Endogenous Mechanisms for Regulating Myocardial Contractility

Schreckenberg, Rolf

doi:10.1007/978-3-319-31251-4_5

Cited by 3 publications

(3 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The increase in cytosolic calcium from 10 À7 molÁL À1 to approximately 10 À5 molÁL À1 is almost entirely due to sarcoplasmic calcium and can be viewed as an initial step in the contraction. The magnitude and dynamics of calcium transients are mainly under the control of PKA, which, after stimulation of β-adrenoceptors, regulates the release via phosphorylation of the L-type calcium channel as well as RyR2 and, via phospholamban, the activity of SERCA2a and, thus, the return of calcium to the SR (Schreckenberg, 2016).…”

Section: Discussionmentioning

confidence: 99%

Cardiac side effects of RNA‐based SARS‐CoV‐2 vaccines: Hidden cardiotoxic effects of mRNA‐1273 and BNT162b2 on ventricular myocyte function and structure

Schreckenberg,

Woitasky,

Itani

et al. 2023

British J Pharmacology

Self Cite

View full text Add to dashboard Cite

Background and PurposeTo protect against SARS‐CoV‐2 infection, the first mRNA‐based vaccines, Spikevax (mRNA‐1273, Moderna) and Comirnaty (BNT162b2, Pfizer/Biontech), were approved in 2020. The structure and assembly of the immunogen – in both cases, the SARS‐CoV‐2 spike (S) glycoprotein – are determined by a messenger RNA sequence that is translated by endogenous ribosomes. Cardiac side effects, which for the most part can be classified by their clinical symptoms as myo‐ and/or pericarditis, can be caused by both mRNA‐1273 and BNT162b2.Experimental ApproachAs persuasive theories for the underlying pathomechanisms have yet to be developed, this study investigated the effect of mRNA‐1273 and BNT162b2 on the function, structure, and viability of isolated adult rat cardiomyocytes over a 72 h period.Key ResultsIn the first 24 h after application, both mRNA‐1273 and BNT162b2 caused neither functional disturbances nor morphological abnormalities. After 48 h, expression of the encoded spike protein was detected in ventricular cardiomyocytes for both mRNAs. At this point in time, mRNA‐1273 induced arrhythmic as well as completely irregular contractions associated with irregular as well as localized calcium transients, which provide indications of significant dysfunction of the cardiac ryanodine receptor (RyR2). In contrast, BNT162b2 increased cardiomyocyte contraction via significantly increased protein kinase A (PKA) activity at the cellular level.Conclusions and ImplicationsHere we demonstrated for the first time, that in isolated cardiomyocytes, both mRNA‐1273 and BNT162b2 induce specific dysfunctions that correlate pathophysiologically to cardiomyopathy. Both RyR2 impairment and sustained PKA activation may significantly increase the risk of acute cardiac events.

show abstract

Section: Discussionmentioning

confidence: 99%

Cardiac side effects of RNA‐based SARS‐CoV‐2 vaccines: Hidden cardiotoxic effects of mRNA‐1273 and BNT162b2 on ventricular myocyte function and structure

Schreckenberg,

Woitasky,

Itani

et al. 2023

British J Pharmacology

Self Cite

View full text Add to dashboard Cite

show abstract

“…For the example in Fig. 4a, after 42 h, we observe the spontaneous transition into tachycardia which is typically accompanied by increased myocardial tension at elevated beating rates (Bowditch effect), a fundamental process underlying the force-frequency relationship of the heart 20 . At the cellular level, this is caused by increased contractility, which we detected as a step-like increase in the maximum and baseline ext (black arrow in Fig.…”

Section: Single Cell Barcodingmentioning

confidence: 96%

Monitoring contractility in cardiac tissue with cellular resolution using biointegrated microlasers

et al. 2020

View full text Add to dashboard Cite

“…For the example in Fig. 4a, after 42 h, we observe the spontaneous transition into tachycardia which is typically accompanied by increased myocardial tension at elevated beating rates (Bowditch effect), a fundamental process underlying the force-frequency relationship of the heart 21 . At the cellular level, this is caused by increased contractility, which we detected as a step-like increase in the maximum and baseline n ext (black arrow in Fig.…”

mentioning

confidence: 96%

Monitoring contractility in single cardiomyocytes and whole hearts with bio-integrated microlasers

Schubert

Woolfson

et al. 2019

Preprint

View full text Add to dashboard Cite

12Cardiac regeneration and stem cell therapies depend critically on the ability to locally resolve the 13 contractile properties of heart tissue 1,2 . Current regeneration approaches explore the growth of 14 cardiac tissue in vitro and the injection of stem cell-derived cardiomyocytes 3-6 (CMs) but scientists 15 struggle with low engraftment rates and marginal mechanical improvements, leaving the estimated 16 26 million patients suffering from heart failure worldwide without effective therapy 7-9 . One 17 impediment to further progress is the limited ability to functionally monitor injected cells as 18 currently available techniques and probes lack speed and sensitivity as well as single cell specificity. 19 Here, we introduce microscopic whispering gallery mode (WGM) lasers into beating cardiomyocytes 20to realize all-optical recording of transient cardiac contraction profiles with cellular resolution. The 21 brilliant emission and high spectral sensitivity of microlasers to local changes in refractive index 22

show abstract

Endogenous Mechanisms for Regulating Myocardial Contractility

Cited by 3 publications

References 54 publications

Cardiac side effects of RNA‐based SARS‐CoV‐2 vaccines: Hidden cardiotoxic effects of mRNA‐1273 and BNT162b2 on ventricular myocyte function and structure

Cardiac side effects of RNA‐based SARS‐CoV‐2 vaccines: Hidden cardiotoxic effects of mRNA‐1273 and BNT162b2 on ventricular myocyte function and structure

Monitoring contractility in cardiac tissue with cellular resolution using biointegrated microlasers

Monitoring contractility in single cardiomyocytes and whole hearts with bio-integrated microlasers

Contact Info

Product

Resources

About