Hearts electrophysiologic effects

The Class I agents decrease excitability, slow conduction velocity, inhibit diastoHc depolarization (decrease automaticity), and prolong the refractory period of cardiac tissues (1,2). These agents have anticholinergic effects that may contribute to the observed electrophysiologic effects. Heart rates may become faster by increasing phase 4 diastoHc depolarization in SA and AV nodal cells. This results from inhibition of the action of vagaHy released acetylcholine [S1-84-3] which, allows sympathetically released norepinephrine [51-41-2] (NE) to act on these stmctures (1,2). 

The electrophysiological effects of amiodarone may be a composite of several properties. In addition to prolonging action potential duration and refractory period in ad tissues of the heart, the compound is an effective sodium channel blocker (49), calcium channel blocker (50), and a weak noncompetitive -adrenoceptor blocking agent (51). Amiodarone slows the sinus rate, markedly prolongs the QT interval, and slightly prolongs the QRS duration (1,2). 

The three P-adrenoreceptor subtypes have varying localizations and functional properties. The brain contains both Pj and Pj receptors the density of Pj receptors varies in different brain areas to a much greater extent than does that of Pj receptors. Pj receptors predominate in the cerebral cortex Pj receptors are more common in the cerebellum. Likewise, there is a coexistence of Pj and Pj receptors in the heart, with both receptor subtypes being coupled to the electrophysiological effects of catecholamines upon the myocardium. Pj receptors tend to predominate in the lung. 

Usui T, Sugiyama A, Ishida Y, Satoh Y, Sasaki Y, Hashimoto K (1998) Simultaneous assessment of the hemodynamic, car-diomechanical and electrophysiological effects of terfenadine on the in vivo canine model. Heart Vessels 13 49-57 Weissenburger J, Nesterenko VV, Antzelevitch C (2000) Transmural heterogeneity of ventricular repolarization under baseline and long QT conditions in the canine heart in vivo torsades de pointes develops with halothane but not pentobarbital anesthesia. Journal of Cardiovascular Electrophysiology ll(3) 290-304... 

Lowe MD, Rowland E, Brown Ml, Grace AA. Beta(2) adrenergic receptors mediate important electrophysiological effects in human ventricular myocardium. Heart 2001 86(1) 45-51. 

Goldberg D, Reiffel JA, Davis JC, Gang E, Livelh F, Bigger JT Jr. Electrophysiologic effects of procainamide on sinus function in patients with and without sinus node disease. Am Heart J 1982 103(l) 75-9. 

Antiarrhythmic drugs can be placed into four. separate classes. ba.sed on their mechanism of action or pattern of electrophysiological effects produced on heart tissue. Table 19-4 summarizes the four-part clas.sification of antiarrhythmic drugs as first proposed by Vaughan Williams in 1970 and expanded in 1984. ° Note that drugs within the same... 

Leaf A, Kang JX, Xiao Y-F, Billman GE, Voskuyl RA. Functional and electrophysiologic effects of polyunsaturated fatty acids on excitable tissues heart and brain. Prostaglandins Leukotrienes Essential Fatty Acids 1999 60 307-312. 

Cardiac glycosides exert electrophysiologic effects on the heart (via PANS) that include central vagal stimulation, facilitation of muscarinic activity, and sensitization of baroreceptors. These effects occur at conventional doses and in the absence of heart failure lead to a decrease in CO... 

Electrophysiologic Effects of Calcium Inhibitory Agents in Normal and Diseased Hearts... 

Ca + CHANNEL BLOCK The major electrophysiological effects resulting from block of cardiac Ca + channels are in slow-response tissues, the sinus and AV nodes. Dihydropyridines such as nifedipine, which are used commonly in angina and hypertension, preferentially block Ca + channels in vascular smooth muscle their cardiac effects, such as heart rate acceleration, result principally from reflex sympathetic activation secondary to peripheral vasodilation. Only verapamil, diltiazem, and bepridil block Ca + channels in cardiac cells at clinically used doses. These drugs generally slow heart rate, although hypotension can cause reflex sympathetic activation and tachycardia. The velocity of AV nodal conduction decreases, so the PR interval increases. AV nodal block occurs as a result of decremental conduction and increased AV nodal refractoriness, which form the basis for the use of channel blockers in reentrant arrhythmias whose circuit involves the AV node, such as AV reentrant tachycardia. 

Moricizine (Ethmozine) (Fig. 26.13) is a phenothiazine analogue that processes the same electrophysiological effects on the heart as those of Class 1C antiarrhythmics. Despite its short half-life after oral administration, its antiarrhythmio effects can persist for many hours, suggesting that some of its metabolites may be active. 

Liu T, Traebert M, Ju H, Suter W, Guo D, Hoffmann P, Kowey PR, Yan GX (Oct 2012). Differentiating electrophysiological effects and cardiac safety of drugs based on the electrocardiogram a blinded validation. Heart Rhythm 9(10) 1706-1715. 

Kenneback G, Bergfeldt L, ValUn H, Tomson T, Edhag O. Electrophysiologic effects and clinical hazards of carbamaze-pine treatment for neurologic disorders in patients with abnormahties of the cardiac conduction system. Am Heart J 1991 121 (5) 1421-9. 

Wit, A. L., Hoffman, B. F. and Rosen, M. R.(1975) Electrophysiology and pharmacology of cardiac arrhythmias. IX. Cardiac electrophysiology effects of beta adrenergic receptor stimuiation and biockade. Part B. Amer. Heart J., 90, 665. 

The antimuscarinic drug atropine, and its derivative ipratropiumbromide, can also be used for antiarrhyth-mic treatment. Muscarinic receptors (M2 subtype) are mainly present in supraventricular tissue and in the AV node. They inhibit adenylylcyclase via G proteins and thereby reduce intracellular cAMP. On the other hand, activation of the M2 receptor leads to opening of hyperpolarizing Ik.acii and inhibits the pacemaker current If probably via the (3y-subunit of the Gi protein associated with this receptor. The results are hyperpolarization and slower spontaneous depolarization. Muscarinic receptor antagonists like atropine lead to increased heart rate and accelerated atrioventricular conduction. There are no or only slight effects on the ventricular electrophysiology. 

The individual modules of the in situ heart can be coupled together to compute a whole sequence from ventricular pressure development, coronary perfusion, tissue supply of metabolites, cell energy consumption, and electrophysiology, to contractile activity and ventricular pressure development in the subsequent beat. The starting point (here chosen as ventricular pressure development) can be freely selected, and drug effects on the system can be simulated. Inserted into a virtual torso, these models allow one to compute the spread of excitation, its cellular basis, and the consequences for an ECG under normal and pathological conditions. 

While many biological molecules may be targets for oxidant stress and free radicals, it is clear that the cell membrane and its associated proteins may be particularly vulnerable. The ability of the cell to control its intracellular ionic environment as well as its ability to maintain a polarized membrane potential and electrical excitability depends on the activity of ion-translocating proteins such as channels, pumps and exchangers. Either direct or indirect disturbances of the activity of these ion translocators must ultimately underlie reperfiision and oxidant stress-induced arrhythmias in the heart. A number of studies have therefore investigated the effects of free radicals and oxidant stress on cellular electrophysiology and the activity of key membrane-bound ion translocating proteins. 

Heightened sensory perceptions Stimulates appetite Perceived slower passage of time Panic or anxiety Dissociative symptoms Physiological Effects Increases heart rate Reduces body temperature Slowed gastrointestinal function Electrophysiology... 

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