Cardiac output and its regulation

The heart is two pumps in series: the right heart drives blood through the pulmonary circulation and the left heart through the systemic circulation, so over any period the two outputs are equal, and a mismatch of even a few percent would soon congest one circuit. The systemic organs are arranged in parallel, each receiving arterial blood at the same pressure and adjusting its own flow through its arterioles, so the flow to one organ can change without directly altering the others. Functionally the vessels form a sequence: the aorta and large arteries are the conduits and pressure reservoir, the arterioles are the resistance vessels that regulate distribution and set arterial pressure, the capillaries are the exchange vessels, and the venules and veins are the capacitance vessels holding most of the blood. Mean pressure falls from about 100 mmHg in the aorta to about 35 mmHg at the arteriolar end of the capillaries, 15 mmHg at their venous end and nearly 0 mmHg in the right atrium; the largest drop is across the arterioles. In the pulmonary circuit the same flow passes at a mean arterial pressure of only about 16 mmHg because pulmonary resistance is about one tenth of systemic. Velocity is inversely related to total cross-sectional area: about 33 cm/s in the aorta, 0.3 mm/s in the capillaries and rising again in the venae cavae. At rest the pulmonary vessels hold about 9 percent of the blood, the heart 7 percent, the arteries 13 percent, the capillaries 7 percent and the systemic veins about 64 percent.

The most important intrinsic property of the heart is that it adapts its output to venous return without any nervous or hormonal signal. When more blood enters the ventricle in diastole, the fibres are stretched, the sarcomeres move toward the length of optimal actin–myosin overlap and calcium sensitivity rises, so the next contraction is stronger and ejects the larger volume. This is the Frank–Starling law of the heart: within limits, the energy of contraction is proportional to the initial length of the fibre. Plotted as stroke volume or cardiac output against right atrial pressure or end-diastolic volume, the ventricular function curve rises steeply at first and then flattens; the failing heart works on a lower, flatter curve, and sympathetic stimulation shifts the curve up and to the left. Stretch of the right atrium also raises the heart rate by 10 to 20 percent through a direct effect on the sinoatrial node and through the Bainbridge reflex. The Frank–Starling mechanism keeps the outputs of the two ventricles matched beat by beat: if the right heart pumps a little more, the extra blood arrives at the left ventricle within seconds, stretches it, and the left output rises to match. A second intrinsic influence is afterload: for a given preload, a rise in aortic pressure reduces the stroke volume, although a healthy heart compensates at the next beats through the Frank–Starling mechanism and the Anrep effect.

The sympathetic nerves reach the whole heart. Their noradrenaline acts on beta-1 receptors, raising cyclic AMP, which increases the rate of diastolic depolarisation in the sinoatrial node (positive chronotropy), speeds conduction through the atrioventricular node (positive dromotropy), increases calcium entry and release so contraction is stronger (positive inotropy) and speeds relaxation (positive lusitropy). Strong sympathetic stimulation can raise the rate to 180 to 200 per minute and double the force of contraction, tripling cardiac output; loss of sympathetic tone lowers output by about 30 percent. The parasympathetic (vagal) fibres are distributed mainly to the sinoatrial and atrioventricular nodes and the atria; acetylcholine acting on muscarinic receptors opens potassium channels and lowers cyclic AMP, slowing the rate, slowing atrioventricular conduction and weakening atrial contraction, with little direct effect on ventricular force. Strong vagal stimulation can stop the sinoatrial node, although a ventricular escape rhythm at 20 to 40 per minute usually takes over. Circulating adrenaline from the adrenal medulla reinforces the sympathetic effects, and thyroid hormone raises rate and contractility over days. The ionic environment sets the background: a high extracellular potassium depolarises the resting membrane, reduces the action potential and the force of contraction, and in severe cases causes conduction block and arrest in diastole; a high extracellular calcium increases the force of contraction and can cause spastic arrest in systole; a low calcium produces flaccidity; acidosis depresses contractility.

Because the heart pumps what returns to it, cardiac output at rest is set mostly by the periphery. Venous return depends on the mean systemic filling pressure (about 7 mmHg, raised by blood volume and venoconstriction), on right atrial pressure (which opposes it) and on the resistance to venous return. Anything that lowers total peripheral resistance, such as exercise, anaemia, hyperthyroidism, beriberi or an arteriovenous fistula, raises venous return and therefore output, which is why these states produce a high-output circulation; anything that raises resistance or lowers filling pressure, such as haemorrhage or venous pooling on standing, lowers it. The maximum output a heart can achieve beyond its resting output is its cardiac reserve, normally 300 to 400 percent, up to 600 percent in athletes and near zero in severe heart failure, where the ventricle is already working at the top of its function curve. Cardiac index normalises output to body surface area: with an output of 5 L/min and a surface of 1.7 m² it is about 3 L/min/m², highest around the age of ten and falling to about 2.4 L/min/m² by eighty. Output rises in proportion to metabolic rate, which is why exercise, fever and pregnancy increase it. The major determinants of stroke volume are therefore preload (venous return), afterload (arterial pressure) and contractility (sympathetic tone and ions), and of heart rate the balance of autonomic tone.

The Fick principle states that the flow through an organ equals the rate at which a substance is taken up or released divided by the arteriovenous concentration difference. Applied to the lungs with oxygen: cardiac output = oxygen consumption ÷ (arterial oxygen content − mixed venous oxygen content), where oxygen consumption is measured by spirometry and mixed venous blood must be sampled from the pulmonary artery through a catheter. With a consumption of 250 ml/min and an arteriovenous difference of 50 ml per litre, output is 5 L/min. In indicator dilution a known amount of dye is injected into a vein and its concentration is followed in an artery; output equals the dose divided by the area under the concentration–time curve, with recirculation excluded. Thermodilution is the clinical version: cold saline injected into the right atrium is sensed by a thermistor in the pulmonary artery, and a computer integrates the temperature curve. Non-invasively, Doppler echocardiography multiplies the velocity–time integral across the aortic valve by the valve area to give stroke volume, and multiplies by rate; the electromagnetic flowmeter around the ascending aorta is used experimentally. Whichever method is used, the result is interpreted against body size as the cardiac index.