The role of blood plasma porphyrins in the effects of He-Ne-laser on human leukocytes

The He-Ne-laser induced effects in human blood leukocytes in the presence of autologic plasma were investigated. Experiments were performed in two ways: (1) He-Ne-laser irradiation of cells in the presence of autologic plasma or (2) laser irradiation and subsequent addition of autologic plasma to the cell suspension. The concentration dependencies of plasma additions were evaluated. To obtain different concentrations of porphyrins in plasma samples, we either diluted the samples with PBS or selected patients with different porphyrin plasma content. The effects of He-Ne-laser irradiation were characterized by the maximum effect dose (Dmax) of irradiation and the degree of maximum cell activation (Amax, priming index). In the first series of experiments, we irradiated leukocytes in the presence of autologic plasma taken from patients with pneumonia and bronchial asthma. It was found that Dmax decreased with increasing porphyrin concentration in plasma. It was observed that, at low porphyrin concentrations, Amax increased severalfold with increasing photosensitizer concentration. At a porphyrin concentration of 0.46 pmol a decrease in Amax was detected as the porhyrin concentration increased. The same effects were revealed at high doses of laser irradiation. Very similar effects were found in experiments with the addition of irradiated plasma to cells. However, the Amax value was considerably less compared to that after irradiation in the presence of plasma (160% vs. 230 - 270% upon combined irradiation of cells and plasma). The Dmax value was higher in the series of experiments in which plasma was irradiated separately. The results suggest that laser-induced leukocyte activation can be mediated by blood plasma porphyrins and the products of lipid peroxidation formed as a result of porphyrin-photosensitized lipid oxidation.     

Contributions of stretch activation to length-dependent contraction in murine myocardium

The steep relationship between systolic force production and end diastolic volume (Frank-Starling relationship) in myocardium is a potentially important mechanism by which the work capacity of the heart varies on a beat-to-beat basis, but the molecular basis for the effects of myocardial fiber length on cardiac work are still not well understood. Recent studies have suggested that an intrinsic property of myocardium, stretch activation, contributes to force generation during systolic ejection in myocardium. To examine the role of stretch activation in length dependence of activation we recorded the force responses of murine skinned myocardium to sudden stretches of 1% of muscle length at both short (1.90 microm) and long (2.25 microm) sarcomere lengths (SL). Maximal Ca(2+)-activated force and Ca(2+) sensitivity of force were greater at longer SL, such that more force was produced at a given Ca(2+) concentration. Sudden stretch of myocardium during an otherwise isometric contraction resulted in a concomitant increase in force that quickly decayed to a minimum and was followed by a delayed development of force, i.e., stretch activation, to levels greater than prestretch force. At both maximal and submaximal activations, increased SL significantly reduced the initial rate of force decay following stretch; at submaximal activations (but not at maximal) the rate of delayed force development was accelerated. This combination of mechanical effects of increased SL would be expected to increase force generation during systolic ejection in vivo and prolong the period of ejection. These results suggest that sarcomere length dependence of stretch activation contributes to the steepness of the Frank-Starling relationship in living myocardium.     

Activation of transcription function in lymphocytes after irradiation with He-Ne-laser

The influence of He-Ne-laser irradiation (lambda = 632.8 nm) in dose 56 J/m2 on the ultrastructure of the nucleolus from human peripheral lymphocytes was studied electronmicroscopically. After 1 h irradiation a well-expressed reaction of the nucleolus was observed in 70% of the lymphocytes under examination. Changes consist in the appearance of a wrong-shaped fibrillar center or in its fragmentation, the increase of RNP-containing fibrillar and granular components, and also in expansion of vacuoli. In a number of irradiated lymphocytes nucleoli with several fibrillar centres and with a strand-like organization of RNP part were observed. The size of these nucleoli increases. Following the accepted functional interpretations the observed changes can be connected with the intensification of RNA metabolism including the synthesis, processing of pre-rRNA and preribosome transport from the nucleolus. Similar rearrangements of the nucleoli were revealed in parallel experiments with phytohemagglutinin-treated lymphocytes. They were observed 1 h after the stimulation of lymphocytes. Taking into account the absence of mitogenic action of He-Ne-laser irradiation on lymphocytes, the ultrastructural changes of nucleoli under the action of irradiation are considered as functional activation of rRNA synthesis in the Go-period.     

Active and passive components in the length-dependent stiffness of tracheal smooth muscle during isotonic shortening.

Contraction of smooth muscle tissue involves interactions between active and passive structures within the cells and in the extracellular matrix. This study focused on a defined mechanical behavior (shortening-dependent stiffness) of canine tracheal smooth muscle tissues to evaluate active and passive contributions to tissue behavior. Two approaches were used. In one, mechanical measurements were made over a range of temperatures to identify those functions whose temperature sensitivity (Q(10)) identified them as either active or passive. Isotonic shortening velocity and rate of isometric force development had high Q(10) values (2.54 and 2.13, respectively); isometric stiffness showed Q(10) values near unity. The shape of the curve relating stiffness to isotonic shortening lengths was unchanged by temperature. In the other approach, muscle contractility was reduced by applying a sudden shortening step during the rise of isometric tension. Control contractions began with the muscle at the stepped length so that properties were measured over comparable length ranges. Under isometric conditions, redeveloped isometric force was reduced, but the ratio between force and stiffness did not change. Under isotonic conditions beginning during force redevelopment at the stepped length, initial shortening velocity and the extent of shortening were reduced, whereas the rate of relaxation was increased. The shape of the curve relating stiffness to isotonic shortening lengths was unchanged, despite the step-induced changes in muscle contractility. Both sets of findings were analyzed in the context of a quasi-structural model describing the shortening-dependent stiffness of lightly loaded tracheal muscle strips.     

Differences between mouse and rat myocardial contractile responsiveness to calcium

Genetically altered mice have become an increasingly important tool for the study of mechanisms of cardiac function, and therefore it is vital to characterize the basic contractile properties of the mouse heart. As a first approach to this goal, we first optimized perfusion conditions and characterized the effect of incremental left ventricular balloon inflation on end-diastolic, systolic and developed pressures in the isovolumically-contracting mouse heart. Under constant loading conditions, we determined developed pressure in response to changing perfusate calcium (1.25, 2.5, 3.75 and 5.0 mM) and perfusate temperature (30 and 37 degrees C). We then compared the intrinsic inotropic responsiveness to changes in extracellular calcium of left ventricular myocardium from mouse to that from the rat. In the baseline state (1.25 mM extracellular calcium; [Ca2+]o), both isometric contraction duration and normalized active force at the peak of the active force-length relationship (Lmax) were less in mouse than in rat myocardium. Under isotonic conditions, temporal parameters of shortening and the relative shortening were less in mouse vs rat myocardium. Increasing [Ca2+]o from 1.25 to 2.5 mM markedly increased active isometric force and rate of force development (+dF/dt) in the mouse. However, rat myocardium responded to a lesser extent. Under isotonic conditions, peak shortening and the rate of shortening also increased to a greater extent in mouse relative to rat myocardium. Increasing the bath calcium concentration to 5.0 mM increased isometric force and +dF/dt further in the rat but not the mouse, suggesting that two species operate at different points on the force vs [Ca2+]o relationship. We conclude that mouse myocardium exhibits increased sensitivity to changes in [Ca2+]o within the physiologic range in comparison to rat. These differences do not appear to be due to differences in loading conditions. The data suggest that differences in inotropic responsiveness to calcium may reflect intrinsic differences in myocardial calcium sensitivity between species.     

Effects of low-level α-myosin heavy chain expression on contractile kinetics in porcine myocardium

Myosin heavy chain (MHC) isoforms are principal determinants of work capacity in mammalian ventricular myocardium. The ventricles of large mammals including humans normally express ～10% α-MHC on a predominantly β-MHC background, while in failing human ventricles α-MHC is virtually eliminated, suggesting that low-level α-MHC expression in normal myocardium can accelerate the kinetics of contraction and augment systolic function. To test this hypothesis in a model similar to human myocardium we determined composite rate constants of cross-bridge attachment (f(app)) and detachment (g(app)) in porcine myocardium expressing either 100% α-MHC or 100% β-MHC in order to predict the MHC isoform-specific effect on twitch kinetics. Right atrial (～100% α-MHC) and left ventricular (～100% β-MHC) tissue was used to measure myosin ATPase activity, isometric force, and the rate constant of force redevelopment (k(tr)) in solutions of varying Ca(2+) concentration. The rate of ATP utilization and k(tr) were approximately ninefold higher in atrial compared with ventricular myocardium, while tension cost was approximately eightfold greater in atrial myocardium. From these values, we calculated f(app) to be ～10-fold higher in α- compared with β-MHC, while g(app) was 8-fold higher in α-MHC. Mathematical modeling of an isometric twitch using these rate constants predicts that the expression of 10% α-MHC increases the maximal rate of rise of force (dF/dt(max)) by 92% compared with 0% α-MHC. These results suggest that low-level expression of α-MHC significantly accelerates myocardial twitch kinetics, thereby enhancing systolic function in large mammalian myocardium.     

Mechanical characteristics of isotonic work and high-energy phosphates in frog ventricle after 1-fluoro-2,4-dinitrobenzene]

The blocking of the creatinphosphokinase by 1-fluoro-2,4-dinitrobenzene (FDNB) allows to investigate the relationship between ATP-supply, contractility and relaxability of the frog's myocardium. In isotonically working isolated ventricles of frogs the time of work, systolic and diastolic volume, velocity of contraction and relaxation as well as the levels of CP, ATP, ADP and AMP were measured at different intervals until termination of each experiment. CP shows a small variation, ATP decreases to 60% and ADP + AMP increase for the same amount under FDNB during the development of a slight inhibition of contractility and a continuously growing inhibition and retardation of relaxation until systolic arrest. ATP content and volume of relaxation correlated strictly. The contracture and the diminished contractility are caused by the decrease of ATP, producing a lack of substrate for Ca transport and actin-myosin-ATPase. This models the course of events during an insufficiency like in angina pectoris and in myocardial infarction.     

Mibefradil improves beta-adrenergic responsiveness and intracellular Ca(2+) handling in hypertrophied rat myocardium

The present study investigated the effects of mibefradil, a novel T-type channel blocker, on ventricular function and intracellular Ca(2+) handling in normal and hypertrophied rat myocardium. Ca(2+) transient was measured with the bioluminescent protein, aequorin. Mibefradil (2 microM) produced nonsignificant changes in isometric contraction and peak systolic intracellular Ca(2+) concentration ([Ca(2+)](i)) in normal rat myocardium. Hypertrophied papillary muscles isolated from aortic-banded rats 10 weeks after operation demonstrated a prolonged duration of isometric contraction, as well as decreased amplitudes of developed tension and peak Ca(2+) transient compared with the sham-operated group. Additionally, diastolic [Ca(2+)](i) increased in hypertrophied rat myocardium. The positive inotropic effect of isoproterenol stimulation was blunted in hypertrophied muscles despite a large increase in Ca(2+) transient amplitude. Afterglimmers and corresponding aftercontractions were provoked with isoproterenol (10(-5) and 10(-4) M) stimulation in 4 out of 16 hypertrophied muscles, but were eliminated in the presence of mibefradil (2 microM). In addition, hypertrophied muscles in the presence of mibefradil had a significant improvement of contractile response to isoproterenol stimulation and a reduced diastolic [Ca(2+)](I), although a mild decrease of peak Ca(2+)-transient was also shown. However, verapamil (2 microM) did not restore the inotropic and Ca(2+) modulating effects of isoproterenol in hypertrophied myocardium. Mibefradil partly restores the positive inotropic response to beta-adrenergic stimulation in hypertrophied myocardium from aortic-banded rats, an effect that might be useful in hypertrophied myocardium with impaired [Ca(2+)](i) homeostasis.     

Correlated reduction of velocity of shortening and the rate of energy utilization in mouse fast-twitch muscle during a continuous tetanus

Isometric tetani of slow-twitch soleus and fast-twitch extensor digitorum longus (EDL) muscles of the mouse were studied at 20 degrees C. The total energy cost for 3- and 9-s isometric tetani was measured as a function of length above L0 and partitioned into a filament overlap-dependent fraction and a smaller filament overlap-independent fraction. In both muscles, the rate of filament overlap-independent energy cost did not change with tetanic duration. In the EDL, but not in the soleus, the rate of filament overlap-dependent energy utilization was greater in a 3-s tetanus than in a 9-s tetanus. The force-velocity relationships were studied after 3 and 9 s of isometric tetanus. In the soleus, Vmax was 2 fiber lengths/s and was not dependent on the duration of isometric tetanus. In contrast, in the EDL, Vmas decreased from 5.9 fiber lengths/s at 3 s to 3.9 fiber lengths/s at 9 s. The velocity of unloaded shortening (Vus) was examined by the slack test method as a function of the duration of isometric tetanus duration over the range of 1-15 s. In the soleus, Vus did not change, whereas in the EDL, Vus declined progressively from 6.4 to 3.2 fiber lengths/s after an isometric tetanus of increasing duration from 1 to 15 s. These results cannot exclude the hypothesis that in a maintained tetanus there is a decrease in the intrinsic cross- bridge turnover rate in the fast-twitch EDL, but not in the slow-twitch soleus muscle.     

Force enhancement above the initial isometric force on the descending limb of the force-length relationship

Edman et al. (J. General Physiol. 80 (1982) 769) observed in single fibres of frog that the steady-state forces following active fibre stretch were greater than the purely isometric force obtained at the length from which the stretch was initiated. Operating on the descending limb of the force-length relationship, such a result can only be explained within the framework of the sarcomere length non-uniformity theory, if some fibre segments shortened during the fibre stretch. However, such a result was not found, leaving Edman's observation unexplained. Force enhancement above the initial isometric force has not been investigated systematically in whole muscle, and therefore it is not known whether this property is also part of whole muscle mechanics. The purpose of this study was to test if the steady-state forces following active stretch of cat semitendinosus were greater than the corresponding purely isometric forces at the muscle length from which the stretch was started. Cat semitendinosus was stretched by various amounts on the descending limb of the force-length relationship, and the steady-state forces following these stretches were compared to the corresponding isometric forces at the initial and final muscle lengths. In 109 of 131 tests, the steady-state forces following stretching were greater than the isometric forces at the initial muscle lengths. Force enhancement increased with increasing amounts of stretching, and force enhancement above the initial isometric force was more likely to occur following stretches of great compared to small amplitude. Passive forces following active muscle stretching were often significantly greater than the passive forces at the same muscle length following an isometric contraction or a passive stretching of the muscle. This observation was made consistently at the longest muscle lengths tested. It appears, therefore, that there is a passive force that accounts for part of the force enhancement above the isometric force at the initial muscle length, and that provides increased passive force when a muscle is actively, rather than passively, stretched at long muscle lengths. We conclude that cat semitendinosus demonstrates steady-state force enhancement above the corresponding purely isometric force at the initial muscle length on the descending limb of the force-length relationship for many contractile conditions, and that a unique, and so far undetected, passive, parallel element contributes to this force enhancement, particularly at long muscle lengths where muscle is assumed to be most vulnerable to injuries associated with sarcomere length instability.     

The effect of irradiation by a He-Ne laser and phytohemagglutinin on lymphocyte mitochondria

Electron-microscopic morphometry has been applied to study mitochondria on ultrathin sections of lymphocytes from human peripheral blood. It has been shown that the stimulation of lymphocytes by the mitogen phytohemagglutinin (PHA) 1 h causes increases in the quantity of mitochondria per cellular section (17%) as well as in the total area of mitochondria per cell section (35%), i.e. an increase in mitochondrial mass. Taking into account known facts about growth and division of mitochondria in late phases of cellular cycle, one can suppose that described above changes in mitochondria during G0----G1 transition under action of PHA belong to an early phase of biogenesis of mitochondria. In the contrary, irradiation of lymphocytes with He-Ne-laser (lambda = 632.8 nm) in dose 56 J/m2 which does not cause the G0----C1 transition, results in the increase in the number of mitochondria per cellular section (20%) but not increase in the total area of mitochondria per cell section. The last finding indicates to some modification of space configuration of the mitochondria without any changes in their mass. The increase in the quantity of mitochondria per cellular section after the irradiation could be related with the increase in electrochemical proton gradient and in phosphorylating activity of mitochondria. He-Ne-laser radiation as well as mitogen PHA cause some deaggregation of mitochondria (this is more pronounced in case of PHA) which may be related to their functional activation.     

The biomechanical function of the heart and its adrenergic regulation after long-term gamma radiation exposure

The study of heart isolated by Langendorf's method has shown that the prolonged gamma irradiation of rats with 1.0 Gy dose (2.8 x 10(-7) Gy/sec) causes the decrease in contraction and relaxation ability, of myocardium, reduces functional response of heart to the stimulation of beta-adrenergic receptors, and increases of myocardium reaction to the stimulation of alpha-adrenergic receptors.     

Acceleration of stretch activation in murine myocardium due to phosphorylation of myosin regulatory light chain

The regulatory light chains (RLCs) of vertebrate muscle myosins bind to the neck region of the heavy chain domain and are thought to play important structural roles in force transmission between the cross-bridge head and thick filament backbone. In vertebrate striated muscles, the RLCs are reversibly phosphorylated by a specific myosin light chain kinase (MLCK), and while phosphorylation has been shown to accelerate the kinetics of force development in skeletal muscle, the effects of RLC phosphorylation in cardiac muscle are not well understood. Here, we assessed the effects of RLC phosphorylation on force, and the kinetics of force development in myocardium was isolated in the presence of 2,3-butanedione monoxime (BDM) to dephosphorylate RLC, subsequently skinned, and then treated with MLCK to phosphorylate RLC. Since RLC phosphorylation may be an important determinant of stretch activation in myocardium, we recorded the force responses of skinned myocardium to sudden stretches of 1% of muscle length both before and after treatment with MLCK. MLCK increased RLC phosphorylation, increased the Ca(2+) sensitivity of isometric force, reduced the steepness of the force-pCa relationship, and increased both Ca(2+)-activated and Ca(2+)-independent force. Sudden stretch of myocardium during an otherwise isometric contraction resulted in a concomitant increase in force that quickly decayed to a minimum and was followed by a delayed redevelopment of force, i.e., stretch activation, to levels greater than pre-stretch force. MLCK had profound effects on the stretch activation responses during maximal and submaximal activations: the amplitude and rate of force decay after stretch were significantly reduced, and the rate of delayed force recovery was accelerated and its amplitude reduced. These data show that RLC phosphorylation increases force and the rate of cross-bridge recruitment in murine myocardium, which would increase power generation in vivo and thereby enhance systolic function.     

Akinetic myocardial infarcts must contain contracting myocytes: finite-element model study

Infarcted segments of myocardium demonstrate functional impairment ranging in severity from hypokinesis to dyskinesis. We sought to better define the contributions of passive material properties (stiffness) and active properties (contracting myocytes) to infarct thickening. Using a finite-element (FE) model, we tested the hypothesis that infarcted myocardium must contain contracting myocytes to be akinetic and not dyskinetic. A three-dimensional FE mesh of the left ventricle was developed with echocardiographs from a reperfused ovine anteroapical infarct. The nonlinear stress-strain relationship for the diastolic myocardium was anisotropic with respect to the local muscle fiber direction, and an elastance model for active fiber stress was incorporated. The diastolic stiffness (C) and systolic material property (isometric tension at longest sarcomere length and peak intracellular calcium concentration, T(max)) of the uninfarcted remote myocardium were assumed to be normal (C = 0.876 kPa, T(max) = 135.7 kPa). Diastolic and systolic properties of the infarct necessary to produce akinesis, defined as an average radial strain between -0.01 and 0.01, were determined by assigning a range of diastolic stiffnesses and scaling infarct T(max) to represent the percentage of contracting myocytes between 0% and 100%. As C was increased to 11 times normal (C = 10 kPa) the percentage of T(max) necessary for akinesis increased from 20% to 50%. Without contracting myocytes, C = 250 kPa was necessary to achieve akinesis. If infarct stiffness is <285 times normal, contracting myocytes are required to prevent dyskinetic infarct wall motion.     

Knee angle-dependent oxygen consumption during isometric contractions of the knee extensors determined with near-infrared spectroscopy.

Fatigue resistance of knee extensor muscles is higher during voluntary isometric contractions at short compared with longer muscle lengths. In the present study we hypothesized that this would be due to lower energy consumption at short muscle lengths. Ten healthy male subjects performed isometric contractions with the knee extensor muscles at a 30, 60, and 90 degrees knee angle (full extension = 0 degrees ). At each angle, muscle oxygen consumption (m.VO2) of the rectus femoris, vastus lateralis, and vastus medialis muscle was obtained with near-infrared spectroscopy. m.VO2 was measured during maximal isometric contractions and during contractions at 10, 30, and 50% of maximal torque capacity. During all contractions, blood flow to the muscle was occluded with a pressure cuff (450 mmHg). m.VO2 significantly (P < 0.05) increased with torque and at all torque levels, and for each of the three muscles. m.VO2 was significantly lower at 30 degrees compared with 60 degrees and 90 degrees and m.VO2 was similar (P > 0.05) at 60 degrees and 90 degrees . Across all torque levels, average (+/- SD) m.VO2 at the 30 degrees angle for vastus medialis, rectus femoris, and vastus lateralis, respectively, was 70.0 +/- 10.4, 72.2 +/- 12.7, and 75.9 +/- 8.0% of the average m.VO2 obtained for each torque at 60 and 90 degrees . In conclusion, oxygen consumption of the knee extensors was significantly lower during isometric contractions at the 30 degrees than at the 60 degrees and 90 degrees knee angle, which probably contributes to the previously reported longer duration of sustained isometric contractions at relatively short muscle lengths.     

Changes in the structure of lymphocyte chromatin after irradiation with He-Ne-laser

The cytofluorometric method was used to study changes occurring in the chromatin structure of lymphocytes during the first few hours following irradiation of lymphocytes with He-Ne-laser (lambda = 632.8 nm) of 28-112 J/m2. The changes were similar to those caused by PHA that is: the increase in acridine-orange binding to DNA during the first 45-90 min, its fall to the control level in 3-4 h and the subsequent increase.     

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.     

Expression of cardiac troponin T with COOH-terminal truncation accelerates cross-bridge interaction kinetics in mouse myocardium

Transgenic mice expressing an allele of cardiac troponin T (cTnT) with a COOH-terminal truncation (cTnT(trunc)) exhibit severe diastolic and mild systolic dysfunction. We tested the hypothesis that contractile dysfunction in myocardium expressing low levels of cTnT(trunc) (i.e., <5%) is due to slowed cross-bridge kinetics and reduced thin filament activation as a consequence of reduced cross-bridge binding. We measured the Ca(2+) sensitivity of force development [pCa for half-maximal tension generation (pCa(50))] and the rate constant of force redevelopment (k(tr)) in cTnT(trunc) and wild-type (WT) skinned myocardium both in the absence and in the presence of a strong-binding, non-force-generating derivative of myosin subfragment-1 (NEM-S1). Compared with WT mice, cTnT(trunc) mice exhibited greater pCa(50), reduced steepness of the force-pCa relationship [Hill coefficient (n(H))], and faster k(tr) at submaximal Ca(2+) concentration ([Ca(2+)]), i.e., reduced activation dependence of k(tr). Treatment with NEM-S1 elicited similar increases in pCa(50) and similar reductions in n(H) in WT and cTnT(trunc) myocardium but elicited greater increases in k(tr) at submaximal activation in cTnT(trunc) myocardium. Contrary to our initial hypothesis, cTnT(trunc) appears to enhance thin filament activation in myocardium, which is manifested as significant increases in Ca(2+)-activated force and the rate of cross-bridge attachment at submaximal [Ca(2+)]. Although these mechanisms would not be expected to depress systolic function per se in cTnT(trunc) hearts, they would account for slowed rates of myocardial relaxation during early diastole.     

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.     

Effect of anoxia on energy supply and isotonic work performance in the myocardium of the frog]

To investigate correlations between energy supply and mechanical work in the frog's myocardium in true anoxia, the stroke volume, systolic and diastolic volumes and the parameters of velocity of contraction and relaxation of frog hearts were compared to the levels of high energy phosphates and the delivery of lactate. During perfusion with N2 saturated Ringer solution, stroke volume, systolic contractility and diastolic relaxation decrease till a contracture. High preload produces a dilatation growing up to the contracture after retarded and weakened relaxation. The ATP-content decreases during the first quarter of the experiment to 60%. CP decreases continuously to 15%, ADP and AMP remain constant. There is a production of lactate increasing considerably with the onset of contracture. The measured glycolysis is not sufficient for production of mechanical work. The effect of anoxia on the action potential and the reduction of the sequestration of Ca++ and of the break of actomyosin bridges following the decrease of ATP are considered as causing the series of the mechanical events.