Partial Mechanical Unloading of the Heart Disrupts L-Type Calcium Channel and Beta-Adrenoceptor Signaling Microdomains.

Introduction: We investigated the effect of partial mechanical unloading (PMU) of the heart on the physiology of calcium and beta-adrenoceptor-cAMP (ßAR-cAMP) microdomains. Previous studies have investigated PMU using a model of heterotopic-heart and lung transplantation (HTHAL). These studies have demonstrated that PMU disrupts the structure of cardiomyocytes and calcium handling. We sought to understand these processes by studying L-Type Calcium Channel (LTCC) activity and sub-type-specific ßAR-cAMP signaling within cardiomyocyte membrane microdomains. Method: We utilized an 8-week model of HTHAL, whereby the hearts of syngeneic Lewis rats were transplanted into the abdomens of randomly assigned cage mates. A pronounced atrophy was observed in hearts after HTHAL. Cardiomyocytes were isolated via enzymatic perfusion. We utilized Förster Resonance Energy Transfer (FRET) based cAMP-biosensors and scanning ion conductance microscopy (SICM) based methodologies to study localization of LTCC and ßAR-cAMP signaling. Results: ß2AR-cAMP responses measured by FRET in the cardiomyocyte cytosol were reduced by PMU (loaded 28.51 ± 7.18% vs. unloaded 10.84 ± 3.27% N,n 4/10-13 mean ± SEM ∗ p < 0.05). There was no effect of PMU on ß2AR-cAMP signaling in RII_Protein Kinase A domains. ß1AR-cAMP was unaffected by PMU in either microdomain. Consistent with this SICM/FRET analysis demonstrated that ß2AR-cAMP was specifically reduced in t-tubules (TTs) after PMU (loaded TT 0.721 ± 0.106% vs. loaded crest 0.104 ± 0.062%, unloaded TT 0.112 ± 0.072% vs. unloaded crest 0.219 ± 0.084% N,n 5/6-9 mean ± SEM ∗∗ p < 0.01, ∗∗∗ p < 0.001 vs. loaded TT). By comparison ß1AR-cAMP responses in either TT or sarcolemmal crests were unaffected by the PMU. LTCC occurrence and open probability (Po) were reduced by PMU (loaded TT Po 0.073 ± 0.011% vs. loaded crest Po 0.027 ± 0.006% N,n 5/18-26 mean ± SEM ∗ p < 0.05) (unloaded TT 0.0350 ± 0.003% vs. unloaded crest Po 0.025 N,n 5/20-30 mean ± SEM NS # p < 0.05 unloaded vs. loaded TT). We discovered that PMU had reduced the association between Caveolin-3, Junctophilin-2, and Cav1.2. Discussion: PMU suppresses' ß2AR-cAMP and LTCC activity. When activated, the signaling of ß2AR-cAMP and LTCC become more far-reaching after PMU. We suggest that a situation of 'suppression/decompartmentation' is elicited by the loss of refined cardiomyocyte structure following PMU. As PMU is a component of modern device therapy for heart failure this study has clinical ramifications and raises important questions for regenerative medicine.

A conducting polymer with enhanced electronic stability applied in cardiac models.

Electrically active constructs can have a beneficial effect on electroresponsive tissues, such as the brain, heart, and nervous system. Conducting polymers (CPs) are being considered as components of these constructs because of their intrinsic electroactive and flexible nature. However, their clinical application has been largely hampered by their short operational time due to a decrease in their electronic properties. We show that, by immobilizing the dopant in the conductive scaffold, we can prevent its electric deterioration. We grew polyaniline (PANI) doped with phytic acid on the surface of a chitosan film. The strong chelation between phytic acid and chitosan led to a conductive patch with retained electroactivity, low surface resistivity (35.85 ± 9.40 kilohms per square), and oxidized form after 2 weeks of incubation in physiological medium. Ex vivo experiments revealed that the conductive nature of the patch has an immediate effect on the electrophysiology of the heart. Preliminary in vivo experiments showed that the conductive patch does not induce proarrhythmogenic activities in the heart. Our findings set the foundation for the design of electronically stable CP-based scaffolds. This provides a robust conductive system that could be used at the interface with electroresponsive tissue to better understand the interaction and effect of these materials on the electrophysiology of these tissues.

High-Dose Intravenous Octreotide Is Safe and May Be Superior to Surgery in Managing Severe Postesophagectomy Chylothorax in High-Risk Patients.

Postesophagectomy chylothorax is a relatively rare but potentially lethal complication. Management can be challenging, especially of patients after radiotherapy. Chest tube drainage, bowel rest, total parenteral nutrition, and adequate fluid replacement are the preferred first-line treatment. Thoracic duct band ligation is the approach of last resort; however, surgical reexploration is often not an option in these patients. The use of octreotide to control chylothorax in adults has been reported, but mainly when given in low subcutaneous doses. We report the successful use of high intravenous doses of octreotide to manage large postesophagectomy chylothorax in an adult after failed band ligation.

Chest X-ray and electrocardiogram in post-cardiac surgery follow-up clinics: should this be offered routinely or when clinically indicated?

OBJECTIVES: Many centres in the UK carry out routine chest X-ray (CXR) and/or electrocardiogram (ECG) when patients attend follow-up clinic after cardiac surgery. Current evidence to support this practice is weak. This study investigated the appropriateness of carrying out these investigations in the absence of clinical indication. METHODS: All patients attending routine 6- to 8-week follow-up clinic after cardiac surgery in this hospital were prospectively reviewed over a 6-month period (October 2011-April 2012). Two groups were identified for comparison. Group A comprised patients who had CXR and/or ECG requested routinely, and those in Group B had the investigations only when clinically indicated. A proforma was designed to screen each patient for cardiac and respiratory symptoms, predischarge CXR abnormalities and the presence of atrial fibrillation/flutter postoperatively. Management alterations based on the findings from the investigations were noted. Patients who had thoracic, major aortic, or heart transplant surgery were excluded from the audit. RESULTS: Three hundred and fifty patients were reviewed: 250 were in Group A and 100 in Group B. No patient had a significant management alteration in the absence of an indication for the tests. There were no differences in outcome between the two groups. In Group A, 111 (45%) patients had CXR and ECG done without indication and no abnormality was detected. In Group B, 52 patients had no indication for either tests and were thus not tested. None of these patients required readmission/intervention following discharge from clinic. Overall, 271 patients had CXR carried out, with only 83 being indicated. This led to a management alteration in 33 patients (12% overall, 40% if indicated). Two hundred and eighty-six patients had ECG carried out with 140 indicated. Management was altered in 122 patients (43% overall, 87% if indicated). The correlation between the clinical indication-based investigation and the resulting change in patient management was found to be significant (Goodman-Kruskal Gamma: 0.99, P = 0.000 for both investigations). CONCLUSIONS: There is a strong correlation between clinical indication for CXR and/or ECG and management alterations. These investigations should be performed during the routine follow-up of adult cardiac surgical patients using a patient-centred approach based on signs and symptoms.

Spontaneous supraceliac isolated abdominal aortic dissection sparing major visceral and renal vessels and presenting as chronic limb ischemia.

Aortic dissections that originate from isolated tears in the abdominal aorta are uncommon. Rarer still are cases of isolated abdominal aortic dissections arising in suprarenal locations, as most appear from infrarenal intimal defects. We present a quite unusual case of a spontaneous supraceliac isolated abdominal aortic dissection sparing the renal and mesenteric arteries and manifesting as chronic rather than acute limb ischemia. The atypical presentation of this case led to repeated misdiagnosis with consequent loss of part of the patient's limb. Better illustration of the natural history of this ill-defined pathology is needed to aid understanding and improve patient care.

Conduits for coronary artery bypass surgery: the quest for second best.

Coronary artery bypass grafting is one of the most outstanding surgical achievements of the 20th century. Over its 50-year history patient outcomes have become excellent owing to technical refinements, myocardial protection, the use of antiplatelet and anticholesterol drugs, and the continued search for better conduits. The performance of conduits used for bypass remains the most important prognostic factor, with the left internal mammary artery being the conduit of choice due to its excellent patency rates. There is, however, uncertainty with regards which conduit is second best. The recent resurgence of the radial artery has led to an increase in its use as surgeons lean towards total arterial revascularization but there is emerging evidence that the performance of the long saphenous vein graft is improving. Furthermore, bilateral internal mammary artery grafting is preferred in some centres as an alternative approach to total arterial revascularization, with multiple reports of superior long-term event-free outcome with its use. This extensive review of current literature reveals an absence of clear consensus as to what mix of conduits provides the best long-term outcomes. The quest for second best continues. Arterial conduits appear to be superior when grafted to tight stenosis but veins remain popular with surgeons. More supportive evidence from the concluding Arterial Revascularization trial and the Radial Artery Patency and Clinical Outcomes trial should guide future practice.

Gluteo-vaginal fistula: a long-term complication of posterior intravaginal slingplasty.

A 67-year-old lady presented to the surgical outpatient clinic with a 4 month history of recurrent purulent discharge from her left buttock. Four years and 4 months prior to this she underwent a posterior intravaginal slingoplasty for vaginal prolapse and urinary stress incontinence. An MRI demonstrated a long gluteo-vaginal fistula tract from the posterior wall of the vaginal vault through the left ischiorectal fossa to the skin. An examination under anaesthesia revealed that the fistulous tract was surrounding the intact mesh used for the posterior intravaginal slingoplasty. The mesh was removed, the fistula tract excised and the perineal wound marsupialised. The patient was discharged 5 days later. The wound healed within 4 weeks and she remains sepsis free 2 years on.