Blockade of vascular ATP-sensitive potassium channels reduces the vasodilator response to ischaemia in humans.

Experimental data show that ATP-sensitive potassium (KATP) channels not only occur in pancreatic beta cells, but also in the cardiovascular system, where they mediate important cardioprotective mechanisms. Sulphonylurea derivatives can block the cardiovascular KATP channels and may therefore interfere with these cardioprotective mechanisms. Therefore, it is of clinical importance to investigate whether sulphonylurea derivatives interact with vascular KATP channels in humans. Using venous-occlusion strain-gauge plethysmography, we investigated whether ischaemia-induced reactive hyperaemia is reduced by the sulphonylurea derivative glibenclamide in 12 healthy male non-smoking volunteers. Forearm vasodilator responses to three periods of arterial occlusion (2, 5 and 13 min) during concomitant infusion of placebo into the brachial artery were compared with responses during concomitant intra-arterial infusion of glibenclamide (0.33 microgram.min-1.dl-1). A control study (n = 6) showed that time itself did not change the vasodilator response to ischaemia. Glibenclamide significantly increased minimal vascular resistance (from 2.1 +/- 0.1 to 2.3 +/- 0.2 arbitrary units, Student's t-test: p = 0.01), and reduced mean forearm blood flow (from 37.5 +/- 2.0 to 35.4 +/- 2.0 ml min-1.dl-1 after 13 min occlusion, ANOVA with repeated measures: p = 0.006) and flow debt repayment during the first reperfusion minute (ANOVA with repeated measures: p = 0.04). In contrast, total flow debt repayment was not affected. Infusion of glibenclamide into the brachial artery resulted in local concentrations in the clinically relevant range, whereas the systemic concentration remained too low to elicit hypoglycaemic effects. Our results suggest that therapeutic concentrations of glibenclamide induce a slight but significant reduction in the early and peak vasodilation during reactive hyperaemia.

The influence of ulnar nerve blockade on skin microvascular blood flow.

Microvascular research is seriously hampered by the great temporal and spatial variability of the measured skin blood flow and variation in sympathetic vasomotor reflexes within and between persons. Therefore skin vasomotor reflexes were studied before and after ulnar nerve blockade within the same person, resulting in a temporal complete denervation of the fifth finger and partial denervation of the fourth finger. Skin temperature and laser Doppler flux (LDF) were registrated to measure predominantly arteriovenous shuntflow. Measurements were performed on the palmar tip of the second and fifth finger in nine healthy volunteers, at baseline, and during a sympathetic reflex test (i.e. inspiratory gasp) and postural response test. Beat-to-beat digital blood pressure was recorded from the third and fourth finger by a Finapres device. Baseline capillary blood cell velocity (CBV) was measured at the nailfold of the second and the fifth finger. After ulnar blockade baseline skin temperature, LDF and CBV increased significantly, with respectively (mean +/- SE) 3.2 +/- 0.9 degrees C, 20.9 +/- 5.9 relative perfusion units and 0.79 +/- 0.40 mm-1 s. The percentage LDF decrease of the fifth finger during inspiratory gasp was 48.2 +/- 5.3% before and 3.1 +/- 0.9% after blockade. The postural response test showed a decrease in LDF of the fifth finger with no significant difference before and after blockade, respectively 12.3 +/- 14.7% and 8.0 +/- 2.7%, while no difference was found in the increase in digital blood pressure in the denervated fourth finger compared to both the same finger before blockade and to the third non-blocked finger.(ABSTRACT TRUNCATED AT 250 WORDS)

An automated computerized method using Finapres for measuring cardiovascular reflexes.

1. The major drawback of the cardiovascular reflex tests used to study autonomic failure is the time involved in calculating the results. To overcome this disadvantage, we have developed an automated computerized program using a FINger Arterial PRESsure instrument for the measurement of beat-to-beat heart rate and blood pressure on a finger. 2. This program calculates heart rate variability during three standardized tests, forced breathing, standing up and the Valsalva manoeuvre, and records blood pressure values in response to standing up and sustained handgrip. The time taken to perform the test and to calculate the results is usually 25 min. 3. The reproducibility of the tests in 21 normal subjects was comparable with the reproducibility obtained with conventional test methods using an ECG and a sphygmomanometer. 4. In addition, we determined the age-dependent normal values of the seven test parameters in 124 subjects aged 20-90 years. 5. Using this program in 10 patients with longstanding (14-50 years) complicated diabetes, in each of them four or more abnormal test results were found.

Adenosine attenuates the vasoconstrictor response to the cold pressor test in humans.

The forearm vasoconstrictor response to a standardized cold pressor test (CPT) was studied twice in eight healthy subjects, once during local intraarterial infusion of adenosine and once during infusion of equipotent dosages of the control vasodilator sodium nitroprusside (SNP). During local SNP infusion, the forearm vascular resistance (FVR) decreased from 70 +/- 14 to 30 +/- 7 arbitrary units (AU). Adenosine induced a comparable vasodilator response, with a decrease in FVR from 56 +/- 14 to 28 +/- 6 AU. Subsequent cold exposure induced a mean percentage increase in FVR of 62 +/- 17% during SNP, whereas the increase was only 27 +/- 12% during adenosine infusion (p = 0.014). There were no differences in the calculated cold-induced changes in forearm production of norepinephrine (NE) between the SNP and the adenosine tests. We conclude that adenosine attenuates forearm vasoconstrictor response to the CPT, probably by a postjunctional mechanism of action.

Localized unilateral hyperhidrosis.

A case of unilateral hyperhidrosis of the face is described. Measurements of the rate of evaporative water loss from other areas of the body, showed a marked left-right difference in the sweating rate on the arms and on the legs which had not been suspected clinically. Unilateral hyperhidrosis is a rare and puzzling disorder. Possible neurological causes are discussed.

Irritant contact dermatitis. Traumiterative and cumulative impairment by cosmetics, climate, and other daily loads.

Based on the results of exposure experiments on living human skin a working hypothesis is launched concerning the possible pathogenesis of irritant contact dermatitis. Below a certain and critical degree of exposure there is no alteration in clinical aspect of the exposed region. However, instrumentally (watervapour-loss measurements, impedance measurements) it is usually possible to register subclinical effects in such a field. These are interpreted as signs of impairment of metabolic homoiostatic systems. It is possible in certain cases to show that the skin is able to adapt its functions to a repeated load (illustrated with exposure experiments to DMSO). It seems useful to distinguish between a traumiterative irritant contact dermatitis (a result of too early repetition of just one type of load; see Aquabrom experiment) and a cumulative irritant contact dermatitis (resulting from a too early repetition of exposures differing in type; see experiment with soap and detergent solutions). In cumulative irritant contact dermatitis the sequence of the different loading factors is of importance: first soap and then detergent or the reverse.

Permeability of surgeons' gloves to methyl methacrylate.

The quick passage of methyl methacrylate at 21 degrees C and 35 degrees C through seven surgeon's glove materials in a diffusion chamber was quantified by gas-chromatographic analysis. Polystyrene-butadiene dissolved in methyl methacrylate, latex and polychlorobutadiene showed reversible expansion, during which material from the samples dissolved. In order to prevent these phenomena from interfering with the analyses, experiments were performed with 4.7 M methyl methacrylate in ethanol. Even then, the time in which methyl methacrylate permeated the membrane was too short for sufficient protection. When using these gloves, the orthopaedic surgeon who is fixing endoprostheses is no doubt occlusively exposed to methyl and other methacrylates, benzoyl peroxide, rubber additives, etc. Of glove materials which are not surgically used, vinyl was inferior to latex, whereas a very thin polyethylene copolymer did not change in methyl methacrylate, showed better resistance to diffusion, but was insufficiently elastic and easily perforated. A better protective material is urgently needed.

Delayed irritation: hexanediol diacrylate and butanediol diacrylate.

Ephemeral topical contact with hexanediol diacrylate and butanediol diacrylate may cause delayed irritant dermatitis. During 4 years' observation of 20 workers utilizing these substances in the electron beam coating department of a door factory, contact sensitization did not occur. The characteristics of delayed contact irritancy are enumerated. The disease must be distinguished from allergic contact dermatitis, acute irritant dermatitis and cumulative irritant dermatitis.