The visceral pericardium: macromolecular structure and contribution to passive mechanical properties of the left ventricle

Jobsis, P. D.; Ashikaga, Hiroshi; Wen, Han; Rothstein, Emily C.; Horvath, Keith A.; McVeigh, Elliot R.; Balaban, Robert S.

doi:10.1152/ajpheart.00967.2007

Cited by 40 publications

(44 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Inertia, from tissue motion and torsion (25); inclusion of resistance, from the deactivation events traditionally thought to be characterized by and L (5,20,22,28); and elasticity, generated recoil force from the stiff, springlike intra-and extracellular elements such as titin, extracellular matrix, and visceral pericardium (8,10,13,21,24): these three terms constitute three physiologically and physically required force-generating mechanisms that contribute to pressure decline during IVR. Characterization of the elastic and resistive mechanisms of IVR are significant, given that resistance (or traditionally relaxation, via ) has been offered as a major cause of "diastolic heart failure," concluding that abnormal "relaxation" is significant based on being viewed as a "pure" measure of relaxation (35).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Physical determinants of left ventricular isovolumic pressure decline: model prediction with in vivo validation

Chung

Kovács

2008

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Chung CS, Kovács SJ. Physical determinants of left ventricular isovolumic pressure decline: model prediction with in vivo validation. Am J Physiol Heart Circ Physiol 294: H1589-H1596, 2008. First published January 25, 2008 doi:10.1152/ajpheart.00990.2007.-The rapid decline in pressure during isovolumic relaxation (IVR) is traditionally fit algebraically via two empiric indexes: , the time constant of IVR, or L, a logistic time constant. Although these indexes are used for in vivo diastolic function characterization of the same physiological process, their characterization of IVR in the pressure phase plane is strikingly different, and no smooth and continuous transformation between them exists. To avoid the parametric discontinuity between and L and more fully characterize isovolumic relaxation in mechanistic terms, we modeled ventricular IVR kinematically, employing a traditional, lumped relaxation (resistive) and a novel elastic parameter. The model predicts IVR pressure as a function of time as the solution of d 2 P/dt 2 ϩ (1/)dP/dt ϩ EkP ϭ 0, where (ms) is a relaxation rate (resistance) similar to or L and Ek (1/s 2 ) is an elastic (stiffness) parameter (per unit mass). Validation involved analysis of 310 beats (10 consecutive beats for 31 subjects). This model fit the IVR data as well as or better than or L in all cases (average root mean squared error for dP/dt vs. t: 29 mmHg/s for model and 35 and 65 mmHg/s for and L, respectively). The solution naturally encompasses and L as parametric limits, and good correlation between and 1/E k ( ϭ 1.15/Ek Ϫ 11.85; r 2 ϭ 0.96) indicates that isovolumic pressure decline is determined jointly by elastic (E k) and resistive (1/) parameters. We conclude that pressure decline during IVR is incompletely characterized by resistance (i.e., and L) alone but is determined jointly by elastic (Ek) and resistive (1/) mechanisms. relaxation; stiffness; hemodynamics; diastole; mechanics; pressure phase plane; isovolumic relaxation IN VIVO ANALYSIS of isovolumic relaxation (IVR) in mammalian hearts has traditionally relied on , the time constant of IVR, to characterize pressure decline. Typically, the rate of pressure decline as a function of time is assumed to be proportional to pressure itself and is therefore a solution to dP dtwhere P o is a constant and P ϱ is the pressure asymptote (32). A geometrically convenient way to determine is to plot Eq. 1A in the time derivative of pressure (dP/dt) vs. time-varying pressure [P(t)] (pressure phase plane, PPP), where it inscribes a straight line (19, 33) with a slope of Ϫ1/, and fit it to the IVR portion of the loop inscribed by P(t) for the cardiac cycle (Fig. 1A). However, a straight line fit to the IVR portion of the loop may not always be physiological, since curvilinear IVR segments exist (Fig. 1B). An alternative empiric constant has been proposed to fit these frequently occurring "curved" IVR segments of PPP trajectories (19). Like , the logistic time constant L provides an empirical fit, where pressure as a function of time obe...

show abstract

Section: Discussionmentioning

confidence: 99%

“…End-systolic stored elastic forces that drive filling (13,14) have been attributed to extracellular matrix, intracellular titin (8,24), microtubules (21), and the heart's visceral pericardium (10). Such an elastic restoring force at end systole must overcome the residual forces of contraction (22).…”

Section: Methodsmentioning

confidence: 99%

Physical determinants of left ventricular isovolumic pressure decline: model prediction with in vivo validation

Chung

Kovács

2008

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

show abstract

“…Emission spectra were collected to optimize the separation of collagen and elastin signals. 24 Emission spectra ( Figure I of the online Data Supplement) reveals that at Ͻ840-nm excitation the near-ultraviolet second-harmonic-generation (SHG) signal was suppressed, likely because of the transmission characteristics of the optics and the inner filter properties of the tissues. 25 Thus, an excitation Ͼ840 nm (ie, 420-nm single photon) was required to detect the collagen SHG.…”

Section: Two-photon Excitation Microscopymentioning

confidence: 99%

Contribution of Macromolecular Structure to the Retention of Low-Density Lipoprotein at Arterial Branch Points

et al. 2008

Self Cite

View full text Add to dashboard Cite

Background-Extracellular deposition of low-density lipoprotein (LDL) in the arterial wall is an essential early step in atherosclerosis. This process preferentially occurs at arterial branch points, reflecting a regional variation in lipoprotein-arterial wall interactions. In this study, we characterized the submicron microstructure of arterial wall collagen and elastin to evaluate its potential role in regional LDL deposition. Methods and Results-With 2-photon microscopy, we used the intrinsic optical properties of collagen and elastin to determine the arterial wall macromolecular microstructure in fresh porcine and murine arteries. This optical approach generated unique nondestructive en face 3-dimensional views of the wall. The collagen/elastin microstructure was found to vary with the topology of the arterial bed. A nearly confluent elastin surface layer was present throughout but was missing at atherosclerosis-susceptible branch points, exposing dense collagen-proteoglycan complexes. In LDL binding studies, this luminal elastin layer limited LDL penetration, whereas its absence at the branches resulted in extensive LDL binding. Furthermore, LDL colocalized with proteoglycans with a sigmoidal dose dependence (inflection point, Ϸ130 mg LDL/dL). Ionic strength and competing anions studies were consistent with the initial interaction of LDL with proteoglycans to be electrostatic in nature. Conclusions-This optical sectioning approach provided a robust 3-dimensional collagen/elastin microstructure of the arterial wall in fresh samples. At atherosclerosis-susceptible vascular branch points, the absence of a luminal elastin barrier and the presence of a dense collagen/proteoglycan matrix contribute to increased retention of LDL. (Circulation.

show abstract

“…The two most well-known and significant contributors to elastic forces are titin and the extracellular matrix (35), which includes the visceral pericardium (47). Titin is the largest protein expressed in the body and operates (in the physiological domain of sarcomere lengths) as a linear, bidirectional spring (33,39,40).…”

Section: Physiology Of Diastolementioning

confidence: 99%

What global diastolic function is, what it is not, and how to measure it

Chung

Shmuylovich

Kovács

2015

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Leonardo da Vinci's observation (circa 1511) that "the atria or filling chambers contract together while the pumping chambers or ventricles are relaxing and vice versa," the dynamics of four-chamber heart function, and of diastolic function (DF) in particular, are not generally appreciated. We view DF from a global perspective, while characterizing it in terms of causality and clinical relevance. Our models derive from the insight that global DF is ultimately a result of forces generated by elastic recoil, modulated by cross-bridge relaxation, and load. The interaction between recoil and relaxation results in physical wall motion that generates pressure gradients that drive fluid flow, while epicardial wall motion is constrained by the pericardial sac. Traditional DF indexes (, E/E=, etc.) are not derived from causal mechanisms and are interpreted as approximating either stiffness or relaxation, but not both, thereby limiting the accuracy of DF quantification. Our derived kinematic models of isovolumic relaxation and suction-initiated filling are extensively validated, quantify the balance between stiffness and relaxation, and provide novel mechanistic physiological insight. For example, causality-based modeling provides load-independent indexes of DF and reveals that both stiffness and relaxation modify traditional DF indexes. The method has revealed that the in vivo left ventricular equilibrium volume occurs at diastasis, predicted novel relationships between filling and wall motion, and quantified causal relationships between ventricular and atrial function. In summary, by using governing physiological principles as a guide, we define what global DF is, what it is not, and how to measure it. diastolic function; echocardiography; hemodynamics; mathematical modeling; suction pump LEFT VENTRICULAR (LV) DIASTOLIC dysfunction is typically reported and indexed as either an increase in myocardial stiffness or a slowing of relaxation (i.e., cross-bridge dissociation). In actuality, diastolic function (DF) is the result of the continuous interaction between the restoring force of elastic recoil and the opposing force generated by cross bridges that have yet to uncouple from the previous systole. The restoring forces seek to lengthen the muscle, while the cross-bridge forces previously acted to shorten the muscle. The simultaneous action of these two opposing forces during both isovolumic relaxation (IVR) and filling result in wall motion, constrained by pericardial sac volume, and simultaneous generation of pressure gradients. This review discusses the governing physical laws and the constraints of DF, as well as which indexes of DF are consistent with diastolic physiology. Deriving and evaluating indexes of DF using this conceptual framework both clarifies and advances our understanding of DF and diastolic dysfunction in health and disease. Physiology of DiastoleCardiovascular physiology is taught using the Wiggers diagram, which segments the cardiac cycle into systole and diastole ( Fig. 1) (49, 124). Systole begins...

show abstract

The visceral pericardium: macromolecular structure and contribution to passive mechanical properties of the left ventricle

Cited by 40 publications

References 37 publications

Physical determinants of left ventricular isovolumic pressure decline: model prediction with in vivo validation

Physical determinants of left ventricular isovolumic pressure decline: model prediction with in vivo validation

Contribution of Macromolecular Structure to the Retention of Low-Density Lipoprotein at Arterial Branch Points

What global diastolic function is, what it is not, and how to measure it

Contact Info

Product

Resources

About