Heart reperfusion arrhythmias

ACE inhibitors inhibit the degradation of bradykinin and potentiate the effects of bradykinin by about 50-100-fold. The prevention of bradykinin degradation by ACE inhibitors is particularly protective for the heart. Increased bradykinin levels prevent postischemic reperfusion arrhythmia, delays manifestations of cardiac ischemia, prevents platelet aggregation, and probably also reduces the degree of arteriosclerosis and the development of cardiac hypertrophy. The role of bradykinin and bradykinin-induced NO release for the improvement of cardiac functions by converting enzyme inhibitors has been demonstrated convincingly with use of a specific bradykinin receptor antagonist and inhibitors of NO-synthase. 

Miyoshi, K., Taniguchi, M., Seki, S., and Mochizuki, S., Effects of magnesium and its mechanism on the incidence of reperfusion arrhythmias following severe ischemia in isolated rat hearts, Cardiovasc. Drugs Ther., 14, 625-633, 2000. 

Isolated heart Adrenergic nerves NA release (carrier-mediated) Ischemia-reperfusion arrhythmias inhibition antiarrhythmic effect Imamura et al., 1996a... 

Koyama M, Heerdt PM, Levi R (2003) Increased severity of reperfusion arrhythmias in mouse hearts lacking histamine H3-receptors. Biochem Biophys Res Commun 306 792-6 Koyama S, Brodie MS, Appel SB (2007) Ethanol inhibition of M-current and ethanol-induced direct excitation of ventral tegmental area dopamine neurons. J Neurophysiol 97 1977-85 Kuzhikandathil EV, Yu W, Oxford GS (1998) Human dopamine D3 and D2l receptors couple to inward rectifier potassium channels in mammalian cell lines. Mol Cell Neurosci 12 390 102 Kuzhikandathil EV, Oxford GS (1999) Activation of human D3 dopamine receptor inhibits P/Q-type calcium channels and secretory activity in AtT-20 cells. J Neurosci 19 1698-1707... 

The response of the failing heart to ischemic stress appears to be variable. Increased incidence of ischemia and reperfusion arrhythmias is observed in hearts from rabbits with heart failure induced by pressure or volume overload.202 Furthermore, hearts from rats with heart failure are shown to be more vulnerable to ischemic injury and acute blockade of RAS with ACE inhibitors improved postischemic recovery of function.203 However, increased susceptibility to ischemia was not evident in specimens of right atrium from patients with impaired ventricular function.204 A number of changes occur in heart failure that potentially could influence the response of the heart to ischemia. Oxidative stress is increased, sustained overexpression of pro-inflammatory mediators is observed, and the activity of the renin-angiotensin system is enhanced. 

M. Koyama, P.M. Heerdt and R. Levi, Increased severity of reperfusion arrhythmias in mouse hearts lacking histamine H3 receptors, Biochem. Biophys. Res. Commun. 306, 792-796 (2003). 

PKG and cyclic nucleotide phosphodiesterases (PDEs) (reviewed by Baxter37). A rapid release of natriuretic peptides and induction of their de novo synthesis occurs in myocardial ischemia. Natriuretic peptides may have a cardioprotective role. BNP-32 administration in perfused rat hearts prior to left main coronary artery occlusion and until 30 min of reperfusion resulted in limitation of infarct size in a concentration dependent manner. Furthermore, this effect was abolished by 5-hydroxydecanoate (presumed to be a selective blocker of mitochondrial KATp channels), L-NAME, an inhibitor of NOS and ODQ, a specific soluble guanyl cyclase inhibitor.38 Similarly, human recombinant ANP limited infarct size and reperfusion arrhythmias in a canine model of coronary occlusion and reperfusion.39... 

Is a reperfusion arrhythmia commonly seen after a Myocardial Infarction (MI). Idioventricular rhythm acts as a ventricular escape rhythm, with the dominant pacemaker originating from the ventricles. This rhythm protects the heart from asystole. It can be identified on the ECG by the wide strangely shaped QRS complexes with the absence of P waves (Fig. 6.38). The rate in Idioventricular rhythm is usually between 20 and 40 BPM. Idioventricular rhythm with a rate above this is termed accelerated Idioventricular rhythm. 

Urata H, Kinoshita A, Misono KS, Bumpus FM. Husain A Identification of a highly specific chy-mase as the major angiotensin Il-forming enzyme in the human heart. J Biol Chem 1990 265 22348. Silver RB, Reid AC, Mackins CJ, Askwith T, Schaefer U, Herzlinger D, Levi R Mast cells a unique source of renin. Proc Natl Acad Sci USA 2004 101 13607. Mackins CJ, Kano S, Sevedi N, Schafer U, Reid AC, Machida T, Silver RB, Levi R Cardiac mast cell-derived renin promotes local angiotensin formation, norepinephrine release, and arrhythmias in ischemia/reperfusion. J Clin Invest 2006 116 1063. 

Bernier, M., Hearse, D.J. and Manning, A.S. (1986). Reperfusion-induced arrhythmias and oxygen-derived free radicals. Studies with anti-free radical interventions and a free radical-generating system in the isolated perfused rat heart. Circ. Res. 58, 331-340. 

Woodward, B. and Zakaria, M.N.M. (1985). Effea of some free radical scavengers on reperfusion induced arrhythmias in the isolated rat heart. J. Mol. Cell. Cardiol. 17, 485—493. 

Cardiovascular effect. Coconut and coconut oil, administered to 32 coronary heart disease patients in 16 age- and sex-matched healthy controls with no difference in the fat, saturated fat, and cholesterol consumption, produced no effecC h Hydrogenated oil, administered to young male Wistar rats, at a dose of 10% of diet for 10 weeks, produced an increase in the risk of ventricular arrhythmias under conditions of both ischemia and reperfusion. The incidence of ventricular fibrillation was 67% in the oil-... 

Different experimental techniques have been also used to investigate ischemia-reperfusion injury. Table 2. Experimental models of isolated hearts cannot consider the contribution of blood components or neurohormonal changes as this occurs in in vivo studies. However, these studies are able to dissect potential underlying mechanisms of the ischemic injury. The mode of perfusion (working heart vs Langendorff mode or constant flow vs constant pressure), the use of pacing, the composition of the perfusate and the end-points chosen to assess myocardial injury (arrhythmias, functional recovery... 

A. Bril, M.C. Forest and B. Gout, Ischemia and reperfusion induced arrhythmias in rabbits with chronic heart failure, Am. J. Physiol. 261, H301-H307 (1991). 

E. F. Du Toit, C. A. Muller, J. McCarthy, L. H. Opie, Levosimendan effects of a calcium sensitizer on function and arrhythmias and cyclic nucleotide levels during ischemia/reperfusion in the Langcndorff-perfused guinea pig heart, J Pharmacol Exp Ther 290, 505-14 (1999). 

Harrison, S.N., Autelitano, D.J., Wang, B.H., Milano, C., Du, X.J., Woodcock, E.A., 1998. Reduced reperfusion-induced Ins(l,4,5)P3 generation and arrhythmias in hearts expressing constitutively active alpha IB adrenergic receptors. Circ. Res. 83, 1232-1240. 

Hearse, D. J., and Tosaki, A. (1987). Free radicals and reperfusion-induced arrhythmias Protection by spin trap agent PBN in the rat heart. Circ. Res. 60, 375-383. 

The ECG can be used as a means to detect cardiac related adverse drug effects or as a diagnostic aid for disease since many of its intervals and segments are sensitive to electrical, biochemical and pathological changes in myocytes. In humans, common causes of arrhythmias include myocardial ischaemia, myocardial infarction or reperfusion of a previously ischaemic myocardium. These conditions can be readily reproduced in both intact and isolated hearts in many species. While the pathology of arrhythmias may not appear to be relevant to the safety pharmacologist, the... 

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