The purpose of this paper is to present recent findings that define in greater detail the mechanical behavior of the myocardium. Investigation of the mechanical events associated with myocardial contraction involves at least three parts: 1) study of the contractile elements of the muscle itself, 2) study of the elastic and hydraulic machinery coupling the forces of the contractile elements to the ventricular cavity, and 3) study of the nature of the load imposed on the ventricular cavity by the distal circulation. Although all three parts bear on this presentation, it is with the first of these, namely, the mechanical nature of the contractile element, that this report is primarily concerned.A. V. Hill's model of skeletal muscle* has been adopted tentatively as a prototype for the mechanical behavior of cardiac muscle. A mathematical model consistent with these views is shown schematically in figure 1. It consists of a circumferential arrangement of contractile elements attached to one another by a series of relatively stiff springs. These springs represent the "series elastic component" of the heart. The elasticity represented by the other spring, shown in figure 1 to be running parallel to the contractile elements, represents the "parallel elastic component" of the heart. During systole both elastic systems will be acting in parallel. Since the stiffness of the heart during systole is many times greater than that during diastole, 2 the stiffness of the parallel elastic component is much less than that of the series elastic component. Thus, to simplify analysis in this report, the presence of parallel elasticity was ignored during systole.In this simple preliminary model one would visualize systolic ejection as a group of contractile elements which are shortening and applying tangential tension through a series of springs to a hollow cavity. The presence of these springs means that the shortening velocity of the contractile elements, in general, will not be the same as the shortening velocity of the muscle as a whole. It will be necessary to incorporate this complicating factor into the analysis of the contractile behavior of the myocardium.Prior to this analysis it will be helpful to review briefly certain outstanding features of muscle behavior. Skeletal muscle exhibits two important mechanical properties. First, Parallel elasticSeries elastic Contractile elementFIGURE 1 Mathematical model of heart according to A. V. Hill's skeletal muscle model. 73 at California Institute of Technology on June 29, 2015 http://circres.ahajournals.org/ Downloaded from 74 FRY, GRIGGS, GREENFIELDthe maximum isometric force that can be developed by a tetanically stimulated muscle increases with length in the physiologic range. 3 The second important property is that for a given length the force that can be developed is a function of the velocity with which the muscle is contracting. 1 ' 4 The velocity of shortening decreases monotonically with the force developed. This "force-velocity" relationship is unique and reproducible for a...

The pressure-diameter relationship in the main pulmonary artery of man was estimated in 11 patients undergoing open-heart surgery. The diameter was measured with a recording caliper sutured to the vessel wall. The lateral intravascular pressure was measured with a 20-gauge needle connected directly to a Statham P23Db strain gauge. In the eight patients with normal pulmonary artery pressure the results indicate: 1) the shapes of the pressure and diameter curves are similar; 2) the mean value for the ratio of change in radius to change in pressure (ΔR/ΔP) x 103 was 8.77 cm/cm H2O (±sd 2.10); 3) the mean value for the pressure-strain elastic modulus (Ep) was 159.0 g/cm2 (±sd 26.0); and 4) the mean change in cross-sectional area during an average cardiac cycle was 22.9% of the diastolic value. In three patients with pulmonary hypertension the value of both ΔR/ΔP and the pressure-strain elastic modulus was lower. Submitted on April 27, 1962

Twenty-three patients exhibiting coronary insufficiency on exercise have been studied at rest and at exercise prior to and following sublingual administration of nitroglycerin. The most consistent and marked effect of nitroglycerin was the reduction in pulmonary artery pressure, total pulmonary resistance, and right ventricular work at rest and during exercise. Our patients were grouped according to the degree of left ventricular failure as indicated by the abnormality of rise in pulmonary artery pressure during exercise. It became evident that nitroglycerin improved left ventricular function in terms of increased output and lessened pulmonary artery pressure in cases in which failure was most severe.

To determine whether transmural metabolite gradients develop in the contracting, ischemic left ventricle due to factors other than a nonuniform distribution of myocardial blood flow, right and left coronary artery inflow was completely stopped with vessel occluders in open-chest dogs for 15 or 30 seconds before a transmural myocardial tissue sample was obtained for regional analysis of creatine phosphate, adenosine triphosphate (ATP), and lactate. Heart rate was controlled, and the decline in left ventricular systolic pressure during the period in which coronary blood flow was stopped was attenuated by aortic constriction. Studies were also performed in dogs that were (1) pretreated with propranolol, (2) subjected to ventricular fibrillation, and (3) volume loaded. Control studies revealed no transmural metabolite gradients in the normally perfused ventricle, but creatine phosphate was slightly lower in the inner region than it was in the outer and middle ventricular wall regions. With coronary blood flow stopped for 30 seconds, a significant lactate gradient, increasing from the outer to the inner region, was present. Propranolol-treated dogs with their coronary blood flow stopped for 30 seconds also exhibited a lactate gradient, but dogs with ventricular fibrillation and their coronary blood flow stopped for 30 seconds did not. Volume-loaded dogs with their coronary blood flow stopped for only 15 seconds had a significant lactate gradient. Reciprocal gradients occurred in creatine phosphate but not in ATP. The findings suggest that the contracting ventricle uses energy unevenly and that in myocardial ischemia one of the factors causing greater subendocardial vulnerability is a greater energy need in this region.• Previous studies from this laboratory have shown that metabolic changes occurring in the left ventricle because of inadequate coronary blood flow are greater in the subendocardium than they are in the subepicardium (1-4). This difference has been attributed primarily to nonuniform systolic compression of the coronary vessels (5, 6) which results in a greater impairment of subendocardial blood flow than it does of subepicardial blood flow (7,8). However, the possibility also exists that other factors, such as a higher subendocardial energy requirement (9-12), a greater capacity of subendocardial tissue cells for glycolysis (13,14), or greater subendocardial beta-adrenergic stimulation, contribute to the uneven metabolic response. The primary purpose of the present study was to investigate these possibilities in open-chest dogs by examining regional metabolite levels in the left ventricle after blood flow had been completely stopped in both the left and right coronary arteries for a brief but metabolically significant interval of time. Heart rate was controlled, and the decline in This work was supported by U. S. Public Health Service Grant HL 11876 from the National Heart and Lung Institute and by the Missouri Heart Association.Received April 7, 1975. Accepted for publication June 30, 1975. ...

The primary objective of this study was to ascertain whether resting coronary blood flow is under tonic restraint due to sympathetically mediated alpha-adrenergic coronary vasoconstriction. To accomplish this, we first developed and verified a technique for selectively sympathectomizing the posterior region of the canine left ventricle. This technique entailed the topical application of phenol in a thin line to specific sites on the myocardium and epicardial vessels. As part of the verification, we demonstrated that left stellate nerve stimulation caused increases in the myocardial extraction ratios for oxygen and lactate in the normally innervated region (I) of the ventricle, but not in the sympathectomized region (Sx). We then measured regional myocardial blood flow with microspheres in phenol-treated animals under conscious, resting conditions. The animals were acclimated to the laboratory environment, and their arterial plasma norepinephrine levels averaged 135 +/- 37 pg/ml. heart rate (81 +/- 3 bpm) and mean aortic pressure (100 +/- 2 mm Hg) were not significantly affected by beta-adrenergic blockade or combined alpha- and beta-adrenergic blockade in these animals. Blood flow in I and Sx averaged 0.87 +/- 0.08 ml/min per g and 0.85 +/- 0.07 ml/min per g, respectively, and the difference was not statistically significant. The endocardial-to-epicardial blood flow ratio in I and Sx averaged 1.23 +/- 0.03 and 1.29 +/- 0.04, respectively, and the difference was not statistically significant. The results were not significantly affected by beta-adrenergic blockade or combined alpha- and beta-adrenergic blockade. We were unable to confirm previous evidence in the literature of significant resting sympathetic coronary vasoconstrictor tone in the conscious animal.