Diastolic Myocardium Research Articles

Load responsiveness of protein synthesis in adult mammalian myocardium: role of cardiac deformation linked to sodium influx.

Exposure of adult mammalian myocardium to increased hemodynamic loads augments cardiac protein synthesis, ultimately leading to hypertrophy of the affected chamber. This established relationship between loading conditions and protein synthesis was examined in terms of two questions. First, is there a basic difference between the anabolic effect of a passive load imposed on diastolic myocardium and that of an active load generated by systolic myocardium? This issue was addressed by measuring [3H]phenylalanine incorporation into muscle protein in either quiescent or contracting ferret papillary muscles, set at known isometric lengths. Myocardial protein synthesis increased in proportion to total muscle tension in each case, with an equivalent relation describing both quiescent and contracting muscles. Synthesis of two contractile proteins, actin and myosin heavy chain, were enhanced by muscle loading. Thus, a quantitative rather than qualitative difference between the anabolic effects of diastolic and systolic loading was demonstrated. Second, since increased sodium influx is an initial cellular response requisite to the growth-inducing activity of many substances, and since sodium entry through stretch-activated ion channels is stimulated by deformation of the sarcolemma, does cardiac deformation during increased loading promote sodium influx as a signal to increase anabolic activity? In either quiescent or contracting papillary muscles, the rate of 24Na+ uptake was found to increase with load. Streptomycin, a cationic blocker of the mechanotransducer ion channels, was without effect on protein synthesis in stimulated but slack muscles; however, it inhibited, in a dose-related manner, the augmented protein synthesis otherwise observed in contracting muscles developing tension. At 500 microM, streptomycin did not reduce active tension, but it did reduce the synthesis of both actin and myosin heavy chain. In a second pharmacologic approach, inotropic agents were chosen which uniformly increased muscle tension development but which had contrasting effects on sodium influx. Protein synthesis increased in the presence of Na+ influx enhancers, monensin or veratridine; however, protein synthesis decreased in the presence of amiloride, a sodium influx inhibitor. Thus, myocardial protein synthesis varied directly with sodium influx despite the positive inotropic effect observed with each of these agents. In addition, inhibition of protein synthesis by ouabain demonstrated that activation of the Na+ pump is required for the anabolic effect of load.(ABSTRACT TRUNCATED AT 400 WORDS)

A non-linear elastic model of contraction of ischaemic segments.

Previous studies have characterised the motion of the myocardium using a linear time varying elastance model, ie, they have sought to characterise the relationship between left ventricular volume and internal pressure as linear, but with time varying slopes over the cardiac cycle. However, the motion of myocardium during regional ischaemia has not been characterized by such models. Studies of totally ischaemic tissue and of myocardium in diastole have characterised the relationship between tension or stress and segment length as exponential. It is the purpose of this study to present a new model in which myocardial contraction is expressed as an exponential, but time varying elastic relationship. In this model tension, T, is related to segment length according to the formula T = e alpha(t)L + beta, where alpha(t) rises with systole and falls in diastole. This model was applied to the motion of hypokinetic segments noted in a series of conscious dogs studied for other purposes. Hypokinetic segments display early systolic bulging, decreased systolic shortening, and early diastolic recoil. These particular types of segment motion are naturally predicted by this model. Furthermore, the motion of myocardial segments as they become increasingly ischaemic may be predicted, including a gradual shift to the right and narrowing of the tension-length loop. alpha was noted to be independent of loading change, and thus may be viewed as an index of contractility. This model thus predicts the pattern of motion of hypokinetic segments and provides new insight into myocardial contractility.

Nonpolar density gradient ultracentrifugation in the direct determination of myocardial subcellular calcium

A new method is described for making direct measurements of compartmentalized subcellular stores of calcium in the isolated perfused dog heart. Cellular calcium was immobilized by freezing the myocardium in diastole with an extremely cold fluorocarbon fluid (-125 degrees C). All subsequent procedures were conducted under conditions which prevented ionic diffusion, either at temperatures well below the freezing point of water or in the absence of water. Sarcolemmal and mitochondrial enriched fractions were segregated from dessicated, homogenized, myocardial tissue by ultracentrifugation utilizing density-gradients composed of blends of silicone and halocarbon on fluids within which physiological salts are insoluble. The total calcium content of these isolated fractions were then determined by atomic absorption spectrophotometry. Ouabain and epinephrine were subsequently used to alter the contractility of the perfused hearts and such contractile alterations were then related to changes noted in the calcium activity of the isolated subcellular fractions. In this study the calcium levels of the enriched mitochondrial fractions were elevated by both ouabain and epinephrine, while the calcium levels of the enriched sarcolemmal fractions were elevated only by ouabain. The advantage of this segregative procedure is that it prevents artifactual intercompartmental calcium rearrangement and preserves calcium levels to those initially fixed in situ at the time of freezing.

Constitutive stress-strain relations for the myocardium in diastole

The importance of stress-strain myocardial constitutive relations is that they provide a criterion for behavior in vivo. Our purpose was to develop constitutive equations which are valid in diastole. The myocardium was assumed to be composed of a nonlinear viscoelastic, inhomogeneous, anisotropic (transversely isotropic) and incompressible material operating under adiabatic and isothermal conditions. The expressions contain five moduli. Two are fixed by the restriction of incompressibility, one is estimated, the remaining two refer to directions along and perpendicular to a fiber. Both possess a bimodal variation with intermodal switching occurring in late rapid filling and diastasis. They are functions of time and material constants. These constants can be observed. A dynamic test is suggested. Constitutive statements complete a set of equations sufficient for the solution of a class of boundary value problems. One type is formulated. They also permit the determination of stress from measured strain. Examples are given.