Normalization of force to muscle cross‐sectional area: A helpful attempt to reduce data scattering in contractility studies?

Pecha, Simon; Koivumäki, Jussi T.; Geelhoed, Bastiaan; Kempe, Romy; Berk, Emanuel; Engel, Andreas K.; Reichenspurner, Hermann; Eschenhagen, Thomas; Ravens, Ursula; Kaumann, Alberto J.; Christ, Torsten

doi:10.1111/apha.13202

Cited by 8 publications

(7 citation statements)

References 6 publications

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“…Muscle thickness is a factor potentially impacting myocardial function (41) and sarcoplasmic reticulum Ca 2ϩ load (33) because of hypoxic core formation (33,38,42), although this recently was disputed for human trabeculae (36). The development of very few SCs in our time-control experiments and the lack of correlation between muscle cross-sectional area and development of SCs (data not shown) indicate that muscle thickness does not seem to play an important role in the susceptibility to developing SCs.…”

Section: Discussionmentioning

confidence: 73%

Acute interaction between human epicardial adipose tissue and human atrial myocardium induces arrhythmic susceptibility

Babakr

Fomison-Nurse

Hout

et al. 2020

American Journal of Physiology-Endocrinology and Metabolism

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Epicardial adipose tissue (EAT) deposition has a strong clinical association with atrial arrhythmias; however, whether a direct functional interaction exists between EAT and the myocardium to induce atrial arrhythmias is unknown. Therefore, we aimed to determine whether human EAT can be an acute trigger for arrhythmias in human atrial myocardium. Human trabeculae were obtained from right atrial appendages of patients who have had cardiac surgery ( n = 89). The propensity of spontaneous contractions (SCs) in the trabeculae (proxy for arrhythmias) was determined under physiological conditions and during known triggers of SCs (high Ca2+, β-adrenergic stimulation). To determine whether EAT could trigger SCs, trabeculae were exposed to superfusate of fresh human EAT, and medium of 24 h-cultured human EAT treated with β1/2 (isoproterenol) or β3 (BRL37344) adrenergic agonists. Without exposure to EAT, high Ca2+ and β1/2-adrenergic stimulation acutely triggered SCs in, respectively, 47% and 55% of the trabeculae that previously were not spontaneously active. Acute β3-adrenergic stimulation did not trigger SCs. Exposure of trabeculae to either superfusate of fresh human EAT or untreated medium of 24 h-cultured human EAT did not induce SCs; however, specific β3-adrenergic stimulation of EAT did trigger SCs in the trabeculae, either when applied to fresh (31%) or cultured (50%) EAT. Additionally, fresh EAT increased trabecular contraction and relaxation, whereas media of cultured EAT only increased function when treated with the β3-adrenergic agonist. An acute functional interaction between human EAT and human atrial myocardium exists that increases the propensity for atrial arrhythmias, which depends on β3-adrenergic rather than β1/2-adrenergic stimulation of EAT.

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Section: Discussionmentioning

confidence: 73%

Acute interaction between human epicardial adipose tissue and human atrial myocardium induces arrhythmic susceptibility

Babakr

Fomison-Nurse

Hout

et al. 2020

American Journal of Physiology-Endocrinology and Metabolism

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“…Superfused working human trabeculae will likely have a hypoxic core due to their size which may confound observed results, especially contractile strength. However, Pecha et al found only a very weak correlation between force generation and cross sectional area 43 . Our studies used trabeculae with a mean width 1.96 ± 0.76 mm and cross‐sectional area of 3.7 ± 2.1 mm 2 , therefore minimizing hypoxia.…”

Section: Discussionmentioning

confidence: 87%

“…However, Pecha et al found only a very weak correlation between force generation and cross sectional area. 43 Our studies used trabeculae with a mean width 1.96 ± 0.76 mm and cross-sectional area of 3.7 ± 2.1 mm 2 , therefore minimizing hypoxia. Second, Munro et al observed a high degree of variability in force generation, when normalized to cross sectional area.…”

Section: Limitationsmentioning

confidence: 99%

Effects of omecamtiv mecarbil on failing human ventricular trabeculae and interaction with (−)‐noradrenaline

Dashwood

Cheesman

Wong

et al. 2021

Pharmacology Res & Perspec

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“…Inotropic effects were given in absolute values. 15 A single cumulative concentration–effect curve was established for (−)-norepinephrine. Any additional contractions besides the 1 Hz rhythm were considered as arrhythmic.…”

Section: Methodsmentioning

confidence: 99%

“…Inotropic effects were given in absolute values. 15 A single cumulative concentration-effect curve was established for…”

Section: Contractility Measurementsmentioning

confidence: 99%

Muscarinic Receptor Activation Reduces Force and Arrhythmias in Human Atria Independent of IK,ACh

Petersen

Castro

Bengaard

et al. 2022

Journal of Cardiovascular Pharmacology

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In human hearts, muscarinic receptors (M-R) are expressed in ventricular and atrial tissue, but the acetylcholine-activated potassium current (I K,ACh ) is expressed mainly in the atrium. M-R activation decreases force and increases electrical stability in human atrium, but the impact of I K,ACh to both effects remains unclear. We used a new selective blocker of I K,ACh to elaborate the contribution of I K,ACh to M-R activation-mediated effects in human atrium. Force and action potentials were measured in rat atria and in human right atrial trabeculae. Cumulative concentration-effect curves for norepinephrine-induced force and arrhythmias were measured in the presence of carbachol (CCh; 1 mM) or CCh together with the I K,ACh -blocker XAF-1407 (1 mM) or in time-matched controls. To investigate the vulnerability to arrhythmias, we performed some experiments also in the presence of cilostamide (0.3 mM) and rolipram (1 mM), inhibiting PDE3 and PDE4. In rat atria and human right atrial trabeculae, CCh shortened the action potential duration persistently. However, the direct negative inotropy of CCh was only transient in human, but stable in rat atria. In rat and human atria, the negative inotropic effect was insensitive to blockage of I K,ACh by XAF-1407. In the presence of cilostamide and rolipram about 40% of trabeculae developed arrhythmias when exposed to norepinephrine. CCh prevented these concentration-dependent norepinephrine-induced arrhythmias, again insensitive to XAF-1407. Maximum catecholamine-induced force was not depressed by CCh. In human atrium, the direct and the indirect negative inotropic effect of CCh are independent of I K,ACh . The same applies to the CCh-mediated suppression of norepinephrine/PDEinhibition-induced arrhythmias.

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Normalization of force to muscle cross‐sectional area: A helpful attempt to reduce data scattering in contractility studies?

Cited by 8 publications

References 6 publications

Acute interaction between human epicardial adipose tissue and human atrial myocardium induces arrhythmic susceptibility

Acute interaction between human epicardial adipose tissue and human atrial myocardium induces arrhythmic susceptibility

Effects of omecamtiv mecarbil on failing human ventricular trabeculae and interaction with (−)‐noradrenaline

Muscarinic Receptor Activation Reduces Force and Arrhythmias in Human Atria Independent of IK,ACh

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