Phenotypic adaptation of the late preconditioned heart: myocardial oxygen consumption is reduced.
OBJECTIVE
Although the signalling pathways of late preconditioning have been extensively investigated, its consequence for myocardial metabolism remains unknown. Thus, myocardial oxygen consumption (MVO2) was evaluated before and under late preconditioning.


METHODS
In 7 chronically instrumented dogs, we measured MVO2 in vivo at baseline and during inotropic stimulation with dobutamine (10 and 20 microg/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 the triple product (heart ratexleft ventricular systolic pressurexleft ventricular maximum dP/dt), MVO2, coronary blood flow, and coronary sinus pO2. At Day 1, the triple product was similar at baseline and at each dose of dobutamine but MVO2 was significantly blunted as compared to Day 0 (-15+/-4%, -22+/-3% and -19+/-4% at baseline, dobutamine 10 and 20 microg/kg/min, respectively). Importantly, the relationship between MVO2 and triple product was significantly rightward shifted with late preconditioning, i.e., MVO2 was reduced for any level of triple product. At Day 1, the relationship between coronary blood flow and MVO2 was not altered as compared to Day 0 but coronary sinus pO2 was significantly increased vs. Day 0 for any level of coronary blood flow, suggesting that late preconditioning exerted no vasomotor effect but rather changed myocardial oxygen handling. These effects were abolished by administration of S-methyl-isothiourea (1.5 mg/kg, i.v.), a iNOS inhibitor.


CONCLUSIONS
This study demonstrates that ischemic late preconditioning is characterized by a major reduction in MVO2, both at baseline and under inotropic stimulation. NO from iNOS contributes to this modification of metabolic phenotype.
Monnet
Xavier
X
INSERM U660, Créteil, F-94010, France.
Ghaleh
Bijan
B
Lucats
Laurence
L
Colin
Patrice
P
Zini
Roland
R
Hittinger
Luc
L
Berdeaux
Alain
A
D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology; D003326:Coronary Circulation; D004280:Dobutamine / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006339:Heart Rate; D006352:Heart Ventricles; D019157:Ischemic Preconditioning, Myocardial; D007550:Isothiuronium / Q000031:analogs & derivatives / Q000494:pharmacology; D023421:Models, Animal; D017202:Myocardial Ischemia / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors; D010101:Oxygen Consumption; D013268:Stimulation, Chemical; D013997:Time Factors; D017725:Ventricular Pressure
D002316:Cardiotonic Agents; D004791:Enzyme Inhibitors; D007550:Isothiuronium; D004280:Dobutamine; D052247:Nitric Oxide Synthase Type II; C027744:S-methylisothiopseudouronium