Phenotypic adaptation of the late preconditioned heart: Myocardial oxygen consumption is reduced

doi:10.1016/j.cardiores.2005.07.005

Cardiovascular Research 2006 70(2):391-398; doi:10.1016/j.cardiores.2005.07.005

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Phenotypic adaptation of the late preconditioned heart: Myocardial oxygen consumption is reduced

Xavier Monnet^a^,b^,c, Bijan Ghaleh^a^,b^,c^,d, Laurence Lucats^a^,b^,c, Patrice Colin^a^,b^,c, Roland Zini^a^,b^,c, Luc Hittinger^a^,b^,c^,d and Alain Berdeaux^a^,b^,c^,d^,*

^aINSERM U660, Créteil, F-94010, France
^bEcole Nationale Vétérinaire d'Alfort, Maisons-Alfort, F-94700, France
^cLaboratoire de Pharmacologie, Faculté de Médecine de Créteil, Université Paris XII, Créteil, F-94000, France
^dFédération de Cardiologie, Hôpital Henri Mondor, Créteil, France

^* Corresponding author. Laboratoire de Pharmacologie, INSERM U660, Faculté de Médecine de Créteil, 8, rue du Général Sarrail, 94010 Creteil Cedex, France. Tel.: +33 1 49 81 36 51; fax: +33 1 49 98 17 77. Email address: berdeaux{at}im3.inserm.fr

Objectives Although the signalling pathways of late preconditioninghave been extensively investigated, its consequence for myocardialmetabolism remains unknown. Thus, myocardial oxygen consumption(MVO₂) was evaluated before and under late preconditioning.

Methods In 7 chronically instrumented dogs, we measured MVO₂in vivo at baseline and during inotropic stimulation with dobutamine(10 and 20 µg/kg/min, i.v.) before (Day 0) and 24 h after(Day 1) a 10-min circumflex coronary artery occlusion.

Results At Day 0, dobutamine dose-dependently increased thetriple product (heart rate x left ventricular systolic pressurex left ventricular maximum dP/dt), MVO₂, coronary blood flow,and coronary sinus pO₂. At Day 1, the triple product was similarat baseline and at each dose of dobutamine but MVO₂ was significantlyblunted as compared to Day 0 (– 15±4%, –22±3% and – 19±4% at baseline, dobutamine10 and 20 µg/kg/min, respectively). Importantly, the relationshipbetween MVO₂ and triple product was significantly rightwardshifted with late preconditioning, i.e., MVO₂ was reduced forany level of triple product. At Day 1, the relationship betweencoronary blood flow and MVO₂ was not altered as compared toDay 0 but coronary sinus pO₂ was significantly increased vs.Day 0 for any level of coronary blood flow, suggesting thatlate preconditioning exerted no vasomotor effect but ratherchanged myocardial oxygen handling. These effects were abolishedby administration of S-methyl-isothiourea (1.5 mg/kg, i.v.),a iNOS inhibitor.

Conclusion This study demonstrates that ischemic late preconditioningis characterized by a major reduction in MVO₂, both at baselineand under inotropic stimulation. NO from iNOS contributes tothis modification of metabolic phenotype.

KEYWORDS Oxygen consumption; Stunning; Nitric oxide; Preconditioning

Time for primary review 20 days

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