Abstract
The spatial and temporal development of myocardial infarction depends on the area at risk (AAR), the severity and duration of blood flow reduction (energy supply) as well as on heart rate and regional wall function (energy demand). Both supply and demand can vary within the AAR of a given heart, potentially resulting in differences in infarct development. We therefore retrospectively analyzed infarct size (IS, %AAR, TTC) in 24 anesthetized pigs in vivo following 90 min hypoperfusion and 120 min reperfusion of the LAD coronary artery, which supplies parts of the LV septum (LVS) and anterior free wall (LVAFW). The total LAD perfusion territory averaged 49.8 ± 14.2 (SD) g (49.2 ± 8.4% of LV); 61.4 ± 8.1% of the AAR was LVAFW. IS within the LVS was 25.3 ± 15.1%, while IS within the LVAFW was 16.6 ± 10.1% (p<0.05). While ischemic blood flow (radiolabeled microspheres) did not differ between LVS (0.05 ± 0.02 ml/min/g) and LVAFW (0.05 ± 0.03 ml/min/g), perivascular connective tissue (56 ± 9 vs. 38±7 µm2, p < 0.05) and the capillary–to–myocyte distance (1.65 ± 0.23 vs. 1.18 ± 0.23 mm, p < 0.05) were larger in LVS than in LVAFW. Interestingly, IS in LVS (9.3 ± 9.6%, n = 24) and LVAFW (9.2 ± 9.1%) were reduced to the same absolute extent by ischemic preconditioning with one cycle of 10 min ischemia and 15 min reperfusion, suggesting that a similar regional difference exists also in the protection afforded by ischemic preconditioning. The mechanism(s) for that remain(s) to be established.
Conclusion
In pigs, regional differences in infarct development and protection from it exist in the LAD perfusion territory, which are independent of ischemic blood flow but apparently related to pre–existing structural differences.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Aker S, Belosjorow S, Konietzka I, Duschin A, Martin C, Heusch G, Schulz R (2003) The serum but not the myocardial TNFα concentration is increased in pacing-induced heart failure in rabbits. Am J Physiol Regul Integ Comp Physiol 285:R463–R469
Balaban RS, Arai A (2001) Function, metabolic, and flow heterogeneity of the heart. The view is getting better. Circ Res 88:265–267
Balzer P, Furber A, Delépine S, Rouleau F, Lethimonnier F, Morel O, Tadéi A, Jallet P, Geslin P, Le Jeune J-J (1999) Regional assessment of wall curvature and wall stress in left ventricle with magnetic resonance imaging. Am J Physiol 277 (46):H901–H910
Bassenge E, Heusch G (1990) Endothelial and neuro-humoral control of coronary blood flow in health and disease. Rev Physiol Biochem Pharmacol 116:77–165
Bassingthwaighte JB, Beard DA, Li Z (2001) The mechanical and metabolic basis of myocardial blood flow heterogeneity. Basic Res Cardiol 96:582–594
Bassingthwaighte JB, Malone MA, Moffett TC, King RB, Little SE, Link JM, Krohn KA (1987) Validity of microsphere depositions for regional myocardial flows. Am J Physiol Heart Circ Physiol 253:H184–H193
Bishop SP, White FC, Bloor CM (1976) Regional myocardial blood flow during acute myocardial infarction in the conscious dog. Circ Res 38:429–438
Boerth RC, Covell JW, Pool PE, Ross Jr J (1969) Increased myocardial oxygen consumption and contractile state associated with increased heart rate in dogs. Circ Res 24:725–734
Bogaert J, Rademakers FE (2001) Regional nonuniformity of normal adult human left ventricle. Am J Physiol Heart Circ Physiol 280:H610–H620
Buckberg GD, Luck JC, Payne DB, Hoffman JIE, Archie JP, Fixler DE (1971) Some sources of error in measuring regional blood flow with radioactive microspheres. J Appl Physiol 31:598–604
Buffington CW, Strum DP, Watanabe S (1994) Regional oxygen consumption persists in dyskinetic canine myocardium. J Cardiovasc Pharmacol 24:37–44
Chareonthaitawee P, Kaufmann PA, Rimoldi O, Camici PG (2001) Heterogeneity of resting and hyperemic myocardial blood flow in healthy humans. Cardiovasc Res 50:151–161
Decking UKM, Skwirba S, Zimmermann MF, Preckel B, Thämer V, Deussen A, Schrader J (2001) Spatial heterogeneity of energy turnover in the heart. Pflügers Arch—Eur J Physiol 441:663–673
Deussen A, Lauer T, Loncar R, Kropp J (2001) Heterogeneity of metabolic parameters in the left ventricular myocardium and its relation to local blood flow. Basic Res Cardiol 96:564–574
Fishbein MC, Meerbaum S, Rit J, Lando U, Kanmatsuse K, Mercier JC, Corday E, Ganz W (1981) Early phase acute myocardial infarct size quantification: validation of the triphenyl tatrazolium chloride tissue enzyme staining technique. Am Heart J 101:593–600
Franzen D, Conway RS, Zhang H, Sonnenblick EH, Eng C (1988) Spatial heterogeneity of local blood flow and metabolic content in dog hearts. Am J Physiol Heart Circ Physiol 254:H344–H353
Ghaleh B, Shen Y-T, Vatner SF (1996) Spatial heterogeneity of myocardial blood flow presages salvage versus necrosis with coronary artery reperfusion in conscious baboons. Circulation 94:2210–2215
Guth BD, Schulz R, Heusch G (1991) Pressure-flow characteristics in the right and left ventricular perfusion territories of the right coronary artery in swine. Pflügers Arch 419:622–628
Guth BD, Schulz R, Thaulow E (1991) Interventricular redistribution of myocardial blood flow during metabolic vasodilation. Pflügers Arch 417:485–492
Hoshino T, Fujiwara H, Kawai C, Hamashima Y (1983) Myocardial fiber diameter and regional distribution in the ventricular wall of normal adult hearts, hypertensive hearts and hearts with hypertrophic cardiomyopathy. Circulation 67:1109–1116
Huang C-H, Kim S-J, Ghaleh B, Kudej RK, Shen Y-T, Bishop SP, Vatner SF (1999) An adenosine agonist and preconditioning shift the distribution of myocardial blood flow in conscious pigs. Am J Physiol 276:H368–H375
Laussmann T, Janosi RA, Fingas CD, Schlieper GR, Schlack W, Schrader J, Decking UKM (2002) Myocardial proteome analysis reveals reduced NOS inhibition and enhanced glycolytic capacity in areas of low local blood flow. Faseb J 16:628–630
Matsumoto T, Kajiya F (2001) Microheterogeneity of myocardial blood flow. Basic Res Cardiol 96:547–552
Mor-Avi V, Caiani EG, Collins KA, Korcarz CE, Bednarz JE, Lang RM (2001) Combined assessment of myocardial perfusion and regional left ventricular function by analysis of contrastenhanced power modulation images. Circulation 104:352–357
Mor-Avi V, Collins KA, Korcarz CE, Shah M, Spencer KT, Lang RM (2001) Detection of regional temporal abnormalities in left ventricular function during acute myocardial ischemia. Am J Physiol Heart Circ Physiol 280:H1770–H1781
Murry CE, Jennings RB, Reimer KA (1986) Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 74:1124–1136
Opie LH, Sack MN (2002) Metabolic plasticity and the promotion of cardiac protection in ischemia and ischemic preconditioning. J Mol Cell Cardiol 34:1077–1089
Post H, Schulz R, Vahlhaus C, Hüsing J, Hirche H, Gallagher KP, Heusch G (1998) Impact of resting and ischemic blood flow on infarct probability in ischemic preconditioning—a new approach to infarct size-blood flow data by logistic regression. J Mol Cell Cardiol 30:2719–2728
Rivas F, Cobb FR, Bache RJ, Green.eld Jr JC (1976) Relationship between blood flow to ischemic regions and extent of myocardial infarction. Serial measurement of blood flow to ischemic regions in dogs. Circ Res 38:439–447
Rooke GA, Feigl EO (1982) Work as a correlate of canine left ventricular oxygen consumption, and the problem of catecholamine oxygen wasting. Circ Res 50:273–286
Savage RM, Guth BD, White FC, Hagan AD, Bloor CM (1981) Correlation of regional myocardial blood flow and function with myocardial infarct size during acute myocardial ischemia in the conscious pig. Circulation 64:699–707
Schaper W, Görge G, Winkler B, Schaper J (1988) The collateral circulation of the heart. Prog Cardiovasc Dis 31:57–77
Schott RJ, Rohmann S, Braun ER, Schaper W (1990) Ischemic preconditioning reduces infarct size in swine myocardium. Circ Res 66:1133–1142
Schulz R, Aker S, Belosjorow S, Konietzka I, Rauen U, Heusch G (2003) Stress kinase phosphorylation is increased in pacing-induced heart failure in rabbits. Am J Physiol Heart Circ Physiol 285:H2084–H2090
Schulz R, Belosjorow S, Gres P, Jansen J, Michel MC, Heusch G (2002) p38 MAP kinase is a mediator of ischemic preconditioning in pigs. Cardiovasc Res 55:693–700
Schulz R, Gres P, Skyschally A, Duschin A, Belosjorow S, Konietzka I, Heusch G (2003) Ischemic preconditioning preserves connexin 43 phosphorylation during sustained ischemia in pig hearts in vivo. Faseb J 17:1355–1357
Schulz R, Miyazaki S, Miller M, Thaulow E, Heusch G, Ross Jr J Guth BD (1989) Consequences of regional inotropic stimulation of ischemic myocardium on regional myocardial blood flow and function in anesthetized swine. Circ Res 64:1116–1126
Schulz R, Post H, Vahlhaus C, Heusch G (1998) Ischemic preconditioning in pigs: A graded phenomenon. Its relation to adenosine and bradykinin. Circulation 98:1022–1029
Schulz R, Rose J, Heusch G (1994) Involvement of activation of ATP-dependent potassium channels in ischemic preconditioning in swine. Am J Physiol Heart Circ Physiol 267:H1341–H1352
Schulz R, Rose J, Martin C, Brodde OE, Heusch G (1993) Development of short-term myocardial hibernation: its limitation by the severity of ischemia and inotropic stimulation. Circulation 88:684–695
Schulz R, Rose J, Post H, Heusch G (1995) Involvement of endogenous adenosine in ischaemic preconditioning in swine. Pflügers Arch 430:273–282
Schwanke U, Deussen A, Heusch G, Schipke JD (2000) Heterogeneity of local myocardial flow and oxidative metabolism. Am J Physiol Heart Circ Physiol 279:H1029–H1035
Skyschally A, Schulz R, Gres P, Konietzka I, Martin C, Haude M, Erbel R, Heusch G (2004) Coronary microembolization does not induce acute preconditioning against infarction in pigs—the role of adenosine. Cardiovasc Res 63:313–322
Skyschally A, Schulz R, Gres P, Korth H-G, Heusch G (2003) Attenuation of ischemic preconditioning in pigs by scavenging of free oxyradicals with ascorbic acid. Am J Physiol Heart Circ Physiol 284:H698–H703
Skyschally A, Schulz R, Heusch G (1993) Cordat II: A new program for data acquisition and on-line calculation of hemodynamic and regional myocardial dimension parameters. Comput Biol Med 23:359–367
Sonntag M, Deussen A, Schultz J, Loncar R, Hort W, Schrader J (1996) Spatial heterogeneity of blood flow in the dog heart. I. Glucose uptake, free adenosine and oxidative/glycolytic enzyme activity. Pflügers Arch 432:439–450
Tanaka M, Fujiwara H, Onodera T, Wu D, Hamashima Y, Kawai C (1986) Quantitative analysis of myocardial fibrosis in normal, hypertensive hearts, and hypertrophic cardiomyopathy. Br Heart J 55:575–581
Unverferth DV, Baker PB, Swift SE, Chaffee R, Fetters JK, Uretsky BF, Thompson ME, Leier CV (1986) Extent of myocardial fibrosis and cellular hypertrophy in dilated cardiomyopathy. Am J Cardiol 57:816–825
Vahlhaus C, Schulz R, Post H, Onallah R, Heusch G (1996) No prevention of ischemic preconditioning by the protein kinase C inhibitor staurosporine in swine. Circ Res 79:407–414
Vahlhaus C, Schulz R, Post H, Rose J, Heusch G (1998) Prevention of ischemic preconditioning only by combined inhibition of protein kinase C and protein tyrosine kinase in pigs. J Mol Cell Cardiol 30:197–209
Vis MA, Bovendeerd PHM, Sipkema P, Westerhof N (1997) Effect of ventricular contraction, pressure, and wall stretch on vessels at different locations in the wall. Am J Physiol 41:H2963–H2975
Weiss HR, Neubauer JA, Lipp JA, Sinha AK (1978) Quantitative determination of regional oxygen consumption in the dog heart. Circ Res 42:394–401
Wieringa PA, Stassen HG, VanKan JJIM, Spaan JAE (1993) Oxygen diffusion in a network model of the myocardial microcirculation. Int J Microcirc Clin Exp 13:137–169
Author information
Authors and Affiliations
Corresponding author
Additional information
Prof. Dr. J. D. Schipke, Düsseldorf, Germany, served as guest editor for the manuscript and was responsible for all editorial decisions, including the selection of reviewers. The policy applies to all manuscripts with authors from the editor’s institution.
Rights and permissions
About this article
Cite this article
Schulz, R., Gres, P., Konietzka, I. et al. Regional differences of myocardial infarct development and ischemic preconditioning. Basic Res Cardiol 100, 48–56 (2005). https://doi.org/10.1007/s00395-004-0497-5
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00395-004-0497-5