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J Kedem

Publications and source records attributed to J Kedem.

At least 55 records · Page 3Linked to original sources

Periodic oscillation of haemodynamic parameters modulated by experimental atrioventricular dissociation.

Recording of blood pressure and flow usually show periodic oscillations of varying frequencies; these include waves produced by cardiac contraction, respiratory movement, and Mayer waves. The present report describes another wave, designated "A-V" wave, whose origin is related to asynchronous contraction of atria and ventricles. In open-chest anaesthetized dogs, aortic blood pressure and flow were measured, as well as vena caval blood flow, right ventricular contractile force, and electrocardiogram. The S-A node was crushed, and atrioventricular conduction block was produced surgically. The atria and ventricles were stimulated independently at various heart rates. Fourier analysis was used to identify and measure each of the waves present in the various recordings. It was found that, at any given atrial rate, the frequency of the A-V waves was linearly related to ventricular heart rate. A-V waves were present at every heart rate examined, although when atrial and ventricular rates are identical, the predicted frequency is zero. These observations suggest that during asynchrony of atrial and ventricular contraction, blood flow is irregular and its pattern is dependent upon the degree of asynchrony.

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Heart rate and myocardial substrate preference during normal and hypoxic perfusion of the heart in vivo.

Selective utilization of carbohydrates and FFA by the heart was studied on the open-chest dog preparation. The heart was paced at frequencies from 120-240/min, and arterial and coronary venous blood samples were taken at these frequencies both during normal ventilation and hypoxia (arterial PO2 similar to 55 mmHg). The concentrations of glucose, lactate, pyruvate, and FFA were determined, and substrate utilization was calculated from these values and coronary blood flow. It was found that increased heart rate, particularly during hypoxia, increased utilization of both glucose and FFA. However, the relative amount of the energy produced from glucose utilization was minimal during hypoxia and most glucose underwent glycolysis only. Thus, whereas in control conditions of the relation between carbohydrate and FFA was about 60% to 40% during hyposia and high frequency the relation was reversed and almost 90% of all energy produced was supplied by FFA.

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Coronary venous flow and O2 saturation during transitional phases between various cardiac rates.

The instantaneous and continuous interrelationship between coronary blood flow and coronary venous O2 saturation was determined during transient periods following abrupt rate change in the electrically paced canine heart. Through a catheter in the coronary sinus, O2 saturation was continuously monitored using a fibreoptics technique, and venous flow was measured with an electromagnetic flowmeter. Various patterns of change in flow and O2 saturation were observed depending both on the absolute values of the cardiac rates as well as on the relative difference between them during changes from one rate to another. Whereas elevation of coronary flow was monophasic when the magnitude of heart rate change was below 75 beats per minute, a drop in flow was observed preceeding its elevation when the difference was greater. At high rates further increase in rate caused either no alteration or led to a monophasic drop in flow during the transitional period. Changes in O2 saturation were observed only when heart rate difference exceeded 60 beats per minute. Between 60-90 beats per minute O2 saturation remained steady except during the transient rate elevation, ending in a lower steady state O2 saturation. The results indicate that both O2 saturation and coronary flow change with heart rate initially because of mechanical consequence of the increased rate on the myocardium, and later according to its new metabolic needs also manifested by changed O2 extraction.

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Regional asynchrony of segmental contraction may explain the "oxygen consumption paradox" in stunned myocardium.

Despite apparently depressed function, stunned myocardium maintains oxygen consumption and has the capacity to increase contractility with inotropic stimulation. We hypothesized that during stunning, O2 demand is maintained because regional segment work is performed, but is asynchronous with global left ventricular contraction, and that inotropic stimulation would restore regional work and synchrony. Thirteen open-chest anesthetized dogs were subjected to three left anterior descending (LAD) coronary artery occlusions (10 min) and reperfusions (15 min) to produce regional myocardial stunning. Segment shortening and force development were measured independently and simultaneously in the LAD (experimental) region and circumflex (control) regions. Regional myocardial work was calculated as the integrated product of instantaneous force and shortening, during two periods: 1) over the entire cardiac cycle (Positive Work), and 2) limited to the systolic portion of the cardiac cycle (Systolic Work). Regional myocardial O2 consumption (MVO2) was calculated from regional blood flow (radiolabeled microspheres) and O2 saturation data (microspectrophotometry). Occlusion of the LAD produced a delay in onset of segment shortening in the ischemic region, but not in regional force development. A time delay of 67-81 ms persisted through the three stages of occlusions and reperfusions. Systolic regional work was depressed to a greater extent (924 +/- 182 to 149 +/- 118 g*mm*min-1) than total positive regional work (1437 +/- 337 to 857 +/- 174 g*mm*min-1). Regional subepicardial MVO2 in the stunned region was not different than in the control region (7.3 +/- 1.5 vs. 6.9 +/- 1.4 ml O2*min-1*100 g-1). Local infusion of isoproterenol reversed the delay in regional shortening from 73 +/- 7 to 21 +/- 8 ms, thereby augmenting systolic work (298%) more than positive work (60%), without a significant increase in MVO2 (7.3 +/- 1.5 to 10.5 +/- 3.2 ml O2*min-1*100 g-1). It is concluded that myocardial stunning decreases regional systolic work due to regional mechanical asynchrony, while MVO2 is used supported total positive work which was not significantly reduced. Isoproterenol restores regional work by restoring synchrony, without greatly affecting regional MVO2.

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The oxygen wasting effect of isoproterenol is altered by chemical denervation and cardiac hypertrophy.

We tested the hypothesis that isoproterenol would increase myocardial work and O2 consumption at reduced efficiency and that both left ventricular hypertrophy and chemical sympathectomy would lead to changes in this myocardial efficiency response. Left ventricular hypertrophy was produced by aortic valve plication in 23 puppies. Six months later, sympathetic denervation (6-hydroxydopamine) was produced in 12 hypertrophied and 10 non-hypertrophied dogs, 5 days prior to acute experiments. Ten non-hypertrophied and 11 hypertrophied animals were not denervated. Measurements were made before and during an isoproterenol infusion (0.5 microgram/kg/ min). Regional myocardial work was calculated as the integrated product of force (miniature transducer) and segment shortening (ultrasonic crystals). Regional O2 consumption was calculated from regional blood flow (microspheres) and regional O2 saturations (microspectrophotometry). In all groups, regional O2 consumption increased with isoproterenol (non-hypertrophied, non-sympathectomized 6.5 +/- 0.8 to 20.3 +/- 5 ml O2/min/100 g, non-hypertrophied, sympathectomized 5.0 +/- 0.7 to 10.0 +/- 1.5, hypertrophied, non-sympathectomized 9.8 +/- 1.3 to 16.2 +/- 2.2, hypertrophied, sympathectomized 6.1 +/- 0.5 to 13.3 +/- 1.6). Regional segment work also increased in all groups with isoproterenol stimulation (non-hypertrophied, non-sympathectomized 781 +/- 73 to 1197 +/- 61 g.mm/min, non-hypertrophied, sympathectomized 996 +/- 221 to 2118 +/- 412, hypertrophied, non-sympathectomized 1031 +/- 145 to 3262 +/- 753, hypertrophied, sympathectomized 721 +/- 116 to 1745 +/- 402). In the non-hypertrophied, non-sympathectomized group, efficiency (work/O2 consumption) was significantly decreased from 122 +/- 17 to 76 +/- 9 g.mm/ml O2/100 g demonstrating an "oxygen wasting" effect. In the hypertrophied, non-sympathectomized group, segment efficiency significantly increased from 94 +/- 19 to 250 +/- 63. In both sympathectomized groups, efficiency was not altered by isoproterenol. Thus the oxygen wasting effect of beta-adrenergic stimulation was reversed by left ventricular hypertrophy and blocked by sympathectomy.

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Effect of dopamine on regional myocardial function and oxygen consumption in experimental left ventricular hypertrophy.

We investigated the hypothesis that the capacity of left ventricular myocardium to respond to an inotropic challenge by dopamine would be diminished in left ventricular hypertrophy induced by plication of the aortic valve. Seven mongrel dogs (LVH group) aged 6-8 weeks and weighing 4-6 kg, were subjected to preliminary surgery in which the noncoronary sinus of Valsalva was plicated. Six months later these animals, as well as a control group of dogs, were subjected to acute experiments in which the effect of dopamine (7.5 and 15 micrograms/kg/min) on regional and global myocardial function and oxygen consumption was studied. Myocardial segment length was measured with ultrasonic dimension transducers, and left ventricular and aortic blood pressures were recorded from catheter-tip transducers. Regional coronary blood flow was determined with radioactive microspheres, and regional oxygen saturation in small arteries and veins was measured using microspectrophotometry. Regional myocardial O2 consumption was calculated from these parameters. Heart weights were significantly elevated in the LVH group, and a pressure gradient of about 25 mm Hg was observed across the aortic valve. In both groups, dopamine infusion produced a dose-dependent increase in heart rate, left ventricular pressure, and LV dP/dtmax. Prior to dopamine infusion, percent shortening per beat was greater in the LVH group (13.97 +/- 1.2%) than in the control group (9.49 +/- 1.07%). Although the maximum speed of segment shortening was elevated by dopamine in both groups, percent shortening was not elevated in the LVH group. Stimulation by the high dose of dopamine produced a threefold elevation in regional coronary blood flow in both groups. Oxygen extraction was unchanged; the proportion of small veins with low O2 saturation was not elevated in LVH hearts, even during dopamine stimulation. Regional myocardial O2 consumption was elevated by dopamine (15 micrograms/kg/min) to about the same extent in both the control and LVH groups (19.1 +/- 2.3 and 17.5 +/- 2.3 ml O2/min/100 g) respectively. It is concluded that, in dogs with six months of aortic stenosis, dopamine does not exhaust functional reserve and the relationship between O2 supply and consumption is not significantly impaired.

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An experimental technique for estimating regional myocardial segment work in vivo.

We determined the capabilities and limitations of an experimental approach to measure segment work (force x distance) of myocardial regions in the in vivo beating heart. In 18 open-chest anesthetized dogs, segment length was measured using ultrasonic dimension transducers, and developed force was measured with miniature force transducers. Work was defined as the integrated multiples of instantaneous force and shortening during a single (averaged) beat, corresponding to the area under the length-force loop. Changes in work over a range of 9.78 x 10(-4) to 2.93 x 10(-2) J/g/min were produced by vena caval constriction, aortic constriction, atrial pacing, and isoproterenol (0.5 and 1.0 micrograms/kg/min). Work was measured in both major and minor axes. In 60% of the animals, work in the minor axis was 9.2-fold greater than in the major axis. In the others, all interventions changed regional work to the same extent in both axes (r = 0.802; p < 0.05). Work changes were also compared between the base, anterior, and posterior walls. The response was directionally similar in all regions, ranging from -79 +/- 1% during caval occlusion to 278 +/- 98% during isoproterenol. The effective size of the measured muscle mass was limited to the transducer area because the amplitude and pattern of both force development and segment shortening were not changed until deep myocardial cuts were as close as 2 mm from the measuring area. We conclude that work measurement in the minor axis is quantitatively representative of fiber work in that region.

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Development and implementation of a general compiler to produce specific programs for minicomputer control of physiological experiments in real time.

A method for automatic generation of specific FORTRAN programs to control physiological experiments with a computer was developed. The general real-time software package is built into a high level language (MAB = MAcro Basic). From this package, the scientist can automatically generate for him/herself specific programs for controlling his own experiments by a simple procedure. The generated programs contain only the relevant code, adjusted dimensions of arrays, names of parameters, and formatting for printing of tables and graphics for the particular experiment. Therefore, the resulting program is efficient both in terms of memory utilization and in execution time.

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