Skip to main content
SpringerLink
Log in

Ischemic tolerance of rat hearts in acute and chronic phases of experimental diabetes

  • Chapter
Book cover Biochemistry of Diabetes and Atherosclerosis

Part of the book series: Developments in Molecular and Cellular Biochemistry ((DMCB,volume 42))

Abstract

Different from clinical studies of diabetes mellitus (DM), experimental data reveal both, higher and lower vulnerability of the heart to ischemic injury. We have previously demonstrated an enhanced resistance to ischemia-induced arrhythmias in isolated rat hearts in the acute phase of DM. Our objectives were thus to extend our knowledge to the effects of DM of different duration on myocardial infarction, in conjunction with susceptibility to arrhythmias, in the in vivo model. DM was induced by streptozotocin (45 mg/kg, i.v.) and following 1 week (acute phase) and 8 weeks (chronic phase), anesthetized open-chest diabetic and age-matched control rats were subjected to 30-min regional ischemia (occlusion of LAD coronary artery) followed by 4-h reperfusion for the evaluation of the infarct size (tetrazolium staining). In the control rats, ventricular tachycardia (VT) represented 45.4% of total arrhythmias and occurred in 90% of the animals. In the acute phase of DM, arrhythmia profile was similar to that in the control animals, and the incidence and severity of arrhythmias were not enhanced. On the other hand, the size of infarct area normalized to the size of area at risk was significantly smaller in the diabetics than in the controls (47.2 ± 2.8 vs. 70.2 ± 2.1%, respectively; p < 0.05). In the chronic phase, only 17.7% of arrhythmias occurred as VT in 44% of the diabetics (p < 0.05 vs. controls). Severity of arrhythmias was also lower (arrhythmia score: 2.1 ± 0.3 vs. 2.9 ± 0.3 in the controls, respectively; p < 0.05). This effect was not due to a smaller infarct size, since the latter did not differ from that in the controls. In conclusion: diabetic rat hearts exhibit rather lower, than higher sensitivity to ischemia. In acute phase of DM, diabetic hearts are more resistant to irreversible cell damage, whereas in the chronic phase they exhibit reduced susceptibility to arrhythmias; these discrepancies might reflect different pathogenesis of arrhythmias and myocardial infarction. (Mol Cell Biochem 249: 167–174, 2003)

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Kannel WB, McGee DL: Diabetes and cardiovascular risk factors. The Framingham Study. Circulation 59: 8–13, 1979

    Article  PubMed  CAS  Google Scholar 

  2. Malmberg K, Ryden L: Myocardial infarction in patients with diabetes mellitus. Eur Heart J 9: 259–264, 1988

    PubMed  CAS  Google Scholar 

  3. Garratt KN, Brady PA, Hassinger NL, Grill DE, Terzic A, Holmes DR: Sulphonylureas drugs increase early mortality in patients with diabetes mellitus after direct angioplasty for acute myocardial infarction. J Am Coll Cardiol 33: 119–124, 1999

    Article  PubMed  CAS  Google Scholar 

  4. Dhalla NS, Liu X, Panagia V, Takeda A: Subcellular remodeling and heart dysfunction in chronic diabetes. Cardiovasc Res 40: 239–247, 1998

    Article  PubMed  CAS  Google Scholar 

  5. Forrat R, Sebbag L, Wiensperger A, Guidollet J, Delaye J, De Lorgeril M: Acute myocardial infarction in diabetic dogs with experimental diabetes. Cardiovasc Res 27: 1908–1912, 1993

    Article  PubMed  CAS  Google Scholar 

  6. Hadour G, Ferrera R, Sebbag L, Forrat R, Delaye J, De Lorgeril M: Improved myocardial tolerance to ischemia in the diabetic rabbit. J Mol Cell Cardiol 30: 1869–1875, 1998

    Article  PubMed  CAS  Google Scholar 

  7. Liu Y, Thornton JD, Cohen MV, Downey JM, Schaffer SW: Streptozotocin-induced non-insulin dependent diabetes protects the heart from infarction. Circulation 88: 1273–1278, 1993

    Article  PubMed  CAS  Google Scholar 

  8. Hekimian G, Khandoudi N, Feuvray D, Beigelman PM: Abnormal cardiac rhythm in diabetic rats. Life Sci 37: 547–551, 1985

    Article  PubMed  CAS  Google Scholar 

  9. Kusama Y, Hearse DJ, Avkiran M: Diabetes and susceptibility to reperfusion-induced ventricular arrhythmias. J Mol Cell Cardiol 24: 411–421, 1992

    Article  PubMed  CAS  Google Scholar 

  10. Tani M, Neely JR: Hearts from diabetic rats are more resistant to in vitro ischemia: Possible role of altered Ca2+metabolism. Circ Res 62: 931–940, 1988

    Article  PubMed  CAS  Google Scholar 

  11. Tosaki A, Engelman DT, Engelman RM, Das DK: The evolution of diabetic response to ischemia/reperfusion and preconditioning in isolated working rat hearts. Cardiovasc Res 31: 526–536, 1996

    PubMed  CAS  Google Scholar 

  12. Feuvray D, Lopaschuk GD: Controversies on the sensitivity of the diabetic heart to ischemic injury: The sensitivity of the diabetic heart to ischemie injury is decreased. Cardiovasc Res 34: 113–120, 1997

    Article  PubMed  CAS  Google Scholar 

  13. Ravingerova T, Stetka R, Volkovova K, Pancza D, Dzurba A, Ziegelhoffer A, Styk J: Acute diabetes modulates response to ischemia in isolated rat heart. Mol Cell Biochem 210: 143–151, 2000

    Article  PubMed  CAS  Google Scholar 

  14. Ravingerová T, Neckář J, Kolář F, Styk J: Response to myocardial ischemia in the diabetic rats in vivo: Are they more or less susceptible to ischemia? J Mol Cell Cardiol 33: A99, 2001

    Article  Google Scholar 

  15. Ravingerová T, Neckar J, Kolář F, Štetka R, Volkovová K, Ziegelhoffer A, Styk J: Ventricular arrhythmias following coronary artery occlusion in rats: Is diabetic heart less or more sensitive to ischemia? Basic Res Cardiol 96: 160–168, 2001

    Article  PubMed  Google Scholar 

  16. Curtis MJ: Characterisation, utilisation and clinical relevance of isolated perfused heart models of ischemia-induced ventricular fibrillation. Cardiovasc Res 39: 194–215, 1998

    Article  PubMed  CAS  Google Scholar 

  17. Neckář J, Papoušek F, Nováková O, Ošt’ádal B, Kolář F: Cardioprotective effects of chronic hypoxia and ischaemic preconditioning are not additive. Basic Res Cardiol: 97: 161–167, 2002

    Article  PubMed  Google Scholar 

  18. Walker MJA, Curtis MJ, Hearse DJ, Campbell RWF, Janse MJ, Yellon DM, Cobbe SM, Coker SJ, Harness JB, Harron DWG, Higgins AJ, Julian DJ, Lab MJ, Manning AS, Northover BJ, Parratt JR, Riemersma RA, Riva E, Rüssel DC, Sheridan DJ, Winslow E, Woodward B: The Lambeth conventions: Guidelines for the study of arrhythmias in ischemia, infarction, and reperfusion. Cardiovasc Res 22: 447–455, 1988

    Article  PubMed  CAS  Google Scholar 

  19. Ganguly PK, Pierce GN, Dhalla KS, Dhalla NS: Defective sarcoplasmic reticular calcium transport in diabetic cardiomyopathy. Am J Physiol 244: E528–E535, 1983

    PubMed  CAS  Google Scholar 

  20. Dhalla NS, Pierce GN, Panagia V, Singal PK, Beamish RE: Calcium movements in relation to heart function. Basic Res Cardiol 77: 117–139, 1982

    Article  PubMed  CAS  Google Scholar 

  21. Curtis MJ, Hearse DJ: Ischemia-induced and reperfusion-induced arrhythmias differ in their sensitivity to potassium: Implications for the mechanisms of initiation and maintenance of ventricular fibrillation. J Mol Cell Cardiol 21: 21–40, 1989

    Article  PubMed  CAS  Google Scholar 

  22. Shimoni Y, Severson D, Giles W: Thyroid status and diabetes modulate regional differences in potassium currents in rat ventricle. J Physiol (Lond) 488: 673–688, 1995

    CAS  Google Scholar 

  23. Rodrigues B, Cam MC, McNeill JH: Myocardial substrate metabolism: Implications for diabetic cardiomyopathy. J Mol Cell Cardiol 27: 169–179, 1995

    Article  PubMed  CAS  Google Scholar 

  24. Goto M, Tsuchida A, Liu Y, Cohen MV, Downey JM: Transient inhibition of glucose uptake mimics ischemic preconditioning by salvaging ischemic myocardium in the rabbit heart. J Mol Cell Cardiol 27: 1883–1894, 1995

    Article  PubMed  CAS  Google Scholar 

  25. Khandoudi A, Bernard M, Cozzone P, Feuvray D: Intracellular pH and role of Na+/H+ exchange during ischemia and reperfusion of normal and diabetic rat hearts. Cardiovasc Res 24: 873–878, 1990

    Article  PubMed  CAS  Google Scholar 

  26. Pierce GN, Ramjiawan B, Dhalla NS, Ferrari R: Na+/H+ exchange in cardiac sarcolemmal vesicles isolated from diabetic rats. Am J Physiol 258: H255–E261, 1990

    PubMed  CAS  Google Scholar 

  27. Meldrum DR, Cleveland JC Jr, Sheridan BC, Rowland RT, Banerjee A, Harken AH: Cardiac preconditioning with calcium: Clinically accessible myocardial protection. J Thorac Cardiovasc Surg 112: 778–786, 1996

    Article  PubMed  CAS  Google Scholar 

  28. Murry CE, Jennings RB, Reimer KA: Preconditioning with ischemia: A delay of lethal cell injury in ischemie myocardium. Circulation 74: 1124–1136, 1986

    Article  PubMed  CAS  Google Scholar 

  29. Liu GS, Downey JM: Preconditioning against infarction in rat heart does not involve pertussis toxin sensitive G protein. Cardiovasc Res 27: 608–611, 1993

    Article  PubMed  CAS  Google Scholar 

  30. Cave AC: Preconditioning induced protection against postischemic contractile dysfunction: Characteristics and mechanisms. J Mol Cell Cardiol 27: 969–979, 1995

    Article  PubMed  CAS  Google Scholar 

  31. Vegh A, Komori S, Szekeres L, Parratt JR: Antiarrhythmic effects of preconditioning in anaesthetised dogs and rats. Cardiovasc Res 26: 487–495, 1992

    Article  PubMed  CAS  Google Scholar 

  32. Mitchell MB, Meng X, Ao L, Brown JM, Harken AH, Banerjee A: Preconditioning of isolated rat heart is mediated by protein kinase C. Circ Res 76: 73–81, 1995

    Article  PubMed  CAS  Google Scholar 

  33. Malhotra A, Reich D, Reich D, Nakouzi A, Sanghi V, Geenen DL, Buttrick PM: Experimental diabetes is associated with functional activation of protein kinase Ce and phosphorylation of troponin I in the heart, which are prevented by angiotensin II receptor blockade. Circ Res 81: 1027–1033, 1997

    Article  PubMed  CAS  Google Scholar 

  34. Moon CH, Jung JS, Lee SH, Baik EJ: Protein kinase C inhibitors abolish the increased resistance of diabetic rat heart to ischemia-reperfusion injury. Jpn J Physiol 49: 409–415, 1999

    Article  PubMed  CAS  Google Scholar 

  35. Noma A: ATP-regulated K+ channels in cardiac muscle. Nature 305: 147–148, 1983

    Article  PubMed  CAS  Google Scholar 

  36. Spinelli W, Sorota S, Siegal M, Hoffman BF: Antiarrhythmic actions of the ATP-regulated K+current activated by pinacidil. Circ Res 68: 1127–1137, 1991

    Article  PubMed  CAS  Google Scholar 

  37. Tan HL, Mazon P, Verberne HJ, Sleeswijk ME, Coronel R, Opthof T, Janse M: Ischemie preconditioning delays ischemia induced cellular electrical uncoupling in rabbit myocardium by activation of ATP sensitive potassium channels. Cardiovasc Res 27: 644–651, 1993

    Article  PubMed  CAS  Google Scholar 

  38. Smith JM, Wahler GM: ATP-sensitive potassium channels are altered in ventricular myocytes from diabetic rats. Mol Cell Biochem 158:43–51, 1996

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Physiology, Academy of Sciences of the Czech Republic, Centre for Experimental Cardiovascular Research, Prague, Czech Republic

    Jan Neckář

  2. Institute for Heart Research, Slovak Academy of Sciences, Bratislava, Slovak Republic

    Táňa Ravingerová & František Kolář

Authors
  1. Táňa Ravingerová
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jan Neckář
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. František Kolář
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Division of Stroke Vascular Disease, St. Boniface General Hospital Research Center, 351 Tache Avenue, R2H 2A6, Winnipeg, Manitoba, Canada

    James S. C. Gilchrist

  2. Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Center, 351 Tache Avenue, R2H 2A6, Winnipeg, Manitoba, Canada

    Paramjit S. Tappia  & Thomas Netticadan  & 

Rights and permissions

Reprints and permissions

Copyright information

© 2003 Springer Science+Business Media New York

About this chapter

Cite this chapter

Ravingerová, T., Neckář, J., Kolář, F. (2003). Ischemic tolerance of rat hearts in acute and chronic phases of experimental diabetes. In: Gilchrist, J.S.C., Tappia, P.S., Netticadan, T. (eds) Biochemistry of Diabetes and Atherosclerosis. Developments in Molecular and Cellular Biochemistry, vol 42. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-9236-9_21

Download citation

  • DOI: https://doi.org/10.1007/978-1-4419-9236-9_21

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-4852-8

  • Online ISBN: 978-1-4419-9236-9

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation