The contractile state as the major determinant in the evolution of left ventricular dysfunction in the spontaneously hypertensive rat.

Female spontaneously hypertensive and normotensive rats were studied at 6, 12, 18, and 24 months of age to determine which characteristics of myocardial performance herald the onset of left ventricular dysfunction. Peak ejection fraction index was derived from measurements of peak stroke volume (in vivo volume loading) and passive pressure-volume relations. The myocardial stiffness constant (km, slope of the incremental modulus-stress relation, EINC = km sigma), chamber stiffness constant (kc, slope of the chamber stiffness-pressure relation, dP/dV = kcP), and left ventricular cavitary volume-to-wall volume ratio at 10 mm Hg) were calculated from the pressure-volume data and the contractile state was assessed from the ejection fraction index-afterload relations. In the normotensive rats, the myocardial stiffness constant was not affected by age, whereas, in the spontaneously hypertensive rats, the myocardial stiffness constant remained within normal limits until 18 months, at which time a significant increase in this index of myocardial stiffness occurred. Baseline and maximal cardiac indices and ejection fraction index of spontaneously hypertensive rats were normal from 6 to 18 months, but were markedly reduced at 24 months. This reduction in cardiac performance was associated with a decrease in the left ventricular chamber stiffness constant, i.e., kc. This decreased chamber stiffness, which occurred at a time when myocardial stiffness was increased, was due to a greater increase in cavity size than in myocardial stiffness. The left ventricular cavity-to-wall volume ratio of normotensive rats was not affected by age, whereas, in the spontaneously hypertensive rats, this ratio markedly declined by 18 months. The ejection fraction index-afterload relations i.e., a measure of the contractile state, of the 6- and 12-month-old spontaneously hypertensive rats were similar to those of the normotensive rats of all ages. However, a depression in the contractile state of the spontaneously hypertensive rats occurred at 18 months and was further depressed at 24 months. This abnormality of the contractile state was evident before the deterioration of cardiac performance, as reflected in a decrease in baseline and maximal cardiac indices, and dilation of the left ventricle occurred. The contractile state (ejection fraction index-afterload relation) is thus the most sensitive indicator of left ventricular dysfunction in spontaneously hypertensive rats.

[1]  S A Glantz,et al.  Ventricular Pressure‐Volume Curve Indices Change with End‐Diastolic Pressure , 1976, Circulation research.

[2]  A. Love.  A treatise on the mathematical theory of elasticity , 1892 .

[3]  J. Pannier.  Contractile state of papillary muscles obtained from cats with moderate right ventricular hypertrophy. , 1971, Archives internationales de physiologie et de biochimie.

[4]  W. Kannel.  Role of blood pressure in cardiovascular morbidity and mortality. , 1974, Progress in cardiovascular diseases.

[5]  A. C. Burton,et al.  The reason for the shape of the distensibility curves of arteries. , 1957, Canadian journal of biochemistry and physiology.

[6]  J. Williams,et al.  Passive Stiffness of Pressure‐Induced Hypertrophied Cat Myocardium , 1981, Circulation research.

[7]  W. Newman,et al.  Adaptation of left ventricle to chronic pressure overload: response to inotropic drugs. , 1980, The American journal of physiology.

[8]  R. Taylor,et al.  Left ventricular response to experimentally induced chronic aortic regurgitation. , 1972, Cardiovascular research.

[9]  Sanford P. Bishop,et al.  Adaptations of the left ventricle to chronic pressure overload , 1976 .

[10]  M. Pfeffer,et al.  Alterations of cardiac performance in rats with established spontaneous hypertension. , 1979, The American journal of cardiology.

[11]  R. Kaufmann,et al.  Disorder in Excitation‐Contraction Coupling of Cardiac Muscle from Cats with Experimentally Produced Right Ventricular Hypertrophy , 1971, Circulation research.

[12]  J. L. Gill,et al.  Design and analysis of experiments in the animal and medical sciences , 1980 .

[13]  E. Braunwald,et al.  Contractile State of Cardiac Muscle Obtained from Cats with Experimentally Produced Ventricular Hypertrophy and Heart Failure , 1967, Circulation research.

[14]  W. Gaasch,et al.  Left Ventricular Stress and Compliance in Man: With Special Reference to Normalized Ventricular Function Curves , 1972, Circulation.

[15]  K. Peterson,et al.  Diastolic Left Ventricular Pressure-Volume and Stress-Strain Relations in Patients with Valvular Aortic Stenosis and Left Ventricular Hypertrophy , 1978, Circulation.

[16]  I. Mirsky,et al.  Assessment of passive elastic stiffness of cardiac muscle: mathematical concepts, physiologic and clinical considerations, directions of future research. , 1976, Progress in cardiovascular diseases.

[17]  M. Giambattista,et al.  Tension Developed by Papillary Muscles from Hypertrophied Rat Hearts , 1961, Circulation research.

[18]  I. Mirsky,et al.  SPECIAL ARTICLE The Effects of Geometry, Elasticity, and External Pressures on the Diastolic Pressure-Volume and Stiffness-Stress Relations , 1979 .

[19]  I. Mirsky,et al.  Diastolic myocardial stiffness in gradually developing left ventricular hypertrophy in dog. , 1982, The American journal of physiology.

[20]  S. Glantz,et al.  Factors which affect the diastolic pressure-volume curve. , 1978, Circulation research.

[21]  M. Pfeffer,et al.  Cardiac function and morphology with aging in the spontaneously hypertensive rat. , 1979, The American journal of physiology.

[22]  I. Mirsky,et al.  Effect of age on passive elastic stiffness of rat heart muscle. , 1976, Biophysical journal.

[23]  J. Fleiss,et al.  Some Statistical Methods Useful in Circulation Research , 1980, Circulation research.

[24]  R. Satava,et al.  Mechanism for the Abnormal Energetics of Pressure‐Induced Hypertrophy of Cat Myocardium , 1973, Circulation research.

[25]  A. Grimm,et al.  Properties of Myocardium in Cardiomegaly , 1963, Circulation research.

[26]  J. Ross,et al.  Hyperfunction with normal inotropic state of the hypertrophied left ventricle. , 1977, The American journal of physiology.

[27]  I. Mirsky,et al.  The role of wall stress in the assessment of ventricular function. , 1981, Herz.

[28]  I. Mirsky,et al.  Ventricular and arterial wall stresses based on large deformation analyses. , 1973, Biophysical journal.

[29]  N. Alpert,et al.  Mechanical and Biochemical Correlates of Cardiac Hypertrophy , 1974, Circulation research.

[30]  N. Alpert,et al.  The Mechanical Characteristics of Hypertrophied Rabbit Cardiac Muscle in the Absence of Congestive Heart Failure: The Contractile and Series Elastic Elements , 1977, Circulation research.

[31]  J. Ross,et al.  Afterload mismatch and preload reserve: a conceptual framework for the analysis of ventricular function. , 1976, Progress in cardiovascular diseases.

[32]  M. Pfeffer,et al.  Pumping Ability of the Hypertrophying Left Ventricle of the Spontaneously Hypertensive Rat , 1976, Circulation research.

[33]  E. Sonnenblick,et al.  Comparison of the Ultrastructural Basis of the Contractile Process in Heart and Skeletal Muscle , 1964, Circulation research.

[34]  B. Strauer,et al.  Left Ventricular Hypertrophy in Chronic Pressure Load Due to Spontaneous Essential Hypertension II. Contractility of the Isolated Left Ventricular Myocardium and Left Ventricular Stiffness , 1981 .

[35]  J. Gunning,et al.  Myocardial oxygen consumption during experimental hypertrophy and congestive heart failure. , 1973, Journal of molecular and cellular cardiology.

[36]  J. Ross,et al.  Effects of changes in preload, afterload and inotropic state on ejection and isovolumic phase measures of contractility in the conscious dog. , 1975, The American journal of cardiology.

[37]  C. Henschke,et al.  Prediction of postoperative performance in aortic valve disease. , 1981, The American journal of cardiology.

[38]  H. Levine,et al.  Mechanical Properties of Rat Cardiac Muscle during Experimental Hypertrophy , 1971, Circulation research.