Early myocardial dysfunction in streptozotocin-induced diabetic mice: a study using in vivo magnetic resonance imaging (MRI).

BACKGROUND: Diabetes is associated with a cardiomyopathy that is independent of coronary artery disease or hypertension. In the present study we used in vivo magnetic resonance imaging (MRI) and echocardiographic techniques to examine and characterize early changes in myocardial function in a mouse model of type 1 diabetes. METHODS: Diabetes was induced in 8-week old C57BL/6 mice with two intraperitoneal injections of streptozotocin. The blood glucose levels were maintained at 19-25 mmol/l using intermittent low dosages of long acting insulin glargine. MRI and echocardiography were performed at 4 weeks of diabetes (age of 12 weeks) in diabetic mice and age-matched controls. RESULTS: After 4 weeks of hyperglycemia one marker of mitochondrial function, NADH oxidase activity, was decreased to 50% of control animals. MRI studies of diabetic mice at 4 weeks demonstrated significant deficits in myocardial morphology and functionality including: a decreased left ventricular (LV) wall thickness, an increased LV end-systolic diameter and volume, a diminished LV ejection fraction and cardiac output, a decreased LV circumferential shortening, and decreased LV peak ejection and filling rates. M-mode echocardiographic and Doppler flow studies of diabetic mice at 4 weeks showed a decreased wall thickening and increased E/A ratio, supporting both systolic and diastolic dysfunction. CONCLUSION: Our study demonstrates that MRI interrogation can identify the onset of diabetic cardiomyopathy in mice with its impaired functional capacity and altered morphology. The MRI technique will lend itself to repetitive study of early changes in cardiac function in small animal models of diabetic cardiomyopathy.

Vertebral endplate architecture and vascularization: application of micro-computerized tomography, a vascular tracer, and immunocytochemistry in analyses of disc degeneration in the aging sand rat.

STUDY DESIGN: Lower lumbar vertebral endplates from young and old sand rats were assessed in an Institutional Animal Care and Use Committee approved study for architectural endplate features using micro-computerized tomography (CT) 3-dimensional (3D) models and vascularization studies by an in vivo vascular tracer or immunocytochemical identification of blood vessels. OBJECTIVE: To assess endplate porosity and vascularization using microCT architectural analysis, an in vivo vascular tracer, and immunocytochemical identification of blood vessels in the endplate. SUMMARY OF THE BACKGROUND DATA: The vertebral endplates, also called cartilage endplates, form the superior and inferior, or cranial and caudal, boundaries of the disc. In the human being and sand rat, the cartilaginous endplate undergoes calcification with aging and is replaced by bone. Endplate sclerosis has long been thought to play a role in disc degeneration by decreasing nutrient availability to the disc, but this is still poorly understood. Previous work has identified increasing bone mineral density with aging and disc degeneration in the sand rat model. METHODS: microCT models of the lower lumbar endplates of vertebrae at L5-6 and L6-7 were constructed from 6 younger (mean age 11 months) and 21 older (mean age 25.6 months) sand rats. Architectural features were scored on a semiquantitative scale for smoothness of the endplate face, irregularities on the endplate margin, and endplate thickness. There were 2 smaller sets of animals (n = 18) evaluated for endplate vascularity following in vivo injection of a fluorescent vascular tracer or by the use of immunocytochemistry to identify blood vessels. RESULTS: microCT revealed a solid bony surface to the endplate, which was not penetrated by vasculature; with aging/disc degeneration, there was roughening and pitting of the plate surface, and the development of irregular margins. In L5-6 and L6-7, sites of prominent disc degeneration evident on radiographs, the proportion of abnormalities in surface smoothness, margin irregularity, and endplate thickening were all statistically significant in both younger and older animals (P < or = 0.0027). More severe changes were evident in the caudal versus cranial endplate surfaces. Histologic study of vascular tracer showed that there was no penetration of the disc by vascular supply from the endplate; this was verified by immunocytochemical identification of blood vessels. The canal system within the endplate was a complex 3D interconnected network. CONCLUSIONS: Findings show that disc degeneration in the sand rat occurs concomitantly with marked architectural bony changes on the endplate face, including loss of smoothness and development of irregular bony margins. Vascular connections were not present between the endplate and disc; this was verified with microCT studies, in vivo vascular tracers, and traditional immunocytochemistry. The canal system within the imaged endplate was revealed to consist of a complex 3D interconnected network.

Preoperative leuprolide acetate combined with Interceed* optimally reduces uterine adhesions and fibrosis in a rabbit model.

OBJECTIVE: To determine the optimal approach to prevent adhesions comparing leuprolide acetate (GnRH-a), Interceed (oxidized regenerated cellulose; Johnson & Johnson Medical, Inc., New Brunswick, NJ), and a combination of leuprolide with Interceed in a rabbit uterine horn adhesion model. DESIGN: Prospective, randomized, blinded study. SETTING: Certified animal care facility. ANIMAL(S): Twenty-eight sexually mature, female New Zealand White rabbits. INTERVENTION(S): Animals were prospectively randomized (by number generator) to receive GnRH-a or saline. After 6 weeks, standard surgical manipulations were performed at three sites in each uterine horn by [1]. suture, [2]. unipolar cautery, and [3]. superficial abrasion. Interceed was applied over one randomly assigned uterine horn only. Six weeks after surgery, uterine adhesions were assessed visually, and tissue fibrosis was assessed by histology. MAIN OUTCOME MEASURE(S): Presence or absence of adhesions and microscopic tissue fibrosis. RESULT(S): Gonadotropin-releasing hormone agonist significantly decreased adhesions, whereas Interceed alone did not reduce adhesions. However, GnRH agonist plus Interceed was the most effective measure to reduce tissue fibrosis. CONCLUSION(S): Preoperative GnRH-a is more effective than Interceed in preventing surgical adhesions in the rabbit uterine horn. However, preoperative GnRH-a plus Interceed may provide optimal results in this animal model, because microscopic tissue fibrosis is minimized with this combination.