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Biomedical subjects

P Sipkema

Publications and source records attributed to P Sipkema.

At least 19 recordsLinked to original sources

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

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

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

Effect of wall stretch on coronary hemodynamics in isolated canine interventricular septum.

The effects of stretch on coronary pressure-flow relations are not well understood. To examine the role of wall stretch per se on coronary hemodynamics, we studied arterially perfused isolated canine interventricular septa in a noncontracting state with vasodilated vessels. We compared the hemodynamic parameters of zero-flow pressure and resistance during passive stretching in the circumferential and the base-to-apex directions alone as well as during simultaneous biaxial stretching in both directions. Even in the unloaded state the zero-flow pressure was positive. Any type of stretching significantly increased the zero-flow pressure and the resistance from their unloaded values. The pressure-flow responses also showed directional dependence. When stretches with matched strains or stresses in each direction were applied sequentially, the resistance increases corresponded to the direction of higher stress. Conversely, the zero-flow pressure response increase corresponded to the direction of greater strain. However, neither response correlated with a measure of global tissue stiffness. Thus there is a complex and tight mechanical interaction between the vessels and the surrounding tissue. These interactions, but not the tissue stiffness, are important determinants of coronary pressure-flow responses during stretch.

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

Linear and nonlinear one-dimensional models of pulse wave transmission at high Womersley numbers.

The accuracy of nonlinear and linear one-dimensional models in describing pulse wave propagation in a uniform cylindrical viscoelastic tube, with Womersley's parameter alpha equal to 7.6 at 1 Hz, was evaluated. To this end calculations of wave propagation using these models were compared with the experimentally determined propagation of the pressure wave in the tube. The experimentally generated pressure pulse had an amplitude of 9.0 kPa and caused a relative radius change of about 17%. The static pressure vs cross-sectional area relation was found to be nonlinear for these pressure changes. Maximum fluid velocity was about 2.9 ms-1, while the phase velocity was about 5.4 ms-1. The radius change and the ratio of fluid and phase velocities violated the linear model assumptions. The nonlinear model with viscous fluid friction modelled on the basis of Poiseuille's law and treating the tube wall as purely elastic, underestimated the damping of the pulse wave and predicted the formation of shock waves, which were not found experimentally. In the linear models, the viscous friction of the blood was modelled according to either Poiseuille's law or Womersley's theory and the tube wall was treated as either linearly elastic or linearly viscoelastic. A description of the viscous friction of the blood based on Poiseuille's law underestimated damping. Disregarding the viscoelasticity of the tube wall resulted in an underestimation of both phase velocity and damping. In spite of the nonlinearity of the system, the linear viscoelastic Womersley model described the pulse wave propagation satisfactorily.

Animals

Varying elastance concept may explain coronary systolic flow impediment.

We measured phasic arterial coronary inflow in the blood-perfused isolated cat heart (n = 5) with a balloon in the left ventricle under well-defined conditions, i.e., constant perfusion pressure, constant vasomotor tone (maximal vasodilation), and heart rate. The normalized amplitude (A) between systolic flow (Fs) and diastolic flow (Fd) [A = (Fd - Fs)/Fd] was related to systolic left ventricular pressure (Ps, range 1.6-17 kPa, 1 kPa = 7.5 mmHg) for different isovolumic beats obtained by changes in balloon volume and for low load isobarically ejecting beats (pressure 0.2 kPa). The data were fitted to A = a + bPs with a = 0.70 +/- 0.15 (SD) and b = 0.005 +/- 0.005 kPa-1. This relation indicates a very weak effect of left ventricular systolic pressure on normalized flow amplitude. Thus the hypothesis that left ventricular pressure is the sole determinant impeding coronary flow could not be confirmed. However, our data could be explained on basis of the time-varying elastance concept (H. Suga, K. Sagawa, and A. A. Shoukas. Circ. Res. 32: 314-322, 1973). The intravascular and luminal (cavity) compartments both are assumed to be subject to a time-varying elastance. The time-varying luminal elastance is similar for isovolumic and isobaric beats. We assume that the elastance of the vascular compartment also behaves the same for these beats, and therefore coronary flow is affected similarly.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Contractility is the main determinant of coronary systolic flow impediment.

We measured the relation between coronary flow amplitude (delta F = Fd-Fs; where d is diastolic and s is systolic) and developed left ventricular pressure (delta PLV = Ps-Pd) at a constant perfusion pressure of 75 mmHg (10 kPa) in the maximally vasodilated blood-perfused isolated cat heart for different steady-state levels of contractility (protocol A) and during transients in contractility (protocol B). Contractility was defined as the slope of the end-systolic pressure-volume relation (Emax). From protocol A it appeared that the coronary flow amplitude was only weakly related to left ventricular pressure at each steady-state level of contractility studied. However, the coronary flow amplitude was strongly related to the different levels of contractility. In protocol B, contractility was changed over a wide range of values (0-100%) but developed pressure and contractility changed simultaneously. Using multiple linear regression analysis, we found that contractility has approximately 10 times (range: 2.8-57.3) stronger effect than left ventricular pressure on coronary flow amplitude (n = 10 experiments). These data and our earlier observations suggest that it is the difference in stiffness of cardiac muscle between systole and diastole that determines coronary flow amplitude.

Animals

Effects of oxygen and flow on the diameter of the femoral artery of the rabbit.

Contradictory results concerning the effects of oxygen and flow on blood vessel dimensions have been published. The aim of this study was to investigate the diameter changes in isolated, cannulated femoral arteries (n = 5) of the rabbit in a preconstricted state (two norepinephrine levels) during high and low pO2 (both inside and outside) at different flow levels. In this way the interaction between oxygen and flow is also investigated. Results were normalized to relative diameters, where the diameter at zero flow, during high pO2 and low norepinephrine concentration was considered as a control diameter (100%). We found three effects in this study: (1) going from high to low oxygen, there was a global vasoconstriction (repeated measures, analysis of variance, p = 0.016 with low norepinephrine and p = 0.015 with high norepinephrine); (2) when flow was increased from 1 to 100 ml/h, we found a significant (p less than 0.001) flow-dependent constriction under all four conditions, and (3) there is an interaction between flow and oxygen, for example at low norepinephrine the constriction due to low oxygen is 16% at zero flow and 1% at a flow of 1 ml/h, at high norepinephrine these numbers are 22 and 10%, respectively.

Animals

Does the endothelium play a role in flow-dependent constriction? A study in the isolated rabbit femoral artery.

We studied the role of the endothelium in diameter changes as a function of flow of the isolated femoral artery of the rabbit (n = 15) perfused and superfused with a physiological salt solution (37 degrees C). In 10 vessels, diameters were studied before and after exposure to gossypol, an agent that impairs the endothelial function pharmacologically. In 5 of these 10 vessels we added albumin (1.5%) to the perfusion solution. The mean external diameter (+/- SEM) after equilibration for 60 min at a transmural pressure of 50 cm H2O (n = 10) was: 1,426 +/- 34 microns. Vessels were then constricted with norepinephrine (1.0-1.5 microM in the superfusion solution) to 70% of the resting diameter, acetylcholine was used to check endothelial function. All vessels constricted as flow was increased (p less than 0.001), irrespective of the impairment of the endothelial function by gossypol or the presence of albumin. It is therefore unlikely that the flow-induced constriction results from a 'wash away' effect of endothelium-derived relaxing factor (EDRF). To test whether EDRF could still play a role after gossypol, we used hemoglobin (n = 5) to bind EDRF. Flow-dependent constriction was still observed, although the mean diameter was decreased. We conclude that flow-dependent constriction is either mediated via the endothelial cells, but not via EDRF, or that the endothelial cells are not involved.

Acetylcholine

Influence of geometric taper on the derivation of the true propagation coefficient using a three point method.

We studied the effect of geometric taper on the derivation of the true propagation coefficient from three pressures determined 10 cm apart ('three-point method'). For this purpose the true propagation coefficients of a uniform latex tube (length 50 cm, outer diameter 12.73 mm, Womersley phase velocity 6.23-6.42 ms-1 (1-10 Hz), Womersley damping coefficient 0.05-0.14 m-1 (1-10 Hz) and of a tapered latex tube (length 50 cm, outer diameter varying from 15.88 to 9.45 mm, in the middle section with same properties as the uniform tube) were determined. The real part of the true propagation coefficient (the damping coefficient) was compared with apparent damping, and with the damping coefficient calculated using Womersley's theory. The imaginary part of the true propagation coefficient (the phase coefficient) was expressed in terms of phase velocity. True phase velocity was compared with measurements of apparent phase velocity, foot-to-foot velocity, and calculations of phase velocity parameters Womersley's theory and the Moens-Korteweg equation. The results show that in the uniform tube the three-point propagation coefficient is in agreement with all other estimates. Taper causes an error in the three-point propagation coefficient. At some frequencies the damping is reversed to amplification (values up to -2 m-1) and the phase velocity may be both overestimated or underestimated (up to 50%). The overestimation of true damping as reported in the literature cannot be explained from vessel taper.

Arteries

Pump perfusion abolishes autoregulation possibly via prostaglandin release.

The influence of pump perfusion on autoregulation was studied in the hindleg of the halothane- and chloralose-anesthetized cat. Flow was measured with an electromagnetic flow probe in a tube between aorta and the vascularly isolated, denervated leg and varied with a calibrated occluder. Perfusion pressure was measured via a T-piece distal to the occluder. The steady-state pressure-flow relations could be fit with a sigmoidal curve. The mean closed-loop gain (0 less than Gc less than 1) for autoregulation in six cats was 0.46 +/- 0.11 (SD). When in these cats a roller pump was used, an almost linear pressure-flow relation was found (Gc = 0.01 +/- 0.09), while the resistance at control flow was decreased by 15 +/- 4%. Administration of indomethacin (5 mg/kg iv), a cyclooxygenase inhibitor, partly restored autoregulation during pumping (Gc = 0.34 +/- 0.09) and slowly increased the resistance to above its original value (20 +/- 13%). In six other cats, pump perfusion had no influence on autoregulation when started after indomethacin administration but resistance increased. This increase could not be prevented with ketanserin, a specific serotonin 2 receptor blocker. We conclude that pump perfusion abolishes autoregulation and decreases resistance via a process that involves prostaglandins. Blockade of the prostaglandin synthesis unmasks a slow vasoconstrictor influence in the bed.

Animals

Changes in coronary pressure-flow relation after transition from blood to Tyrode perfusion.

In six isolated, diastolic-arrested, maximally vasodilated cat hearts, we studied changes in coronary pressure-flow relations (zero-flow pressure intercept, resistance) during the first 25 min, after a change of perfusate, from blood to Tyrode. The apparent intercept (zero-flow) pressure changed from 2.0 +/- 0.94 (+/- SD) kPa during blood perfusion to 2.5 +/- 0.55, 2.6 +/- 0.68, 2.5 +/- 0.94, and 2.7 +/- 1.34 kPa during Tyrode perfusion for 2:15, 5:30, 10:30, and 25:00 min, respectively. Intercept pressures during Tyrode perfusion were significantly different from the intercept pressure during blood perfusion, except for the one measured after 25 min of Tyrode perfusion (P less than 0.05). Resistance (defined as the ratio of perfusion pressure and flow at 10 kPa perfusion pressure) steadily rose to approximately 170% of the value during blood perfusion. The observation that the apparent intercept pressure is maintained, when a particle-free (Newtonian) isotonic perfusate is used, may indicate that this intercept is not a result of blood rheology alone. The increase rather than decrease in resistance suggests an effect of edema, which increases interstitial volume at the expense of intravascular volume.

Animals

Aortic input impedance during Mueller maneuver: an evaluation of "effective length".

Aortic input impedance was calculated in seven subjects in the control state (normal reflection) and during the Mueller maneuver (increased reflection) to evaluate "effective arterial length" under altered physiological conditions. Regional foot-to-foot pulse wave velocities and pressure waveforms along the aorta were used to define an "apparent anatomic length" or distance to a dominant discrete site of reflection "seen" by the ejecting ventricle. Time of wave travel was taken to be one-half the interval from the foot of the incident wave to the midsystolic inflection point. Knowing the time of travel from the returning reflection and velocity, distances calculated to the "apparent anatomic length" were 35 +/- 2 and 34 +/- 2 during control and Mueller maneuver, respectively (P = NS). The frequency of the first minimum of the modulus (fmin) and the first zero crossing of the phase angle (f phi) were determined from the input impedance spectra. During baseline conditions, fmin (3.9 +/- 0.2 Hz) approximately equaled f phi (4.2 +/- 0.2 Hz), and the resulting "effective lengths" calculated using the quarter-wavelength formula were similar to the apparent anatomic length. These data suggested that the aortic region incorporating the renal arterial branches as a site of discrete reflection and that terminal load was not significantly frequency dependent. During Mueller maneuver, however, f min (3.3 +/- 0.2 Hz) and f phi (5.1 +/- 0.2 Hz) were significantly discordant, the terminal load became strongly frequency dependent, and effective length calculated from f min was dissimilar (P less than 0.05) from the unchanged apparent anatomic length.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult