G. Kissling

Pressure-Volume Relations, Elastic Modulus, and Contractile Behaviour of the Hypertrophied Left Ventricle of Rats with Goldblatt II Hypertension*

SummaryIn young male Wistar rats, an increase in systolic blood pressure to above 200 mm Hg was induced by constricting one renal artery (Goldblatt II). This led to cardiac hypertrophy with an increase in left ventricular weight of about 40% after 4 weeks as compared with controls of the same age. Four and 8 weeks after the operation, the systolic and enddiastolic pressure-volume relations of the left ventricle were determined under isovolumetric conditions in open-chest Goldblatt rats and in control animals of the same age. The systolic and diastolic wall stress and the tangential elastic modulus were calculated, assuming a thick-walled sphere.The diastolic pressure-volume curves were shifted to greater volumes after 4 weeks, apparently due to a temporary augmentation of blood volume. However, no significant difference between the diastolic pressure-volume curves of Goldblatt and control ventricles was found after 8 weeks. The isovolumetrically developed pressure was found to be increased in both stages of Goldblatt hypertension at the optimum of the pressure-volume diagram (maximum distance between end-diastolic and systolic pressure-volume curves).The diastolic wall stress rose only after 4 weeks in the hypertrophied ventricles due to the additional volume load. For a given diastolic wall stress, the elastic modulus tended to higher values in the Goldblatt hearts. Sarcomere length was measured after 8 weeks at the same end-diastolic transmural pressure at which the heart works in the closed chest. There was no significant difference between sarcomere length in the left ventricles of Goldblatt rats (1.99±0.03 μm) and control animals

Ventricular pressure-volume relations as the primary basis for evaluation of cardiac mechanics return to Frank's diagram

{\text{[1}}{\text{.97 }} \pm {\text{0}}{\text{.01}} \mu m(\bar x \pm s_{\bar x} ){\text{]}}

Left ventricular end-systolic pressure-volume relationships as a measure of ventricular performance

. The peak systolic wall stress, calculated from after loaded contractions, was not enhanced. However, the developed isovolumetric stress and the rate of stress development showed a significant increase in Goldblatt rats.These results indicate that the work capacity of the hypertrophied ventricle as a whole is enhanced. This enhancement of the contractile force per unit of cross-sectional area and its first derivative does not, however, allow the conclusion that there is an improvement in the elementary contractile process as the maximum myocardial shortening velocity at zero load (Vmax) is decreased whilst the content of contractile proteins is augmented.

Dynamics of the hypertrophied left ventricle in the rat. Effects of physical training and chronic pressure load

Based on investigations of various models of experimental cardiac hypertrophy (renal hypertension, spontaneous hypertension, aortic stenosis, swimming training, thyrotoxicosis), an attempt has been made to characterize adaptive and pathological alterations that are inherent to or accompany the process of hypertrophy. In principle, the designation of a process as adaptive is rooted in a teleological point of view and implies that the basic tendency of the respective structural and functional alterations is appropriate for coping with the altered functional requirements. This does not mean, however, that such alterations are favorable under all conditions and in all stages of hypertrophy. Since organisms generally reveal relatively stereotypic reaction patterns, the terms “adaptive” and “pathological” are not mutually exclusive in the final analysis. In the chronically pressure-loaded ventricle, nearly all alterations are ambiguous (myocardial mass increase, prolongation of the action potential, overproportional increase of intracellular contractile material, decrease of myofibrillar ATPase activity). The altered ATPase activity, which is based on a shift in the isoenzyme pattern of myosin in the direction of isoenzyme V3, is accompanied by a decrease in unloaded shortening velocity but an increase in the efficiency of tension development, as is reflected in reduced oxygen consumption (per wall stress and heart rate) of the whole heart under isovolumetric conditions. This change in the elementary contractile process and the myofibrillar ATPase activity need not be interpreted a priori as negative. However, the ability to adapt to other types of loading, e.g., physical exertion with corresponding increase in heart rate, is limited by the specialization for coping with enhanced pressure load. The term “overadaptation” should be reserved for stages and degrees of hypertrophy in which the negative effects of double-faced alterations predominate. Rapid, excessive increase in pressure loading, as well as long-term hemodynamic overloading, leads to degenerative alterations of the myocardium. At the level of the whole ventricle, structural dilatation results in a decreased cardiac efficiency. Fibrosis of the ventricular wall, the pathogenesis of which is not always unequivocal, is also a negative factor for mechanical performance. Since there are pronounced degrees of hypertrophy without connective tissue increase, e.g., in thyrotoxicosis, fibrosis and accompanying decreased distensibility of the myocardium apparently are not necessarily involved in the development of hypertrophy. Ischemically induced alterations stemming from vasculopathy should be distinguished from hypertrophy-induced changes. The adaptive alteration of the heart in swim-trained rats, which involves an increase in myofibrillar ATPase activity and a shift in the myosin isoenzyme pattern in the direction of V1, leads to an increase in functional capacity at all levels and is in agreement with the generally accepted concept of contractility.

Geometric and muscle physiological factors of the frank-starling mechanism

SummaryConsidering ventricular function from the vantage point of the pressure-volume (P-V) diagram permits not only quantification of ventricular working capacity under normal and pathophysiological conditions but also promotes understanding of cardiac dynamics including prediction of the effects of mechanical and pharmacological interventions. Therefore it seems appropriate, at least intellectually, to classify all measured volume and pressure data into the scheme of the P-V diagram. The use of so-called contractility indices and also the restriction to the end-systolic P-V relation alone means deliberate renunciation of important information. In principle, Franks original concept can be confirmed which, under afterloaded conditions, implies the existence of distinct end-systolic P-V curves each related to a particular end-diastolic volume. As an approximation, however, the assumption of one common end-systolic P-V relation seems tolerable. — Based on Franks diagram, a concept for assessment of ventricular and myocardial function is presented following a discussion of the determinants of the diastolic and end-systolic P-V relations, as well as the methodological difficulties and different notions with regard to the end-systolic P-V curve. The P-V area between the curves of systolic maxima and diastolic minima, up to a defined end-diastolic pressure, is recommended as a measure for quantitative evaluation of ventricular working capacity. Transformation into stress-length (σ−1) relations is indispensable for assessment of myocardial function under the conditions of changed ventricular geometry. The normalized σ−1 area yields a measure for interindividual evaluation of myocardial working capacity. This concept of evaluation does not mean acknowledgement of the visco-elastic theory of muscle contraction nor of the Emax concept.The P-V and σ−1 relations must, however, be complemented by time related parameters in order to estimate ventricular and myocardial power capacity.After a long-lasting search through international literature for “contractility indices” of general applicability and significance it seems appropriate to return to Franks diagram as the primary basis for evaluating cardiac mechanics.

The influence of myosin isoenzyme pattern on increase in myocardial oxygen consumption induced by catecholamines.

A new heart preparation was developed which permits in situ measurements of myocardial oxygen consumption and substrate uptake in small animals. Using this new method the mechanical activity, as well as oxygen consumption and substrate uptake of the heart, was measured in Goldblatt rats with left ventricular hypertrophy of about 40%. 1 In agreement with former investigations on the hypertrophied rat heart, this model also shows that both the performance of the whole ventricle, as well as the contractile force per unit of cross-sectional area, is increased in the state of stable hypertrophy. 2 The absolute values of oxygen consumption and substrate uptake are increased in the hypertrophied hearts. However, oxygen consumption and substrate uptake as related to muscle mass and to wall stress were largely identical in hypertrophied and control hearts. 3 Hypertrophied hearts and controls utilize substrates according to their respec tive arterial blood concentration. Under our experimental conditions approxi mately 50% of the total energy in both groups is obtained from glucose, 30% from lactate, and 20% from fat. The relatively high consumption of lactate could be explained by the glucose uptake and lactate release of the erythrocytes.

Die Aussagekraft verschiedener Kontraktilitätsindizes beim Herzen in situ

SummaryThe extent to which conclusions about myocardial performance may be drawn from end-systolic pressure-volume relations was investigated. Left ventricular isovolumetric and end-systolic pressure-volume relationships were measured in the rat, under acute impairment of contractility (hexobarbital), at chronic pressure overload (spontaneously hypertensive rats), and at chronic volume overload (aortocaval shunt). Our results confirm the classic conception of Otto Frank where the curves of the isovolumetric maxima and the curves of the end-systolic pressure-volume relations follow separate courses. Acute alterations in contractility can be detected from shifts in the end-systolic pressure-volume relations. In chronic pressure or volume overloaded hearts the end-systolic pressure-volume relations do not render conclusions about ventricular or myocardial performance since in chronically altered hearts, the course of the end-systolic pressure-volume relations is primarily influenced by geometric factors.

Inotrope Wirkungen des Nervus Vagus am Hundeventrikel in situ

SummaryLeft ventricular hypertrophy of about 40% was produced in rats by narrowing one renal artery (Goldblatt II) and of about 6% by swimming-training for 2 hours a day for 14 weeks. The dynamics of the hypertrophied ventricles were investigated by means of the isovolumic systolic and diastolic pressure-volume relations, the stress development during afterloaded and isovolumic contractions, and the force-velocity relation. The following results were obtained: The performance of the whole hypertrophied ventricle is increased. The developed stress and the maximum rate of stress development are enhanced, probably as a consequence of the increased density of the contractile proteins. The maximum shortening velocity can be reduced at the same time.ZusammenfassungAn Ratten wurde eihe linksventrikuläre Hypertrophie von ca. 40% durch Einengung einer Nierenarterie (Goldblatt II) und von ca. 6% durch ein Schwimmtraining (während 14 Wochen täglich 2 Stunden) erzeugt. Die Dynamik des hypertrophierten Ventrikels wurde anhand der isovolumetrischen systolischen und diastolischen Druck-Volumen-Beziehungen, der Spannungsentwicklung bei auxotonischer und isovolumetrischer Herztätigkeit sowie anhand der Kraft-Geschwindigkeit-Beziehung untersucht. Folgende Ergebnisse wurden erhoben: Die Arbeitskapazität des hypertrophierten Gesamtventrikels ist gesteigert. Die isovolumetrische Spannungsentwicklung und die Geschwindigkeit der Spannungsentwicklung nehmen zu, wahrscheinlich infolge der erhöhten Dichte der kontraktilen Strukturen. Die maximale Verkürzungsgeschwindigkeit kann bereits in diesem Stadium der Hypertrophie vermindert sein.