Does Heart Affect Peripheral Vascular Resistance Following Myocardial Ischemia and Reperfusion?

Document Type: Original Article

Authors

1 Department of Physiology, The School of Veterinary Medicine, Ferdowsi University, Mashhad, Iran

2 Department of Physiology, Biology Group, Islamic Azad University, Mashhad, Iran

Abstract

Objective(s)
The aim of this study was to investigate the overall effect of cardiac vasoactive factors during coronary occlusion and reperfusion on peripheral vascular tone, using a sequential isolated rabbit heart-ear perfusion model.
Materials and Methods
Isolated ears were perfused with the effluent of isolated hearts subjected to ischemia (30 min) and reperfusion (180 min, n=6). The comparator groups consisted of a sham operated group (no ischemia, n=5) and the ears that were directly perfused with modified Krebs (n=10). At the end of previous experiment, the perfusion mode of the sequentially perfused ears was converted to non-sequential perfusion with modified Krebs for 10 min and vice versa. In a separate experiment, samples collected from heart effluent during different stages of the first experiment were perfused to isolate stabilized ears (3 min; n=5) or hearts (1 min; n=5). The possible effects of the samples on the tone of isolated femoral artery rings were also studied using an organ bath (n=5).
Results
Coronary occlusion and reperfusion did not exert significant effects on the heart rate or the perfusion pressure of the sequentially perfused ears. The samples collected during different stages of ischemia and reperfusion did not affect the vascular tone in isolated ears or femoral artery rings either.
Conclusion
The current study suggests that isolated heart, even following ischemia and reperfusion, does not release vasoactive substances in concentrations sufficient enough to affect peripheral resistance.

Keywords


1.Zhang Y, Oliver JR, Horowitz JD. The role of endothelin in mediating ischemia/hypoxia-induced atrial natriuretic peptide release. J Cardiovasc Pharmacol 2004; 43:227-233.

2.Tennessen T, Giaid A, Saleh D, Naess PA, Yanagisawa M, Christensen G. Increased in vivo expression and production of endothelin-1 by porcine cardiomyocytes subjected to ischemia. Circ Res 1995; 76:767-772.

3.Blass KE, Forster W, Zehl U. Coronary vasodilation: interactions between prostacyclin and adenosine. Br J Pharmacol 1980; 69:555-559.

4.Lee BH, Kim WH, Choi MJ, Rho JR, Kim WG. Chronic heart failure model in rabbits based on the concept of the bifurcation/trifurcation coronary artery branching pattern. Artif Organs 2002; 26:360-365.

5.Blattner R, Classen HG, Dehnert H, Doring HJ. Experiments on Isolated Smooth Muscle Preparations. 1st ed. Germany: Hugo Sachs Elektronik KG; 1978. p. 158-162.

6.Dostal DE, Baker KM. The cardiac renin-angiotensin system: conceptual, or a regulator of cardiac function? Circ Res 1999; 85:643-650.

7.Neri Semen GG, Boddi M, Coppo M, Chechi T, Zarone N, Moira M, et al. Evidence for the existence of a functional cardiac renin-angiotensin system in humans. Circulation 1996;94:1886-1893.

8.Gavras H, Brunner HR. Role of angiotensin and its inhibition in hypertension, ischemic heart disease, and heart failure. Hypertension 2001; 37:342-345.

9.Berry C, Touyz R, Dominiczak AF, Webb RC, Johns DG. Angiotensin receptors: signaling, vascular pathophysiology, and interactions with ceramide. Am J Physiol Heart Circ Physiol 2001; 281:H2337-H2365.?

10.Seyedi N, Koyama M, Mackins CJ, Levi R. Ischemia promotes renin activation and angiotensin formation in sympathetic nerve terminals isolated from the human heart: contribution to carrier-mediated norepinephrine release. J Pharmacol Exp Ther 2002; 302:539-544.

11.Jalowy A, Schulz R, Heusch G. AT1 receptor blockade in experimental myocardial ischemia/reperfusion. J Am Soc Nephrol 1999; 10:S129-S136.

12.Divisova J, Vavrinkova H, Tutterova M, Kazdova L, Meschisvili E. Effect of ACE inhibitor captopril and L- arginine on the metabolism and on ischemia-reperfusion injury of the isolated rat heart. Physiol Res 2001; 50:143-152.

13.Zhu B, Sun Y, Sievers RE, Browne AE, Pulukurthy S, Sudhir K, et al. Comparative effects of pretreatment with captopril and losartan on cardiovascular protection in a rat model of ischemia-reperfusion. J Am Coll Cardiol 2000; 35:787-795.

14.Carlsson L, Abrahamsson T, Almgren O. Release of noradrenaline in myocardial ischemia--importance of local inactivation by neuronal and extraneuronal mechanisms.J Cardiovasc Pharmacol 1986; 8:545-553.

15.Schomig A, Dart AM, Dietz R, Mayer E, Kubler W. Release of endogenous catecholamines in the ischemic myocardium of the rat. Part A: Locally mediated release. Circ Res 1984; 55:689-701.

16.Schomig A, Fischer S, Kurz T, Richardt G, Schomig E. Nonexocytotic release of endogenous noradrenaline in the ischemic and anoxic rat heart: mechanism and metabolic requirements. Circ Res 1987; 60:194-205.

17.Mackins CJ, Kano S, Seyedi N, Schafer U, Reid AC, Machida T, et al. Cardiac mast cell-derived renin promotes local angiotensin formation, norepinephrine release, and arrhythmias in ischemia/reperfusion. J Clin Invest 2006; 116:1063-1070.

18.Stewart DJ, Kubac G, Costello KB, Cernacek P. Increased plasma endothelin-1 in the early hours of acute myocardial infarction. J Am Coll Cardiol 1991; 18:38-43.

19.Omland T, Lie RT, Aakvaag A, Aarsland T, Dickstein K. Plasma endothelin determination as a prognostic indicator of 1-year mortality after acute myocardial-infarction. Circulation 1994; 89:1573-1579.

20.Singh AD, Amit S, Kumar OS, Rajan M, Mukesh N. Cardioprotective effects of bosentan, a mixed endothelin type A and B receptor antagonist, during myocardial ischaemia and reperfusion in rats. Basic Clin Pharmacol Toxicol 2006; 98:604-610.

21.Ozdemir R, Parlakpinar H, Polat A, Colak C, Ermis N, Acet A. Selective endothelin a (ETA) receptor antagonist (BQ-123) reduces both myocardial infarct size and oxidant injury. Toxicology 2006; 219:142-149. 

22.Grover GJ, Sleph PG, Fox M, Trippodo NC. Role of endothelin-1 and big endothelin-1 in modulating coronary vascular tone, contractile function and severity of ischemia in rat hearts. J Pharmacol Exp Ther 1992; 263:1074-1082.

23.Vitola JV, Forman MB, Holsinger JP, Kawana M, Atkinson JB, Quertermous T, et al. Role of endothelin in a rabbit model of acute myocardial infarction: Effects of receptor antagonists. J Cardiovasc Pharmacol 1996; 28:774-783.

24.Wang QD, Hemsen A, Li XS, Lundberg JM, Uriuda Y, Pernow J. Local overflow and enhanced tissue content of endothelin following myocardial ischaemia and reperfusion in the pig: modulation by L-arginine. Cardiovasc Res 1995; 29:44-49.

25.Chokkukanan J, Zeitlin IJ, Wainwright CL. Modulation of endothelin-1 release by a transmissible factor from ischemic myocardium. J Cardiovasc Pharmacol 1998; 31:S427-S430.

26.Brunner F. Tissue endothelin-1 levels in perfused rat heart following stimulation with agonists and in ischaemia and reperfusion. J Mol Cell Cardiol 1995; 27:1953-1963

27.Dupuis J, Stewart DJ, Cernacek P, Gosselin G. Human pulmonary circulation is an important site for both clearance and production of endothelin-1. Circulation 1996;94:1578-1584.

28.Burkhardt M, Barton M, Shaw SG. Receptor- and non-receptor-mediated clearance of big-endothelin and endothelin-1: differential effects of acute and chronic ETA receptor blockade. J Hypertens 2000; 18:273-279.

29.Kitakaze M, Node K, Komamura K, Minamino T, Inoue M, Hori M, et al. Evidence for nitric oxide generation in the cardiomyocytes: its augmentation by hypoxia. J Mol Cell Cardiol 1995; 27:2149-2154.

30.Prasan AM, McCarron HC, Zhang Y, Jeremy RW. Myocardial release of nitric oxide during ischaemia and reperfusion: effects of L-arginine and hypercholesterolaemia. Heart Lung Circ 2007; 16:274-281.

31.Park KH, Rubin LE, Gross SS, Levi R. Nitric oxide is a mediator of hypoxic coronary vasodilatation. Relation to adenosine and cyclooxygenase-derived metabolites.Circ Res 1992; 71:992-1001.

32.Brunner F. Interaction of nitric oxide and endothelin-1 in ischemia/ reperfusion injury of rat heart. J Mol Cell Cardiol 1997; 29:2363-2374.

33.Kelm M, Schrader J. Control of coronary vascular tone by nitric oxide. Circ Res 1990; 66:1561-1575.

34.Stangl V, Frank TM, Schror K, Stangl K, Baumann G, Felix SB. Interaction of adenosine and prostacyclin in coronary flow regulation after myocardial ischemia. Eur J Pharmacol 1999; 377:43-50.

35.Klabunde RE. Cardiovascular physiology Concepts. Philadelphia: Lippincott Williams & Wilkins; 2005.

36.Mohrman DE, Heller LJ. Cardiovascular physiology. New York: Lange Medical Books/ McGraw-Hill

Companies; 2006.

37.Zeitlin IJ, Fagbemi SO, Parratt JR. Enzymes in normally perfused and ischemic dog hearts which release a substance with kinin like activity. Cardiovasc Res 1989; 23:91-97.

38.Moshi MJ, Zeitlin IJ, Parratt JR. An acidic kininogenase in rat ventricular myocardium. J Cardiovasc Risk 1995; 2:331-337.

39.Ahmad M, Zeitlin IJ, Parratt JR. The release of kininase from rat isolated hearts during myocardial ischemia. Immunopharmacol. 1996; 33:299-300.

40.Linz W, Wiemer G, Scholkens BA. Beneficial effects of bradykinin on myocardial energy metabolism and infarct size. Am J Cardiol 1997; 80.118A-123A.

41.Meghji P, Middleton KM, Newby AC. Absolute rates of adenosine formation during ischemia in rat and pigeon hearts. Biochem J 1988; 249:695-703.

42.Obata T. Adenosine production and its interaction with protection of ischemic and reperfusion injury of the myocardium. Life Sci 2002; 71:2083-2103.

43.Frangogiannis NG, Entman ML. Identification of mast cells in the cellular response to myocardial infarction. Methods Mol Biol 2006; 315:91-101.

44.Miyauchi T, Yanagisawa M, Tomizawa T, Sugishita Y, Suzuki N, Fujino M, et al. Increased plasma concentrations of endothelin-1 and big endothelin-1 in acute myocardial infarction. Lancet 1989; 2:53-54.

45.Lechleitner P, Genser N, Mair J, Maier J, Artnerdworzak E, Dienstl F, Puschendorf B. Plasma-immunoreactive endothelin in the acute and sub-acute phases of myocardial-infarction in patients undergoing fibrinolysis. Clin Chem 1993; 39:955-959.

46.Geist A, Marx J, Muller S, Uzan A, Von Specht BU, Haberstroh J. Combination of enoxaparin and fibroblast growth factor-1 increases myocardial blood flow and capillary density after myocardial infarction in rabbits. Eur Surg Res 2005; 37:191-198.

47.Bolcal C, Yildirim V, Doganci S, Sargin M, Aydin A, Kuralay E, et al. Do N-acetylcystein, beta-glucan, and coenzyme Q10 mollify myocardial ischemia-reperfusion injury? Heart Surg Forum 2007; 10:E222-E227.

48.Taheri SA, Yeh J, Batt RE, Fang Y, Ashraf H, Heffner R, et al. Uterine myometrium as a cell patch as an alternative graft for transplantation to infarcted cardiac myocardium: a preliminary study. Int J Artif Organs 2008; 31:62-67.

49.McCue JD, Swingen C, Feldberg T, Caron G, Kolb A, Denucci C, et al. The real estate of myoblast cardiac transplantation: negative remodeling is associated with location. J Heart Lung Transplant 2008; 27:116-123. 

50.Hale SL, Kloner RA. Location as a determinant of myocardial infarction in rabbits. J Mol Cell Cardiol 2000; 32:505-510.

51.Felix SB, Stangl V, Frank TM, Harms C, Berndt T, Kastner R, et al. Release of a stable cardiodepressant mediator after myocardial ischaemia during reperfusion. Cardiovasc Res 1997; 35:68-79.

52.Brunner F, Du Toit EF, Opie LH. Endothelin release during ischaemia and reperfusion of isolated perfused rat hearts. J Mol Cell Cardio. 1992; 24:1291-1305.

53.Watts JA, Chapat S, Johnson DE, Janis RA. Effects of nisoldipine upon vasoconstrictor responses and binding of endothelin-1 in ischemic and reperfused rat hearts. J Cardiovasc Pharmacol 1992; 19:929-36.