BackgroundDiabetes is associated with coronary arteriolar endothelial dysfunction. We investigated the role of the small/intermediate (SKCa/IKCa) conductance of calcium-activated potassium channels in diabetes-related endothelial dysfunction.Methods and ResultsCoronary arterioles (80 to 150 μm in diameter) were dissected from discarded right atrial tissues of diabetic (glycosylated hemoglobin = 9.6±0.25) and nondiabetic patients (glycosylated hemoglobin 5.4±0.12) during coronary artery bypass graft surgery (n=8/group). In-vitro relaxation response of precontracted arterioles was examined in the presence of the selective SKCa/IKCa activator NS309 and other vasodilatory agents. The channel density and membrane potential of diabetic and nondiabetic endothelial cells was measured by using the whole cell patch-clamp technique. The protein expression and distribution of the SKCa/IKCa in the human myocardium and coronary arterioles was examined by Western blotting and immunohistochemistry. Our results indicate that diabetes significantly reduced the coronary arteriolar response to the SKCa/IKCa activator NS309 compared to the respective responses of nondiabetic vessels (P<0.05 versus nondiabetes). The relaxation response of diabetic arterioles to NS309 was prevented by denudation of endothelium (P=0.001 versus endothelium-intact). Diabetes significantly decreased endothelial SKCa/IKCa currents and hyperpolarization induced by the SKCa/IKCa activator NS309 as compared with that of nondiabetics. There were no significant differences in the expression and distribution of SKCa/IKCa proteins in the coronary microvessels.ConclusionsDiabetes is associated with inactivation of endothelial SKCa/IKCa channels, which may contribute to endothelial dysfunction in diabetic patients.

Background We investigated the effects of cardiopulmonary bypass (CPB) on peripheral arteriolar reactivity and associated signaling pathways in poorly controlled (UDM), controlled (CDM), and case-matched non-diabetic (ND) patients undergoing coronary artery bypass grafting. Methods and Results Skeletal muscle arterioles were harvested pre- and post-CPB from the UDM patients (hemoglobin A1c [HbA1c] = 9.0 ± 0.3), the CDM patients (HbA1c = 6.3 ± 0.15) and the ND patients (HbA1c = 5.2 ± 0.1) undergoing CABG surgery (n = 10/group). In vitro relaxation responses of pre-contracted arterioles to endothelium-dependent vasodilators adenosine 5’-diphosphate (ADP) and substance P and the endothelium-independent vasodilator sodium nitroprusside (SNP) were examined. The baseline responses to ADP, substance P and SNP of arterioles from the UDM patients were decreased as compared to microvessels from the ND or CDM patients (P <0.05). The post-CPB relaxation responses to ADP and substance P were significantly decreased in all three groups compared to pre-CPB responses (P <0.05). However, these decreases were more pronounced in the UDM group (P <0.05). The post-CPB response to SNP was significantly decreased only in the UDM group, not in the other two groups compared to pre-CPB. The expression of PKC-α, PKC-β, protein oxidation and nitrotyrosine in the skeletal muscle were significantly increased in the UDM group as compared with those of ND or CDM groups (P<0.05). Conclusion Poorly controlled diabetes results in impaired arteriolar function before and after CPB. These alterations are associated with the increased expression/activation of PKC-α and PKC-β, and enhanced oxidative and nitrosative stress.

Hypotension occurs during cardiopulmonary bypass (CPB), in part because of induction of the inflammatory response, for which nitric oxide and guanylate cyclase play a central role. In this study we examined the hemodynamic effects of methylene blue (MB), an inhibitor of guanylate cyclase, administered during cardiopulmonary bypass (CPB) to patients taking angiotensin-converting enzyme inhibitors. Thirty patients undergoing cardiac surgery were randomized to receive either MB (3 mg/kg) or saline (S) after institution of CPB and cardioplegic arrest. CPB was managed similarly for all study patients. Hemodynamic data were assessed before, during, and after CPB. The use of vasopressors was recorded. All study patients experienced a similar reduction in mean arterial blood pressure (MAP) and systemic vascular resistance (SVR) with the onset of CPB and cardioplegic arrest. MB increased MAP and SVR and this effect lasted for 40 minutes. The saline group demonstrated a persistently reduced MAP and SVR throughout CPB. The saline group received phenylephrine more frequently during CPB, and more norepinephrine after CPB to maintain a desirable MAP. The MB group recorded significantly lower serum lactate levels despite equal or greater MAP and SVR. In conclusion, administration of MB after institution of CPB for patients taking angiotensin-converting enzyme inhibitors increased MAP and SVR and reduced the need for vasopressors. Furthermore, serum lactate levels were lower in MB patients, suggesting more favorable tissue perfusion.

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Cataract surgery has undergone many changes with the size of incision progressively decreasing over time with an incision of 12.0 mm for intracapsular cataract extraction to 2.2–2.8 mm in phacoemulsification. However, phacoemulsification due to high cost and equipment maintenance cannot be employed widely in developing countries. Manual small-incision cataract surgery (MSICS) offers similar advantages with the merits of wider applicability, less time consuming, a shorter learning curve, and lower cost. MSICS can be performed in high-volume setups due to fast technique. Here, we review the various techniques, safety and efficacy of MSICS, and its progress and utility in developing and underdeveloped countries.

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Background We investigated the effects of cardioplegic arrest and reperfusion (CP/Rep) on coronary arteriolar responses to endothelium-dependent and -independent vasodilators and associated signaling pathways in poorly controlled diabetic, well controlled diabetic and case-matched non-diabetic patients undergoing coronary artery bypass grafting (CABG). Methods and Results Coronary arterioles from harvested right-atrial tissues were dissected pre- and post-CP/Rep from poorly controlled diabetic (n = 10, hemoglobin A1c [HbA1c] = 9.3 ± 0.3), well controlled diabetic (n = 10, HbA1c = 6.2 ± 0.2) and non-diabetic patients (n = 10, HbA1c = 5.1 ± 0.1) undergoing CABG surgery. The baseline microvascular response to ADP, substance P and SNP of arterioles from poorly controlled diabetic patients were decreased as compared to the respective response from non-diabetic or well controlled diabetic patients (P < 0.05). The vasodilatory responses to ADP, and substance P after CP/Rep were significantly decreased in all three groups compared to pre-CP/Rep responses (P < 0.05). However, these decreases were more pronounced in the poorly controlled diabetic group (P < 0.05). The expression of protein kinase C-α (PKC-α), PKC-β, and protein oxidation in atrial tissues was significantly increased in the poorly controlled diabetic group as compared with those of non-diabetes or controlled diabetes. Conclusion Poorly controlled is associated with endothelium-dependent and -independent vascular dysfunction of coronary arterioles. Additionally, poorly controlled diabetes worsens the recovery of coronary arteriolar function after CP/Rep. These alterations are associated with the increased expression/activation of PKC-α and PKC-β, and enhanced oxidative stress.

Background: Diabetic (DM) inactivation of small conductance calcium-activated potassium (SK) channels contributes to coronary endothelial dysfunction. However, the mechanisms responsible for this down-regulation of endothelial SK channels are poorly understood. Thus, we hypothesized that the altered metabolic signaling in diabetes regulates endothelial SK channels and human coronary microvascular function. Methods: Human atrial tissue, coronary arterioles and coronary artery endothelial cells (HCAECs) obtained from DM and non-diabetic (ND) patients (n = 12/group) undergoing cardiac surgery were used to analyze metabolic alterations, endothelial SK channel function, coronary microvascular reactivity and SK gene/protein expression/ localization. Results: The relaxation response of DM coronary arterioles to the selective SK channel activator SKA-31 and calcium ionophore A23187 was significantly decreased compared to that of ND arterioles (p b 0.05). Diabetes increases the level of NADH and the NADH/NAD + ratio in human myocardium and HCAECs (p b 0.05). Increase in intracellular NADH (100 μM) in the HCAECs caused a significant decrease in endothelial SK channel currents (p b 0.05), whereas, intracellular application of NAD + (500 μM) increased the endothelial SK channel currents (p b 0.05). Mitochondrial reactive oxygen species (mROS) of HCAECs and NADPH oxidase (NOX) and PKC protein expression in the human myocardium and coronary microvasculature were increased respectively (p b 0.05). Conclusions: Diabetes is associated with metabolic changes in the human myocardium, coronary microvasculature and HCAECs. Endothelial SK channel function is regulated by the metabolite pyridine nucleotides, NADH and NAD + , suggesting that metabolic regulation of endothelial SK channels may contribute to coronary endothelial dysfunction in the DM patients with diabetes.