Activation myocardium

Enhanced automaticity occurs in hypoxia, hypokalemia, hypercarbia, excessive sympathetic nervous system stimulation, or high concentrations of catecholamines. These conditions may lead to arrhythmias. Decreased automaticity may also lead to production of arrhythmias by enhancing ectopic activity in latent pacemakers (ectopic foci) or by altering conductivity and refractoriness in conduction pathways of myocardium. 

The increased concentrations of K, Ca, Fe, Br, Se and Rb in infarction and scar areas are observed for patient with the recent infarction. For the patients with old infarction the levels of these elements are decreased in the same areas. This reflects the intensity of metabolic processes in the pathological area of myocardium. Additionally, the elevated levels of Se was find out in myocardium of right ventricle in both patients, that may be caused by the increasing the activity of the glutathione peroxidase enzyme. 

Normal rhythmic activity is the result of the activity of the sinus node generating action potentials that are conducted via the atria to the atrioventricular node, which delays further conduction to the His-Tawara-Purkinje system. From the Purkinje fibres, action potentials propagate to the ventricular myocardium. Arrhythmia means a disturbance of the normal rhythm either resulting in a faster rhythm (tachycardia, still rhythmic) or faster arrhythmia (tachyarrhythmia) or slowed rhythm (bradycardia, bradyarrhythmia). 

Inhibition of the Na+/K+-ATPase leads to a loss of potassium and an increase of sodium within the cell. Secondary intracellular calcium is increased via the Na VCa -exchanger. This results in a positive inotropic effect in the myocardium, with an increase of peak force and a decrease in time to peak tension. Besides this, cardiac glycosides increase vagal activity by effects on the central vagal nuclei, the nodose ganglion and increase in sensitivity of the sinus node to acetylcholine. 

Natriuretic peptides are a family of peptide hormones. All of them contain a 17-amino acid long ring that is closed by a disulfide bond between two cysteine residues. ANP (atrial natriuretic peptide) is mainly expressed in the atria of the heart, whereas BNP (B-type natriuretic peptide) is synthesized in the ventricular myocardium. CNP occurs mainly in the endothelium and is thought to have a paracrine function. ANF and BNF lower blood pressure by a direct effect on smooth muscle and on the salt retention in the kidney. Natriuretic peptides bind and activate particulate guanylyl cyclases. 

The most important potential complication of phenol-based peels is cardiotoxicity. Phenol is directly toxic to myocardium. Studies in rats have shown a decrease in myocardial contraction and in electrical activity following systemic exposure to phenol [i6]. Since fatal doses ranged widely in these studies, it seems that individual sensitivity of myocardium to this chemical exists. In humans neither sex/age nor previous cardiac history/blood phenol levels are accurate predictors for cardiac arrhythmia susceptibility [17]. 

CR is distributed in various organs with highest concentrations in skeletal muscle, myocardium, and brain and lesser amounts in the gastrointestinal tract, uterus, urinary bladder, and kidney ( ). The CR content of liver and red blood cells is negligible so that diseases of these tissues are unlikely to increase the serum CR activity. The serum CR level begins to increase in 2-4 hours after myocardial infarction and reaches a peak in 24-36 hours and returns to normal in about 3 days. 

The Vaughan-Williams classification of antiarrhythmic drugs has been criticized for a number of reasons. The classification is based on the effects of drugs on normal, rather than diseased, myocardium. In addition, many of the drugs may be placed into more than one class. For example, the class IA drugs prolong repolarization/refractoriness, either via the parent drug8,9 or an active metabolite,10 and therefore also maybe placed in class III. Sotalol is also a 3-blocker, and therefore fits into class II. Amiodarone inhibits sodium and potassium channels, is a non-competitive inhibitor of 3-receptors, and inhibits calcium... 

Ehlert FJ. Gallamine allosterically antagonizes muscarinic receptor-mediated inhibition of adenylate cyclase activity in the rat myocardium. J Pharmacol Exp Ther 1988 247 596-602. 

Nesiritide is manufactured using recombinant techniques and is identical to the endogenous B-type natriuretic peptide secreted by the ventricular myocardium in response to volume overload. Consequently, nesiritide mimics the vasodilatory and natriuretic actions of the endogenous peptide, resulting in venous and arterial vasodilation increases in cardiac output natriuresis and diuresis and decreased cardiac filling pressures, sympathetic nervous system activity, and renin-angiotensin-aldosterone system activity. 

The activity of this enzyme is regulated by changes in the concentrations of ATP and phosphate the former inhibits whereas the latter activates it. These are the signals that increase the concentration of adenosine. It is transported out of the cell, so that the extracellular concentration also increases. This then stimulates relaxation of the smooth muscle in the arterioles which results in vasodilation and increased blood flow and consequently a greater supply of oxygen to the cardiomyocytes. The blood flow will be increased to those parts of the myocardium that are not totally occluded by the clot, so that more mitochondrial generation of ATP can occur. Provided the portion of the myocardium that is totally occluded is not too large, the heart can then continue to function as a pump. 

Three proteolytic enzymes, streptokinase, urokinase and tissue plasminogen activator, hydrolyse peptide bonds in fibrin which loosens the stracture of the clot and can results in its dispersal. This can restore flow of blood to the part of the myocardium affected by the clot. These are known as clot-busting enzymes. One or more of these enzymes is introduced into the circulation, and provided that this is done very soon after an infarct, damage to that part of the myocardium can be minimised. 

Figure 22.17 Summary of mechanisms to maintain the ATP/ADP concentration ratio in hypoxic myocardium. A decrease in the ATP/ADP concentration ratio increases the concentrations of AMP and phosphate, which stimulate conversion of glycogen/ glucose to lactic acid and hence ATP generation from glycolysis. The changes also increase the activity of AMP deaminase, which increases the formation and hence the concentration of adenosine. The latter has two major effects, (i) It relaxes smooth muscle in the arterioles, which results in vasodilation that provides more oxygen for aerobic ATP generation (oxidative phosphorylation). (ii) It results in decreased work by the heart (i.e. decrease in contractile activity), (mechanisms given in the text) which decreases ATP utilisation.

Toxicity is remarkably low for a compound of such activity. In mice, the LDso value is about three times that of chlorpromazine [166] while none of the effects of the latter drug on the myocardium, liver, skin or eye have appeared in the studies of oxypertine. It is, however, still too early to appraise its chronic toxicity in man. As indicated earlier, dangerous interactions are likely to follow concurrent use of a MAO inhibitor, though simultaneous use of anti-Parkinsonism drugs, for example, to control the relatively minor extra-pyramidal symptoms seems to present no unusual problems. Hypotension may occasionally occur with high doses. 

The decreased work capacity of the in-farcted myocardium leads to a reduction in stroke volume (SV) and hence cardiac output (CO). The fall in blood pressure (RR) triggers reflex activation of the sympathetic system. The resultant stimulation of cardiac 3-adreno-ceptors elicits an increase in both heart rate and force of systolic contraction, which, in conjunction with an a-adren-oceptor-mediated increase in peripheral resistance, leads to a compensatory rise in blood pressure. In ATP-depleted cells in the infarct border zone, resting membrane potential declines with a concomitant increase in excitability that may be further exacerbated by activation of p-adrenoceptors. Together, both processes promote the risk of fatal ventricular arrhythmias. As a consequence of local ischemia, extracellular concentrations of H+ and K+ rise in the affected region, leading to excitation of nociceptive nerve fibers. The resultant sensation of pain, typically experienced by the patient as annihilating, reinforces sympathetic activation. 

Selected entries from Methods in Enzymology [vol, page(s)] Cobra venom phospholipase A2 Naja naja naja, 197, 359 phospholipase A2 from rat liver mitochondria, 197, 365 assay and purification of phospholipase A2 from human synovial fluid in rheumatoid arthritis, 197, 373 purification of mammalian nonpan-creatic extracellular phospholipases A2, 197, 381 spleen phospholipases A2, 197, 390 purification and characterization of cytosolic phospholipase A2 activities from canine myocardium and sheep platelets, 197, 400. 

Dobutamine is a selectively activating drug at cardiac -adrenoreceptors, as well as adrenoreceptors of the blood vessels and j-adrenoreceptors of the myocardium. The mechanism of its action is very complex. 

Dobutamine is used in simations where, during severe cardiac decompensation, it is necessary to temporarily strengthen contractions of the myocardium, and in particular during decompensation of cardiac activity associated with surgical intervention on the heart or in organic diseases. A synonym of dobutamine is dobutrex. 

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