Biomedical subjects

N Westerhof

Publications and source records attributed to N Westerhof.

At least 37 records · Page 2Linked to original sources

PubMed1999

Pulmonary arterial compliance in dogs and pigs: the three-element windkessel model revisited.

In six dogs and six weight-matched miniature pigs at baseline and after pulmonary embolization, pulmonary arterial compliance was determined using the pulse pressure method (C(PPM)), the three-element windkessel model (C(WK-3)), and the ratio of stroke volume to pulse pressure (SV/PP). C(PPM) was lower in pigs than in dogs at baseline (0.72 +/- 0.23 vs. 1.14 +/- 0.29 ml/mmHg, P < 0.05) and after embolism (0.37 +/- 0.14 vs. 0.54 +/- 0.16 ml/mmHg, P = 0. 07) at matched flow, but not at matched flow and pressure. C(PPM) showed the expected inverse relation with pressure and a direct relation with flow. C(WK-3) was closely correlated with C(PPM), except for all dogs at baseline where C(WK-3) was up to 100% higher than C(PPM). Excluding these data, regression analysis yielded C(WK-3) = -0.01 + 1.30. C(PPM) (r(2) = 0.97). C(WK-3) was found to be unreliable when input impedance first harmonic modulus was close to characteristic impedance, i.e., when reflections were small. SV/PP correlated well with C(PPM) (SV/PP = -0.10 + 1.76. C(PPM), r(2) = 0.89). We conclude that 1) C(PPM) is a consistent estimate of pulmonary arterial compliance in pigs and dogs, 2) C(WK-3) and SV/PP overestimate compliance, and 3) C(WK-3) is unreliable when wave reflections are small.

Animals↗

PubMed1999

Role of total arterial compliance and peripheral resistance in the determination of systolic and diastolic aortic pressure.

The goal of the study was to define the major arterial parameters that determine aortic systolic (Ps) and diastolic (Pd) pressure in the dog. Measured aortic flows were used as input to the two-element windkessel model of the arterial system, with peripheral resistance calculated as mean pressure over mean flow and total arterial compliance calculated from the decay time in diastole. The windkessel model yielded an aortic pressure wave from which we obtained the predicted systolic (Ps, wk) and diastolic (Pd, wk) pressure. These predicted pressures were compared with the measured systolic and diastolic pressures. The measurements and calculations were carried out in 7 dogs in control conditions, during aortic occlusion at four locations (the trifurcation, between trifurcation and diaphragm, the diaphragm and the proximal descending thoracic aorta) and during occlusion of both carotid arteries. Under all conditions studied the predicted systolic and diastolic pressure matched the experimental ones very well: Ps, wk = (1.000 +/- 0.0055) Ps with r = 0.958 and Pd, wk = (1.024 +/- 0.0035) Pd with r = 0.995. Linear regression for pulse pressure gave PPwk = (0.99 +/- 0.016) PP (r = 0.911). We found the accuracy of prediction equally good under control conditions and in presence of aortic or carotid artery occlusions. Multiple regression between pulse pressure and arterial resistance and total arterial compliance yielded a poor regression constant (r2 = 0.19) suggesting that the two arterial parameters alone cannot explain pulse pressure and that flow is an important determinant as well. We conclude that, for a given ejection pattern (aortic flow), two arterial parameters, total arterial resistance and total arterial compliance are sufficient to accurately describe systolic and diastolic aortic pressure.

Animals↗

PubMed1998

Left coronary pressure-flow relations of the beating and arrested rabbit heart at different ventricular volumes.

OBJECTIVE: To study the effect of cardiac contraction on left coronary artery pressure-flow relations at different vascular volumes and to compare these relations in the beating heart with those in the heart arrested in systole and diastole. METHODS: Maximally vasodilated, Tyrode perfused, rabbit hearts (n = 6) with an intra-ventricular balloon were used. The left coronary artery was separately perfused via a cannula in the left main coronary artery. The slopes and the intercepts of left coronary pressure-flow relations were determined in the beating and arrested heart at different chamber volumes. A 3-factor design with repeated measures was used to compare the effect of three factors: phase of contraction (systole and diastole), chamber volume (V0 and V1, left ventricular end-diastolic pressure 1.4 and 20 mm Hg, respectively) and the type of contraction (beating and arrested; a measure of capacitive effects). RESULTS: The phase of contraction has a significant effect on the intercepts (> 40 mmHg, p = 0.00032) but not on the slopes of the pressure-flow relations. Chamber volume had a small effect on the intercepts (< 5 mm Hg, p = 0.037), but not on the slopes of the pressure-flow relations. The type of contraction has a significant effect on the slopes (approximately 10%, p = 0.00021) but not on the intercepts of the pressure-flow relations. CONCLUSIONS: In the isolated Tyrode perfused rabbit heart left coronary pressure-flow relations are mainly determined by contraction, while left ventricular chamber volume and capacitive effects contribute little.

Animals↗

PubMed1998

Perfusion-induced changes in cardiac contractility depend on capillary perfusion.

The perfusion-induced increase in cardiac contractility (Gregg phenomenon) is especially found in heart preparations that lack adequate coronary autoregulation and thus protection of changes in capillary pressure. We determined in the isolated perfused papillary muscle of the rat whether cardiac muscle contractility is related to capillary perfusion. Oxygen availability of this muscle is independent of internal perfusion, and perfusion may be varied or even stopped without loss of function. Muscles contracted isometrically at 27 degrees C (n = 7). During the control state stepwise increases in perfusion pressure resulted in all muscles in a significant increase in active tension. Muscle diameter always increased with increased perfusion pressure, but muscle segment length was unaffected. Capillary perfusion was then obstructed by plastic microspheres (15 microns). Flow, at a perfusion pressure of 66.6 +/- 26.2 cmH2O, reduced from 17.6 +/- 5.4 microliters/min in the control state to 3.2 +/- 1.3 microliters/min after microspheres. Active tension developed by the muscle in the unperfused condition before microspheres and after microspheres did not differ significantly (-12.8 +/- 29.4% change). After microspheres similar perfusion pressure steps as in control never resulted in an increase in active tension. Even at the two highest perfusion pressures (89.1 +/- 28.4 and 106.5 +/- 31.7 cmH2O) that were applied a significant decrease in active tension was found. We conclude that the Gregg phenomenon is related to capillary perfusion.

Animals↗

PubMed1998

Physical basis of pressure transfer from periphery to aorta: a model-based study.

We propose a new method to derive aortic pressure from peripheral pressure and velocity by using a time domain approach. Peripheral pressure is separated into its forward and backward components, and these components are then shifted with a delay time, which is the ratio of wave speed and distance, and added again to reconstruct aortic pressure. We tested the method on a distributed model of the human systemic arterial tree. From carotid and brachial artery pressure and velocity, aortic systolic and diastolic pressure could be predicted within 0.3 and 0.1 mmHg and 0.4 and 1.0 mmHg, respectively. The central aortic pressure wave shape was also predicted accurately from carotid and brachial pressure and velocity (root mean square error: 1.07 and 1.56 mmHg, respectively). The pressure transfer function depends on the reflection coefficient at the site of peripheral measurement and the delay time. A 50% decrease in arterial compliance had a considerable effect on reconstructed pressure when the control transfer function was used. A 70% decrease in arm resistance did not affect the reconstructed pressure. The transfer function thus depends on wave speed but has little dependence on vasoactive state. We conclude that central aortic pressure and the transfer function can be derived from peripheral pressure and velocity.

Animals↗

PubMed1998

Determinants of pulse pressure.

We have searched to define the major arterial parameters that determine aortic systolic (Ps) and diastolic (Pd) pressure in the dog. Measured aortic flows were used as input to the 2-element windkessel model of the arterial system, with peripheral resistance calculated as mean pressure divided by mean flow and total arterial compliance calculated from the decay time in diastole. The windkessel model yielded an aortic pressure wave from which we obtained the predicted systolic (Ps,wk) and diastolic (Pd,wk) pressures. These predicted pressures were compared with the measured systolic and diastolic pressures. The measurements and calculations were performed for 7 dogs under control conditions during aortic occlusion at 4 locations (the trifurcation, between the trifurcation and diaphragm, the diaphragm, and the proximal descending thoracic aorta) and during occlusion of both carotid arteries. Under all conditions studied, the predicted systolic and diastolic pressures matched the experimental ones very well: Ps,wk=(1.000+/-0.0055) Ps with r=0.958 and Pd,wk=(1.024+/-0.0035) Pd with r=0.995. Linear regression for pulse pressure (PP) resulted in PPwk=(0.99+/-0.016) PP with r=0.911. We found the accuracy of prediction equally good under control conditions and in the presence of aortic or carotid artery occlusion. Multiple regression between pulse pressure and arterial resistance and total arterial compliance yielded a poor regression constant (R2=0.19), suggesting that the 2 arterial parameters alone cannot explain pulse pressure and that flow is an important determinant as well. We conclude that for a given ejection pattern (aortic flow), 2 arterial parameters, total arterial resistance and total arterial compliance, are sufficient to accurately describe systolic and diastolic aortic pressure.

Animals↗

PubMed1997

How cardiac contraction affects the coronary vasculature.

We modeled the influence of cardiac contraction on maximally dilated coronary blood vessels, whether single or in juxtaposition, taking into account the nonlinear material properties of both the vascular wall and the myocardium. We calculated pressure-area relations of single, embedded coronary blood vessels, and used these relations to calculate diastolic and systolic coronary pressure-flow relations in a model of the coronary vasculature. The model shows that the change in myocardial material properties during contraction can explain the decrease in coronary vessel area and coronary flow generally observed in experiments. The model also shows that arterioles can be protected from the compressive action of the cardiac muscle by the presence of accompanying venules, which is favorable for coronary blood flow.

Animals↗

PubMed1997

Low- and high-blood flow regions in the normal pig heart are equally vulnerable to ischaemia during partial coronary stenosis.

Myocardial perfusion is heterogeneous, even in the normal heart. It is unknown whether the resting normal blood flow level predicts the severity of mismatch between local blood flow and metabolism during acute ischaemia. In the present study local blood flow (measured with radioactively labelled microspheres) and metabolic indicators of ischaemia [tissue contents of lactate and inosine (INO), a breakdown product of adenosine triphosphate (ATP)] were determined in 84-102 simultaneously frozen samples (approximately 0.9 g) of normal (n = 7) and partially ischaemic (n = 4) porcine left ventricles. Ischaemia was induced for 20 min by partially occluding the left anterior descending artery to reduce perfusion pressure from 107 +/- 17 mm Hg to 39 +/- 10 mm Hg (mean +/- SD). Flow reduction in the ischaemic region was strongly variable, both within the subepicardium (range 6-66%, average 34%) and the subendocardium (range 33-84%, average 57%), indicating redistribution of blood flow inside transmural layers in addition to the well-known preferential decrease in subendocardial perfusion. The relative flow reduction during stenosis was not dependent on normal local perfusion level (Spearman rank correlation coefficient -0.002, P = 0.99). Samples with low or high myocardial blood flows before stenosis showed similar increases in lactate content and INO/ATP content ratio, as long as the percentage blood flow reduction was the same. It is concluded that regions with low and high resting flows in the normally perfused heart are equally susceptible to metabolism-perfusion mismatch resulting from coronary stenosis.

Adenosine Triphosphate↗

PubMed1997

Reoxygenated effluent of Tyrode-perfused heart affects papillary muscle contraction independent of cardiac perfusion.

OBJECTIVE: We determined, via a bioassay, if inotropic factors are released in the coronary circulation of the rat heart and if changes in cardiac perfusion change papillary muscle inotropy. METHODS: An isolated isometrically contracting rat papillary muscle (n = 5, acceptor) was superfused with Tyrode or with reoxygenated coronary venous effluent from an isolated isovolumically beating rat heart (donor) at 27 degrees C, which was perfused with Tyrode according to Langendorff. The superfusion solution in the muscle bath was exchanged completely in 90 s. During coronary venous effluent superfusion, the flow of the heart (donor) was changed in steps. RESULTS: The peak force of the papillary muscle (acceptor) was unaffected by a change from Tyrode to coronary venous effluent superfusion, but time to half relaxation (RT 1/2) significantly increased by 23.0 +/- 9.0% (mean +/- s.d.) and positive dF/dtmax significantly decreased by 14.6 +/- 4.7%. These twitch characteristics were unaffected by changes in coronary perfusion while in the heart isovolumic developed left ventricular pressure did increase with perfusion (the Gregg phenomenon). CONCLUSIONS: Factors that affected papillary muscle contractility are released into the coronary circulation, but their effect is independent of the magnitude of coronary perfusion.

Animals↗

PubMed1997

Perfusion-induced changes in cardiac contractility and oxygen consumption are not endothelium-dependent.

OBJECTIVE: Are substances released from rat coronary endothelial cells responsible for the increase in contractility and oxygen consumption (Gregg phenomenon) seen with an increase in cardiac perfusion? METHODS: In an isovolumically contracting, Langendorff, crystalloid perfused rat heart (n = 6) at 27 degrees C, coronary flow was changed (from 4.4 to 15.4 ml.min-1.gww(-1)) before and after the endothelium was made dysfunctional by Triton X-100. Vascular endothelium and smooth muscle function were tested with bradykinin (BK, 1 microM, an endothelium-dependent dilator) and papaverine (PAP, 1 microM, an endothelium-independent dilator) in a preconstricted vascular bed (vasopressin, VP, 3 nM). RESULTS: Before Triton X-100, coronary resistance (at constant flow) decreased significantly in response to BK and to PAP. After Triton X-100 treatment the dilatory response to BK was abolished while the PAP response was still present, suggesting endothelial dysfunction with intact smooth muscle function. Due to Triton X-100 treatment, coronary resistance increased significantly. Therefore coronary flow changes were also applied during a similar increase in coronary resistance induced by VP infusion (3 nM) before Triton X-100 treatment. During control, developed left ventricular pressure (dev Plv) increased with 68 +/- 21% and oxygen consumption (VO2) increased with 122 +/- 25% in response to the maximal increase in coronary flow. During increased coronary resistance with and without functional endothelium, dev Plv increased by 57 +/- 16 and 64 +/- 22%, respectively, and VO2 increased by 126 +/- 21 and 103 +/- 20%, respectively, in response to the maximal increase in flow. These changes were not significantly different from control. CONCLUSION: The results suggest that the arterial endothelium is not involved in the Gregg phenomenon.

Animals↗

PubMed1997

Modeling pressure-flow relations in cardiac muscle in diastole and systole.

Pressure-flow relations were calculated for a symmetrical, maximally dilated, crystalloid-perfused coronary vascular network embedded in cardiac muscle in (static) diastole and (static) systole at two muscle lengths: slack length and 90% of maximal muscle length (Lmax). The calculations are based on the "time-varying elastance concept." That is, the calculations include the mechanical properties of the vascular wall and the (varying) mechanical properties of the myocardial tissue (in cross-fiber direction). We found that, at any given perfusion pressure, coronary flow is smaller in systole than in diastole. Relative reduction in vascular cross-sectional area, which forms the basis of flow impediment, was largest for the smallest arterioles. At a constant perfusion pressure of 62.5 mmHg, the transition from (static) diastole to (static) systole at constant muscle length ("isometric contraction") was calculated to reduce flow by 74% (from 18.9 to 5.0 ml x min(-1) x g(-1)) and by 64% (from 12.6 to 4.6 ml x min(-1) x g(-1)) for the muscle fixed at slack length and 90% of Lmax, respectively. At this perfusion pressure, contraction with 14% shortening (from 90% of Lmax in diastole to slack length in systole) was calculated to reduce flow by 61% (from 12.6 to 5.0 ml x min(-1) x g(-1)). Increasing muscle length from slack length to 90% of Lmax decreases coronary flow by 34% in diastole and by 8% in systole. We conclude that modeling cardiac contraction on the basis of the time-varying elastic properties of the myocardial tissue can explain coronary flow impediment and that contractions, with or without shortening, have a larger effect on coronary flow than changes in muscle length.

Animals↗

PubMed1997

Effects of contraction, perfusion pressure, and length on intramyocardial pressure in rat papillary muscle.

If intramyocardial pressure (IMP) is the pressure that causes coronary flow to stop, i.e., "backpressure," then it should be equal to the zero-flow perfusion pressure intercept (Pzf). Therefore we determined Pzf and IMP at zero flow (IMPzf) in papillary muscles suspended isometrically in a bath, superfused with a well-oxygenated Tyrode solution (27 degrees C), and perfused with Tyrode solution via the septal artery. For the IMP (servo-null) measurements, we used unbeveled glass micropipettes with a tip diameter of 3-4 microns. During diastolic arrest and systolic contracture (2 mM Ba21), perfusion pressure steps were applied, and the corresponding flow and IMP values were recorded. Fitting of the relationships, yielded Pzf and IMPzf. In the diastolically arrested muscle, perfusion pressure affected IMP. Pzf was much higher in systolically contracted muscle than in diastolically arrested muscle. The IMPzf in both conditions was significantly smaller than Pzf. Thus, even in this preparation with no ventricular pressure, IMP increases during contraction. We conclude that IMP arises from contraction per se but is not the pressure that causes the flow to stop.

Animals↗

PubMed1997

Effect of ventricular contraction, pressure, and wall stretch on vessels at different locations in the wall.

A cylindrical model of the heart was used to calculate the influence of ventricular filling and (isovolumic and isobaric) contraction on the cross-sectional area and resistance of a subendocardial and subepicardial maximally dilated arteriole and venule. Contraction is defined as the difference between static diastole and static systole. Furthermore, a small piece of rectangular myocardium containing the vessel was modeled to distinguish between the individual contributions of contractility (i.e., myocardial elastic properties), ventricular pressure, and local circumferential stretch to the changes in vascular area and resistance during contraction. Calculations were performed assuming the muscle fibers ran in either an apex-to-base or a circumferential direction. The results were similar for the two directions. Assuming constant, physiological arteriolar and venular pressures of 45 and 10 mmHg, respectively, coronary blood vessels were predicted not to collapse during ventricular contraction. Moreover, vascular area reduction was found to be larger for the arteriole (approximately 50%) than for the venule (approximately 30%) during both isovolumic and isobaric contractions. Consequently, arteriolar resistance was found to increase more than venular resistance (approximately 340 and 120%, respectively). Subendocardial area reductions were found to be somewhat smaller than subepicardial area reductions for the venule (by approximately 10%) but not for the arteriole. Contractility was found to be the main contributor to the changes in vascular area and resistance in the subepicardium but to contribute by < 50% to the changes in the subendocardium. Because pressure does, but stretch does not, contribute to the area change during isovolumic contraction and the reverse is true during isobaric contraction, it was concluded that although changes in vascular area and resistance may be similar for different contractions, the causes for these changes are very different.

Arterioles↗

PubMed1997

Compression of intramyocardial arterioles during cardiac contraction is attenuated by accompanying venules.

It was calculated how cardiac contraction influences the luminal cross-sectional area of a maximally dilated coronary arteriole (37-micron inner diameter at a pressure of 35 mmHg) that is accompanied by two equal venules (45-micron inner diameter at a pressure of 17 mmHg), forming a so-called "triad." It was found that, during a contraction with 14% cardiac muscle shortening, arteriolar area is virtually unaffected (increase of 4%) at the expense of a large (55%) decrease in venular area. For comparison, the areas of an unaccompanied arteriole and an unaccompanied venule were calculated to be reduced by 45 and 36%, respectively, demonstrating the "protective effect" on accompanied arterioles in a triad. During contraction, the overall resistance of a system consisting of one arteriole in series with two parallel venules of equal length was calculated to increase about twice as much for nonaccompanied vessels (resistance increases by a factor of 2.8) than for vessels in a triad arrangement (resistance increased by a factor of 1.4). The calculations show that the extravascular (intramyocardial) pressure, which determines vascular area, is not an independent variable as in the intramyocardial pump and waterfall models but depends on the vascular "loading" conditions. Thus the small venular pressure together with the large venular compliance causes the extravascular pressure to remain low during contraction, thereby protecting the stiff arteriole at high pressure. We conclude that the triad arrangement of intramyocardial coronary vessels attenuates the increase in coronary resistance during cardiac contraction and thus has an important functional advantage.

Arterioles↗

PubMed1996

Transesophageal cardiac pacing during magnetic resonance imaging: feasibility and safety considerations.

The feasibility and safety of transesophageal cardiac pacing during clinical MRI at 1.5 Tesla is considered. An MRI compatible pace catheter was developed. In vitro testing showed a normal performance of the pulse generator, image artifacts that extended less than 11 mm from the catheter, and a less than 5% increase in noise. Cardiac stimulation induced by MRI was not observed and, theoretically, is not expected. Potentially, tissue around the catheter tip may become heated. This heating (delta tau) was monitored. Eight dogs were exposed to MRI during pacing. For low RF radiation exposure, a time-averaged squared B1 field below 0.08 p tau 2 (SAR < 0.03 W/kg), delta tau was below 1 degree C. For high RF radiation exposure, but at normal RF radiation specific absorption rate (0.4 W/kg) delta tau was 5 degrees C. Thus, transesophageal atrial pacing during MRI at low RF exposure seems to be possible to perform cardiac stress studies or to correct unstable heart rates.

Animals↗

PubMed1996

Assessment of flow in the right human coronary artery by magnetic resonance phase contrast velocity measurement: effects of cardiac and respiratory motion.

Flow in the human right coronary artery was determined using magnetic resonance phase contrast velocity quantification. Two methods were applied to reduce respiratory motion: Imaging during breath holding, which is fast, and retrospective respiratory gating, which has a high temporal resolution (32 ms) in the cardiac cycle. Vessel cross-sectional area, through-plane velocity, and volume flow were determined in six healthy subjects. In-plane vessel displacement during the cardiac cycle, caused by cardiac contraction, was about 2-4 mm within a time frame of 32 ms in systole and early diastole. The motion resulted in blurring of images obtained during breath holding caused by the large acquisition time window (126 ms) within the cardiac cycle. Therefore, only with a high temporal resolution correct velocity images over the entire cardiac cycle could be obtained. The time- and cross-sectionally averaged velocity was 7 +/- 2 cm/s, and the volume flow was 30 +/- 10 ml/min.

Adult↗

PubMed1996

Intramyocardial pressure measurements in the isolated perfused papillary muscle of rat heart.

The intramyocardial pressure (IMP) plays a role in the interaction between heart contraction and coronary flow. In order to measure IMP we developed the isolated perfused papillary muscle. The papillary muscle was suspended in a muscle bath with oxygenated Tyrode's solution. Perfusion with Tyrode's solution took place via the septal artery. Diastolic intramyocardial pressure was measured with micropipettes with a tipdiameter of 3 to 4 microns in combination with the servo-null technique. After an equilibration period of at least a half hour where the muscle was perfused with a perfusion pressure of 40 cmH2O and stimulated with 0.2 Hz the IMP measurements started. Pressure changes resulting from changes in perfusion pressure and injection of ink via the pipette made it possible to distinguish between interstitial and vascular localization. No leakage along the shaft of the pipette to the outside was found. Perfusion caused interstitial edema in the muscle so that the cross-sectional area (CSA) of myocytes relative to total muscle CSA decreased from 71% in non-perfused muscle to 51% in perfused muscle. Interstitial edema increased approximately from 10% to 30%. The amount of edema was reduced by rapid pacing (3.3 Hz) as judged from decreased muscle diameter and a lower IMP. It is concluded that reliable IMP measurements can be made in the isolated papillary muscle and that increased filling of the interstitium increases its pressure.

Animals↗

PubMed1996

Determinants of stroke volume and systolic and diastolic aortic pressure.

We investigated how parameters describing the heart and the arterial system contribute to the systolic and diastolic pressures (Ps and Pd, respectively) and stroke volume (SV). We have described the heart by the varying-elastance model with six parameters and the systemic arterial tree by the three-element windkessel model, leading to a total of nine parameters. Application of dimensional analysis led to a total of six dimensionless parameters describing dimensionless Ps and Pd, i.e., pressures with respect to venous pressure (Ps/Pv and Pd/Pv). SV was normalized with respect to unloaded ventricular volume (Vd). Sensitivity analysis showed that Ps/Pv, Pd/Pv, and SV/Vd could be accurately described by four, three, and three dimensionless parameters, respectively. With this limited number of parameters, it was then possible to obtain empirical analytical expressions for Ps/Pv, Pd/Pv, and SV/Vd. The analytic predictions were tested against the model values and found to be as follows: Ps predicted = (1.0007 +/- 0.0062) Ps, r = 0.987; Pd predicted = (1.016 +/- 0.0085) Pd, r = 0.992; and SV predicted = (0.9987 +/- 0.0028) SV, r = 0.996. We conclude that aortic Ps, Pd, and SV can be accurately described by a limited number of parameters and that, for any condition of the heart and the arterial system, Ps, Pd, and SV can be presented in analytical form.

Animals↗