Trabeculated embryonic myocardium shows rapid stress relaxation and non-quasi-linear viscoelastic behavior

Passive viscoelastic behavior is important in embryonic cardiovascular function, influencing the rate and magnitude of contraction and relaxation. We hypothesized that if viscoelastic behavior is influenced by interstitial fluid flow, then the stage-21 (312d) and stage-24 (4d) chick myocardium with large intertrabecular spaces will exhibit much different viscoelastic behavior than stage-16 (212d) and stage-18 (3d) compact myocardium and a non-quasi-linear response. Excised left ventricular sections were tested with ramp-and-hold stress relaxation tests at axial stretch ratios of 1.05:1.1:1.2:1.3. The measured stress relaxation was much more rapid than previously observed in the compact, non-trabeculated myocardium. The reduced relaxation curves depended significantly on the stretch level. A continuous-spectrum quasi-linear relaxation function described their shape well but the model-fit parameters also depended on the stretch level. Sinusoidal stretching of ventricular sections at rates from 0.2 to 25Hz showed that the steepening of stress-strain curves with increasing strain rate was half as much as predicted by a quasi-linear model. Hysteresis ranged from 25-35%, varied little with loading rate from 0.2 to 8Hz, and was twice that predicted from a quasi-linear model. Doubling the viscosity of the perfusate in stress-relaxation tests produced increased stiffness and decreased relaxation rate. These results demonstrate that the passive viscoelastic behavior of the trabeculated embryonic myocardium is markedly different from that of younger, compact myocardium and is not quasi-linear.     

Restriction of stress-induced activation of lipid peroxidation by small doses of thyroid hormones]

The experiments on 57 female rats demonstrated that small doses of thyroid hormones (thyroidin) significantly (55-118%) restrict stress induced increase in the concentration of initial and terminal products of lipid peroxidation (LP) in the myocardium and in the blood plasma. After hormone injection stress decreases the activity of key antioxidant enzyme, superoxide dismutase of erythrocytes (SOD), to a lesser degree and increases the rate of malonyldialdehyde (MDA) production induced by Fe2+ in homogenates of the myocardium to the same degree as well in comparison with rats that had not been injected thyroidin. In normal rates thyroidin does not influence the concentration of products of LP, increases the activity of SOD and decreases increment of MDA induced by Fe2+ in homogenates of the myocardium. Thus, small doses of thyroid hormones restrict significantly stress induced activity of LP membranes, increasing the power of antioxidant systems both in the myocardium and in the organism.     

Alterations in the cardiovascular system that occur in advanced age.

Recent information appears to solidify the concept that the left ventricle hypertrophies with age in normal adult man. The stimulus for this moderate increase in wall thickness has not been precisely determined but an attractive hypothesis suggests that the stimulus may be an increased load imposed by the peripheral vascular resistance. The mechanism for the well-documented diminished cardiovascular response to maximal exercise in normal aged man still remains unclear. Evidence in the canine model indicates that a diminished chronotropic response to catecholamines could in part explain a limitation in maximal heart rate response. The reflex change in heart rate in respone to hypercapnia, hypoxia, and sustained isometric handgrip in normal man is diminished with age. The precise mechanism of this age-associated phenomenon remains to be elucidated, but the chronotropic responsiveness to catecholamines is likely a contributing factor. Finally, there is evidence of slowed myocardial relaxation in hearts of aged animals and man. A decrement in the speed at which the sarcoplasmic reticulum from hearts of aged rats accumulates calcium has been demonstrated and appears to be involved in the mechanism of prolonged contraction in aged myocardium.     

Damage induced arrhythmias: mechanisms and implications

Little is known about the role played by non-uniform myocardial stress and strain distributions and by non-uniform excitation contraction coupling in mechanisms underlying the premature beats that initiate an arrhythmia. We will review the evidence in support of a mechanism in which both non-uniform contraction and increased Ca2+ load of cells adjacent to acutely damaged cells are essential in the "spontaneous" generation of Ca2+ transients during the relaxation phase of the electrically driven twitch. The putative mechanism of initiation of the propagating Ca2+ waves involves feedback of rapid length (or force) changes to dissociation of Ca2+ from the contractile filaments. A novel aspect of this concept is that these mechanically elicited Ca2+ transients induce propagating Ca2+ waves that travel into the adjacent normal myocardium and cause after-depolarizations, which, in turn, may cause premature action potentials. These premature action potentials will further load the cells with Ca2+, which promotes the subsequent generation of propagating Ca2+ transients and leads to triggered arrhythmias. The damage-induced premature beats may also initiate re-entry arrhythmias in non-uniform myocardium. These observations strongly support the concept that abnormal cellular Ca2+ transport plays a crucial role in the initiation of arrhythmias in damaged and non-uniform myocardium.     

Prevention of stress-induced changes in coronary autoregulation of vasodilative reserve of the coronary vessels and contractile function of the isolated heart with small doses of thyroid hormones

The possibility to restrict stress disturbances of coronary blood flow and contractile myocardium function with small doses of thyroid hormones has been studied on 46 hearts of female rats isolated by the Langendorff method. It is found that small doses of thyroidin increase the force of systoles and adequately increase relative coronary blood flow, coronary reserve vasodilatation, significantly prevent stress disturbances of coronary autoregulation, the force and rate of the myocardium contraction and relaxation, that restricts disproportion between contractive function and coronary blood flow.     

The effect of He-Ne laser radiation on myocardium mechanical activity in rats

In isolated papillary muscles, a 5-minute irradiation with the He-Ne-laser Shuttle-1 enhances the maximal strength of isometric contraction and acceleration of relaxation. In physiological mode of mechanical loads, the irradiation with the laser red light enhances the myocardium contractability at all final systolic lengths with simultaneous enhancement of the isometric relaxation velocity at great systolic lengths and a deceleration of the relaxation at lesser lengths. Under the He-Ne-laser effect, restoration of rhythm-inotropic relationships occurred in the myocardium.     

Mechanics of left ventricular relaxation, early diastolic lengthening, and suction investigated in a mathematical model

We investigated the determinants of ventricular early diastolic lengthening and mechanics of suction using a mathematical model of the left ventricle (LV). The model was based on a force balance between the force represented by LV pressure (LVP) and active and passive myocardial forces. The predicted lengthening velocity (e') from the model agreed well with measurements from 10 dogs during 5 different interventions (R = 0.69, P < 0.001). The model showed that e' was increased when relaxation rate and systolic shortening increased, when passive stiffness was decreased, and when the rate of fall of LVP during early filling was decreased relative to the rate of fall of active stress. We first defined suction as the work the myocardium performed to pull blood into the ventricle. This occurred when contractile active forces decayed below and became weaker than restoring forces, producing a negative LVP. An alternative definition of suction is filling during falling pressure, commonly believed to be caused by release of restoring forces. However, the model showed that this phenomenon also occurred when there had been no systolic compression below unstressed length and therefore in the absence of restoring forces. In conclusion, relaxation rate, LVP, systolic shortening, and passive stiffness were all independent determinants of e'. The model generated a suction effect seen as lengthening occurring during falling pressure. However, this was not equivalent with the myocardium performing pulling work on the blood, which was performed only when restoring forces were higher than remaining active fiber force, corresponding to a negative transmural pressure.     

Phosphorylation of phospholamban and troponin I in beta-adrenergic-induced acceleration of cardiac relaxation

Activation of cAMP-dependent protein kinase A (PKA) in ventricular myocytes by isoproterenol (Iso) causes phosphorylation of both phospholamban (PLB) and troponin I (TnI) and accelerates relaxation by up to twofold. Because PLB phosphorylation increases sarcoplasmic reticulum (SR) Ca pumping and TnI phosphorylation increases the rate of Ca dissociation from the myofilaments, both factors could contribute to the acceleration of relaxation seen with PKA activation. To compare quantitatively the role of TnI versus PLB phosphorylation, we measured relaxation rates before and after maximal Iso treatment for twitches of matched amplitudes in ventricular myocytes and muscle from wild-type (WT) mice and from mice in which the PLB gene was knocked out (PLB-KO). Because Iso increases contractions, even in the PLB-KO mouse, extracellular [Ca] or sarcomere length was adjusted to obtain matching twitch amplitudes (in the presence and absence of Iso). In PLB-KO myocytes and muscles (which were allowed to shorten), Iso did not alter the time constant (tau) of relaxation ( approximately 29 ms). However, with increasing isometric force development in the PLB-KO muscles, Iso progressively but modestly accelerated relaxation (by 17%). These results contrast with WT myocytes and muscles where Iso greatly reduced tau of cell relaxation and intracellular Ca concentration decline (by 30-50%), independent of mechanical load. The Iso treatment used produced comparable increases in phosphorylation of TnI and PLB in WT. We conclude that the effect of beta-adrenergic activation on relaxation is mediated entirely by PLB phosphorylation in the absence of external load. However, TnI phosphorylation could contribute up to 14-18% of this lusitropic effect in the WT mouse during maximal isometric contractions.     

Relaxation of the myocardium of the perfused and ischaemic rabbit heart

The decrease in the rate of relaxation of the myocardium during ischaemic impairment of metabolic processes is accompanied by a decrease in the size of contraction. If we stimulate the ischaemic heart with irregularly distributed pulses we can achieve, by an extrasystolic potentiation mechanism, isolated contractions. If we stimulate the ischaemic heart with irregularly distributed pulses we can achieve, by an extrasystolic potentiation mechanism, isolated contractions of the same size as average contractions in normal perfusion. When comparing the relaxation of such contractions in 15 perfused rabbit hearts, we found a linear correlation between the relaxation rate and the size of the contractions. If we relate to relaxation rate to contraction size, the relaxation rate in early ischaemia (1 min after stopping perfusion) is thus in most cases normal, despite the marked decrease in the size of the contractions. The size of the contractions of the ischaemic mammalian myocardium thus seems to diminish before relaxation (which is likewise energy-dependent) is affected.     

Effect of calmodulin inhibitors on rat and guinea pig myocardial contractility

The effects of phenothiazine drugs with different affinities for calmodulin (trifluoperazine, frenolone, majeptile and aminazine) on the contractility of rat and guinea pig papillary muscles were studied. The phenothiazine-induced changes in the contraction-relaxation parameters were shown to correlate with the degree of calmodulin inhibition. These parameters are relaxation-onset index, relaxation index and terminal relaxation index in rats, and relaxation index and maximal developed tension in guinea pigs. An essential role of calmodulin in myocardium relaxation in both animal species is postulated.     

Energy and plastic metabolism of the heart muscle in rabbits undergoing thyroid irradiation with decimeter waves

The functional state of myocardial mitochondria, the glycogen and nucleic acid contents in myocardium, and morphometry of structural elements of cardiomyocytes and myocardial capillary network were investigated in order to select the optimal regimen of decimeter wave exposures with power density of 10, 120 and 240 mW/cm2 on the area of thyroid gland. It was shown that the thyroid gland exposure to decimeter waves at these intensities resulted in functional shifts in energy and plastic processes in myocardium and capillary blood supply. These changes increased to a considerable extent as the intensity of exposure was increasing and reached the maximum at power density of 240 mW/cm2 but event at this intensity there was not found the injurious effect of decimeter waves on the myocardium.     

Frequency-dependent contractile response of isolated cardiac trabeculae under hypo-, normo-, and hyperthermic conditions.

The body is from time to time exposed to nonnormothermic conditions; both hypo- and hyperthermia can occur as a result of external (environment) or internal (pathogens, allergens) stressors. To preserve life under hypo- and hyperthermic conditions, adequate perfusion of vital organs is mandated. Although cardiac output regulation under hyperthermic conditions has been studied, the mechanical response of basic contractile function of the myocardium itself is incompletely understood. Accordingly, we set out to test mechanical output of isolated myocardium under hyperthermic conditions and to compare the results with the hypo- and normothermic response in the same tissue. We observed that, in absence of a frequency change, developed force decreased markedly. At a physiological normal stimulation rate of 6 Hz, developed force decreases to 67.2 +/- 2.6% at 42 degrees C compared with 37 degrees C. In addition, twitch timing characteristics also accelerate, allowing for a faster relaxation; time from peak tension to 50% relaxation is approximately 23% faster (from 31.4 +/- 2.6 to 24.4 +/- 1.7 ms). Although this faster relaxation in turn prevents a steep increase in diastolic tension at high frequencies, the very fast calcium kinetics now prevent a more complete activation of the myofilaments, resulting in a lower twitch-force maximum at hyperthermic conditions. Even at maximal beta-adrenergic stimulation, developed force is well below levels reached at physiological temperature.     

Contraction–relaxation coupling is unaltered by exercise training and infarction in isolated canine myocardium

The two main phases of the mammalian cardiac cycle are contraction and relaxation; however, whether there is a connection between them in humans is not well understood. Routine exercise has been shown to improve cardiac function, morphology, and molecular signatures. Likewise, the acute and chronic changes that occur in the heart in response to injury, disease, and stress are well characterized, albeit not fully understood. In this study, we investigated how exercise and myocardial injury affect contraction–relaxation coupling. We retrospectively analyzed the correlation between the maximal speed of contraction and the maximal speed of relaxation of canine myocardium after receiving surgically induced myocardial infarction, followed by either sedentary recovery or exercise training for 10–12 wk. We used isolated right ventricular trabeculae, which were electrically paced at different lengths, frequencies, and with increasing β-adrenoceptor stimulation. In all conditions, contraction and relaxation were linearly correlated, irrespective of injury or training history. Based on these results and the available literature, we posit that contraction–relaxation coupling is a fundamental myocardial property that resides in the structural arrangement of proteins at the level of the sarcomere and that this may be regulated by the actions of cardiac myosin binding protein C (cMyBP-C) on actin and myosin.     

Comparison of contractile function of diaphragm and cardiac muscle in response to paired electrical stimulation

Paired pacing has been shown to potentiate contractile function of cardiac muscle, and it has been suggested that this may enhance contractile function of diaphragmatic muscle. The primary goal of this study was to study the effect of paired pacing on potentiation of contractile function of diaphragmatic muscle compared to atrial and ventricular myocardium. Diaphragmatic muscle was isolated from mouse and rat, and atrial and ventricular myocardium from dogs. Potentiation was induced by isolated extrastimuli (equal in duration and intensity to the pacing stimulus) and by repetitive extrastimuli (i.e. paired pacing) at a paced rate of 12, 30 and 60 beats/min. Baseline studies were performed while preparations were isometrically contracting at L(max) in oxygenated Krebs-Henseleit solution at 28 degrees C. Maximal force generation in response to a premature stimulus was determined at each rate by scanning the coupling interval between paced beats. Under baseline conditions, diaphragmatic muscle contracted faster than atrial and ventricular muscle. In all tissues, maximum potentiation (increase in force above baseline) was approximately 100% of baseline force, and peak potentiation occurred at shorter coupling intervals with increasing rates of stimulation. Single and paired pacing of diaphragm potentiated the contraction during which the extrastimuli were introduced, while in cardiac muscle, extrastimuli potentiated the contraction following the extrastimulus. The maximum potentiated response occurred when the extrastimulus was introduced prior to the development of peak force in diaphragmatic muscle. In contrast, in atrial and ventricular muscle, a single or paired premature stimulus potentiated the subsequent beat when delivered late during relaxation. In cardiac muscle, maximal potentiation gradually occurred following several repetitive stimuli. Following cessation of single and paired pacing, the beat following the potentiated response immediately returned to baseline in diaphragmatic muscle, while a gradual decline was evident over several subsequent beats in cardiac muscle. Increasing the bath temperature from 28 to 37 degrees C resulted in a leftward shift in the peak potentiated force vs. coupling interval curve without a decline in the magnitude of potentiated force in diaphragmatic muscle. In diaphragm muscle, exposure to ryanodine markedly decreased baseline force and maximal potentiation. We conclude that closely timed extrastimuli applied to diaphragmatic muscle can potentiate developed force in a given contraction, while in cardiac tissue a delayed stimulus potentiates the subsequent beat. These differences in contractile responsiveness are not due to differences in loading conditions, but appear to reflect intrinsic differences in calcium handling.     

Prospect of Stress Testing

A new method for analyzing the data of stress electrocardiography, based on physiologically justified approximations of trends in the heart rate (HR) and ST, is discussed. The method makes it possible to determine how the HR and ST of an individual vary with time during graded exercise and how these parameters and the times of their regulation depend on the workload; to reveal general patterns of their behavior; and to derive new physiological characteristics. Analysis of the general patterns of only the load time dependences of HR and ST and of the workload dependence of HR in patients with ischemic heart disease allows us to detect brief episodes of myocardial ischemia; to assess the anaerobic thresholds of locally injured areas of the myocardium and of the whole body; and to propose unified parameters for assessing the coronary reserve, the physical working capacity, and the severity of ischemic injury to the myocardium. The proposed method of analysis of stress electrocardiographic data and the combined use of stress electrocardiography, positron emission tomography, myocardial scintigraphy, and stress echocardiography offer new opportunities for a better understanding of myocardial ischemia.     

Effect of prolonged running on physiological responses to subsequent exercise

The purpose of this study was to compare metabolic and cardiopulmonary responses for submaximal and maximal exercise performed several days preceding (pre-test) and 45 min after (post-test) 21 miles of high intensity (70% VO2 max) treadmill running. Seven aerobically trained subjects' oxygen uptake, oxygen pulse, respiratory exchange ratio, heart rate, pulmonary ventilation, ventilatory equivalent of oxygen, and blood lactate concentration were determined for exercise during the pre- and post-test sessions. No differences were found for submaximal oxygen uptake, oxygen pulse, pulmonary ventilation and ventilatory equivalent of oxygen between the pre- and post-test values. Generally, submaximal heart rate responses were higher, and respiratory exchange ratio values were lower during the post-test. Reductions of maximal work time (12%), maximal oxygen uptake (6%) and maximal blood lactate concentration (47%) were found during the post-test. Thermal stress and glycogen depletion are possible mechanisms which may be responsible for these observed differences.     

Temperature,contractility and high energy phosphates in anoxic fish heart muscle

Summary Isolated, electrically paced ventricular tissue of rainbow trout, Oncorhynchus mykiss, was examined at 20 and 10°C for the effects of different metabolic inhibitions on isometric force development and cellular content of phosphocreatine, creatine, ATP, ADP and AMP. At 20 relative to 10°C, twitch force was the same, but both twitch development and relaxation occurred over a shorter time and at a considerably higher maximal rate. Inhibition of cellular respiration caused twitch force and phosphocreatine to decrease, both about twice as fast at 20 as at 10°C. This doubling of energy degradation, i.e. in decrease of phosphocreatine, ATP, and loss of twitch force also occurred in preparations in which the energy liberation was totally blocked by iodoacetate in combination with N₂ and cyanide; both anaerobic energy degradation and anaerobic energy liberation expressed as lactate production were doubled. The similar effect of temperature on degradation and liberation of energy might explain why loss of twitch force during a 1-h period of anoxia was the same at both temperatures. The latter result was also found in the myocardium of eel Anguilla anguilla. In spite of its large influence on the time-course of twitch force development, the difference in temperature had no evident effects on the relationship between twitch force and phosphocreatine.Abbreviation Cr_t total creatine (creatine and phosphocreatine) - EDTA ethylenediminetetra-acetate - IAA iodoacetate - PCr phosphocreatine - TPT time-to-peak force - TR ₇₅ time for relaxation - V _F maximal rate of force development - V _R maximal rate of relaxation     

Prevention of disorders of cardiomyocyte ultrastructure in experimental myocardial infarction in immobilization-induced stress by administration of thyroid hormones

In the experiment, carried out on 48 non-inbred male rats ultrastructural changes in cardiomyocytes in non-ischemized parts of the heart at experimental infarction of myocardium under conditions of immobilization stress have been studied, as well as possibility to correct these changes by means of thyroid hormones. The stress intensifies dystrophic processes, developed outside the infarction zone, increases the mass of the necrotized tissue, essentially decreases the areas occupied by mitochondria and myofibrils, as well as their ratio in the section area. Small doses of thyroid hormones prevent the heart from the damaging effect of the stressor: decreasing area; occupied by mitochondria, myofibrils and their relation in the section, as well as they stimulate intracellular regenerative processes (accumulation of polymorphous mitochondria with clearly manifested cristae, membranes of the endoplasmic reticulum) and decrease the myocardial necrotized zone). Thus, structural lesions, resulted from the effect of ischemic necrosis and stress, can be prevented by small doses of thyroid hormones+.     

Streaming potentials maps are spatially resolved indicators of amplitude, frequency and ionic strength dependant responses of articular cartilage to load.

Streaming potential distributions were measured on the surface of articular cartilage in uniaxial unconfined compression using a linear array of microelectrodes. Potential profiles were obtained for sinusoidal and ramp/stress-relaxation displacements and exhibited dependencies on radial position, sinusoidal amplitude and frequency, time during stress relaxation, and on ionic strength. The measurements agreed with trends predicted by biphasic and related models. In particular, the absolute potential amplitude was maximal at the disk center, as was the predicted fluid pressure and the potential gradient (the electric field) was seen to be maximal at the disk periphery, as was the predicted fluid velocity. We also observed a similarity between non-linear behavior of streaming potential amplitude and load amplitude with respect to sinusoidal displacement amplitude. Taken together, these results support many of the phenomena concerning relative fluid-solid movement and fluid pressurization predicted by biphasic and related models, and they indicate the general utility of spatially resolved measurements of streaming potentials for the investigation of electromechanical phenomena in tissues. For example, these streaming potential maps could be used to non-destructively diagnose cartilage extracellular matrix composition and function, as well as to quantify spatially and temporally varying physical signals in cartilage that can induce cellular and extracellular biological responses to load.     

Effect of length and caffeine on isometric tetanus relaxation of frog sartorius muscles

In an isometric tetanus of frog sartorius muscle the total relaxation time increased linearly with change in length from 0.7 to 1.4 times rest length. Maximal rate of relaxation, measured from the time derivative (dp/dt) of tension decay, decreased with both decrease and increase from rest length in correlation with the generated tetanus tension. Stretching the muscle did not significantly affect the times to maximal rate, positive and negative inflexion points but greatly increased the time to total relaxation from the negative inflexion point. Caffeine at 2 mM, acting on muscles at rest length, also slowed the relaxation and decreased the maximal rate of tension decay. However, caffeine increased the times to maximal rate, positive and negative inflexion points without significantly affecting time to total relaxation from the negative inflexion point. These results suggest that caffeine slows an earlier step in relaxation, while stretch slows a later step. It is proposed that muscle relaxation is a two step process: an initial step that is regulated by the rate of Ca2+ uptake by sarcoplasmic reticulum, and a later step that is mostly controlled by the speed of dissociation of remaining cross-bridges.