Effect of a novel molybdenum ascorbate complex on ex vivo myocardial performance in chemical diabetes mellitus.
BACKGROUND
The insulin-like action of metal complexes on target tissues, including the heart, has been reported in experimental diabetes mellitus. Since streptozotocin-induced diabetes is associated with insulin deficiency and left ventricular dysfunction, this study was designed to determine whether the novel metal complex molybdenum ascorbate [MoO(2)(aa)(2)] would improve cardiac function in this model of diabetes.


METHODS
Diabetes was induced in Sprague-Dawley rats (n = 6) following an intravenous injection of streptozotocin (60 mg/kg). After 8 weeks of diabetes, cardiac function was determined in isolated working hearts perfused with 11 mmol/L glucose, 1.2 mmol/L palmitate and 3% albumin. MoO(2)(aa)(2 )was added directly into the perfusate of working hearts at a concentration of 200 micromol/L for a period of 30 minutes. Age-matched control rats served as controls (n = 6).


RESULTS
Cardiac function, expressed as heart rate (HR) and aortic flow, was significantly decreased in diabetic hearts compared with control hearts. The diabetic state was associated with 23% and 60% reductions in HR and aortic flow, respectively. Short-term addition of MoO(2)(aa)(2) was beneficial and partially prevented the attenuation in diabetic rat heart function. MoO(2)(aa)(2 )increased HR by 15%, while aortic flow was increased by 85%. In control hearts, MoO(2)(aa)(2) had no effect on HR and increased aortic flow by 12%.


CONCLUSIONS
This study extends previous observations on the benefit of metal complexes in experimental diabetes. Our results indicate that short-term treatment with MoO(2)(aa)(2) partially reversed the left ventricular dysfunction associated with the streptozotocin model of diabetes.
Department of Physiology, Midwestern University, Glendale, Arizona 85308, USA. tbrod@midwestern.edu
Tom L
TL
Broderick
John
J
Bailey
Karen J
KJ
Gagnon
Sarah J
SJ
Lord
Christopher M
CM
Vogels
Stephen A
SA
Westcott
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000503:physiopathology; D001205:Ascorbic Acid / Q000737:chemistry / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight; D003326:Coronary Circulation / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000503:physiopathology*; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008982:Molybdenum / Q000737:chemistry / Q000494:pharmacology*; D009929:Organ Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy; D014815:Vitamins / Q000737:chemistry / Q000494:pharmacology
D014815:Vitamins; D008982:Molybdenum; D001205:Ascorbic Acid