Relationship between connexin expression and gap-junction resistivity in human atrial myocardium.

BACKGROUND: The relative roles of the gap-junctional proteins connexin40 (Cx40) and connexin43 (Cx43) in determining human atrial myocardial resistivity is unknown. In addressing the hypothesis that changing relative expression of Cx40 and Cx43 underlies an increase in human atrial myocardial resistivity with age, this relationship was investigated by direct ex vivo measurement of gap-junctional resistivity and quantitative connexin immunoblotting and immunohistochemistry. METHODS AND RESULTS: Oil-gap impedance measurements were performed to determine resistivity of the intracellular pathway (Ri), which correlated with total Cx40 quantification by Western blotting (rs=0.64, P<0.01, n=20). Specific gap-junctional resistivity (Rj) correlated not only with Western immunoquantification of Cx40 (rs=0.63, P=0.01, n=20), but also more specifically, with the Cx40 fraction localized to the intercalated disks on immunohistochemical quantification (rs=0.66, P=0.02, n=12). Although Cx43 expression showed no correlation with resistivity values, the proportional expression of the 2 connexins, (Cx40/[Cx40+Cx43]) correlated with Ri and Rj (rs=0.58, P<0.01 for Ri and rs=0.51, P=0.02 for Rj). Advancing age was associated with a rise in Ri (rs=0.77, P<0.0001), Rj (rs=0.65, P<0.001, n=23), Cx40 quantity (rs=0.54, P=0.01, n=20), and Cx40 gap-junction protein per unit area of en face disk (rs=0.61, P=0.02, n=12). CONCLUSIONS: Cx40 is associated with human right atrial gap-junctional resistivity such that increased total, gap-junctional, and proportional Cx40 expression increases gap-junctional resistivity. Accordingly, advancing age is associated with an increase in Cx40 expression and a corresponding increase in gap-junctional resistivity. These findings are the first to demonstrate this relationship and a mechanistic explanation for changing atrial conduction and age-related arrhythmic tendency.

Feasibility and safety of minimized cardiopulmonary bypass in major aortic surgery.

OBJECTIVES: Conventional cardiopulmonary bypass causes haemodilution and is a trigger of systemic inflammatory reactions, coagulopathy and organ failure. Miniaturized cardiopulmonary bypass has been proposed as a way to reduce these deleterious effects of conventional cardiopulmonary bypass and to promote a more physiological state. The use of miniaturized cardiopulmonary bypass has been reported in low-risk patients undergoing valve and coronary artery bypass graft (CABG) surgery. However, little is known about its application in major aortic surgery. METHODS: From February 2007 to September 2010, 49 patients underwent major aortic surgery using the Hammersmith miniaturized cardiopulmonary bypass (ECCO, Sorin). Data were extracted from medical records to characterize preoperative comorbidities (EuroSCORE), perioperative complications and the use of blood products. The same data were collected and described for 328 consecutive patients having similar surgery with conventional cardiopulmonary bypass at the Bristol Heart Institute, our twinned centre, during the same period. RESULTS: The miniaturized cardiopulmonary bypass group had a median EuroSCORE of 8 [inter-quartile range (IQR): 5-11], 13% had preoperative renal dysfunction and 20% of operations were classified as emergency or salvage. Thirty-day mortalities were 6.4; and 69, 67 and 74% had ≥ 1 unit of red cells, fresh frozen plasma (FFP) and platelets transfused, respectively. Eight percent of patients experienced a renal complication, and 8% a neurological complication. The conventional cardiopulmonary bypass group was similar, with a EuroSCORE of 8 (IQR: 6-10); 30-day mortalities were 9.4; and 68, 62 and 74% had ≥ 1 unit of red cells, FFP and platelets transfused, respectively. The proportions experiencing renal and neurological complications were 14 and 5%. CONCLUSIONS: Our experience suggests that miniaturized cardiopulmonary bypass is safe and feasible for use in major aortic cardiac surgery. A randomized trial is needed to evaluate miniaturized cardiopulmonary bypass formally.

Leptin is an endothelial-independent vasodilator in humans with coronary artery disease: Evidence for tissue specificity of leptin resistance.

AIMS: We sought to define the mechanisms and correlates of leptin's vascular actions in humans with coronary artery disease. METHODS AND RESULTS: In 131 patients (age 65.7+/-0.7 years mean+/-SEM), ex vivo vascular reactivity to leptin (10(-13)-10(-7) M) was assessed in saphenous vein (SV) rings. Leptin led to SV relaxation (maximal relaxation 24.5+/-1.6%). In separate experiments, relaxation to leptin was unaffected by L-NMMA (17.4+/-3.4 vs.17.8+/-3.3%, P = 0.9) or endothelial denudation (17.4+/-4.4 vs. 22.5+/-3.0%, P = 0.4). We explored the possibility that leptin's vascular effects are mediated via smooth muscle hyperpolarization. In the presence of KCl (30 mmol/L) to inhibit hyperpolarization, the vasodilator effect of leptin was completely blocked (0.08+/-4.1%, P < 0.001 vs. control). Similar results were demonstrated in internal mammary artery rings. The only independent correlate of leptin-mediated vasodilatation was plasma TNF-alpha (r = 0.25, P < 0.05). Neither body mass index nor waist circumference correlated with leptin-mediated vasorelaxation. This lack of a correlation with markers of total body fat/fat distribution suggests that leptin resistance may not extend to the vasculature. CONCLUSION: Leptin is a vasoactive peptide in human SV and internal mammary artery. Its action is not nitric oxide or endothelial-dependent. Markers of body fat did not correlate with leptin-mediated vasodilatation, raising the intriguing possibility of selective resistance to leptin's actions.

Incidence of sternal infection in diabetic patients undergoing bilateral internal thoracic artery grafting.

BACKGROUND: Bilateral internal thoracic artery (BITA) bypass grafts have advantages over single internal thoracic artery (SITA) bypass grafts in the medium term, particularly in diabetics. However, the perceived higher sternal complication rates seen in diabetics have led many surgeons to avoid the use of BITA surgery. The aim of our study was to assess the validity of this approach by assessing the incidence of sternal infections over a 10-year period in one institution. METHODS: A retrospective analysis was made of our coronary artery bypass graft (CABG) patients over a 10-year period (7,581 patients). Nine hundred and twenty-two of the patients were diabetics (261 insulin-dependent diabetes mellitus [IDDM]). Of the insulin-dependent diabetics, 166 had SITA, and 95 had BITA grafts. RESULTS: There was no significant difference in this subgroup in terms of gender, preoperative angina, dyspnea class, left ventricular function, and number of distal anastomoses. Comparing the rates of sternal wound complications of SITA and BITA in IDDM are the following: (1) superficial sternal infection, 6.6% in SITA, 1.1% in BITA (p = 0.04); (2) deep sternal infection, 1.2% in SITA, 3.2% in BITA (p = 0.27); (3) sternal dehiscence, 1.2% in SITA, 3.2% in BITA (p = 0.27). CONCLUSIONS: Our data do not support the perception that BITA grafting increases the risk of sternal complications in insulin-dependent diabetic patients.