OBJECTIVES: Free fatty acid (FFA) oxidation is depressed in the postischaemic stunned myocardium and recovers in parallel with the normalization of contractile performance. Assuming a causal role for this metabolic disturbance in the pathogenesis of stunning, we questioned whether exogenous administration of high dose triglycerides during reperfusion of postischaemic myocardium, could improve its functional recovery. METHODS: Thirteen dogs were chronically instrumented to measure global and regional haemodynamics and to produce a 10 min episode of regional myocardial ischaemia. In 7 dogs, Intralipid 20% was administered i.v. during the reperfusion phase. Contractile recovery of stunned myocardium was compared with control saline treatments. The series were repeated in another 6 animals, but oxfenicine (CPT I inhibitor) preceeded Intralipid during reperfusion. RESULTS: Contractile recovery of stunned myocardium was faster and more extensive when Intralipid was administered during reperfusion than with saline treatment (wall thickening fraction 86 +/- 6% of preischaemic controls versus 52 +/- 11% at 90 min post-reperfusion; P < 0.05). Oxfenicine pretreatment completely abolished this beneficial effect. CONCLUSIONS: Exogenous administration of triglycerides during reperfusion of postischaemic myocardium improves functional recovery from stunning. This beneficial effect most likely operates through enhanced FFA availability and/or oxidation since it could be abolished by selective inhibition of the carnitine palmitoyl I enzyme.
OBJECTIVES:Free fatty acid (FFA) oxidation is depressed in the postischaemic stunned myocardium and recovers in parallel with the normalization of contractile performance. Assuming a causal role for this metabolic disturbance in the pathogenesis of stunning, we questioned whether exogenous administration of high dose triglycerides during reperfusion of postischaemic myocardium, could improve its functional recovery. METHODS: Thirteen dogs were chronically instrumented to measure global and regional haemodynamics and to produce a 10 min episode of regional myocardial ischaemia. In 7 dogs, Intralipid 20% was administered i.v. during the reperfusion phase. Contractile recovery of stunned myocardium was compared with control saline treatments. The series were repeated in another 6 animals, but oxfenicine (CPT I inhibitor) preceeded Intralipid during reperfusion. RESULTS: Contractile recovery of stunned myocardium was faster and more extensive when Intralipid was administered during reperfusion than with saline treatment (wall thickening fraction 86 +/- 6% of preischaemic controls versus 52 +/- 11% at 90 min post-reperfusion; P < 0.05). Oxfenicine pretreatment completely abolished this beneficial effect. CONCLUSIONS: Exogenous administration of triglycerides during reperfusion of postischaemic myocardium improves functional recovery from stunning. This beneficial effect most likely operates through enhanced FFA availability and/or oxidation since it could be abolished by selective inhibition of the carnitine palmitoyl I enzyme.
Authors: Jing Li; Michael Fettiplace; Sy-Jou Chen; Benjamin Steinhorn; Zuohui Shao; Xiangdong Zhu; Changqing Li; Shaun Harty; Guy Weinberg; Terry L Vanden Hoek Journal: Crit Care Med Date: 2014-12 Impact factor: 7.598
Authors: Michael R Fettiplace; Belinda S Akpa; Richard Ripper; Brian Zider; Jason Lang; Israel Rubinstein; Guy Weinberg Journal: Anesthesiology Date: 2014-04 Impact factor: 7.892
Authors: Phing-How Lou; Eliana Lucchinetti; Liyan Zhang; Andreas Affolter; Marcus C Schaub; Manoj Gandhi; Martin Hersberger; Blair E Warren; Hélène Lemieux; Hany F Sobhi; Alexander S Clanachan; Michael Zaugg Journal: PLoS One Date: 2014-01-30 Impact factor: 3.240