Diffuse reflectance spectroscopy: Systemic and microvascular oxygen saturation is linearly correlated and hypoxia leads to increased spatial heterogeneity of microvascular saturation.

The microvascular oxygen saturation (SmvO(2)) in the skin and tongue (sublingual mucosa) in pigs (n=6) was characterised using diffuse reflectance spectroscopy (DRS). The correlation between arterial oxygen saturation (SaO(2)) and SmvO(2) as well as the spatial heterogeneity of SmvO(2) was examined during hypoxia. DRS uses shallow-penetrating visible light to assess microvascular oxygen saturation (SmvO(2)) in superficial tissue. Hypoxia was induced by gradual reduction in ventilation or reduction of the inspiratory oxygen fraction. The spatial heterogeneity of SmvO(2) was expressed as the coefficient of variation (CV) of repeated SmvO(2) measurements. Baseline SmvO(2) before interventions was 20.2% (10.3%-38.1%, median with range) in groin skin, 32.9% (13.0%-49.3%) in the ear and 42.2% (32.1%-51.5%) in the tongue. SmvO(2) in the groin was significantly lower than venous oxygen saturation (SvO(2)) (p<0.05) and SmvO(2) in the tongue (p=0.03). There was a significant linear correlation between SaO(2) and SmvO(2) in all measuring sites for both interventions (p<0.05). Similarly there was a significant correlation between CV of repeated SmvO(2) measurements and SmvO(2) in all measuring sites for both interventions (p<0.01). The results from baseline measurements indicate a surprisingly high oxygen extraction in the measurement volume of DRS, especially in the groin skin. A reduction of SmvO(2) with decreasing SaO(2) was found and additionally the results suggest that spatial heterogeneity of microvascular oxygen saturation increases during hypoxia. Microvascular disturbances have been demonstrated in both local vascular diseases and systemic conditions such as shock and sepsis, an assessment of microvascular oxygen saturation using DRS may be useful in the monitoring of the microcirculation in such patients. This study is a part of an ongoing characterization of the DRS technique.

Assessments of skin and tongue microcirculation reveals major changes in porcine sepsis.

AIM: To examine the relation between central hemodynamics, clinical severity and microvascular findings in tongue and skin during sepsis. MATERIALS AND METHODS: Skin and tongue microcirculation was examined using laser Doppler and video microscopy techniques before and 200 min after inducing sepsis in pigs (n=6) by inactivated Neisseria meningitides and in two control animals. RESULTS: All infected pigs developed clinical signs of sepsis. Pericapillary bleedings developed in the tongue in the two pigs with the most severe disease. Capillary density increased in the groin skin in infected pigs after 200 min as compared to baseline (P<0·02). In the same period, mean capillary flow velocity was reduced in groin skin and tongue in septic pigs (P<0·02). At 200 min a fraction of capillaries had developed 'no flow' or 'brisk flow', patterns hardly seen at baseline. Laser Doppler perfusion was reduced in ear and tongue after 200 min (P<0·02 for both). The described pathology was more pronounced in the pigs with the most severe sepsis. CONCLUSION: Capillary bleedings may be used as an early indication of severe sepsis. Examination of skin and tongue microcirculations may be used to characterize severity of sepsis and possibly to assess effect of treatment.

Human microvascular imaging: a review of skin and tongue videomicroscopy techniques and analysing variables.

Imaging techniques are increasingly important in clinical diagnostic work. Microcirculation is essential for function and survival of all tissues, but imaging techniques for microvascular monitoring of patients have only been used to a limited extent in clinical practice. The microcirculation is complex with its static and dynamic feature, and only skin and oral mucosa are readily accessible for microscopic examination. In addition, there is a no general agreement on which microvascular parameters and analysing techniques that could be useful. The aim of this article is to give an overview of techniques for human intra-vital microscopy and to describe software and variables used to analyse pictures and film sequences of human microcirculation. We also present clinical examples where microvascular examinations have been shown to be of diagnostic value. Improved techniques for assessing microvascular morphology and physiology will probably become important tools in clinical work in many disciplines in the near future.

Sevoflurane-induced malignant hyperthermia during cardiopulmonary bypass and moderate hypothermia.

A 56-year old man was admitted for elective mitral valve repair and coronary artery bypass surgery due to mitral valve leakage and unstable angina. After induction of anaesthesia he developed a combined metabolic and respiratory acidosis. Different diagnosis were considered and we decided to treat the patient with dantrolene due to suspicion of malignant hyperthermia (MH). The patient received one dose of dantrolene 2,5 mg/kg during cardiopulmonary bypass (CPB) and a second dose of dantrolene 2,5 mg/kg during weaning from CPB. The first arterial blood gas sample taken in the intensive care unit showed relapse of the acidosis and we administered an infusion of 150 mg dantrolene over 3 hours. The patient gradually recovered without sequel and MH was verified by muscle biopsy testing.

Myocardial extracellular signal regulatory kinases are activated by laser treatment.

AIM: Transmyocardial laser revascularization (TMR) and percutaneous transluminal myocardial laser revascularization (PTMR) have anti-anginal effects on certain groups of patients with ischemic heart disease, possibly by inducing myocardial neoangiogenesis through the mechanical injury. Here we examine the effects of TMR and PTMR on extracellular signal regulatory kinases (ERKs), which have been implicated in the control of neoangiogenesis in vitro. METHODS: Eight pigs were anesthetized with ketamine and fentanyl. In five pigs TMR was performed in the left ventricular anterior wall and PTMR in the posterior wall. Biopsies were taken either after 2 hours, 3, 7, 14, and 30 days. Three pigs served as controls and provided samples for baseline values and time-matched controls at 2 hours and 3 days. ERKs activity was determined by increased phosphorylation of myelin basic protein. Total ERKs protein abundance was determined by Western blot with an antibody against ERK1 and ERK2. RESULTS: It was found that ERKs activity was higher in all samples from the laser treated myocardium than in the control sample at baseline (TMR: >or=1878 pmol Pi x min(-1) mg pr(-1) vs 104 pmol Pi x min(-1) mg pr(-1), respectively, p<0.05. PTMR: >or=346 pmol Pi x min(-1) mg pr(-1) vs 136 pmol Pi min(-1) mg pr(-1), respectively, p<0.05). The time-matched samples showed increased activities of ERKs after laser treatment. The protein level of ERKs in myocardium treated with TMR and PTMR parallelled the data on ERKs activity. CONCLUSIONS: Our data suggest that the ERKs system is activated in the porcine heart by the mechanical injury of TMR and PTMR.

The CarboMedics supraannular top hat valve improves prosthesis size in the aortic root.

BACKGROUND AND AIM OF THE STUDY: Aortic valve replacement can result in patient-valve mismatch and attenuated left ventricular remodeling. Using CarboMedics mechanical valves, we examined if the supraannular Top Hat prosthesis provided a size advantage over the intraannular valve. METHODS: Seventeen patients with aortic stenosis and aortic root < or = 23 mm were randomized to receive a CarboMedics supraannular Top Hat valve (n = 7) or an intraannular valve (n = 10). Doppler echocardiography was performed preoperatively, and after three months. RESULTS: There was no difference in aortic annulus size, but mean prosthesis size was significantly larger in the Top Hat group than in the intraannular group (25.00 mm versus 21.60 mm); the mean size improvement for Top Hat patients was 3.14 mm. After three months, all patients had excellent functional improvement and low transvalvular pressure gradients, with slightly higher effective valve opening area in the Top Hat group. CONCLUSION: The supraannular Top Hat valve provides an advantage of one to two sizes over the intraannular valve, and improves the effective valve opening area. Both valves offer favorable hemodynamic performance and functional improvement.

Adoption of new health care services in Norway (1993-1997): specialists' self-assessment according to national criteria for priority setting.

OBJECTIVES: To identify health care services adopted in Norway in the period 1993-1997, and examine them according to proposed national guidelines for priority setting. These guidelines define core services. DESIGN: Two-stage self-administered questionnaire. SETTING: The Norwegian public healthcare system. SUBJECTS: Presidents of all relevant specialist and sub-specialist associations in the Norwegian Medical Association (n=56). OUTCOME MEASURES: Number of adopted services satisfying the priority criteria of core services, according to physician's self-assessment. Number and type of interventions suited for the priority-setting criteria. RESULTS: Thirty-two percent of new technologies satisfied the definition of core services according to specialists' own assessment. Of the 88 responses analysed for the second stage of our survey, fifteen answers (17%) indicated lack of applicability of the priority setting criteria. Loss of applicability was related to diagnostic and procedure-related technologies. CONCLUSIONS: Less than one-half of the assessed technologies adopted in Norway in the period 1993-1997 satisfy proposed national criteria for priority setting. The guidelines are applicable for most interventions, but fail in most evaluations of diagnostic and procedure-related improvements. Independent and systematic evaluations of new technologies are needed within the context of priority setting.

Sequestrated thrombolysis: comparative evaluation in vivo.

PURPOSE: Lysis of a thrombus is a function of the local concentration of thrombolytic enzymes. This study was designed to determine in a porcine model of acute deep vein thrombosis (DVT) whether perithrombic sequestration of small volumes of a concentrated enzyme solution can accelerate the process of thrombolysis. METHODS: DVT was induced in both hind limbs using a previously described technique (n = 32). Thirty minutes later the animal was heparinized and unilateral thrombolysis was attempted using 8 mg recombinant tissue plasminogen activator (rt-PA); saline was administered in the opposite leg. For conventional high-volume infusion (CI) (n = 5) rt-PA (0.067 mg/ml) was infused at 1 ml/min. For sequestrated thrombolysis the external iliac vein was endoluminally occluded, and rt-PA (0.25 mg/ml) administered either for proximal injection (ST-P) (n = 5), as a bolus every 3 min through a microcatheter placed via the balloon catheter, or for transthrombic injection (ST-T) (n = 5), as a bolus every 3 min through a Katzen wire in the balloon catheter. At autopsy, the thrombus mass in the iliofemoral veins was measured, and the extent of residual thrombosis in the venous tributaries graded at four sites. From these data a thrombolysis score was calculated. RESULTS: One pig died before thrombolysis could be performed. Only with ST-T was residual thrombus mass in the test limb normalized to control, residual thrombus index (RTI), consistently less than unity. The median RTI of this group was 0.50 (range 0.39-0.97) compared with 1.22 (0.64-1.38) for ST-P and 0.88 (0.37-1.13) for CI. Compared with contralateral controls, a lower grade of residual thrombosis in tributaries was observed in test limbs at more venous sites with ST-T (8/20; 95% confidence interval 5-13) and ST-P (9/20; confidence interval 5-13) than with CI (2/20; confidence interval 0-5) (p = 0.04). A trend toward lower thrombolysis scores was observed with ST-T (p = 0.08). Systemic fibrinogenolysis was not observed in any of the groups. Changes in coagulation parameters during thrombolysis were similar irrespective of treatment protocol. CONCLUSIONS: "Transthrombic" sequestrated thrombolysis may offer some advantages over conventional selective infusion for the treatment of acute DVT. However further refinements will be necessary before it can be considered an alternative to the latter.

Microvascular arteriovenous shunting is a probable pathogenetic mechanism in erythromelalgia.

Erythromelalgia is a condition consisting of red, warm, and burning painful extremities. Symptoms are relieved by cold and aggravated by heat. A wide variety of etiologic conditions can cause erythromelalgia, but one common pathogenetic mechanism, microvascular arteriovenous shunting, has been hypothesized. The aim of this study was to test this hypothesis. Quantification of skin microvascular perfusion using laser Doppler perfusion imaging and skin temperature at rest and after central body heating was performed in 14 patients with erythromelalgia and 11 controls. Attacks of erythromelalgia were induced in eight patients after heat provocation. In the plantar region of the foot, the location of numerous anatomical arteriovenous shunts, these patients significantly increased the skin perfusion as compared with asymptomatic patients with erythromelalgia and controls. In the dorsal region with few arteriovenous shunts no significant differences between the groups were demonstrated. The results show a relation between clinical symptoms and increased perfusion in the region of numerous anatomical arteriovenous shunts, and support the hypothesis of increased thermoregulatory arteriovenous shunt flow during attacks in primary erythromelalgia.

Transmyocardial laser treatment reduces ischemia-induced ventricular fibrillation during the early phase (1a) after coronary artery occlusion in open chest anesthetized pigs.

INTRODUCTION: It has previously been shown that transmyocardial revascularization with laser (TMR) prior to coronary artery occlusion decreases the occurrence of ischemia-induced arrhythmias. The aim of the present study was to determine the effects of TMR on ventricular fibrillation and other arrhythmias during the early (1a) and late phase (1b) of ischemia in pigs. METHODS: In six pigs TMR was performed in the anterior wall of the left ventricle 60 minutes prior to occlusion of the proximal LAD. Six other pigs were subjected to coronary occlusion without preceding TMR and served as controls. RESULTS: During the 30 min period with LAD occlusion ventricular fibrillation occurred 22 times in 5 of 6 control animals (20 episodes in phase la, 2 in phase 1b), whereas none of the animals subjected to TMR prior to the coronary artery occlusion developed ventricular fibrillation (p<0.01). The total number of premature beats per animal was lower during the early phase (la) after LAD occlusion in the TMR group than in the control group (18+/-13 vs 248+/-82, p<0.05). CONCLUSIONS: TMR prior to occlusion of LAD reduced the occurrence of early phase (la) ischemia-induced ventricular fibrillation and premature beats. This anti-fibrillatory effect might explain the improved survival observed in experimental studies after TMR prior to coronary artery occlusion found by others.

Erythromelalgia in a patient with AIDS.

Erythromelalgia is a clinical syndrome characterized by burning pain in the extremities together with erythema and increased skin temperature. Typically, the patients experience relief from cold, and aggravation from warmth. Symptoms are hypothesized to be caused by arteriovenous shunting and reduced nutritive skin capillary perfusion with corresponding tissue hypoxia. Erythromelalgia is most often primary, but may be secondary to a wide variety of diseases. We report erythromelalgia in a patient with acquired immune deficiency syndrome (AIDS). At peak pain intensity he actively cooled hands and feet for more than 12 h/day. Many doctors handling human immunodeficiency virus/AIDS patients are unfamiliar with erythromelalgia, and the condition can easily be overlooked, especially the more common milder cases.

Placement of a spring filter during interventional treatment of deep venous thrombosis to reduce the risk of pulmonary embolism.

PURPOSE: To assess the efficacy of the Spring filter during interventional treatment of deep venous thrombosis in vivo. MATERIAL AND METHODS: A model of inferior vena cava thrombosis was used. Part I: The thrombus was treated by the pulse-spray technique (PT) (urokinase 250,000 IU; n=7) or a rotatory basket catheter, Thrombolizer (MT) (activated with compressed air at 7 atm; n=5). Part II: Following placement of a Spring filter, the animal underwent PT (n=5) or MT (n=5). Based on the results of part I, the treatment protocol was modified (PT, urokinase 500,000 IU; MT, compressed air at 8 atm). Embolus volumes trapped by the filter and found in the lungs were calculated and the filtering efficacy quantified. RESULTS: Part I: Pulmonary emboli (1 to 4 mm in diameter) were observed in 3 animals in the PT group and 1 animal in the MT group, respectively. Median reduction in thrombus volume was 21% and 4% by PT and MT, respectively. Part II: In the PT group, 58% and 100% of the total embolus load was trapped in 2 animals, while the filter failed to trap emboli (1 to 1.5 mm in diameter) in 1 animal. In the remaining 2 animals, no embolus was found trapped by the filter or in the lungs. In the MT group, 55 97% (median 83%) of the embolus load was trapped. Emboli found in the lungs did not exceed 4 mm in diameter. CONCLUSION: Preceding interventional treatment of venous thrombosis with placement of the Spring filter reduced the embolic burden on the lungs.

Transventricular non-transmural laser treatment of hypoperfused porcine myocardium acutely reduces left ventricular contractile function.

OBJECTIVE: Creation of non-transmural myocardial channels by lasers transmitted through endovascular fiberoptics is a novel therapeutic option in the management of patients with coronary artery disease. The acute effect of transventricular laser treatment (TvL) on coronary blood flow, myocardial metabolism and left ventricular function are not well established. METHODS: In five anesthetized pigs, flow in the proximal left anterior descending coronary artery (LAD) was reduced and maintained at 70% of baseline. A venous shunt had previously been established draining the hypoperfused region. At 30 min of ischemia, non-transmural myocardial channels were created through the endocardium using a Ho:YAG laser. We measured (a) left ventricular, central venous and arterial pressures, (b) ascending aortic, LAD and coronary venous blood flows, as well as (c) lactate concentration and blood gases in arterial and coronary venous blood, prior to ischemia (baseline), before and 30 min after TvL. Data (given as mean +/- SD) were analyzed with repeated measures ANOVA. RESULTS: Reduction of LAD blood flow resulted in reduced regional coronary venous blood flow and myocardial oxygen consumption, conversion of regional myocardial lactate uptake to release and adaptation of left ventricular contractility to a lower level. Following transventricular laser, the peak left ventricular systolic pressure declined from 86 +/- 12 to 77 +/- 11 mmHg (P < 0.05), its maximal first positive derivative (LV dP/dt) declined from 900 +/- 221 to 763 +/- 127 mmHg/s (P < 0.05) and the stroke volume decreased from 19.2 +/- 4.1 to 16.4 +/- 5.4 ml (P < 0.05). The changes in regional coronary venous flow, myocardial oxygen consumption and myocardial lactate release after TvL were not significant compared to before TvL. Significant intramural hematomas and tissue destruction were found around the channels at autopsy and by histologic examination. CONCLUSION: Transventricular laser treatment of hypoperfused myocardium decreased left ventricular contractility in the acute phase, possibly due to development of perichannel hematomas and disruption of the wall architecture. In addition, TvL did not alter the regional myocardial oxygen supply/demand balance. These results call for caution in the treatment of patients with coronary artery disease by transventricular Ho-YAG laser when there is significant impairment of the left ventricular contractile function.

Selective venous thrombolysis with the nipple-balloon catheter: comparative evaluation in vivo.

PURPOSE: To compare in an animal model of deep vein thrombosis, an intramural drug delivery catheter, the nipple-balloon catheter, with an occlusion balloon-infusion guide wire system. MATERIALS AND METHODS: Ten juvenile pigs were used for the study. Deep vein thrombosis was induced in both hind limbs by using a previously described technique. Heparin was administered 30 minutes later (2,500 IU intravenously) and bilateral thrombolysis was attempted with use of 8 mg of alteplase as a 0.25 mg/mL solution containing heparin 50 IU/mL (n = 10) and sodium/meglumine ioxaglate 40 mgI2/mL (n = 5). In one limb, the external iliac vein was endoluminally occluded, and 0.8 mL of alteplase was administered every 3 minutes through a multisideport infusion wire placed coaxially through the balloon catheter. On the other side, a nipple-balloon catheter was used: alteplase was injected as two 0.4-mL aliquots every 3 minutes in overlapping segments of the vessel. Blood samples were taken at predetermined intervals to determine the partial thromboplastin time and plasma fibrinogen concentration. At autopsy, the thrombus mass in the iliofemoral veins was measured, and the extent of residual thrombosis in the venous tributaries was graded at four sites. The heart and the lungs were also examined for thromboemboli (n = 5). Venous specimens were then subjected to X-ray fluorescence spectrometry to determine iodine content (n = 5). RESULTS: Bilateral thrombolysis could be successfully completed in all animals. No procedural problem associated with the use of the nipple-balloon catheter was encountered. The mass of residual thrombus in the axial veins was significantly lower in this group (P = .005). The drug delivery system used did not appreciably influence thrombolysis in the tributaries. Signs of macroscopic damage to the veins were not observed in any animal. None of the venous specimens had detectable levels of iodine. Small thromboemboli were found in the pulmonary circulation in three of five animals. Fibrinogen levels did not decrease during the procedure. CONCLUSIONS: The significantly lower residual thrombus burden associated with use of the nipple-balloon catheter suggests that the device may have the potential to be an effective delivery system for selective thrombolysis in veins.

Transmyocardial laser induces coronary hyperemia and reduces ischemia-related arrhythmias, but fails to delay development of myocardial necrosis after coronary artery occlusion in pigs.

BACKGROUND: Several investigators have reported that transmyocardial revascularization (TMR) prior to acute coronary artery occlusion improves regional myocardial function and reduces the infarct size in animals with significant coronary collateral circulation. Whether the protective effect of TMR is due to perfusion through the laser-made channels, increased collateral flow or other mechanisms remains unresolved. The aim of this study was to investigate whether TMR performed prior to acute coronary artery occlusion could offer protection from ischemic injury in the pig, an animal with limited native collateral coronary circulation. METHODS: In one group (n=4), TMR was performed in the anterior wall of the left ventricle 30 minutes prior to occlusion of the proximal LAD for 45 minutes. The other group (n=6) was subjected to transient ischemia of the same duration without previous TMR. Area at risk and infarct size were determined after sacrifice. RESULTS: No significant difference was found in the infarct size between the two groups (69+/-2% in the TMR group versus 62+/-4% in the control group). However, the arrhythmic index during the period of ischemia was significantly lower in the TMR group (1.0+/-0.3 vs 8.3+/-2.2, p<0.001). Blood flow in LAD increased to a maximum of 135+/-6% of baseline level three minutes after the end of the TMR procedure. CONCLUSIONS: TMR failed to reduce the infarct size following acute coronary artery occlusion in the pig, an animal with a small collateral coronary flow capacity, but reduced ischemia-related arrhythmias and increased coronary flow transiently.

In vivo evaluation of the adjustable temporary venous spring filter and the RF02 temporary filter: comparative study.

RATIONALE AND OBJECTIVES: The authors performed this study to compare the in vivo efficacies of the temporary venous spring filter and the RF02 filter in an animal model. MATERIALS AND METHODS: Either the spring filter or the RF02 filter was placed in the inferior vena cava of 10 pigs each, and two clots (5 x 20 mm) were funneled into the filters at 1-hour intervals. The second clots were funneled without removing the first clots captured by the filters. Clot-trapping ability, caval occlusion associated with the clot-trapping procedure, arterial blood gas concentrations, and changes in arterial and iliac venous pressures were evaluated. RESULTS: Placement of the RF02 filter caused elevation of iliac venous pressure with a maximum of 2.2 mm Hg (median) (n = 13, P = .003). Placement of the spring filter parallel to venous flow enabled capture of 90% (nine of 10) and 100% (six of six) of the first and second clots, respectively. The RF02 filter captured clots consistently. The difference between filters was not statistically significant. Both filters equally contributed to elevation of iliac venous pressure (median, 9.3 and 7.2 mm Hg [n = 9] with the spring filter and RF02 filter, respectively). Caval occlusion occurred in 17% (one of six) and 67% (six of nine) of animals after two clots were trapped in the spring filter and RF02 filter, respectively (P = .06). Other parameters were not influenced by the clot-trapping procedure. CONCLUSION: Although a larger version should be developed and better stability of the filter is needed, the spring filter proved to be an efficient filtering device and had a lower rate of caval occlusion compared with the RF02 filter.

Periprosthetic leak and rupture after endovascular repair of abdominal aortic aneurysm: the significance of device design for long-term results.

We present a case of abdominal aortic aneurysm treated with an endovascular bifurcated aortic graft in which a periprosthetic leak caused by a tear in the polyester prosthesis appeared between 9 and 12 months after surgery. The tear appeared adjacent to a suture breakage that caused separation of two struts of the nitinol wire framework in the body of the stent graft. The leak was sealed with insertion of a new endovascular tube graft into the body of the bifurcation. Eight months later, the patient had a nonfatal rupture of the abdominal aortic aneurysm because detachment of the second limb from the bifurcation caused a new major periprosthetic leak. According to the manufacturer of this device, suture breakage with separation of metal components is commonly seen, but perforation of the polyester prosthesis caused by movement of the metal stent against the fabric has not been reported. It is likely that this occurred in our patient. Detachment of the second limb from the bifurcated stent, causing a rupture, has been described before. Increasing angulation and tortuosity of the stent graft, as a result of either remodeling of the sac or elongation of the stent, and reduced compliance to angulation after the stent-in-stent procedure might have contributed to the detachment in this case.

Oscillations in the human cutaneous blood perfusion signal modified by endothelium-dependent and endothelium-independent vasodilators.

The purpose of the present study was to compare the effects of endothelium-dependent [acetylcholine (ACh)] and endothelium-independent [sodium nitroprusside (SNP)] vasodilators on the oscillatory components of the cutaneous blood perfusion signals in humans. The unstimulated basal blood perfusion and the blood perfusion during iontophoretically delivered ACh and SNP were measured using laser Doppler flowmetry (LDF). The wavelet transform was calculated before spectral analysis of the measured signals. In the frequency interval from 0.0095 to 1.6 Hz the LDF signal consists of oscillations with five different characteristic frequencies. In addition to the cardiac (1 Hz) and respiratory (0.3 Hz) rhythms, three other oscillations in the regions around 0.1, 0.04, and 0.01 Hz were detected. The oscillations with the different frequencies were observed in unstimulated blood flow and also during stimulation with ACh and SNP. Compared to the unstimulated blood flow, both ACh and SNP increased the mean amplitude of the total spectrum (P < 0. 005 for both substances). The only significant difference between the effects of ACh and SNP was observed in the amplitude of oscillations with the frequency of around 0.01 Hz. ACh increased the absolute amplitude of this frequency to a greater extent than SNP in athletes (P = 0.03), whereas only a trend was observed in controls (P = 0.2). The relative amplitude, defined as the ratio between the absolute amplitude of a particular frequency interval and the mean amplitude of the total spectrum, was also higher for ACh compared to SNP both in controls (P = 0.008) and in athletes (P = 0.004), only for oscillations with the frequency of around 0.01 Hz. We conclude that ACh selectively influences the oscillatory component of around 0.01 Hz in the cutaneous blood perfusion signal to a greater extent than SNP. This finding indicates that endothelium-mediated vasodilatation is manifested as oscillations with a repetition time of approximately 1 min. The mechanisms for the endothelial dependency of this frequency remain to be elucidated. Our data indicate that spectral analysis based on wavelet transform of the cutaneous perfusion signal can be used clinically to investigate endothelial function. The described noninvasive method might be used to evaluate endothelial function for research, for diagnostic purposes, and maybe also to assess effects of therapy in cardiovascular diseases.