title: Effects of isoproterenol infusion on the myocardial uptake of fatty acids and other substrates in lambs with an aortopulmonary shunt.
abstract: Isoproterenol, used in the management of infants with left-to-right shunts and circulatory congestion, increases myocardial work load and oxygen consumption. In addition, it may selectively enhance myocardial fatty acid utilization. The less efficient oxidation of FFA could induce an oxygen wasting effect and thus further increase myocardial oxygen consumption. The combination of such an oxygen wasting effect and the chrono- and inotropic effects of isoproterenol could induce an imbalance between myocardial oxygen supply and demand in hearts of which resting oxygen consumption is already elevated. We studied myocardial substrate uptake (FFA, triglycerides, glucose, lactate, pyruvate, beta-OH-butyrate, and acetoacetate) in 10 7-wk-old lambs with an aortopulmonary left-to-right shunt (57 +/- 4% of left ventricular output, mean +/- SEM) and 9 control lambs during isoproterenol infusion (0.1 mumol.min-1.kg-1). Myocardial blood flow and oxygen consumption increased in both groups but less in shunt than in control lambs because of the smaller rise in heart rate in the shunt lambs. The arterial FFA concentration increased 3-fold in both groups and was not different between the two groups. The FFA arteriocoronary sinus difference, however, was not affected by the isoproterenol infusion. The myocardial FFA uptake thus followed the changes in myocardial blood flow and did not increase more in shunt than in control lambs. Isoproterenol infusion does, in spite of a 3-fold increase in arterial FFA concentration, not induce a shift toward a greater percentage uptake of fatty acids compared with other substrates in lambs with aortopulmonary left-to-right shunt, so that the possibility of an oxygen wasting effect can be ruled out as an unwanted side effect.
authors.affiliation: Department of Thoracic Surgery of the University Hospital, University of Groningen, Netherlands.
authors.forename: J W
authors.initials: JW
authors.lastname: Gratama
authors.forename: J J
authors.initials: JJ
authors.lastname: Meuzelaar
authors.forename: M
authors.initials: M
authors.lastname: Dalinghaus
authors.forename: W G
authors.initials: WG
authors.lastname: Zijlstra
authors.forename: J R
authors.initials: JR
authors.lastname: Kuipers
mesh_terms: D000818:Animals; D001166:Arteriovenous Shunt, Surgical; D005227:Fatty Acids / Q000493:pharmacokinetics*; D007261:Infusions, Intra-Arterial; D007545:Isoproterenol / Q000494:pharmacology*; D009206:Myocardium / Q000378:metabolism*; D012756:Sheep
chemical_list: D005227:Fatty Acids; D007545:Isoproterenol