The positive staircase (force-frequency relationship) and the Frank-Starling mechanism are altered in atrial myocardium of patients in end-stage heart failure transplanted for dilative cardiomyopathy

Kayhan, N; Bodem, Jens; Vahl, C.-F.; Hagl, S.

doi:10.1016/s0041-1345(02)03197-4

“…It has been reported that not all tissue blocks show these cellular morphological alterations [26]. This focal localization of structural changes [26] in diseased myocardium may explain part of the variations in the results obtained for the length‐/preload‐dependent measurements in human myocardium [7,27–29].…”

Section: Discussionmentioning

confidence: 97%

Altered hetero‐ and homeometric autoregulation in the terminally failing human heart

Brixius

¹

,

Reuter

²

,

Bloch

³

et al. 2005

European J of Heart Fail

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Objective and methods: To further investigate length-dependent force generation in human heart, nonfailing (donor hearts, NF) and terminally failing (heart transplants, dilated cardiomyopathy, DCM) left ventricular myocardium was studied under various preload (4 -40 mN/mm 2 ) or length conditions. In addition, morphological studies (van Giesson Trichrome staining, electron microscopy) were performed. Results: In NF, a biphasic increase in force of contraction (FOC) was observed after elevating the preload (4 -40 mN/mm 2 ): there was an immediate fast increase (FOC f, ), followed by a slow increase over several minutes (FOC s ), which was paralleled by an increase in the systolic fura-2 transient. In DCM, FOC f , FOC s and the systolic fura-2 transient were blunted and diastolic tension was increased at increasing muscle length. Only in NF, a stretched induced increase in diastolic fura-2 ratio was observed. In DCM, no obvious interstitial fibrosis and no difference in basement membrane structure and attachment were observed. Conclusions: Since FOC f has been attributed to the Frank-Starling mechanism, whereas FOC s represents a length-dependent increase in the intracellular Ca 2 + -transient, the impaired length-dependent force generation in failing myocardium results from a dysregulation of both myofibrillar Ca 2 + -sensitivity as well as the intracellular Ca 2 + -homeostasis. Interstitial fibrosis may have only minor impact on force generation in human end-stage heart failure.

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“…12 The FSM response is attributed to an increase of myofilament calcium sensitivity; however, the underlying mechanisms are still controversial. In isolated rabbit hearts, the intramyocardial nitric oxide (NO) concentration changed in parallel to the cardiac cycle and was increased by additional preload.…”

Section: Clinical Perspective See P 55mentioning

confidence: 99%

“…This is in line with previous data 45 that a given rise in Na ϩ increases Ca 2ϩ transients and developed force in nonfailing myocardium but not in failing myocardium. Kayhan et al 12 demonstrated a stretch-induced increase in diastolic Ca 2ϩ using FURA-2 in failing human atrial myocardium whereas diastolic Ca 2ϩ levels were not altered in nonfailing atrial myocardium. This is consistent with the larger increase in diastolic tension in the failing group in the present study strengthening the evidence of stretch-induced diastolic Ca 2ϩ -overload as a mechanism underlying the reduced SFR in failing myocardium and the impaired Na ϩ -contraction coupling.…”

Section: Role Of Na ؉ and Ca 2؉ Homeostasismentioning

confidence: 99%

Reduced Stretch-Induced Force Response in Failing Human Myocardium Caused by Impaired Na ⁺ -Contraction Coupling

Lewinski

¹

,

Kockskämper

²

,

Zhu

³

et al. 2009

Circ: Heart Failure

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Background-Stretch elicits an immediate, followed by a delayed, inotropic response in various animal models and failing human myocardium. This study aimed to characterize functional differences in the stretch response between failing and nonfailing human myocardium. Methods and Results-Experiments were performed in muscle tissue from 86 failing and 16 nonfailing human hearts.Muscles were stretched from 88% to 98% of optimal length.

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“…The characterization of the action potential was measured with amplitude and the APD at 30 and 90% of the repolarization. The excitation-contraction coupling phenom was measured, using the time between the maximum voltage of the action potential and the maximum force of the contraction, including the delay between the start of the action potential with the start of the force of contraction [30].…”

Section: Cardiac Functionmentioning

confidence: 99%

Ventricular Dysfunction in Obese and Nonobese Rats with Metabolic Syndrome

Torres-Jácome

¹

,

Ortiz-Fuentes

²

,

Bernabé-Sánchez

³

et al. 2022

Journal of Diabetes Research

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Obesity and dyslipidemias are both signs of metabolic syndrome, usually associated with ventricular arrhythmias. Here, we tried to identify cardiac electrical alteration and biomarkers in nonobese rats with metabolic syndrome (MetS), and these findings might lead to more lethal arrhythmias than obese animals. The MetS model was developed in Wistar rats with high-sucrose diet (20%), and after twenty-eight weeks were obtained two subgroups: obese (OMetS) and nonobese (NOMetS). The electrocardiogram was used to measure the ventricular arrhythmias and changes in the heart rate variability. Also, we measured ventricular hypertrophy and its relationship with electrical activity alterations of both ventricles, using micro-electrode and voltage clamp techniques. Also, we observed alterations in the contraction force of ventricles where a transducer was used to record mechanical and electrical papillary muscle, simultaneously. Despite both subgroups presenting long QT syndrome ( 0.66 ± 0.05 and 0.66 ± 0.07 ms with respect to the control 0.55 ± 0.1 ms), the changes in the heart rate variability were present only in OMetS, while the NOMetS subgroup presented changes in QT interval variability (NOMetS SD = 1.8 , SD 2 = 2.8 ; SD 1 / SD 2 = 0.75 ). Also, the NOMetS revealed tachycardia (10%; p < 0.05 ) with changes in action potential duration (63% in the right papillary and 50% in the left papillary) in the ventricular papillary which are correlated with certain alterations in the potassium currents and the force of contraction. The OMetS showed an increase in action potential duration and the force of contraction in both ventricles, which are explained as bradycardia. Our results revealed lethal arrhythmias in both MetS subgroups, irrespectively of the presence of obesity. Consequently, the NOMetS showed mechanical-electrical alterations regarding ventricle hypertrophy that should be at the NOMetS, leading to an increase of CV mortality.

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The positive staircase (force-frequency relationship) and the Frank-Starling mechanism are altered in atrial myocardium of patients in end-stage heart failure transplanted for dilative cardiomyopathy

Cited by 10 publications

References 25 publications

Altered hetero‐ and homeometric autoregulation in the terminally failing human heart

Altered hetero‐ and homeometric autoregulation in the terminally failing human heart

Reduced Stretch-Induced Force Response in Failing Human Myocardium Caused by Impaired Na ⁺ -Contraction Coupling

Ventricular Dysfunction in Obese and Nonobese Rats with Metabolic Syndrome

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The positive staircase (force-frequency relationship) and the Frank-Starling mechanism are altered in atrial myocardium of patients in end-stage heart failure transplanted for dilative cardiomyopathy

Cited by 10 publications

References 25 publications

Altered hetero‐ and homeometric autoregulation in the terminally failing human heart

Altered hetero‐ and homeometric autoregulation in the terminally failing human heart

Reduced Stretch-Induced Force Response in Failing Human Myocardium Caused by Impaired Na + -Contraction Coupling

Ventricular Dysfunction in Obese and Nonobese Rats with Metabolic Syndrome

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Reduced Stretch-Induced Force Response in Failing Human Myocardium Caused by Impaired Na ⁺ -Contraction Coupling