The effect of alpha-lipoic acid on the neurovascular reflex arc in patients with diabetic neuropathy assessed by capillary microscopy.

Patients with diabetic polyneuropathy are known to have an impaired neurovascular reflex arc compared to healthy controls. This is seen in a delayed decrease in microcirculation of the ipsilateral hand after cooling of the contralateral hand. The aim of this pilot study was to investigate whether intravenous alpha-lipoic acid (ALA) (Thioctacid, Asta Medica) therapy might be able to improve this impaired neurovascular reflex arc in patients with diabetic neuropathy. In addition, clinical effects were evaluated with the aid of the neuropathy symptom score (NSS) and the neuropathy disability score (NDS). Ten patients with diabetes mellitus and polyneuropathy (5 females, 5 males, 2 smokers, 5 IDDM, 5 NIDDM, body mass index 26.1 +/- 1.0 kg/m2, age 58.3 +/- 9.5 years, diabetes duration 15.7 +/- 11.2 years, Hb A1c 6.8 +/- 0.3%) were investigated by nail-fold capillaroscopy after contralateral cooling before and after intravenous therapy with 600 mg alpha-lipoic acid per day over 3 weeks. Cardiac autonomic neuropathy was excluded by beat-to-beat variation analysis. Symptoms of diabetic neuropathy were evaluated before and after therapy with the aid of the NSS and NDS. Capillary blood cell velocity (CBV) of the hand was determined before, during, and for the following 30 min after cooling (3 min at 15 degrees C) of the contralateral hand. Blood pressure, heart rate, and local skin temperature were monitored at 2-min intervals. ALA therapy resulted in a significant improvement of the microcirculatory response to cooling, as seen by an immediate decrease in CBV of 12. 3% (P < 0.02 vs before treatment), which was absent before therapy. Blood pressure, heart rate, and local skin temperature were not different between investigations. There was a significant improvement of the NSS after therapy (5.4 +/- 1.1 vs 8.6 +/- 1.1 points, P < 0.01). These results demonstrate that intravenous therapy with ALA has a positive influence on the impaired neurovascular reflex arc in patients with diabetic neuropathy.

Fenofibrate improves microcirculation in patients with hyperlipidemia.

In order to investigate the effect of fenofibrate on microcirculation, 16 patients (5 female, 11 male, age 58 +/- 8 years) were studied with the aid of nailfold capillaroscopy before and after treatment with 200 mg fenofibrate per day over six weeks. Fenofibrate resulted in a significant decrease in triglycerides, total and LDL-cholesterol and apolipoprotein B and an increase in apolipoprotein A. As a parameter of an improved microcirculation the time to peak capillary blood cell velocity during postreactive hyperemia (occlusion of the lower arm for 2 minutes, 200 mmHg) decreased markedly from 45 +/- 5 to 16 +/- 3 s, p < 0.0001). Fibrinogen levels were significantly decreased (p < 0.04) in contrast to other parameters with a possible impact on microvascular perfusion (hemoglobin, hematocrit, mean platelet volume, total protein) and to blood pressure and heart rate. These findings suggest that fenofibrate treatment improves microcirculation in patients with hyperlipidemia. This beneficial effect of fenofibrate may arise from two leading mechanisms. One of these might be the decrease in fibrinogen levels reducing plasma viscosity, the other mechanism might be an indirect effect on functional abnormalities of the vascular endothelium arising from hyperlipdidemia. By lowering plasma lipids fenofibrate is likely to restore the impaired formation or efficacy of the endothelium derived relaxing factor (nitric oxide, NO).

Endothelin during cardiovascular surgery: the effect of diltiazem and nitroglycerin.

To investigate whether the vasoconstrictor peptide endothelin (ET) is elevated during cardiovascular surgery and might predispose to perioperative vasoconstriction and ischemia, we compared the effect of the calcium channel blocker diltiazem with that of the nitric oxide (NO) donor nitroglycerin on ET and hemodynamics in 32 patients undergoing coronary artery bypass grafting (CABG). Following a double-blind protocol, 16 patients (3 women, 13 men; ages 63 +/- 10 years) received 1 microgram/kg/min nitroglycerin and 16 patients (5 women, 11 men; ages 64 +/- 8 years) received 3 micrograms/kg/min diltiazem intravenously 30 min before until 12 h after CABG. ET was measured in the superior vena cava before, during, and 1 h after CABG. Compared with ET levels before CABG, ET was significantly elevated during CABG and further increased after CABG (p < 0.05). During and after surgery, ET levels were lower in patients receiving diltiazem than in those receiving nitroglycerin (both p < 0.01). Mean arterial blood pressure and heart rate were lower in patients receiving diltiazem compared with those receiving nitroglycerin (both p < 0.05). These data demonstrate that diltiazem is more effective than nitroglycerin in preventing ET increase during cardiovascular surgery. Studies using ET receptor antagonists may be useful in assessing the clinical relevance of ET levels with respect to the risk for perioperative vasoconstriction and ischemia.