scholarly journals Why Myocardial Relaxation Always Slows at Cardiac Pathology?

Kardiologiia ◽  
2019 ◽  
Vol 59 (12) ◽  
pp. 44-51 ◽  
Author(s):  
V. I. Kapelko
Keyword(s):  
Left Ventricle ◽  
Maximum Rate ◽  
Experimental Models ◽  
Restoring Force ◽  
Cardiac Pathology ◽  
Myocardial Relaxation ◽  
Sarcomeric Protein ◽  
Myosin Filaments ◽  
Pressure Development ◽  
Pressure Fall

Chronic heart failure (CHF) in most cases is due to a decrease in myocardial contractility. In particular, this results in a reduction in the maximum rate of the pressure development in the left ventricle. At the same time the maximal rate of pressure fall at relaxation is also reduced. This is not surprising, since both depend on Ca ++ myoplasmic concentration. But most of cardiac pathologies have been associated with the impairement of myocardial relaxation to a greater extent than the contraction. In the review a new view has been proposed according to which this phenomenon is attributable to restructuring of titin, the sarcomeric protein that connects the ends of myosin filaments with the sarcomeric board, lines Z. A spring-like molecule of titin shrinks at sarcomeric contraction and straightens in parallel with removing of Ca ++ from myofibrils. A reduction of its stiffness, facilitating the filling of the left ventricle, can reduce restoring force of titin and thereby slow relaxation. The survey provides information about the functions of the calcium transport system and titin in the normal heart and in CHF observed both in experimental models and in patients.

Effects of chronic supraventricular pacing tachycardia on relaxation rate in isolated cardiac muscle cells

1995 ◽  
Vol 268 (5) ◽  
pp. H2104-H2113 ◽  
Author(s):  
M. R. Zile ◽  
R. Mukherjee ◽  
C. Clayton ◽  
S. Kato ◽  
F. G. Spinale
Keyword(s):  
Left Ventricle ◽  
Relaxation Process ◽  
Left Atrial ◽  
Atrial Pacing ◽  
Direct Relation ◽  
Restoring Force ◽  
Cardiac Muscle Cells ◽  
Myocardial Relaxation ◽  
Relaxation Velocity ◽  
Restoring Forces

Chronic supraventricular pacing tachycardia (SVT) causes abnormalities in both ventricular and cellular relaxation. The mechanisms causing these abnormalities have not been fully determined. To examine two of the possible mechanisms, a decrease in restoring force or an impairment of the intrinsic myocardial relaxation process, cardiocytes were enzymatically isolated from the left ventricle of pigs subjected to left atrial pacing at 240 beats/min for 3 wk and normal control pigs. SVT caused a decrease in the extent of cardiocyte shortening and the velocity of cardiocyte lengthening. To determine whether the changes in the relaxation velocity merely reflected a concomitant decrease in the extent of cardiocyte shortening (and a resultant decrease in restoring forces) or, in addition, reflected impairment in intrinsic relaxation properties, the relation between cardiocyte relaxation velocity and cardiocyte shortening extent was examined. There was a direct relation between relaxation velocity and shortening extent in both control and SVT cardiocytes. However, SVT decreased the relaxation velocity at any common extent of shortening and decreased the slope of the direct relation (slope 5.91 in control vs. 3.51 s-1 in SVT, P < 0.05). Therefore, these data suggested that SVT caused a primary impairment in the intrinsic myocardial relaxation process independently of a decrease in restoring force.

Myocardial relaxation in regionally stunned left ventricle

1996 ◽  
Vol 270 (2) ◽  
pp. H509-H517 ◽  
Author(s):  
A. F. Leite-Moreira ◽  
T. C. Gillebert
Keyword(s):  
Left Ventricle ◽  
Systolic Pressure ◽  
Initial Pressure ◽  
Myocardial Relaxation ◽  
Load Dependence ◽  
Anesthetized Dogs ◽  
Load Regulation ◽  
Different Response ◽  
Delayed Transition ◽  
Pressure Fall

Load regulation of pressure fall was analyzed in regionally stunned left ventricles (LV) of anesthetized dogs. Stunning delayed and slowed pressure fall. When partial aortic occlusions elevated systolic pressure by 12.5 +/- 0.4 mmHg, the rate of pressure fall remained unchanged at baseline but slowed after stunning. This different response after stunning could be attributed entirely to decreased contractility and decreased development of peak isovolumetric pressure. Total aortic occlusions were then performed at various timings during ejection. With early occlusions and isovolumetric heartbeats, systolic pressure was lower after stunning, but pressure fall slowed to the same extent. With midocclusions the stunned LV developed relatively more systolic pressure, and pressure fall slowed more. This suggested a delayed transition from contraction to relaxation. With late occlusions pressure fall did not slow as with earlier occlusions, but initial pressure fall accelerated both at baseline and after stunning. The data suggested that load dependence was preserved with stunning and that, even if myocardial inactivation might be delayed, this delay did not contribute to the observed slowing of pressure fall.

Rhythm effects on contractility of the beating isovolumic left ventricle

1960 ◽  
Vol 199 (6) ◽  
pp. 1115-1120 ◽  
Author(s):  
B. Lendrum ◽  
H. Feinberg ◽  
E. Boyd ◽  
L. N. Katz
Keyword(s):  
Heart Rate ◽  
Left Ventricle ◽  
Systolic Pressure ◽  
Ventricular Volume ◽  
Contractile Force ◽  
Postextrasystolic Potentiation ◽  
Pressure Development ◽  
Induced Changes ◽  
Electrical Alternans

Variation in contractile force of the isovolumic contracting left ventricle of the dog was studied in open-chested in situ hearts. The electrocardiogram and intraventricular pressures were recorded at various heart volumes. Spontaneous changes in heart rate and rhythm occurred at all volumes. Isovolumic systolic pressure development (contractile force) varied with rate and rhythm. Contractile force increased with heart rate (treppe) regardless of pacemaker origin. When a premature beat was followed by a compensatory pause, the premature beat showed a decrease and the next beat an increase in contractile force (postextrasystolic potentiation). The magnitude of the changes varied directly with the prematurity of the beat. Mechanical alternans was observed with electrical alternans, despite the absence of significant volume change. Rate-induced changes, postextrasystolic potentiation and mechanical alternans were additive when they occurred simultaneously. For practical purposes, ventricular volume (filling), hence muscle fiber length, remained constant during these rate and rhythm change, therefore could not affect the strength of contraction. Contractile force changes directly attributable to rate and rhythm changes do, therefore, occur in the intact mammalian heart.

Abstract 1581: Extension of Titin as a Function of Filling Pressure and Sarcomere Length in the Porcine Left Ventricle

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Martin M LeWinter ◽  
Joseph Popper ◽  
Lori Nyland ◽  
Stephen B Bell ◽  
Henk Granzier
Keyword(s):  
Left Ventricle ◽  
Sarcomere Length ◽  
Filling Pressure ◽  
Passive Tension ◽  
Large Mammals ◽  
Myocardial Stiffness ◽  
Sarcomeric Protein ◽  
Equilibrium Volume ◽  
Slack Length

The giant sarcomeric protein titin is a molecular spring that is the chief source of cardiomyocyte passive tension and a major determinant of myocardial stiffness. The spring portion is located in the I band and consists of PEVK, Ig repeat and N2B and N2A elements. Titin occurs as two isoforms. N2B is a smaller and stiffer isoform that contains only the N2B element and predominates in the left ventricle (LV) of rodents. N2BA titin contains both N2A and N2B elements. N2B and N2BA are co-expressed in the sarcomere of large mammals (~60:40 ratio). As a result, passive cardiomyocyte and myocardial stiffness in large mammals is less than in rodents. Details of titin extension as a function of sarcomere length (SL) have been elucidated in rodents but not in large mammals, where the presence of both isoforms would be expected to modify extension and passive tension. Accordingly, we studied titin extension in miniswine. We first established the relation between filling pressure and SL in the anterior LV wall of the in situ, freshly arrested (KCl) heart. SL was determined over a range of filling pressures using a light microscopic method that minimizes shrinkage. At equilibrium volume (transmural pressure 0 mmHg), SL was between 2.00–2.10 μm, longer than slack length of ~1.85 μm in muscle strips. SL reached a maximum of ~2.50 βm when the LV was over-distended (filling pressure >40 mmHg). We then examined extension of titin in myocardial strips using electron microscopy and immuno-labeling of selected epitopes. The chief difference between isoforms was that the N2B-Us epitope segment in N2B titin lengthened ~four times more than the N2B-Us segment in N2BA titin over SLs from ~1.80 to ~2.50 μm. This difference remained large over the SL range present in the in situ LV. Linear fits of the measured end-to-end length of N2B-Us segments were used to estimate the force-SL relation of single N2B and N2BA molecules. This analysis predicted a much steeper relation for N2B titin. Thus, over the range of SLs present in the in situ LV the most prominent difference in extension of N2B and N2BA titin is greater lengthening of the N2B segment of N2B titin. This predicts a much greater in situ stiffness for N2B titin and demonstrates how passive stiffness can be exquisitely controlled by varying isoform expression.

Asynchrony and ryanodine modulate load-dependent relaxation in the canine left ventricle

1995 ◽  
Vol 268 (1) ◽  
pp. H17-H24 ◽  
Author(s):  
W. Y. Lew
Keyword(s):  
Left Ventricle ◽  
Time Constant ◽  
Cardiac Cycle ◽  
Left Ventricular ◽  
Pressure Load ◽  
Single Cardiac Cycle ◽  
Anesthetized Dogs ◽  
Pressure Fall

Load-dependent relaxation was studied in six anesthetized dogs by inflating an intra-aortic balloon to increase peak left ventricular (LV) pressure by 1–20 mmHg within a single cardiac cycle. A series of timed and graded pressure loads was produced by inflating the balloon either during diastole (early loads) or midsystole (midsystolic pressure loads). The rate of LV pressure fall was measured with the time constant (tau). There was a significant increase in tau with 63 midsystolic pressure load [tau increased 1.4 +/- 0.1% (SE)/mmHg increase in peak LV pressure] but not with 67 early pressure loads (-0.5 +/- 0.1%/mmHg). This difference remained with LV pacing-induced asynchrony (tau increased 1.8 +/- 0.1%/mmHg with 54 midsystolic pressure loads compared with -0.2 +/- 0.1%/mmHg with 56 early pressure loads) and after 5 micrograms/kg of intravenous ryanodine (tau increased 1.0 +/- 0.2%/mmHg with 58 midsystolic pressure loads compared with -0.7 +/- 0.1%/mmHg with 59 early pressure loads). When compared with control, asynchrony significantly augmented and ryanodine significantly attenuated the effects of midsystolic pressure loads. In conclusion, asynchrony and ryanodine modulate the extent of load-dependent relaxation in the intact left ventricle.

Congestive Heart Failure in Copper-Deficient Mice

2003 ◽  
Vol 228 (7) ◽  
pp. 811-817 ◽  
Author(s):  
Laila Elsherif ◽  
Raymond V. Ortines ◽  
Jack T. Saari ◽  
Y. James Kang
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Left Ventricle ◽  
Diastolic Pressure ◽  
Systolic Pressure ◽  
Pressure Rise ◽  
Experimental Models ◽  
Left Ventricular ◽  
Mouse Heart ◽  
Total Period

Copper Deficiency (CuD) leads to hypertrophic cardiomyopathy in various experimental models. The morphological, electrophysiological, and molecular aspects of this hypertrophy have been under investigation for a long time. However the transition from compensated hypertrophy to decompensated heart failure has not been investigated in the study of CuD. We set out to investigate the contractile and hemodynamic parameters of the CuD mouse heart and to determine whether heart failure follows hypertrophy in the CuD heart. Dams of FVB mice were fed CuD or copper-adequate (CuA) diet starting from the third day post delivery and the weanling pups were fed the same diet for a total period of 5 weeks (pre- and postweanling). At week 4, the functional parameters of the heart were analyzed using a surgical technique for catheterizing the left ventricle. A significant decrease in left ventricle systolic pressure was observed with no significant change in heart rate, and more importantly contractility as measured by the maximal rate of left ventricular pressure rise (+dP/dt) and decline (−dP/dt) were significantly depressed in the CuD mice. However, left ventricle end diastolic pressure was elevated, and relaxation was impaired in the CuD animals; the duration of relaxation was prolonged. In addition to significant changes in the basal level of cardiac function, CuD hearts had a blunted response to the stimulation of the β-adrenergic agonist isoproterenol. Furthermore, morphological analysis revealed increased collagen accumulation in the CuD hearts along with lipid deposition. This study shows that CuD leads to systolic and diastolic dysfunction in association with histopathological changes, which are indices commonly used to diagnose congestive heart failure.

Effect of theophylline and dipyridamole on the respiratory response to isocapnic hypoxia in normal human subjects

1991 ◽  
Vol 80 (2) ◽  
pp. 107-112 ◽  
Author(s):  
S. T. Parsons ◽  
T. L. Griffiths ◽  
J. M. L. Christie ◽  
S. T. Holgate
Keyword(s):  
Oxygen Saturation ◽  
Maximum Rate ◽  
Human Subjects ◽  
Minute Ventilation ◽  
Physiological Role ◽  
Respiratory Control ◽  
Inspiratory Pressure ◽  
Respiratory Response ◽  
Peripheral Chemoreceptor ◽  
Pressure Development

1. Twelve healthy young men took part in this investigation of the effect of oral theophylline and dipyridamole (two drugs known to affect the pharmacological effects of the purine nucleoside adenosine) on the respiratory response to isocapnic hypoxia. 2. The subjects underwent hypoxic rebreathing manoeuvres after 3-day pretreatments with each of the drugs for 12 h and were at least 2 h postprandial. For each in-Minute ventilation, the maximum rate of isometric inspiratory pressure development at the mouth and the ratio of inspiratory duration to total breath duration were analysed breath-by-breath and regressions of these variables upon the haemoglobin oxygen saturation were performed. 3. The slopes and intercepts of the lines describing the relationships of minute ventilation and the maximum rate of isometric inspiratory pressure development at the mouth with haemoglobin oxygen saturation were unaffected by the study drugs, and no differences in the pattern of breathing were observed. 4. We conclude that oral administration of these drugs does not result in alteration of the response of the respiratory system to progressive isocapnic hypoxia. 5. This suggests that either adenosine has no physiological role in hypoxic respiratory control as measured, or that it has opposing peripheral chemoreceptor and central respiratory centre effects which could not be distinguished by the techniques used.

scholarly journals Sarcomeric protein modification during adrenergic stress enhances cross-bridge kinetics and cardiac output

2017 ◽  
Vol 122 (3) ◽  
pp. 520-530 ◽  
Author(s):  
Kenneth S. Gresham ◽  
Ranganath Mamidi ◽  
Jiayang Li ◽  
Hyerin Kwak ◽  
Julian E. Stelzer
Keyword(s):  
Cardiac Output ◽  
Posttranslational Modifications ◽  
Troponin I ◽  
Ventricular Contractility ◽  
Protein Modifications ◽  
Sarcomeric Protein ◽  
Cross Bridge ◽  
Myosin Binding Protein ◽  
Myosin Binding Protein C ◽  
Pressure Development

Molecular adaptations to chronic neurohormonal stress, including sarcomeric protein cleavage and phosphorylation, provide a mechanism to increase ventricular contractility and enhance cardiac output, yet the link between sarcomeric protein modifications and changes in myocardial function remains unclear. To examine the effects of neurohormonal stress on posttranslational modifications of sarcomeric proteins, mice were administered combined α- and β-adrenergic receptor agonists (isoproterenol and phenylephrine, IPE) for 14 days using implantable osmotic pumps. In addition to significant cardiac hypertrophy and increased maximal ventricular pressure, IPE treatment accelerated pressure development and relaxation (74% increase in dP/d tmax and 14% decrease in τ), resulting in a 52% increase in cardiac output compared with saline (SAL)-treated mice. Accelerated pressure development was maintained when accounting for changes in heart rate and preload, suggesting that myocardial adaptations contribute to enhanced ventricular contractility. Ventricular myocardium isolated from IPE-treated mice displayed a significant reduction in troponin I (TnI) and myosin-binding protein C (MyBP-C) expression and a concomitant increase in the phosphorylation levels of the remaining TnI and MyBP-C protein compared with myocardium isolated from saline-treated control mice. Skinned myocardium isolated from IPE-treated mice displayed a significant acceleration in the rate of cross-bridge (XB) detachment (46% increase) and an enhanced magnitude of XB recruitment (43% increase) at submaximal Ca2+ activation compared with SAL-treated mice but unaltered myofilament Ca2+ sensitivity of force generation. These findings demonstrate that sarcomeric protein modifications during neurohormonal stress are molecular adaptations that enhance in vivo ventricular contractility through accelerated XB kinetics to increase cardiac output. NEW & NOTEWORTHY Posttranslational modifications to sarcomeric regulatory proteins provide a mechanism to modulate cardiac function in response to stress. In this study, we demonstrate that neurohormonal stress produces modifications to myosin-binding protein C and troponin I, including a reduction in protein expression within the sarcomere and increased phosphorylation of the remaining protein, which serve to enhance cross-bridge kinetics and increase cardiac output. These findings highlight the importance of sarcomeric regulatory protein modifications in modulating ventricular function during cardiac stress.

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