Endotoxin-induced Myocardial Dysfunction in Senescent Rats

Overview

Journal Crit Care

Specialty Critical Care

Date 2006 Sep 1

PMID 16942612

Citations 9

Authors

Sandrine Rozenberg

Sophie Besse

Helene Brisson

Elsa Jozefowicz

Abdelmejid Kandoussi

Alexandre Mebazaa

Bruno Riou

Benoit Vallet

Benoit Tavernier

Affiliations

Soon will be listed here.

Abstract

Introduction: Aging is associated with a decline in cardiac contractility and altered immune function. The aim of this study was to determine whether aging alters endotoxin-induced myocardial dysfunction.

Methods: Senescent (24 month) and young adult (3 month) male Wistar rats were treated with intravenous lipopolysaccharide (LPS) (0.5 mg/kg (senescent and young rats) or 5 mg/kg (young rats only)), or saline (senescent and young control groups). Twelve hours after injection, cardiac contractility (isolated perfused hearts), myofilament Ca2+ sensitivity (skinned fibers), left ventricular nitric oxide end-oxidation products (NOx and NO2) and markers of oxidative stress (thiobarbituric acid reactive species (TBARS) and antioxidant enzymes) were investigated.

Results: LPS (0.5 mg/kg) administration resulted in decreased contractility in senescent rats (left ventricular developed pressure (LVDP), 25 +/- 4 vs 53 +/- 4 mmHg/g heart weight in control; P < 0.05) of amplitude similar to that in young rats with LPS 5 mg/kg (LVDP, 48 +/- 7 vs 100 +/- 7 mmHg/g heart weight in control; P < 0.05). In contrast to young LPS rats (0.5 and 5 mg/kg LPS), myofilament Ca2+ sensitivity was unaltered in senescent LPS hearts. Myocardial NOx and NO2 were increased in a similar fashion by LPS in young (both LPS doses) and senescent rats. TBARS and antioxidant enzyme activities were unaltered by sepsis whatever the age of animals.

Conclusion: Low dose of LPS induced a severe myocardial dysfunction in senescent rats. Ca2+ myofilament responsiveness, which is typically reduced in myocardium of young adult septic rats, however, was unaltered in senescent rats. If these results are confirmed in in vivo conditions, they may provide a cellular explanation for the divergent reports on ventricular diastolic function in septic shock. In addition, Ca2+-sensitizing agents may not be as effective in aged subjects as in younger subjects.

Citing Articles

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References

Yang S, Hsu C, Lue S, Hsu H, Liu M . Protein kinase a activity is increased in rat heart during late hypodynamic phase of sepsis. Shock. 1997; 8(1):68-72. DOI: 10.1097/00024382-199707000-00011. View

Parrillo J . Pathogenetic mechanisms of septic shock. N Engl J Med. 1993; 328(20):1471-7. DOI: 10.1056/NEJM199305203282008. View

Meng X, Ao L, Meldrum D, CAIN B, Shames B, Selzman C . TNF-alpha and myocardial depression in endotoxemic rats: temporal discordance of an obligatory relationship. Am J Physiol. 1998; 275(2):R502-8. DOI: 10.1152/ajpregu.1998.275.2.R502. View

Tavernier B, Garrigue D, Boulle C, Vallet B, Adnet P . Myofilament calcium sensitivity is decreased in skinned cardiac fibres of endotoxin-treated rabbits. Cardiovasc Res. 1998; 38(2):472-9. DOI: 10.1016/s0008-6363(98)00028-5. View

Abi-Gerges N, Tavernier B, Mebazaa A, Faivre V, Paqueron X, Payen D . Sequential changes in autonomic regulation of cardiac myocytes after in vivo endotoxin injection in rat. Am J Respir Crit Care Med. 1999; 160(4):1196-204. DOI: 10.1164/ajrccm.160.4.9808149. View

Layland J, Solaro R, Shah A . Regulation of cardiac contractile function by troponin I phosphorylation. Cardiovasc Res. 2005; 66(1):12-21. DOI: 10.1016/j.cardiores.2004.12.022. View

Andrades M, Ritter C, Moreira J, Dal-Pizzol F . Oxidative parameters differences during non-lethal and lethal sepsis development. J Surg Res. 2005; 125(1):68-72. DOI: 10.1016/j.jss.2004.11.008. View

Morelli A, De Castro S, Teboul J, Singer M, Rocco M, Conti G . Effects of levosimendan on systemic and regional hemodynamics in septic myocardial depression. Intensive Care Med. 2005; 31(5):638-44. DOI: 10.1007/s00134-005-2619-z. View

Lukaszewicz A, Mebazaa A, Callebert J, Mateo J, Gatecel C, Kechiche H . Lack of alteration of endogenous nitric oxide pathway during prolonged nitric oxide inhalation in intensive care unit patients. Crit Care Med. 2005; 33(5):1008-14. DOI: 10.1097/01.ccm.0000163233.00458.dd. View

10.

Layland J, Cave A, Warren C, Grieve D, Sparks E, Kentish J . Protection against endotoxemia-induced contractile dysfunction in mice with cardiac-specific expression of slow skeletal troponin I. FASEB J. 2005; 19(9):1137-9. DOI: 10.1096/fj.04-2519fje. View

11.

Faivre V, Kaskos H, Callebert J, Losser M, Milliez P, Bonnin P . Cardiac and renal effects of levosimendan, arginine vasopressin, and norepinephrine in lipopolysaccharide-treated rabbits. Anesthesiology. 2005; 103(3):514-21. DOI: 10.1097/00000542-200509000-00014. View

12.

Rabuel C, Mebazaa A . Septic shock: a heart story since the 1960s. Intensive Care Med. 2006; 32(6):799-807. DOI: 10.1007/s00134-006-0142-5. View

13.

Zhang Q, Molino B, Yan L, Haim T, Vaks Y, Scholz P . Nitric oxide and cGMP protein kinase activity in aged ventricular myocytes. Am J Physiol Heart Circ Physiol. 2001; 281(6):H2304-9. DOI: 10.1152/ajpheart.2001.281.6.H2304. View

14.

Zieman S, Gerstenblith G, Lakatta E, Rosas G, Vandegaer K, Ricker K . Upregulation of the nitric oxide-cGMP pathway in aged myocardium: physiological response to l-arginine. Circ Res. 2001; 88(1):97-102. DOI: 10.1161/01.res.88.1.97. View

15.

Ming M, Hu D, Chen H, Liu L, Nan X, Hua C . Effect of MCI-154, a calcium sensitizer, on calcium sensitivity of myocardial fibers in endotoxic shock rats. Shock. 2000; 14(6):652-6. DOI: 10.1097/00024382-200014060-00014. View

16.

Marik P, Zaloga G . The effect of aging on circulating levels of proinflammatory cytokines during septic shock. Norasept II Study Investigators. J Am Geriatr Soc. 2001; 49(1):5-9. DOI: 10.1046/j.1532-5415.2001.49003.x. View

17.

Tavernier B, Li J, Lanone S, Yang Z, Trayer I, Mebazaa A . Cardiac contractile impairment associated with increased phosphorylation of troponin I in endotoxemic rats. FASEB J. 2001; 15(2):294-6. DOI: 10.1096/fj.00-0433fje. View

18.

Tavernier B, Mebazaa A, Mateo P, Sys S, Ventura-Clapier R, Veksler V . Phosphorylation-dependent alteration in myofilament ca2+ sensitivity but normal mitochondrial function in septic heart. Am J Respir Crit Care Med. 2001; 163(2):362-7. DOI: 10.1164/ajrccm.163.2.2002128. View

19.

Vieillard Baron A, Schmitt J, Beauchet A, Augarde R, Prin S, Page B . Early preload adaptation in septic shock? A transesophageal echocardiographic study. Anesthesiology. 2001; 94(3):400-6. DOI: 10.1097/00000542-200103000-00007. View

20.

Saito H, Papaconstantinou J . Age-associated differences in cardiovascular inflammatory gene induction during endotoxic stress. J Biol Chem. 2001; 276(31):29307-12. DOI: 10.1074/jbc.M103740200. View