What pulse is located in the groove between the medial malleolus and the achilles tendon?

Developmental Differences in Myocardial Structure and Excitation-Contraction Coupling.

Generation of myocardial contractile force increases with maturation.20-22 Developmental differences in contractility are mostly caused by age-related differences in myocardial structure (Fig. 30.3).

The immature myocyte is smaller and has greater intracellular spatial disorganization than its mature counterpart.22 Also, a large proportion of the immature myocyte is inhabited by noncontractile organelles that do not contribute to force generation. The small, spherical structure of the immature myocyte and the central location of noncontractile elements impose a biophysical disadvantage to shortening.22

Immature myofibrils assume a random arrangement rather than the parallel arrangement seen in adult myocytes.21-23 There are also far fewer myofilaments—the fundamental units of cross-bridge formation.23 An increased number of myofilaments correlates with an increase in myocardial force generation.24 Isoform switching of myofibrillar proteins with development also contributes to improved contractile efficiency with age.25,26

The calcium-handling mechanism in the neonate is both underdeveloped and inefficient.23 The cytosolic calcium concentration is primarily dependent on transsarcolemmal flux of calcium because T-tubules and sarcoplasmic reticulum are scarce and intracellular calcium regulatory proteins are functionally immature.27-30 Neonatal myocardium is more sensitive to changes in extracellular ionized calcium and relies more on glucose metabolism. Thus there is a greater risk for myocardial dysfunction given the neonates' decreased stores of calcium, inadequate glycogen stores, and impaired gluconeogenesis.31

Adult myocardium is densely innervated by a plexus of sympathetic nerves.32 However, sympathetic innervation in neonatal myocardium is incomplete.24,32 Parasympathetic tone predominates, and hypotensive episodes are easily evoked.33

Cardiac stores of norepinephrine, a reflection of sympathetic innervation, is lowest in late-term fetuses but approaches adult levels by 4 weeks of age.34 This is despite no significant quantitative difference between neonatal and adult beta-adrenergic receptors on the myocardial cell surface.35,36 Functional uncoupling of beta-receptor–G protein–adenylate cyclase complex in the newborn limits the effectiveness of catecholamine-modulated contractility in this age-group.37

Myocardial contractility

Local anesthetics produce a dose-dependent decrease in myocardial contractile force. Recent investigations have shown that receptors other than voltage-gated Na+ channels may be significant. Local anesthetic blockade of cardiac Ca2+ channels causes decreased inward Ca2+ influx, a shortened action potential, and therefore weakened contraction of the myocardium.27 Potent effects on the potassium channel may contribute as well. Disruption of cellular energy metabolism can occur. Especially, the inhibition of cyclic adenosine monophosphate (cAMP) production (most potently by bupivacaine) may contribute to the negative inotropy and interfere with resuscitation with epinephrine.28 Bupivacaine depresses contractility more than lidocaine at equipotent doses, as demonstrated by injecting the local anesthetic directly into the coronaries while avoiding other systemic effects such as vasomotor changes. This may be due to a fivefold greater potency of bupivacaine over lidocaine as a Ca2+ channel blocker.27

Peripheral Pulses

A quick assessment of all peripheral pulses would help assess heart rate, rhythm, and force. Peripheral pulses include radial, brachial, carotid, popliteal, posterior tibial, and dorsalis pedis pulses. The peripheral pulse is felt by the gentle compression of the artery against the underlying structures such as bone or the soft tissues. The radial pulse is felt by palpating the artery at the lower end of the radius bone anteriorly. The brachial artery can be felt at the cubital fossa just medial to the biceps tendon. A posterior tibial pulse is felt 1 inch below and behind the medial malleoli, against the body of calcaneum, in the groove between the medial malleolus and the Achilles tendon. Dorsalis pedis pulses are felt at the ankle in the first interosseous space of the feet, medial to the external hallucis tendon. While examining the peripheral pulse, it is necessary to appreciate the rate, rhythm (regular vs. irregular), and character (normal vs. weak vs. bounding) of the sound, as well as the condition of the vessel wall (e.g., calcified arteries in elderly can feel like fibrous cords). It is also a good practice to feel both radial pulses simultaneously to appreciate any radio-radial delay (e.g., aortic dissection) and the radial and femoral pulses to appreciate radio-femoral delay (e.g., coarctation of the aorta).

To obtain an accurate reading of the radial pulse, the clinician can count the number of beats in 30 s; if the beats are regular, multiply this number by two to obtain the number of beats per minute (bpm). However, if the beats are irregular, it is recommended to count the number of beats for the full minute. The normal heart rate for adults is 60–100 bpm. Children are expected to have higher heart rate ranges (e.g., newborns: 70–170 bpm, 1- to 6-year-olds: 75–160 bpm, 6- to 12-year-olds: 80 to 120 bpm).

VIII. SUMMARY

Calcium ions are essential for cardiac excitation–contraction coupling and cardiac contractile force development. Although mitochondria are known to serve as Ca2+ sinks in cardiomyocytes, the intracellular concentration of Ca2+ is mainly controlled by two major membrane systems: sarcolemma and sarcoplasmic reticulum. This process of Ca2+ control in the cell is regulated by protein phosphorylation and dephosphorylation, which are in turn mediated by protein kinases and phosphatases, respectively. Defects in the mechanisms for the entry or removal of Ca2+ at the level of sarcolemma, as well as abnormalities in Ca2+ release or Ca2+ uptake processes at the sarcoplasmic reticulum, are known to result in the development of intracellular Ca2+ overload. The increased concentration of Ca2+ activates different proteases and phospholipases and thus produces changes in the structure of cardiomyocytes. The elevated level of cytosolic Ca2+ also results in an excessive accumulation of Ca2+ in mitochondria, which impairs the process of energy production and lowers the energy status of the myocardium. Accordingly, intracellular Ca2+ overload is considered to produce myocardial cell damage, metabolic derangement, and heart dysfunction.

Several lines of evidence have been put forward implicating Ca2+ overload as a mechanism for the occurrence of myocardial ischemia–reperfusion injury. Acidosis, depletion of high-energy phosphate stores, mitochondrial dysfunction, and the generation of reactive oxygen species are some of the plausible contributing factors in the occurrence of Ca2+ overload. The duration and the severity of the ischemic insult are major determinants in the degree of ischemic injury. The depression of contractile function for a prolonged period upon reperfusing of the ischemic heart is commonly called myocardial stunning. Severe ischemic injury associated with cell necrosis is correlated with the occurrence of Ca2+ overload. However, hearts adapted to a state of reduced myocardial oxygen supply (hibernation) maintain the ability to regulate intracellular levels of Ca2+. Although experimental evidence is not available, Ca2+ overload has been suggested to be a critical factor underlying the incomplete recovery of heart function in the maimed myocardium. Preconditioning of the heart has been reported to be a possible therapeutic tool against Ca2+ induced cardiac injury. This protection has been shown to be mediated by several mechanisms, including the activation of protein kinases, antioxidants, and cardioprotective proteins. Several procedures are used to induce myocardial preconditioning and these include short periods of ischemia and pharmacological treatments with agents such as adenosine and norepinephrine.

1 Introduction

Maintenance of arterial blood pressure is carried out by varying vessel diameter along with heart rate and force of contraction causing changes in resistance and cardiac output, respectively. This allows matching of metabolic demand with the supply of oxygen and glucose to the respiring tissues and the removal of carbon dioxide and metabolic by-products from such tissues. It should be noted that this is also dependent on coordination with the respiratory system. Regulation of the cardiovascular system is carried out by the autonomic system with the heart (cardiac output) being regulated by sympathetic and parasympathetic (vagal) nerves, whereas regional blood flow and total peripheral resistance is only regulated by the sympathetic nervous system. In addition, hormones released from the brain such as vasopressin (antidiuretic hormone), kidney (renin), adrenal gland, and locally produced factors, e.g., endothelins and nitric oxide also regulate vessel diameter and the heart. Thus, the cardiovascular system is regulated via neural control, hormones, and local autoregulation; the latter two will not be dealt with in this chapter. Neuronal regulation is carried out in response to changes detected by stretch receptors, indicating changes in pressure. These stretch receptors are located in the carotid bifurcation and the aortic arch and are known as the carotid sinus and arterial baroreceptors. Further, low-pressure baroreceptors are found in the atria but will not be dealt with in this chapter. In addition, specialized chemoreceptive neurones and glia are also located in this region (in the carotid bodies), and they detect changes in oxygen, increases in carbon dioxide, and falls in pH of the blood. Chemoreceptors are also located near the ventrolateral surface of medulla oblongata, in the retrotrapezoid nucleus (parafacial respiratory group) [1] and/or the raphé pallidus [2], but these central chemoreceptors will not be considered in this chapter. The other reflex that will be considered is the cardiopulmonary reflex (von Bezold-Jarisch reflex), which has its sensory receptors in the heart and lungs and whose afferent fibers run in the vagus. These afferents can be also activated by veratrum alkaloids, nicotine, histamine, and 5-hydroxytryptamine (5-HT); the latter via 5-HT3 receptors and this reflex has been referred to as a chemoreflex. The cardiopulmonary reflex functions to regulate right and left ventricular outputs to compensate for changes in systemic venous return, thus maintaining of pulmonary circulatory variables optimum levels (see Ref. [3]). Overall this reflex is also considered to regulate changes in blood volume (see Ref. [4]). Finally, there is the diving response, which counters normal homeostatic control [5] and is basically two reflexes, the trigeminal cardiac and chemoreceptor reflex, which combine to cause bradycardia, sympathoexcitation and apnoea (see Refs. [5,6]). The afferents fibers of all these reflexes terminate in the nucleus tractus solitarii (NTS) located near the dorsal surface of the brainstem (see Ref. [7]; Fig. 13.1). The NTS itself is richly innervated by fibers containing 5-HT (serotonin; Fig. 13.2), the majority originating centrally [8,9]. However, some of these terminals may also arise from vagal primary afferents whose cell bodies are located in the nodose ganglia [10–12] and also from baroreceptor and chemoreceptor afferents running in the glossopharyngeal nerve, whose cell bodies are located in the petrosal ganglia [12]. The NTS contains many of the 14 5-HT receptor subtypes, 5-HT1A and 5-HT1B [13,14], 5-HT2A and 5-HT2C [15–17], 5-HT3 [18], 5-ht5A [19], and 5-HT7 [20–22]. This chapter will review how 5-HT regulates blood pressure, utilizing these different receptors within the major brainstem areas involving cardiovascular regulation: the NTS, the site cardiovascular afferent termination, the nucleus ambiguus (NA), the major site of regulation of parasympathetic control of the heart along with the dorsal vagal nucleus (DVN). Finally, the rostral and caudal ventrolateral medulla, the sites of regulation sympathetic outflow, will be considered, although the role of 5-HT at this level is far from clear, as little data are available.

Abstract

For the atrial and ventricular walls of a fish heart to constrict and eject blood out of the heart, force has to be generated by the cardiac muscle cells (cardiomyocytes) when they contract. Cardiomyocytes contract, as all muscle cells do, when intracellular Ca2+ concentrations rise and Ca2+ binds to the contractile element, the cellular machinery responsible for powering the contraction. This binding allows the formation of cross-bridges between the actin thin filament and the myosin thick filament under the regulation of the troponin complex (troponin I, troponin T, and troponin C) and tropomyosin. Like all biochemical processes, the contractile reaction is sensitive to changes in temperature, with a decrease in temperature significantly reducing the ability of the cardiomyocyte to contract. The rainbow trout (Oncorhynchus mykiss) heart functions effectively at temperatures low enough to stop a human heart and over a range of temperatures that reflects their seasonal water temperatures (5–20 °C). The ability of the rainbow trout heart to function at low temperatures, and therefore remain active throughout the year, is due to adaptations in the proteins of the contractile element. This article reviews the components and regulation of the contractile element and considers various adaptations that allow the fish heart to function over a range of environmental temperatures.

Exercise

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In anticipation of exercise, the vagus nerve impulses to the heart are inhibited and the sympathetic nervous system is activated by central command. The result is an increase in heart rate, myocardial contractile force, cardiac output, and arterial pressure.

With exercise, vascular resistance increases in skin, kidneys, splanchnic regions, and inactive muscles and decreases in active muscles.

The increase in cardiac output is accomplished mainly by the rise in heart rate. Stroke volume increases only slightly. In well-trained endurance athletes, stroke volume increases substantially during exercise.

During exercise total peripheral resistance decreases, O2 consumption and blood O2 extraction increase, and systolic and mean blood pressures rise slightly.

As body temperature rises during exercise, the skin blood vessels dilate. However, when the heart rate becomes maximal during severe exercise, the skin vessels constrict. This enlarges the effective blood volume but causes greater increases in body temperature and a feeling of exhaustion.

The limiting factor in exercise performance is the delivery of blood to the active muscles.

Abstract

The heart produces the arterial pressure by virtue of pumping blood from the low-pressure, venous side of the circulation, into the high-pressure, arterial side. Constriction of the vascular system, however, raises the pressure by virtue of having less compliant vessels in which the heart forces the blood. The total volume of blood in the arterial side, relative to its compliance, also contributes to the blood pressure. Regulation of blood pressure is thus achieved by regulating the strength of the heart beat (cardiac contractility), vascular smooth muscle contractility, and the blood volume. This is achieved through nerves, hormones, and renal mechanisms. The nervous regulation includes the baroreceptor system, in which stretch sensors in the carotid sinus increase their firing rate with increased pressure, which activates parasympathetic output to the heart to reduce heart rate. Hormones include the renin–angiotensin–aldosterone system, andidiuretic hormone, and atrial natriuretic peptide.

3.2 Structure of lymphatic vessels

Lymphatic vessels resemble veins in structure with the following exceptions:

Lymphatics have thinner walls.

Lymphatics contain more valves.

Lymphatics contain lymph nodes located at certain intervals along their course.