Treatment with XMU-MP-1 erases hyperglycaemic memory in hearts of diabetic mice.

Hyperglycaemic memory refers to the damages occurred under early hyperglycaemic environment in organs of diabetic patients persisting after intensive glycaemic control. Mammalian sterile 20-like kinase 1 (Mst1) contributes to the development of diabetic cardiomyopathy. Here, we investigated the role of Mst1 in hyperglycaemic memory and test the effect of XMU-MP-1, a Mst1 inhibitor, on hyperglycaemic memory in hearts. Eight weeks after induction of type 1 diabetes by injection with streptozotocin (STZ) in mice, glycaemic control was obtained by means of insulin treatment and maintained for 4 additional weeks. In the diabetic mice, insulin treatment alone did not reduce phosphorylation of Mst1 or improve cardiac function. Treatment with XMU-MP-1 alone immediately after induction of diabetes for 12 weeks did not improve myocardial function in mice. But treatment with XMU-MP-1 for the later 4 weeks relieved myocardial dysfunction when glycaemic control was obtained by insulin treatment simultaneously. Mst1 deficiency and glycaemic control synergistically improved myocardial function and reduced apoptosis in myocardium of diabetic mice. Mechanistically, when Mst1 was deficient or inhibited by XMU-MP-1, AMPK was activated and mitochondrial dysfunction was attenuated. In vitro, treatment with AMPK activator reversed the detrimental effects of Mst1 overexpression in cultured cardiomyocytes. XMU-MP-1 might thus be envisaged as a complement for insulin treatment against diabetic cardiomyopathy.

Superior vena cava syndrome early after pacemaker implantation in a patient with lung carcinoma: A case report.

Superior vena cava (SVC) syndrome is typically dramatic. Although the diagnosis is usually easy, elucidation of the etiology is difficult. We present a patient who developed SVC syndrome early after transvenous pacemaker implantation and who was subsequently diagnosed with lung carcinoma. The pathogenesis seems to be explained by a combination of two etiologies: lung carcinoma plus transvenous pacemaker implantation. We emphasize that common etiologies such as malignancy should be considered first when faced with SVC syndrome.

[Effect of catheter-based renal sympathetic denervation in pigs with rapid pacing induced heart failure].

OBJECTIVE: This study investigated the effect of catheter-based renal sympathetic denervation (RDN) in pigs with rapid pacing induced heart failure. METHODS: Heart failure was induced by rapid right ventricular pacing in 12 pigs and pigs were randomly divided into RDN group (n = 6): pacing+RDN at 7 days post pacing; control group (n = 6): pacing only. Echocardiography examination (LVEF, LVEDD and LVESD) was performed before pacing and at 1 and 2 weeks post pacing. Serum biochemical markers including renin, aldosterone and creatinine were also measured at baseline, 1 and 2 weeks after pacing. Repeated renal artery angiography was performed at 1 week after RDN. All pigs were sacrificed to examine the heart and renal pathology and renal artery sympathetic nerve staining at 2 weeks post pacing. RESULTS: LVEF decreased 1 week after rapid pacing from (60.5 ± 6.0)% to (35.3 ± 9.8)%. LVEF was significantly higher [(42.8 ± 5.9) % vs. (33.4 ± 9.7)%, P = 0.001 8] while LVESD was significantly lower [(28.4 ± 3.7) mm vs. (33.0 ± 2.0) mm, P = 0.001 6] in the RDN group than in the control group at 2 weeks post pacing. At 2 weeks after pacing, plasma concentrations of renin and aldosterone were significantly lower in RDN group compared to the control group (all P < 0.05) . Kidney function and blood pressure were comparable between the two groups at 2 weeks post pacing. There were no signs of renal damages such as renal artery stenosis, dissection and thrombus in all pigs after 2 weeks pacing. Sympathetic neurons of adventitia were injured in RND group. CONCLUSION: RDN could significantly improve cardiac function and attenuate left ventricular remodeling via inhibiting renin-angiotensin-aldosterone system in this pacing induced pig heart failure model.

A new rapamycin-abluminally coated chitosan/heparin stent system accelerates early re-endothelialisation and improves anti-coagulant properties in porcine coronary artery models.

PURPOSE: Drug-eluting stents (DES) in percutaneous coronary intervention are more effective in preventing in-stent restenosis compared with bare metal stents (BMS); however, DES may cause late stent thrombosis, which has limited its use. In this study, the functional properties of a newly developed DES (RAP/CS/HEP), in which rapamycin was abluminally-loaded onto a chitosan/heparin coating stent (CS/HEP), were investigated in large animal artery injury models. METHODS: The effectiveness of BMS, RAP (the traditional version of rapamycin DES), CS/HEP and RAP/CS/HEP stents in preventing coagulation and promoting re-endothelialisation was examined and compared in the porcine coronary artery models with arteriovenous shunt, high load thrombus and coronary balloon injury at day 7 and 28, respectively, after stent implantation. The re-endothelialisation on these stents was further evaluated in terms of endothelial gene expression using quantitative RT-PCR. RESULTS: In the porcine coronary artery injury models, both RAP and RAP/CS/HEP stents were potent in reducing neointimal thickness, thus enlarging lumen area efficiently in the stented artery region compared with BMS and CS/HEP. RAP/CS/HEP stents facilitated re-endothelialisation and inhibited thrombosis more efficiently than BMS and RAP. Consistent with this, the expression of endothelial genes, such as CD31, CD34, eNOS and VEGF, was significantly elevated with RAP/CS/HEP stents compared with RAP and BMS stents. CONCLUSION: Abluminal coating of rapamycin onto the endothelialisation-accelerated CS/HEP stent and may prove to be an efficient treatment for tackling the late stent thrombosis associated with the traditionally circumferential RAP stent. This new RAP/CS/HEP stent system exhibits considerably improved therapeutic activity.