99mTc-glucarate for detection of isoproterenol-induced myocardial infarction in rats.

Infarct-avid radiopharmaceuticals are necessary for rapid and timely diagnosis of acute myocardial infarction. The animal model used to produce infarction implies artery ligation but chemical induction can be easily obtained with isoproterenol. A new infarct-avid radiopharmaceutical based on glucaric acid was prepared in the hospital radiopharmacy of the INCMNSZ. 99mTc-glucarate was easy to prepare, stable for 96 h and was used to study its biodistribution in rats with isoproterenol-induced acute myocardial infarction. Histological studies demonstrated that the rats developed an infarct 18 h after isoproterenol administration. The rat biodistribution studies showed a rapid blood clearance via the kidneys. Thirty minutes after 99mTc-glucarate administration the standardised heart uptake value S(h)UV was 4.7 in infarcted rat heart which is six times more than in normal rats. ROIs drawn over the gamma camera images showed a ratio of 4.4. The high image quality suggests that high contrast images can be obtained in humans and the 96 h stability makes it an ideal agent to detect, in patients, early cardiac infarction.

Effects of omapatrilat on blood pressure and insulin sensitivity in an animal model of insulin resistance.

OBJECTIVE: To assess the effects of omapatrilat, fosinopril and placebo on blood pressure, plasma insulin, glucose and triglycerides concentrations in Zucker rats, a model for insulin resistance. DESIGN: Double blind, parallel, prospective trial. METHODS: Forty-two male obese Zucker (falfa) rats (aged 13-18 week) initially weighing 400-600 g were used for the experiments. Omapatrilat (n = 14), placebo (n = 14) or fosinopril (n = 14) were administrated once daily at 10 micromol/kg oral for 15 days. At baseline and at the end of the study, a tail-cuff blood pressure measurement was performed; an oral glucose tolerance test was done at the end of the study. RESULTS: Omapatrilat and fosinopril resulted in significant lower systolic blood pressure compared to the placebo group (p < 0.001). This parameter was significantly lower in the omapatrilat group compared with fosinopril-treated rats (116+/-9 vs 125+/-4 mmHg, p < 0.05). After an overnight fast, there was no difference in the fasting glucose concentrations among treatment groups. The basal and post-glucose challenge insulin concentrations were lower in the omapatrilat group compared to the placebo group. No difference was observed in the fasting triglycerides concentrations between the treatment groups. CONCLUSIONS: Compared to placebo and fosinopril treatment, omapatrilat results in lower arterial blood pressure in an animal model of insulin resistance. The results suggest that omapatrilat may have a positive effect on insulin sensitivity.