Skip to main content

Advertisement

SpringerLink
Log in

Cardiac vulnerability to ischemia/reperfusion injury drastically increases in late pregnancy

  • Original Contribution
  • Published:
Basic Research in Cardiology Aims and scope Submit manuscript

Abstract

Although the murine late pregnant (LP) heart is speculated to be a better functioning heart during physiological conditions, the susceptibility of LP hearts to I/R injury is still unknown. The aims of this study were to investigate the cardiac vulnerability of LP rodents to ischemia/reperfusion (I/R) injury and to explore its underlying mechanisms. In vivo female rat hearts [non-pregnant (NP) or LP] or ex vivo Langendorff-perfused mouse hearts were subjected to I/R. The infarct size was approximately fourfold larger in LP animals compared with NP both in vivo and ex vivo. The heart functional recovery was extremely poor in LP mice compared with NP (~10 % recovery in LP vs. 80 % recovery in NP at the end of reperfusion, P < 0.01). Interestingly, the poor functional recovery and the larger infarct size in LP were partially restored one day post-partum and almost fully restored 1 week post-partum to their corresponding NP levels. Mitochondrial respiratory function and the threshold for opening of the mitochondrial permeability transition pore were significantly lower in LP compared with NP when they both were subjected to myocardial I/R injury [Respiratory control ratio = 1.9 ± 0.1 vs. 4.0 ± 0.5 in NP, P < 0.05; calcium retention capacity (CRC) = 167 ± 10 vs. 233 ± 18 nmol/mg protein in NP, P < 0.01]. Cardiac reactive oxygen species (ROS) generation, as well mitochondrial superoxide production, was approximately twofold higher in LP compared with NP following I/R. The phosphorylation levels of Akt, ERK1/2, and STAT3, but not GSK3β, were significantly reduced in the hearts from LP subjected to I/R. In conclusion, increased mitochondrial ROS generation, decreased CRC as well as impaired activation of Akt/ERK/STAT3 at reperfusion are the possible underlying mechanisms for higher vulnerability of LP hearts to I/R.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Abdallah Y, Gkatzoflia A, Gligorievski D et al (2006) Insulin protects cardiomyocytes against reoxygenation-induced hypercontracture by a survival pathway targeting SR Ca2+ storage. Cardiovasc Res 70(2):346–353. doi:10.1016/j.cardiores.2006.02.020

    Article  PubMed  CAS  Google Scholar 

  2. Birnbaum Y, Long B, Qian J, Perez-Polo JR, Ye Y (2011) Pioglitazone limits myocardial infarct size, activates Akt, and upregulates cPLA2 and COX-2 in a PPAR-gamma-independent manner. Basic Res Cardiol 106(3):431–446. doi:10.1007/s00395-011-0162-3

    Article  PubMed  CAS  Google Scholar 

  3. Boengler K, Buechert A, Heinen Y et al (2008) Cardioprotection by ischemic postconditioning is lost in aged and STAT3-deficient mice. Circ Res 102(1):131–135. doi:10.1007/s00395-010-0124-1

    Article  PubMed  CAS  Google Scholar 

  4. Boengler K, Hilfiker-Kleiner D, Drexler H, Heusch G, Schulz R (2008) The myocardial JAK/STAT pathway: from protection to failure. Pharmacol Ther 120(2):172–185. doi:10.1007/s00395-010-0124-1

    Article  PubMed  CAS  Google Scholar 

  5. Boengler K, Hilfiker-Kleiner D, Heusch G, Schulz R (2010) Inhibition of permeability transition pore opening by mitochondrial STAT3 and its role in myocardial ischemia/reperfusion. Basic Res Cardiol 105(6):771–785. doi:10.1007/s00395-010-0124-1

    Article  PubMed  CAS  Google Scholar 

  6. Bopassa JC, Eghbali M, Toro L, Stefani E (2010) A novel estrogen receptor GPER inhibits mitochondria permeability transition pore opening and protects the heart against ischemia-reperfusion injury. Am J Physiol Heart Circ Physiol 298(1):H16–H23. doi:10.1152/ajpheart.00588.2009

    Article  PubMed  CAS  Google Scholar 

  7. Breivik L, Helgeland E, Aarnes EK, Mrdalj J, Jonassen AK (2011) Remote postconditioning by humoral factors in effluent from ischemic preconditioned rat hearts is mediated via PI3K/Akt-dependent cell-survival signaling at reperfusion. Basic Res Cardiol 106(1):135–145

    Article  PubMed  CAS  Google Scholar 

  8. Callies F, Stromer H, Schwinger RH et al (2003) Administration of testosterone is associated with a reduced susceptibility to myocardial ischemia. Endocrinology 144(10):4478–4483

    Article  PubMed  CAS  Google Scholar 

  9. Cantor EJ, Babick AP, Vasanji Z, Dhalla NS, Netticadan T (2005) A comparative serial echocardiographic analysis of cardiac structure and function in rats subjected to pressure or volume overload. J Mol Cell Cardiol 38(5):777–786. doi:10.1016/j.yjmcc.2005.02.012

    Article  PubMed  CAS  Google Scholar 

  10. Cao W, Xie YH, Li XQ et al (2011) Burn-induced apoptosis of cardiomyocytes is survivin dependent and regulated by PI3K/Akt, p38 MAPK and ERK pathways. Basic Res Cardiol 106(6):1207–1220. doi:10.1007/s00395-011-0199-3

    Article  PubMed  CAS  Google Scholar 

  11. Carabello BA (2002) Concentric versus eccentric remodeling. J Card Fail 8(6 Suppl):S258–S263. doi:10.1054/jcaf.2002.129250

    Article  PubMed  Google Scholar 

  12. Chalupsky K, Cai H (2005) Endothelial dihydrofolate reductase: critical for nitric oxide bioavailability and role in angiotensin II uncoupling of endothelial nitric oxide synthase. Proc Natl Acad Sci USA 102(25):9056–9061. doi:10.1073/pnas.0409594102

    Article  PubMed  CAS  Google Scholar 

  13. Chapman AB, Abraham WT, Zamudio S et al (1998) Temporal relationships between hormonal and hemodynamic changes in early human pregnancy. Kidney Int 54(6):2056–2063

    Article  PubMed  CAS  Google Scholar 

  14. Christian TF, Schwartz RS, Gibbons RJ (1992) Determinants of infarct size in reperfusion therapy for acute myocardial infarction. Circulation 86(1):81–90. doi:10.1161/01.CIR.86.1.81

    Article  PubMed  CAS  Google Scholar 

  15. Cohen MV, Yang XM, Downey JM (2008) Acidosis, oxygen, and interference with mitochondrial permeability transition pore formation in the early minutes of reperfusion are critical to postconditioning’s success. Basic Res Cardiol 103(5):464–471. doi:10.1007/s00395-008-0737-9

    Article  PubMed  Google Scholar 

  16. Crompton M (1999) The mitochondrial permeability transition pore and its role in cell death. Biochem J 341(Pt 2):233–249

    Article  PubMed  CAS  Google Scholar 

  17. Daniels SR, Meyer RA, Liang YC, Bove KE (1988) Echocardiographically determined left ventricular mass index in normal children, adolescents and young adults. J Am Coll Cardiol 12(3):703–708

    PubMed  CAS  Google Scholar 

  18. Eghbali M, Deva R, Alioua A et al (2005) Molecular and functional signature of heart hypertrophy during pregnancy. Circ Res 96(11):1208–1216. doi:10.1161/01.RES.0000170652.71414.16

    Article  PubMed  CAS  Google Scholar 

  19. Eghbali M, Wang Y, Toro L, Stefani E (2006) Heart hypertrophy during pregnancy: a better functioning heart? Trends Cardiovasc Med 16(8):285–291. doi:10.1016/j.tcm.2006.07.001

    Article  PubMed  Google Scholar 

  20. Fujio Y, Nguyen T, Wencker D, Kitsis RN, Walsh K (2000) Akt promotes survival of cardiomyocytes in vitro and protects against ischemia-reperfusion injury in mouse heart. Circulation 101(6):660–667. doi:10.1161/01.CIR.101.6.660

    Article  PubMed  CAS  Google Scholar 

  21. Ghaboura N, Tamareille S, Ducluzeau PH et al (2011) Diabetes mellitus abrogates erythropoietin-induced cardioprotection against ischemic-reperfusion injury by alteration of the RISK/GSK-3beta signaling. Basic Res Cardiol 106(1):147–162. doi:10.1007/s00395-010-0130-3

    Article  PubMed  CAS  Google Scholar 

  22. Gomez L, Paillard M, Thibault H, Derumeaux G, Ovize M (2008) Inhibition of GSK3beta by postconditioning is required to prevent opening of the mitochondrial permeability transition pore during reperfusion. Circulation 117(21):2761–2768. doi:10.1161/CIRCULATIONAHA.107.755066

    Article  PubMed  CAS  Google Scholar 

  23. Halestrap AP, Clarke SJ, Javadov SA (2004) Mitochondrial permeability transition pore opening during myocardial reperfusion—a target for cardioprotection. Cardiovasc Res 61(3):372–385. doi:10.1016/S0008-6363(03)00533-9

    Article  PubMed  CAS  Google Scholar 

  24. Halestrap AP, Kerr PM, Javadov S, Woodfield KY (1998) Elucidating the molecular mechanism of the permeability transition pore and its role in reperfusion injury of the heart. Biochim Biophys Acta 1366(1–2):79–94

    PubMed  CAS  Google Scholar 

  25. Hausenloy DJ, Lecour S, Yellon DM (2011) Reperfusion injury salvage kinase and survivor activating factor enhancement prosurvival signaling pathways in ischemic postconditioning: two sides of the same coin. Antioxid Redox Signal 14(5):893–907. doi:10.1089/ars.2010.3360

    Article  PubMed  CAS  Google Scholar 

  26. Hausenloy DJ, Ong SB, Yellon DM (2009) The mitochondrial permeability transition pore as a target for preconditioning and postconditioning. Basic Res Cardiol 104(2):189–202. doi:10.1007/s00395-009-0010-x

    Article  PubMed  CAS  Google Scholar 

  27. Hausenloy DJ, Tsang A, Mocanu MM, Yellon DM (2005) Ischemic preconditioning protects by activating prosurvival kinases at reperfusion. Am J Physiol Heart Circ Physiol 288(2):H971–H976. doi:10.1152/ajpheart.00374.2004

    Article  PubMed  CAS  Google Scholar 

  28. Heusch G, Boengler K, Schulz R (2010) Inhibition of mitochondrial permeability transition pore opening: the Holy Grail of cardioprotection. Basic Res Cardiol 105(2):151–154. doi:10.1007/s00395-009-0080-9

    Article  PubMed  Google Scholar 

  29. Heusch G, Boengler K, Schulz R (2008) Cardioprotection: nitric oxide, protein kinases, and mitochondria. Circulation 118(19):1915–1919. doi:10.1161/CIRCULATIONAHA.108.805242

    Article  PubMed  Google Scholar 

  30. Heusch G, Musiolik J, Gedik N, Skyschally A (2011) Mitochondrial STAT3 activation and cardioprotection by ischemic postconditioning in pigs with regional myocardial ischemia/reperfusion. Circ Res 109(11):1302–1308. doi:10.1161/CIRCRESAHA.111.255604

    Article  PubMed  CAS  Google Scholar 

  31. Hilfiker-Kleiner D, Kaminski K, Podewski E et al (2007) A cathepsin D-cleaved 16 kDa form of prolactin mediates postpartum cardiomyopathy. Cell 128(3):589–600. doi:10.1016/j.cell.2006.12.036

    Article  PubMed  CAS  Google Scholar 

  32. James AH, Jamison MG, Biswas MS, Brancazio LR, Swamy GK, Myers ER (2006) Acute myocardial infarction in pregnancy: a United States population-based study. Circulation 113(12):1564–1571. doi:10.1161/CIRCULATIONAHA.105.576751

    Article  PubMed  Google Scholar 

  33. James PR (2001) Drugs in pregnancy. Cardiovascular disease. Best Pract Res Clin Obstet Gynaecol 15(6):903–911. doi:10.1053/beog.2001.0237

    Article  PubMed  CAS  Google Scholar 

  34. Jin ZQ, Goetzl EJ, Karliner JS (2004) Sphingosine kinase activation mediates ischemic preconditioning in murine heart. Circulation 110(14):1980–1989. doi:10.1161/01.CIR.0000143632.06471.93

    Article  PubMed  CAS  Google Scholar 

  35. Kam KW, Qi JS, Chen M, Wong TM (2004) Estrogen reduces cardiac injury and expression of beta1-adrenoceptor upon ischemic insult in the rat heart. J Pharmacol Exp Ther 309(1):8–15. doi:10.1124/jpet.103.058339

    Article  PubMed  CAS  Google Scholar 

  36. Keeley EC, Boura JA, Grines CL (2003) Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials. Lancet 361(9351):13–20. doi:10.1016/S0140-6736(03)12113-7

    Article  PubMed  Google Scholar 

  37. Kelly RF, Lamont KT, Somers S et al (2010) Ethanolamine is a novel STAT-3 dependent cardioprotective agent. Basic Res Cardiol 105(6):763–770. doi:10.1007/s00395-010-0125-0

    Article  PubMed  CAS  Google Scholar 

  38. Kevin LG, Novalija E, Stowe DF (2005) Reactive oxygen species as mediators of cardiac injury and protection: the relevance to anesthesia practice. Anesth Analg 101(5):1275–1287. doi:10.1213/01.ANE.0000180999.81013

    Article  PubMed  Google Scholar 

  39. Korge P, Ping P, Weiss JN (2008) Reactive oxygen species production in energized cardiac mitochondria during hypoxia/reoxygenation: modulation by nitric oxide. Circ Res 103(8):873–880. doi:10.1161/CIRCRESAHA.108.180869

    Article  PubMed  CAS  Google Scholar 

  40. Kuch M, Janiszewski M, Mamcarz A, Cudnoch-Jedrzejewska A, Dluzniewski M (2009) Major adverse cardiac event predictors in survivors of myocardial infarction with asymptomatic left ventricular dysfunction or chronic heart failure. Med Sci Monit 15(6):H40–H48

    Google Scholar 

  41. Lacerda L, Somers S, Opie LH, Lecour S (2009) Ischaemic postconditioning protects against reperfusion injury via the SAFE pathway. Cardiovasc Res 84(2):201–208. doi:10.1093/cvr/cvp274

    Article  PubMed  CAS  Google Scholar 

  42. Ladner HE, Danielsen B, Gilbert WM (2005) Acute myocardial infarction in pregnancy and the puerperium: a population-based study. Obstet Gynecol 105(3):480–484. doi:10.1097/01.AOG.0000151998.50852.31

    Article  PubMed  Google Scholar 

  43. Lecour S (2009) Multiple protective pathways against reperfusion injury: a SAFE path without Aktion? J Mol Cell Cardiol 46(5):607–609. doi:10.1016/j.yjmcc.2009.01.003

    Article  PubMed  CAS  Google Scholar 

  44. Lemasters JJ, Qian T, He L et al (2002) Role of mitochondrial inner membrane permeabilization in necrotic cell death, apoptosis, and autophagy. Antioxid Redox Signal 4(5):769–781. doi:10.1089/152308602760598918

    Article  PubMed  CAS  Google Scholar 

  45. Madamanchi NR, Runge MS (2007) Mitochondrial dysfunction in atherosclerosis. Circ Res 100(4):460–473. doi:10.1161/01.RES.0000258450.44413.96

    Article  PubMed  CAS  Google Scholar 

  46. Matsui T, Tao J, del Monte F et al (2001) Akt activation preserves cardiac function and prevents injury after transient cardiac ischemia in vivo. Circulation 104(3):330–335. doi:10.1161/01.CIR.104.3.330

    Article  PubMed  CAS  Google Scholar 

  47. Nahrendorf M, Frantz S, Hu K et al (2003) Effect of testosterone on post-myocardial infarction remodeling and function. Cardiovasc Res 57(2):370–378. doi:10.1016/S0008-6363(02)00701-0

    Article  PubMed  CAS  Google Scholar 

  48. Nam UH, Wang M, Crisostomo PR et al (2007) The effect of chronic exogenous androgen on myocardial function following acute ischemia-reperfusion in hosts with different baseline levels of sex steroids. J Surg Res 142(1):113–118. doi:10.1016/j.jss.2006.11.019

    Article  PubMed  CAS  Google Scholar 

  49. Oak JH, Cai H (2007) Attenuation of angiotensin II signaling recouples eNOS and inhibits nonendothelial NOX activity in diabetic mice. Diabetes 56(1):118–126

    Article  PubMed  CAS  Google Scholar 

  50. Ong SB, Subrayan S, Lim SY, Yellon DM, Davidson SM, Hausenloy DJ (2010) Inhibiting mitochondrial fission protects the heart against ischemia/reperfusion injury. Circulation 121(18):2012–2022. doi:10.1161/CIRCULATIONAHA.109.906610

    Article  PubMed  CAS  Google Scholar 

  51. Pedretti S, Raddatz E (2011) STAT3alpha interacts with nuclear GSK3beta and cytoplasmic RISK pathway and stabilizes rhythm in the anoxic-reoxygenated embryonic heart. Basic Res Cardiol 106(3):355–369. doi:10.1007/s00395-011-0152-5

    Article  PubMed  CAS  Google Scholar 

  52. Penpargkul S, Scheuer J (1970) The effect of physical training upon the mechanical and metabolic performance of the rat heart. J Clin Invest 49(10):1859–1868

    Article  PubMed  CAS  Google Scholar 

  53. Pluim BM, Zwinderman AH, van der Laarse A, van der Wall EE (2000) The athlete’s heart. A meta-analysis of cardiac structure and function. Circulation 101(3):336–344. doi:10.1161/01.CIR.101.3.336

    Article  PubMed  CAS  Google Scholar 

  54. Rahman S, Li J, Bopassa JC et al (2011) Phosphorylation of GSK-3beta mediates intralipid-induced cardioprotection against ischemia/reperfusion injury. Anesthesiology 115(2):242–253. doi:10.1097/ALN.0b013e318223b8b9

    Article  PubMed  CAS  Google Scholar 

  55. Riedhammer HH, Rafflenbeul W, Weihe WH, Krayenbuhl HP (1976) Left ventricle contractile function in trained dogs with cardial hypertrophy. Basic Res Cardiol 71(3):297–308

    Article  PubMed  CAS  Google Scholar 

  56. Robson SC, Dunlop W, Moore M, Hunter S (1987) Combined Doppler and echocardiographic measurement of cardiac output: theory and application in pregnancy. Br J Obstet Gynaecol 94(11):1014–1027

    Article  PubMed  CAS  Google Scholar 

  57. Roth A, Elkayam U (1996) Acute myocardial infarction associated with pregnancy. Ann Intern Med 125(9):751–762

    PubMed  CAS  Google Scholar 

  58. Roth A, Elkayam U (2008) Acute myocardial infarction associated with pregnancy. J Am Coll Cardiol 52(3):171–180. doi:10.1016/j.jacc.2008.03.049

    Article  PubMed  Google Scholar 

  59. Rottlaender D, Boengler K, Wolny M et al (2010) Connexin 43 acts as a cytoprotective mediator of signal transduction by stimulating mitochondrial KATP channels in mouse cardiomyocytes. J Clin Invest 120(5):1441–1453. doi:10.1172/JCI40927

    Article  PubMed  CAS  Google Scholar 

  60. Rottlaender D, Boengler K, Wolny M et al (2012) Glycogen synthase kinase 3beta transfers cytoprotective signaling through connexin 43 onto mitochondrial ATP-sensitive K+ channels. Proc Natl Acad Sci USA 109(5):E242–E251. doi:10.1073/pnas.1107479109

    Article  PubMed  CAS  Google Scholar 

  61. Saito T, Ciobotaru A, Bopassa JC, Toro L, Stefani E, Eghbali M (2009) Estrogen contributes to gender differences in mouse ventricular repolarization. Circ Res 105(4):343–352. doi:10.1161/CIRCRESAHA.108.190041

    Article  PubMed  CAS  Google Scholar 

  62. Schannwell CM, Zimmermann T, Schneppenheim M, Plehn G, Marx R, Strauer BE (2002) Left ventricular hypertrophy and diastolic dysfunction in healthy pregnant women. Cardiology 97(2):73–78

    Article  PubMed  Google Scholar 

  63. Skyschally A, van Caster P, Boengler K et al (2009) Ischemic postconditioning in pigs: no causal role for RISK activation. Circ Res 104(1):15–18. doi:10.1161/CIRCRESAHA.108.186429

    Article  PubMed  CAS  Google Scholar 

  64. Suleman N, Somers S, Smith R, Opie LH, Lecour SC (2008) Dual activation of STAT-3 and Akt is required during the trigger phase of ischaemic preconditioning. Cardiovasc Res 79(1):127–133. doi:10.1093/cvr/cvn067

    Article  PubMed  CAS  Google Scholar 

  65. Tamareille S, Ghaboura N, Treguer F et al (2009) Myocardial reperfusion injury management: erythropoietin compared with postconditioning. Am J Physiol Heart Circ Physiol 297(6):H2035–H2043. doi:10.1152/ajpheart.00472.2009

    Article  PubMed  CAS  Google Scholar 

  66. Toescu V, Nuttall SL, Martin U, Kendall MJ, Dunne F (2002) Oxidative stress and normal pregnancy. Clin Endocrinol (Oxf) 57(5):609–613. doi:10.1046/j.1365-2265.2002.01638.x

    Article  CAS  Google Scholar 

  67. Tuteja N, Ahmad P, Panda BB, Tuteja R (2009) Genotoxic stress in plants: shedding light on DNA damage, repair and DNA repair helicases. Mutat Res 681(2–3):134–149. doi:10.1016/j.mrrev.2008.06.004

    PubMed  CAS  Google Scholar 

  68. Yang XM, Krieg T, Cui L, Downey JM, Cohen MV (2004) NECA and bradykinin at reperfusion reduce infarction in rabbit hearts by signaling through PI3K, ERK, and NO. J Mol Cell Cardiol 36(3):411–421. doi:10.1016/j.yjmcc.2003.12.008

    Article  PubMed  CAS  Google Scholar 

  69. Youn JY, Wang T, Cai H (2009) An ezrin/calpain/PI3K/AMPK/eNOSs1179 signaling cascade mediating VEGF-dependent endothelial nitric oxide production. Circ Res 104(1):50–59. doi:10.1161/CIRCRESAHA.108.178467

    Article  PubMed  CAS  Google Scholar 

  70. Zhang J, Cai H (2010) Netrin-1 prevents ischemia/reperfusion-induced myocardial infarction via a DCC/ERK1/2/eNOS s1177/NO/DCC feed-forward mechanism. J Mol Cell Cardiol 48(6):1060–1070. doi:10.1016/j.yjmcc.2009.11.020

    Article  PubMed  CAS  Google Scholar 

  71. Zhuo C, Wang Y, Wang X, Wang Y, Chen Y (2011) Cardioprotection by ischemic postconditioning is abolished in depressed rats: role of Akt and signal transducer and activator of transcription-3. Mol Cell Biochem 346(1–2):39–47. doi:10.1007/s11010-010-0589-0

    Article  PubMed  CAS  Google Scholar 

  72. Zoratti M, Szabo I (1995) The mitochondrial permeability transition. Biochim Biophys Acta 1241(2):139–176. doi:10.1016/0304-4157(95)00003-A

    PubMed  Google Scholar 

Download references

Acknowledgments

Supported by NIH Grants HL089876 (M.E.), HL089876S1 (M.E.), HL077440 (H.C.) and HL088975 (H.C.).

Author information

Authors and Affiliations

  1. Departments of Anesthesiology, Division of Molecular Medicine, David Geffen School of Medicine at UCLA, BH-160CHS, 650 Charles E Young Dr, Los Angeles, CA, 90095-7115, USA

    Jingyuan Li, Soban Umar, Andrea Iorga, Ji-Youn Youn, Yibin Wang, Hua Cai & Mansoureh Eghbali

  2. Cardiovascular Research Laboratories, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA

    Yibin Wang, Hua Cai & Mansoureh Eghbali

  3. Institute of Gender in Medicine and Center for Cardiovascular Research, Charite University Hospital, Berlin, Germany

    Vera Regitz-Zagrosek

Authors
  1. Jingyuan Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Soban Umar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Andrea Iorga
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ji-Youn Youn
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yibin Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Vera Regitz-Zagrosek
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hua Cai
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Mansoureh Eghbali
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mansoureh Eghbali.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 47 kb)

Fig. S (PDF 3836 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Li, J., Umar, S., Iorga, A. et al. Cardiac vulnerability to ischemia/reperfusion injury drastically increases in late pregnancy. Basic Res Cardiol 107, 271 (2012). https://doi.org/10.1007/s00395-012-0271-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00395-012-0271-7

Keywords

Search

Navigation