1.Acetyl-l-carnitine and oxfenicine on cardiac pumping mechanics in streptozotocin-induced diabetes in male Wistar rats.
Wang CH;Wang SS;Ko WJ;Chen YS;Chang CY;Chang RW;Chang KC PLoS One. 2013 Jul 26;8(7):e69977. doi: 10.1371/journal.pone.0069977. Print 2013.
INTRODUCTION: ;In the treatment of patients with diabetes, one objective is an improvement of cardiac metabolism to alleviate the left ventricular (LV) function. For this study, we compared the effects of acetyl-l-carnitine (one of the carnitine derivatives) and of oxfenicine (a carnitine palmitoyltransferase-1 inhibitor) on cardiac pumping mechanics in streptozotocin-induced diabetes in male Wistar rats, with a particular focus on the pressure-flow-volume relationship.;METHODS: ;Diabetes was induced by a single tail vein injection of 55 mg kg(-1) streptozotocin. The diabetic animals were treated on a daily basis with either acetyl-L-carnitine (1 g L(-1) in drinking water) or oxfenicine (150 mg kg(-1) by oral gavage) for 8 wk. They were also compared with untreated age-matched diabetic controls. LV pressure and ascending aortic flow signals were recorded to calculate the maximal systolic elastance (E max) and the theoretical maximum flow (Q max). Physically, E max reflects the contractility of the myocardium as an intact heart, whereas Q max has an inverse relationship with the LV internal resistance.;RESULTS: ;When comparing the diabetic rats with their age-matched controls, the cardiodynamic condition was characterized by a decline in E max associated with the unaltered Q max.
2.Assessment of the energetic role of endogenous substrates in the tail artery of rat by means of enzyme inhibitors.
Savino EA;Varela A;Carregal M Rev Esp Fisiol. 1996 Mar;52(1):9-13.
The rat tail artery during a 180 min incubation period in a medium containing glucose plus oxfenicine (an inhibitor of fatty acid oxidation) did not show changes in the contractile responses to adrenaline. In a substrate-free medium the extent of the contractions underwent a slight decrease during the last 60 min of incubation. When the substrate-free medium contained 2-deoxyglucose (an inhibitor of glycolysis and glycogenolysis) or oxfenicine, the decline of the contractile activity developed faster and attained a similar extent with each inhibitor. When the substrate-free medium contained 2-deoxyglucose together with oxfenicine or methylpalmoxirate (an inhibitor of fatty acid oxidation) the arteries displayed a pronounced and early fall in the contraction strength. These data suggest that in the presence of glucose the reserve substrates are not necessary as fuel source for the arterial contractions. However, in substrate-free conditions they constitute an important energy source. Furthermore, glycogen and triacylglycerol share the supply of energy and there does not seem to be any other reserve material in the smooth muscle of the rat tail artery.
3.Quantitation of myocardial fatty acid metabolism using PET.
Bergmann SR;Weinheimer CJ;Markham J;Herrero P J Nucl Med. 1996 Oct;37(10):1723-30.
Abnormalities of fatty acid metabolism in the heart presage contractile dysfunction and arrhythmias. This study was performed to determine whether myocardial fatty acid metabolism could be quantified noninvasively using PET and 1-(11)C-palmitate.;METHODS: ;Anesthetized dogs were studied during control conditions; during administration of dobutamine; after oxfenicine; and during infusion of glucose. Dynamic PET data after administration of 1-(11)C-palmitate were fitted to a four-compartment mathematical model.;RESULTS: ;Modeled rates of palmitate utilization correlated closely with directly measured myocardial palmitate and total long-chain fatty acid utilization (r = 0.93 and 0.96, respectively, p < 0.001 for each) over a wide range of arterial fatty acid levels and altered patterns of myocardial substrate use (fatty acid extraction fraction ranging from 1% to 56%, glucose extraction fraction from 1% to 16% and myocardial fatty acid utilization from 1 to 484 nmole/g/ min). The percent of fatty acid undergoing oxidation could also be measured.;CONCLUSION: ;The results demonstrate the ability to quantify myocardial fatty acid utilization with PET. The approach is readily applicable for the determination of fatty acid metabolism noninvasively in patients.