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oxygen delivery: role of circulating ATP Circ Res 2002;91:1046-55 e8 Abstract: Myocardial (macroscopic and microscopic) structure and function are described in this chapter to help the reader understand the physiologic principles (e.g., Frank-Starling mechanism, force-frequency relationship, end-systolic pressure-volume relationship) that govern the normal heart Regulation of stroke volume, myocardial metabolism, and the effect of ischemia on cardiac function are also explored Finally, the systemic vasculature and control of vascular tone are reviewed After reading this chapter, the reader will be able to understand the determinants of cardiac output and how the heart adapts to meet changing metabolic demands Key words: Segmental anatomy, myocyte, sarcomeres, cardiac output, systemic vasculature, cardiac function 24 Regional Peripheral Circulation PETER OISHI, JULIEN I HOFFMAN, BRADLEY P FUHRMAN, AND JEFFREY R FINEMAN PEARLS • • • • When delivering critical care, one must understand the specific properties that characterize the various regional circulations because therapies that benefit one region may be detrimental to another Vascular tone is influenced by (1) innervation and neural processes, (2) circulating endocrine and neuroendocrine mediators, (3) local metabolic products, (4) blood gas composition, (5) endothelial-derived factors, and (6) myogenic processes The transition from the fetal pulmonary circulation to the postnatal pulmonary circulation is marked by a dramatic fall in pulmonary vascular resistance and rise in pulmonary blood flow The failure to successfully make this transition is integral to a number of neonatal and infant diseases An important feature unique to the cerebral circulation is the presence of a blood-brain barrier As a result, the cerebral • • • vasculature responds differently from other vascular beds to humoral stimuli Regulation of myocardial perfusion is tailored to match regional myocardial oxygen supply to demand over the widest possible range of cardiac workload Increases in myocardial oxygen demand must be met by increases in myocardial blood flow Critically ill patients are at risk for impaired splanchnic blood flow that can impair the two chief functions of the gastrointestinal system: (1) digestion and absorption of nutrients and (2) maintenance of a barrier to the translocation of enteric antigens Splanchnic ischemia is associated with increased morbidity and mortality in critically ill patients Although renal blood flow remains constant over a wide range of renal artery perfusion pressures, urinary flow rate varies as a function of renal perfusion pressure General Features Basic Physiology General Anatomy Blood flow to a regional vascular bed is determined primarily by inflow pressure, vascular resistance, and outflow pressure Inflow pressure is usually systemic arterial pressure Outflow pressure approximates venous pressure but may exceed venous pressure at times if vascular tone is great enough to close the circulation above venous pressure or if external pressure impinges on the vasculature In a model to explain the relation of arterial pressure to flow, the circulation is represented by two capacitance vessels separated by a resistance A standpipe full of blood is allowed to discharge its contents into the arterial vasculature (the proximal capacitance) Blood flows across the resistance site (the arterioles), traverses the venous vasculature (the distal capacitance), and drains to a reservoir at some outflow pressure (Po; Fig 24.1) The pressure head of the system (Pi) is generated by the weight of the column of blood in the standpipe and is proportional to its height (Pi blood column height in cm H2O) As the standpipe discharges, the height decreases and Pi decreases This, in turn, decreases the rate of flow (Q) through the vasculature Q decreases almost linearly with Pi until the column is quite low Ultimately, flow will cease while there is still pressure in the standpipe Blood vessels comprise several distinct layers Moving from the innermost layer outward are the metabolically active endothelium, intima (with nerves and vasa vasorum), media, and adventitia Some vessels have fewer layers depending on the position and function of the vessel within the circulation The large arteries are elastic Their media contain concentric lamellae of perforated elastic tubes crosslinked by transverse collagen and smooth muscle When smooth muscle contracts, the wall becomes stiffer Smaller arteries have fewer lamellae The media are bounded by the internal and external elastic laminae Arterioles are less elastic, have no lamellae, and have a thin medium with circular or spiral smooth muscle and inner and outer elastic laminae Capillaries are thin walled and nonmuscular, ideal for transport of materials to and from the tissues Veins have medial muscle but thinner walls relative to lumen diameter compared with arteries The vascular endothelium has important metabolic characteristics, which may differ between vessel types (i.e., arteries vs veins) and different regions.1,2 203 204 S E C T I O N I V Pediatric Critical Care: Cardiovascular Standpipe Pump Pi RA AO Reservoir A V Rm V V V Po • Fig 24.1 Model P for facilitating interpretation of vascular pressure-flow relations When valves (V) are properly positioned, fluid filling the standpipe to height Pi discharges across the circulation to the reservoir at outflow pressure Po A, Artery; Rm, microvascular resistance; V, vein • Pi Pc Po Q • Fig 24.2 As the standpipe in Fig 24.1 discharges, Pi falls Flow conse- quently slows and ultimately stops when Pi Pc, the critical closing pressure of the circulation Pi reaches outflow pressure Po only if Po Pc The pressure at which flow ceases is the critical closing pressure of the circulation (Pc).3 Pi below Pc is insufficient to maintain vessel patency and permit continued flow (Fig 24.2) Incremental resistance to flow is generally defined as the change in pressure per unit change in flow (dPi/dQ) At pressures well above critical closing pressure, this is nearly identical to the vascular resistance (R) defined clinically as R ( Pi Po ) Q When Pi does not greatly exceed Pc but Pc does greatly exceed Po, however, incremental resistance can differ substantially from this clinical estimate Thus, an increase in Pc can be confused with a true increase in incremental resistance For example, a diagnosis of intrinsic pulmonary vascular disease (e.g., pulmonary arterial hypertension) based on measured pulmonary artery pressures in a patient receiving mechanical ventilation with high airway pressures (that raise Pc) may be spurious Ve ins Cv Pc es eri Art Ca Pi Rm • Fig 24.3 Model for facilitating interpretation of the relation of venous return to right atrial pressure The heart is replaced by a mechanical roller pump The right atrium (RA) is drained by the pump, and blood is infused into the aorta (AO) Blood then traverses the arteries, which have a capacitance (Ca) at an inflow pressure (Pi) determined by flow rate and microvascular resistance (Rm) Blood then returns through veins having capacitance (Cv) and critical closing pressure (Pc) to the right atrium Venous Return and Cardiac Output A second model illustrates the relationship of cardiac output to intrinsic mechanical properties of the systemic vasculature In this model, the heart acts as a roller pump, creating a circulation much like that achieved during venoarterial extracorporeal support (Fig 24.3) The roller pump displaces blood from the veins to the arteries and then across the resistance imposed by the arterioles As Q increases, more blood resides in the arteries and less in the veins This partitioning of blood depends on arterial capacitance (Ca), venous capacitance (Cv), and resistance to flow At maximal Q, Pi and arterial blood volume are high and venous pressure (Pv) is low When Pv reaches Pc, the roller pump cannot be increased further because the veins will collapse when Pv is less than Pc As Q is reduced, by turning down the roller pump, arterial pressure (Pi) and volume fall and Pv increases As Q approaches zero, venous pressure approaches the mean circulatory pressure (Pm; Fig 24.4) The importance of this model is that it can be used to illustrate the role of venous return as an independent determinant of cardiac output The Starling curve that describes the relationship between preload and contractility (and, hence, cardiac output) is illustrated in Fig 24.5 Over the steep portion of the curve, optimization of myocardial preload increases ventricular stroke volume This curve (see Chapter 23) can be superimposed on the venous return curve Cardiac output occurs at the theoretical intersection of these two curves, representing a given state of cardiac function (Starling curve) and simultaneous set of vascular characteristics (venous return curve; see Fig 24.5) It is important to recognize that the venous return curve is influenced by changes in blood volume and vascular tone Transfusion elevates the maximal venous return and thus cardiac output that can be achieved before the system reaches Pc Hemorrhage has the opposite effect Because neither transfusion nor hemorrhage directly alters vascular tone, the slope of the curve is not altered (Fig 24.6) Both interventions alter mean circulatory pressure because they change blood volume ... are less elastic, have no lamellae, and have a thin medium with circular or spiral smooth muscle and inner and outer elastic laminae Capillaries are thin walled and nonmuscular, ideal for transport... e8 Abstract: Myocardial (macroscopic and microscopic) structure and function are described in this chapter to help the reader understand the physiologic principles (e.g., Frank-Starling mechanism,... explored Finally, the systemic vasculature and control of vascular tone are reviewed After reading this chapter, the reader will be able to understand the determinants of cardiac output and how the