Effect of local cold provocation on systolic blood pressure and skin blood flow in the finger.

Demonstration of increased vascular cold reactivity in patients with Raynaud's syndrome is difficult. For medico-legal reasons, it is important to get objective measures of vasospasm in these patients. Evaluation of the degree of vasospasm also provides prognostic information which is useful for patient management. In this study, we compare two methods of arterial circulation measurement. The laser Doppler scanning is a new method, which uses the recently developed laser Doppler perfusion imaging (LDPI) instrument. The aim of the present study was to compare the effect on finger skin blood flow measured with LDPI with changes in finger systolic blood pressure during local cold provocation. The effect of such provocation, skin blood flow and systolic blood pressure, were studied in 15 healthy controls. Six patients with known traumatic vasospastic disease (TVD) were also tested with both methods. Finger skin blood flow was measured with LDPI on the distal phalanx of the index finger of the left hand, every minutes during 6 min of local heating at 40 degrees C followed by local cooling for 3 min at 15 degrees C and then for 3 min at 10 degrees C. Finger systolic blood pressure was measured with strain-gauge method before and after local cooling to 10 degrees C with a cuff perfused with water of desired temperature. The test was performed in the same finger within a week of the laser Doppler scanning. Local finger cooling to 15 degrees C and 10 degrees C caused a significant decrease in blood flow, most marked at 10 degrees C. There was, however, no correlation between the decrease in blood flow and blood pressure. In the TVD-patients decreases in skin blood flow were similar compared with the healthy controls. In contrast, the changes in systolic blood pressure, were outside normal range (systolic quotient <0.65) in five of the six patients (83%), and also in 11 of the 15 healthy controls (73%). In conclusion, there is no correlation between the decrease in finger skin blood flow and systolic blood pressure during local cold provocation. For diagnosis of traumatic vasospastic disease (TVD), local cold-induced changes in finger systolic blood pressure seems superior to changes in skin blood flow, but the ideal clinical method for demonstrating increased cold-induced vasospasm is, however, still lacking.

Sympathetic skin vasoconstriction--further evaluation using laser Doppler techniques.

The aim of this study was to quantify the reflex sympathetic vasoconstriction in skin at different depths. Twenty healthy subjects were studied. Finger skin blood flow was measured using laser Doppler perfusion imaging (LDPI) and laser Doppler perfusion monitoring (LDPM). In LDPM, a probe with fibres separated 0.25 mm (deep) and 0.14 mm (superficial) from the illuminating fibre was used. Local heating (40 degrees C) was achieved with a Peltier element, and reflex vasoconstriction induced by immersion of the contra-lateral hand and forearm for 3 min in water at 15 degrees C. The change in skin blood flow was measured and a vasoconstriction index (VAC: cooling/before cooling) calculated. VAC indices of LDPI, LDPM-0.25 and LDPM-0.14 were 0.60, 0.59 and 0.60, respectively. The two components of the LDPM perfusion value, blood cell velocity and concentration, were studied separately. Their contributions in LDPM-0.25 were roughly the same, whereas the velocity component dominated in LDPM-0.14, although their relative responses in the two channels were similar. We conclude that sympathetic skin vasoconstriction does not significantly differ in two compartments, as probed with fibres separated by 0.25 and 0.14 mm. Blood cell velocity is influenced in a proportional way, as is concentration.

Sympathetic dysfunction in patients with primary Sjögren's syndrome.

OBJECTIVE: To investigate autonomic nervous system function in patients with primary Sjögren's syndrome (SS) and relate the findings to clinical variables. METHODS: Autonomic nervous system function was determined in 30 patients with primary SS using the finger skin blood flow test [vasoconstrictory (VAC) index], deep-breathing test [expiration/inspiration (E/I) ratio], and the tilt table (orthostatic) test [acceleration index (AI), brake index (BI), and orthostatic blood pressure]. The results were compared with age matched control materials (finger skin blood flow test, n = 80, and deep-breathing and tilt table tests, n = 56). RESULTS: The VAC index was found to be significantly increased and the E/I ratio significantly decreased in patients compared to controls, indicating both a sympathetic and a parasympathetic dysfunction. Further, the patients, especially the anti-SSA and anti-SSB antibody seropositives, were found to have an abnormal blood pressure reaction to tilt compared to controls. No correlations were found between autonomic nerve function variables measured and the clinical ophthalmologic or the oral tests, performed at the time of diagnosis. CONCLUSION: Patients with primary SS show signs of both sympathetic and parasympathetic dysfunction. Further, immunological mechanisms seem to influence blood pressure in patients with primary SS.

Detection of autonomic sympathetic dysfunction in diabetic patients. A study using laser Doppler imaging.

OBJECTIVE: To study signs of the disturbed reflex autonomic sympathetic nerve function in type 1 and type 2 diabetic patients. RESEARCH DESIGN AND METHODS: Measurements were made on 15 type 1 (duration 13-32 years) and on 50 recently diagnosed type 2 diabetic patients (duration 3-4 years). The vasoconstrictor responses in the distal phalanx of the middle finger (locally heated to 40 degrees C) to the cooling of the contralateral arm were measured using Laser Doppler Imaging (LDI). A vasoconstriction index (VAC) was calculated taking age into account and was compared with reference values obtained in 80 control subjects. The diabetic patients were also studied with deep-breathing tests (i.e., the heart-rate variation expressed as the expiration-to-inspiration [E/I] ratio, a test of parasympathetic nerve function). RESULTS: The vasoconstrictor responses to indirect cooling (VAC) were significantly reduced in the fingers of the diabetic patients, both type 2 (0.77 +/- 0.02 V; P < 0.01) and type 1 (0.83 +/- 0.04 V; P < 0.001), compared with the healthy control subjects (0.65 +/- 0.01); the age-corrected VAC (VACz) was slightly more impaired in type 1 than in type 2 diabetic patients. The frequency of an abnormal VACz corresponded well to the frequency of an abnormal E/I ratio in type 1 diabetic patients (approximately 50%), whereas the frequency of an abnormal VACz was significantly higher than an abnormal E/I ratio among type 2 diabetic patients (11/50 vs. 4/50; P < 0.05). CONCLUSIONS: Both type 1 and type 2 diabetic patients have impaired cutaneous blood flow regulation. The VAC index seems to be a promising tool for detection of subclinical changes in autonomic sympathetic function.

The effects of alpha-trinositol on haemodynamic variables and neuropeptide Y levels in a pilot study of hypertensives and healthy volunteers.

AIMS: The aim of this study was to examine the effects of D-myo-inositol-1,2,6-trisphosphate (alpha-trinositol) on haemodynamic variables and neuropeptide Y (NPY) levels in hypertensives and healthy volunteers. METHODS: Hypertensives (n = 13) and normotensives (n = 11) were recruited after a screening of cardiovascular risk factors of all men aged 40 living in a well defined area. The hypertensives were previously unmedicated. The effect of alpha-trinositol was studied after intravenous infusion at rest, and during and after a maximal exercise test in a double-blind crossover manner with placebo. RESULTS: Haemodynamic variables and NPY levels were recorded. NPY levels did not differ between normotensives and mild hypertensives at the start of the study. However, a significant increase was seen in hypertensives after they had risen to the sitting position. During exercise, the NPY levels increased significantly both in normotensives and hypertensives. After the exercise test, the NPY levels were significantly higher in hypertensives than in normotensives; alpha-trinositol did not modify these responses. In normotensives no significant difference in systolic blood pressure was seen during or after the exercise test whether they were on alpha-trinositol or placebo. In the hypertensives on active drug, however, the blood pressure tended to be approximately 5 mmHg lower during the exercise test as compared with the placebo group. In the hypertensives on active drug, the heart rate increased significantly more during exercise as compared with the placebo groups. In normotensives, the same tendency was seen, but it did not reach statistical significance. CONCLUSIONS: The NPY antagonist, alpha-trinositol, tends to reduce the increase in systolic blood pressure induced by maximal exercise and increases the heart rate in hypertensives but not in normotensives.

Is transcutaneous PO2 monitoring during exercise a reliable alternative to arterial PO2 measurements?

Arterial PO2 measurement during exercise is an important part in the evaluation of pulmonary disease but requires an intra-arterial cannula. However, in clinical work it would be preferable to assess PO2 non-invasively. To evaluate such a technique, simultaneous measurements of transcutaneous PO2 (tcPO2) and arterial PO2 (PaO2), sampled from an indwelling arterial radial cannula, were made before, during and after a fatigue or symptom-limited bicycle exercise test in 16 patients referred to hospital because of dyspnoea. In total 181 paired measurements were made. Mean values (range) of PaO2 and tcPO2 were 11.2 kPa (5-16) and 9.5 (5-13.3), respectively. The correlation coefficient between PaO2 and TcPO2 was only 0.36 (P < 10(-5)). By normalizing the values of tcPO2 and PaO2 to corresponding values at supine rest before exercise, the correlation coefficient increased to 0.80 (P < 10(-6). Using PaO2 as golden standard, tcPO2 described the trend in pO2 during exercise reasonably well in all cases and this information is often sufficient for assessing the degree of pulmonary insufficiency. Thus, transcutaneous blood gas monitoring during exercise is useful for clinical evaluation of pulmonary disease, but a single arterial blood sample at rest before exercise is recommended for baseline correlation.

Distal blood pressure as a predictor for the level of amputation in diabetic patients with foot ulcer.

The predictive value of distal blood pressure measurements for the level of amputation was studied prospectively in 161 consecutive diabetic patients with foot ulcers. The patients were treated as outpatients except for periods of surgery and when complications requiring hospital care occurred. All patients were treated pre- and postoperatively by the same multidisciplinary foot care team. Either ankle or toe blood pressure measurement was available in 86% of the patients. Incompressible arteries, ulcer or gangrene at the measuring site, previous amputation, poor general condition, and an emergency situation were factors that excluded standardized ankle and toe blood pressure measurements in 24% and 27% of the patients, respectively. An absolute lower ankle pressure level of 50 mm Hg was found, below which a minor amputation was never sufficient to achieve healing. An ankle pressure below 75 mm Hg was seldom sufficient, and at or above that pressure level, the ankle pressure had no predictive value in this respect. At a toe pressure below 15 mm Hg, a minor amputation was seldom sufficient. Ankle and toe pressure indices gave no further information.

A study of exercise-induced microalbuminuria in type I (insulin-dependent) diabetes mellitus.

Microalbuminuria is thought to be an important prognostic factor in diabetes mellitus. To study the influence of changes in blood pressure on the development of microalbuminuria during exercise, two exercise tests were carried out. A total of 32 insulin dependent diabetic men whose age at onset was less than 30 years, mean duration of diabetes 14 years (range 7 to 21) and mean age 29 years (range 21 to 40), and who did not have albuminuria (N-labstix negative) were studied. The diabetic patients were compared with a total of 29 age-matched male control subjects. Urinary albumin excretion was measured during two exercise tests: at a standardised workload (150 W) for 30 min, and at a standardised heart rate for 25 min. The diabetic patients had higher albumin excretion rates during both exercise tests compared with the control subjects. Blood pressure and heart rate during exercise were significantly higher in diabetic patients compared with control subjects in the standardised workload test. If the test was individualised to achieve the same standardised heart rate there was no significant difference in blood pressure between the diabetic patients and the control subjects. These results indicate that the diabetic kidneys were more sensitive than the healthy kidneys to similar degrees of haemodynamic stress induced by exercise.

Ketanserin in the treatment of diabetic foot ulcer with severe peripheral vascular disease.

The aim of this study was to evaluate if ketanserin, a selective serotoninantagonist, could improve wound healing in diabetic patients with foot ulcers and severe peripheral vascular disease. In a double blind study 40 diabetic patients with foot ulcer and a systolic toe pressure below 45 mmHg were randomly allocated to either ketanserin (20-40 mg three times a day) or placebo for a period of 3 months. The treatment was carried out on an out-patient basis by a combined medical/orthopedic foot care team at the Department of Internal Medicine, University Hospital, Lund, Sweden. Both groups were comparable regarding age, sex, duration and treatment of diabetes, cardiovascular disease and type of lesion. Wound healing (defined as intact skin for at least 3 months) or wound size reduction of 50% or more were sen in 11 out of 19 (58%) in the ketanserin group and in 7 out of 19 (37%) in the placebo group. Gangrene developed in 6 patients with placebo and 2 with ketanserin. Two patients died during the study and their ulcers were not evaluated. The systolic toe pressure was measured at admission, at end of run in, after 1 month and 3 months with strain gauge technique. Only one out of nine patients (11%) with a toe pressure below 30 mmHg in the placebo group healed or improved their ulcers compared to nine out of 16 (56%) in the ketanserin group. The healing rate in the ketanserin group was higher than expected considering the lower systolic toe pressure in this group compared to placebo at randomization (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Wound classification is more important than site of ulceration in the outcome of diabetic foot ulcers.

The importance of wound classification and site of ulceration was evaluated in 314 consecutive diabetic patients with foot ulcers. The ulcers were classified as superficial (through the full thickness of the dermis; n = 150), deep (n = 50), osteomyelitis and/or abscess (n = 46), minor gangrene (n = 39) or major gangrene (n = 29). Wound healing was defined as intact skin for at least 6 months. In patients with superficial and deep ulcers, primary healing occurred in 88% and 78%, respectively, compared with 57% in those patient who developed an abscess and/or osteomyelitis. Only 2 out of 68 patients with gangrene healed (through mummification) without amputation. Patients with gangrene had lower ankle and toe blood pressure than patients with all other types of ulcers. There were only marginal differences in primary healing rate between different ulcer sites. The highest rate was seen in ulcers localized to the metatarsal heads (78%). Patients with multiple ulcers had the lowest primary healing rate (5%) compared with single ulcers at all sites. These differences were probably due to circulatory factors, since patients with multiple ulcers had lower distal perfusion pressures compared with all other groups.

Prognostic value of systolic ankle and toe blood pressure levels in outcome of diabetic foot ulcer.

The prognostic value of distal blood pressure measurements has been studied in 314 consecutive diabetic patients with foot ulcers. Systolic toe blood pressure was measured with a strain-gauge technique, and ankle pressure was measured with strain-gauge or Doppler techniques. Wound healing was defined as intact skin for at least 6 mo. One hundred ninety-seven patients healed primarily, 77 had amputations, and 40 died before healing had occurred. In 294 of 300 patients, it was possible to measure either ankle or toe pressure. Fourteen patients were not available for pressure measurements. Of these, 10 patients healed primarily, and 4 died before healing occurred. Both ankle and toe pressures were higher (P less than .001) among patients who healed without amputation compared with those who underwent amputation or died before healing. No differences were seen in ankle or toe pressure levels among those who had amputations or died. No patient healed primarily with an ankle pressure less than 40 mmHg. An upper limit above which amputation was not required could not be defined. Primary healing was achieved in 139 of 164 patients (85%) with a toe pressure level greater than 45 mmHg, whereas 43 of 117 patients (36%; P less than .001) healed without amputation when toe pressure was less than or equal to 45 mmHg. In conclusion, a combination of ankle and toe pressure measurements is a useful tool to predict primary healing in diabetic foot ulcers.

Improvements of the lipoprotein profile after coronary bypass surgery: additional effects of an exercise training program.

We have followed physical working capacity and the plasma lipoprotein pattern in 37 males who underwent coronary artery surgery for severe disabling angina pectoris. In order to evaluate the effect of exercise training, 18 patients were randomized to a supervised bicycle training programme three times a week for 12 weeks starting 6 weeks after surgery. Before surgery, working capacity was severely reduced in all subjects. The mean HDL cholesterol level was low (0.8 +/- 0.2 mmol l-1) and the mean plasma LDL concentration moderately elevated (4.6 +/- 0.9 mmol l-1). In the non-training group, physical working capacity increased significantly, and 18 weeks after surgery reached a plateau about 45% above the preoperative values. In the training group, a further improvement to about 60% above preoperative levels was registered at the end of the training program. In the non-training group, HDL cholesterol concentrations rose rapidly to levels between 10 and 15% above the preoperative values. One year after surgery, HDL cholesterol levels were 20% higher than before surgery. There was a parallel rise in apolipoprotein A1 concentrations by about 10% which indicates that the increase in HDL occurred mainly in the lipid rich HDL2 subfraction. There were no changes in plasma lipids or in LDL cholesterol concentrations. In the training group, the increase in HDL was about 20% during the first 26 weeks. One year after surgery, HDL levels were 23% above preoperative values. In this group, we also registered a significant decrease in plasma triglyceride levels by about 25% after two months of exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Exercise stimulation in insulin-dependent diabetics, normal increase in albuminuria with abnormal blood pressure response.

Increased urinary albumin excretion rate (AER), microalbuminuria, has been regarded as a sign of incipient nephropathy. The influence of exercise on AER was investigated in 10 male type I diabetics and in 12 age-matched male controls. The duration of diabetes was 7-31 years (median 14 years). The exercise tests were performed both as a combined submaximal workload-waterload test and as a maximal workload test. Urinary albumin was measured with an ELISA technique. During exercise in both tests, no difference was seen in the AER between diabetics and their controls. However, the increase in systolic blood pressure was significantly more marked in the diabetics. There was no correlation between the blood pressure response during exercise and the AER, neither in the diabetics, nor in their controls. It is concluded, that, increased blood pressure response during exercise does not necessarily result in increased AER in type I diabetics.

Left ventricular diastolic and systolic function during isometric exercise: an echocardiographic study.

Normal subjects of both sexes between 20 and 63 years were examined with M-mode echocardiography. Blood pressure (BP), heart rate (HR), and left ventricular (LV) diastolic and systolic function were measured at rest and at the end of a standardized maximal isometric handgrip test. BP and HR increased about 25%. This increase in cardiac work had no significant influence on LV systolic function. Diastolic function (myocardial relaxation and maximum rate of LV filling), however, improved significantly. Isometric handgrip test is a suitable exercise test in combination with M-mode echocardiography. Studies on LV function during exercise may improve the sensitivity for detection of mild LV dysfunction.

Incidence of deep vein thrombosis in bedridden non-surgical patients.

In order to detect deep vein thrombosis (DVT), 101 patients with acute medical or infectious disorders were examined with the 125I-fibrinogen uptake test. All patients were bedridden on admission and were scanned daily from the second to the eighth day. Thirteen patients developed a positive fibrinogen uptake test. Thus, if a positive test is interpreted as DVT, the incidence of DVT was 13% in our bedridden patients. Of the patients admitted because of heart disease or pneumonia 20% had DVT, but only 4% of those admitted with other diagnoses. Other clinical "risk factors" studied, could not identify patients who developed DVT.

Effects of alpha-adrenoceptor subtype-selective antagonists on the human saphenous vein in vivo.

The effects of the alpha-adrenoceptor subtype-selective antagonists prazosin (alpha 1) and yohimbine (alpha 2) on the saphenous vein of six healthy male subjects were investigated in vivo. The drugs were infused locally into the congested (40 mmHg), long saphenous vein constricted by simultaneous local infusion of noradrenaline (NA). Prazosin 10(-9) M (concentration in the infusion solution, infusion rate 0.3 ml min-1) did not reduce the NA-induced venoconstriction, but at a concentration of 10(-8) M there was a significant reduction; in two subjects no response to NA could be elicited in the presence of 10(-8) M prazosin. Prazosin 10(-7) M caused no further reduction of the NA effect compared to that produced by 10(-8) M in three of the subjects, whereas in one, prazosin 10(-9), 10(-8) and 10(-7) M caused a dose-dependent blockade. Yohimbine, 10(-9), 10(-8) and 10(-7) M caused a dose-dependent reduction of the NA-induced venoconstriction in all subjects. The results suggest that the human saphenous vein is endowed with functionally important populations of both alpha 2- and alpha 1-adrenoceptors.

Monitoring 24-hour blood pressure in a drug trial. Evaluation of a noninvasive device.

To test the usefulness of noninvasive ambulatory 24-hour blood pressure recording, the Del Mar Avionics system was used in a double-blind clinical trial in which 31 hypertensive patients were randomly allocated to receive placebo or pafenolol (25 mg or 50 mg), a novel, long-acting, highly selective beta-blocker, once daily. The results of 24-hour blood pressure and heart rate recording after 4 weeks of treatment were compared with a previous 24-hour recording performed after a 4-week placebo run-in period using the 3-hour mean of recordings performed every 7.5 minutes both day and night. Furthermore, 24-hour means were analyzed in each patient before and after 4 weeks. The system was easy to use and, judging from two placebo periods in the same patients, the reproducibility was good. The 24-hour blood pressure and heart rate recordings showed a clear dose-response relationship for pafenolol that could not be detected by ordinary casual readings. A daily dose of 25 mg of pafenolol significantly reduced blood pressure during the 9 hours after tablet intake (p less than 0.01), while 50 mg per day of pafenolol resulted in a significant reduction throughout the 24-hour period (p less than 0.01). The same pattern was seen for heart rate, which indicates a greater degree of beta-blockade during treatment with the higher dose. These results indicate that the tested noninvasive equipment is a useful tool for monitoring ambulatory 24-hour blood pressure. It gives important information impossible to obtain from single casual readings. This noninvasive method should be further evaluated to define its place in clinical work and as a research tool.

A comparison of 100 mg atenolol and 100 mg metoprolol once a day at rest and during exercise in hypertensives.

The effects of once daily dosage of the two cardioselective beta-adrenoceptor blocking agents, atenolol and metoprolol, were studied in 26 patients with primary hypertension. The study was a randomized double-blind cross-over trial with placebo run-in and wash-out. Assessment of effect was performed about 1 and 25 hours after dosing. At rest, both atenolol and metoprolol lowered the blood pressure (BP) and heart rate (HR) compared to placebo. Atenolol induced a more effective BP reduction than metoprolol, especially 25 hours after drug intake. During exercise 1 hour after dosing both drugs reduced BP and HR to a similar extent, whereas 25 hours after dosing atenolol gave a more efficient BP and HR reduction than metoprolol. Our data show that both 100 mg atenolol and 100 mg metoprolol are effective antihypertensive beta-blockers at rest and during exercise, 1 hour after intake. Metoprolol was less effective than atenolol 25 hours after dosing probably due to its shorter plasma half-life, thus implying a twice daily regimen for metoprolol in standard preparation.