Biomedical subjects

G Elzinga

Publications and source records attributed to G Elzinga.

At least 73 records · Page 4Linked to original sources

PubMed1987

Diffusional shunting of oxygen in saline-perfused isolated rabbit heart is negligible.

Diffusional shunting of oxygen in the saline-perfused heart was studied by comparing the time course of the coronary venous concentrations of oxygen and an intravascular indicator following a simultaneous step-like change in their arterial concentrations. To this end 7 rabbit hearts were perfused according to Langendorff with Tyrode solution at a perfusion flow rate of 3.8 +/- 1.4 ml.min-1.g-1 (wet weight) at 37 degrees C. In the reference situation arterial (Pao2) and venous oxygen tensions (Pvo2) were about 610 and 290 mmHg, respectively. Step changes in Pao2 were made to a 60 mmHg lower level and back. Simultaneously the arterial concentration of albumin-bound indocyanine green, an intravascular indicator, was changed. No deflection in PvO2 was detected before the venous dye concentration changed. The venous dye concentration crossed 5% of its step amplitude 4 s after the arterial change, on average 2.3 s before Pvo2 crossed its 5% level. We conclude that shunt diffusion of oxygen from arterioles to venules and from arterial to venous ends of the capillary bed is negligible in saline-perfused hearts and thus cannot explain the high value of Pvo2 in these preparations.

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PubMed1987

Relation between force and calcium ion concentration in different fibre types of the iliofibularis muscle of Xenopus laevis.

Calcium activated isometric force was measured in segments of single muscle fibres of the iliofibularis muscle of Xenopus laevis skinned by freeze-drying. A subdivision in five different fibre types was made, based on the location of the fibres inside the muscle, fibre diameter and a quantitative histochemical assay for succinate dehydrogenase activity. The Ca2+ sensitivity was characterized by fitting a Hill curve to the force levels reached at different Ca2+ concentrations. The parameter n of this equation indicates the steepness and pK the midpoint of this force-pCa relation. A considerable variability in the Ca2+ sensitivity characteristics was found between different fibres. The parameter n varied between 1.1 and 4.2 while pK varied between 5.5 and 6.6. The distribution of the data indicates the presence of three groups with different Ca2+ sensitivity; a group of fibres with low Ca2+ sensitivity but with considerable variation of the steepness of the Ca2+ sensitivity curves (type 1 fibres), an intermediate group (type 2, 3 and 4 fibres) with also considerable variation in steepness of the Ca2+ sensitivity curves, in which the lowest values for n are found in type 3 and 4 fibres and a group with high Ca2+ sensitivity and low n containing at least one tonic (type 5) fibre. At sub-saturating Ca2+ concentrations occasionally a transient decrease of the rate of force development was found which resembled the force oscillation reported for some mammalian muscle fibres.

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PubMed1987

Stable maintenance heat rate and contractile properties of different single muscle fibres from Xenopus laevis at 20 degrees C.

1. Different types of fibres were isolated from the iliofibularis muscle of Xenopus laevis. Resting length was adjusted to obtain a sarcomere length of 2.3 microns as judged by laser diffraction. Heat production was measured during tetanic contractions lasting 0.3-2 s at 20 degrees C. From twenty fibres the force-velocity relationship was determined as well. 2. After correcting the records for heat loss, and taking the relevant heat capacities into account, stable maintenance heat rate was determined by fitting the corrected heat records from 0.35 s after the onset of contraction onwards by a straight line. The value obtained was then normalized on the dry weight of the fibre. The force-velocity relationships were fitted according to Hill's equation, yielding values for a and Vmax (Hill, 1938). 3. Stable maintenance heat rate (hb) depended on fibre type and ranged from 0.05 to 0.86 W g-1 dry wt. Isometric tetanic force per cross-sectional area (P0) varied between 190 and 427 kN m-2. Therefore the variations in hb were not proportional to the variations in P0. 4. The maximum velocity of shortening (Vmax) differed considerably from fibre to fibre (4.6-10.3 lengths s-1). Between Vmax and hb a non-linear relationship was found. The curvature of this relationship was such that its slope (delta hb/delta Vmax) increased with Vmax. 5. A proportional relationship was found between the rate of force redevelopment, following a period of rapid shortening, and hb. 6. Maximum power output during loaded shortening as derived from the force-velocity (P-V) relationships was on average 2.2 times higher than hb. 7. The curvature of the force-velocity relationship, as reflected by the value of a/P0, varied between fibres from 0.18 to 0.53. A larger value of a/P0 i.e. a less curved relationship, corresponded with a larger value of hb. 8. Since hb reflects the rate at which ATP is hydrolysed during contraction, the results suggest that the maximum velocity of shortening and the in vivo actomyosin ATPase under isometric conditions are non-linearly related. This would imply that these two variables are not dominated by the same rate-limiting step of the cross-bridge cycle.

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PubMed1987

Heat production during contraction in skeletal muscle of hypothyroid mice.

The effect of hypothyroidism on tension-independent and -dependent heat produced during a twitch and a tetanic contraction of extensor digitorum longus (EDL) and soleus muscle of mice was examined. The amount of heat produced during a twitch and the rate of heat development during a tetanus of EDL and soleus were measured at and above optimal length. The effect of hypothyroidism on force production was less than 30%. Straight lines were used to fit the relation between heat production and force. Hypothyroidism significantly decreases tension-independent heat during contraction of EDL and soleus muscle. Because the tension-independent heat is considered to be related to the Ca2+ cycling, these findings suggest that ATP splitting due to the Ca2+ cycling is reduced in hypothyroid mice. This conclusion was strengthened by the observation that the oxalate-supported Ca2+-uptake activity and Ca2+-loading capacity of muscle homogenates from hypothyroid mice were reduced, respectively, to 51 and to 65% in soleus and to 63 and 73% in EDL muscle as compared with euthyroid mice. The tension-dependent rate of heat development during a tetanus was also decreased in soleus muscle of hypothyroid mice. This suggests a lower rate of ATP hydrolysis related to cross-bridge cycling in this muscle due to the hypothyroid state.

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PubMed1987

Temperature distribution cannot predict local cardiac metabolism.

The objective of this study was to investigate if local myocardial metabolism can be determined from the transmural temperature distribution. Heat produced metabolically in the myocardium is carried away by the coronary blood and by diffusion. Transport by coronary flow (convectional heat loss) was determined from the coronary blood flow and the transcoronary temperature difference. This measured value was compared with one predicted from measured oxygen consumption, assuming a slab of tissue for the left ventricular free wall with homogeneous flow distribution and homogeneous metabolism. Measured and predicted convectional heat loss could not be shown to differ. Endocardial and epicardial heat production were estimated in two ways: 1) from the transmural temperature distribution (AT) and 2) from local flow (radioactive microspheres) and oxygen consumption (AO2). Ideally the ratio AT/AO2 should be unity. For flows in the resting physiological state (up to 100 ml X min-1 X 100 g-1) this ratio was not statistically different from one for both endocardium and epicardium: 0.86 +/- 0.11 and 1.09 +/- 0.07 (SE), respectively. For larger flows the ratio reduced to 0.66 +/- 0.08 endocardially. It is concluded that overall left ventricular metabolism can be predicted from conventional heat loss and that for physiological, but not for increased flow, the transmural temperature distribution predicts local metabolism.

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PubMed1987

Beat-to-beat estimation of peripheral resistance and arterial compliance during pressure transients.

We have used a computer-based parameter estimation method to obtain peripheral resistance, total arterial compliance, and characteristic resistance from the measurement of aortic pressure and flow in the open-thorax cat, assuming the three-element windkessel as a model of the systemic arterial tree. The method can be applied on a beat-to-beat basis in the steady state and in transients. We have validated this method by analyzing nonsteady-state data obtained from an electrical analog with fixed values of the resistances and compliance and by showing that the values obtained by this procedure were within 5% of the fixed values of the circuit. Changes in total peripheral resistance and arterial compliance were studied before, during, and after acute heart rate changes in five open-thorax cats with blocked autonomous nervous system. As expected, the peripheral resistance, estimated during the heart rate transient [3.93 +/- 0.94 (SE) kPa X ml-1 X s] was the same as before the transient (3.53 +/- 0.83 kPa X ml-1 X s); total arterial compliances were also identical (0.28 +/- 0.04 vs. 0.27 +/- 0.03 ml/kPa). In six cats without nervous blockade we obtained similar results. Calculation of peripheral resistance during transients from the mean pressure-to-mean flow ratio, i.e., without correction for arterial compliance, suggested changes in resistance values of less than or equal to 57%, which shows that correction is necessary. The findings indicate that peripheral resistance and total arterial compliance can be estimated in vivo on a beat-to-beat basis, even during hemodynamic transients.

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PubMed1987

Time course of aerobic recovery after contraction of rabbit papillary muscle.

The time course of oxygen uptake after isometric twitch contractions of isolated rabbit papillary muscles was determined at 20 degrees C by continuous polarographic measurement of the partial pressure of oxygen in a 219-microliters glass chamber in which the fluid circulated rapidly. The response time of the oxygen-measuring system was characterized by a delay of 1.1 s and a time constant of 2.1 s after that delay. Depending on the stimulation frequency (0.125-1.0 Hz) the total amount of oxygen uptake for 120 twitches varied from 5.3 to 32.7 nmol/mg dry wt, and the steady-state oxygen consumption rate varied from 0.4 to 8.5 nmol X min-1 X mg dry wt-1. On the basis of a diffusion model we eliminated the effect of oxygen storage on the measured time course of oxygen consumption to determine the mitochondrial kinetics. We found a time constant of an average 19-22 s of mitochondrial off kinetics. By use of this time constant for the change in oxygen consumption rate after contraction, it can be estimated that 9-10% of the oxygen required to restore ATP levels is already taken up by the mitochondria during the twitch.

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PubMed1986

How to quantify an arterial stenosis: a study on the femoral arteries of dog and man.

The blood supply to the femoral bed was studied in anaesthetised dogs before and after producing arterial stenoses. The blood supply system consisted of the vessels proximal to the site of measurement in the femoral artery and was characterised by a supply graph, which related mean perfusion pressure to mean flow. The different pressures and flows were obtained using an artificial periphery, the impedance of which was changed from beat to beat. The supply graph was approximated by a parabola with two parameters: the intercepts with the pressure and flow axes, the latter indicating the maximum mean flow. For constant aortic pressure the maximum mean flow appeared to be linearly related to the cross sectional area of the stenosed section (r = 0.98). Maximum mean flow was already considerably reduced before the stenosis became critical--that is, before physiological flow was measurably diminished. The change in maximum mean flow was therefore used to quantify the haemodynamic effects of stenoses that were less than critical. Blood supply graphs of the superficial femoral arteries were determined also in seven patients undergoing a femoropopliteal bypass operation. The maximum mean flow correlated well with the degree of obstruction determined from the preoperative angiograms (r = 0.90).

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PubMed1986

Feline left ventricle does not always operate at optimum power output.

In a previous study we showed that under a variety of conditions the feline left ventricle operates at optimum external power. This condition was defined as matching. In the present study matching of left ventricle and systemic arterial tree has been further investigated in the open-thorax cat during control, after volume loading (n = 8), and during norepinephrine infusion (n = 8). The pump-function graph relating mean left ventricular pressure and mean flow was fitted with a parabola characterized by two parameters, the pressure axis and the flow axis intercepts (Pmax and Fmax, respectively). After volume loading, as well as during norepinephrine infusion, the pump-function graph showed an outward shift plus a clockwise rotation. Pmax and Fmax increased 27 and 8% during volume loading and 37 and 8% during norepinephrine. In the steady states the mean flows at the working point and at the point of optimum external power were determined. During control and volume loading these flow values could not be shown to differ. However, during norepinephrine infusion, flow at the working point was found to be smaller than at optimal external power. This finding implies that during norepinephrine, the left heart does not operate at optimum external power; so a mismatch of heart and periphery is obtained.

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PubMed1985

Optimal power generation by the left ventricle. A study in the anesthetized open thorax cat.

We studied the interaction of the left ventricle and the systemic arterial bed in the open thorax cat. In the steady state, the ventricle can be characterized by the pump function graph (i.e., the relationship between mean left ventricular pressure and mean outflow). From this pump function graph, the apparent source resistance of the heart is found. Apparent source resistance is defined as the ratio of the difference between maximal and actual mean left ventricular pressure, and mean outflow. The arterial system can be characterized by the ratio of mean aortic pressure and mean flow (peripheral resistance). The pressure and flow at which the heart operates is defined as the working point. We have investigated whether the ventricle in the intact cat is working optimally, i.e., that it cannot increase work output further at the end-diastolic volume, contractile state, and prevailing heart rate. This condition is considered as "matching" of ventricle and load. It could be shown that optimal power is transferred when the ratio of peripheral and apparent source resistance equals twice the ratio of mean aortic and mean left ventricular pressure (the matching principle). In four cats, we observed that mean aortic and mean left ventricular pressures are proportionally related. Mean external power (the time integral of the product of pressure and flow divided by cycle length) and steady power (the product of mean pressure and mean flow) were found to be proportional as well. These proportionalities allow for the calculation of peripheral resistance and mean external power from the pump function graph. Pump function graphs were determined in three groups: control (n = 9), atrial pacing (n = 8), and halothane (n = 5). We compared the ratio of peripheral and source resistance at the working point and at the point of optimal work output (expressed in steady ventricular power). It could be shown that, in all investigated groups, the power optimum and the working point coincide. It was concluded that circulatory control in the intact anesthetized cat keeps the ventricle at optimal work output under the conditions studied.

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PubMed1984

Stretch of contracting muscle fibres: evidence for regularly spaced active sites along the filaments and enhanced mechanical performance.

Single frog skeletal muscle fibres were stretched during fused tetanic contractions. The force increase during stretch exhibited a breakpoint at a mean critical length change of 16.6 nm per half sarcomere that was independent of stretch velocity and sarcomere length. The early decaying extra force after stretch (component 2) was removed by a small quick release, leaving a longer lasting component (component 3). The amplitude of release required increased with time up to the angle in the force record during stretch, was constant for the remainder of the stretch and decreased with time after the end of stretch; it was consistently less than the critical amplitude of stretch (above). Component 3 occurred at sarcomere lengths above 2.3 microns and was amplitude dependent. The final force after stretch was usually higher than the isometric force at the starting length of the stretch. Non-uniformity as a cause of this component was examined by (a) laser diffraction studies which showed sarcomere stretch at all locations and (b) 0.6-0.7 mm long segments along the entire fibre which all elongated during stretch. After stretch the sarcomeres and segments were significantly more stable than during control isometric tetani. Segments which were clamped by a servo system demonstrated component 3. Shortening during contraction followed by stretch back to the starting length led to nearly as much force enhancement as stretch alone, suggesting that component 3 is not due to a passive elastic element recruited during activation. An increase in temperature decreased components 1 (velocity dependent force during stretch) and 2 but increased component 3. The critical length features of component 2 suggest a cross-bridge mechanism. However, the sarcomere length dependence of all components differs from that of isometric force and from predictions based on filament overlap.

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PubMed1984

Interaction of heart and arterial system.

We have studied the interrelation of left ventricle and arterial system in the anesthetized open-thorax cat. The ventricle was characterized by its pump function graph, relating mean ventricular pressure (Plv) and mean aortic flow (F). The pump function graph was determined by means of an artificial periphery and on a beat-to-beat basis. The periphery was characterized by relating mean aortic pressure (Pao) and mean flow. Mean aortic and mean left ventricular pressure could be related over a wide range of values by a proportionality factor Pao = a . Plv. In a series of five separate experiments a value of a = 1.72 +/- 0.14 (mean +/- SD) was found. This simplified relation allows direct comparison of apparent source resistance (i.e., slope of pump function graph), (Rs), and peripheral resistance (Rp). It was also found experimentally that total external power (w) could be calculated from mean aortic pressure and mean flow as well as from mean left ventricular pressure and mean flow (thus from the pump function graph) by w = c . Pao . F = c . a . Plv . F. The value of c = 1.16 +/- 0.12 (mean +/- SD, n = 4). Maximum external power was predicted for Rp/Rs = Pao/Plv = a. In six different cats Rp/Rs ratio in the working point (i.e., mean left ventricular pressure and mean flow when the normal periphery loaded the heart) was found to be Rp/Rs = 2.63 +/- 0.92. This value could not be shown to differ from that in the point where maximal external power was found, i.e., Rp/Rs = 1.81 +/- 0.08 (n = 6).

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PubMed1984

Oxygen uptake of frog skeletal muscle fibres following tetanic contractions at 18 degrees C.

Oxygen consumption following isometric tetanic contractions of single fibres and multifibre preparations of the tibialis anterior muscle of Rana temporaria was determined by continuous polarographic measurement of the PO2 in a 280 microliter glass chamber. Mixing of the fluid surrounding the muscle was achieved by an Archimedian screw. Force was measured via a stainless-steel wire leaving the chamber via a glass capillary. The characteristics of the oxygen-measuring system were assessed by injection of 1.6 microliter dye into the chamber and filming its subsequent distribution, and by injection of 1.6 microliter Ringer solution with a high (or low) oxygen content into the chamber and measuring the subsequent change of oxygen. It was found that a change in oxygen was measured after a true delay of 3 s and with an over-all time constant of 3.25 s following that delay. For seven single fibres the oxygen consumption following a 3 s tetanus was on average 2.46 mumol g-1; the average integrated value of the developed stress was 0.98 N mm-2 s. These two values were on average about 45% lower for the same tetani of multifibre preparations, but the average ratio of oxygen consumption to integrated stress was the same. Oxygen consumption was varied by changing tetanus duration. When the amount of oxygen consumed was plotted against stress integral a non-linear relationship was found because oxygen consumption increased less than the integrated stress value with longer tetani. Oxygen consumption did not start at the onset of contraction but about 10 s later. It then followed an exponential time course with an average time constant of 120 s. Delay and time constant were independent of the amount of oxygen consumed. The finding that oxygen consumption follows contraction after a delay of a few seconds confirms a similar conclusion drawn indirectly from studies on recovery heat by other investigators. A dependency of the time course of oxygen consumption on tetanus duration, as reported in the literature for frog muscle at 0 degree C, was not found.

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PubMed1984

The sarcomere length dependence of the rate of heat production during isometric tetanic contraction of frog muscles.

Heat production and force have been measured as a function of sarcomere length between 1.6 and 3.0 microns during isometric tetani at 0 degree C for two types of frog muscle: sartorius and extensor longus digiti iv (e.l.d. iv). Stable heat rate declines linearly with increasing sarcomere length above 2.20 microns for both e.l.d. iv and sartorius muscles. In sartorius muscle stable heat rate remains at or near its maximum value between 1.75 and 2.20 microns while force decreases. In e.l.d. iv muscle, both stable heat rate and force decline linearly as sarcomere length decreases below 2.20 microns.

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PubMed1984

Heat transport in the canine left ventricular wall.

The rate of rise of local myocardial temperature (dT/dt) evoked by left coronary artery main stem occlusion has been proposed in the literature as a measure of local metabolic heat production, assuming heat loss due to diffusion to be negligible. In a previous study (ten Velden, G. H. M., G. Elzinga, and N. Westerhof. Circ. Res. 50: 63-73, 1982), we showed that this assumption was not valid. With this information in mind, in an attempt to study local metabolism, we compared, in anesthetized dogs, the dT/dt with the temperature distribution over the left ventricular wall. We found the value of dT/dt to be reproducible in time and to reproducibly depend on location. Negative values as well as positive values were measured; values even higher than the maximal possible temperature slope, calculated from the energy equivalent of left ventricular oxygen consumption and the specific heat of cardiac tissue, were found. Transmural distribution of the dT/dt showed positive values epicardially and negative values endocardially, while, as previously shown, a parabola-like shape of the transmyocardial temperature distribution existed. Our findings demonstrate that dT/dt by left coronary main stem occlusion cannot be used as a measure of local myocardial heat production.

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PubMed1984

Does the history of contraction affect the pressure-volume relationship?

A comparison is made between two descriptions of the hemodynamic properties of the heart: the ventricular pressure-volume (P-V) relationship, modeled by a time-varying elastance, and the ventricular pump function graph, i.e., the relationship between mean ventricular pressure and output. It appears that, although both descriptions seem to reflect the same myocardial properties, an unexplained discrepancy exists between the assumed linear nature of the time-varying elastance and the curvature of the pump function graph. It is argued that this discrepancy may reflect deviations from the ideal time-varying elastance behavior, such as those observed in isolated cardiac muscle, where the history of contraction affected the P-V relationship.

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PubMed1983

The effect of cardiac denervation and beta-blockade on control of cardiac output in exercising dogs.

Normal and cardiac denervated dogs, with an electromagnetic aortic flowprobe implanted at least 14 days before the experiments, ran at different speeds on a 25% graded treadmill. The experiments were carried out before and after blockade of betareceptors in the heart by PO administration of 125 mg X kg-1 practolol per day. Changes in stroke volume, heart rate, and cardiac output were measured. After beta-adrenergic blockade, only two of the seven dogs with denervated hearts were prepared to run at a limited number of speeds. Time constants of the cardiac output changes at the onset of exercise were significantly different (P less than 0.001) for the normal (11.5 +/- 0.7 s, mean +/- SEM) and the denervated dogs (29.5 +/- 1.1 s), but in normal dogs did not change with practolol (11.8 +/- 0.8 s). The steady state relationship between cardiac output (CO) and work per unit time performed on the treadmill (P) was for normal dogs: CO = 156 + 1.55P, for normal dogs after practolol treatment: CO = 156 + 0.43P (slope significantly different, P less than 0.05), and for dogs with denervated hearts: CO = 121 + 2.06P (not significantly different from normal dogs). It was concluded that changes in the venous or arterial system alone are not sufficient to increase cardiac output appreciably during exercise. The magnitude of the cardiac output increase depends more on the presence of intact beta-receptors than on the presence of intact cardiac nerves.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1983

The effect of palmitate and lactate on mechanical performance and metabolism of cat and rat myocardium.

Fourteen isolated ejecting hearts were perfused with a suspension of red cells in Tyrode solution. In five hearts comparison was made between glucose alone as substrate and glucose plus free fatty acid (palmitate). In five hearts the effect of additional lactate was studied. In the remaining hearts no substrate changes were made (controls). There were only transient changes in cardiac output of the hearts (at fixed mean aortic pressure) when the perfusion media were switched from one to another. There were no consistent steady-state changes in myocardial oxygen consumption, mean external power, efficiency, cardiac output or coronary blood flow associated with any of the changes in substrate consumption. Thus we were unable to confirm an increase in oxygen consumption and decrease in efficiency associated with either free fatty acid or lactate as substrates. Isolated rat trabeculae were deprived of exogenous substrate; their mechanical performance remained constant for approximately 10 min. Subsequent deterioration was restored by any of the three exogenous substrates. We conclude that there is no oxygen wasting effect of these substrates as has previously been postulated, nor any deleterious effect of changing exogenous or endogenous carbohydrate or lipid substrate.

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