scholarly journals Stretching single titin molecules from failing human hearts reveals titin’s role in blunting cardiac kinetic reserve

2019 ◽  
Vol 116 (1) ◽  
pp. 127-137
Author(s):  
Mei-Pian Chen ◽  
Salome A Kiduko ◽  
Nancy S Saad ◽  
Benjamin D Canan ◽  
Ahmet Kilic ◽  
...  
Keyword(s):  
Heart Rate ◽  
Single Molecule ◽  
Left Ventricular ◽  
Passive Tension ◽  
Frequency Dependent ◽  
Heart Rates ◽  
Human Cardiomyocytes ◽  
Sarcomeric Protein ◽  
Novel Approach ◽  
Speed Up

Abstract Aims Heart failure (HF) patients commonly experience symptoms primarily during elevated heart rates, as a result of physical activities or stress. A main determinant of diastolic passive tension, the elastic sarcomeric protein titin, has been shown to be associated with HF, with unresolved involvement regarding its role at different heart rates. To determine whether titin is playing a role in the heart rate (frequency-) dependent acceleration of relaxation (FDAR). W, we studied the FDAR responses in live human left ventricular cardiomyocytes and the corresponding titin-based passive tension (TPT) from failing and non-failing human hearts. Methods and results Using atomic force, we developed a novel single-molecule force spectroscopy approach to detect TPT based on the frequency-modulated cardiac cycle. Mean TPT reduced upon an increased heart rate in non-failing human hearts, while this reduction was significantly blunted in failing human hearts. These mechanical changes in the titin distal Ig domain significantly correlated with the frequency-dependent relaxation kinetics of human cardiomyocytes obtained from the corresponding hearts. Furthermore, the data suggested that the higher the TPT, the faster the cardiomyocytes relaxed, but the lower the potential of myocytes to speed up relaxation at a higher heart rate. Such poorer FDAR response was also associated with a lesser reduction or a bigger increase in TPT upon elevated heart rate. Conclusions Our study established a novel approach in detecting dynamic heart rate relevant tension changes physiologically on native titin domains. Using this approach, the data suggested that the regulation of kinetic reserve in cardiac relaxation and its pathological changes were associated with the intensity and dynamic changes of passive tension by titin.

scholarly journals Heart Rate–Induced Myocardial Ca 2+ Retention and Left Ventricular Volume Loss in Patients With Heart Failure With Preserved Ejection Fraction

2020 ◽  
Vol 9 (17) ◽  
Author(s):  
Daniel N. Silverman ◽  
Mehdi Rambod ◽  
Daniel L. Lustgarten ◽  
Robert Lobel ◽  
Martin M. LeWinter ◽  
...  
Keyword(s):  
Heart Failure ◽  
Heart Rate ◽  
Ejection Fraction ◽  
Sinus Rhythm ◽  
Left Ventricular ◽  
Atrial Pacing ◽  
Preserved Ejection Fraction ◽  
Volume Loss ◽  
Heart Rates ◽  
Patients With Heart Failure

Background Increases in heart rate are thought to result in incomplete left ventricular (LV) relaxation and elevated filling pressures in patients with heart failure with preserved ejection fraction (HFpEF). Experimental studies in isolated human myocardium have suggested that incomplete relaxation is a result of cellular Ca 2+ overload caused by increased myocardial Na + levels. We tested these heart rate paradigms in patients with HFpEF and referent controls without hypertension. Methods and Results In 22 fully sedated and instrumented patients (12 controls and 10 patients with HFpEF) in sinus rhythm with a preserved ejection fraction (≥50%) we assessed left‐sided filling pressures and volumes in sinus rhythm and with atrial pacing (95 beats per minute and 125 beats per minute) before atrial fibrillation ablation. Coronary sinus blood samples and flow measurements were also obtained. Seven women and 15 men were studied (aged 59±10 years, ejection fraction 61%±4%). Patients with HFpEF had a history of hypertension, dyspnea on exertion, concentric LV remodeling and a dilated left atrium, whereas controls did not. Pacing at 125 beats per minute lowered the mean LV end‐diastolic pressure in both groups (controls −4.3±4.1 mm Hg versus patients with HFpEF −8.5±6.0 mm Hg, P =0.08). Pacing also reduced LV end‐diastolic volumes. The volume loss was about twice as much in the HFpEF group (controls −15%±14% versus patients with HFpEF −32%±11%, P =0.009). Coronary venous [Ca 2+ ] increased after pacing at 125 beats per minute in patients with HFpEF but not in controls. [Na + ] did not change. Conclusions Higher resting heart rates are associated with lower filling pressures in patients with and without HFpEF. Incomplete relaxation and LV filling at high heart rates lead to a reduction in LV volumes that is more pronounced in patients with HFpEF and may be associated with myocardial Ca 2+ retention.

Effect of heart rate on myocardial blood flow in dogs with left ventricular hypertrophy

1980 ◽  
Vol 239 (5) ◽  
pp. H621-H627
Author(s):  
T. R. Vrobel ◽  
W. S. Ring ◽  
R. W. Anderson ◽  
R. W. Emery ◽  
R. J. Bache
Keyword(s):  
Heart Rate ◽  
Blood Flow ◽  
Left Ventricular Hypertrophy ◽  
Myocardial Blood Flow ◽  
Ventricular Hypertrophy ◽  
Lateral Wall ◽  
Left Ventricular ◽  
Myocardial Mass ◽  
Previous Suggestion ◽  
Heart Rates

Because of the previous suggestion that subendocardial perfusion may be inadequate in the hypertrophied heart, this study was carried out to examine the response of transmural myocardial blood flow to pacing induced tachycardia in dogs with chronic left ventricular hypertrophy. Myocardial hypertrophy, produced by banding the ascending aorta of puppies at 5-6 wk of age, resulted in an 87% average increase in relative left ventricular mass compared with the control dogs. Myocardial blood flow was examined during ventricular pacing at heart rates of 100, 200, and 250 beats/min using radionuclide-labeled microspheres. Mean blood flow per unit myocardial mass was similar in the two groups of dogs at a heart rate of 100 beats/min and increased regularly during pacing in both groups of animals. Increasing heart rates did not change the transmural pattern of myocardial blood flow in the normal dogs, but in the animals with left ventricular hypertrophy pacing at 250 beats/min resulted in a significant redistribution of perfusion away from the subendocardium, with the ratio of subendocardial/subepicardial blood flow falling from 1.03 +/- 0.08 at 100 beats/min to 0.83 +/0 0.06 at 250 beats/min (P < 0.01). This redistribution of blood flow away from the subendocardium was especially marked in the regions encompassing the papillary muscles and the intervening left ventricular lateral wall.

scholarly journals Hemodynamic Consequence of Different Pacing Modes after Aortic Valve Replacement

2018 ◽  
Vol 21 (2) ◽  
pp. 090
Author(s):  
Arndt H Kiessling
Keyword(s):  
Heart Rate ◽  
Cardiac Output ◽  
Aortic Valve ◽  
Left Ventricular Hypertrophy ◽  
Aortic Valve Replacement ◽  
Diastolic Function ◽  
Valve Replacement ◽  
Ventricular Hypertrophy ◽  
Left Ventricular ◽  
Heart Rates

Objectives: Ventricular pacemaker stimulation may cause deterioration of hemodynamics in patients with left-ventricular hypertrophy following aortic valve replacement. Since the diastolic function is often impaired, it remains unclear which heart rate best optimizes cardiac output. Low heart rates are suggested to treat impaired diastolic function chronically, but it is possible that cardiac output may be augmented by increasing the heart rate in patients with a fixed stroke volume (SV). The aim of this study is the identification of the best pacing mode and heart rate for the surrogate parameter SV and cardiac index(CI) in patients with left ventricular hypertrophy.Methods: Various pacemaker stimulation modes and different heart rates, as well as their influence on hemodynamics, were tested following aortic valve replacement in 48 patients with severe left-ventricular hypertrophy (Intraventricular septum (IVS)>1.5 cm) and aortic stenosis. SV and cardiac output were recorded by pulse curve analysis. Four modes of stimulation (right ventricular pacemaker stimulation (DDDright), left ventricular pacemaker stimulation (DDDleft), biventricular pacemaker stimulation (DDDbi), atrial pacemaker stimulation (AAI)) were documented at five different rates (60, 80, 100, 120, 140 beats/min) and three different postoperative time points (intraoperatively, 3h and 24h postoperatively).Results: The highest CI was found at linear rates between 60 to 140bpm. AAI was the best mode of stimulation in the majority of cases (35%), but in others, either left, right and/or biventricular stimulation was found to be better (15%). SV showed a u-shaped trend with a peak at 100 beats/min.Conclusion: An increase in the heart rate does not lead to a notable drop in SV postoperatively in left-ventricular hypertrophy; hence a rise in cardiac output can be anticipated up to a rate of 100 beats/min. A standardized response in terms of an ideal pacemaker stimulation mode could not be identified.

Hypertrophic Cardiomyopathy: Non-Invasive Assessment of Diastolic and Systolic Functional Parameters in Relation to Heart Rate

1985 ◽  
Vol 24 (05) ◽  
pp. 196-200
Author(s):  
R. P. Spielmann ◽  
M. Geiger ◽  
A. Clausen ◽  
K.-H. Kuck ◽  
R. Montz ◽  
...  
Keyword(s):  
Heart Rate ◽  
Hypertrophic Cardiomyopathy ◽  
Radionuclide Ventriculography ◽  
Left Ventricular ◽  
Right Atrial ◽  
Atrial Pacing ◽  
Heart Rates ◽  
Ventricular Compliance ◽  
The Individual ◽  
Left Ventricular Compliance

SummaryHypertrophic cardiomyopathy (HC) is characterized by reduced left ventricular compliance and subsequent filling abnormalities. To study the pathophysiologic changes in parameters of left ventricular systolic and diastolic performance as a function of increasing heart rate 14 patients with HC (32 ± 12 yrs; 11 M, 4 F) and 4 normal individuals were subjected to equilibrium radionuclide ventriculography (99mTc-labelled red blood cells) at rest and during incremental right atrial pacing; heart rate was increased in steps of 20 beats per min from basal state to the individual symptom-limited endpoint. Mean symptom-limited heart rate was 141 ± 28 in HC and 160 in normals (p <.01.). At each pacing level filling and ejection parameters as well as the left ventricular endsystolic (LVESV) and enddiastolic volume (LVEDV) were determined relative to resting volumes at a heart rate of 78 ± 8. At the individual maximal pacing rate HC revealed a decline in LVEDV to 61 ± 4 % (p C.001) and an increase in LVESV to 117 ± 14% (p <.001) resulting in decreasing ejection fractions at heart rates above 120. Peak LV filling rates initially increased but subsequently decreased steeply at heart rates above 100; peak LV ejection rates in HC showed a similar pattern with increasing frequency. Time inter- vais to peak ejection and peak filling rate did not differ from normal. Thus, patients with HC demonstrated combined left ventricular diastolic and systolic abnormalities with increasing heart rate leading into a low-input low-output circulatory state. This probably explains not only the symptoms associated with HC, but also supports the concept of “hemodynamic syncope” in HC.

The Effect of Swimming Activity and Section of the Vagus Nerves on Heart Rate in Rainbow Trout

1974 ◽  
Vol 60 (2) ◽  
pp. 305-319 ◽  
Author(s):  
IMANTS G. PRIEDE
Keyword(s):  
Heart Rate ◽  
Maximum Rate ◽  
Critical Speed ◽  
Swimming Activity ◽  
Vagus Nerves ◽  
Maximum Heart Rate ◽  
Heart Rates ◽  
Cardiac Responses ◽  
Different Temperatures ◽  
Speed Up

1. Heart rates associated with swimming activity were measured in intact and vagotomized fish at 6.5 and 15 °C. 2. Low swimming speeds had no effect on heart rate but above a threshold speed it increased logarithmically with swimming speed up to the critical speed and maximum heart rate. 3. Times for recovery after exercise increased rapidly above the critical speed. 4. Bilaterally vagotomized fish at 6.5 °C showed high resting heart rates and erratic cardiac responses to exercise. 5. In bilaterally vagotomized fish at 15 °C heart rates were normal except for a low maximum rate. 6. It is concluded that the vagus nerve can function differently at different temperatures.

Heart rate-independent energetics and systolic pressure-volume area in dog heart

1983 ◽  
Vol 244 (2) ◽  
pp. H206-H214 ◽  
Author(s):  
H. Suga ◽  
R. Hisano ◽  
S. Hirata ◽  
T. Hayashi ◽  
O. Yamada ◽  
...  
Keyword(s):  
Heart Rate ◽  
Oxygen Consumption ◽  
Left Ventricle ◽  
Mechanical Energy ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Canine Heart ◽  
Heart Rates ◽  
Dog Heart ◽  
Total Mechanical Energy

Left ventricular (LV) systolic pressure-volume area (PVA), a new measure of total mechanical energy for the contraction, linearly correlates with its oxygen consumption per beat (VO2) regardless of contraction mode in a canine heart with stable chronotropism and inotropism. PVA is the area in the pressure-volume (PV) diagram circumscribed by the end-systolic and end-diastolic PV relation curves and the systolic segment of the PV loop and has dimensions of energy. We investigated whether primary changes in heart rate would affect the VO2-PVA relation. In the excised cross-circulated canine heart with left ventricular load controlled with a servo pump, we changed heart rate by pacing to compare the VO2-PVA relations at low [124 +/- 17 (SD) min-1] and high (193 +/- 23) heart rates. In 15 left ventricles, VO2 (ml O2 X beat-1 X 100 g LV-1) was (1.75 +/- 0.57) X 10(-5) PVA (mmHg X ml X beat-1 X 100 g LV-1) + 0.031 +/- 0.011 (ml O2 X beat-1 X 100 g LV-1). The VO2-PVA relation was virtually independent of heart rate in individual hearts. We conclude that the load-independent VO2-PVA relationship is not affected by chronotropism in a given canine left ventricle.

Abstract 253: Complete Reversal of Xylazine-induced Bradycardia With Intralipid in Female Mice

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Negar Motayagheni ◽  
Mansoureh Eghbali
Keyword(s):  
Heart Rate ◽  
Cardiac Arrest ◽  
Isolated Heart ◽  
Ischemia Reperfusion ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Ventricular Pressure ◽  
Control Group ◽  
Heart Rates ◽  
Female Mice

Sudden cardiac arrest accounts for 300 000 to 400 000 deaths annually in united states both in men and women. Cardiac arrest could be due to abnormally slow heart rate known as bradycardia. Bradycardia is a catastrophic event which is associated with significant mortality and morbidity. We have previously shown that Intralipid, an emulsion of soy bean oil, egg yolk phospholipids and glycerol, protects the heart against ischemia/reperfusion injury as well as Bupivacaine induced cardiotoxicity. Here we examined whether intralipid can protects the heart against bradycardia. Wild type female mice C57/Bl6 (2-4 month old) were anesthetized by isoflurane after heparinization. The heart was removed immediately and placed in cold Krebs-Henseleit buffer. The aorta was cannulated and the isolated heart (Langendorff) was perfused with Krebs-Henseleit at 37°C for 15 min for stabilization. Xylazine (100-300 mg) was directly applied to the heart surface for 1-2 min until bradycardia was achieved. The heart was then perfused with either Krebs-Henseleit (KH) solution (control group), or 1% ILP (intralipid group). Hemodynamic parameters and heart rates were recorded with a catheter directly inserted into left ventricle (n=5-8 per group). The heart rates at the baseline before inducing bradycardia was 224±7 beats/min and the left ventricular pressures was 64±4 mmHg. Administration of Xylazine decreased the heart rate significantly to 81±9 beats/min and left ventricular pressure to 5±2 mmHg (p<0.001). Perfusion of the heart with intralipid rapidly restored the heart rate to 209±30 and left ventricular pressure to 59±4 which were not significantly different than their values before inducing bradycardia at the baseline. In the hearts that received Krebs-Henseleit after bradycardia, the heart rate (81±10 beats/min) and left ventricular pressure (20±8 mmHg) were significantly lower than intralipid group. In conclusion Intralipid has the ability to rapidly reverse bradycardia in female mice.

Bainbridge reflex in conscious, unrestrained, and tranquilized baboons

1981 ◽  
Vol 240 (2) ◽  
pp. H164-H167 ◽  
Author(s):  
S. F. Vatner ◽  
M. Zimpfer
Keyword(s):  
Heart Rate ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Ventricular Pressure ◽  
Increase Heart Rate ◽  
Cardiac Rate ◽  
Volume Loading ◽  
Heart Rates ◽  
Cholinergic Blockade ◽  
Bilateral Vagotomy

The effects of volume loading were examined in conscious, unrestrained, and tranquilized baboons (20-25 kg) 1-3 mo after instrumentation with miniature left ventricular pressure and diameter gauges. The response to volume loading was accompanied by significant increases (P less than 0.01) in cardiac rate (32 +/- 4 beats/min) in tranquilized baboons. When rapid saline infusion was accomplished in conscious unrestrained baboons by means of activating a remote-controlled interrogator, heart rate also rose significantly (41 +/- 8 beats/min, P less than 0.01). After cholinergic blockade with atropine, ganglionic blockade with hexamethonium, bilateral vagotomy, or combined cholinergic and beta-adrenergic blockades, volume loading failed to increase heart rate. In two smaller (12-14 kg) intact conscious baboons with relatively high spontaneous heart rates, volume loading did not alter heart rate. These experiments suggest that the Bainbridge reflex exists in larger primates with relatively low spontaneous heart rates.

Cardiac performance: independence of adrenergic inotropic and chronotropic effects

1978 ◽  
Vol 234 (5) ◽  
pp. H525-H532
Author(s):  
A. Ilebekk ◽  
J. Lekven ◽  
F. Kiil
Keyword(s):  
Heart Rate ◽  
Stroke Volume ◽  
Ventricular Volume ◽  
Left Ventricular ◽  
Right Atrial ◽  
Diastolic Filling ◽  
Atrial Pacing ◽  
Heart Rates ◽  
Systolic Volume ◽  
End Diastolic Volume

During right atrial pacing in open-chest anesthetized dogs, the relationships between reduction in stroke volume and rise in heart rate were identical in control experiments, during intravenous infusion of isoproterenol, and after blockade of adrenergic beta-receptors by propranolol. To examine the mechanism of this constant relationship, left ventricular volume was estimated by continuous recordings of myocardial chord length (MCL) between ultrasonic elements inserted into the anterior ventricular wall. Diastolic filling curves were curtailed by raising heart rate and end-diastolic MCL was reduced. At constant heart rate, end-diastolic MCL was not altered by isoproterenol infusion, except for a slight rise at heart rates exceeding 220 beats/min. End-systolic MCL, however, was reduced, accounting for larger stroke volume during isoproterenol than during propranolol infusion. The reduction in end-systolic MCL was constant at all heart rates examined. Hence, chronotropic changes influence end-diastolic volume and inotropic changes influence end-systolic volume; their effects on stroke volume regulation are, therefore, virtually independent.

scholarly journals Simultaneous multicolor DNA-PAINT without sequential fluid exchange using spectral demixing

2021 ◽  
Author(s):  
Niclas Gimber ◽  
Sebastian Strauss ◽  
Ralf Jungmann ◽  
Jan Schmoranzer
Keyword(s):  
Single Molecule ◽  
Spatial Relationship ◽  
Dna Origami ◽  
Fluid Exchange ◽  
Nanoscale Structures ◽  
Novel Approach ◽  
Speed Up ◽  
Localization Precision ◽  
Relationship Of ◽  
Single Molecule Localization Microscopy

Several variants of multicolor single-molecule localization microscopy (SMLM) have been developed to resolve the spatial relationship of nanoscale structures in biological samples. The oligonucleotide-based SMLM approach DNA-PAINT robustly achieves nanometer localization precision and can be used to count binding sites within nanostructures. However, multicolor DNA-PAINT has primarily been realized by Exchange-PAINT that requires sequential exchange of the imaging solution and thus leads to extended acquisition times. To alleviate the need for fluid exchange and to speed up the acquisition of current multichannel DNA-PAINT, we here present a novel approach that combines DNA-PAINT with simultaneous multicolor acquisition using spectral demixing (SD). By using newly designed probes and a novel multichannel registration procedure we achieve simultaneous multicolor SD-DNA-PAINT with minimal crosstalk. We demonstrate high localization precision (3 - 6 nm) and multicolor registration of dual and triple-color SD-DNA-PAINT by resolving patterns on DNA origami nanostructures and cellular structures.

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