Evaluation of the transcutaneous oxygen method used at 37 degrees C for measurement of reactive hyperaemia in the skin

The transcutaneous oxygen electrode used at an electrode temperature of 35-37 degrees C measures changes in PO2 at the skin surface that are mainly determined by changes in skin blood flow. Simultaneously, information about tissue PO2 in a defined skin area can be obtained by calculation. The reproducibility of this new application of the transcutaneous PO2 technique and factors influencing the recordings were analysed. Reactive hyperaemia was best recorded at 37 degrees C, where the coefficient of variation (CV) was 14% and the correlation coefficient was 0.90 between duplicate measurements within 15 min (n = 57). The day-to-day variation was greater (CV 19-28%). No significant spatial differences in reactive hyperaemia were noted when the distance between the electrodes was no more than 3 cm on the same forearm. A slightly lower reactive hyperaemia was noted when the arm with the electrode was elevated above the level of the heart, as compared with a lower position. Age and sex had significant influence, children (n = 34) exhibiting a greater postocclusive peak tcPO2 response than adults (n = 67). In adults, females (n = 30) showed significantly higher peak tcPO2 values during reactive hyperaemia than males. This method is a new application of the tcPO2 technique and can be used as a noninvasive tool for simultaneous blood flow and tissue PO2 studies in microcirculatory research.     

Endogenous prostaglandins as local regulators of blood flow in man: effect of indomethacin on reactive and functional hyperaemia.

1. The contribution of endogenously formed prostaglandins of the E series (PGE) to the development of reactive and functional hyperaemia was studied in the human forearm. 2. Forearm blood flow was recorded using venous occlusion plethysmography. The concentration of prostaglandin E-like substances (PLS) in the venous effluent from the muscle was analysed using bio-assay. For inhibition of PG biosynthesis, indomethacin (1-25 mg/kg body weight) was administered. 3. Following 5 min of arterial occlusion, a marked hyperaemia developed during the next 150 sec. Indomethacin, while not affecting the resting arterial blood flow, significantly decreased the peak level as well as the duration of the hyperaemia. The total reactive hyperaemia was 25 ml./100 ml. tissue before, and 13 ml./100 ml. tissue after administration of indomethacin. 4. During sustained isometric forearm contraction, and following isometric and dynamic forearm muscle activity, a moderate hyperaemia was observed. This was significantly diminished when indomethacin had been administered, although not to the same extent as the reactive hyperaemia. The total hyperaemia in the absence and presence of indomethacin was 113 and 77 ml./100 ml. tissue, respectively, in connexion with isometric contraction and 206 and 120 ml./100 ml. tissue, respectively, following dynamic work. 5. The venous concentration of PLS was very low at rest. A significantly increased concentration was observed after ischaemia. This increased release of PLS was entirely suppressed by indomethacin. With the present assay method, muscular activity elicited no detectable change in the venous concentration of PLS. 6. It is concluded that reactive hyperaemia depends to a considerable extent on an intact PGE synthesis. It is furthermore suggested that endogenous PGE may contribute to the functional hyperaemia that appears during and after muscle activity.     

Effect of cigarette smoking on reactive hyperaemia in the human finger

The effect elicited by cigarette smoking on the reactive hyperaemia that develops following release of arterial occlusion in human skin was investigated, and compared to the corresponding effects elicited by oral administration of indomethacin (an inhibitor of the prostaglandin-forming enzyme cyclo-oxygenase) or nicotine, or by smoking of nicotine-free cigarettes. Finger blood flow was determined in human volunteers, using venous occlusion plethysmography, in the basal state and after 5 min of arterial occlusion. All subjects were studied before and after they had smoked two tobacco cigarettes, two herbal (nicotine-free) cigarettes, or chewed a nicotine chewing gum. The determinations before and after tobacco smoking were repeated after administration of indomethacin. In separate series, the effects of smoking on heart rate and systemic blood pressure were recorded. The basal finger blood flow was significantly (P less than 0.05) diminished following cigarette smoking, by about 35%, and so was the reactive hyperaemia (P less than 0.05), by about 55%. The reactive hyperaemia after administration of indomethacin in combination with cigarette smoking did not differ from that obtained after cigarette smoking alone. The reactive hyperaemia was not affected by oral administration of nicotine, or by smoking of two herbal cigarettes. Cigarette smoking elicited increases in heart rate and systemic blood pressure that were of similar magnitude before and after indomethacin. From these data, we conclude that cigarette smoking elicits an inhibitory effect on the reactive hyperaemia in the human finger. This effect is probably not caused by nicotine, and seems to act via blockade of the vascular relaxation normally medicated by locally formed cyclo-oxygenase products.     

Effects of dipyridamole and theophylline on reactive hyperaemia in subcutaneous adipose tissue in humans

The importance of adenosine for reactive hyperaemia in subcutaneous adipose tissue was studied in healthy volunteers, using the adenosine uptake inhibitor dipyridamole (bolus 0.1 mg/kg i.v. followed by infusion of 0.7 microgram/kg/min) and the adenosine receptor antagonist theophylline (4 or 6 mg/kg i.v.). Basal blood flow, total blood flow and hyperaemia (total minus basal flow) after a 20-min arterial occlusion were measured in the distal femoral region by the 133Xe washout technique with and without drug treatment. Basal blood flow (mean +/- SEM) was 2.4 +/- 0.3 ml/min/100 g, while total post-occlusive flow and total reactive hyperaemia were 97.3 +/- 8.4 and 61.8 +/- 6.5 ml/100 g, respectively, without drug treatment. Basal blood flow was unaffected by dipyridamole but the total flow and hyperaemia were enhanced by 49 +/- 24 and 60 +/- 31%, respectively (P less than 0.05 for both). This enhancement was due to increases in both amplitude and duration of the hyperaemia. Neither basal blood flow, total post-occlusive flow nor hyperaemia were significantly altered by theophylline. The amplitude of the enhanced hyperaemia during dipyridamole was not significantly counteracted by simultaneous theophylline treatment (6 mg/kg) but the duration of hyperaemia was reduced from 13 +/- 1 to 8 +/- 1 min (P less than 0.01). The results suggest that endogenous adenosine does not regulate basal blood flow or reactive hyperaemia of limited duration in human adipose tissue. However, reactive hyperaemia may be enhanced by pharmacological elevation of endogenous adenosine levels.     

Effect of long-term beta-adrenergic-blockade on calf blood flow in hypertensive patients

The effect of a four-week treatment with propranolol and metoprolol on blood pressure and regional haemodynamics of the lower extremity at rest, after exercise and during reactive hyperaemia was studied in 34 patients with essential hypertension, but without peripheral arterial disease, in a randomized placebo-controlled trial. No significant difference in side-effects recorded during the trial was observed between these two drugs. Treatment with beta-adrenergic blocking drugs reduced systemic blood pressure. Calf blood flow during vasodilatation was also decreased. The most marked changes were observed during reactive hyperaemia; mean calf blood flow was reduced from about 250 ml/min/litre of tissue to 200 ml/min/litre of tissue (P less than 0.01) by propranolol and to 214 ml/min/litre of tissue (P less than 0.01) by metoprolol. Both drugs caused a significant increase in peripheral resistance above the initial level during reactive hyperaemia (P less than 0.05). No significant difference in peripheral resistance was observed, however, when the active drugs were compared with the placebo. There was no difference between propranolol and metoprolol in any of the parameters. Thus, the flow reduction can mainly be attributed to the diminished perfusion pressure due to the decreased cardiac output caused by beta-blockade of the heart.     

Elastic porous tube model of reactive hyperaemia

Reactive hyperaemia is the term given to the temporary increase in blood flow that follows release of an occlusion of the arterial supply. Measurement of reactive hyperaemia in the leg below the knee is useful in assessment of the vascular system, as resting flows remain unaffected even in the presence of quite severe occlusive arterial disease. An elastic porous tube representation of the vascular system is used to develop equations for the variation of the mean pressure, flow and vessel calibre in the vascular system. The tube represents the arteries and large arterioles, which respond passively to changes in pressure. Leakage through the tube walls represents flow into the small arterioles, which respond actively to the rise in pressure following release of the occlusion by constricting (the myogenic response). The capillaries are represented by rigid tubes, and the venous system is represented by a single compliant vessel. The model predicts variations in the flow, pressure and vessel calibre that are in agreement with experimental observations, and identifies that the pressure gradient is important in determining the initial transient increase in the flow following release of the occlusion. The subsequent development in the flow is governed by the small arteriolar flow, which is determined by the magnitude and duration of the myogenic response.     

Effects of C-peptide on forearm blood flow and brachial artery dilatation in patients with type 1 diabetes mellitus

Recent studies suggest that C-peptide increases blood flow in both exercising and resting forearm in patients with type 1 diabetes. Now we have studied the effect of C-peptide administration on endothelial-mediated and non-endothelial-mediated arterial responses as well as central haemodynamics in 10 patients with type 1 diabetes in a placebo-controlled double-blind study. Euglycaemia was maintained with an i.v. insulin infusion before and during the study. A high-resolution ultrasound technique and Doppler echocardiography were used to assess haemodynamic functions. Brachial artery blood flow and brachial artery diameter were measured in the basal state, 1 and 10 min after reactive hyperaemia and 4 min after sublingual glyceryl trinitrate administration (GTN; endothelial-independent vasodilatation), both before and after the end of 60-min C-peptide (6 pmol kg-1 min-1) or saline infusion periods. Echocardiographic measurements were also performed before and at the end of the infusion periods. Seven healthy age-matched males served as controls for vascular studies. The patients showed a blunted brachial dilatation after reactive hyperaemia in comparison with the healthy controls (2.1 +/- 0.5% vs. 9.3 +/- 0.3%, P < 0.001), indicating a disturbed endothelial function. C-peptide infusion compared with saline resulted in increased basal blood flow (33 +/- 6%, P < 0.001) and brachial arterial dilatation (4 +/- 1%, P < 0.05). Left ventricular ejection fraction seemed to be improved (5 +/- 2%, P < 0.05) at the end of C-peptide infusion compared with placebo. The vascular response to reactive hyperaemia and GTN was not affected by C-peptide infusion. Our results demonstrate that physiological concentrations of C-peptide increase resting forearm blood flow, brachial artery diameter and left ventricular systolic function in patients with type 1 diabetes.     

Cerebral reactive hyperaemia and arterial pressure in anaesthetized goats

The effects of arterial pressure on cerebral reactive hyperaemia were studied in anaesthetized goats measuring electromagnetically middle cerebral artery flow and performing arterial occlusions of 5–30 s. Under normotension (mean arterial pressure, MAP = 11± 0.3 kPa), reactive hyperaemia (peak hyperaemic flow to control flow and repayment to debt ratios) increased, and cerebrovascular resistance during peak hyperaemic flow decreased, as ischaemia duration lengthened; the virtual maximal changes were obtained after 20 s ischaemia. During hypertension by aorta constriction (MAP = 18 ± 0.7 kPa) or by i. v. infusion of noradrenaline (MAP = 19 ± 0.8 kPa) middle cerebral artery flow did not change significantly and cerebrovascular resistance increased 25 and 46%, respectively (P < 0.05). During both types of hypertension reactive hyperaemia was over 50% higher, and the decrement in cerebrovascular resistance during peak hyperaemic flow was also higher, than under normotension. During hypotension by constriction of the inferior vena cava (MAP = 5 ±.5 kPa) or by i. v. infusion of isoproterenol (MAP = 6±.5 kPa), middle cerebral artery flow decreased 35% or did not change, and cerebrovascular resistance decreased 41 and 45 %, respectively (P < 0.05). In these conditions, reactive hyperaemia and the decrement in cerebrovascular resistance during peak hyperaemic flow were reduced SOY, and it was similar in both types of hypotension. The absolute levels of cerebrovascular resistance obtained during peak hyperaemia were similar during normotension, hypertension and hypotension. Thus, arterial pressure is a main determinant of postocclusive cerebral reactive hyperaemia, and myogenic mechanisms may be of significance in determining the early stage of cerebral reactive hyperaemia after brief ischaemias. Adrenergic mechanisms might be of minor significance in this type of cerebral reactive hyperaemia.     

Blood flow in the triceps brachii muscle in humans during sustained submaximal isometric contractions

The main purpose of this study was to determine the extent to which blood flow through the profunda artery within the triceps brachii muscle may be compromised during maintained low-force isometric fatiguing contractions. Doppler ultrasound techniques were used to record mean blood velocity and arterial diameter of the profunda brachii artery during sustained isometric contractions of 20% maximal voluntary contraction. The arterial diameter did not change throughout the contraction. Thus, blood velocity was considered to be an indicator of blood flow. The mean blood velocity increased initially and then remained constant during the contraction period. When compared to rest [0.06 (SD 0.03) m s^–1] mean blood velocity was significantly larger at the start of the contraction [0.13 (SD 0.07) m s^–1] and larger yet during recovery following the contraction [0.30 (SD 0.14) m s^–1]. Although blood flow through the conduit artery did not drop during the contraction, the post-contraction hyperaemia suggested that circulatory compromise might have occurred at the level of the capillary beds. Electronic Publication     

Coronary reactive hyperaemia and arterial pressure in anaesthetized goats

To study the effects of arterial pressure on coronary reactive hyperaemia, left circumflex coronary artery flow was measured, and reactive hyperaemia was determined after 5, 10 or 20 s of occlusion of this artery in anaesthetized goats during normotension, hypertension and hypotension. During hypertension induced by aortic constriction (mean arterial pressure, MAP = 140 +/- 6 mmHg) coronary vascular resistance (CVR), reactive hyperaemia (ratio of peak in hyperaemic flow to control flow and ratio of repayment to debt) and the decrease in CVR during the peak in hyperaemic flow were comparable to those during normotension. During hypertension induced by noradrenaline (MAP = 144 +/- 6 mmHg) CVR was 16% lower (P < 0.05), reactive hyperaemia was reduced by 14-25% (P < 0.05) and the decrease in CVR during the peak in hyperaemic flow was lower than the values of these parameters during normotension. During hypotension induced by constriction of the caudal vena cava (MAP = 40 +/- 4 mmHg) CVR was 22% lower (P < 0.05), reactive hyperaemia was reduced by 25-65% (P < 0.05) and the decrease in CVR during the peak in hyperaemic flow was less compared to the values of these parameters during normotension. During hypotension induced by isoprenaline (MAP = 45 +/- 4 mmHg) CVR was 59% lower, reactive hyperaemia was reduced by 55-100% (P < 0.01) and the decrease in CVR during the peak in hyperaemic flow was less compared to the values of these parameters during normotension. Arterial pressure is a main determinant of coronary reactive hyperaemia after brief periods of ischaemia, and the relationship between arterial pressure and reactive hyperaemia may depend in part on changes in CVR after variations in arterial pressure. These changes in CVR may be related to the action on coronary vessels of myocardial factors and vascular myogenic mechanisms.     

Skin capillary blood cell velocity in patients with arterial obliterative disease and polycythaemia: a disturbed reactive hyperaemia response

Nailfold skin capillary blood cell velocity (CBV) was studied at rest and during post-occlusive reactive hyperaemia after a 1 min arterial occlusion (PRH1) in: (i) both hands of patients with arterial obliterative disease (AOD) of one arm, (ii) patients with polycythaemia, before and after a moderate haemodilution and (iii) healthy controls. CBV was analysed by videophotometric cross-correlation utilizing the different optical densities produced by the passage of erythrocytes, leucocytes and plasma gaps through the monitored capillary. Resting CBV in the patients with unilateral AOD was similar in equivalent fingers of both hands. However, the time to peak (p)CBV during PRH was significantly prolonged in the low-pressure arm as compared to the contralateral arm. pCBV was also delayed in the patients with polycythaemia as compared to the healthy controls. This delay was not affected by the replacement of 500-750 ml of blood with the same amount of a 6% Dextran 70 solution. The mean capillary blood cell velocity during rest (rCBV) did not differ between controls and patients before or after the haemodilution. The prolonged time to pCBV in the polycythaemic patients may be attributed to increased blood viscosity that is presumably not significantly influenced by a moderate haemodilution using Dextran 70. The marked delay to pCBV observed distal to the arterial obstruction in patients with AOD probably is an effect of the lower arterial pressure, presumably involving an alteration of vascular smooth muscle function.     

Postprandial impairment of resistance vessel function in insulin treated patients with diabetes mellitus type-2.

Reduced postischaemic reactive hyperaemia, is considered a marker of impaired resistance vessel function. Acute postprandial hyperlipidaemia has been shown to induce vascular dysfunction. In the present study, the impact of postprandial hyperglycaemia on resistance vessel reactivity was investigated in insulin treated type-2 diabetic patients. The study was performed in 16 insulin treated type-2 diabetics (eight male/eight female, age 47 +/- 3 years, HbA1c 7.2 +/- 0.2) and 16 controls. Reactive hyperaemia was measured in the forearm by venous occlusion plethysmography after 5 min of ischaemia in the fasting state and 90 min after a test meal. In diabetics, blood glucose increased from 8.7 +/- 1.1 to 15.3 +/- 1.0 mmol l-1 (P<0.001) postprandially. This resulted in (i) a significant increase of resting blood flow (3.4 +/- 0.3 to 4.8 +/- 0.4 ml min-1 100 ml-1, P<0.01) and (ii) in a reduced peak reactive hyperaemia (52.3 +/- 7.4 to 36.8 +/- 4.3 ml min-1 100 ml-1, P<0.005). In controls, a similar effect of the meal on resting flow was observed but reactive hyperaemia was unaltered. In the absence of a test meal, basal flow as well as peak reactive hyperaemia remained unchanged in diabetic as well as in non-diabetic subjects. Our data provide evidence that in the postprandial state resistance vessel reactivity becomes reduced in insulin treated type-2 diabetic patients.     

Resistance responses in proximal arterial vessels, arterioles and veins during reactive hyperaemia in skeletal muscle and their underlying regulatory mechanisms

The reactive hyperaemia response cat skeletal muscle to 2-120 s arterial occlusions was analysed with regard to amplitude, duration, 'excess blood flow' and site of dilator action along the vascular bed. The last-mentioned was assessed with a new whole-organ technique permitting continuous segmental resistance recordings in arterial vessels greater than 25 microns, arterioles less than 25 microns and veins. Peak amplitude, duration and excess flow all increased with increasing occlusion length, of which excess flow was linearly related to occlusion length. The site of active dilatation was preferentially confined to arterioles less than 25 microns in which complete relaxation was observed after only 20 s occlusion, although the duration of the response continued to increase with more prolonged occlusions. A graded, but less pronounced, dilatation occurred in the arterial vessels greater than 25 microns and in the veins, the former exhibiting a 63% inhibition of tone as a maximum response at 120 s occlusion. The recovery phase was characterized by a vivid active constrictor component apparently protecting the capillaries from excessive pressure load upon arterial occlusion release, but this constriction became attenuated at long occlusions, thereby prolonging the hyperaemia response. The role of myogenic regulatory mechanisms in the responses was assessed from observed segmental resistance reactions to selectively applied transmural pressure stimuli similar to those elicited by arterial occlusion/release. It was concluded that myogenic mechanisms alone could explain the amplitude of the reactive hyperaemia response at short (up to 30 s) occlusions. Metabolic mechanisms seemed to be responsible for further relaxation of the proximal arterial vessels at longer occlusions, and also for the increased duration of the hyperaemia response at occlusions exceeding 10 s. Blockade of nitric oxide formation (endothelium-derived relaxing factor) did not seem to affect the reactive hyperaemia response.     

Heterogeneous blood flow distribution within single skeletal muscles in the rabbit: role of vasomotion, sympathetic nerve activity and effect of vasodilation

A major heterogeneous distribution of blood flow has been described on a non-microvascular level within single skeletal muscles at rest and during exercise hyperaemia both in the dog and in the rabbit. The heterogeneity in blood flow distribution could be composed of both a steady-state region-to-region variability (spatial) and a time-dependent variability (temporal) in blood flow to each region. In the present study we estimated their relative contributions to the variations in blood flow within the muscles. Furthermore, we determined whether sympathetic nerve activity contributed to and whether pharmacologically induced vasodilation affected the heterogeneous blood flow pattern. Regional blood flow measurements were based on microsphere infusions into anaesthetized rabbits. Blood flow was determined under both resting conditions and during exercise hyperaemia in regions weighing 0.25 g each within hind leg muscles. The coefficient of variation for the spatial variability was twice that of the temporal one: 0.32 and 0.16 (mean) respectively. Neither stimulation of the sympathetic nerves, sympathectomy nor vasodilation affected the heterogeneity in blood flow. When exercise hyperaemia was induced, blood flow increased in all regions so that a positive (P less than 0.05) correlation was present between resting and exercising blood flow values in the individual regions. Although regional variation in vascularization could explain the observations during exercise hyperaemia, we have at present no fully satisfying explanation for the observed regional heterogeneity in blood flow.     

Measurement by laser-Doppler flowmetry of microcirculation in lower leg muscle at different blood fluxes in relation to electromyographically determined contraction and accumulated fatigue

Single-fibre percutaneous laser-Doppler flowmetry (LDF) of the tibialis anterior muscle was performed continuously for measurement of the microcirculation during different blood fluxes, as well as in relation to different muscle activities and fatigue determined electromyographically (EMG). The laser-Doppler power spectrum density function was studied in a frequency range of 0–8.2 Hz as representing the blood flow most selectively. Reduced blood flow from tourniquet inflation caused a decrease in signal power density, compared to that of intact blood flow at rest. During postocclusion reactive hyperaemia an increased signal power was recorded. This reached its maximum within 4.4 (SD 1.88) s after deflation of the tourniquet. The different fluxes were recorded at high sensitivity and disturbances were small. Periods of 1-min static dorsi-flexion of the foot at 10, 20, 30, 40, and 50% MVC (maximal voluntary contraction) with 1-min rest between were associated with a significant increase in LDF, the recordings obtained during the rest periods showing a tendency towards an increase. A decrease in the EMG mean power frequency (MPF) indicated accumulated fatigue. The LDF. for the rest periods that followed upon continuous contractions up to the same MVC levels showed a tendency towards an increase but variability was large. With further development, these techniques may be useful in the evaluation of insufficiency of the peripheral circulation.     

Redistribution of skin blood flow during leg dependency in peripheral arterial occlusive disease.

A disturbed autoregulation of cutaneous blood flow in legs with peripheral arterial occlusive disease (PAOD) has previously been demonstrated for circumscribed skin areas. In the present study, posturally-induced changes of skin perfusion distribution along ischaemic limbs were investigated topographically in 35 PAOD patients by means of fluorescein perfusography. Among the 68 legs studied, 7 had patent arteries and 61 could be assigned to FONTAINE stages I to IV. Limbs with peripheral skin lesions (stage IV) were further differentiated according to either healing (stage IV+) or non-healing (stage IV-) on conservative treatment. Sitting-up always led to prolonged calf as well as foot fluorescein appearance times (AT) except for legs in stage III or IV- disease. In the latter two groups, decreased sitting as compared to supine AT foot-to-calf ratios indicated a relative shift of dye delivery from proximal towards distal skin regions during posture. In contrast, this measure of blood flow redistribution did not change in the other groups. The redirection of fluorescein influx was significantly correlated with the systolic arterial pressure ankle-to-arm ratios. In conclusion, besides small perfusion pressure increases or passive microvessel distension, a shift of the peripheral resistance ratios may contribute to the improved blood supply of ischaemic skin regions during leg dependency. An arteriolar vasoparalysis does not regularly exist in limbs with skin lesions not primarily originating from ischaemia (stage IV+).     

Effects of C‐peptide on forearm blood flow and brachial artery dilatation in patients with type 1 diabetes mellitus

Recent studies suggest that C‐peptide increases blood flow in both exercising and resting forearm in patients with type 1 diabetes. Now we have studied the effect of C‐peptide administration on endothelial‐mediated and non‐endothelial‐mediated arterial responses as well as central haemodynamics in 10 patients with type 1 diabetes in a placebo‐controlled double‐blind study. Euglycaemia was maintained with an i.v. insulin infusion before and during the study. A high‐resolution ultrasound technique and Doppler echocardiography were used to assess haemodynamic functions. Brachial artery blood flow and brachial artery diameter were measured in the basal state, 1 and 10 min after reactive hyperaemia and 4 min after sublingual glyceryl trinitrate administration (GTN; endothelial‐independent vasodilatation), both before and after the end of 60‐min C‐peptide (6 pmol kg^–1 min^–1) or saline infusion periods. Echocardiographic measurements were also performed before and at the end of the infusion periods. Seven healthy age‐matched males served as controls for vascular studies. The patients showed a blunted brachial dilatation after reactive hyperaemia in comparison with the healthy controls (2.1 ± 0.5% vs. 9.3 ± 0.3%, P < 0.001), indicating a disturbed endothelial function. C‐peptide infusion compared with saline resulted in increased basal blood flow (33 ± 6%, P < 0.001) and brachial arterial dilatation (4 ± 1%, P < 0.05). Left ventricular ejection fraction seemed to be improved (5 ± 2%, P < 0.05) at the end of C‐peptide infusion compared with placebo. The vascular response to reactive hyperaemia and GTN was not affected by C‐peptide infusion. Our results demonstrate that physiological concentrations of C‐peptide increase resting forearm blood flow, brachial artery diameter and left ventricular systolic function in patients with type 1 diabetes.     

Myogenic vascular regulation in skeletal muscle in vivo is not dependent of endothelium-derived nitric oxide.

The hypothesis, based on in vitro experiments on large conduit arteries, that endothelium-derived nitric oxide is a mediator of vascular myogenic reactivity was tested in cat gastrocnemius muscle in vivo. This was done by comparing, in the absence and presence of effective endothelium-derived nitric oxide blockade by the specific inhibitors NG-monomethyl-L-arginine or NG-nitro-L-arginine methyl ester, myogenic responses in defined consecutive vascular sections to dynamic vascular transmural pressure stimuli, to arterial occlusion (reactive hyperaemia), and to arterial pressure changes (autoregulation of blood flow and capillary pressure). The results demonstrated that the myogenic vascular reactivity to quick ramp transmural pressure stimuli was not attenuated by endothelium-derived nitric oxide blockade, but rather reinforced. The amplitude of the reactive hyperaemia response was unaffected by endothelium-derived nitric oxide blockade, but its duration was shortened because of faster myogenic constriction, especially of large-bore arterial resistance vessels greater than 25 microns, in the recovery phase. Both the improved myogenic responsiveness to transmural pressure stimuli and the shortening of the reactive hyperaemia by endothelium-derived nitric oxide blockade suggested that endothelium-derived nitric oxide released in vivo acts as a 'metabolic' factor which certainly does not improve, but rather depresses myogenic vascular reactivity. Autoregulation of blood flow and capillary pressure were well preserved in the presence of endothelium-derived nitric oxide blockade. It was concluded from the results of these multifaceted tests that myogenic vascular regulation in skeletal muscle in vivo seems independent of endothelium-derived nitric oxide.(ABSTRACT TRUNCATED AT 250 WORDS)     

A non-invasive measure of changes in blood flow in the human anterior tibial muscle

We used photoplethysmography (PPG) to monitor blood flow changes in the human anterior tibial muscle during arterial occlusion and during isometric and concentric contractions. Single-fibre laser-Doppler flowmetry (LDF) was used as a reference in 12 healthy subjects (5 men, 7 women; mean age 24 years). Post-exercise hyperaemic muscle blood flow (MBF) was measured immediately after isometric dorsiflexion of the ankle joint at maximal contraction for 1 min and full range-of-motion dorsiflexion and plantar flexion of the ankle joint for 1 min. A thigh tourniquet was applied for the evaluation of post-occlusive reactive hyperaemia. The MBF (baseline=100%) was [mean (SD)] 150 (31)% (P=0.003) by PPG (880 nm) and 182 (66)% (P=0.012) by LDF. After 1 min of maximal isometric contraction, MBF increased to 150 (51)% (P=0.003) by PPG (880 nm) and to 169 (43)% (P=0.005) by LDF. After 1 min of maximal concentric contractions, MBF increased to 158 (59)% (P=0.003) by PPG (880 nm) and to 170 (99)% (P=0.008) by LDF. Skin blood flow, PPG (560 nm), did not change significantly after isometric or concentric contractions. The results indicate that reactive hyperaemia after exercise and arterial occlusion can be assessed in the human anterior tibial muscle using PPG. Electronic Publication     

Validity and reproducibility of electrical impedance tomography for measurement of calf blood flow in healthy subjects

The Sheffield electrical impedance tomography; (EIT) system produces images of changes in the distribution of resistivity within tissue. The paper reports on the application of electrical impedance tomography in monitoring volume changes in the limb during venous occlusion. The aim of the study is to assess the feasibility, reproducibility and validity of calf blood flow measurements by EIT. In 14 healthy volunteers calf blood flow is compared, as determined in a calf segment by strain-gauge plethysmography (SGP), with the impedence changes measured by EIT during rest and post-ischaemic hyperaemia. The measurements are repeated to assess reproducibility. The reproducibility for the EIT, assessed from the repeated measurements and expressed as a reproducibility coefficient, is 0.88 during rest and 0.89 during hyperaemia. The reproducibility coefficient for SGP data is 0.83 at rest and 0.67 during hyperaemia. Flow measurements, assessed by means of two methods, correlate well at rest (r=0.89), but only moderately during hyperaemia (r=0.51). The correlation coefficient for the pooled flow measurements is 0.98. It is concluded that EIT is a valid and reliable method for assessing blood flow in the limb. Possible applications of EIT in localising fluid changes are discussed.