CLINICAL AND PATHOPHYSIOLOGIC CONSIDERATIONS Delivery of oxygen and nutrients is predominantly regulated by cardiac output and microvascular blood flow Cardiac output is calculated by multiplying the stroke volume (volume of blood ejected by the left ventricle) by the heart rate (ejection cycles per minute) The stroke volume depends on the filling volume of the ventricle (preload), myocardial contractility and rhythm, and the systemic vascular resistance (SVR) against which the ventricle is pumping blood to the body (afterload) Heart rate, preload, contractility, rhythm, and afterload are regulated through a variety of neurohumoral and metabolic factors, including the sympathetic nervous system, endogenous catecholamine release, tissue pH and oxygen tension, nitric oxide, reactive oxygen species, and calcium homeostasis, that themselves respond to changes in blood volume, circulating inflammatory cytokines, and endothelial cell activation ( Fig 10.2 ) Infants require special consideration, as they have relatively little reserve myocardial contractility to increase stroke volume and thus depend almost exclusively on heart rate to increase cardiac output