Papers by vincent schouten
Pfl�gers Archiv European Journal of Physiology, 1989
The whole-cell patch-clamp technique was used to study the effects of holding potential and frequ... more The whole-cell patch-clamp technique was used to study the effects of holding potential and frequency on the Ca 2 + current in frog ventricular myocytes. INa was blocked by TTX, and ica was activated with depolarizing clamps from different holding potentials. Variation of the holding potential revealed three new effects on/Ca: (1) At-40 mV ica declined with a time constant of 15 min, while at-90 mV, this irreversible decline (run down) in iCa did not occur. (2) The decline of ica at-40 mV was biphasic: run down was preceeded by a slow inactivation with a time constant of 40 s, which was reversible upon returning the holding potentia! to-90 mV. (3) Increasing the frequency of the clamp pulses from 0.1 to I Hz led to a rapid decline of/ca when the holding potential was positive to-60 mV, but at-90 mV had either no effect or increased/ca by 35%, if cAMP was included in the dialyzing solution. On the other hand, cAMP did not alter the time course of the run down and the slow inactivation. Replacement of extracellular Ca 2 § by Ba 2 § markedly slowed ic, kinetics, but did not change the very slow inactivation or the frequency-induced enhancement of/ca-Injection of cAMP led to a transient increase of ic,. The phosphodiesterase inhibitor theophylline enhanced the amplitude of the transient and slowed its decay. This effect was mimicked by increased frequency. It is concluded that frequency-induced enhancement of iCa is highly dependent on the holding potential, independent of Ca 2 +, and may involve elevation of the intracellular level of cAMP via inhibition of phosphodiesterase activity. The new type of very slow inactivation is probably under direct voltage control and independent of Ca 2 + and cAMP .
production in rat heart. Sarcolemma, sarcoplasmic reticulum, and sarcomeres as limiting factors i... more production in rat heart. Sarcolemma, sarcoplasmic reticulum, and sarcomeres as limiting factors in force
Clinical Science, 1982
Medical Restnrch Society is well documented but the concurrent effects on glucose assimilation in... more Medical Restnrch Society is well documented but the concurrent effects on glucose assimilation in the body have not been invwtigated. Iherefore we have studied foream glucose uptake (m) b i m t l y in six n o d men and compared the responses after a 758 o r a l glucose load and a mixed meal con-75g carbabydrats. The rise in arterial glucose levels after the meal was considerably less than after glucose loading but the overall insulin response (assessed as& ie the incremental area under the curve 0-180 min) was not statistically different. meal than after glucose loading but the elevation was more sustained and at the termination of the study significantly exceeded that following glucose ingestion. The results show that while after the meal, the glucose response was only 26% of that following the glucose load, the rise in FGU reached 62% of the latter. in glycaemia, the increase in peripheral glucose uptake rae significantly greater after the meal; the mean (*S) ratio AiWl/Aglucose after the meal and glucose load respectively were 43.7a14.4 and 13.7*3.7, pC.05. Glucagon levels were unaltered after the meal but a significant stimulation in somatostatin concentrations was recorded. Conclusion: Relative to the rise in arterial glucose levels, peripheral glucose uptake is greater after a meal than after glucose loading with an equivalent carbohydrate challenge. These findings could have important implications for the dietary management of diabetes. Fou rose less rapidly after the Thus relative to the change
Developments in Cardiovascular Medicine, 1983
The purpose of this study was to analyze whether and to what extent (i) the force-interval relati... more The purpose of this study was to analyze whether and to what extent (i) the force-interval relationship, (ii) the forces-arcomere length relationship and (iii) the force-velocity relationship are modified in acute hypertrophy. Mechanical properties of trabeculae that were dissected from the right ventricle of rats were studied. Three experimental models were used: (i) 3–4 months’ old Wistar rats with normal blood pressure served as controls; (ii) hyperthyroid Wistar rats of 3–4 months of age were studied after two weeks of triiodothyronine injections (50 µg daily); (iii) rats of the same age after 2–4 weeks of hypobaric hypoxia which leads to hypertrophy of the right ventricle as a result of pulmonary hypertension at elevated cardiac output. The muscles were studied in a bath, which was rapidly perfused with modified oxygenated Krebs Henseleit solution at 25 oC at pH 7.4. Force was measured with a strain gauge. Muscle length was measured and controlled with a servomotor. Sarcomere length was measured and controlled by means of laser diffraction techniques. Mechanical recovery curves in controls and hearts following hypobaric hypoxia showed a rapid rise in the first 600 ms followed by a slow rise to plateau level that was attained at 60 seconds. Mechanical recovery in hyperthyroid muscles showed only the rapid phase of recovery. Force at test intervals between 800 ms and 100 s was 100% of steady-state value. Both passive force (F), sarcomere length (SL) relations and active F-SL relations, studied at external calcium concentration = 2.5 mM were comparable for the three groups. No difference in stress development between the three groups was observed. The influence of Ca++ on the shape of F-SL relations in controls and trabeculae of T3 rats was identical. The F-SL curve at Ca++ = 2.5 mM in trabeculae following hypobaric hypoxia was slightly steeper than in controls. Maximal shortening velocity of the sarcomeres (Vo) was 13.6 ± 3.0 µm/s (mean ± 1 SD) in controls; 17.9 ± 2.1 µ m/s in T3 rats; and 8.62 ± 2.0 µ m/s in muscle of hypobaric hypoxia rats. Results suggest 1) increased capacity and transport rate of Ca++ in structures coupling excitation with contraction in T3 hypertrophy compared to controls and hypertrophy resulting from hypobaric hypoxia; 2) no appreciable effect of hypertrophy on length dependence of activation; 3) changes of Vo in the hypertrophy states correlate with reported changes in myosin isoenzyme composition.
The Journal of Physiology, 1982
1. The contractility (maximum rate of rise of left ventricular pressure) and action potential dur... more 1. The contractility (maximum rate of rise of left ventricular pressure) and action potential duration were measured in intact closed‐chest anaesthetized dogs with complete atrioventricular dissociation and β‐adrenergic blockade.2. Measurements were confined to test beats following a 1 sec interval. Prior to the test interval (priming period) a variety of potentiating stimulus trains were introduced.3. When the frequency of stimulation was increased in the priming period (frequency potentiation), there was an inverse relationship between action potential duration and contractility of the test beat.4. When the test beat was potentiated by a single beat terminating the priming period with one short interval (post‐extrasystolic potentiation), there was no relationship between the action potential duration and contractility of the test beat.5. Paired pulse stimulation was used for any given frequency to vary contractility by short interval potentiation. For any given frequency of stimul...
Pflügers Archiv, 1986
Peak force and membrane potential were recorded from papillary muscles and trabeculae excised fro... more Peak force and membrane potential were recorded from papillary muscles and trabeculae excised from the ventricles of adult rat hearts. Experiments were performed at 2.5 mM Ca2+ and 26 degrees C. In thick preparations (diameter 0.2-1.2 mm) an increase of stimulation frequency caused a reduction of peak force and action potential duration as has been found in many studies previously. In thin preparations (diameter less than 0.2 mm) both peak force and action potential duration were almost independent of stimulation frequency. When the flow of Tyrode solution through the muscle bath was reduced an increase of stimulation frequency caused a reduction of peak force and action potential duration in thin preparations. We conclude that the reduced peak force and action potential duration in papillary muscles at high stimulation frequencies is due to insufficient exchange of metabolites and oxygen between the medium and the core of the muscle. The results indicate that the critical diameter for the preparations is about 0.2 mm.
The Journal of the Acoustical Society of America, 2003
There is provided an implanted system and method for delivering subsonic mechanical waves to one ... more There is provided an implanted system and method for delivering subsonic mechanical waves to one or more selected patient areas, said areas including the patient's heart and/or lungs. The mechanical waves are delivered for the purpose of treating fibrillation or like arrhythmias, for enhancing lung gas exchange, enhancing cardiac muscle fiber relaxation, and enhancing coronary perfusion. Mechanical waves are generated in a frequency range of about 1,100,000 Hz, and preferably 1-50,000 Hz. The waves may be delivered continuously for short or long time periods, or may be controlled in timing either with respect to detected portions of a patient's heartbeat signal or in response to a detected event such as fibrillation. In one preferred embodiment, the implantable system includes a defibrillation shock generator and control for responding to a defibrillation event by first delivering a sequence of mechanical waves and then delivering an electrical defibrillation shock. In another embodiment, the system and method treat incipient fibrillation or arrhythmia by delivering mechanical waves of predetermined timing to the patient's heart and/or lungs. In a specific embodiment, mechanical waves are delivered through an array of transducers to the patient's atrial wall, to treat atrial fibrillation.
Journal of Molecular and Cellular Cardiology, 1983
Journal of Molecular and Cellular Cardiology, 1981
Cardiovascular Research, 1990
The plateau of the action potential in heart muscle is largely due to the inward Ca2+ current, ic... more The plateau of the action potential in heart muscle is largely due to the inward Ca2+ current, ica; however, Ca2+ extrusion via Na+/Ca2+ exchange may also generate a significant current, ina/ca. The aim was to assess the influence of ina/ca on the action potential in isolated human heart muscle. Action potentials and force of isometric contractions were recorded in ventricular trabeculae. The muscle was subjected to various stimulus patterns, Ca2+ antagonists, and variations in the ionic composition of the extracellular medium. From 49 patients, aged 0.5 to 14 years, small right ventricular trabeculae were obtained during open heart surgery. The operations concerned corrections of ventricular septal defects. Data presented in this paper were from nine preparations in which action potentials were recorded during several hours. The results confirmed that: (1) the amplitude of the early part of the plateau was depressed by low [Ca2+] and by Ca2+ antagonists, showing that ica dominates this early part; and (2) that low [Na2+] and post-extrasystolic potentiation also depressed the early component of the plateau of the action potential, which can be explained by inactivation of ica due to increased levels of intracellular Ca2+. A novel observation was that post-extrasystolic potentiation led to an increase in action potential duration (APD). An explanation is that the potentiated contraction follows from an increased amount of intracellular Ca2+ which also activates an inward current, possibly ina/ca. This assumption is strengthened by the finding that lengthening of APD after extrasystoles was abolished: (a) at low [Ca2+], ie, when force was small and there was little Ca2+ to be extruded; and (b) at low [Na+], ie, when force was large but the driving force of the Na+ gradient for extrusion of Ca2+ was small. The early part of the plateau is dominated by ica, whereas ina/ca is relatively more important during the later part, and tends to lengthen the action potential.
Canadian Journal of Physiology and Pharmacology, 1987
In this paper, we present evidence in support of the hypothesis that electrogenic Na+–Ca2+ exchan... more In this paper, we present evidence in support of the hypothesis that electrogenic Na+–Ca2+ exchange is responsible for three phenomena in rat cardiac muscle: (i) the slow repolarization phase of the action potential, (ii) the time course of the mechanical recovery process, and (iii) the development of triggered arrhythmias. It was shown that the duration of the slow phase of repolarization of the action potential varies in proportion to the Na+ concentration gradient and inversely with the Ca2+ concentration gradient over the cell membrane. This suggested that Na+–Ca2+ exchange can generate a current of sufficient magnitude to maintain the membrane depolarized at a level of −60 mV. The mechanical restitution process of rat cardiac trabeculae was shown to exhibit three phase. The first phase, α, probably reflects rapid transport of calcium in the sarcoplasmic reticulum from the uptake sites to the release sites. After the initial increase of force during α, force rises further during...
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Papers by vincent schouten