Triiodothyronine Activates Lactate Oxidation Without Impairing Fatty Acid Oxidation and Improves Weaning From Extracorporeal Membrane Oxygenation

Abstract

Background Extracorporeal membrane oxygenation (ECMO) provides a rescue for children with severe cardiac failure. It has previously been shown that triiodothyronine (T3) improves cardiac function by modulating pyruvate oxidation during weaning. This study focused on fatty acid (FA) metabolism modulated by T3 for weaning from ECMO after cardiac injury. Methods and Results Nineteen immature piglets (9.1–15.3 kg) were separated into 3 groups with ECMO (6.5 h) and wean: normal circulation (Group-C); transient coronary occlusion (10 min) for ischemia-reperfusion (IR) followed by ECMO (Group-IR); and IR with T3 supplementation (Group-IR-T3). 13-Carbon (13C)-labeled lactate, medium-chain and long-chain FAs, was infused as oxidative substrates. Substrate fractional contribution (FC) to the citric acid cycle was analyzed by 13C-nuclear magnetic resonance. ECMO depressed circulating T3 levels to 40% of the baseline at 4 h and were restored in Group-IR-T3. Group-IR decreased cardiac power, which was not fully restorable and 2 pigs were lost because of weaning failure. Group-IR also depressed FC-lactate, while the excellent contractile function and energy efficiency in Group-IR-T3 occurred along with a marked FC-lactate increase and [adenosine triphosphate]/[adenosine diphosphate] without either decreasing FC-FAs or elevating myocardial oxygen consumption over Group-C or -IR. Conclusions T3 releases inhibition of lactate oxidation following IR injury without impairing FA oxidation. These findings indicate that T3 depression during ECMO is maladaptive, and that restoring levels improves metabolic flux and enhances contractile function during weaning.

Effect of Abciximab Therapy in Patients Undergoing Coronary Angioplasty for Acute ST-Elevation Myocardial Infarction Complicated by Cardiogenic Shock

“…24 Advanced left ventricular support systems (Impella, Tandem Heart and extracorporeal membrane oxygenator) were not used in the present study, although further investigations are required to verify the effectiveness of these devices in patients with STEMI and CS. [25][26][27][28][29] Finally the present results should be validated in a larger multicenter study.…”

Differential effects of octanoate and heptanoate on myocardial metabolism during extracorporeal membrane oxygenation in an infant swine model

“…2A. Pigs were initially sedated with an intramuscular injection of ketamine (33 mg/kg) and xylazine (2 mg/kg) and were mechanically ventilated with an oxygen (40 -50%) and isoflurane (1-2%) mixture, as described previously (8,9,11). After median sternotomy, recordings of aortic and coronary sinus return flow (Transonic Systems, Ithaca, NY) and left ventricular (LV) pressure (Millar Instruments, Houston, TX) were taken during the experiment, and a veno-arterial ECMO [a roller peristaltic pump console (Sarns 8000) and a hollow fiber membrane oxygenator (CX-RX05RW; Terumo, Tokyo, Japan)] was established by central cannulation via the ascending aorta and right atrium.…”

“…1. 13 C from [5,6,[7][8][9][10][11][12][13] C3]heptanoate metabolizes to CAC without the conversion to acetyl-CoA, and these data were used for analysis of the anaplerotic component to the CAC. NMR data were acquired on a Varian Direct Drive (VNMRS) 600-MHz spectrometer (Agilent Technologies) equipped with a Dell Precision T3500 Linux workstation running VNMRJ 3.2.…”

“…The anaplerotic contribution through propionyl-CoA from [5,6,[7][8][9][10][11][12][13] C3]heptanoate relative to acetyl-CoA entry was calculated by using several parameters obtained from the 13 C-NMR spectrum. The general scheme for the labeling pattern of glutamate is shown in Fig.…”

Thyroid Hormones and the Heart; a Paradigm of Exquisite Fine Tuning, Combining Ancient Hellenic and Oriental Wisdom

“…Matoba [20] based on the findings of Kajimoto et al [21] that triiodothyronine activates lactate oxidation without impairing fatty acid oxidation and improves weaning from extracorporeal membrane oxygenation, proposes T3 administration as therapy for cardiac metabolism in the failing heart. It should be noted that Kajimoto et al [21] gave T3 for about 8 hours.…”