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F Mast

Publications and source records attributed to F Mast.

34 records · Page 2Linked to original sources

Myocardial force production and energy turnover in anoxia.

ATP turnover of isolated rabbit papillary muscles, contracting isometrically at 20 degrees C, was determined in oxygen and during 40 min of exposure to nitrogen (anoxia). Stimulus frequency was 0.2 hertz (Hz) in oxygen and 0.2 or 1.0 Hz in nitrogen. In oxygen, ATP turnover was determined from oxygen consumption using a P/O2 ratio of 6.3. The time-dependent rate of ATP turnover in nitrogen was found from the production of lactate, and the changes in adenine nucleotides and phosphocreatine, measured in rapidly frozen preparations at different time-points during the anoxic period. A P/lactate ratio of 1.5 was used. In muscles stimulated at 0.2 Hz, twitch force dropped during the anoxic period to 33% while force production of muscles stimulated at 1.0 Hz stopped completely. However, in the latter muscles, resting force rose to 19% of the twitch force in oxygen. The rate of ATP hydrolysis in anoxia depended strongly on stimulus frequency, indicating that it is not solely determined by the glycolytic capacity. In the 0.2 Hz-stimulated muscles the decrease in energy turnover occurred in parallel with the drop in force. However, the rise in resting force in muscles stimulated at 1.0 Hz occurred when ATP turnover was close to zero. It was concluded that anoxia hardly affects the energy required for twitch force production, but that the rise of resting force measured when twitch force had disappeared occurred when the rates of cross-bridge cycling and calcium turnover were very low.

Adenine Nucleotides↗

Oxidative and glycolytic ATP formation of rabbit papillary muscle in oxygen and nitrogen.

Contraction-related O2 consumption of rabbit papillary muscles was determined at 20 degrees C by measuring change in saline PO2 during and after trains of 120 twitches at 0.125-1 Hz in a microrespirometer. Although anoxic cores occurred at twitch frequencies greater than 0.2 Hz, no lactate was found in saline after twitch train. To measure lactate accumulation in muscle, fully oxygenated muscles were frozen at rest and during steady-state twitches at 0.2 Hz. We also measured nucleotides and creatine (Cr) compounds. There were no differences in lactate, ATP, and phosphocreatine (PCr) content between the resting and active muscles. When a P-to-O2 ratio of 6.3 is assumed, aerobic ATP formation was compared with glycolytic ATP formation during anoxia at a stimulus frequency of 0.2 Hz. The latter value was obtained by freezing muscles between 6 and 25 min after changing from O2- to N2-saturated saline. Withdrawal of O2 caused the ratio of PCr to total Cr to fall in less than 6 min from 0.77 to 0.23, while ATP remained at approximately 15 mumol/g dry wt. Force fell initially within 4 min to approximately 70% of control value, decreasing thereafter more slowly to approximately 40% at 20 min. From the relationship between amount of lactate formed and duration of anoxia, rate of anaerobic ATP formation was calculated assuming a P-to-lactate ratio of 1. We found that despite continuing contractile activity, anaerobic ATP formation was less than that required by a fully oxygenated resting muscle and was about the same magnitude as the estimated ATP hydrolysis for the contractions in N2. We conclude that in fully oxygenated rabbit papillary muscles no net lactate is produced during stimulation and that in anoxia anaerobic glycolytic capacity may not provide sufficient ATP for processes other than the uptake of Ca by the sarcoplasmic reticulum and cross-bridge cycling.

Adenosine Triphosphate↗

Analysis of thermopile records from contracting isolated cardiac muscle.

Recovery heat production after contraction in rabbit papillary muscle at 20 degrees C occurs at an exponentially declining rate. The time constant describing this decline is 25 s; it is not different when 10 twitches or when a steady-state twitch train is studied, and it is unaltered by changing stimulus frequency from 0.125 to 0.2 Hz. The same value has previously been found after single twitches. If it is assumed that phosphocreatine (PCr) resynthesis is the cause of recovery heat production and that it occurs also during contractions at a rate proportional to the amount of PCr depletion, it is possible to divide the total heat production for any period of stimulation into that caused by this recovery process (R) and that caused by initial (I) processes (presumed to be PCr splitting). The value of R/I obtained by using this method is 1.10 +/- 0.04 (means +/- SE, n = 27 muscles), close to the theoretical value of 1.13. The correspondence between the measured and the predicted ratio supports the assumptions underlying the measurement. Thus in heart muscle the heat produced during and after contraction can be explained by PCr splitting and reformation. The older Bugnard method of analysis applied to the same data gives an R/I value of 1.5; the reasons for the discrepancy are described.

Animals↗

Heat released during relaxation equals force-length area in isometric contractions of rabbit papillary muscle.

It has been claimed that the mechanical performance and the related energy turnover of the left ventricle can be reliably predicted on the basis of its time-varying elastance behavior. In its most elementary form, this behavior can be mathematically described by E(t) = P(t)/[V(t)-Vd], where E is ventricular elastance, t is time, P is ventricular pressure, V is ventricular volume, and Vd is the intercept of the end-systolic pressure-volume line on the volume axis. To find out how this behavior of the ventricle as a whole is related to the properties of the myocardium, we tested the energetic prediction for the ventricle that the pressure-volume area of an isovolumic contraction equals the energy released in relaxation in experiments on isolated rabbit papillary muscle at 20 degrees C. To that end, the energy (joules) contained by the force-length area of the muscles, contracting isometrically, was compared with the heat (joules) liberated in relaxation as measured with thermopiles. Mechanical performance of the muscles was varied by altering initial muscle length and external calcium. The slope of the resulting relation between force-length area and heat liberated in relaxation (n = 26) was not significantly different from unity. Thus, the energetic prediction of the time-varying elastance model developed for the whole left ventricle was confirmed by experiments on rabbit papillary muscle at 20 degrees C.

Animals↗

Energy demand, supply, and utilization in hypoxia, and force recovery after reoxygenation in rabbit heart muscle.

In rabbit papillary muscle contracting at 20 degrees C in nitrogen at 0.2 Hz, glycolytic ATP formation is just enough to support the diminished contractile activity. Basal metabolism, important to maintain cellular function and integrity, is strongly inhibited. In the present study, we address the question of whether the inhibition of basal processes in hypoxia determines redevelopment of force in reoxygenation. By not stimulating the muscle during hypoxia, we try to make more ATP available for basal processes. Isometric force of papillary muscles (0.2-Hz stimulation) is measured before, during, and after 40 minutes of hypoxia. ATP formation and utilization in hypoxia are estimated from lactate production and changes in nucleotides and creatine compounds. After reoxygenation, muscles stimulated during hypoxia produce a steady-state force of 78% of the aerobic control; resting muscles recover to 94%. In contrast to expectation, lactate production in hypoxic resting muscles is only 30% of that in contracting ones. The findings indicate that basal metabolic rate of hypoxic muscles at rest is 14% of that of quiescent, well-oxygenated myocardium. We conclude that in hypoxic myocardium little ATP is available for basal metabolism, irrespective of the energy demand of the contractile system. It is therefore unlikely that the lower force found after reoxygenation in muscles stimulated during hypoxia is related to the degree of inhibition of basal processes.

Adenosine Triphosphate↗

Comparison of rigid and flexible rings for annuloplasty of the porcine mitral valve.

Seven rigid (Carpentier) and six flexible (Duran) annuloplasty rings were implanted in healthy pigs. First, in the intact pig, cinefluoroscopy was used to record movements of the anulus. Results were compared with data from three pigs instrumented with a continuous radiopaque marker on the anulus. Pump function of all hearts with annuloplasty rings and function of the mitral valve were studied 4-6 weeks after the operation, first in the exposed heart and then subsequently in the isolated heart in a perfusion chamber at maximal filling pressure and normal or low arterial pressure. Separation of the blood-perfused coronary circulation from the crystalline solution pumped by the left heart allowed videoendoscopy of the working valve. Flexible rings interfered less with normal movements of the mitral anulus than rigid rings and caused less impairment of filling of the basal part of the ventricle, and the unloaded stroke volume was 16% larger. For normal arterial pressures, the differences were smaller and will be difficult to detect in clinical situations. A stiff anulus was seen to be pushed underneath the aortic valve during systole, which caused a mild subvalvular obstruction. The mean diastolic pressure gradient across rigid annuloplasty rings was slightly larger than across flexible rings of the same or slightly smaller diastolic size. Rigid rings change the pattern of movement of the leaflets; the mural leaflet remains immobile throughout diastole. Although Duran rings interfere less with valvular function and filling of the basal part of the ventricle than do Carpentier rings, the differences are small and probably only of limited clinical importance.

Animals↗

Metabolic recovery of acidotic rabbit cardiac muscle: effects of low pH and oxygen shortage.

Heat production during and after contraction of isolated rabbit papillary muscles was measured at 20 degrees C with metal-film thermopiles. Under control conditions (0.2 Hz, pH 7.4) total heat and steady-state force production due to 120 twitches were 1.0 +/- 0.4 J/g and 29.5 +/- 5.1 mN/mm2 (mean +/- SD; n = 5), respectively. Increasing the CO2 of the bicarbonate-buffered superfusate from 5% (pH 7.4) to 24% (pH 6.6) led to a decrease of force and heat production, 54% and 72%, respectively, of the control value. The recovery heat-time constant, reflecting the time course of oxidative phosphorylation, increased from 23.0 +/- 5.1 seconds at pH 7.4 to 69.5 +/- 34.7 seconds at pH 6.6. The ratio of recovery and initial heat equaled 1.06 under both conditions. Enhancing the metabolic rate by increasing the stimulation frequency to 1.0 Hz led, after an initial maximum, to a decline of force and heat presumably as the consequence of shortage of oxygen in the muscle core. The recovery phase in this case was characterized by a double exponential function having time constants of 7.6 and 64.4 seconds. When pH was lowered to 6.6 together with the enhancement of the stimulation frequency to 1 Hz, an additional exothermal process, unrelated to force production, was observed during contraction and for some time thereafter. It was concluded that severe acidosis slows down the rate of oxidative phosphorylation and may reduce the economy of contraction. However, it does not change the nature of recovery and initial heat processes.(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis↗

Energy turnover in hypoxic heart muscle.

In isolated rabbit papillary muscles at 20 degrees C, we studied the relationship between demand, supply, and utilisation of energy in hypoxia. Since shortage of energy is an important factor in loss of contractile performance following an hypoxic period, we tried to find a relationship between the loss of force production upon reoxygenation and the demand, supply, and utilisation of energy. Energy demand in hypoxia was defined as the -P turnover found in oxygen under further identical conditions. Energy supply in hypoxia was determined from lactate formation, using a P/lactate ratio of 1, while energy utilisation in hypoxia was obtained from the sum of: -P supply, the decrease of PCr and ATP, and the increase of AMP. Energy demand in hypoxia was varied by stimulating the hypoxic muscles at 0.2 Hz or not at all. For contracting hypoxic muscles energy supply by glycolysis was only 23% of energy demand. After 40 min of hypoxia force did only partially recover (78%) upon reoxygenation. For muscles at rest in hypoxia, force recovery was significantly (p less than 0.05) better (94% of control). However, energy supply was no more than 15% of the demand because supply was almost proportionally lower. It is concluded that the loss of force production upon reoxygenation is not related to the supply: demand ratio. By taking the integrated difference after 40 min of hypoxia between energy demand and utilisation, the energy deficit built up in hypoxia was estimated. In contracting muscle this was 2 times higher than in resting ones. It is suggested that a relationship could exist between the energy deficit and the loss of contractile performance upon reoxygenation. Experiments to test this idea are discussed.

Animals↗

Recovery heat production of isolated rabbit papillary muscle at 20 degrees C.

Using metal-film thermopiles, heat production of isolated rabbit papillary muscles was measured under aerobic conditions at 20 degrees C. The time course of total heat production resulting from a single contraction (average of 10) and a twitch train of 10 contractions (0.2 Hz) was separated into initial (I) and recovery heat (R). The time course of recovery heat production of single twitches was characterized by a time constant of 25.4 +/- 1.7 s (mean +/- SE; n = 10). The recovery ratio, R/I, was 1.18 +/- 0.08 (mean +/- SE; n = 7). Total heat produced 25.2 +/- 2.9 mJ.gdw-1 (mean +/- SE; n = 11). After trains of 10 contractions a time constant of 25.2 +/- 1.6 s (mean +/- SE; n = 9) was found. The recovery ratio was 1.14 +/- 0.09 (mean +/-SE; n = 9). Total heat produced was 489 +/- 41 mJ.gdw-1 (mean +/- SE; n = 9). Time constants and recovery ratios for 1 and 10 twitches were not significantly different. This suggests that only the extent but not the nature of the chemical processes after contraction changes when the preparation produces about 20 times more heat. Since the recovery ratio values did not differ largely from the value derived theoretically the conclusion is justified that, under normal aerobic conditions, PCr splitting and its oxidative resynthesis are the major metabolic processes responsible for the energy supply of isolated cardiac muscle.

Animals↗

Mechanical determinants of myocardial energy turnover.

Energy turnover of the left ventricle does not differ in isovolumic contractions and contractions where pressure is released from peak to zero. This experimental result corresponds to predictions from a time varying elastance model of the mechanical and energetic properties of the left ventricle. To assess the validity of this model for cardiac muscle in general, experiments were designed to investigate whether mechanical and energetic behaviour of isolated cardiac muscle preparations could also be predicted from the time varying elastance model. The results obtained so far indicate, however, that not all experimental results can be accommodated by the model. This suggests that the value of the model may be limited.

Animals↗

Heat production and oxygen consumption following contraction of isolated rabbit papillary muscle at 20 degrees C.

The time course of oxygen uptake following isometric twitch contractions of isolated rabbit papillary muscles was measured using a polarographic oxygen electrode. Using a diffusion model we eliminated the effect of oxygen storage on the measured time course of oxygen uptake to determine the time constant of mitochondrial "off" kinetics. Two different approaches were followed. In Method 1, two steady-state levels were compared, whereas in Method 2, the time course of mitochondrial "off" kinetics was studied. Using Method 1 we found tau = 20 +/- 8 seconds (n = 7), whereas Method 2 yielded tau = 26 +/- 9 seconds (n = 11). These findings were compared with preliminary measurements of recovery heat production of the same preparation and at the same temperature. Heat produced after a train of 10 twitch contractions appeared to follow a monoexponential time course with a time constant of 24.9 +/- 9.5 seconds (n = 9). These results suggest that aerobic metabolism in isolated rabbit papillary muscle constitutes the only recovery process.

Animals↗

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.

Animals↗