment length were negligible (-0.2 +/- 1.5%, n = 11). Force-length relationships at different perfusion pressures show that the perfusion-induced increase in force was generally larger than the maximum increase in force that could be induced by stretch. Furthermore, the time course of stretch and perfusion effects on force was different. We conclude that Gregg's phenomenon is not related to changes in fibre length, i.e. the hypothesis of pressure-induced stretch ('garden hose' effect) does not apply to papillary muscles. 5. The pressure-induced changes in the force-length relationship were similar to the changes obtained with interventions that increase contractility, such as increased [Ca2+]. 6. Since hypoxia and length effects were not involved, and the effect of perfusion pressure was similar to that of inotropic interventions, we conclude that Gregg's phenomenon is a change in contractility. Possible explanations include changes in the ionic composition or volume of the interstitium, and inotropic factors produced by the endothelium or intramyocardial neurons.

Animals↗

PubMed1992

Global left ventricular perfusion: noninvasive measurement with cine MR imaging and phase velocity mapping of coronary venous outflow.

Velocity and volumetric flow of left ventricular venous outflow in the distal coronary sinus were measured with magnetic resonance (MR) velocity mapping techniques in 24 healthy men. A total of 16-21 velocity maps were acquired throughout the cardiac cycle. To determine the accuracy of the MR velocity-mapping pulse sequence, measurements were obtained with a flow phantom. Mean blood flow was 144 mL/min +/- 62 (standard deviation); mean velocity, 2.1 cm/sec +/- 1.0; and mean cross-sectional area, 1.2 cm2. Phasic measurements revealed a biphasic flow pattern in the coronary sinus, with a first peak in systole (257 mL/min +/- 174) and a second peak in early diastole (1,090 mL/min +/- 487). The cross-sectional area varied between 0.5 cm2 +/- 0.2 at end diastole and 1.9 cm2 +/- 0.6 in systole, a finding that suggests a capacitance function for venous outflow. Mean blood flow measurements were in agreement with measurements obtained invasively in previous studies. It is concluded that MR velocity mapping can enable noninvasive measurement of coronary venous outflow and global left ventricular perfusion and may become clinically useful in assessment of coronary blood flow reserve.

Adult↗

PubMed1992

Calculation of oxygen diffusion across the surface of isolated perfused hearts.

Although exact mathematical descriptions of oxygen diffusion into unperfused isolated organs are known, no analytic solution is available for perfused organs. Here, we derive an equation for oxygen diffusion across the epicardial surface of perfused hearts. Our oxygen transport model incorporates oxygen delivery from the capillary perfusate, oxygen consumption, diffusion among adjacent capillary exchange regions, and diffusion across the epicardial surface. The wall of the heart is modeled by a slab of tissue. The derived equation fits experimental data on the diffusive oxygen flux across the surface of isolated saline-perfused guinea pig hearts, obtained by measuring oxygen uptake from the perfusate at various oxygen tensions in the surroundings of the isolated heart. The model predicts that in isolated arrested guinea pig hearts suspended in air, 25% of the oxygen taken up from the saline perfusate (PO2 approximately 680 mmHg) diffuses out of the heart across the surface. In beating isolated guinea pig hearts, 5% of the oxygen taken up from the perfusate diffuses across the surface.

Animals↗

PubMed1991

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↗

PubMed1991

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↗

PubMed1991

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↗

PubMed1991

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↗

PubMed1991

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↗

PubMed1991

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↗

PubMed1990

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↗

PubMed1990

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↗

PubMed1990

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↗

PubMed1990

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↗

PubMed1990

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↗