A method to reconstruct myocardial sarcomere lengths and orientations at transmural sites in beating canine hearts

1992 ◽  
Vol 263 (1) ◽  
pp. H293-H306 ◽  
Author(s):  
E. K. Rodriguez ◽  
W. C. Hunter ◽  
M. J. Royce ◽  
M. K. Leppo ◽  
A. S. Douglas ◽  
...  
Keyword(s):  
Sarcomere Length ◽  
Deformation Gradient ◽  
Local Deformation ◽  
Left Ventricular ◽  
Reference State ◽  
Cellular Processes ◽  
Chamber Volume ◽  
Length Changes ◽  
Whole Heart ◽  
Cyclic Changes

The ability to measure cyclic changes in myocardial sarcomere lengths and orientations during cardiac ejection and filling would improve our understanding of how the cellular processes of contraction relate to the pumping of the whole heart. Previously, only postmortem sarcomere measurements were possible after arresting the heart in one state and fixing it for histology. By combining such histological measurements with direct observations of the deformation experienced by the same myocardial region while the heart was beating, we have developed a method to reconstruct sarcomere lengths and orientations throughout the cardiac cycle and at several transmural layers. A set of small (1 mm) radiopaque beads was implanted in approximately 1 cm3 of the left ventricular free wall. Using biplane cineradiography, we tracked the motion of these markers through various cardiac cycles. To quantify local myocardial deformation (as revealed by the relative motion of the markers), we calculated the local deformation gradient tensors. As the heart deforms, these describe how any short vectorial line segment alters its length and orientation relative to a reference state. Specifically, by choosing the reference state to be the arrested and fixed heart and by measuring the sarcomere vector in that state, we could then use the deformation gradient tensors to reconstruct the sarcomere vector that would exist in the beating heart. As ventricular chamber volume varied over its normal range of operation, the range of reconstructed sarcomere lengths (approximately 1.7-2.4 microns) was comparable to other histological studies and to measurements of sarcomere length in excised papillary muscles or trabeculae. The pattern of sarcomere length changes was markedly different, however, during ejection vs. filling.

In vivo microvascular structural and functional consequences of muscle length changes

1997 ◽  
Vol 272 (5) ◽  
pp. H2107-H2114 ◽  
Author(s):  
D. C. Poole ◽  
T. I. Musch ◽  
C. A. Kindig
Keyword(s):  
Blood Flow ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Oxygen Delivery ◽  
Sarcomere Length ◽  
Flow Dynamics ◽  
Capillary Diameter ◽  
Luminal Diameter ◽  
Length Changes

As muscles are stretched, blood flow and oxygen delivery are compromised, and consequently muscle function is impaired. We tested the hypothesis that the structural microvascular sequellae associated with muscle extension in vivo would impair capillary red blood cell hemodynamics. We developed an intravital spinotrapezius preparation that facilitated direct on-line measurement and alteration of sarcomere length simultaneously with determination of capillary geometry and red blood cell flow dynamics. The range of spinotrapezius sarcomere lengths achievable in vivo was 2.17 +/- 0.05 to 3.13 +/- 0.11 microns. Capillary tortuosity decreased systematically with increases of sarcomere length up to 2.6 microns, at which point most capillaries appeared to be highly oriented along the fiber longitudinal axis. Further increases in sarcomere length above this value reduced mean capillary diameter from 5.61 +/- 0.03 microns at 2.4-2.6 microns sarcomere length to 4.12 +/- 0.05 microns at 3.2-3.4 microns sarcomere length. Over the range of physiological sarcomere lengths, bulk blood flow (radioactive microspheres) decreased approximately 40% from 24.3 +/- 7.5 to 14.5 +/- 4.6 ml.100 g-1.min-1. The proportion of continuously perfused capillaries, i.e., those with continuous flow throughout the 60-s observation period, decreased from 95.9 +/- 0.6% at the shortest sarcomere lengths to 56.5 +/- 0.7% at the longest sarcomere lengths and was correlated significantly with the reduced capillary diameter (r = 0.711, P < 0.01; n = 18). We conclude that alterations in capillary geometry and luminal diameter consequent to increased muscle sarcomere length are associated with a reduction in mean capillary red blood cell velocity and a greater proportion of capillaries in which red blood cell flow is stopped or intermittent. Thus not only does muscle stretching reduce bulk blood (and oxygen) delivery, it also alters capillary red blood cell flow dynamics, which may further impair blood-tissue oxygen exchange.

Abstract 13820: Diastolic Dysfunction is Not Associated With Increased Diastolic Calcium During Experimental Uremic Cardiomyopathy

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Pamela D Winterberg ◽  
Rong Jiang ◽  
Bo Wang ◽  
Sonal Harbaran ◽  
Mary B Wagner
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Left Ventricular Hypertrophy ◽  
Diastolic Dysfunction ◽  
Ventricular Hypertrophy ◽  
Sarcomere Length ◽  
Treatment Options ◽  
Strain Analysis ◽  
Left Ventricular ◽  
Uremic Cardiomyopathy ◽  
Underlying Mechanisms

Introduction: The underlying mechanisms contributing to uremic cardiomyopathy during chronic kidney disease (CKD) are poorly understood, limiting treatment options. Hypothesis: We aimed to determine if altered calcium (Ca2+) handling in cardiomyocytes contributes to diastolic dysfunction in a mouse model of CKD. Methods: CKD was induced in male 129X1/SvJ mice through five-sixths nephrectomy in a two-stage surgery. Age-matched mice served as controls. Transthoracic echocardiography and speckle-tracking based strain analysis (Vevo2100, VisualSonics, Toronto, Canada) were performed at 8 weeks post-CKD (n=7-8) to assess heart structure and function. Cardiomyocytes isolated from mice with or without CKD (n=3 mice per group, 10-12 cells/mouse) were loaded with Fura 2-AM, paced by field stimulation (1 Hz), and imaged with a dual-excitation fluorescence photomultiplier system (IonOptix Inc, Milton, MA) to measure Ca2+ transients and sarcomere length. Sarcoplasmic reticulum Ca2+ content was determined following rapid application of caffeine.[[Unable to Display Character: &#8232;]] Results: CKD mice displayed left ventricular hypertrophy (LVAW;d 1.46 ± 0.134 vs 1.04 ± 0.129 mm; p<0.001) and decreased longitudinal strain (19 ± 4.1% vs 30 ± 2.3%; p<0.0001) compared to control mice. Resting sarcomere length was significantly shorter in cardiomyocytes isolated from CKD mice compared to normal mice (1.86 ± 0.054 vs 1.89 ± 0.047 nm; p = 0.016), but relaxation time was unchanged (0.21 ± 0.12 vs 0.21 ± 0.15 seconds, p=0.4). Unexpectedly, the baseline cytosolic Ca2+ content was lower in uremic myocytes (1.22 ± 0.353 vs 1.46 ± 0.252 AU, p=0.002). However, the Ca2+ transient amplitude (0.39 ± 0.177 vs 0.41 ± 0.167 AU, p=0.4) and sarcoplasmic reticulum Ca2+ content (1.15 ± 0.321 vs 1.24 ± 0.550 AU, p=0.4) were comparable between CKD and normal cardiomyocytes.[[Unable to Display Character: &#8232;]] Conclusions: Mice with CKD have signs of left ventricular hypertrophy and diastolic dysfunction on echocardiography. Cardiomyocytes isolated from mice with CKD have shorter diastolic sarcomere length implying impaired relaxation, yet paradoxically have decreased diastolic calcium. Thus Ca2+ accumulation during diastole does not appear to contribute to impaired relaxation in this model.

Abstract 5402: Two Photon Microscopy Measurements Of Sub-epicardial Sarcomere Length In Perfused Rat Hearts

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Patrizia Camelliti ◽  
Gil Bub ◽  
Daniel J Stuckey ◽  
Christian Bollensdorff ◽  
Damian J Tyler ◽  
...  
Keyword(s):  
Sarcomere Length ◽  
Left Ventricular ◽  
Model Systems ◽  
Future Research ◽  
Fundamental Parameter ◽  
Rat Hearts ◽  
Perfused Hearts ◽  
Over Time

Sarcomere length (SL) is a fundamental parameter underlying the Frank Starling relation in the heart, as it offers an absolute representation of myocardial stretch. Previous studies addressed the Frank Starling relation by measuring SL in isolated myocytes or muscle strips. Here, we report first data obtained using a novel technique to measure sub-epicardial SL in perfused hearts. Rat hearts were Langendorff perfused (normal Tyrode solution) at a constant pressure of 90mmHg, labeled with the fluorescent membrane marker di-4-ANEPPS, and then arrested with high-K + Tyrode for either 2-photon microscopy (n=4) or MRI (n=4). Image analysis software was developed to extract SL at the cell level from >1,400 2-photon images (Fig 1 ) and correct for cell angle. SL increased by 10±2 % between 30 and 80 min of perfusion (1.98±0.04 to 2.17±0.03 μm; p<0.05; Fig 1 ). Measurements of left ventricular myocardial volume (LVMV) were made in vivo and in perfused hearts using 3D MRI. LVMV increased by 24±7% from in vivo to 30 min of perfusion, and by 11±3 % between 30 and 90 min (539±35; 664±44; 737±49 mm 3 , respectively; p<0.05; Fig 1 ). We show that SL can be measured in isolated perfused hearts. The method allowed monitoring of changes in SL over time, and showed that SL and LVMV increase to a similar extent during 30–80 min perfusion with crystalloid solution, probably due to tissue oedema. This result, together with the increase in LVMV during the first 30 min, highlights the pronounced differences between in vivo , in situ , and in vitro model systems for studies of cardiac physiology and mechanics. Future research will compare changes in SL in healthy hearts and disease models involving contractile dysfunction. Figure 1: Left: 2-photon microscopy image of di-4-ANEPPS labeled myocardium. Right: SL and LVMV changes over time.

Contractile function in canine right ventricle

1980 ◽  
Vol 239 (6) ◽  
pp. H794-H804 ◽  
Author(s):  
G. D. Meier ◽  
A. A. Bove ◽  
W. P. Santamore ◽  
P. R. Lynch
Keyword(s):  
High Speed ◽  
Animal Studies ◽  
Contractile Function ◽  
Minor Component ◽  
Local Deformation ◽  
Wall Thickening ◽  
Free Wall ◽  
Ventricular Performance ◽  
Length Changes ◽  
Principal Directions

Regional right ventricular (RV) motion was examined in six acutely instrumented dogs by implanting radiopaque markers in three regions of the free wall: the apex, the midventricle, and the outflow tract. These markers were filmed at the paced heart rate of 180 beats/min with a high-speed biplane X-ray system, and their motion was analyzed with a digital computer. Local deformation was separated into percent length changes in the two mutually perpendicular principal directions. The major component exhibited shortening along a path from apex to conus. (apex - 13.6%, midventricle -13.1%, conus -8.7%); the minor component exhibited small amounts of lengthening and some shortening (apex +4.7%, midventricle +1.8%, conus -0.5%). From these two measurements we calculated the peak RV free wall thickening (apex 13.6%, midventricle 14.1%, conus 10.9%). The experimental technique developed for this study was found to be suitable for the repeated analysis of intact ventricular performance in chronic animal studies. The results reveal that in systole the RV free wall undergoes a sequential contraction, which begins at the apex and ends in the conus.

Fasudil prevents KATP channel-induced improvement in postischemic functional recovery

2005 ◽  
Vol 288 (6) ◽  
pp. H3011-H3015 ◽  
Author(s):  
Kenya Nishizawa ◽  
Paul E. Wolkowicz ◽  
Tadashi Yamagishi ◽  
Ling-Ling Guo ◽  
Martin M. Pike
Keyword(s):  
Diastolic Pressure ◽  
Rho Kinase ◽  
High Energy ◽  
Left Ventricular ◽  
High Energy Phosphate ◽  
Cellular Processes ◽  
Rat Hearts ◽  
Perfused Rat Hearts ◽  
Rock Activity ◽  
Mechanical Recovery

Whereas activation of ATP-dependent potassium (KATP) channels greatly improves postischemic myocardial recovery, the final effector mechanism for KATP channel-induced cardioprotection remains elusive. RhoA is a GTPase that regulates a variety of cellular processes known to be involved with KATP channel cardioprotection. Our goal was to determine whether the activity of a key rhoA effector, rho kinase (ROCK), is required for KATP channel-induced cardioprotection. Four groups of perfused rat hearts were subjected to 36 min of zero-flow ischemia and 44 min of reperfusion with continuous measurements of mechanical function and 31P NMR high-energy phosphate data: 1) untreated, 2) pinacidil (10 μM) to activate KATP channels, 3) fasudil (15 μM) to inhibit ROCK, and 4) both fasudil and pinacidil. Pinacidil significantly improved postischemic mechanical recovery [39 ± 16 vs. 108 ± 4 mmHg left ventricular diastolic pressure (LVDP), untreated and pinacidil, respectively]. Fasudil did not affect reperfusion LVDP (41 ± 13 mmHg) but completely blocked the marked improvement in mechanical recovery that occurred with pinacidil treatment (54 ± 15 mmHg). Substantial attenuation of the postischemic energetic recovery was also observed. These data support the hypothesis that ROCK activity plays a role in KATP channel-induced cardioprotection.

Losartan prevents contractile dysfunction in rat myocardium after left ventricular myocardial infarction

2001 ◽  
Vol 281 (5) ◽  
pp. H2150-H2158 ◽  
Author(s):  
Marcel C. G. Daniëls ◽  
Rebecca S. Keller ◽  
Pieter P. de Tombe
Keyword(s):  
Myocardial Infarction ◽  
Sarcomere Length ◽  
Contractile Function ◽  
Left Ventricular ◽  
Contractile Dysfunction ◽  
Treatment Results ◽  
Twitch Force ◽  
Rat Hearts ◽  
Myofilament Function ◽  
Active Peak

We studied the effects of chronic losartan (Los) treatment on contractile function of isolated right ventricular (RV) trabeculae from rat hearts 12 wk after left ventricular (LV) myocardial infarction (MI) had been induced by ligation of the left anterior descending artery at 4 wk of age. After recovery, one-half of the animals were started on Los treatment (MI+Los; 30 mg · kg−1 · day−1per os); the remaining animals were not treated (MI group). Rats without infarction or Los treatment served as controls (Con group). MI resulted in increases in LV and RV weight and unstressed LV cavity diameter; these were partially prevented by Los treatment. The active peak twitch force-sarcomere length relation was depressed in MI compared with either Con or MI+Los. Likewise, maximum Ca2+saturated twitch force was depressed in MI, whereas twitch relaxation and twitch duration were prolonged. Myofilament function, as measured in skinned trabeculae, was not significantly different among the Con, MI, and MI+Los groups. We conclude that Los prevents contractile dysfunction in rat RV trabeculae after LV MI. Our results suggest that the beneficiary effect of Los treatment results not from improved myofilament function but rather from improved myocyte Ca2+homeostasis.

Mechanisms underlying ischemic diastolic dysfunction: relation between rigor, calcium homeostasis, and relaxation rate

2003 ◽  
Vol 284 (3) ◽  
pp. H758-H771 ◽  
Author(s):  
Niraj Varma ◽  
James P. Morgan ◽  
Carl S. Apstein
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Coronary Flow ◽  
Diastolic Pressure ◽  
Left Ventricular ◽  
Relaxation Cycle ◽  
Relaxation Velocity ◽  
Butanedione Monoxime ◽  
Length Changes ◽  
Severe Ischemia

Increased diastolic chamber stiffness (↑DCS) during ischemia may result from increased diastolic calcium, rigor, or reduced velocity of relaxation. We tested these potential mechanisms during severe ischemia in isolated red blood cell-perfused isovolumic rabbit hearts. Ischemia (coronary flow reduced 83%) reduced left ventricular (LV) contractility by 70%, which then remained stable. DCS progressively increased. When LV end-diastolic pressure had increased 5 mmHg, myofilament calcium responsiveness was altered with 50 mmol/l NH4Cl or 10 mmol/l butanedione monoxime. These affected contractility (i.e., a calcium-mediated force) but not ↑DCS. Second, quick length changes reversed ↑DCS, supporting a rigor mechanism. Third, ischemia increased the time constant of isovolumic pressure decline from 47 ± 3 to 58 ± 3 ms ( P < 0.02) but concomitantly abbreviated the contraction-relaxation cycle, i.e., pressure dissipation occurred earlier without diastolic tetanization. Finally, to assess any link between rate of relaxation and ↑DCS, hearts were exposed to 10 mmol/l calcium. Calcium doubled contractility and accelerated relaxation velocity, but without affecting ↑DCS. Thus ↑DCS developed during ischemia despite severely reduced contractility via a rigor (and not calcium mediated) mechanism. Calcium resequestration capacity was preserved, and reduced relaxation velocity was not linked to ↑DCS.

Sarcomere length operating range of vertebrate muscles during movement

2001 ◽  
Vol 204 (9) ◽  
pp. 1529-1536 ◽  
Author(s):  
T.J. Burkholder ◽  
R.L. Lieber
Keyword(s):  
Skeletal Muscle ◽  
Sarcomere Length ◽  
Narrow Range ◽  
Analytical Techniques ◽  
Operating Range ◽  
Physiological Importance ◽  
Rigor State ◽  
Secondary Purpose ◽  
Length Measurements ◽  
Length Changes

The force generated by skeletal muscle varies with sarcomere length and velocity. An understanding of the sarcomere length changes that occur during movement provides insights into the physiological importance of this relationship and may provide insights into the design of certain muscle/joint combinations. The purpose of this review is to summarize and analyze the available literature regarding published sarcomere length operating ranges reported for various species. Our secondary purpose is to apply analytical techniques to determine whether generalizations can be made regarding the “normal” sarcomere length operating range of skeletal muscle. The analysis suggests that many muscles operate over a narrow range of sarcomere lengths, covering 94+/−13 % of optimal sarcomere length. Sarcomere length measurements are found to be systematically influenced by the rigor state and methods used to make these measurements.

Abstract 17468: Left Ventricular Remodeling Index (LVRI) in patients after breast cancer therapy in the long-term follow-up

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Felix Heggemann ◽  
Hanna Buggisch ◽  
Grit Welzel ◽  
Christina Doesch ◽  
Jochen Hansmann ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Therapy ◽  
Radiation Dose ◽  
Ventricular Remodeling ◽  
Left Ventricular ◽  
High Dose ◽  
Breast Cancer Therapy ◽  
Additional Chemotherapy ◽  
Whole Heart

Introduction: Cardiotoxic side effects are of concern in long-term survivors of left-sided breast cancer therapy. 3-dimensional conventional radiotherapy (3DCRT) deposits high doses in defined regions of the heart. Intensity modulated radiotherapy (IMRT) reduces local high-dose exposition at the expense of exposing more heart tissue to lower doses. Cardio-MRI was performed in this study to assess MRI-morphologic and functional alterations after 3DCRT and IMRT/ additional chemotherapy, with IMRT only performed in patients that would have been exposed to unacceptably high heart doses with 3DCRT. Methods: 49 patients with left-sided breast cancer (38 3DCRT and 11 IMRT; 20 patients with additional adjuvant chemotherapy (ACH) (13 3DCRT, 7 IMRT) were included prospectively. Baseline (pre-treatment) and 24 months post-treatment MRI was performed. With MRI, enddiastolic left ventricular mass (LVM), enddiastolic left ventricular volume (LVEDV) and stroke volume (SV) were assessed. LVRI was calculated with the formula LVM/LVEDV. Results: Mean dose for the whole heart was higher in IMRT than in 3DCRT patients (12.9±3.9 vs. 4.5 ±2.4 Gy). Larger regions received a higher radiation dose (>40Gy) in 3DCRT than in IMRT patients (3.3% vs. 1.3% of the whole heart). High local radiation dose > 50 Gy only occurred in the 3DCRT group (0.74% of the heart volume). After 24 months LVRI decreased significantly in patients with ACH (0.80 vs. 0.70, p=0.028). Non-significant decrease of LVRI was observed in the whole cohort (0.85 vs. 0.79), after IMRT (0.74 vs. 0.71), after 3DCRT (0.88 vs. 0.82) and without ACH (0.87 vs. 0.84). Decrease of LVRI in patients with ACH was caused by significant decrease of LVM (102.4 vs. 89.7 g, p=0.028) whereas LVEDV was stable (128.3 vs. 128.1g). In all groups, no significant decrease of SV could be assessed after 24 months. Conclusions: 24 months after therapy, significant decrease of LVRI due to decreased LVM could be found only in patients with additional chemotherapy. Radiotherapy alone did not have a significant impact on LVRI, LVM and SV. Low doses to the whole heart with IMRT did not cause significant decreases in LVRI, LVM and SV. LVM and LVRI are to be assessed in larger cohorts in patients with cancer therapy especially with additional chemotherapy.

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