Biomedical subjects

N Westerhof

Publications and source records attributed to N Westerhof.

At least 73 records · Page 4Linked to original sources

PubMed1994

Cardiac high-energy phosphates adapt faster than oxygen consumption to changes in heart rate.

To investigate the dynamic control of cardiac ATP synthesis, we simultaneously determined the time course of mitochondrial oxygen consumption with the time course of changes in high-energy phosphates following steps in cardiac energy demand. Isolated isovolumically contracting rabbit hearts were perfused with Tyrode's solution at 28 degrees C (n = 7) or at 37 degrees C (n = 7). Coronary arterial and venous oxygen tensions were monitored with fast-responding oxygen electrodes. A cyclic pacing protocol in which we applied 64 step changes between two different heart rates was used. This enabled nuclear magnetic resonance measurement of the phosphate metabolites with a time resolution of approximately 2 seconds. Oxygen consumption changed after heart-rate steps with time constants of 14 +/- 1 (mean +/- SEM) seconds at 28 degrees C and 11 +/- 1 seconds at 37 degrees C, which are already corrected for diffusion and vascular transport delays. Doubling of the heart rate resulted in a significant decrease in phosphocreatine (PCr) content (11% at 28 degrees C, 8% at 37 degrees C), which was matched by an increase in inorganic phosphate (P(i)) content, although oxygen supply was shown to be nonlimiting. The time constants for the change of both P(i) and PCr content, approximately 5 seconds at 28 degrees C and 2.5 seconds at 37 degrees C, are significantly smaller than the respective time constants for oxygen consumption.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗

PubMed1994

Heart period is proportional to body length.

The RR interval, i.e. the heart period (T), increases with body mass (M) as: T = T0M0.27. The characteristic time of the arterial system (arterial decay time or decay time of aortic pressure in diastole, tau) equals peripheral resistance times total arterial compliance. Peripheral resistance equals mean systemic pressure over cardiac output. It can be derived that total arterial compliance is proportional to cardiac output times aortic length. Because mean aortic pressure is similar in different mammals the arterial decay time is proportional to the length of the aorta. Since aortic length and body length are related to body mass with the same exponent it follows that the arterial decay time is proportional to body length. It was found that the arterial decay time is related to body mass as tau = tau oM0.29. The heart period and the duration of diastole have similar exponents. We suggest that the heart period is matched to the arterial decay time to provide similar conditions for coronary perfusion. Since the arterial decay time is proportional to body length, heart period is also proportional to body length.

Animals↗

PubMed1993

Nontriggered magnetic resonance velocity measurement of the time-average of pulsatile velocity.

The feasibility of the determination of the time-average of pulsatile velocity obtained via a nontriggered magnetic resonance (MR) acquisition is studied. The advantage of this method, in comparison with a triggered acquisition, is a considerable reduction (approximately 15x) in acquisition time. However, pulsatility causes image artifacts, known as ghosts, and the Fourier transform technique required for the imaging procedure accomplishes time-averaging of the complex MR signal. Both effects can result in errors in the velocity determined. Calculations show that these errors depend on the velocity time function and the acquisition parameters. In vivo comparison of triggered and nontriggered MR velocity measurements in the femoral artery of volunteers (n = 7) shows larger statistical and systematic errors in the latter, which depend on the excitation angle. Therefore, this nontriggered average velocity measurement is only useful as a fast and rough estimation of the time-averaged velocity.

Blood Flow Velocity↗

PubMed1993

Why smaller animals have higher heart rates.

Diastolic blood pressure is the main driving pressure for coronary perfusion. Diastolic pressure depends on mean pressure and the ratio of the decay time of aortic pressure in diastole (tau) and the duration of diastole (Td). The ratio of tau, a morphological, arterial parameter, and Td, a functional, cardiac parameter, is the same in all mammals. This could mean that smaller animals have higher heart rates i.e. shorter duration of diastole to match the shorter time constant of the diastolic pressure decay and to guarantee adequate coronary perfusion.

Animals↗

PubMed1993

Acidosis slows the response of oxidative phosphorylation to metabolic demand in isolated rabbit heart.

The purpose of this study was to investigate the effect of acidosis on the mean response time of mitochondrial oxygen consumption to steps in heart rate and in left ventricular balloon volume. The mean response time may be viewed as the average delay between a change in adenosine triphosphate (ATP) hydrolysis and oxygen consumption. The mean response time is calculated by subtracting the transport time, required for diffusion of oxygen and for convective transport through the coronary vessels, from the response time measured in the coronary venous effluent. Eight isolated rabbit hearts were perfused according to Langendorff using Tyrode solution at 28 degrees C. Arterial perfusate pH was lowered from 7.30 +/- 0.03 (mean +/- SD) to 6.59 +/- 0.02 by increasing the CO2 tension. At pH 7.3 the mean response time was 12.6 +/- 1.6 s, independent of the time after isolation of the heart. During acidosis, applied 40-75 min after isolation of the heart, the mean response time was 21.4 +/- 0.7 s and increased to 32.6 +/- 4.3 s during acidosis, 85-120 min after isolation. Thus the retardation of the metabolic response by acidosis might depend on the condition of the heart. A decrease of mitochondrial ATP synthetic capacity during acidosis may contribute to the retardation of the metabolic response. Since determination of the mean response time at 37 degrees C is not yet feasible, the experiments were done at 28 degrees C. Extrapolation of our findings to 37 degrees C appears premature.

Adenosine Triphosphate↗

PubMed1993

Smooth muscle responses of the rat septal artery are not influenced by surrounding passive cardiac tissue.

We investigated the possible contribution of surrounding passive cardiac tissue to the smooth muscle responses of coronary arteries. The vasoactive properties of the intramyocardial septal artery (outer diameter 350-400 microns) of the rat heart were investigated when it was freed from the surrounding cardiac tissue (dissected artery) and when it remained in the left ventricle and was thus embedded in passive cardiac tissue (in situ). The changes in external diameter relative to the maximal diameter (isoproterenol) resulting from the application of 125 mM KCl and 1,000 microU/ml vasopressin were measured at 37 degrees C, a transmural pressure of 100 cm H2O, and zero flow. In the dissected septal arteries (n = 5) the maximum diameter was 402 +/- 16 microns, while during exposure to KCl and vasopressin the diameter was reduced to 66.1 +/- 4.6% and 74.2 +/- 3.0%, respectively. For the in situ arteries (n = 6), the maximal diameter was 386 +/- 28 microns, a value not statistically different from the dissected vessels and the diameters reduced to 63.2 +/- 5.5% and 65.6 +/- 7.2% due to KCl and vasopressin, respectively. The constrictions of dissected arteries and in situ arteries were statistically not different. The results show that the maximally-dilated diameter and the constriction responses of intramyocardial conduit arteries of the rat heart are not affected by the surrounding passive cardiac tissue.

Animals↗

PubMed1993

Mitochondrial dehydrogenase activity affects adaptation of cardiac oxygen consumption to demand.

The effect of regulation of mitochondrial dehydrogenase activities on the mean response time of mitochondrial oxygen consumption, which characterizes the delay between changes in ATP hydrolysis and changes in oxygen consumption, was investigated in isolated rabbit hearts and perfused with Tyrode solution at 28 degrees C. Perfusion with ruthenium red (RR) blocks mitochondrial calcium uptake and thus decreases mitochondrial dehydrogenase activities. Perfusion with pyruvate increases pyruvate dehydrogenase activity. The mean response time was 11.8 +/- 0.7 s (means +/- SE) during control, 12.2 +/- 1.2 s during perfusion with 0.9 microgram/ml RR, and 20.7 +/- 3.4 s during perfusion with 2.1 micrograms/ml RR. Blockade with 0.9 microgram/ml RR, which is presumably partial, did not slow the response, suggesting that mitochondrial calcium uptake may not be rate limiting. Strong blockade of mitochondrial calcium uptake increases the mean response time, presumably due to decreased calcium activation of the mitochondrial dehydrogenases. Perfusion with pyruvate significantly decreased the mean response time to 10.0 +/- 1.4 s compared with 11.9 +/- 0.7 s during perfusion with glucose. This decrease with pyruvate is not compatible with a shift to regulation by high-energy phosphates but may reflect increased mitochondrial oxidative capacity caused by increased NADH levels.

Adaptation, Physiological↗

PubMed1993

Coronary arterial inflow impediment during systole is little affected by capacitive effects.

During cardiac contraction coronary arterial inflow is impeded, whereas venous flow is augmented. These effects are assumed to be caused by diameter reductions of intramyocardial blood vessels. The reduction in vascular diameter (and thus vascular volume) during contraction increases coronary resistance and/or decreases back pressure so that flow decreases and the rate of change of volume results in a capacitive flow. The aim of this study was to estimate the contribution of capacitive flow to total coronary inflow impediment. Isolated blood-perfused (100 mmHg and constant), maximally vasodilated, ryanodine-pretreated rat hearts (n = 8) with intraventricular balloons were used. The coronary inflow impediment during isovolumic beats at a heart rate of 2-3 Hz (dynamic contractions) and during prolonged systoles obtained by fast pacing (static contractions, no capacitive flow impediment) were compared. Changing left ventricular balloon volume enabled us to vary left ventricular pressure and to relate systolic flow to systolic left ventricular pressure. We found that for the same contractility (expressed in terms of systolic pressure-volume relationship and maximal elastance) and same left ventricular pressure, the ratio of coronary inflow impediment in dynamic and static contractions is not significantly different from unity (P < 0.005). This implies that under our experimental conditions coronary inflow impediment in dynamic contractions is little affected by capacitive effects.

Animals↗

PubMed1993

Adaptation speed of cardiac mitochondrial oxygen consumption decreases with higher heart rate.

The purpose of the present study was to determine whether the mean response time of cardiac mitochondrial oxygen consumption after a step in metabolic demand is constant in heart muscle, as has already been found for skeletal muscle. The mean response time reflects the average delay between the change in ATP hydrolysis due to a heart rate step and mitochondrial ATP production. Isolated rabbit hearts with a water-filled balloon in the left ventricle were perfused according to Langendorff with a constant flow of Tyrode solution at 28 degrees C. The mean response time increased significantly from 7.6 s for a step in heart rate from 60 to 70 min-1 to 12.1 s for a step from 60 to 120 min-1. The mean response times for heart rate steps downward from 120 min-1 were all approximately 12 s, but for the step from 120 to 140 min-1 the response time was 16.8 s. These results demonstrate that the mean response time of cardiac mitochondrial oxygen consumption in most cases increases with heart rate. These findings are in contrast to those obtained in skeletal muscle, where the response time at which ATP synthesis adapts to a change in work load is constant.

Adaptation, Physiological↗

PubMed1993

Dynamics of myocardial lactate efflux after a step in heart rate in isolated rabbit hearts.

We investigated whether a glycolytic burst contributes to the initial adaptation of ATP synthesis to increased cardiac metabolic demand. Six isolated rabbit hearts were perfused with glucose-containing Tyrode solution at 28 degrees C. In venous and arterial samples the lactate concentration was determined with a sensitive enzymatic cycling method. After the heart rate was doubled from 60 to 120 beats/min, lactate efflux increased from 0.23 +/- 0.10 (SE) to 0.45 +/- 0.12 mumol.min-1.g-1 dry weight with a mean response time of 21.3 s but without an overshoot. The transport time for lactate is longer than 15.7 s, suggesting that lactate production adapts with a mean response time of less than 6 s. Because no overshoot in lactate efflux was found, it is unlikely that a glycolytic burst after a step in heart rate contributes to the fast adaptation of ATP synthesis to demand in the isolated rabbit heart, although it might be possible that a change in cytosolic lactate production is not reflected in an increase in lactate efflux. Extrapolation of the results of this study to the in vivo situation should be done with caution.

Animals↗

PubMed1993

Arterial blood pressure wave forms in radial and posterior tibial arteries in critically ill newborn infants.

The aim of this study was to document arterial blood pressure wave forms at two sites along the arterial tree of the neonate: in the radial and posterior tibial arteries. Using a high-fidelity catheter tip-transducer system, peripheral arterial blood pressure wave forms in 26 critically newborn infants were studied. In 14 infants the radial artery and in 12 infants the posterior tibial artery was cannulated. Radial artery blood pressure waves resembled those of proximal aortic rather than those of the radial artery in adults. Quantitative analysis of the waves was performed to reassure this finding. Blood pressure waves obtained from posterior tibial artery resembled those of femoral artery rather than those of posterior tibial artery waves in adults. We conclude that radial and posterior tibial artery wave forms in neonates appear to have a central appearance. This phenomenon might be explained by the close proximity of the radial and posterior tibial artery to the central aorta and femoral artery respectively, due to the small and short limbs of the neonate. The finding allows an "easy central pressure look" at both ends of the neonatal aorta.

Birth Weight↗

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↗