Thermomechanical analysis of collagen crosslinking in the developing lamb pericardium

Wa, Naimark; Waldman, Stephen D.; Rj, Anderson; Suzuki, Boonsiva; Ca, Pereira; Lee, Jang-Ming

doi:10.1016/s0006-355x(98)00016-x

Cited by 24 publications

(18 citation statements)

References 25 publications

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“…The collagen T d fell by 1.1-2.3°C during pregnancy. Although this reduction may seem small in absolute terms, it is very similar to the 1.3°C fall in T d seen in collagen of the maternal pericardium during pregnancy (13) and similar in size to the rise in T d seen during perinatal development of pericardium (36) or heart valves (2). A fall in denaturation temperature may indicate reduced collagen cross-linking, but it can also indicate a destabilization associated with poor fibrillar packing [reduced polymer-in-a-box stabilization (35)] or even reduced stabilization via other matrix molecules like GAGs or proteoglycans (48).…”

Section: Discussionsupporting

confidence: 53%

Pregnancy-induced remodeling of heart valves

Pierlot

Moeller

Lee

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

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Recent studies have demonstrated remodeling of aortic and mitral valves leaflets under the volume loading and cardiac expansion of pregnancy. Those valves' leaflets enlarge with altered collagen fiber architecture, content, and cross-linking and biphasic changes (decreases, then increases) in extensibility during gestation. This study extends our analyses to right-sided valves, with additional compositional measurements for all valves. Valve leaflets were harvested from nonpregnant heifers and pregnant cows. Leaflet structure was characterized by leaflet dimensions, and ECM composition was determined using standard biochemical assays. Histological studies assessed changes in cellular and ECM components. Leaflet mechanical properties were assessed using equibiaxial mechanical testing. Collagen thermal stability and cross-linking were assessed using denaturation and hydrothermal isometric tension tests. Pulmonary and tricuspid leaflet areas increased during pregnancy by 35 and 55%, respectively. Leaflet thickness increased by 20% only in the pulmonary valve and largely in the fibrosa (30% thickening). Collagen crimp length was reduced in both the tricuspid (61%) and pulmonary (42%) valves, with loss of crimped area in the pulmonary valve. Thermomechanics showed decreased collagen thermal stability with surprisingly maintained cross-link maturity. The pulmonary leaflet exhibited the biphasic change in extensibility seen in left side valves, whereas the tricuspid leaflet mechanics remained largely unchanged throughout pregnancy. The tricuspid valve exhibits a remodeling response during pregnancy that is significantly diminished from the other three valves. All valves of the heart remodel in pregnancy in a manner distinct from cardiac pathology, with much similarity valve to valve, but with interesting valve-specific responses in the aortic and tricuspid valves. HEART VALVES ARE COMPLEX and dynamic biological structures. They play important roles toward efficient cardiac pumping, ensuring unidirectional blood flow while opening and closing 3 billion times in a lifetime. The extent and the mechanisms via which the valves may adapt to changing loading conditions in either physiology or pathology remain unclear. Many investigations of valve adaptation have focused on physiological development (8,20,(51)(52)(53) or pathological conditions such as left ventricular (LV) dysfunction (10), mitral valve regurgitation (58), myxomatous degeneration (19), or heart failure (17). Recent studies from our laboratory, however, have demonstrated the capacity of maternal heart valve leaflets to remodel under the altered hemodynamics of pregnancy, a nonpathological condition (38,39,60). Pregnancy is accompanied by an increase in blood volume and cardiac output of ϳ50%, as the maternal circulation accommodates the developing fetoplacental unit. This volume overload produces cardiac enlargement (21, 45, 60) with expansion of valve orifices (areas increasing from 12-53% in humans; see Refs. 9 and 43). These changes in geometry then elevate...

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Section: Discussionsupporting

confidence: 53%

Pregnancy-induced remodeling of heart valves

Pierlot

Moeller

Lee

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

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“…In general, fetal collagenous tissues have the highest degree of immature crosslinking, with the lowest content of mature (and overall) crosslinking. 5,26,29,39 It is for this reason that we have not emphasized the changes within each valve from the fetal to the neonatal state. While each valve experiences altered mechanical loading at birth, these changes are superimposed over the normal maturation process from the fetal to the neonatal state.…”

Section: Discussionmentioning

confidence: 99%

Differential Changes in the Molecular Stability of Collagen from the Pulmonary and Aortic Valves During the Fetal-to-Neonatal Transition

2010

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During the fetal-to-neonatal transition, transvalvular pressures (TVPs) on the aortic and pulmonary valves change dramatically-but differently for each valve. We have examined changes in the molecular stability and crosslinking of collagen during this transition. Aortic and pulmonary valves were harvested from fetal and neonatal cattle. Using differential scanning calorimetry (DSC), denaturation of valvular collagen was examined and, using HPLC, the types and quantities of enzymatic crosslinks were examined. No difference in hydrothermal stability was found between the collagens in the fetal aortic and pulmonary valves; this was expected since the TVP is approximately the same across both valves before birth. Only in the neonatal samples was the collagen from aortic valves (higher TVP) less stable than that from pulmonary valves (lower TVP). Surprisingly, the enthalpy of denaturation did not differ either between valve type or with age, suggesting an entropic mechanism of altered molecular stability. A significant difference in immature-to-mature crosslink ratio was found between neonatal aortic and pulmonary valves: a difference absent in fetal valves. This ratio-indicative of remodeling rate-parallels (and may be a function of) the changing in vivo load. This study highlights the relationship between in vivo load and both (i) molecular stability and (ii) collagen remodeling in heart valves.

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“…Further developmental changes must also occur later in life as the lungs only account for between 25 and 30% of the total constraint experienced by the adult heart (Kingma et al 1987). Although both a decrease in chest-wall compliance (Agostoni, 1959) and an alteration in the properties of the pericardium (Naimark, 1995;Naimark et al 1998) are likely to contribute to the changes in ventricular constraint that accompany development, our current findings suggest for the first time that developmental alterations in the properties of the lungs themselves are also important. Brookhart & Boyd (1947) recognised that, while filling, the heart displaces the lung and, as a result, the intrathoracic pressure within the cardiac fossa exceeds that of the lateral regions.…”

Section: Discussionmentioning

confidence: 99%

“…However, this constraint is largely eliminated immediately following the aeration of the lungs at birth (Grant et al 1992a(Grant et al , 1994. Within days of birth, the lungs once again significantly constrain the heart and produce up to 50% of the total constraint experienced by the neonatal heart (Grant et al 1994); by contrast, in the adult only 25-30% of the total cardiac constraint arises from the lung (Kingma et al 1987).Although developmental changes in the chest wall (Agostoni, 1959) and pericardium (Naimark, 1995;Naimark et al 1998) 1. In order for diastolic filling to occur, the heart must displace the lung.…”

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confidence: 99%

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Age‐related differences in the distortion of the sheep lung in response to localised pleural stress

Grant

Walker

Fauchère

2001

The Journal of Physiology

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'As a means of relief from the leaping heart when passion is excited . . . they [the engendered sons of God] contrived and implanted the form of the lung -soft and bloodless . . . as a kind of padding around the heart . . .' (Plato, (Cournand, 1982) Although our understanding of the physiology of the lung has greatly changed since the time of Plato, the interaction between the heart and the lungs is still recognised to affect both respiratory and cardiac function. For example, cardiogenic gas mixing, though partially a result of instantaneous changes in the rate of O 2 consumption and CO 2 production , largely results from direct mechanical interactions between the heart and the lung. Lung gas volume decreases during diastole and increases during systole as the filling and emptying heart displaces the lungs Lloyd, 1989). Just as the heart influences lung gas volume, the presence of the lung surrounding the heart also significantly limits ventricular filling and thus limits cardiac output via the Frank-Starling mechanism. Brookhart & Boyd (1947) observed that the interaction between the heart and the lung results in intra-thoracic pressure within the cardiac fossa exceeding that in the lateral pleural space, and that an increase in lung volume is accompanied by an increase in extra-cardiac pressure. It was subsequently recognised that this increase in extra-cardiac pressure is the mechanism whereby the application of positive endexpiratory pressure and increasing lung volume act to constrain ventricular filling and limit cardiac output (Fewell et al. 1980a,b;Kingma et al. 1987).Not only does the constraint applied to the heart by the lungs change when airway pressure and lung volume are changed, it also changes with developmental age. In the fetus, the lungs are liquid filled and significantly constrain ventricular filling (Grant et al. 1992b;Grant & Walker, 1996). However, this constraint is largely eliminated immediately following the aeration of the lungs at birth (Grant et al. 1992a(Grant et al. , 1994. Within days of birth, the lungs once again significantly constrain the heart and produce up to 50% of the total constraint experienced by the neonatal heart (Grant et al. 1994); by contrast, in the adult only 25-30% of the total cardiac constraint arises from the lung (Kingma et al. 1987).Although developmental changes in the chest wall (Agostoni, 1959) and pericardium (Naimark, 1995;Naimark et al. 1998) 1. In order for diastolic filling to occur, the heart must displace the lung. Given the changes in lung structure and compliance that follow birth, we sought to determine whether the neonatal lung resists neighbouring structures encroaching into its space more than the adult lung and whether the lung surface making up the cardiac fossa resists distortion more than the lateral surface does.2. Pleural distortions, induced by applied pressures (P appl ) of 20-120 g cm _2 at airway pressures (P aw ) of 2.5-15 cmH 2 O, were recorded in isolated lungs of adult, neonatal (4-week-old) and newborn (1-week-old) sheep...

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Thermomechanical analysis of collagen crosslinking in the developing lamb pericardium

Cited by 24 publications

References 25 publications

Pregnancy-induced remodeling of heart valves

Pregnancy-induced remodeling of heart valves

Differential Changes in the Molecular Stability of Collagen from the Pulmonary and Aortic Valves During the Fetal-to-Neonatal Transition

Age‐related differences in the distortion of the sheep lung in response to localised pleural stress

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