Passive stiffness of myocardium from congenital heart disease and implications for diastole.
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.


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 approximately 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.
Division of Cardiology, Hospital for Sick Children, 555 University Ave, Toronto M5G 1X8, Canada. rajiv.chaturvedi@sickkids.ca
Rajiv R
RR
Chaturvedi
Todd
T
Herron
Robert
R
Simmons
Darryl
D
Shore
Pankaj
P
Kumar
Babulal
B
Sethia
Felix
F
Chua
Efstathios
E
Vassiliadis
Jonathan C
JC
Kentish
D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D003094:Collagen / Q000378:metabolism; D064211:Connectin; D003971:Diastole / Q000502:physiology*; D004108:Dilatation, Pathologic / Q000378:metabolism / Q000503:physiopathology; D004548:Elasticity / Q000502:physiology*; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D006321:Heart / Q000503:physiopathology*; D006331:Heart Diseases / Q000151:congenital* / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000378:metabolism / Q000503:physiopathology; D007223:Infant; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D011494:Protein Kinases / Q000378:metabolism; D018487:Ventricular Dysfunction, Left / Q000378:metabolism / Q000503:physiopathology; D055815:Young Adult
D064211:Connectin; D009124:Muscle Proteins; C577285:TTN protein, human; D003094:Collagen; D011494:Protein Kinases