Ejection fraction, ventricular pressure—volume

Ideally biomarkers of activity should be identified at various times over the course of the study to support the pharmacodynamic activity (e.g., normalization of insulin, improvement in beta cell function as measured by C-peptide level, or control of glucose following transplantation of P pancreatic islet cells) improvement of motor coordination in mice with spinal cord damage following transplant of neurons or repair of heart function (e.g., functional measures such as LV ejection fraction, pressure volume loops, ventricular pressure and heart wall thickness). Such markers may also be useful in subsequent clinical... 

Figure 13-2. Ventricular function (Frank-Starling) curves. The abscissa can be any measure of preload—fiber length, filling pressure, pulmonary capillary wedge pressure, etc. The ordinate is a measure of useful external cardiac work—stroke volume, cardiac output, etc. In congestive heart failure, output is reduced at all fiber lengths and the heart expands because ejection fraction is decreased. As a result, the heart moves from point A to point B. Compensatory sympathetic discharge or effective treatment allows the heart to eject more blood, and the heart moves to point C on the middle curve.

FIGURE 8.5 Ventricular and root aortic pressures (solid curves, left ordinate) and ventricular outflow (dashed curve, right ordinate) computed using the model of Equation 8.8 for a normal canine left ventricle pumping into a normal arterial circulation. The topmost solid curve corresponds to a clamped aorta (isovolumic). This ventricle has initial volume of 45 ml and pumps out 30 ml, for an ejection fraction of 66%, about normal. 

The cardiac pump theory advocates that there is (direct) pressure on the ventricles. This is supported by indications that compression depth is related to output, that cardiac (or more specifically ventricular) deformation is related to stroke volume, that the duration of compression has no effect, and that an increased compression rate will increase flow [17]. In the original manuscripts, as well as over time, 1.5 to 2 in. (4 to 5 cm) has been maintained as standard. Forward flow of blood is assumed to be caused by competent atrioventricular valves and sufficient competence of the aortic and pulmonary valves to avoid regurgitation during CPR diastole. Implicitly, ventricular filling is essential and artificial systole must be sufficiently frequent to generate acceptable flow, as stroke volumes may be relatively small compared to the normal 60 to 100 ml per beat at ejection fractions of 40 to 75%. Mitral valve closure during CPR systole is deemed essential for the cardiac pump theory to work. 

In mammals, there are characteristic variations in cardiac function with heart size. In the power law relation for heart rate as a function of body mass (analogous to Equation 54.3), the coefficient k is 241 beats.min and the power a is —0.25 [5]. In the smallest mammals, hke soricine shrews that weigh only a few grams, maximum heart rates exceeding 1000 beats.min have been measured [ 57]. Ventricular cavity volume scales linearly with heart weight, and ejection fraction and blood pressure are reasonably invariant from rats to horses. Hence, stroke work also scales directly with heart size [58], and thus work rate and energy consumption would be expected to increase with decreased body size in the same manner as heart rate. However, careful studies have demonstrated only a twofold increase in myocardial heat production as body mass decreases in mammals ranging from humans to rats, despite a 4.6-fold increase in heart... 

To answer the question of optimal matching between the ventricle and arterial load, we developed a framework of analysis which uses simplified models of ventricular contraction and arterial input impedance. The ventricular model consists only of a single volume (or chamber) elastance which increases to an endsystolic value with each heart beat. With this elastance, stroke volume SV is represented as a linearly decreasing function of ventricular endsystolic pressure. Arterial input impedance is represented by a 3-element Windkessel model which is in turn approximated to describe arterial end systolic pressure as a linearly increasing function of stroke volume injected per heart beat. The slope of this relationship is E. Superposition of the ventricular and arterial endsystolic pressure-stroke volume relationships yields stroke volume and stroke work expected when the ventricle and the arterial load are coupled. From theoretical consideration, a maximum energy transfer should occur from the contracting ventricle to the arterial load under the condition E = Experimental data on the external work that a ventricle performed on extensively varied arterial impedance loads supported the validity of this matched condition. The matched condition also dictated that the ventricular ejection fraction should be nearly 50%, a well-known fact under normal condition. We conclude that the ventricular contractile property, as represented by is matched to the arterial impedance property, represented by a three-element windkessel model, under normal conditions. 

Similar changes are noted when the right ventricle s contractile state is halved (c = 0.5). The right ventricular ejection fraction drops from 46 to 24%, root pulmonary artery pulse pressure decreases from 49/15 to 29/12 mmHg, and right stroke volume decreases from 64 to 44 ml, with an increased end-diastoHc volume of 164 ml, from 141 ml. Conversely, c can be increased in any heart chamber to depict administration of an inotropic drug. Although not plotted, pressures, flows, and volumes are available at any circuit site, all as functions of time. 

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