scholarly journals Troponin I phosphorylation is essential for cardiac reserve

2021 ◽  
Vol 154 (9) ◽  
Author(s):  
Sarah L. Sturgill ◽  
Lorien G. Salyer ◽  
Vikram Shettigar ◽  
Elizabeth A. Brundage ◽  
Brandon J. Biesiadecki ◽  
...  
Keyword(s):  
Heart Rate ◽  
Strain Rate ◽  
Diastolic Function ◽  
Troponin I ◽  
Contractile Function ◽  
Radial Strain ◽  
Left Ventricular ◽  
Resting Heart Rate ◽  
Cardiac Reserve ◽  
Systolic And Diastolic Function

With an increase in the body’s metabolic demand (e.g., exercise), the heart must increase its pumping performance. To achieve this increased performance, the heart relies on its cardiac reserve, which is the ability to increase its systolic and diastolic function. The mechanism responsible for cardiac reserve is poorly understood. The myofilaments are essential for contraction/relaxation, with troponin I (the inhibitory subunit of troponin, TnI) being a key regulatory protein. Studies have shown that TnI serine 23/24 (S23/S24) phosphorylation is a key mechanism for accelerating relaxation by decreasing Ca2+ sensitivity. However, the role of TnI in cardiac reserve is unknown. For this study, we characterized the systolic and diastolic reserve in TnI S23/S24 phosphorylation-null transgenic mice (S23/S24 mutated to alanine [AA] mice). Even with increased Ca2+ sensitivity, the AA mice exhibited normal function at resting heart rate with no difference in cardiac structure compared with wild type. To examine the role TnI S23/S24 phosphorylation in systolic and diastolic reserve, we assessed hemodynamics via left ventricular catheterization on the Bowditch effect (i.e., an increase in contractile function with increasing heart rate) by increasing heart rate (from 240 to 420 beats per minute) and sympathetic stimulation (dobutamine). Our data exhibited a clear loss of diastolic and systolic reserve in the AA mice with increasing heart rate and dobutamine. Since we observed a clear inability to increase systolic and diastolic function in AA mice, we performed speckle tracking echocardiography to quantitatively characterize function at resting heart rate. We observed that AA mice demonstrated normal systolic function (radial strain rate) and impaired directional diastolic function (reverse radial strain rate) at resting heart rate. We conclude that TnI S23/S24 phosphorylation is essential for cardiac reserve by enhancing systolic and diastolic function. A blunted cardiac reserve leads to heart disease making TnI S23/S24 phosphorylation a potential therapeutic strategy.

Abstract MP209: Troponin I Phosphorylation Is Essential For Cardiac Reserve

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Sarah L Sturgill ◽  
Lorien G Salyer ◽  
Vikram Shettigar ◽  
Elizabeth Brundage ◽  
Brandon J Biesiadecki ◽  
...  
Keyword(s):  
Heart Rate ◽  
Strain Rate ◽  
Diastolic Function ◽  
Troponin I ◽  
Contractile Function ◽  
Radial Strain ◽  
Left Ventricular ◽  
Resting Heart Rate ◽  
Cardiac Reserve ◽  
Systolic And Diastolic Function

In response to increase in metabolic demand (e.g., exercise), the heart must increase its pumping performance to meet this demand. To achieve this increase, the heart relies on its cardiac reserve, which is the ability to increase in its contractile and diastolic function. The mechanism responsible for cardiac reserve is poorly understood. The myofilament is the mechanism responsible for contraction and relaxation. Troponin I (the inhibitory subunit of troponin, TnI) is a key regulatory protein. Studies have shown TnI serine 23/24 (S23/S24) phosphorylation, the most abundant and important TnI phosphorylation, is a key mechanism for accelerating relaxation by decreasing Ca 2+ senstivity. The role of TnI in cardiac reserve is unknown. For this study, we thoroughly characterized the systolic and diastolic reserve in TnI S23/S24 phosphorylation-null transgenic mice (S23/S24 mutated to alanine, AA mice). Even with increased Ca 2+ sensitivity, the AA mice exhibited normal function at resting heart rate and no difference in cardiac structure compared to wildtype. To increase in vivo heart performance, the most important system is the Bowditch effect (i.e., an increase in contractile function with increasing heart rate). To examine the role TnI S23/S24 phosphorylation in systolic and diastolic reserve, we assessed hemodynamics via left ventricular catheterization on the Bowditch effect by increasing heart rate from 240 to 420 beats per minute. Our data exhibited a clear loss of diastolic and systolic reserve in the AA mice. Since we observed a clear inability to increase systolic and diastolic function in AA mice, we performed speckle tracking echocardiography to more quantitatively investigate AA mice function. We observed that AA mice demonstrated normal systolic function (radial strain rate) and impaired directional diastolic function (reverse radial strain rate) at resting heart rate. We conclude that TnI S23/S24 phosphorylation is essential for cardiac reserve by enhancing systolic and diastolic function. A blunted cardiac reserve leads to heart disease making TnI S23/S24 phosphorylation a potential therapeutic strategy.

Changes in vascular and cardiac function after prolonged strenuous exercise in humans

2008 ◽  
Vol 105 (5) ◽  
pp. 1562-1568 ◽  
Author(s):  
Ellen A. Dawson ◽  
Greg P. Whyte ◽  
Mark A. Black ◽  
Helen Jones ◽  
Nicola Hopkins ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Strain Rate ◽  
Vascular Function ◽  
Troponin I ◽  
Venous Blood ◽  
Radial Strain ◽  
Left Ventricular ◽  
Strenuous Exercise ◽  
Cardiac Strain ◽  
The Impact

Prolonged exercise has been shown to result in an acute depression in cardiac function. However, little is known about the effect of this type of exercise on vascular function. Therefore, the purpose of the present study was to investigate the impact of an acute bout of prolonged strenuous exercise on vascular and cardiac function and the appearance of biomarkers of cardiomyocyte damage in 15 male (32 ± 10 yr) nonelite runners. The subjects were tested on two occasions, the day before and within an hour of finishing the London marathon (229 ± 38 min). Function of the brachial and femoral arteries was determined using flow-mediated dilatation (FMD). Echocardiographic assessment of cardiac strain, strain rate, tissue velocities, and flow velocities during diastole and systole were also obtained. Venous blood samples were taken for later assessment of cardiac troponin I (cTnI), a biomarker of cardiomyocyte damage. Completion of the marathon resulted in a depression in femoral ( P = 0.04), but not brachial ( P = 0.96), artery FMD. There was no change, pre- vs. postmarathon, in vascular shear, indicating that the impaired femoral artery function was not related to hemodynamic changes. The ratio of peak early to atrial radial strain rate, a measure of left ventricular diastolic function, was reduced postmarathon ( P = 0.006). Postrace cTnI was elevated in 12 of 13 runners, with levels above the recognized clinical threshold for damage in 7 of these. In conclusion, when taken together, these data suggest a transient depression in cardiac and leg vascular function following prolonged intensive exercise.

P183 Arterial stiffness was inversely associated with left ventricular diastolic function in indigenous Papuan populations

2020 ◽  
Vol 41 (Supplement_1) ◽  
Author(s):  
A Ishida ◽  
A Isotani ◽  
M Fujisawa ◽  
E Garcia Del Saz ◽  
K Okumiya ◽  
...  
Keyword(s):  
Heart Rate ◽  
Diastolic Function ◽  
Wave Velocity ◽  
Wave Reflection ◽  
Left Ventricular ◽  
Volume Index ◽  
Arterial Hemodynamics ◽  
Age Related ◽  
Systolic And Diastolic Function ◽  
Lv Diastolic Function

Abstract Background Age-related increase in systolic pressure is known to be absent in indigenous Papuan populations, partially because of their life-long low-sodium and high-potassium diets. Purpose The aim of this study was to investigate the age-related change in left ventricular (LV) systolic and diastolic function and the relationship with arterial hemodynamics among the indigenous Papuan highland people.  Methods Indices of arterial hemodynamics were measured using oscillometric brachial cuff-based sphygmomanometer (Mobil-O-Graph). Brachial-ankle pulse wave velocity (baPWV) was measured using a semiautomatic device (form ABI/baPWV). LV systolic and diastolic function was evaluated by 2-dimensional echocardiography and tissue-Doppler imaging using Vivid iq. Results A total of 81 native Papuans (median age 42 years, 47% women) were enrolled in this study. None of the subjects took any medicines, particularly antihypertensive drugs. All participants presented in sinus rhythm. With ageing, LV mass index remained unchanged, and LV ejection fraction increased, but mildly reduced (40–50%) in 3 participants. Transmitral E-wave velocity slightly decrease but the change was not significant. Transmitral A-wave velocity markedly increased (ρ=0.60, P < 0.001) and E/A ratio decreased with age (ρ=-0.52, P < 0.001). Age-related change of E-wave deceleration time was not significant. Septal e′ (ρ=-0.60, P < 0.001) and lateral e′ decreased (ρ=-0.53, P < 0.001) and average E/e′ increased with age (ρ=0.44, P < 0.001). Left atrial volume index did not change significantly with age. In multivariate regression analysis, baPWV was independently associated with E/e" ratio both before and after adjustment for age, sex, body mass index, mean arterial pressure, and heart rate; however, indices of wave reflection including augmentation index and reflection magnitude were not associated with E/e′. Only age and heart rate were inversely associated with E/A ratio.  Conclusion LV systolic function was preserved in indigenous Papuan populations; however, LV diastolic function decreased with ageing. Age-related arterial stiffening, not wave reflection, was inversely related to LV diastolic function.

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