Georgios Galanopoulos

Thyroid hormone improves the mechanical performance of the post-infarcted diabetic myocardium: a response associated with up-regulation of Akt/mTOR and AMPK activation.

OBJECTIVE Thyroid hormone (TH) is shown to be protective against cardiac and pancreatic injury. Thus, this study explored the potential effects of TH treatment on the functional status of the postinfarcted diabetic myocardium. Diabetic patients have worse prognosis after acute myocardial infarction (AMI). MATERIALS/METHODS AMI was induced by left coronary ligation in rats previously treated with 35 mg/kg streptozotocin (STZ), (DM-AMI). TH treatment was initiated at 2 weeks after AMI and continued for 6 weeks (DM-AMI+TH), while sham-operated animals served as control (DM-SHAM). RESULTS TH treatment increased cardiac mass, improved wall stress and favorably changed cardiac geometry. TH significantly increased echocardiographic left ventricular ejection fraction (LVEF%): [54.2 (6.5) for DM-AMI+TH vs 37 (2.0) for DM-AMI, p<0.05]. TH treatment resulted in significantly increased insulin and decreased glucose levels in serum. The ratios of phosphorylated (p)-Akt/total Akt and p-mTOR/total mTOR were increased 2.0 fold and 2.7 fold in DM-AMI+TH vs DM-AMI respectively, p<0.05. Furthermore, the ratio of p-AMPK/total AMPK was found to be increased 1.6 fold in DM-AMI+TH vs DM-AMI, p<0.05. CONCLUSION TH treatment improved the mechanical performance of the post-infarcted myocardium in rats with STZ-induced diabetes, an effect which was associated with Akt/mTOR and AMPK activation.

The Beneficial Effects of Ranolazine on Cardiac Function After Myocardial Infarction Are Greater in Diabetic Than in Nondiabetic Rats

Ranolazine (RAN) is known to exert both anti-ischemic and antidiabetic actions. Thus, this study has explored the hypothesis that RAN would have greater effect on the recovery of cardiac function in diabetic mellitus (DM) rat hearts following myocardial infarction (MI). Myocardial infarction was induced in nondiabetic (MI, n = 14) and diabetic (streptozotocin induced; DM-MI, n = 13) Wistar rats by permanent ligation of the left coronary artery. Cardiac function was evaluated using echocardiography (left ventricular ejection fraction %) and in isolated heart preparations by measuring left ventricular developed pressure (LVDP), and the positive and negative first derivative of LVDP (±dp/dt). Ranolazine (20 mg/kg, ip once a day) was administered 24 hours after surgical procedure for 4 weeks to nondiabetic (MI + RAN, n = 17) and diabetic rats (DM-MI + RAN, n = 15). The RAN improved the recovery of function in both the nondiabetic and the diabetic postinfarcted hearts but this effect was greater and achieved statistical significance only in the diabetic group. The RAN resulted in increased levels of phosphorylated protein kinase B (Akt) and mammalian target of rapamycin (mTOR, a component of Akt signaling) in both nondiabetic and diabetic infarcted hearts without changes in the activation of mitogen-activated protein kinases (MAPKs; p38 MAPK, c-Jun N-terminal kinase, and extracellular signal-regulated kinase). In addition, in diabetic hearts, RAN resulted in a significant increase in the ratio of sarcoplasmic Ca2+-ATPase/phospholamban (a target of Akt signaling, 2.0-fold increase) and increased levels of phosphorylated calcium-regulated adenosine monophosphate-activated protein kinase (AMPK; 2.0-fold increase). In diabetic animals, RAN increased insulin and lowered glucose levels in serum. In conclusion, the beneficial effect of RAN on the recovery of cardiac function after MI was greater in DM rats. This response was associated with activation of Akt/mTOR and AMPK. These findings provide a plausible explanation for the results of the Type 2 Diabetes Evaluation of Ranolazine in Subjects With Chronic Stable Angina (TERISA) trial, which showed a greater antianginal effect of RAN in patients with coronary artery disease and diabetes.

Minimally invasive treatment of varicose veins: Endovenous laser ablation (EVLA)

Varicose veins are a frequently encountered medical condition. In the era of minimally invasive surgery, several techniques, in the treatment of varicose veins, have been developed in the last few years. One of the most frequently used new techniques is endovenous laser ablation. Fibrotic sealing of the treated vein lumen is the final result. The vein ablation is obtained under local - tumescent anaesthesia and the patients can be treated in an office setting with immediate return to full activity. Safety and effectiveness seem to be the major characteristics and advantages of this technique.

Primary brachial vein transposition for hemodialysis access: Report of a case and review of the literature

The superiority of autogenous fistulae in patients with end‐stage renal disease, performing hemodialysis, is well established and largely accepted. However, in case that superficial veins in the upper arm are not available for fistula construction, brachial vein transposition may be a viable alternative prior to graft placement. This transposition could be done as a primary or staged procedure, depending on the vein size. We present the case of a 63‐year‐old male patient with a thrombosed arteriovenous graft in the forearm and a large brachial vein in the ipsilateral upper arm. A one‐stage (primary) brachial vein transposition was performed. The fistula, 10 months after its construction, is still patent. No complications have occurred.

Infectious complications of prosthetic arteriovenous grafts for hemodialysis: prevention is better than cure

Abstract Synthetic arteriovenous grafts for hemodialysis constitute the second choice in comparison with native arteriovenous fistulas. Lower patency rates and significantly more frequent infections are the main disadvantages of hemodialysis grafts over fistulas. Infectious complications could vary between a simple local erythema at a puncture site that resolves easily with antibiotics to septicemia and death. As a corollary, this kind of complications continue to be among the most important causes of morbidity and mortality in end-stage renal disease patients receiving long-term hemodialysis. The cornerstone is prevention of infections. It is generally accepted that following simple measures during the intervention of graft insertion and consecutively in every hemodialysis session could consistently reduce the risk of infection.

Inadvertent parathyroidectomy risk factors in 1,373 thyroidectomies—male gender and presence of lymphadenopathy, but not size of gland, independently increase the risk

Background Inadvertent parathyroidectomy (IP) during thyroid operations is a recognised phenomenon. We evaluated the incidence of IP during thyroid operations in a large case-series and identified the risk factors involved. Methods Retrospective review of all thyroidectomy operations [total thyroidectomies (TT) and near-total thyroidectomies (NTT)] performed in a single institution from January 2004 to January 2009. We excluded re-operative cases, combined thyroid and parathyroid pathology, hemithyroidectomies and neck lymph nodes (LN) dissections. Pathology reports were correlated with operative records to identify the details of the IP glands. Relevant data (patient demographic data, preoperative diagnosis and operative details) were collected and a logistic regression was performed. Results One thousand three hundred and seventy-three patients were included in our study, 1,149 of them females (84%). IP rate was 11.3%. Univariate analysis showed that gender, thyroid gland weight, thyroid activity pre-operatively and type of operation are associated with IP. Logistic regression analysis has shown that female gender and the absence of LN in pathology were associated with less likelihood in developing IP than males and patients with presence of LN (P=0.051 and 0.014 respectively). IP occurs 2.14 and 2.28 times more often in TT and NTT when compared to the combination of TT and NTT (P=0.047 and 0.048 respectively). Conclusions We present the largest single-centre case series on this topic, to our knowledge. The presence of LN, female gender and the type of operation are positively correlated to the IP rate. These factors could alert the surgeon to consider early calcium supplementation if the parathyroid glands (PG) have not been identified intraoperatively.

The stuck dialysis catheter: A nasty astonishment

Removal of a tunneled cuffed central venous catheter can be challenging and risky. In some cases, the catheter firmly adheres to the surrounding tissues, becoming an integrated part of the vessel wall. We present the case of an adult female hemodialysis (HD) patient with a dysfunctioning HD tunneled cuffed catheter. The catheter removal procedure proved mazy. After several attempts, the catheter was removed together with the peri-catheter fibrin sheath. However, the post-procedure period was uneventful.

085 Thyroid hormone receptor alpha1 is down regulated during the progression to congestive heart failure after myocardial infarction

Aim Thyroid hormone (TH) signaling is altered in response to various stresses including myocardial ischaemia. The present study investigated potential implication of TH in the pathophysiology of postischaemic remodeling. Methods Acute myocardial infarction was induced in rats by coronary artery ligation (AMI). After 34 wk, n = 6 animals were on congestive heart failure (CHF) as indicated by measurements in lung and right ventricular weight. N = 7 animals were in compensated state (non-CHF) and n = 8 SHAM operated animals served as controls (SHAM). Results Progression to congestive heart failure was characterized by marked decrease in EF% and all other functional echocardiographic parameters. Furthermore, β-MHC expression was significantly increased in CHF. A distinct pattern of TR expression was observed in the course of postischaemic remodeling; TRα1 was up-regulated and TRβ1 was down-regulated in non-CHF and TRα1 expression was markedly decreased during the transition from non-CHF to CHF resulting in tissue hypothyroidism. Circulating T3 and T4 remained unchanged. This response was associated with marked decrease in ERK and mTOR activation. A potential link between ERK, mTOR and TRα1 expression was shown in a neonatal cardiomyocytes model of PE (phenylephrine) induced pathological growth. PE increased the expression of TRα1 in nucleus and this response was abrogated after inhibition of mTOR or ERK. Conclusion Progression to congestive heart failure after myocardial infarction is associated with suppressed expression of TRα1 and results in tissue hypothyroidism. This process may at least in part be mTOR and ERK dependent.

084 Diabetes prevents compensatory hypertrophy after myocardial infarction and impairs cardiac function; possible implication of stretch induced kinase growth signaling

Aim The present study investigated possible mechanisms underlying postischemic remodeling in diabetic hearts. Diabetes (DM) accelerates postischaemic cardiac remodeling and increases mortality after myocardial infarction. Methods Acute myocardial infarction (AMI) was induced in rats with type I diabetes (DM) and non diabetic rats (NDM-AMI) while sham operated animals served as controls (SHAM). All groups were subjected to echocardiographic analysis 2 weeks after infarction. Results AMI resulted in increased expression of β-MHC and distinct changes in cardiac function and geometry. EF% was decreased in DM-AMI as compared to NDM-AMI. Systolic and diastolic chamber dimensions were increased without concomitant increase in wall thickness and thus, WTI (the ratio of LVIDd/2*Posterior Wall thickness), an index of wall stress, was significantly increased in DM-AMI hearts. The absence of wall thickening in DM-AMI hearts was associated with different pattern of activation of stretch induced kinase hypertrophic signaling p38 MAPK and ERK; Phosphorylated ERK and p38 MAPK levels were increased in NDM-AMI hearts, while were not changed in DM-AMI as compared to non infarcted diabetic hearts (DM-SHAM). TH administration after AMI resulted in decreased β-MHC expression, increased wall thickening and normalized wall stress, while stretch induced p38 MAPK activation was restored. Conclusions Diabetes reduces the ability of the myocardium to adapt after myocardial infarction by preventing the development of compensatory hypertrophy. This is, at least in part due to inactivation of stress induced kinase signalling.

258 Post-ischemic cardiac remodeling is accelerated in diabetic rats: similarities to clinical and tissue hypothyroidism

We investigated whether postischemic cardiac remodeling (REM) is accelerated in diabetic rats with possible involvement of thyroid hormone (TH) signaling in this response. Changes in TH signaling occur during REM after acute myocardial infarction (MI) and contribute to cardiac dysfunction. Diabetes was induced in Wistar rats by streptozotocin injection (35mg/Kg i.p.). After 30 days diabetic rats (DM-AMI, n=9) were subjected to MI, while control rats were either sham-operated (SHAM, n=10) or subjected to MI (AMI(1), n=10). After 2 weeks, TRα1 and TRα1 expression and TH levels were measured. Hypothyroid rats by propyl-thiouracil administration (0.05%) in water for 3 weeks were subjected to MI (HYPO-AMI, n=6) while untreated MI rats served as controls (AMI(2), n=6). LV dimensions (LVEDD and LVEDS) and ejection fraction (EF%) were used to assess contractility and REM 2 weeks after MI using echocardiography. Cardiac function was markedly decreased in DM –AMI. Scar (mm 2 ) LVEDD (mm) LVEDS (mm) EF% SHAM ----- 6.5 (0.1) 3.8 (0.2) 76 (2.6) AMI(1) 79 (4.0) 7.7 (0.2) * 5.7 (0.2) * 52 (1.5) * DM-AMI 83 (4.9) 8.5 (0.2) ** 7.0 (0.3) ** 39 (2.1) ** * p ** p In AMI(1), TRα1 and TRβ1 protein expression were not changed significantly as compared to SHAM while in DM-AMI, both TRα1 and TRβ1 were decreased 1.7 and 1.9 fold respectively as compared to SHAM, p 0.05], showed a similar unfavorable functional response : EF% was found to be markedly reduced [24 (0.9) in HYPO-AMI vs 36.2 (1.0) in AMI(2), p