Stroke volume control

Although blood pressure control follows Ohm s law and seems to be simple, it underlies a complex circuit of interrelated systems. Hence, numerous physiologic systems that have pleiotropic effects and interact in complex fashion have been found to modulate blood pressure. Because of their number and complexity it is beyond the scope of the current account to cover all mechanisms and feedback circuits involved in blood pressure control. Rather, an overview of the clinically most relevant ones is presented. These systems include the heart, the blood vessels, the extracellular volume, the kidneys, the nervous system, a variety of humoral factors, and molecular events at the cellular level. They are intertwined to maintain adequate tissue perfusion and nutrition. Normal blood pressure control can be related to cardiac output and the total peripheral resistance. The stroke volume and the heart rate determine cardiac output. Each cycle of cardiac contraction propels a bolus of about 70 ml blood into the systemic arterial system. As one example of the interaction of these multiple systems, the stroke volume is dependent in part on intravascular volume regulated by the kidneys as well as on myocardial contractility. The latter is, in turn, a complex function involving sympathetic and parasympathetic control of heart rate intrinsic activity of the cardiac conduction system complex membrane transport and cellular events requiring influx of calcium, which lead to myocardial fibre shortening and relaxation and affects the humoral substances (e.g., catecholamines) in stimulation heart rate and myocardial fibre tension. 

Discuss the factors that control stroke volume... 

Silicon micropumps offer major advantages in terms of system miniaturization and control over low flow rates with a stroke volume 160 nL.14 The micropump has the characteristics of very small in size, implantability in the human body, low flow rates (in the range of 10 pL/min), moderate pressure generation from the microactuator to move the drug, biocompatibility, and most important, a reliable design for safe operation. The implantable device is particularly suitable (over the injectable drug delivery systems) for patients with Parkinson s disease, Alzhiemer s disease, diabetes, and cancer, as well as chronically ill patients, because the catheter that is attached to the device can transport drug to the required site. 

A discernible trend in modem pump design is towards the use of very small pistons (stroke volume around 100 pi). These tiny pistons have to be operated at very high driving speeds, to provide the flow rates required in analytical HPLC. However, when they are used in combination with electronic feedback pulse control mechanisms, as described above, they can provide extremely stable solvent delivery characteristics. Such is the efficacy of this approach that single piston pumps designed in this way are able to easily out-perform older dual piston pumps, and are consequently beginning to account for a major part of the LC pump market. 

Coenzyme QIO is a powerful antioxidant naturally occurring in the mitochondria of myocardium, and it is an electron carrier in the mitochondrial synthesis of ATP. Patients with heart failure have lower myocardial levels of coenzyme QIO, but supplementation has been demonstrated to have variable benefits in randomized controlled trials. One meta-analysis on the use in congestive heart failure showed improvements in stroke volume, ejection fraction, cardiac output, cardiac index, and end diastolic volume index. " Another antioxidant associated with beneficial effects in cardiac patients is lycopene, a natural constituent of tomatoes. Lycopene is the major carotenoid found in human serum, and epidemiological studies have indicated an effect of dietary supplementation in reducing heart disease. Few dietary interventions have been reported one study showed a mild but significant hypocholesterolemic effect, and another showed a significant reduction in LDL oxidation. " Animal studies show an antiatherogenic effect of DHEA, and a review of the clinical trials and studies on DHEA in males with coronary heart disease reported a favorable or neutral effect. Plasma levels of DHEA are decreased in patients with chronic heart failure in proportion to its severity. ... 

Dofetilide has a small positive inotropic effect in animal hearts (15,33). In a double-blind, placebo-controlled study of oral dofetilide 125, 250, or 500 mg bd for the maintenance of sinus rhythm after cardioversion of sustained atrial fibrillation or flutter in 201 patients, there were small changes in echocardiographic measures of atrial contractility, but no changes in stroke volume or cardiac output (34). 

The function of the cardiovascular system is to maintain adequate tissue perfusion. Cardiac output is the product of heart rate (rhythm) and cardiac contractility (giving rise to stroke volume). These factors are under neuronal, hormonal and mechanical control systems. Pharmacological manipulation of any of these contributors will result in changes in cardiovascular function and hence peripheral blood flow. In human medicine, the primary goal is to increase life expectancy, while maintenance of performance and quality of life are the main priorities in equine medicine. 

Heart rate is controlled by the autonomic nervous system. Stroke volume, or the volume of blood ejected during systole, depends on preload, afterload, and contractility. As defined by the Frank-Starling mechanism, the ability of the heart to alter the force of contraction... 

Although -blockers and calcium chaimel blockers have taken a more prominent role in acutely controlling rate in patients with rapid atrial fibrillation or flutter, a cautionary note must be made. That is, most patients with these tachycardias also have concomitant symptoms of heart failure, and these two forms of drug therapy may worsen the situation initially. Usually, a prompt decline in rate and increase in stroke volume balances the decrease in contractility seen with p blockers or calcium chaimel blockers such that heart failure symptoms remain unchanged. However, occasionally, severe reactions and hypotension may occur one study implies that diltiazem may be safer than verapamil. ... 

Blood pressure (BP) is a product of the total peripheral resistance (TPR) times the cardiac output (CO). The CO is equal to the heart rate (HR) times the stroke volume (SV). The autonomic (neural) system helps regulate the BP through feedback control involving the baroreceptors, the cardiovascular centers in the brain stem, and the PANS and SANS, which act in an opposing but coordinated manner to regulate the pressure. 

With innervation intact, the circulation at rest maintains constant ventricular stroke volume and blood pressure, on average. In addition, the regulation of cardiac output is accomplished primarily through the control of peripheral resistance. Then, the slow changes in heart rate ( ) are directly related to cardiac output (CO) and inversely to peripheral resistance (Rs), so that, fh oc CO oc 1/Rg [Berne and Levy, 1977]. This relationship is fundamental to the vascular theory of heart rate variation [Hering, 1924] and underscores the role of a time varying peripheral resistance. In this chapter, the dynamics of peripheral resistance control is examined analytically as an explanation of the very low frequency variation in heart rate. 

The evolution of the upright posture has provided a unique challenge to a blood pressnre control system that had principally evolved to meet the needs of animals that spent the majority of their time in a dorsal position (6-9). The ANS provides the principal means for both short- and long-term responses to changes in position (10). When standing, there is a gravity-mediated downward displacement of approximately 300-800 ml of blood to the vasculature of the abdomen and lower extremities (11). This represents a volume drop of between 25 and 30%, half of which occurs within the first few minutes of standing. This sudden redistribution of blood results in a fall in venous return to the heart. Because the heart can only pump the blood that it receives, this causes a fall in stroke volume of approximately 40% and a decline in arterial pressure. 

Figure 2. Flow chart of the procedures to test the ventricular model (in terms of end-systolic pressure-volume relationship) and the arterial model by end-systolic pressure-stroke volume relationship using one control set of loads (4 preloads and 1 afterload) and 8 noncontrol load sets (4 preloads and 8 afterloads).

Figure 9.15 Half stroke volumes of the circle-shaped IPMC diaphragm (Reproduced with permission from Lee, S., Kim, K. J. and Park, H. C. (2006) Modeling of an IPMC Actuator-driven Zero-Net-Mass-Flux Pump for Flow Control, J. Intelligent Mat. Systems and Structures, 17, 6, 533 1. Sage Publications).

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