Ventricular function. Is the total more than the sum of the parts?
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Actins↗
Biomedical subjects
S U Sys
Publications and source records attributed to S U Sys.
Physiologic aspects of relaxation of the myocardium.
To understand relaxation in the intact heart, an appreciation of myocardial relaxation in controlled isometric and isotonic twitches is a prerequisite. Load dependence of myocardial relaxation is manifest as the temporal separation of relaxation in isotonic and isometric twitches, i.e. rapid isotonic lengthening in contrast to slower isometric force decline. Although both isotonic and isometric relaxation modes are governed by the same determinants of crossbridge kinetics (life cycle of individual crossbridges along with regulatory properties of the contractile proteins, and calcium sequestration particularly by the sarcoplasmic reticulum), the contribution of these determinants in controlling onset and rate of relaxation is different in isometric force decline and in isotonic lengthening. In an isometric twitch, cooperative activity will, through a process of force development-induced increased sensitivity of the contractile proteins, upgrade the development and maintenance of force throughout contraction and relaxation. On the other hand, a functional calcium sequestration by the sarcoplasmic reticulum will, in the presence of a reduced effect of cooperative activity in the isotonic twitch, allow for load-induced rapid lengthening. Marked mechanical nonuniformity is observed in intact cardiac muscle. Nonuniformity in cardiac muscle mechanics is usually considered as a nuisance. Uniform behaviour of overall muscle does occur, however, despite or perhaps through nonuniform behaviour of longitudinal muscle segments. A limited but variable degree of nonuniformity therefore probably constitutes an essential property of the heart. A quantitative analysis of nonuniformity in isolated cat papillary muscle is proposed. Pathological considerations require extrapolation of our understanding from isolated muscle relaxation to ventricular relaxation.(ABSTRACT TRUNCATED AT 250 WORDS)
Calcium↗
Is stiffness increased during ischemia?
Possible sources of increased ventricular stiffness can be more easily appreciated when pressure and volume patterns are considered as a function of time. A discussion on sources of effective or apparent stiffness or stiffness changes includes viscoelastic properties and active behavior at the muscular level. Chamber geometry and coronary vascular pressure and flow are intrinsic ventricular components. Together with the pressure head and crosstalk as extraventricular components, all these properties are integrated to determine intact heart behavior in late relaxation and diastole.
Animals↗
Influence of loading patterns on peak length-tension relation and on relaxation in cardiac muscle.
To analyze the influence of loading patterns on cardiac pump performance and cardiac relaxation [corrected], the effects of preload on peak length-tension relation [corrected] and of systolic load clamps on peak length-tension relation and on relaxation were analyzed in isolated cat papillary muscles. Preload reduction and early loading clamps induced a shift to the left of the peak length-tension relation, that is, a smaller muscle length for the same tension at peak shortening. Unloading clamps induced a shift to the right of the peak length-tension relation, that is, a larger muscle length for the same tension at peak shortening. The effects of load clamps on relaxation depended on when they were applied during isotonic shortening. Changes induced by load clamps could not be summarized in terms of enhanced or delayed relaxation, illustrating that shortening duration, isometric tension decline and isotonic lengthening have different determinants. In conclusion, not only peak or mean systolic pressure but also the entire loading pattern has to be taken into account whenever pressure-volume data or relaxation variables are interpreted.
Animals↗
Determinants of force decline during relaxation in isolated cardiac muscle.
Determinants of the time course of isometric force decline are less well known than those of peak rate of force decline. We studied the influence of loading history, nonuniformity, extracellular calcium, and muscle length on force decline in isolated right ventricular cat papillary muscle. Changes in contraction load affected the time of onset but not time course of force decline at any given length and contractile state. Despite delayed time of onset of force decline (up to 80% of time to peak twitch), rate of force decline was identical at equal force levels. No direct influence of nonuniform behavior of longitudinal segments on the pattern of muscle force decline was observed. The rate of terminal force decline (toward the end of relaxation) was not influenced by extracellular calcium but significantly increased at short muscle lengths: its time constant (means +/- SE) averaged 85 +/- 12 ms at optimal length and decreased by 20 +/- 6 ms per 10% reduction in length. Force control of rate of force decline and its modulation by length can be understood by considering the influence of force and length on sensitivity of contractile proteins to calcium.
Animals↗
Relaxation and diastole of the heart.
In the present review, we adopted the viewpoint of the physiologist looking at the global function of the heart, during relaxation and diastole, as an integrated muscle-pump system. We first focused our attention on properties of relaxation and diastole at the subcellular (SR, contractile proteins), cellular, and multicellular scales of cardiac muscle and then at the scale of the ventricle and intact global heart. At each lower scale we derived properties from experimental facts and examined the extent to which these properties could be extrapolated conceptually to the higher scale. From this muscle-pump approach, we learned that a general and fundamental property of relaxation of the heart as a muscle-pump system is load dependence, i.e., the mutually independent behavior of the time patterns of slow force decline and pressure fall and of rapid lengthening and rapid filling. Load dependence is found at all hierarchic scales, irrespective of whether it is examined under strictly isotonic-isometric or isometric-isotonic or auxotonic loading conditions and despite often substantial nonuniformity. Relaxation is governed by the interaction of the loading conditions and the two major determinants of the inactivation process, i.e., Ca2+ reuptake by the SR and the properties of the contractile proteins. Load dependence is the mere mechanical expression of the unequal contribution, during the two phases of relaxation, of these three interacting determinants of relaxation (load, SR, and contractile proteins). During force decline in isolated muscle and pressure fall in the ventricle, the properties of the contractile proteins predominate over load and SR; during muscle lengthening and rapid ventricular filling, load and SR become more important. As the relative importance of the phenomena above is different during pressure fall in comparison to rapid filling, it is not surprising that directional changes in pressure fall may not predict those in filling. We also saw that the overall time pattern of pressure fall in contrast to rapid filling may sometimes be markedly altered, e.g., with simultaneous increases in peak-dP/dt, indicating more rapid early pressure relaxation, and prolonged time constant tau, indicating slower late pressure relaxation, or vice versa. From this muscle-pump approach, it should also be remembered that optimal efficiency of the heart limits the extent to which nonuniformity may exist. At all hierarchic scales, variations in the degree of nonuniformity, however small, constitute an important physiological modulator of performance throughout systole and diastole.(ABSTRACT TRUNCATED AT 400 WORDS)
Diastole↗
Effects of ryanodine on relaxation in isolated myocardium from different animal species.
Relaxation in mammalian ventricular cardiac muscle is sensitive to the prevailing load. This "load dependence of relaxation" (LD) can be demonstrated only when an efficient sarcoplasmic reticulum (SR) is present. To define further the role of the SR in LD, we studied contraction and relaxation in cat, rat and frog cardiac muscle after exposure to ryanodine. Ryanodine is a selective inhibitor of calcium release from the SR. This view was confirmed in the present study in single cardiac rat myocytes with functioning SR. Ryanodine did not affect LD in multicellular mammalian myocardium even though it had already significantly depressed contractility, suggesting that calcium release from the SR plays no role in establishing LD. Calcium accumulation in the SR as a consequence of the inhibited release can account for the late depression of LD in the presence of ryanodine.
Alkaloids↗
Postextrasystolic potentiation worsens fast filling of the hypertrophied left ventricle in aortic stenosis and hypertrophic cardiomyopathy.
Impaired left ventricular (LV) filling in aortic stenosis (AS) and in hypertrophic cardiomyopathy (HCM) is caused by slow LV pressure decay, which could be explained by depressed inactivation of hypertrophied myocardium. Postextrasystolic potentiation (PESP), which increases activator calcium, could lead to further deterioration of LV relaxation. The influence of PESP on LV filling dynamics was, therefore, investigated in normal controls and in patients with LV hypertrophy caused by AS or by HCM. LV hemodynamics and LV hemodynamic relaxation indexes were determined during normal sinus rhythm (NSR) and after PESP. LV pressures were recorded by micromanometer tip catheters (controls, n = 10; AS, n = 17; HCM, n = 11). Simultaneous mitral flow Doppler echocardiograms were obtained in patients with LV hypertrophy (AS, n = 8, HCM, n = 5). Despite significant increases of LV dP/dtmax after PESP in all three study groups, PESP affected LV hemodynamic relaxation indexes differently. The time constant of LV pressure decay (TPB) derived from exponential curve fits with nonzero asymptote pressure remained unaltered after PESP in normal controls, rose from 62 +/- 17 to 74 +/- 21 msec (p less than 0.02) in patients with AS, and rose from 74 +/- 18 to 84 +/- 19 msec (p less than 0.02) in patients with HCM. Early diastolic LV pressure decay was measured by phi (phase of the first harmonic of a Fourier transform applied to the diastolic LV pressure waves) and by t (time interval from LV dP/dtmin to LV minimum diastolic pressure). After PESP, phi remained unaltered in normal controls but decreased in AS from 42.8 +/- 19.1 degrees to 24.0 +/- 28.8 degrees (p less than 0.001) and in HCM from 39.7 +/- 15.4 degrees to 26.9 +/- 15.7 degrees (p less than 0.001). Similarly, t was unchanged after PESP in normal controls but prolonged in AS from 146 +/- 48 to 205 +/- 86 msec (p less than 0.001) and in HCM from 168 +/- 40 to 208 +/- 53 msec (p less than 0.02).(ABSTRACT TRUNCATED AT 400 WORDS)
Adult↗
Effects of damaging the endocardial surface on the mechanical performance of isolated cardiac muscle.
The mechanical properties of mammalian ventricular cardiac muscle have been studied in the presence and in the absence of an intact endocardial surface. Isotonic and isometric twitch contractions were obtained from papillary muscles of the right ventricle of cat at 29 degrees and 37 degrees C, at different extracellular calcium concentrations ([Ca2+]o), and at different initial muscle lengths. The endocardial surface was damaged by gentle abrasion of the muscle surface with a plastic blade or by brief immersion for 1 second with 1% Triton X-100. Although there was no evidence of damage to myocardial cells, damaging the endocardial surface resulted in an immediate and irreversible abbreviation of the twitch contractions with, except at the highest ([Ca2+]o, a decrease in peak isometric twitch tension. These changes induced 1) an asymmetrical shift of the tension-[Ca2+]o relation towards increasing [Ca2+]o but with no effect at the highest [Ca2+]o, and 2) a rightward and downward shift of the length-tension relation. Both shifts were significantly more pronounced at 37 degrees C than at 29 degrees C; they were not accompanied by significant changes in Vmax. The asymmetrical shift of the tension-[Ca2+]o relation suggests that the endocardium-mediated chain of events may be mediated by changes in the sensitivity of the contractile proteins to Ca2+. This hypothesis is also supported by the similar pattern of changes (i.e., modulation of the onset of early tension decline) induced by decreasing length at each [Ca2+]o and by the removal of a functional endocardium. Accordingly, the endocardium may help to control the performance of the heart by modulating peak contractile performance and relaxation of the underlying myocardium.
Adenosine Triphosphate↗
Atriopeptin III induces early relaxation of isolated mammalian papillary muscle.
Atrial natriuretic peptide, released by mammalian atria in response to volume overload, induces vasodilation and natriuresis. In this study, a direct effect on cardiac mechanical performance was demonstrated. Atriopeptin III (10(-9)-10(-7) M) induced early relaxation and decreased peak twitch of isometric and isotonic twitches of isolated papillary muscles of cat and rat, without affecting maximal unloaded velocity of shortening. This effect resembled the effects of dibutyryl cyclic GMP and of sodium nitroprusside on cardiac muscle. The action of atriopeptin III, but not of dibutyryl cyclic GMP or sodium nitroprusside, was abolished by mechanically or chemically damaging the endocardial endothelial surface. Thus, the early relaxation of cardiac muscle induced by atrial natriuretic peptide may be mediated through receptors on the endocardial endothelium.
Animals↗
Endocardial control of myocardial performance.
Impairment of the endocardial surface has a profound influence on the mechanical performance of the underlying undamaged myocardium. It immediately and irreversibly shortens the duration of twitch tension development, particularly at a physiological extracellular [Ca++] and temperature, thereby affecting the relationship of peak isometric twitch tension development to both [Ca++]0 and length. Accordingly, the endocardium as the most primitive structure of the heart, may help to control the performance of the underlying myocardium by modulating the onset of early tension decline. These effects will result in important variations of peak contractile performance and of relaxation of the underlying myocardium.
Animals↗
Positive inotropic and vasodilating effects of amrinone and milrinone in isolated canine heart.
The question has been raised whether the in vivo positive inotropic effect of amrinone and milrinone is a primary effect or secondary to vasodilation. The effects of each drug on isolated trabeculae and resistance vessels obtained from the same dog hearts were determined separately. The positive inotropic and vasodilatory effects coincided over the same concentration range for amrinone. The active isometric force of trabeculae and resistance vessels was increased, and respectively decreased by 20% at comparable concentrations of amrinone--20% ED (effective dose) ranging between 9.5 and 18 microM. By contrast, the vasodilatory properties of milrinone (20% ED, 15-34 microM) appeared only at concentrations at which milrinone had already evoked a maximal positive inotropic response in trabecular muscle (20% ED, 0.36-0.38 microM). Based on the present experiments and their limitations, it would thus appear that, in the intact heart and at therapeutic doses, positive inotropic and vasodilatory effects may be equally present for amrinone, whereas, for milrinone, the positive inotropic effect would largely predominate the vasodilatory effect.
Amrinone↗
Post-reextension force decay of relaxing cardiac muscle.
Residual active cardiac muscle force during ventricular filling causes deviations of the pressure-volume and pressure-segment length relations from passive left ventricular compliance curves. A possible interaction at the myocardial level between muscle reextension and subsequent active force decay has not yet been investigated. We therefore studied the relation between isolated cat papillary muscle reextension, load during reextension, and isometric force decay after isotonic reextension. Both timing and extent of the isotonic muscle reextension phase were altered while load during reextension was lowered, subsequent residual isometric force was decreased. The extent of reextension or the final muscle length did not alter residual active isometric force after isotonic reextension at an identical load. Moreover, irrespective of the loading history of the shortening phase of the contraction, equal loads during reextension resulted in superimposable subsequent isometric force decay traces. From these results it therefore appears that residual isometric force after isotonic reextension is determined by the load during reextension. Extrapolation of these results to the filling ventricle implies the existence of a dynamic interaction between instantaneous extent of filling, wall stress, and residual force development.
Animals↗
Comments on "Role of glycolytic products in damage to ischemic myocardium".
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Animals↗
Inotropic effects of amrinone and milrinone on contraction and relaxation of isolated cardiac muscle.
The inotropic response to amrinone and milrinone in isolated cat papillary muscle is characterized by a dose-dependent increase in contractility, with milrinone about five times as potent as amrinone, no effect on load dependence of relaxation, no change in timing and duration of the contraction-relaxation cycle, and marked temperature dependence. This response necessitates, at least in part, the presence of a well-functioning sarcoplasmic reticulum (SR). Amrinone and milrinone are less active when the SR is poorly developed, as in frog myocardium, mammalian atrial myocardium, Purkinje fibers, and ventricular muscle from fetal and newborn animals; when the SR has been destroyed, as in single mammalian cardiac cells; and when the SR, for reasons still under investigation, has become inactive, as in isolated human ventricular myocardium. Amrinone and milrinone are also less active or may depress contractility under conditions in which the SR is known to function near maximal calcium saturation (as in rat ventricular myocardium) or to be overloaded with calcium (as during reoxygenation). This depressant action suggests concomitant desensitization of the contractile proteins to calcium.
3',5'-Cyclic-AMP Phosphodiesterases↗
Effects of AQA39 on contractile performance of isolated mammalian ventricular myocardium.
AQA39 is a new cardioactive agent with, at low dosages, a minute positive inotropic action on ventricular myocardial tissue probably mediated through the calcium sequestering membraneous systems. At higher concentrations AQA39 depressed myocardial performance probably due to inhibition of the slow calcium channels.
Animals↗
Mechanisms of hypoxia-induced decrease of load dependence of relaxation in cat papillary muscle.
Relaxation of mammalian cardiac muscle is very sensitive to the prevailing load, but becomes largely load-independent during hypoxia. This effect was previously ascribed to a delayed removal of activating myoplasmic calcium. To further elucidate the underlying mechanisms of this effect of hypoxia, relaxation was now studied in 26 cat papillary muscles, in which hypoxia-induced decrease of load dependence of relaxation was compared with the effects of low [Ca2+]o (1.0, 0.5, 0.375 mM), verapamil (1 microM) and nifedipine (0.1 microM). Load dependence of relaxation was quantified by comparing force and time coordinates at the onset of the isometric relaxation phase in several after-loaded isotonic twitch contractions with the relaxation of the isometric control contraction. Hypoxia, low [Ca2+]o, verapamil and nifedipine decreased load dependence of relaxation. Although low [Ca2+]o, verapamil and nifedipine had a more marked negative inotropic effect on the contraction phase than hypoxia, the decrease of load dependence with hypoxia was significantly more pronounced and it included two phases: an early and fast drop, followed by a slower and longer-lasting decrease. The early fast phase was neutralized in low [Ca2+]o and also diminished after administration of verapamil or nifedipine. An impaired calcium reuptake by the sarcoplasmic reticulum would underly only the second phase of decreased load dependence. The first phase on the other hand originated mainly from changes in the isometric relaxation of the papillary muscles.
Animals↗
Triple control of relaxation: implications in cardiac disease.
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Animals↗