[Recurrent nevus: Case-report about a pagetoid form occurring from a congenital nevus in infancy]. / Une forme pagétoïde de pseudomélanome d'Ackerman secondaire à un naevus congénital dans l'enfance : à propos d'un cas.

INTRODUCTION: Recurrent nevus (RN) is a cutaneous benign tumour with similarities with malignant lesions. Typically, it occurs after a partial resection of commun-acquired nevus. Its incidence varies from 0.3 to 27% according to the studies. We present here a pediatric case of a pagetoid form of a recurrent nevus occurring from a congenital nevus. CASE REPORT: A congenital nevus was removed from a 9-month-old girl. Pathologists concluded to a commun-acquired nevus of complete exeresis. Two other cutaneous lesions appeared and we decided to realise a total removal. Analysis showed a recurrent nevus with some atypical histological features. No recurrence has occurred during the three post-operative of follow-up. DISCUSSION: It is an interesting case because of the occurrence of a RN after the removal of a congenital nevus in a child. Furthermore, it displayed some atypical histological features. Practicians, such as surgeons, dermatologists or pathologists, have to be aware of the risk of misdiagnosis with this lesion, which presents some similarities with SSM melanoma. It would be interesting to determinate some markers to statuate about its benign feature. There is no management recommendation about this lesion but it seems to be necessary to remove it to eliminate a malignant tumour.

The role of cigarette smoking and statins in the development of postmenopausal osteoporosis: a pilot study utilizing the Marshfield Clinic Personalized Medicine Cohort.

SUMMARY: A cohort of postmenopausal osteoporotic females and controls with normal bone mineral density, the interleukin 6 (IL6) -634G > C (rs1800796) C allele of the promoter region showed association with osteoporosis. The lipoprotein receptor-related protein 5 (LRP5) gene showed association between C135242T C/T alleles and osteoporosis only in smokers, suggesting a role for environmental interaction. INTRODUCTION: A nested case-control study within a population-based cohort was undertaken to assess the relative impact of cigarette smoking, statin use, genetic polymorphisms, and one-way interaction of these factors on development of osteoporosis in postmenopausal women. METHODS: Genotyping of 14 single-nucleotide polymorphisms (SNPs) corresponding to vitamin D receptor gene, estrogen receptor 1, collagen type 1 alpha 1, IL6, transcription growth factor beta, apolipoprotein E, and LRP5 genes was performed in cases (n = 309) with osteoporosis and controls (n = 293) with normal bone mineral density drawn from a homogeneous Caucasian population. SNPs were chosen based on known functional consequences or prior evidence for association and genotyped using matrix-assisted laser desorption ionization time-of-flight technology. RESULTS: Cases differed from controls relative to body mass index, age, and smoking but not statin use. After adjusting for age, the IL6 -634G > C (rs1800796) allele showed association with osteoporosis (odds ratio (OR) for CC + CG = 2.51, p = 0.0047)), independent of statin use or smoking status. On stratification for smoking, association with LRP5 C135242T (rs545382) and osteoporosis emerged (OR 2.8 in smokers for CT alleles, p = 0.03)), suggestive of potential environmental interaction. CONCLUSION: Evidence suggested a role for genetic variation in IL6 and LRP5 in conferring risk for osteoporosis in Caucasian women, with the latter manifest only in smokers.

Characterisation of the Selective Reduced Uteroplacental Perfusion (sRUPP) Model of Preeclampsia.

Preeclampsia is a complication of pregnancy characterised by gestational hypertension, proteinuria and/or end organ disease. The reduced uteroplacental perfusion (RUPP) model, via partial occlusion of the lower abdominal aorta, mimics insufficient placental perfusion as a primary causal characteristic of preeclampsia. However, a major limitation of the RUPP model is that perfusion is reduced to the entire hindquarters of the rat resulting in hindlimb ischemia. We hypothesised that clipping the uterine and ovarian arteries in the selective (s)RUPP model would provoke signs of preeclampsia while avoiding systemic ischemia. Sham, RUPP or sRUPP procedures were performed in pregnant Sprague Dawley rats on gestational day (GD)14. On GD21 uterine blood flow was significantly reduced in both the RUPP and sRUPP models while aortic flow was reduced only in RUPP. Both models resulted in increased MAP, increased vascular oxidative stress (superoxide generation), increased pro-inflammatory (RANTES) and reduced pro-angiogenic (endoglin) mediators. Vascular compliance and constriction were unaltered in either RUPP or sRUPP groups. In summary, refinements to the RUPP model simultaneously maintain the characteristic phenotype of preeclampsia and avoid peripheral ischemia; providing a useful tool which may be used to increase our knowledge and bring us closer to a solution for women affected by preeclampsia.

Isolated unilateral temporalis muscle hypertrophy: First case in an 8-year-old boy and review.

INTRODUCTION: Isolated unilateral temporalis muscle hypertrophy (IUTMH) was first described in 1990 and few cases have been published since then. This disease occurs mainly in adults. There is no clear etiology of IUTMH, but bruxism is one of the risk factors. Only two cases have been described before the age of 20 years. To our knowledge, no cases have been described in persons younger than 15 years old. We report the first case of IUTMH in an 8-year-old and review the literature. MATERIAL AND METHODS: This section is separated into 3 parts: (1) search for and description of clinical cases of IUTMH in our department; (2) literature search to find similar cases; (3) data analysis of all cases found. RESULTS: Ten patients, including our case, were found over a period of 23 years: five females and five males with a mean age of 32.8 years. One patient was 15 years old. Time between onset and diagnosis was 16.7 months. Half of the patients reported pain and three had experienced bruxism. Most of the patients had non-surgical treatment. One patient evolved favorably with no treatment. One recurrence occurred 10 years later. DISCUSSION: IUTMH can occur in childhood in a high-stress environment. Diagnosis is based on the history and clinical and imaging findings. Biopsy helps to confirm the diagnosis, but electromyograms and neurological tests contribute little. Bruxism should be taken into account. The treatment with the least inconvenience must be given.

Carcinoma cuniculatum of the lip: A case report.

Carcinoma cuniculatum, a very well differentiated sub-type of epidermoid carcinoma, is a rare invasive tumor with a low risk of metastasis. It principally affects the lower limbs, notably the soles of the feet. Facial involvement is exceptional. A case of a patient with carcinoma cuniculatum of the lower lip is presented and diagnostic difficulties of head locations of this tumor, as well as their management are discussed.

Classification proposed of malignant intraosseous odontogenic tumors (MIOT).

Malignant intraosseous odontogenic tumors (MIOT) of the jaws are very rare. The diagnosis is difficult. Clinical, paraclinical and histological diagnostic criteria, strict are well established. But the International Union Against Cancer (UICC) does not provide TNM classification that will allow harmonization of the treatment. Indeed, despite their location, they cannot be classified as primary tumors of the oral cavity because of their localization in the bone marrow, making them systematically classified as T4. We propose a classification taking into account the clinical and radiological data.

[Traumatic superior orbital fissure syndrome: Update]. / Syndrome de la fissure orbitaire supérieure post-traumatique : mise au point.

The traumatic superior orbital fissure syndrome is an uncommon complication of craniomaxillofacial trauma. The diagnosis is clinical and associates ophtalmoplegia (constantly at initial clinical examination), ptosis and anaesthesia of the forehead. Young men victim of road traffic accidents are most often affected. CT-scan usually shows facial and/or craniofacial fractures more or less spreading towards the superior orbital fissure. The absence of fracture seen at the X-rays does not eliminate the diagnosis. Initial management should be multidisciplinary (maxillofacial surgeons, ophthalmologists and neurosurgeons) and conducted early if possible. It combines high-dose corticosteroids and decompression surgery if necessary. Abstention may be indicated in cases of delayed diagnosis with spontaneous improvement. Symptoms improve early but follow-up should be extended over several months given the recovery time.

Inducible nitric oxide synthase mediates delayed myocardial protection induced by activation of adenosine A(1) receptors: evidence from gene-knockout mice.

BACKGROUND: The mechanism of delayed preconditioning induced by activation of adenosine A(1) receptors (A(1)ARs) is not fully understood. We determined the role of inducible nitric oxide synthase (iNOS) in mediating adenosine-induced late cardioprotection using pharmacological inhibitors and iNOS gene-knockout mice. METHODS AND RESULTS: Adult male mice were treated with saline or an A(1)AR agonist, 2-chloro-N(6)-cyclopentyladenosine (CCPA). Twenty-four hours later, the hearts were perfused in Langendorff mode and subjected to 30 minutes of global ischemia followed by 30 minutes of reperfusion. 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX; 0.1 mg/kg IP) and S-methylisothiourea (SMT; 3 mg/kg IP) were used to block A(1)ARs and iNOS, respectively. Infarct size (IS) was measured by triphenyltetrazolium chloride staining, and iNOS expression was measured by Western blots. Myocardial IS was reduced from 24.0+/-3. 2% in the saline group to 12.2+/-2.5% in CCPA-treated mice (P<0.05). The infarct-reducing effect of CCPA was abrogated by DPCPX (29.3+/-3. 4%) and SMT (32.3+/-2.6%) and was absent in mice with targeted ablation of iNOS (23.9+/-1.6%). CCPA produced improvement in postischemic end-diastolic pressure, developed pressure, and rate-pressure product, which was also blocked by DPCPX and SMT. Increased iNOS protein expression observed in CCPA-treated hearts was diminished by DPCPX. CONCLUSIONS: Selective activation of A(1)ARs produces delayed cardioprotection against ischemia/reperfusion injury in the mouse. Increased iNOS expression concomitant with the lack of protective effect of A(1)AR activation in iNOS gene-knockout mice suggests a direct cause-and-effect relationship of iNOS in adenosine-induced late cardioprotection.

Peripheral extracorporeal membrane oxygenation (ECMO) in patients with posttransplant cardiac graft failure.

INTRODUCTION: We sought to report the usefulness of extracorporeal membrane oxygenation (ECMO) in heart transplant patients. PATIENTS: Between March 2002 and August 2004, 14 heart transplant patients (11 men and three women, 36 +/- 15 years old, range = 12 to 50) with primary graft failure underwent peripheral ECMO implantation. Three patients had pulmonary hypertension and three had been transplanted with hearts from marginal donors. At the time of implantation, all were in severe cardiogenic shock despite maximal inotropic support. In six patients, the ECMO was implanted in the operating room since cardiopulmonary bypass could not be weaned. In the eight remaining patients, ECMO was implanted in the intensive care unit, during the first 48 hours in seven cases. In one patient, implantation was performed during external resuscitation. In all cases, femoral vessels were canulated using the Seldinger technique after anterior wall exposure. Distal arterial perfusion of the lower limb was systematically used. RESULTS: Pump outflow was high enough in all the cases (mean: 2.6 +/- 0.2 L/min/m(2)). Three patients died on circulatory support. One patient was implanted with a total artificial heart after a few hours and another one underwent unsuccessful emergent retransplantation. Nine patients were weaned from ECMO after a mean duration of 5 +/- 2.5 days. Among them, one died of infection at 10 days after weaning and seven others were discharged to rehabilitation centers. CONCLUSION: Fast operating room or bedside implantation of a peripheral ECMO allows the physician to stabilize the hemodynamic status of patients with cardiac graft failure, potentially leading toward myocardial recovery.

Prevention of atrial fibrillation or flutter by acebutolol after coronary bypass grafting.

Supraventricular tachyarrhythmias are common after coronary artery bypass graft surgery (CABG) and may have deleterious hemodynamic consequences. To determine if acebutolol, a cardioselective beta-blocking drug, prevents such tachyarrhythmias after CABG, 100 consecutive patients, aged 30 to 77 years (mean +/- standard deviation 53 +/- 9), were entered into a randomized, controlled study. Exclusion criteria were: contraindications to beta-blocking drugs, left ventricular aneurysm, major renal failure, history of cardiac arrhythmia and cardiac arrhythmia during the immediate postoperative period. From 36 hours after surgery until discharge (usually on the seventh day), 50 patients were given 200 mg of acebutolol (or 400 mg if weight was more than 80 kg) orally twice a day (dosage than modified to maintain a heart rate at rest between 60 and 90 beats/min). The 50 patients in the control group did not receive beta-blocking drugs after CABG. The 2 groups were comparable in angina functional class, ejection fraction, number of diseased vessels, antianginal therapy before CABG, number of bypassed vessels and duration of cardiopulmonary bypass All patients were clinically evaluated twice daily and had continuous electrocardiographic monitoring and daily electrocardiograms. A 24-hour continuous electrocardiogram was recorded in the last 20 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Prosthetic valve endocarditis with ring abscesses. Surgical management and long-term results.

From January 1978 to December 1988, 71 patients underwent surgical intervention at our institution for prosthetic valve endocarditis with ring abscesses. These procedures involved 59 aortic prostheses and 12 mitral prostheses. No causative agent could be identified in 19 patients (26.7%). The operation was performed during antibiotic therapy in 63 patients and after a planned course of antibiotic therapy in 8 patients. At the aortic level, abscesses were remedied by suturing in 3 cases, by pericardial patches in 34 cases, and by complex procedures in 22 cases (subcoronary valved conduit in 11 cases, supracoronary valved conduit with coronary bypass grafts in 10 cases, apicoaortic valved conduit in 1 case). At the mitral level, ring abscesses were cured in 10 cases by intraatrial implantation of the prosthesis. In one case, the prosthesis was anchored inside the left ventricle; and in one case the valve could be seated on the anulus. The overall operative mortality rate was 17%. Long-term survival was 54% +/- 8% at 6 years. Fifteen (26%) of the survivors needed a third valve replacement (four operative deaths); a complex reconstruction was performed in seven patients. Better detection of ring abscesses and earlier surgical intervention before annular destruction and hemodynamic failure can improve the operative mortality rate for prosthetic valve endocarditis. When it is necessary, complex reconstruction, in spite of a high mortality rate, seems to eradicate the infectious seat, and the outlook for the patient's condition appears good.

Fluid percussion injury transiently increases then decreases brain oxygen consumption in the rat.

The oxygen consumption (VO2 microL/h/mg) of sham and of traumatized rat brains within 30 min and 6 h after a lateral fluid percussion injury (FPI) was measured with the Cartesian microrespirometer. Brain slices were cut at the plain of injury and site-specific 20-60-microg cores of tissue were transferred to the microrespirometer. In sham brains, the cortical VO2 (CVO2) was 13.78+/-0.64 and the hippocampal VO2 (HPVO2) was 11.20+/-0.58 microL/h/mg (p<0.05). Within 30 min of the injury, the respective values of 16.89+/-0.55 and 14.91+/-0.06 were significantly increased (p<0.05). The combined VO2 (CVO2, HPVO2) of 12.49+/-0.06 microL/h/mg in shams was significantly less than the combined VO2 of 15.90+/-0.59 microL/h/mg at 30 min post FPI (p<0.001). The maximal CVO2 of 19.49+/-1.10 microL/h/mg and the maximal HPVO2 of 15.98+/-0.99 microL/h/mg were both obtained from the ipsilateral side of the injury. Whereas the contralateral cortical value for injured brains was not significantly different from that of the shams, both ipsilateral and contralateral hippocampal values were significantly greater than that of the shams in response to injury (p<0.05). By 6 h postinjury, the combined VO2 had dropped to 10.01+/-0.84 microL/h/mg but was not significantly lower than the sham values. The data indicate that normal CVO2 is greater than normal HPVO2. The FPI produces significant increases in both CVO2 and HPVO2. Also, while the immediate increase in CVO2 appears to be injury-site dependent, that is, regional, the increase in HPVO2 appears to be global.

Bridge to transplantation with the Jarvik-7 (CardioWest) total artificial heart: a single-center 15-year experience.

BACKGROUND: At our institution, the total artificial heart (TAH) Jarvik-7 (CardioWest) has been used since 1986 as a bridge to transplantation for the most severely ill patients with terminal congestive heart failure. METHODS: Between 1986 and 2001, 127 patients (108 males, mean age 38 +/- 13) were bridged to transplantation with the Jarvik-7 TAH. All were in terminal biventricular failure despite high-dose inotropic support. Nine patients had a body surface area (BSA) of <1.6 m(2). In Group I patients (78%), the etiology of cardiac failure was dilated cardiomyopathy, either idiopathic (n = 60) or ischemic (n = 38). The other 29 patients (Group II) had disease of miscellaneous origin. We analyzed our experience with regard to 3 time periods: 1986 to 1992 (n = 63); 1993 to 1997 (n = 36); and 1998 to 2001 (n = 33). RESULTS: Although Group II patients represented 30% of indications before 1992, they comprised only 15% during the 2 subsequent periods. Duration of support for transplant patients increased dramatically after 1997, reaching 2 months for the most recent period (5 to 271 days). In Group I, the percentage of transplanted patients increased from 43% before 1993 to 55% between 1993 and 1997, and reached 74% thereafter. The major cause of death was multiorgan failure (67%). The clinical thromboembolic event rate was particularly low with no instance of cerebrovascular accident and 2 transient ischemic attacks. Total bleeding complication rate was 26%, including 2 deaths related to intractable hemorrhage and 2 others related to atrial tamponade. The cumulative experience was 3,606 total implant days with only 1 instance of mechanical dysfunction. CONCLUSIONS: TAH is a safe and efficient bridge for patients with terminal congestive heart failure awaiting cardiac transplantation.

Induced mitochondrial failure in the feline brain: implications for understanding acute post-traumatic metabolic events.

OBJECTIVE: Recently, evidence has become available implicating mitochondrial failure as a crucial factor in the pathogenesis of acute brain damage following severe traumatic brain injury (TBI). However, it remains unclear how mitochondrial dysfunction affects cerebral metabolism. Therefore the aim of the study was to evaluate the impact of 'isolated' mitochondrial failure on local cerebral metabolism. METHODS: Cerebral mitochondrial metabolism was blocked by local microdialysis perfusion with cyanide in seven cats. Local brain tissue oxygen tension (p(tiO(2))), carbon dioxide tension (p(tiCO(2))) and pH, as well as extracellular cerebral fluid, glucose, lactate, pyruvate and glutamate were monitored, using a Neurotrend sensor and microdialysis, respectively. Tissue oxygen consumption was measured in a microrespirometric system, and ultrastructural changes evaluated via electron microscopy. RESULTS: Brain tissue oxygen tension increased from a baseline of 31+/-9 mmHg to 84+/-30 mmHg after 60 min of cyanide perfusion (P<0.05), concomitant a decrease in oxygen consumption from 14.45+/-3.91 microl/h/mg to 10.83+/-1.74 microl/h/mg (P<0.05). Brain tissue pH was decreased after 60 min of cyanide perfusion (6.83+/-0.16) compared to baseline (7.07+/-0.39) (P<0.05), whereas p(tiCO(2)) did not show significant changes. Lactate massively increased from a baseline of 599+/-270 micromol/l to 2609+/-1188 micromol/l immediately after cyanide perfusion (P<0.05). The lactate:glucose ratio increased from 0.79+/-0.15 before cyanide perfusion to 6.40+/-1.44 at 40 min after cyanide perfusion (P<0.05), while no significant changes in the lactate:pyruvate ratio could be observed. Glutamate increased from a baseline of 11.6+/-7.2 micromol/l to 61.4+/-44.7 micromol/l after cyanide perfusion (P<0.05). CONCLUSION: The results of this study show that 'isolated' cerebral mitochondrial failure initiates changes in cerebral substrates and biochemistry, which are very similar to most of the changes seen after severe human head injury, except for the early fall in p(tiO(2)), further indicating a crucial involvement of mitochondrial impairment in the development of brain damage after TBI.

Effects of respiratory gases on cytochrome A in intact cerebral cortex: is there a critical Po2?

Changes in the redox level of cytochrome a and in the amount of oxygenated hemoglobin were measured by dual wavelength reflectance spectrophotometry in the intact cerebral cortex of cats (cerveau isolé preparation) and in unanesthetized rabbits with chronically implanted cranial windows. Increases in inspired oxygen were accompanied by an increase in the oxidation level of cytochrome a and an increase in the amount of oxygenated hemoglobin in the optical field. These changes were larger in the presence of 5% CO2. Reduction of the inspired oxygen concentration produced a decrease in the oxidation/reduction ratio of cytochrome a and a disoxygenation of hemoglobin. The presence of CO2 at these lower oxygen levels diminished the reduction of cytochrome a and the disoxygenation of hemoglobin. These data indicate that, in the resting subject, the reduction levels of cytochrome a are well above the low values seen in isolated mitochondria. They also indicate that the blood supply to the cerebral cortex is regulated at a level of slight hypoxia.

Oxidative metabolic activity of cerebral cortex after fluid-percussion head injury in the cat.

To assess the metabolic and vascular effects of head trauma, fluid-percussion pressure waves were transmitted to the brains of anesthetized, paralyzed, and artificially ventilated cats. Changes in the redox state of cytochrome a,a3, and relative local blood volume were measured in situ by dual-wavelength reflection spectrophotometry of the cortical surface viewed through an acrylic cranial window implanted within the closed skull. Initial fluid-percussion impacts of 0.5 to 2.8 atm peak pressure produced consistent transient oxidation of cytochrome a,a3 and increases of cortical blood volume. These changes occurred despite the presence of transient posttraumatic hypotension i some cases. Also, impact-induced alterations of vascular tone occurred, independent of the presence or absence of transient hypertension in the posttraumatic period. These data demonstrate that hypoxia does not play a role in the immediate posttraumatic period in cerebral cortex, and are consistent with the idea that after injury there is increased cortical energy conservation. These data also support the concept that head trauma alters the relationship of metabolism and cerebral circulation in the period immediately after injury.

Combined effect of respirator-induced ventilation and superoxide dismutase in experimental brain injury.

The function-specific enzyme superoxide dismutase (SOD) was tested for its protective effect in severe experimental fluid-percussion brain injury (4.45 +/- 0.10 atm) in 30 of 60 randomly selected male Sprague-Dawley rats. A respirator was used only in the event of need. The number of animals with permanent resumption of spontaneous breathing (Type I respiratory response) remained essentially the same in each group. However, when Type II apnea (cannot maintain recovery) and Type III apnea (never recovers from the initial apnea) were terminated with a respirator, all rats with Type II responses from each group were successfully converted to a state of sustained spontaneous breathing. In contrast, only five (41.7%) of the 12 rats with Type III response were salvaged in the control group while five (83.3%) of six Type III rats in the SOD-treated group were saved. The results reveal the nature of the therapeutic effectiveness of superoxide radical scavengers in the overall outcome of head injury in this animal model. While SOD alone did not increase the number of spontaneous survivors, the drug shifted a number of animals from the critically injured rats with Type III respiratory response to the less critical Type II condition. Whereas induced respiration as the sole therapy in the control group lowered the mortality rate to 23.3%, respiratory assistance together with SOD treatment reduced the "mortality" to a single animal with Type III apnea (3.3%) which was alive but still required the respirator after 2 hours (p less than 0.001). The results show that respiratory assistance alone accounted for a 33% decrease in mortality rate and that SOD, given in addition to induced ventilation, further decreased mortality by 20%. Since SOD enzymes are reactively specific for superoxide, the increased survival rate of the brain-injured rat must have been due either to preventing or to minimizing pathophysiological changes, probably in the brain stem, caused by oxygen free radicals.

Effect of neonatal capsaicin treatment on neurogenic pulmonary edema from fluid-percussion brain injury in the adult rat.

The frequent occurrence of acute death from pulmonary failure in experimental head injury studies on Sprague-Dawley rats prompted an investigation into the manner in which acute neurogenic pulmonary edema develops in these animals as a result of an applied fluid pressure pulse to the cerebral hemispheres. Studies were performed in adult animals using histamine H1 and H2 blocking agents, or in adult animals treated as neonates with capsaicin to destroy unmyelinated C-fibers. Recordings were made of either the pulmonary arterial or the right ventricular pressure, and the left atrial and femoral arterial pressures before, during, and after injury to provide a record of the hemodynamic response throughout the development of neurogenic pulmonary edema. Head injury triggered the almost immediate development of pressure transients with and without neurogenic pulmonary edema. All rats, regardless of treatment, reacted with nearly identical systemic arterial pressure responses; however, the pulmonary responses followed a time course that was independent of systemic arterial pressure changes. Acute neurogenic pulmonary edema was always associated with a substantial increase in pulmonary arterial and left atrial pressures; conversely, pressure increases of similar magnitude were not always associated with edema. Histamine H1 and H2 blockers significantly reduced the pulmonary pressure surges only in rats free of neurogenic pulmonary edema. All capsaicin-treated rats showed suppressed pulmonary pressure responses, normal lung water content, elevated lung surface tension, and significantly reduced levels of immunoreactive substance P in the spinal cord and vagus nerve. While the pressures cannot clarify how edema influences the observed hemodynamics, they do not support the view that edema is the direct consequence of pulmonary hypertension. It is proposed that neurogenic pulmonary edema is a functional disturbance provoked by adverse stimuli from outside the lungs and that in the rat the primary afferent fiber is essential to the production of this entity.

Pial arteriolar vessel diameter and CO2 reactivity during prolonged hyperventilation in the rabbit.

Hyperventilation reduces intracranial pressure (ICP) acutely through vasoconstriction, but its long-term effect on vessel diameter is unknown. In seven rabbits with a cranial window implanted 3 weeks earlier, the effect of prolonged hyperventilation on vessel diameter was studied. Anesthesia was maintained for 54 hours with a pentobarbital drip (1 mg/kg/hr). The pH, CO2, and HCO3- levels were measured in arterial blood and cisterna magna cerebrospinal fluid (CSF). The diameter of 31 pial arterioles was measured with an image splitter. After baseline measurements, pCO2 was reduced from 38 to 25 mm Hg and allowed to return to 38 mm Hg for 10 minutes every 4 hours. There was an initial vasoconstriction of 13%, which progressively diminished by 3% every 4 hours. Thus, by the 20th hour, vessel diameters at a pCO2 of 25 mm Hg had returned to slightly above baseline values obtained at a pCO2 of 38 mm Hg. The temporary return of pCO2 to 38 mm Hg every 4 hours caused vasodilation: 12% at 4 hours, gradually increasing to 16% at 52 hours. Thus, at 52 hours, the vessel diameters were 105% of baseline at a pCO2 of 25 mm Hg and increased to 122% at a pCO2 of 38 mm Hg. Arterial pH had returned to baseline at 20 hours, and CSF pH had returned at 24 hours. Bicarbonate in blood and CSF remained decreased throughout the experiments. In three control experiments during which normocapnia was maintained, vessel diameter and pH and bicarbonate levels remained unaltered over the same period. The CO2 reactivity, tested by brief periods of hyperventilation every 4 hours, also did not change. These results indicate that hyperventilation is effective in reducing cerebral blood volume for less than 24 hours and that it should be used only during actual ICP elevations. If used preventively, its effect may have worn off by the time ICP starts to rise for other reasons, and further decreases in pCO2 cannot be obtained. Moreover, the reduction in buffer capacity with lower bicarbonate renders the vessels more sensitive to changes in PaCO2. This could lead to more pronounced elevations in ICP during transient rises in PaCO2, such as during endotracheal suctioning in head-injured patients.

Effect of indomethacin pretreatment on acute mortality in experimental brain injury.

The effect of indomethacin administration on the mortality rate of brain-injured rats was studied in four groups of animals subjected to a level of injury with a fluid-percussion apparatus predetermined to cause 50% mortality (50% lethal dose, or LD50). There were 24 animals in each of the following groups: 1) a control group, on which the LD50 was evaluated; 2) an ethanol-treated group with a mean blood serum level of 0.32 +/- 0.03 gm% (+/- standard error of the mean); 3) an indomethacin-treated group at a dose level of 3 mg/kg body weight administered intraperitoneally 10 to 15 minutes before injury; and 4) an indomethacin/ethanol-treated group. Significant differences in mortality rates were found in these experimental groups; namely, 50%, 58%, 8.3% (p less than 0.005), and 25% (p less than 0.05), respectively. The predetermined LD50 level of a 2.5- to 2.6-atm peak pressure pulse produced immediate apnea in all animals, which was either sustained (Type III), followed by temporary respiratory recovery (Type II), or followed by permanent resumption of breathing (Type I). The most important effect of indomethacin on respiratory function was manifested by a much higher percentage of Type I respiratory responses and a much lower percentage of Type II and III responses (hence a lower mortality rate). There was also a more rapid return to normal breathing in the postapneic period of recovery. Suppression of prostaglandin synthesis and of superoxide anion production at the of trauma may explain, at least in part, these favorable effects of indomethacin.