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.

Inhibitory effects of tachykinin receptor antagonists on thermally induced inflammatory reactions in a rat model.

Recent studies have proposed that activation of the sensory nervous system after thermal injury induces the release of vasoactive neuropeptides, including tachykinins which contribute to the local inflammatory reaction as well as to the nociceptive transmission at the spinal cord level. Effects of the tachykinins substance P and neurokinin A are mediated by the neurokinin 1 and 2 (NK1, NK2) receptors. The aim of the present study was to investigate the modulatory role of NK1 and NK2 antagonists on edema formation, and on hindpaw withdrawal latency to experimentally asses nociception. Thermal injury was inflicted on the anaesthetized rat by dipping the right hindpaw into hot water at 60 degrees C for 20 s. The amount of edema formation was calculated by measuring the hindpaw volume with a plethysmograph before and during 420 min after scalding. In other studies scalding was inflicted under brief anesthesia, and hindpaw withdrawal latencies (HWL) to mechanical stimulation were recorded before injury and at 180 min after. The effect on edemic reactions of rats treated locally with NK1 and NK2 receptor antagonist were studied, as well as the effect of the same compounds on HWL after intrathecal injection. Scalding induced a progressive edema formation which was reduced significantly in rats treated with local injection of 100 nmol of NK1 and NK2 antagonists 45 min after the injury. The thermally induced inflammation was followed by significant decrease of the latency of hindpaw withdrawal response to mechanical stimulation. Intrathecal injection of 30 nmol of the same drugs 180 min after scalding was followed by significant increase in HWL. The results indicate that SP and NKA contribute to the inflammatory reactions after thermal injury and that the tachykinin receptor antagonists possess the ability to reduce both the local edemic reaction as well as the nociceptive transmission at the spinal cord level.

Effects of calcitonin gene-related peptide on tissue survival, blood flow and neutrophil recruitment in experimental skin flaps.

Local administration of calcitonin gene-related peptide (CGRP) has been shown to improve tissue survival in surgical skin flaps. Moreover, topical CGRP has been demonstrated to exert anti-inflammatory effects in different animal models of skin inflammation. The aim of the present study was to establish whether systemic treatment with low doses of CGRP may improve survival and reduce neutrophil accumulation in surgical skin flaps. Using a well-established dorsal skin-flap model in the rat, we found that intraperitoneal (i.p.) pretreatment with low doses of CGRP dose-dependently increased flap survival. Thus, in untreated animals flap survival at day 7 after surgery was 42%, as compared to 44%, 60%, 69% and 73% survival after a single preoperative i.p. injection of 10(-15), 10(-12), 10(-9) and 10(-6) mol CGRP, respectively (P < 0.05 versus control for the three highest doses). The three effective doses had no detectable effects on either flap blood flow (laser Doppler) or mean arterial blood pressure. On the other hand, 5 x 10(-9) mol CGRP i.p. significantly reduced the marked surgery-induced accumulation of flap myeloperoxidase (a marker for neutrophil recruitment) without affecting the circulating neutrophil count. Taken together, our findings demonstrate that low systemic doses of CGRP can cause a major improvement in skin-flap survival in the rat, possibly via inhibition of surgically induced neutrophil recruitment.

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.

Contribution of the sensory and sympathetic nervous system to scalding-induced edema in the rat paw.

It has recently been hypothesized that both the sensory and sympathetic nervous system contribute to the inflammatory reaction. A scalding model was developed in anaesthetized rats to investigate the contribution of neuropeptides in heat-induced edema localized to the hindpaw. After immersing the paw in water at 60 degrees C for 10, 20, 30 and 60 s, edemic reactions were registered as change of paw volume in a plethysmograph and hindpaw perfusates collected to measure the content of neuropeptides by radioimmunoassay. A scalding period of 30 s induced the most prominent edemic reaction. There was a marked increase of the sensory neuropeptide neurokinin A and the sympathetic related transmitter neuropeptide Y in hindpaw perfusates after scalding. The effect of peripheral nerve ligation on edemic reaction and on the release of neuropeptides was investigated in rats scalded for 30 s at 60 degrees C. There was a significant decrease of edema formation in the scalded nerve ligated paw as compared with the scalded paw on the non-ligated side. Neurokinin A was not detected in nerve ligated rats before or after scalding, whereas mononeuropathic rats showed increased concentrations of neuropeptide Y. The present results indicate that the sensory as well as the sympathetic nervous system, possibly through the release of neuropeptides, may contribute to scald-induced edema.

Opioids modulate the calcitonin gene-related peptide8-37-mediated hindpaw withdrawal latency increase in thermally injured rats.

The present study was performed to explore the modulatory potential of different endogenous opioid systems on transmission of presumed nociceptive information at the spinal cord level in thermally injured rats. Thermal injury was performed by dipping the left paw into water 60 degrees C for 20 s. This induced a significant bilateral decrease in hindpaw withdrawal latency HWL to pressure. Intrathecal administration of 10 nmol of CGRP8-37 induced a significant bilateral increase in HWL in the thermally injured group and in the intact controls. The effect of different opioid receptor antagonists on the increased latency to withdrawal response induced by intrathecal injection of 10 nmol of CGRP8-37 was explored in the thermally injured rats. The effect was reversed by intrathecal injection of 40 and 80 nmol of: b-funaltrexamine (mu opioid receptor antagonist) and naltrindole (delta opioid receptor antagonist), but not by norbinaltorphimine (kappa opioid receptor antagonist). The results of the present study show that intrathecal CGRP8-37 increases hindpaw withdrawal latency in thermally injured rats, an effect reduced by a mu as well as by a delta opioid receptor antagonist.

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.

Effects of environmental stress on tissue survival and neutrophil recruitment in surgical skin flaps in relation to plasma corticosterone levels in the rat.

OBJECTIVE: Because glucocorticoid treatment can improve the survival of surgical skin flaps, we examined the influence of environmental stress on skin flap survival in the rat. MATERIAL: Female Sprague-Dawley rats. TREATMENT: Dexamethasone (1 mg/kg i.p.). METHODS: A standardized dorsal skin flap was raised and sutured back into position, and six days latter the percentage of flap survival was assessed. Corticosterone in rat plasma was measured using radioimmuno assay, and skin flap myeloperoxidase accumulation (reflecting neutrophil recruitment) was determined spectrophotometrically. RESULTS: Skin flap survival decreased gradually during a 10 day acclimatization period after transportation of the animals from the supplier, and plasma corticosterone levels were increased during the first 5 days of acclimatization compared to day 7 and 10. Dexamethasone treatment of rats accustomed to their new environment for 10 days increased flap survival to a level close to that observed in animals operated at day 1 after arrival. Flap surgery induced pronounced neutrophil recruitment into flap tissue, and this cell accumulation was greatly reduced in both the dexamethasone treated rats and in rats with elevated corticosterone levels. CONCLUSIONS: Skin flap survival in rats exposed to environmental stress may be significantly increased as compared to animals accustomed to their new environment for one week, possibly as a consequence of anti-inflammatory actions exerted by stress-induced elevations in plasma corticosterone. These findings emphasize the importance of strictly controlling environmental stress factors in studies of inflammation and tissue damage after surgical skin trauma.

Intrathecal CGRP(8-37) results in a bilateral increase in hindpaw withdrawal latency in rats with a unilateral thermal injury.

The present study was performed to explore the effects of intrathecal administration of calcitonin gene-related peptide8-37 (CGRP(8-37)) on the hindpaw withdrawal latency (HWL) to pressure in rats with one thermally injured hindpaw. Furthermore, the interaction of CGRP(8-37)and naloxone was studied. Thermal injury was performed by dipping the left paw into 60 degrees C for 20 s. This induced a significant increase in the volume of the left hindpaw (P<0.001) and significant bilateral decreases of the latency of hindpaw withdrawal response to mechanical stimulation (Left: P<0.001; right: P<0.05). Intrathecal administration of 10, 20 and 40 nmol of CGRP(8-37), but not of 1 or 5 nmol, induced a significant bilateral increase in HWLs (P<0.001). The effect of CGRP(8-37) was partly reversed by intrathecal injection of naloxone at a dose of 32 and 64 microg respectively. Using radioimmunoassay, we found a significant bilateral increase in the concentration of CGRP-like immunoreactivity in the perfusate of both hindpaws 24 h after unilateral thermal injury (left: P< 0.001; right: P< 0.05). There was also an increase in the amount of CGRP-like immunoreactivity in the cerebrospinal fluid (P< 0.001), but not in plasma. The results indicate that CGRP plays a role in the transmission of nociceptive information in the spinal cord of thermally injured rats. Furthermore, our findings suggest that opioids can modulate CGRP-related effects in the spinal cord.

Limb-body wall complex with anophthalmos and choroidal coloboma.

A 23-year-old primigravida underwent induced abortion in the 17th week of pregnancy because ultrasound fetometry had indicated possible encephalocele/hygroma of the skull and deformities of limbs and abdominal wall. The fetus delivered showed a deep facial cleft, absence of nose and maxilla, absence of parietal and frontal bones, missing right upper extremity, and a large thoracoabdominal defect with herniation of internal organs. The placenta was large, with an amniotic fold across the fetal surface. The brain was holoprosencephalic with a midline monoventricle and with focal brain wall dysplasia. The right orbit and eye were absent. The left eye was microphthalmic, with an abnormal cornea, a large choroidal coloboma inferiorly, a dysplastic retina, and a cataractous spherical lens. Theories discussed are pathogenesis of the limb-body wall complex (LBWC) and ocular malformations, particularly uveal coloboma. Previous cases of anophthalmos and uveal coloboma are listed. Microscopic examination of the eye was performed in only one of these. The present case is the sixth case published of choroidal coloboma in association with the LBWC.

Uterine microcurettage with combined endometrial histopathology and cytology. An alternative to conventional curettage.

A new disposable mechanical curette, the Inocurette, was used to obtain endometrial samples for histopathology and cytology. The instrument was tested on 120 patients; 37 patients were known from a previous conventional curettage (D & C) to have an endometrial cancer and 83 patients were referred to the County Hospital of Trelleborg for curettage because of dysfunctional bleedings. In all 120 patients a D & C followed the microcurettage procedure. The samples were randomized, coded and analyzed blind without any clinical information. In all but 3 patients with a known endometrial cancer, sufficient microcurettage sample material for either histopathology or cytology was obtained. In all but one of these 34 patients either a malignant diagnosis or seriously atypical cells were found. Using only cytology five out of 34 samples were designated adequate but normal. In a further 5 of the 37 patients the samples obtained at the subsequent D & C were inadequate for diagnosis; one sample was denoted as normal. In the 83 patients with dysfunctional bleedings, sufficient material for diagnosis after microcurettage, cytology and D & C was obtained in 74, 83 and 79 patients respectively. One endometrial cancer was disclosed by all three methods. Inocurette sampling causes little discomfort and requires no special training. The combined microcurettage--cytology procedure may be recommended as an alternative to conventional curettage, though, for the time being, D & C should not be replaced for cytology alone.

Continuous transcutaneous carbon dioxide measurement from the fetal scalp during labor and during first minutes of extrauterine life.

An electrode for continuous transcutaneous carbon dioxide (tcPco2) monitoring was attached to the fetal scalp in 25 consecutive vaginal deliveries. In six patients the electrode fell off or was deliberately removed when the fetal head was on the pelvic floor, while eight patients were delivered with the electrode in situ, making it possible to study changes in the fetal carbon dioxide level when the fetus changed from placental to lung breathing. The mean recording time was 136 minutes (range 10-348). Fifteen patients were recorded until delivery and analysis of cord blood showed a statistically highly significant correlation between tcPco2 in both umbilical venous and arterial blood. The mean fetal tcPco2 during the late first stage of labor was 56 torr (range 40-75; n = 18). The post partum tcPco2 level in newborns was stable 20 minutes after delivery with a mean level of 51 torr (range 40-60). Fetuses with a normal fetal heart rate tracing showed a lower mean tcPco2 level than fetuses with fetal heart rate tracing abnormalities. The experience with the current technique indicates that both Apgar score and fetal heart rate tracing are rather crude methods to judge fetal blood gas status.

Site tenacity and nomadism in Tengmalm's owl (Aegolius funereus (L.)) in relation to cyclic food production.

In northern Sweden breeding males of Tengmalm's owls (Aegolius funereus (L.)) were site tenacious during and between the peaks of the vole (staple food) cycles, but females only during the peaks. Most of these adults shifted nest boxes between successive years. They selected nest boxes randomly in a radius of 3 km. Juveniles, in contrast to site tenacious adults, dispersed outside their natal area. The females moved longer than the males prior to their first breeding. Five adult females were found to be nomadic. One of these nomadic females previously bred site tenaciously as long as food was abundant. Juveniles and adult males were not found to be nomadic. Emigration of adult females and juveniles occurred most frequently when vole populations declined. The breeding population increased sharply and received immigrants suggesting that nomadism may be essential in the population dynamics. Site tenacity and nomadism are discussed in terms of costbenefit to males and females, respectively. Emphasis is on the main functional roles of males (feeding femle and young) and females (incubation).

Cycles in voles and small game in relation to variations in plant production indices in Northern Sweden.

Population dynamics for voles (Cricetidae), Tengmalm's owl (Aegolius funereus (L.)), red fox (Vulpes vulpes (L.)) willow grouse (Lagopus lagopus (L.)), black grouse (Lyrurus tetrix (L.)), capercaillie (Tetrao urogallus L.), hazel hen (Tetrastes bonasia (L.)), mountain hare (Lepus timidus L.) and tularemia (Francisella tularensis (McCoy & Chapin)) and game bird recruitment were studied by index methods in northern Sweden. In addition contemporary temperature records and spruce (Picea abies (L.) Karst.) and pine (Pinus silvestris L.) cone crops (as indices for plant production) and the occurrence of forest damage, caused by voles eating bark, were studied.During 1970-80 two synchronous 4-year cycles were observed for voles, predators (Tengmalm's owl and red fox) and their alternative prey species (grouse and mountain hare). In grouse the change of numbers was correlated with that of recruitment. Autumn vole numbers peaked about a year before the other species and extensive forest damage occurred at winter peak densities of voles. These population fluctuations are consistent with a predator-prey model for their regulation. In short the model suggests that vole-food plant interactions trigger the cycle of voles, that voles generate the cycle of predators and that these in turn synchronize alternative prey populations to the others at vole declines.For voles, grouse and red fox the amplitude was higher in the first cycle compared to the second one whilst the opposite was true for the mountain hare. Although temperature and cone crops showed large interannual variations they still implied that herbivore food conditions were 'better' during the former cycle. Hence, the reduction of the amplitude of the vole cycle may be explained by inter-cyclic differences in plant food conditions, implying food shortage (as indicated by bark-eating) at different population levels. The similar decrease of grouse and red fox populations may also be explained by deteriorated food conditions and/or for the fox by an outbreak of sarcoptic mange (Sarcoptes scabiae var. vulpes). The increased amplitude of the mountain hare cycle was part of a long-term rise in numbers after a tularemia epidemic in 1967. This is interpreted as a recovery, probably towards the generally higher pre-epidemic population level.

Alveolar hypoventilation treated with medroxyprogesterone.

Two children aged 1 and 20 months developed alveolar hypoventilation syndrome. They suffered severe apnoeic episodes and periodically required assisted ventilation. Their ventilatory response to carbon dioxide was lower than that of normal children and the transcutaneous oxygen tension during sleep was well below the normal range. Treatment with medroxyprogesterone acetate resulted in an improved response to carbon dioxide, and assisted ventilation was no longer needed. Oxygen and carbon dioxide tensions improved but were still slightly abnormal during sleep. There were no clinical side effects of treatment but one infant had slight pituitary suppression.

Cardiotocographic distortion of fetal heart rate variability. Theoretical considerations and exemplification by computerized simulation.

The error arising when evaluating FHR variability on CTG curves is demonstrated. Visual estimation is based on the appreciation of oscillation amplitude (O.A.) which is necessarily dependent on basic heart frequency and the changes therein. It reflects variability in a distorted way--the distortion can be as great as 33% even when the basic heart frequency remains within the normal range of 120-160 beats per minute.

Subjective recording of fetal movements. I. Limits and acceptability in normal pregnancies.

Maternal counting of fetal movements is increasingly used as a clinical method for assessment of fetal health. The present study established normal limits for two methods of subjective fetal movement recording. Four hundred-and-seventeen randomly selected women with low-risk pregnancies recorded the time necessary for 10 fetal movements every morning and also the number of fetal movements during 15 min every evening. The study was carried out between gestational week 34 and parturition. Two hundred-and-twenty-two consecutive women answered a questionnaire after the end of the study. 70% of the women counted fetal movements every day; 66.5% preferred the evening to the morning recording. In a strictly selected normal group (n = 129), no significant change was found in the number of fetal movements or in the time for 10 fetal movements with advancing gestation or approaching parturition. The results of the evening sessions were not influenced by maternal parity, fetal weight, or fetal sex. The great interindividual variation in the results does not allow the application of general normal limits. A method for establishing individual normal low limits for each pregnancy was designed.

pH measurement from the fetus during labor--a task for the midwife?

After theoretical education on the development of fetal acidosis and the fetal blood sampling technique, 12 midwives in a training program carried out or assisted in 40 fetal blood sampling procedures. Sampling was possible at a cervical dilatation of 1.5 cm. 11/12 midwives were successful in their first sampling attempt. The instrument used for analysis was an automated microprocessor device with a minimum sampling volume of 15 microliter of blood. There was a statistically highly significant correlation between the results obtained with the instrument tested and the reference device (r = 0.9; n = 36). 82% of the measurements fell within +/- 0.04 pH units of the reference device. With the instrument placed in the labor room, and using the current technique with very small blood samples, it is possible to obtain a fetal pH value within 10 minutes after the development of a pathological fetal heart rate pattern.

Perinatal mortality: changes in the diagnostic panorama 1974-1980.

During the period 1974-1980, all late abortions (greater than 19 completed gestational weeks) (LA), late fetal deaths (LFD) and early neonatal deaths (END) were surveyed in a continuous material of 17813 births with an ascertained gestational age established by early ultrasound fetometry. There was no maternal death during the period. The total perinatal mortality (PM) was 0.98% with an END rate of 0.51%. In about 45% of LFD no diagnosis was found. Intrapartum death was extremely rare as was END caused by asphyxia or infection. In END, death from immaturity constituted the major group in the beginning of the period, while after 1977 lethal malformations was the dominating diagnosis. There was a continuous decrease in Idiopathic Respiratory Distress Syndrome (IRDS) as a cause of END. The proportion of END in extremely premature children showed a constant decrease in the beginning of the period. No difference in sex was found in END except for lethal malformations where there was a significant male preponderance. As a consequence of a more active obstetrical care, some fetuses who would previously have been classified as LA were probably delivered liveborn, extremely premature and appeared as END. The question of where to set the limits for what should be included in PM is thus highly relevant.