Tachykinins potently stimulate human small bowel blood flow: a laser Doppler flowmetry study in humans.

BACKGROUND: The two tachykinins substance P and neurokinin A are abundantly present in the gastrointestinal tract. Substance P preferring neurokinin 1 receptors are mainly found in submucosal blood vessels while neurokinin A preferring neurokinin 2 receptors seem to be confined to smooth muscle cells. Tachykinin effects on intestinal mucosal blood flow in humans are not known. AIM: To study the effects of substance P and neurokinin A on small bowel mucosal blood flow in humans. METHODS: A manometry tube supplied with single fibre microprobes recorded mucosal blood flow in the proximal small bowel using laser Doppler flowmetry, concomitant with luminal manometry, defining phases I, II, and III of the migrating motor complex. Simultaneously, flowmetry of temporal skin was performed. Under fasting conditions saline was infused intravenously over four hours followed by infusion of substance P, neurokinin A, or saline. RESULTS: During phase I, substance 1-6 pmol/kg/min increased mucosal blood flow dose dependently by a maximum of 158%. Blood flow of the temporal skin increased in parallel. Neurokinin A 6-50 pmol/kg/min increased mucosal blood flow maximally by 86% at 25 pmol/kg/min while blood flow of temporal skin increased at all doses. Substance P at all doses and neurokinin A at the highest dose only, increased pulse rate. Systolic blood pressure was unchanged by either peptide while substance P at the highest dose decreased diastolic pressure. CONCLUSION: Tachykinins increase blood flow of the small bowel and temporal skin. With substance P being more potent than neurokinin A, these effects are probably mediated through neurokinin 1 receptors.

Endoscopic transthoracic sympathicotomy and peripheral microcirculation: effects of electric sympathetic chain stimulation, thermocoagulation and anaesthetic agents.

BACKGROUND: During endoscopic transthoracic sympathicotomy (ETS) in patients with hyperhidrosis it is useful to assess the effect of surgery peroperatively. However, the autonomic system is affected in various ways by different anesthetic agents. In the present study, the effect of ETS during either isoflurane or propofol anesthesia was evaluated by measuring changes in the finger pulp microcirculation using laser Doppler flowmetry (LDF). Electric stimulation of the sympathetic chain was used for identifying the sympathetic chain and to explore whether the anesthetic agents differentially influenced the LDF response to stimulation. METHODS: From a group of 12 patients with incapacitating palmar hyperhidrosis, six were randomly assigned to isoflurane and six to propofol anesthesia. LDF probes were attached to the ipsilateral finger pulp for continuous recording of peripheral blood flow during the ETS procedure. Electric stimulation (1 Hz, 10 Hz, and 100 Hz) was applied to the sympathetic paravertebral chain at the levels of the 2nd and 3rd sympathetic ganglia via a custom designed bipolar electrode. In eight of the patients LDF recordings were also performed in the awake state and compared with records obtained from eight healthy subjects. FINDINGS: In patients anesthetized with isoflurane, the base line finger pulp blood flow did not significantly differ from that of awake normal subjects, while those anesthetized with propofol had a lower base line flow, similar to that of awake subjects with hyperhidrosis. Stimulation of the sympathetic chain induced marked reduction of finger pulp microcirculation in both anesthetic groups, and this effect was frequency dependent during isoflurane anesthesia. After ETS a significant increase in flow was recorded only in the propofol group. Interpretation. The study demonstrates that the completeness of the sympathicotomy can only be peroperatively evaluated if an anesthetic agent with relatively low vasodilatory capacity, as e.g. propofol, is utilized.

Arterial blood flow and microcirculatory changes in a rat groin flap after thrombosis induced by electrical stimulation of the artery.

An experimental model of acute arterial thrombosis was developed in a rat groin flap model. Electrical stimulation was delivered to the flap artery while measuring blood flow in the artery and in the flap microcirculation using a laser Doppler system. Electrical stimulation produced an occlusive thrombosis in 10 rats within 68.1 +/- 19.26 (mean +/- SE) min. Thrombosis formation produced a rapid decrease of the LDF readings in the artery (90%) and in the flap (70%), the decrease being fairly parallel. Following the spontaneous thrombolysis, the artery perfusion recovered to baseline level but the flap blood flow only recovered by 10-20%. During electrical stimulation there was no change of the systemic blood pressure. The dynamic course of thrombus formation was documented on a videotape recorder through a microscope-mounted video camera and monitored on a television screen. Segments of the artery were obtained during and at the end of the experiments. The histological examination revealed arterial thrombosis composed of red blood cells, fibrin, and white blood cells, without any significant architectural and endothelial changes in the vessel walls. The study suggests that this model using electric vessel stimulation is effective for inducing arterial thrombosis and provides a simple method for recording the dynamic course of thrombus formation.

Arterial blood flow and microcirculatory changes in the rat groin flap after ischemia provocation by electrical stimulation of the artery.

An island groin flap based on the inferior epigastric vessels was raised in 10 rats in order to monitor simultaneous ischemic changes in arterial blood flow and skin microcirculation induced by electrical stimulation of the feeding artery. A modified laser Doppler perfusion system recorded blood flow in the epigastric artery and in the skin microcirculation of the flap before and for 40 min after the experimentally induced ischemia. Sections of the stimulated segment of the vessel were obtained at the end of the experimental procedure for histological analysis to determine the extent of endothelial changes, if any. Artery blood flow and the flap microcirculation decreased significantly immediately after stimulation, both slowly increasing to prestimulation levels after 30 min. Artery perfusion was quicker than microcirculation to recover to the baseline value, indicating that reperfusion of larger vessels could involve mechanisms fundamentally different from those active in the resolution of ischemia at the capillary level. Histological artery examination revealed no significant endothelial damage at the stimulation site, thus demonstrating that electrical stimulation induces reproducible ischemia without visible endothelial damage. The differential effects on the feeding artery and on capillary perfusion indicate recruitment of several different mechanisms.

Longitudinal studies on the microcirculation around the TheraCyte immunoisolation device, using the laser Doppler technique.

Encapsulation of cellular grafts in an immunoisolation membrane device may make it possible to perform transplantation without having to give immunosuppressive drugs. A common problem is the development of an avascular fibrotic zone around the implants, leading to impaired graft survival. The TheraCyte macroencapsulation device has therefore been designed to facilitate neovascularization of the device's surface. In this study, we evaluated the microcirculation around empty TheraCyte devices implanted SC in rats at various times after implantation, using a laser Doppler probe introduced via the device port. Studies were performed on day 1 or at 1, 2, and 4 weeks or at 2, 3, and 12 months after implantation. The mean flow was 158+/-42, 148+/-50, 133+/-28, 72+/-17, 138+/-41, 165+/-43, and 160+/-29 perfusion units (PU), respectively. Thus, the microcirculation around the device was significantly reduced at 4 weeks after implantation (p < 0.01) while, from 2 months onwards the circulation had improved and did not differ significantly from that on day 1. The present study shows time-related changes in the microcirculatory flow around TheraCyte macroencapsulation devices that agree with our previous microdialysis studies on in vivo exchange of insulin and glucose between the device and the circulation. Laser Doppler flowmetry seems to provide a reliable technique for screening blood perfusion around macroencapsulation devices.

Impaired acetylcholine-induced vascular relaxation in low birth weight infants: implications for adult hypertension?

Low birth weight is associated with an increased risk of adult hypertension. To elucidate whether this association reflects altered vascular physiology already at birth, we studied acetylcholine-induced vasodilation. Forty newborn infants and their mothers were studied 3 d after delivery. Vasodilation in skin was induced by local application of acetylcholine and local heating to 44 degrees C. Perfusion changes were measured with the laser Doppler technique. In response to acetylcholine, the mean skin perfusion increased by 240% in low birth weight infants compared with 650% in normal birth weight controls (p < 0.001). In contrast, mothers of low birth weight infants showed a mean increase in perfusion of 1100% after acetylcholine administration compared with 680% in mothers of control infants (p < 0.05). The perfusion increase at 44 degrees C local skin temperature did not differ between the two groups of infants or between their mothers. Blood pressure was normal in all subjects. We conclude that low birth weight infants show signs of endothelial dysfunction at birth. Such findings may help us understand the link between low birth weight and adult hypertension.

Adrenergic modulation of small bowel haemodynamics in interdigestive motility state of man.

OBJECTIVE: We previously reported a new application of semi-invasive laser-Doppler flowmetry (LDF) to record small intestinal haemodynamics in man under basal motor conditions, i.e. during phase I of the migrating motor complex (MMC). In the present study, we evaluated the complete MMC cycle and its haemodynamics in humans; specifically, adrenergic influence on blood flow in all three MMC phases was studied. DESIGN: Twenty-one fasting healthy male volunteers (21-44 years) were studied during two complete MMC cycles: the first as control period, the second as experimental period with different adrenergic drugs or saline. METHODS: Recording of LDF of intestinal blood flow was performed by attaching two single-fibre microprobes to a small intestinal manometry tube, which simultaneously monitored luminal pressure changes. RESULTS: Clonidine and oxymetazoline, two alpha2-adrenoceptor agonists, significantly decreased blood flow during all phases of the MMC cycle. In contrast, the non-selective beta-adrenoceptor agonist isoprenaline induced phase II-like activity with a significant increase in blood flow. Propranolol, a beta-adrenoceptor antagonist, did not alter motility but decreased blood flow throughout the MMC cycle. CONCLUSIONS: Both alpha- and beta-adrenergic mechanisms modifying small bowel haemodynamics are in operation throughout phases I, II and III of MMC. Our findings support the use of the semi-invasive LDF technique to measure drug-induced haemodynamic changes in the fasting gut.

Antagonists of sensory neuropeptides inhibit the secondary phase of increased circulation following thermally induced inflammation.

A model of thermally induced inflammation in the anesthetized rat was used to measure acute microcirculatory reactions after heat exposure. The thermal injury was inflicted by dipping the right hindpaw into hot water at 60 degrees for 20 s. Local blood flow was recorded simultaneously in both hindpaws and continuously by laser Doppler flowmetry before, during and for 2 h after the thermal injury and the mean arterial blood pressure (MAP) was displayed on a chart recorder. To assess the contribution of the nervous system to the vascular changes seen, neuropeptide antagonists directed toward substance P (SP), neurokinin A (NKA), and calcitonin gene-related peptide (CGRP) were administered. The neurokinin antagonists (NK1, NK2) and the CGRP antagonist (CGRP8-37) were injected via a catheter into the jugular vein. During the first few minutes after thermal injury to the controls, an immediate increase in blood perfusion of about 351% was recorded, followed by a slow decrease of circulation. At 30 min after thermal injury, there was a secondary phase of increased microcirculation of approximately 329%. A slow decline of cutaneous circulation then followed and, after another 30 min, the value stabilized at a level about 100% above the level before injury. Pretreatment with intravenous injections of the NK1 antagonist, NK2 antagonist, and CGRP8-37 attenuated the first phase and almost abolished the secondary phase. No significant change of perfusion was observed on the unscalded paw. The MAP remained at a stable level throughout the experiment and was not affected by the thermal injury or by the administration of the antagonists as compared to controls. Our results show that sensory neuropeptides play a significant role in the blood flow increase seen following thermal injury.

Two neural mechanisms for respiration-induced cutaneous vasodilatation in humans?

1. In humans, a deep breath is known to induce cutaneous vasoconstriction in the warm state, and vasodilatation in the cold state. To investigate whether vasodilatation in the cold state is related to reduction of sympathetic vasoconstrictor nerve traffic, we studied the effect of a deep breath on vascular resistance in a skin area on the dorsum of the hand, in which release of noradrenaline from sympathetic nerves was blocked by iontophoretic pretreatment with bretylium tosylate. Simultaneous measurements were made in two control areas. In eight healthy subjects, data were obtained from deep breaths taken before bretylium in the warm state, after general cooling to a finger skin temperature below 25 C and after rewarming to above 32 C. 2. In the warm state before bretylium pretreatment, the deep breath evoked short-lasting vasoconstrictions at all sites. In the cold state there was no change of vascular resistance in the bretylium-pretreated area, whereas in the control areas an initial tendency towards vasoconstriction was followed by a significant transient vasodilatation. After rewarming, transient vasoconstrictions reappeared at the control sites, whereas only a transient vasodilatation occurred at the bretylium-pretreated site. 3. In six healthy subjects we also monitored the effects of a deep breath on skin sympathetic nerve activity (recorded by microneurography in the peroneal nerve), and skin vascular resistance within the innervation zone of the impaled nerve fascicle in the foot. Data from thirty deep breaths per subject were averaged. 4. In the cold state, the deep breath induced a strong increase in neural discharge, followed by a transient reduction of nerve traffic lasting approximately 15 s and associated with a subsequent reduction of vascular resistance. 5. We conclude that the deep breath-induced vasodilatation in the cold state is due to reduction of sympathetic vasoconstrictor nerve traffic. The vasodilatation after bretylium treatment in the warm state raises the possibility that a deep breath induces two simultaneous neural reactions, a vasoconstrictor and an active vasodilator component, the latter being weaker and normally masked by the strong vasoconstrictor component.

Evaluation of the vascular reaction in pharyngeal mucosa.

The patency of the upper airways during inspiration is maintained by reflexogenic muscular dilation, mediated by afferent nerves. Our hypothesis is that a local disturbance in these nerves might explain the increased tendency of upper airways to collapse in patients with obstructive sleep apnea. The vascular reaction in the mucosal microcirculation is regulated by afferent nerves. To investigate this, we developed the laser Doppler perfusion monitoring method and electrical nerve stimulation for investigations of the soft palatal mucosa in non-snoring subjects. A 12 cm probe with integrated bipolar electrodes and a special probe-holder were designed. The bandwidths 12 and 24 kHz were compared and the latter was better able to detect a high blood-flow. A dose response relation was found between the voltage stimulation level and percentage increase in blood-flow. Three series of stimuli (40 V) in 10 subjects caused reproducible vascular reactions. In conclusion, this method seems to be safe, tolerable and valuable for investigations of patients with obstructive sleep apnea or other pharyngeal disorders, e.g. dysphagia, in the search for local nerve lesions.

Baroreceptor-mediated reduction of jejunal mucosal perfusion, evaluated with endoluminal laser Doppler flowmetry in conscious humans.

Reduction of central blood volume elicits a peripheral vasoconstrictor reflex in various tissues including skin, skeletal muscle and the hepatomesenteric region. The aim of the present study was to investigate whether this reaction includes a decreased perfusion of the jejunal mucosa in man. Laser Doppler flowmetry (LDF) was used to monitor jejunal mucosal and skin perfusion simultaneously in eleven healthy volunteers. LDF recordings were performed during quiescent (phase 1) periods of the migrating motor complex. Seven subjects demonstrated cycling changes of jejunal mucosal perfusion (vasomotion). The average minimum jejunal flux value was 72 +/- 6 perfusion units. The average intraindividual coefficient of variation was 18 +/- 2%. Lower body negative pressure (LBNP) was used to elicit controlled reductions of central blood volume. LBNP of 10 mm Hg induced a 12 +/- 4% (P < 0.05) decrease in jejunal perfusion and a 43 +/- 11 (P < 0.001) decrease in cutaneous perfusion. Corresponding responses to LBNP of 20 mm Hg were 17 +/- 5% (P < 0.01) and 37 +/- 10% (P < 0.01) reductions in jejunal mucosal and skin perfusion, respectively. Cardiac index was significantly reduced by the LBNP procedure, whereas heart rate remained unchanged and blood pressure changes were minor and inconsistent. These findings indicate that the reflex vasoconstriction induced by mild central hypovolemia includes a significant reduction of jejunal mucosal perfusion in supine resting humans. This reflex may provide one mechanism for the intestinal ischemia often occurring in critically ill patients.

Habitual snorers and sleep apnoics have abnormal vascular reactions of the soft palatal mucosa on afferent nerve stimulation.

A local disturbance in the afferent nerves involved in the reflexogenic dilation of the upper airways (UAs) could contribute to the increased collapsibility seen in patients with obstructive sleep apnea (OSA). Laser Doppler perfusion monitoring, combined with electrical stimulation, is a method for investigating the afferent nerve regulation of the microcirculation. It was used in the mucosa of the soft palate in 35 patients with various degrees of UA obstruction and in 13 control subjects, all nonsmoking men. In a majority of snorers and patients with mild OSA, stimulation induced an exaggerated vasodilation, compared with controls. In contrast, in patients with severe OSA, the vasodilation was significantly reduced, compared with controls. These signs of disturbances in the microcirculation support the hypothesis of a local progressive afferent nerve lesion in heavy snorers with or without OSA.

Acute microcirculatory changes after scalding of the rat paw.

A scalding model in the anaesthetized rat was used to measure acute circulatory reactions after heat exposure. Local blood flow of both hindpaws was recorded simultaneously and continuously by laser Doppler flowmetry before, during and for 2 hours following scalding. The scalding injury was inflicted by dipping the right hindpaw into hot water at 60 degrees C for 20 s. Concomitantly, the mean arterial blood pressure (MAP) was displayed on a chart recorder. MAP was obtained by cannulation of the common carotid artery. Oedema formation was calculated by measuring the volume changes of the hindpaws in a plethysmometer before and 30, 60 and 120 min after scalding. Scalding was followed by a biphasic increase of cutaneous circulation. During the first minute after heat provocation, an immediate increase in blood perfusion of about 400% was recorded, followed by a slow decrease of circulation. At 30 min after scalding, there was a secondary phase of increased microcirculation of approximately 230%. A slow decline of cutaneous circulation then followed, and after about 60 min the value was stabilized at approximately 100% above pre-burn level throughout the observation time. Almost no change of perfusion was observed on the contralateral unscalded paw. The scalding injury was followed by a progressive oedema formation on the scalded paw, measured by a volume increase of approximately 72% during the observation period, whereas the non-scalded paw showed no change. MAP remained at a stable level throughout the experiment except for a short-lasting transient increase of approximately 10% at the same time as the first peak of blood perfusion. We could thus confirm that scalding in the present model is accompanied by an immediate and marked increase in the peripheral circulation of the scalded paw followed by a later propagation of oedema, and that these inflammatory changes do not appear to be related to central haemodynamic alterations.

Abnormal afferent nerve endings in the soft palatal mucosa of sleep apnoics and habitual snorers.

Habitual snoring precedes obstructive sleep apnea (OSA), but the pathophysiological mechanisms behind progression are still unclear. The patency of upper airways depends on a reflexogen mechanism reacting on negative intrapharyngeal pressure at inspiration, probably mediated by mucosal receptors, i.e., via afferent nerve endings. Such nerves contain a specific nerve protein, protein-gene product 9.5 (PGP 9.5) and in some cases substance P (SP) and calcitonin gene-related (CGRP). Biopsies of the soft palatial mucosa were obtained from non-smoking men ten OSA patients, 11 habitual snorers and 11 non-snoring controls. The specimens were immunohistochemically analyzed for PGP 9.5, SP and CGRP. As compared to controls, an increased number of PGP-, SP- and CGRP-immunoreactive nerves were demonstrated in the mucosa in 9/10 OSA patients and 4/11 snorers, in addition to varicose nerve endings in the papillae and epithelium. Using double staining methodology, it could be shown that SP- and CGRP-like immunoreactivities (LIs) often coexisted in these fibres, as did CGRP- and PGP 9.5-LIs. The increased density in sensory nerve terminals are interpreted to indicate an afferent nerve lesion. Our results support the hypothesis of a progressive neurogenic lesion as a contributory factor to the collapse of upper airways during sleep in OSA patients.

Semi-invasive laser-Doppler flowmetry technique. New application for recordings of hemodynamics in combination with manometry of human small intestine.

A small-bowel manometry tube was supplied with two single-fiber microprobes, which recorded blood flow in the proximal small intestine by the laser-Doppler flowmetry (LDF) technique. In all experiments, saline was infused intravenously as control during the first migrating motor complex (MMC) cycle, and a drug or another saline control given intravenously during the second MMC cycle. Recordings were performed during phase 1 of MMC, i.e. when motor pattern showed quiescence. Adrenaline increased blood perfusion values by 140% in proximal duodenum and 95% in distal duodenum. The alpha 2-adrenoceptor agonist clonidine decreased the corresponding values by 34 and 25%, respectively, while oxymetazoline decreased perfusion by 33 and 44% at the same levels. The beta-adrenoceptor agonist isoprenaline increased blood perfusion values by 172% in the proximal duodenum and 194% in the distal duodenum, whereas the antagonist propranolol decreased the corresponding values by 45 and 52%, respectively. In a separate group of subjects, propranolol was given after adrenaline. The increase in blood perfusion regularly seen after adrenaline was blocked after propranolol administration. In conclusion, our findings validate semi-invasive LDF technique for studies of hemodynamics in human small intestine under basal motor conditions and in drug-induced blood flow changes.

Photochemically induced ischaemic lesion of the rat sciatic nerve. A novel method providing high incidence of mononeuropathy.

The incidence of behavioural signs of mononeuropathy in rats subjected to chronic constriction injury (CCI) of the sciatic nerve is unpredictable and often low. In the present study, an ischaemic lesion of the rat sciatic nerve was induced photochemically using a low power laser. In these rats tactile allodynia developed with a considerably greater incidence (95%) than in control rats subjected to CCI (45%). The allodynia lasted longer and was more prominent. Responses to thermal stimulation did not markedly differ between the two groups. The ischaemic lesions displayed marked degeneration, particularly of large myelinated fibres. The results suggest that laser irradiation of a peripheral nerve inducing a local photochemical reaction followed by Wallerian degeneration may be a convenient and reproducible experimental method of producing signs of peripheral mononeuropathy.

Facilitated diffusion by iontophoresis of vasoactive agents to the rat incisor pulp.

The use of iontophoresis for facilitated diffusion of vasoactive agents into the dental pulp was investigated in lower incisor teeth of anaesthetized rats. Acetylcholine, carbachol and noradrenaline were iontophoresed with anodal and sodium nitroprusside with cathodal direct current through a superficial dentin exposure. Pulpal blood flow was measured with laser Doppler flowmetry. Current intensities below 100 microA of both polarities, using sodium chloride as a medium, caused no or minor afferent nerve-induced vasodilation, but excited sympathetic fibres of the pulp in a current-dependent manner. The current threshold for facilitated diffusion of acetylcholine was about 20 microA. The vascular responses to the cholinergic and noradrenergic drugs appeared within a minute after the onset of current and they were abolished by systemic administration of atropine and phenoxy benzamine, respectively. Iontophoresis of acetylcholine (40-100 microA for 20-120 s) caused a 3-fold increase of pulpal blood flow which was not dose-dependent; carbachol provoked a high-magnitude, long-lasting vasodilation and so did sodium nitroprusside. Noradrenaline caused a long-lasting vasoconstriction. In denervated rats iontophoresis of carbachol had effects similar to those seen in intact animals. None of the drugs used locally had any effect on systemic blood pressure. The results of this study indicate that iontophoresis can be used for delivery of vasoactive agents from an exposed dentin surface into the pulp in sufficient quantity to elicit drug-specific local vascular responses without causing systemic vascular effects.

Haemodynamic changes in the small intestine correlate to migrating motor complex in humans.

OBJECTIVE: To evaluate local intestinal blood flow and its relationship to fasting gut motility in humans. DESIGN AND METHODS: Regional laser Doppler flowmetry (LDF) was carried out for 8 h in 14 tasted volunteers. LDF measured as perfusion units (PU) was performed using two single-fibre microprobes attached to a small intestinal manometry tube, which monitored migrating motor complexes (MMCs). Luminal pressures of small intestine were registered in analogue and digital recordings. RESULTS: During phase 1 of MMC, PU values of 65 (33-95) and 37 (20-100) in proximal and distal duodenum were measured. During phase 2, PU values increased by 17% and 38%, respectively (each P < 0.001). At phase 3 of MMC, corresponding PU values increased by 363% and 443% (each P < 0.001) and remained at high levels until termination of phase 3. During phase 3 there was aboral propagation of LDF activity. Computerized recordings allowed detailed analysis of relationships between LDF pattern and luminal pressures. At pressures below 48 (42-54) mmHg, individual LDF cycles and contraction cycles were phase displaced at 180 degrees, indicating low perfusion during contractions. When pressures exceeded 48 (42-54) mmHg, a decrease in PU was registered and the cycling pattern of LDF was abolished. Then, as luminal pressure decreased below 33 (25-41) mmHg, PU increased by 246%. CONCLUSION: Our findings show a relationship between fasting motility and blood flow in the human gut, in which the blood flow exhibited a pattern similar to phase 1, 2 and 3 of the MMC.

Comparison of vascular effects of calcitonin gene-related peptide and lidocaine on human veins.

Arterial and venous constriction during microsurgery are among the leading causes of flap failure. So far, pharmacologic tools have been proposed only for arterial constriction, and local anesthetics are commonly used to counteract the vascular spasm. The purpose of this study was to investigate the vascular effects of two known arterial vasodilators on human veins, in order to evaluate the possibility of their potential use during microsurgery. In vitro experiments were performed on 31 greater saphenous vein (SV) rings obtained from 20 patients and on 12 cephalic vein (CV) rings from 7 patients. The rings were mounted in organ baths and their isometric contractile activity was measured. Experiments were conducted by cumulatively adding calcitonin gene-related peptide (CGRP) or lidocaine to the organ baths. The endothelium was mechanically removed in 18 SV rings and in 6 CV rings. Results demonstrated that in vitro CGRP produced vasodilation only; no constrictive effects were seen. Lidocaine produced a biphasic response with contraction at low concentrations (1.5 x 10(-5) M, 1.5 x 10(-3) M) and release of the maximal contraction at higher concentrations, similar to that observed in arteries. Removal of the endothelium did not significantly affect contractile activity in either CGRP- or lidocaine-treated vessels. The data supported the conclusion that CGRP could be used to relieve venous constriction, and it is suggested that further studies on the clinical use of CGRP in microsurgery is warranted.

Continuous measurement of changes in regional cerebral blood flow following cortical compression contusion trauma in the rat.

Laser Doppler flowmetry (LDF) was used to study acute ipsilateral and contralateral disturbances of regional cerebral blood flow (rCBF) in a rat model of cerebral cortical contusion trauma. Twelve rats were intubated and artificially ventilated during and after trauma. Injury was produced with a weight drop technique (21 g from 35 cm) allowing 1.5 mm maximum compression of the right parietal cortex. Stationary laser Doppler probes were used for continuous blood flow measurements on the ipsilateral side adjacent to the traumatized tissue and on the contralateral side. Within 2 min blood flow decreased to 60% (+/- 9%) of the pretrauma rCBF level on the ipsilateral side and remained at this level for at least 20 min. On the contralateral side there was an initial increase to 172% (+/- 27%) at 4 min. This hyperperfusion phase was followed by a mild hypoperfusion phase with a flow of 78% (+/- 8%) of baseline, lasting approximately 60 min. An attempt was made to measure rCBF++ within the trauma site using a removable probe. We found that probe replacement in traumatized (as compared to control) animals caused a baseline shift with a considerable variability making interpretation difficult. However, the pattern of rCBF change did not differ from the measurements adjacent to the injury site. We tentatively conclude that the posttraumatic hypoperfusion phase was similar within the trauma region. The observed rCBF changes following trauma are similar to those seen following cortical spreading depression (CSD). We propose that CSD, known to occur on the ipsilateral side in our model, is one of the factors involved in acute blood flow decreases seen following cerebral trauma.