Dipeptidyl peptidase-4 inhibitors and GLP-1 reduce myocardial infarct size in a glucose-dependent manner.

BACKGROUND: The dipeptidyl peptidase-4 (DPP-4) inhibitors Sitagliptin and Vildagliptin lower blood glucose by augmenting endogenous levels of glucagon-like peptide-1 (GLP-1), an incretin which also confers cardioprotection. As such, we hypothesized that treatment with DPP-4 inhibitors are also cardioprotective. METHODS: In ex vivo experiments: Male Sprague-Dawley rats were randomized to receive by oral gavage either Vildagliptin (20 mg/kg/day), Sitagliptin (100 mg/kg/day), or water for 2 weeks. Excised hearts were Langendorff-perfused with buffer containing either 5 mmol/L or 11 mmol/L glucose and subjected to 35 minutes ischaemia/120 minutes reperfusion. In in vivo experiments: Male young Wistar and Sprague-Dawley rats, middle aged Wistar and Goto-Kakizaki diabetic rats were randomized to receive by oral gavage either Sitagliptin (100 mg/kg/day), or water for 2 weeks. Rats were then subjected to 30 minutes ischaemia/120 minutes reperfusion and infarct size ascertained. RESULTS: Two weeks pre-treatment with either Vildagliptin or Sitagliptin reduced ex vivo myocardial infarction (MI) size in hearts perfused with buffer containing 11 mmol/L glucose but not 5 mmol/L glucose. This effect was abolished by Exendin 9-39 (GLP-1 receptor antagonist) and H-89 (PKA antagonist). Treatment of perfused hearts with native GLP-1 was also glucose-sensitive, reducing MI size, at glucose concentrations 7, 9, and 11 mmol/L but not at 5 mmol/L. Finally, Sitagliptin reduced in vivo MI size in middle aged Wistar (7-8 mmol/L glucose) and Goto-Kakizaki (9-10 mmol/L glucose) rats where blood glucose was elevated, but not in young Wistar (5 mmol/L glucose) or Sprague-Dawley (5 mmol/L glucose) rats, where blood glucose was normal. CONCLUSIONS: We find that chronic treatment with DPP-4 inhibitors reduced MI size, via the GLP-1 receptor-PKA pathway, in a glucose-dependent manner. Glucose-sensitive cardioprotection of endogenous GLP-1 in diabetic patients may in part explain why intensive control of serum glucose levels has been associated with increased cardiovascular risk.

The use of vacuum-assisted wound closure therapy in thoracic operations.

BACKGROUND: Conventional treatment of complex, nonresolving empyemas after an episode of pneumonia or a chest operation often requires an open-window thoracostomy. This necessitates frequent, often painful dressing changes and is associated with prolonged hospitalization. The wound is often malodorous, causing significant social distress to patients and unquestionably affects their quality of life. We assessed the value of using vacuum-assisted closure (VAC) therapy in managing patients with a persistent infected pleural space. METHODS: The study included 10 patients. All patients signed an informed consent and were debriefed before the procedure. An empyema developed in 1 patient after an episode of pneumonia. The other 9 had recently undergone a thoracic surgical procedure. All patients underwent initial open drainage of the pleural cavity and debridement. A VAC therapy system was then inserted intraoperatively or on the first postoperative day. The patients were discharged home with a portable VAC therapy system in situ. Subsequent dressing changes were managed by tissue-viability nurses in the community, without the need for further anesthesia or analgesia. Over a period of time, the cavity was sterilized and eventually obliterated spontaneously. RESULTS: All patients were mobilized early and fast-tracked through the hospital. This prevented the need for daily dressing changes; hence, minimizing the disruption of normal activities and reducing the need for nursing care. Overall, the length of hospitalization was shorter, and the VAC therapy facilitated closure of the infected wound cavity. The use of the VAC therapy system negated the need for a second surgical procedure to close the wound cavity. None of the patients reported pain, odor, or inconvenience associated with the VAC therapy system. CONCLUSIONS: Our observations suggest that the use of VAC therapy to treat such patients is safe, facilitates early discharge and recovery, and offers a "civilized," cost-effective treatment in a community setting.