Cardiovascular system cardiac

Figure 15.4 Effects of the autonomic nervous system on mean arterial pressure. The baroreceptors, chemoreceptors, and low-pressure receptors provide neural input to the vasomotor center in the brainstem. The vasomotor center integrates this input and determines the degree of discharge by the sympathetic and parasympathetic nervous systems to the cardiovascular system. Cardiac output and total peripheral resistance are adjusted so as to maintain mean arterial pressure within the normal range.

Adverse Effects. Quinine is associated with many adverse effects involving several primary organ systems. This drug may produce disturbances in the CNS (headache, visual disturbances, ringing in the ears), gastrointestinal system (nausea, vomiting, abdominal pain), and cardiovascular system (cardiac arrhythmias). Problems with hypersensitivity, blood disorders, liver dysfunction, and hypoglycemia may also occur in some individuals. 

Despite conflicting results, enflurane is generally considered to have httle effect on the cardiovascular system. Cardiac output was mildly influenced in healthy men and the negative inotropic effects of enflurane (2) were more pronounced in patients with congestive heart failure (3). Myocardial damage was suggested to be an unhkely comphcation of enflurane anesthesia, even in patients with ischemic heart disease (4). 

Histamine in the Cardiovascular System. It has been known for many years that histamine is present in sympathetic nerves and has a distribution within the heart that parallels that of norepinephrine (see Epinephrine and norepinephrine). A physiological role for cardiac histamine as a modulator of sympathetic responses is highly plausible (15). A pool of histamine in rat heart located neither in mast cells nor in sympathetic nerves has been demonstrated. The turnover of this metaboHcaHy active pool of histamine appears to be maintained by normal sympathetic activity. 

The heart, a four-chambered muscular pump has as its primary purpose the propelling of blood throughout the cardiovascular system. The left ventricle is the principal pumping chamber and is therefore the largest of the four chambers in terms of muscle mass. The efficiency of the heart as a pump can be assessed by measuring cardiac output, left ventricular pressure, and the amount of work requHed to accomplish any requHed amount of pumping. 

Mean arterial pressure and cardiac output, an expression of the amount of blood that the heart pumps each minute, are the key Indicators of the normal functioning of the cardiovascular system. Mean arterial pressure is strictly controlled, but by changing the cardiac output, a person can adapt, e.g., to increased oxygen requirement due to increased workload. Blood flow in vital organs may vary for many reasons, but is usually due to decreased cardiac output. However, there can be very dramatic changes in blood pressure, e.g., blood pressure plummets during an anaphylactic allergic reaction. Also cytotoxic chemicals, such as heavy metals, may decrease the blood pressure. 

Angiotensin converting enzyme (ACE) plays a central role in cardiovascular hemostasis. Its major function is the generation of angiotensin (ANG) II from ANGI and the degradation of bradykinin. Both peptides have profound impact on the cardiovascular system and beyond. ACE inhibitors are used to decrease blood pressure in hypertensive patients, to improve cardiac function, and to reduce work load of the heart in patients with cardiac failure. 

The substrate specificity of ACE is low. ACE cleaves a variety of pairs of amino acids from the carboxy-terminal part of several peptide substrates. The conversion of ANGI to ANGII and the degradation of bradykinin to inactive fragments are considered the most important functions of ACE. Both peptides have profound impact on the cardiovascular system and beyond. ACE is thus an important target for ACE inhibitors. These compounds are frequently and efficiently used in the treatment of hypertension and cardiac failure. 

Ca2+ is an important intracellular second messenger that controls cellular functions including muscle contraction in smooth and cardiac muscle. Ca2+ channel blockers inhibit depolarization-induced Ca2+ entry into muscle cells in the cardiovascular system causing a decrease in blood pressure, decreased cardiac contractility, and antiarrhythmic effects. Therefore, these drugs are used clinically to treat hypertension, myocardial ischemia, and cardiac arrhythmias. 

Pathological observations indicate that lesions of the cardiovascular system can be a cause of death in patients with anaphylaxis [2], Myocardial lesions might be the anatomical basis for the irreversible cardiac failure occasionally associated with systemic anaphylaxis [3]. There is compelling evidence that the heart is directly and/or indirectly involved in several forms of anaphylaxis in man [1,4,5]. 

Atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) are members of a family of so-called natriuretic peptides, synthesized predominantly in the cardiac atrium, ventricle, and vascular endothelial cells, respectively (G13, Y2). ANP is a 28-amino-acid polypeptide hormone released into the circulation in response to atrial stretch (L3). ANP acts (Fig. 8) on the kidney to increase sodium excretion and glomerular filtration rate (GFR), to antagonize renal vasoconstriction, and to inhibit renin secretion (Ml). In the cardiovascular system, ANP antagonizes vasoconstriction and shifts fluid from the intravascular to the interstitial compartment (G14). In the adrenal cortex, ANP is a powerful inhibitor of aldosterone synthesis (E6, N3). At the hypothalamic level, ANP inhibits vasopressin secretion (S3). It has been shown that some of the effects of ANP are mediated via a newly discovered hormone, called adreno-medullin, controlling fluid and electrolyte homeostasis (S8). The diuretic and blood pressure-lowering effect of ANP may be partially due to adrenomedullin (V5). 

Smith, E.R., Pathophysiology of cardiac electrical disturbances, in Physio-pathology of the Cardiovascular System, Alpert, J.S., Ed., Little, Brown, Boston, 1984, chap. 14. 

The development of cardiac assist devices and other instrumentation and components which come in contact with the cardiovascular system requires materials which will perform in a physiological environment. One particularly difficult application is the diaphragm for blood pumps, which requires an elastomer to undergo cyclic deformation and/or flexing while in contact with blood. 

The recommended initial daily dose for older patients or those with known cardiac disease is 25 mcg/day titrated upward in increments of 25 meg at monthly intervals to prevent stress on the cardiovascular system. 

One of the pollutants known to interfere with cardiovascular development is 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD). TCDD is a persistent, bioaccumulative environmental contaminant, as well as a potent developmental toxicant and human carcinogen [30]. Piscine, avian, and mammalian cardiovascular systems are sensitive to TCDD toxicity, with effects including cardiac enlargement, edema, and several dysfunctions. In zebrafish embryos, these effects include areduction in cardiomyocyte number at 48 hpf, decreased heart size, altered vascular remodeling, pericardial edema, and decreased ventricular contraction culminating in ventricular standstill [31-34]. 

Action on the CNS depends directly on the dose of administered drug, and can be manifested as fatigue, anxiety, tremors, and even convulsions in relatively high doses. Theophylline acts on the cardiovascular system by displaying positive ionotropic and chronotropic effects on the heart, which, can likely be linked to the elevated influx of calcium ions by modulated cyclic adenosine monophosphate and its action on specific cardiac phosphodiesterases. In the gastrointestinal system, methylxanthines simultaneously stimulate secretion of both gastric juice and digestive enzymes. 

Anaphylactic or anaphylactoid reactions may occur following administration of any dose or course of muromonab-CD3. Serious and occasionally life-threatening systemic, cardiovascular, and CNS reactions have been reported. These have included the following Pulmonary edema, especially in patients with volume overload shock cardiovascular collapse cardiac or respiratory arrest seizures coma. Hence, a patient being treated with muromonab-CD3 must be managed in a facility equipped and staffed for cardiopulmonary resuscitation. 

The triazolopyridine trazodone does not have an appreciable effect on the re-uptake of the neurotrans-mittors dopamine or noradrenaline. It is a weak inhibitor of serotonin re-uptake but is a potent antagonist of the serotonin 5-HT2 receptor. Clinical experience has shown unpredictable efficacy. Trazodone has little antimuscarinic activity and has little if any action on cardiac conduction. Like mianserin it can therefore safely be used in patients for which anticholinergics are contraindicated and there are no absolute contraindications for patients with concomitant diseases of the cardiovascular system. 

The most important actions of the (3-blocking drugs are on the cardiovascular system. -Blockers decrease heart rate, myocardial contractility, cardiac output, and conduction velocity within the heart. These effects are most pronounced when sympathetic activity is high or when the heart is stimulated by circulating agonists. 

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