Andersons pediatric cardiology 1964

Atrial receptors are located in the walls of the right and left atria and in pulmonary venous and caval-atrial junctions.123,124 Two types of atrial receptors are described based on their discharge pattern in relation to atrial pressure changes Type A receptors signal atrial contraction and hence respond to an increase in central venous pressure These receptors send impulses via myelinated fibers in the vagus nerve, and the efferent portion consists of sympathetic activation The tachycardia in relation to stimulation of sinuatrial node caused by atrial stretch is termed the Bainbridge reflex Type B baroreceptors are stretch receptors stimulated by volume distension of the atria and their firing during ventricular systole The afferents are unmyelinated vagal fibers Atrial distension decreases sympathetic activity Receptors that respond to stretch and contractility are also present in the ventricles These receptors provide afferent input to the medulla via unmyelinated C fibers.125 Stimulation of these fibers decreases sympathetic tone and causes bradycardia and vasodilation Stretching of the atrial and ventricular myocardium also leads to the release of natriuretic peptides, as discussed earlier Apart from the reflex-triggered short-term control of the circulation, the central pathways responsible for the central command responses—such as those occurring at the onset of exercise or evoked by a threatening stimulus—are now better understood.126 Evidence suggests the existence of a supramedullary integrative loop that connects the brain stem and paraventricular nucleus of the hypothalamus The loop is composed of ascending noradrenergic projections from the nucleus of the solitary tract and caudal ventrolateral medulla and descending oxytocinergic and vasopressinergic neurons in the paraventricular nucleus of the hypothalamus projecting to brain stem areas It is likely that reflex-triggered control interacts with the central command responses to regulate the cardiovascular response during exercise Groups of neurons in the hypothalamus can project to synapse directly with sympathetic preganglionic fibers in the spinal cord, implying that the medullary vasomotor center is perhaps not the only region that directly controls sympathetic outflow.127 The autonomic nervous system represents the efferent component of the neural control of the circulation Up to three types of fibers may innervate blood vessels: sympathetic vasoconstrictor fibers, sympathetic vasodilator fibers, and parasympathetic vasodilator fibers As the size of vessel decreases, the density of autonomic innervation increases The small arteries and arterioles are therefore the most richly innervated arteries Sympathetic vasoconstrictor fibers release noradrenaline upon nerve stimulation and constitute the most important components in the neural control of the circulation Postsynaptically the α1-adrenoceptor is the predominant receptor mediating vasoconstriction Although noradrenaline is the principal neurotransmitter in the sympathetic nervous system, it coexists with adenosine triphosphate and neuropeptide Y in sympathetic neurons.128 Sympathetic vasoconstriction of arterioles increases vascular resistance, while constriction of capacitance vessels alters the circulating blood volume In larger arteries, contraction of vascular smooth muscle in response to sympathetic activation causes less significant change in arterial caliber but alters vascular tone and hence arterial stiffness Sympathetic vasodilator fibers are scarce and not tonically active Evidence suggests that sympathetic vasodilator fibers regulate skeletal vascular tone in many animal species Both cholinergic129 and nitric oxide–dependent130,131 mechanisms contribute to the vasodilator effect Parasympathetic vasodilator fibers are found in blood vessels of the salivary gland, cerebral arteries, and coronary arteries The vasodilator effect is mediated via release of acetylcholine with hyperpolarization of the vascular smooth muscle Long-term neural regulation of the circulation is modulated by humoral and other factors Angiotensin II is an important facilitator of sympathetic transmission It may enhance neurotransmitter release at sympathetic nerve terminals, sympathetic transmission through sympathetic ganglia,132 and perhaps central activation of sympathetic nervous activity.133 Nitric oxide interacts with the autonomic nervous system at both the central and peripheral levels.134 Centrally, nitric oxide decreases sympathetic vasoconstrictor outflow Peripherally, augmented vasoconstriction to nitric oxide synthase inhibition has been demonstrated in denervated forearm in humans.135 Interaction between nitric oxide and cholinergic vasodilator fibers is also evidenced by significant pressor response to nitric oxide synthase inhibition with cholinergic blockade.136 Finally, the hypothalamic paraventricular nucleus, which plays a role in the central command responses as discussed earlier, may mediate sustained increases in sympathetic nerve secondary to a variety of stimuli.119 Stress, anxiety, or pathologic conditions such as heart failure may hence exert a long-term influence on neural control of the circulation through the tonic activation of sympathoexcitatory neurons located in the paraventricular nuclei of the hypothalamus.118,126 Modeling of the Systemic Circulation Models From the mechanical perspective, the systemic arterial system can be envisaged as a network of elastic tubes that receive pulsatile blood flow from left ventricular ejection and transmit it distally as a steady stream into capillaries Hence, apart from acting as a low-resistance conduit, the systemic arterial tree functions as a cushion to smooth out pressure and flow pulsations generated by cycles of left ventricular contraction Although the success of the conduit function depends primarily on a low peripheral vascular resistance, the efficiency of cushioning function depends on the elastic properties, described in terms of stiffness, of the arterial system Modeling of the arterial circulation has contributed significantly to the understanding of the behavior of the arterial system and the effects of arterial load on the systemic ventricle The lumped model of arterial circulation, commonly termed the Windkessel model, was first described in the 18th century In his book Haemastaticks, Hales drew an analogy between the arterial system and an air-filled dome of the fire engine compression chamber (Windkessel) (Fig 74.1).137 The cushioning function of the dome smooths out the pulsatile blood flow and protects the peripheral vascular beds from exposure to large fluctuations in pressure The electrical analogues of the systemic arterial system are shown in Fig 74.2 The two-element electrical analogue of the Windkessel model comprises a capacitor, which represents the arterial compliance, and a resistor, the total peripheral resistance The modified Windkessel model138 takes into account the input impedance (see later) of the proximal aorta by the addition of a resistor proximal the two-element capacitance-resistance model A fourelement Windkessel model, with the addition of an inertial term, has further been proposed and shown to be superior to the three-element Windkessel as a lumped model of the entire systemic tree.139 Inertance is due to the mass of the fluid and, physiologically, it can be regarded as the inertial effect secondary to simultaneous acceleration of the blood mass within the vessel However, intrinsic shortcomings of the Windkessel models include the limitation of vessel elasticity to one site, lack of a finite velocity of propagation of the pulse wave, and failure to consider the significance of wave reflection