The mitochondrial K(ATP) channel and cardioprotection

Adenosine triphosphate (ATP)-sensitive potassium (K(ATP)) channels allow coupling of membrane potential to cellular metabolic status. Two K(ATP) channel subtypes coexist in the myocardium, with one subtype located in the sarcolemma (sarcK(ATP)) membrane and the other in the inner membrane of the mitochondria (mitoK(ATP)). The K(ATP) channels can be pharmacologically modulated by a family of structurally diverse agents of varied potency and selectivity, collectively known as potassium channel openers and blockers. Sufficient evidence exists to indicate that the K(ATP) channels and, in particular, the mitoK(ATP) channels play an important role both as a trigger and an effector in surgical cardioprotection. In this review, the biochemistry and surgical specificity of the K(ATP) channels are examined.     

Blood flow and muscle metabolism in chronic fatigue syndrome

The purpose of this study was to determine if chronic fatigue syndrome (CFS) is associated with reduced blood flow and oxidative delivery to skeletal muscle. Patients with CFS according to CDC (Center for Disease Control) criteria ( n =19) were compared with normal sedentary subjects ( n =11). Muscle blood flow was measured with Doppler ultrasound after cuff ischaemia and exercise. Muscle oxygen delivery was measured as the rate of post-exercise and post-ischaemic oxygen-haem resaturation. Oxygen-haem resaturation was measured in the medial gastrocnemius muscle using continuous wavelength near-IR spectroscopy. Muscle metabolism was measured using (31)P magnetic resonance spectroscopy. CFS patients and controls were not different in the peak blood flow after cuff ischaemia, the rate of recovery of phosphocreatine after submaximal exercise, and the rate of recovery of oxygen saturation after cuff ischaemia. In conclusion, CFS patients showed no deficit in blood flow or oxidative metabolism. This suggests that CFS symptoms do not require abnormal peripheral function.     

Femoral artery diameter and arteriogenic cytokines in healthy women

Animal studies have identified monocyte chemoattractive protein-1 (MCP-1) and vascular endothelial growth factor (VEGF) as critical mediators of arterial diameter enlargement in response to chronic increases in blood flow (arteriogenesis). Furthermore, cellular studies have shown that the shear stresses resulting from increased blood flow stimulate synthesis of MCP-1, which in turn stimulates synthesis of VEGF. The purpose of this study was to determine if these mechanisms are evident in healthy women. Resting femoral artery diameter and blood flow, lean leg mass, MCP-1 and VEGF concentrations, and aerobic capacity were measured in 34 healthy women along with plasma concentrations of lipids associated with cardiovascular disease risk. Femoral artery diameter was independently related to metabolically active (lean) leg mass (b = 0.41, P = 0.008) and aerobic capacity (b = 0.45, P = 0.004). Plasma MCP-1 correlated negatively with the ratio of femoral artery diameter to lean leg mass (b = ? 0.42, P = 0.009) and positively with serum triglycerides (b = 0.46, P = 0.005). Plasma VEGF exhibited similar correlations and strongly correlated with MCP-1 (R = 0.92, P < 0.0001). The results indicate that circulating MCP-1 and VEGF concentrations are associated with both arteriogenic and atherogenic stimuli in healthy women.     

Breast MRI: Early experience with a 3-D fat-suppressed Gradient Echo Sequence in the evaluation of breast lesions

The early clinical experience with a 3-Dimensional Fourier Transform Gradient Echo sequence with fat suppression in the evaluation of breast masses is reported. Ten female patients with breast malignancies were pre-operatively evaluated with this sequence and the results compared with the pathological specimens. The scanning protocol included a noncontrast sequence followed by an immediate post-contrast sequence (completed 4.5 min after intravenous contrast injection) and a delayed sequence. Images were assessed for maximum lesion and parenchymal enhancement, lesion size and additional enhancing abnormalities. In six patients, malignant masses enhanced maximally on the immediate post-contrast sequence with parenchyma enhancing maximally on delayed images. In three cases, there was preferential enhancement of malignant lesions over normal parenchyma but to a similar degree on both post-contrast sequences. In one case, both the lesion and parenchyma enhanced maximally on the delayed sequence. Magnetic resonance assessed lesion size accurately and also detected satellite malignancies in one case. However, lesion grade, associated in situ carcinoma and lymphovascular invasion did not impact on lesion enhancement. In this small series, a contrast-enhanced, fat-suppressed 3-D Gradient Echo Sequence detected breast carcinoma with high sensitivity. The technique holds promise but further evaluation is required.     

Inflammatory bowel disease and predisposition to osteopenia

The prevalence of osteopenia in children with inflammatory bowel disease (IBD) is unknown. The effect of nutritional state, disease activity, and steroid therapy on bone mineral content (BMC) of whole body, lumbar spine, and left femoral neck measured by dual energy x ray absorptiometry in 32 children with IBD was assessed by comparison with 58 healthy local school children. Using the control data, a predicted BMC was calculated taking into account bone area, age, height, weight, and pubertal stage. The measured BMC in children with IBD was expressed as a percentage of this predicted value (% BMC). Mean (SD) % BMC was significantly reduced for the whole body and left femoral neck in the children with IBD (97.0 (4.5)% and 93.1 (12.0)% respectively, p < 0.05). Of the children with IBD, 41% had a % BMC less than 1 SD below the mean for the whole body and 47% at the femoral neck. Reduction in % BMC was associated with steroid usage but not with the magnitude of steroid dose, disease activity, or biochemical markers of bone metabolism. In conclusion, osteopenia is relatively common in childhood IBD and may be partly related to the previous use of steroids.