Enhancement of glucose disposal in patients with type 2 diabetes by alpha-lipoic acid.

Insulin resistance of skeletal muscle glucose uptake is a prominent feature of Type II diabetes (NIDDM); therefore pharmacological interventions should aim to improve insulin sensitivity. Alpha-lipoic acid (CAS 62-46-4, thioctic acid, ALA), a natural occurring compound frequently used for treatment of diabetic polyneuropathy, enhances glucose utilization in various experimental models. To see whether this compound also augments insulin mediated glucose disposal in NIDDM, 13 patients received either ALA (1000 mg/Thioctacid/500 ml NaCl, n = 7) or vehicle only (500 ml NaCl, n = 6) during a glucose-clamp study. Both groups were comparable in age, body-mass index and duration of diabetes and had a similar degree of insulin resistance at baseline. Acute parenteral administration of ALA resulted in a significant increase of insulin-stimulated glucose disposal; metabolic clearance rate (MCR) for glucose rose by about 50% (3.76 ml/kg/min = pre vs. 5.82 ml/kg/min = post, p < 0.05), whereas the control group did not show any significant change (3.57 ml/kg/min = pre vs. 3.91 ml/kg/min = post). This is the first clinical study to show that alpha-lipoic acid increases insulin stimulated glucose disposal in NIDDM. The mode of action of ALA and its potential use as an antihyperglycemic agent require further investigation.

A modified ex-vivo rabbit lung reperfusion model for the study of lung preservation techniques.

Extracorporeal reperfusion models have proved to be particularly useful for the experimental assessment of donor lung preservation techniques. One disadvantage of the models employed to date is what with the low reperfusion rates used, any minimal lung damage is compensated for and is thus not detected or at least not detected promptly. By permitting reperfusion at physiological flow rates, use of a membrane deoxygenator in a closed circuit permits early detection of damage due to ischaemia or reperfusion. A modified ex-vivo reperfusion model is presented which permits assessment of lung function under almost physiological conditions after varying periods of ischaemia and varying conditions of preservation.

The influence of verapamil on lung preservation. A study on rabbit lungs with a reperfusion model allowing physiological loading.

Calcium-channel blockers have recently been shown to improve myocardial and renal preservation. It was presumed that this should apply also for donor lungs. Extracorporeal reperfusion models have proved to be particularly useful for the experimental assessment of donor-lung preservation techniques. One disadvantage of the models employed to date is that with the low reperfusion rates used, any minimal lung damage is compensated for and is thus not detected or at least not detected promptly. The aim of this study was the investigation of the effect of verapamil in a modified reperfusion model with physiological volume/time flow ratio during reperfusion. The application of verapamil into the flush and into the reperfusion blood of an ex-vivo lung transplantation model renders, particularly after 12 hr of preservation, a statistically significant improvement of the organ function.