TY - JOUR
T1 - Passive Stiffness of Myocardium From Congenital Heart Disease and Implications for Diastole
AU - Chaturvedi, Rajiv R.
AU - Herron, Todd
AU - Simmons, Robert
AU - Shore, Darryl
AU - Kumar, Pankaj
AU - Sethia, Babulal
AU - Chua, Felix
AU - Vassiliadis, Efstathios
AU - Kentish, Jonathan C.
PY - 2010/3
Y1 - 2010/3
N2 - Background-In ventricular dilatation or hypertrophy, an elevated end-diastolic pressure is often assumed to be secondary to increased myocardial stiffness, but stiffness is rarely measured in vivo because of difficulty. We measured in vitro passive stiffness of volume-or pressure-overloaded myocardium mainly from congenital heart disease.
Methods and Results-Endocardial ventricular biopsies were obtained at open heart surgery (n = 61; pressure overload, 36; volume-overload, 19; dilated cardiomyopathy, 4; normal donors, 2). In vitro passive force-extension curves and the stiffness modulus were measured in skinned tissue: muscle strips, strips with myofilaments extracted (mainly extracellular matrix), and myocytes. Collagen content (n = 38) and titin isoforms (n = 16) were determined. End-diastolic pressure was measured at cardiac catheterization (n = 14). Pressure-overloaded tissue (strips, extracellular matrix, myocytes) had a 2.6- to 7.0-fold greater force and stiffness modulus than volume-overloaded tissue. Myocyte force and stiffness modulus at short stretches (0.05 resting length, L-0) was pressure-overloaded > normal approximate to volume-overloaded > dilated cardiomyopathy. Titin N2B: N2BA isoform ratio varied little between conditions. The extracellular matrix contributed more to force at 0.05 L-0 in pressure-overloaded (35.1%) and volume-overloaded (17.4%) strips than normal myocardium. Stiffness modulus increased with collagen content in pressure-overloaded but not volume-overloaded strips. In vitro stiffness modulus at 0.05 L-0 was a good predictor of in vivo end-diastolic pressure for pressure-overloaded but not volume-overloaded ventricles and estimated normal end-diastolic pressure as 5 to 7 mm Hg.
Conclusions-An elevated end-diastolic pressure in pressure-overloaded, but not volume-overloaded, ventricles was related to increased myocardial stiffness. The greater stiffness of pressure-overloaded compared with volume-overloaded myocardium was due to the higher stiffness of both the extracellular matrix and myocytes. The transition from normal to very-low stiffness myocytes may mark irreversible dilatation. (Circulation. 2010; 121: 979-988.)
AB - Background-In ventricular dilatation or hypertrophy, an elevated end-diastolic pressure is often assumed to be secondary to increased myocardial stiffness, but stiffness is rarely measured in vivo because of difficulty. We measured in vitro passive stiffness of volume-or pressure-overloaded myocardium mainly from congenital heart disease.
Methods and Results-Endocardial ventricular biopsies were obtained at open heart surgery (n = 61; pressure overload, 36; volume-overload, 19; dilated cardiomyopathy, 4; normal donors, 2). In vitro passive force-extension curves and the stiffness modulus were measured in skinned tissue: muscle strips, strips with myofilaments extracted (mainly extracellular matrix), and myocytes. Collagen content (n = 38) and titin isoforms (n = 16) were determined. End-diastolic pressure was measured at cardiac catheterization (n = 14). Pressure-overloaded tissue (strips, extracellular matrix, myocytes) had a 2.6- to 7.0-fold greater force and stiffness modulus than volume-overloaded tissue. Myocyte force and stiffness modulus at short stretches (0.05 resting length, L-0) was pressure-overloaded > normal approximate to volume-overloaded > dilated cardiomyopathy. Titin N2B: N2BA isoform ratio varied little between conditions. The extracellular matrix contributed more to force at 0.05 L-0 in pressure-overloaded (35.1%) and volume-overloaded (17.4%) strips than normal myocardium. Stiffness modulus increased with collagen content in pressure-overloaded but not volume-overloaded strips. In vitro stiffness modulus at 0.05 L-0 was a good predictor of in vivo end-diastolic pressure for pressure-overloaded but not volume-overloaded ventricles and estimated normal end-diastolic pressure as 5 to 7 mm Hg.
Conclusions-An elevated end-diastolic pressure in pressure-overloaded, but not volume-overloaded, ventricles was related to increased myocardial stiffness. The greater stiffness of pressure-overloaded compared with volume-overloaded myocardium was due to the higher stiffness of both the extracellular matrix and myocytes. The transition from normal to very-low stiffness myocytes may mark irreversible dilatation. (Circulation. 2010; 121: 979-988.)
U2 - 10.1161/CIRCULATIONAHA.109.850677
DO - 10.1161/CIRCULATIONAHA.109.850677
M3 - Article
SN - 1524-4539
VL - 121
SP - 979
EP - 988
JO - Circulation (Baltimore)
JF - Circulation (Baltimore)
IS - 8
ER -
