In perfused hearts of streptozotocin-diabetic rats the kinetics of a fluoresce indicator transit was measured after pulse injection of FITC-dextran 3. The fluorescence changes on the left ventricle could be described by two pseudo first-order processes with half times in the range of seconds (t/2) corresponding to the intravascular washout and a slow process (T/2) corresponding to the exchange between the extra- and the intravascular space. In diabetes both half times became prolonged, and the amount of FITC-dextran 3 exchanged between the two compartments was reduced, indicating an impaired transcoronary transport in diabetic hearts. There was a time-dependent reduction in the basal release of prostacyclin in hearts of control and diabetic rats. However, studied hearts of diabetic rats released less 6-keto-prostaglandin F1 alpha (PGF1 alpha) than controls. This impaired release of 6-oxo-PGF1 alpha could be prevented partly by adrenalectomy. Because diabetic hearts release more 6-oxo-PGF1 alpha than controls after application of arachidonic acid, these data suggest that the supply of arachidonic acid for the synthesis of prostaglandins is impaired in diabetes, but not the cyclooxygenase pathway itself. The reduced transcoronary transport and the impaired synthesis of prostacyclin might be early steps in the development of microangiopathic myocardial alterations in diabetes.

Objective: This retrospective chart review assessed the efficacy, dose, and safety of methotrimeprazine in palliating end-of-life symptoms in children and infants. Methods: A retrospective chart review was conducted of 18 hospitalized pediatric patients who were treated with methotrimeprazine in their last two weeks of life. Data collected included age, diagnosis, symptoms, methotrimeprazine dose, route, efficacy, and any documented adverse effects. Results: Patients’ ages ranged from 16 days to 17 years. Underlying conditions included malignancies, trauma, and various neurodegenerative and congenital diseases. All patients (n=18) were treated for symptoms of agitation, delirium, or restlessness. Most patients also experienced respiratory secretions/congestion (n=15), pain (n=13), and/ or dyspnea (n=9). Less common symptoms included nausea/emesis (n=5) and spasticity (n=1). Methotrimeprazine dosages ranged from 0.02 mg/kg/dose to 0.5 mg/kg/dose. Routes of administration included intravenous (n=13), oral/gastrostomy tube (n=6), or subcutaneous (n=4). Sedation (n=6) was the only documented adverse effect, although when agitation was present, this was potentially an intended and perceived-to-be-beneficial effect. Conclusion: Methotrimeprazine, an old drug with diverse receptor activity and multiple routes of administration, appears to be an effective tool in treating complicated end-of-life symptoms in children and infants. This study provides a foundation for analysis with prospective and comparative trials, which may further quantify its benefit.

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