[Clinical characteristics and follow-up of 60 patients with recent diagnosis of giant cell arteritis, NEWTON study]. / Caractéristiques et profils évolutifs des patients avec un diagnostic récent d'artérite à cellules géantes, étude NEWTON.

INTRODUCTION: The management of giant cell arteritis (GCA) has evolved with the arrival of tocilizumab (TCZ) and the use of PET/CT. Our objective is to describe the characteristics and followup of patients with recent diagnosis of GCA in current care. PATIENTS AND METHODS: The NEWTON cohort is a monocentric retrospective cohort based on data collected from 60 GCA patients diagnosed between 2017 and 2022 according to the ACR/EULAR 2022 criteria. RESULTS: The median age at diagnosis was 73 [68.75; 81] years old. At diagnosis, the main manifestations were unusual temporal headaches in 48 (80 %) and an inflammatory syndrome in 50 (83 %) patients. Temporal artery biopsy confirmed the diagnosis in 49/58 (84 %) patients. Doppler of the temporal arteries found a halo in 12/23 (52 %) patients. The PET/CT found hypermetabolism in 19/43 (44 %) patients. Prednisone was stopped in 17.5 [12.75; 24.25] months. During follow-up, 22 (37 %) patients received TCZ. At least one complication of corticosteroid therapy was observed in 22 (37 %) patients. After a median follow-up of 24 [12; 42] months, 25 (42 %) patients relapsed. At the end of the follow-up, 29 (48.3 %) patients were weaned from corticosteroid therapy and 15 (25 %) were on TCZ. CONCLUSION: Despite the increasing use of TCZ in the therapeutic arsenal and of the PET/CT in the imaging tools of GCA patients, relapses and complications of corticosteroid therapy remain frequent, observed in more than a third of patients.

Characteristics of deep vein thrombosis in the critically ill COVID-19 patient - an observational cohort study with Doppler ultrasound measurements.

OBJECTIVE: COVID-19 is associated with an increased prevalence of deep venous thrombosis (DVT), mainly in the lower limbs. However, the characteristics and rheological conditions, which contribute to facilitating DVT occurrence have been poorly investigated. We aimed to report DVT characteristics, vein diameters and peak blood flow velocities (PBFV) in the common femoral veins (CFVs) of critically ill COVID-19 patients. PATIENTS AND METHODS: We conducted a prospective single-center cohort study in March-October 2020 including all consecutive mechanically ventilated COVID-19 adults. Doppler ultrasound of the lower limbs was performed systematically during the first week of hospitalization. In DVT-free patients, a second Doppler ultrasound was performed seven days later. Data are expressed as medians (interquartile ranges) or percentages. Comparisons were performed using Mann-Whiney and Wilcoxon signed-rank tests or Fischer's exact tests, as appropriate. RESULTS: Fifty-five patients [age, 63 years (56-74); female/male ratio, 0.62; body-mass index, 29 kg/m2 (26-33); hypertension, 47%; diabetes, 38%; ischemic heart disease, 11%] were included. DVT was diagnosed in 19 patients (35%) including in 5 femoral (9%), 2 popliteal (4%) and 12 below-the-knee sites (22%). CFV diameter was increased to 12.0 mm (11.0-15.0) (normal range, 9.1-12) and PBFV reduced to 11.9 cm/s (8.8-15.8) (normal range, 21.3-49.2) [right-side values]. In four patients who had ultrasound before intubation, CFV diameter increased from 12.5 mm (11.8-13.3) before to 14 mm (13.6-15.3) after intubation (p = 0.008). CONCLUSIONS: DVT in the CFV occurred in 9% of the critically ill COVID-19 patients with an overall 35%-DVT prevalence. Venous return difficulty evidenced by larger than normal CFV diameters and lower than normal PBFVs may have facilitated proximal DVT occurrence.

How to screen and diagnose deep venous thrombosis (DVT) in patients hospitalized for or suspected of COVID-19 infection, outside the intensive care units.

INTRODUCTION: The Coronavirus disease-2019 outbreak (COVID-19) has been declared a pandemic by the World Health Organization. Studies report both a severe inflammatory syndrome and a procoagulant state in severe COVID-19 cases, with an increase of venous thromboembolism, including pulmonary embolism (PE) and deep vein thrombosis (DVT). In this context, we discuss the use of doppler ultrasonography (DUS) in the screening and diagnosis of DVT in ambulatory and hospitalized patients with, or suspected of having, COVID-19, outside the intensive care unit (ICU). MATERIAL AND METHODS: Non-systematic review of the literature. RESULTS: In patients hospitalized for or suspected of COVID-19 infection with the presence of either (a) DVT clinical symptoms, (b) a strong DVT clinical probability (Wells score>2) or (c) elevated D-dimer levels without DVT clinical symptoms and without PE on lung CT angio-scan, DVT should be investigated with DUS. In the presence of PE diagnosed clinically and/or radiologically, additional systematic DVT screening using DUS is not recommended during the COVID-19 pandemic. The use of 4-points compression DUS for DVT screen and diagnosis is the most appropriate method in this context. DISCUSSION: Systematic DUS for DVT screening in asymptomatic COVID patients is not recommended unless the patient is in the ICU. This would increase the risk of unnecessarily exposing medical staff to SARS-CoV-2 and monopolizing limited resources during this period.

Imbalance between procoagulant factors and natural coagulation inhibitors contributes to hypercoagulability in the critically ill COVID-19 patient: clinical implications.

OBJECTIVE: Coronavirus Disease-2019 (COVID-19) predisposes patients to thrombosis which underlying mechanisms are still incompletely understood. We sought to investigate the balance between procoagulant factors and natural coagulation inhibitors in the critically ill COVID-19 patient and to evaluate the usefulness of hemostasis parameters to identify patients at risk of venous thromboembolic event (VTE). PATIENTS AND METHODS: We conducted an observational study recording VTEs defined as deep vein thrombosis or pulmonary embolism using lower limb ultrasound (92% of the patients), computed tomography pulmonary angiography (6%) and both tests (2%). We developed a comprehensive analysis of hemostasis. RESULTS: Ninety-two consecutive mechanically ventilated COVID-19 patients (age, 62 years [53-69] (median [25th-75th percentiles]); M/F sex ratio, 2.5; body-mass index, 28 kg/m2 [25-32]; past hypertension (52%) and diabetes mellitus (30%)) admitted to the Intensive Care Unit (ICU) from 03/11/2020 to 5/05/2020, were included. When tested, patients were receiving prophylactic (74%) or therapeutic (26%) anticoagulation. Forty patients (43%) were diagnosed with VTE. Patients displayed inflammatory and prothrombotic profile including markedly elevated plasma fibrinogen (7.7 g/L [6.1-8.6]), D-dimer (3,360 ng/mL [1668-7575]), factor V (166 IU/dL [136-195]) and factor VIII activities (294 IU/dL [223-362]). We evidenced significant discrepant protein C anticoagulant and chromogenic activities, combined with slightly decreased protein S activity. Plasma D-dimer >3,300 ng/mL predicted VTE presence with 78% (95%-confidence interval (95% CI), 62-89) sensitivity, 69% (95% CI, 55-81) specificity, 66% (95% CI, 51-79) positive predictive value and 80% (95% CI, 65-90) negative predictive value [area under the ROC curve, 0.779 (95%CI, 0.681-0.859), p=0.0001]. CONCLUSIONS: Mechanically ventilated COVID-19 patients present with an imbalance between markedly increased factor V/VIII activity and overwhelmed protein C/S pathway. Plasma D-dimer may be a useful biomarker at the bedside for suspicion of VTE.

Prediction of clinical outcome using blood flow volume in the superior mesenteric artery in patients with pseudomyxoma peritonei treated by cytoreductive surgery.

BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare carcinomatosis limited to the peritoneal cavity, mainly supplied by the superior mesenteric artery (SMA). The only curative treatment is cytoreductive surgery (CRS) associated with hyperthermic intraperitoneal chemotherapy. This study aimed to evaluate the ability of blood flow volume (BFV) recorded in the SMA using Doppler ultrasonography pre-operatively to predict the extent and resectability of the disease and post-operatively to assess clinical outcome. METHODS: BFV was measured in the SMA of forty-nine patients before and the year following CRS. Patients were categorized in 3 groups according to clinical and surgical outcomes: group-1 (n = 22): patient with completed CRS, group-2 (n = 16): incomplete resection with slowly progressive disease (alive at 2 years without severe clinical symptoms), group-3 (n = 11): incomplete resection and with severe clinical symptoms or dead within two years. RESULTS: Pre-operative mean SMA BFV was higher in group-2 (510 mL/min, p = 0.027) and in group-3 (572 mL/min, p = 0.004) than in group-1 (378 mL/min). After surgery, BFV dropped to normal values (203 mL/min, p = 0.001) in group-1, and to 423 mL/min (p = 0.047) in group-2. It remained elevated in group-3 (626 mL/min, p = 0.566). BFV allowed stratification of 1) resectability before CRS (group-2 and -3 vs group-1, area under the ROC curve: 0.794 [0.650-0.939]), and 2) non progression after incomplete CRS (group-3 vs group-2, area under the ROC curve: 0.827 [0.565-1.00]. CONCLUSIONS: Pre-operative BFV in the SMA correlates with extent and resectability of PMP. After incomplete surgery, post-operative BFV might aid in identifying patients who may benefit of post-operative therapy.

Early Recruitment of Cerebral Microcirculation by Neuronal Nitric Oxide Synthase Inhibition in a Juvenile Ischemic Rat Model.

BACKGROUND: The development of collateral circulation is proposed as an inherent compensatory mechanism to restore impaired blood perfusion after ischemia, at least in the penumbra. We have studied the dynamic macro- and microcirculation after ischemia-reperfusion in the juvenile rat brain and evaluated the impact of neuronal nitric oxide synthase (nNOS) inhibition on the collateral flow. METHODS: Fourteen-day-old (P14) rats were subjected to ischemia-reperfusion and treated with either PBS or 7-nitroindazole (7-NI, an nNOS inhibitor, 25 mg/kg). Arterial blood flow (BF) was measured using 2D-color-coded pulsed ultrasound imaging. Laser speckle contrast (LSC) imaging and sidestream dark-field videomicroscopy were used to measure cortical and microvascular BF, respectively. RESULTS: In basal conditions, 7-NI reduced BF in the internal carotids (by ∼ 25%) and cortical (by ∼ 30%) BF, as compared to PBS. During ischemia, the increased mean BF velocity in the basilar trunk after both PBS and 7-NI demonstrated the establishment of collateral support and patency. Upon re-flow, BF immediately recovered to basal values in the internal carotid arteries under both conditions. The 7-NI group showed increased collateral flow in the penumbral tissue during early re-flow compared to PBS, as shown with both LSC imaging and side-stream dark-field videomicroscopy. The proportion of perfused capillaries was significantly increased under 7-NI as compared to PBS when given before ischemia (67.0 ± 3.9 vs. 46.8 ± 8.8, p < 0.01). Perfused capillaries (63.1 ± 17.7 vs. 81.1 ± 20.7, p < 0.001) and the BF index (2.4 ± 0.6 vs. 1.3 ± 0.1, p < 0.001) significantly increased under 7-NI given at the re-flow onset. CONCLUSIONS: Collateral support in the penumbra is initiated during ischemia, and may be increased during early re-flow by neuronal NOS inhibition (given in pre- and post-treatment), which may preserve brain tissue in juvenile rats.

[High-resolution ultrasound imaging of the mouse]. / L'échographie haute résolution de la souris.

Small-animal ultrasound imaging has been made possible using high-resolution imaging devices. The spatial resolution is therefore sufficient to accurately measure anatomical parameters in mice. This paper reviews some of the main applications of high-resolution ultrasound imaging of the mouse and highlights what could be the forthcoming advances.

[An uncommon form of delayed radio-induced brachial plexopathy]. / Une forme inhabituelle de plexopathie brachiale radio-induite tardive.

Radiation therapy of the neck or axillary areas for cancer may result in delayed brachial plexus palsy. Differential diagnosis between radiation and tumor brachial plexopathy is difficult. We report the case of a 38-year-old woman, treated by radiation therapy for osteosarcoma of the humeral head 22 years before, who exhibited a rapidly progressive incomplete hand palsy. EMG study revealed a conduction block at the level of the lateral cord. In this case, MRI could not distinguish between a delayed radiation injury and tumor infiltration. The diagnosis was clarified with an ultrasonographic examination. Neurolysis and epineurotomy of the median trunk in the brachial and axillary areas were performed. Histological examination confirmed radiation-induced nerve injury. The characteristics of this uncommon form are reviewed with regard to the previously reported descriptions.

[Direct and indirect effects of epoietin alpha in an experimental model of thrombosis and bleeding in the rabbit]. / Etude des effets directs et indirects de l'érythropoïétine dans un modèle expérimental de thrombose et de saignement chez le lapin.

OBJECTIVES: To study direct and indirect effects of EPO on haemostasis. STUDY DESIGN: Experimental, randomised. ANIMALS: Forty-eight New Zealand rabbits. METHOD: Animals were anaesthetised, ventilated and monitored continuously for blood pressure, heart rate, body temperature, and carotid blood flow variations and were randomised into four groups: control, EPO bolus 2400 IU kg(-1), fractionated EPO (one injection a week of 600 IU kg(-1) for 4 weeks), homologous red blood cell transfusion to reach the Ht level of the fractionated EPO group. A compression injury and a 75% stenosis of the carotid artery triggered a series of cyclic flow reductions (CFRs). CFRs were observed for a 20 min period in each group. Ear immersion bleeding time (BT) and hepato-splenic bleeding were performed at the end of the experiment. Biology was performed at the end of the thrombosis period: blood cells count, Hte, activated partial thromboplastin time, fibrinogen, arachidonic-induced platelet aggregation, EPO dosages. RESULTS: No significant increase in thrombosis (CFRs) in the two EPO groups and in the transfused group. Increase in Hte in the fractionated EPO group versus control. Group EPO bolus: decrease in BT and hepato-splenic bleeding versus control; decrease in hepato-splenic bleeding versus fractionated EPO group, increase in platelet aggregation velocity versus control. CONCLUSION: EPO did not increase the thrombotic risk in this rabbit model. EPO bolus decreased BT and hepato-splenic bleeding.

Cutaneous microvascular effects of mid-term hormone replacement therapy in healthy postmenopausal women: a prospective placebo controlled trial.

OBJECTIVE: To study the mid-term effects of Hormone Replacement Therapy (HRT) on cutaneous microcirculatory blood flow and reactivity in healthy postmenopausal women. DESIGN: In a double-blind placebo controlled randomized study, 16 healthy postmenopausal women received either placebo or HRT (micronized estradiol: 1 mg/day, day 1-28, promegestrone: 0.25 mg/day, day 14-28). This regimen was completed 6 times. Cutaneous microcirculatory blood flow was recorded by laser-Doppler velocimetry on the foot dorsum, in the supine and then dependent positions, and after post-ischemic hyperemia. RESULTS: At day 0, the two groups were similar and none of the following data differed significantly between treated and placebo group: (supine flux: 11.8 +/- 1.8 u vs. 13.2 +/- 3.9, venoarteriolar reflex: 5.6 +/- 1.3 vs. 6 +/- 3.3, and post-ischemic hyperemia: 35.2 +/- 3.9 vs.48.3+/-11). At the end of the study (day 26-28 of 6th cycle), the supine flux was 9.8 +/- 2.1 in the HRT group vs.12.9 +/- 6 in the placebo group (NS), the venoarteriolar reflex, 1.2 +/- 2 vs. 7+/-1.7 (p=0.04), and post ischemic hyperemia, 31.8 +/- 5.4 vs. 39.5 +/- 4.6 (NS). Intragroup values did not change significantly for any of the microcirculatory parameters measured, which remained stable throughout the 6 months of the study. Intergroup values for these parameters did not change either, except for the venoarteriolar reflex, which was lower at the end of the study in the HRT (EP period, cycle 6 day 26-28) than placebo group (p=0.04). CONCLUSIONS: HRT does not impair the resting supine cutaneous microcirculation blood flow or post-ischemic hyperemia.

Doppler sonograpy with dynamic testing in a case of aortic dissection extending to the innominate and right common carotid arteries.

A 50-year-old woman with Marfan's syndrome was admitted for an aortic dissection with an intimal flap extending from the sinus of Valsalva to the descending aorta and aortic valve incompetence. Ultrasonography revealed a double lumen in the innominate and right common carotid (RCCA) arteries. The false lumen extended from the aortic arch to the distal RCCA and compressed and nearly occluded the true lumen in the innominate artery. At the end of the RCCA was a large tear allowing communication between the false and true lumens. Colour-coded Doppler sonography showed blood passing from the false lumen into the true lumen and antegrade flow in the false lumen but reverse flow in the true channel. A dynamic test, as used in accessing for subclavian steal syndrome, producing reactive hyperaemia, showed the retrograde flow in the true channel to be markedly increased, supplying the subclavian artery. We emphasie the importance of functional description of an abnormal haemodynamic situation, which in this case helped to avoid unnecessary surgery to the supra-aortic arteries.

Enhanced flow-dependent vasodilatation after bed rest, a possible mechanism for orthostatic intolerance in humans.

We investigated the alteration in flow-dependent-dilatation in the orthostatic intolerance occurring after bed-rest deconditioning. Eight men [aged mean (SEM) 32 (2) years] underwent two consecutive periods of 7 days of head-down-tilt (HDT, -6 degrees) during bed rest. A control age and sex matched group [n = 8, 30 (2) years], maintained its usual physical activity. Blood flow velocity (BFV) and diameter (Doppler and echotracking systems) were measured in the brachial artery, under basal conditions and during the post ischaemic hyperaemia following occlusion. The increase in BFV post-ischaemia did not change before, during and after HDT but the relative increase in the diameter was greater on the 7th day of the HDT period than before HDT [+8.8(1.6)% compared to +3.7(1.0)%, P < 0.001]. After HDT, 11 of 16 standing tests (comprising eight subjects in the two HDT periods) had to be stopped because of orthostatic intolerance. The flow-dependent-dilatation measured at the end of HDT was negatively correlated with the post-bed-rest duration of orthostatic tolerance (r = 0.78, P < 0.01). After the sublingual administration of glyceryl trinitrate, there was no change in the increase in diameter. No significant changes were observed in the control group. Bed-rest deconditioning enhances the flow-dependent vasodilatation of large arteries and might contribute to the orthostatic intolerance observed following bed-rest.

Cricohyoepiglottopexy: long-term results in 55 patients.

Near total laryngectomy with cricohyoepiglottopexy (CHEP) allows cure of glottic carcinomas with voice preservation. The subject of this study was to evaluate CHEP in terms of tumour control and functional result in T1 and T2 glottic carcinomas. This study reviewed retrospectively 55 consecutive cases of CHEP performed between January 1, 1981 and September 1, 1992 with the exclusion of post-radiotherapy salvage surgery. CHEP was indicated for a T1a limit to the anterior commissure and/or with dysplasia of the other vocal fold (10 cases), T1b (11 cases) and T2 (34 cases) glottic carcinomas. All our patients have a follow-up of more than five years. The post-operative course after this surgery was generally uneventful. The median time to decannulation was 18 days, to removal of the nasogastric tube was 15 days and to discharge from hospital was 23 days. No significant difference was observed according to the preservation of one or both arytenoid cartilages. The long-term functional result can be considered to be good in three-quarters of cases, with normal oral swallowing and an easily understood voice. The remaining one quarter had a whispery voice and sometimes episodes of aspiration when swallowing liquids. In terms of oncological results, the five-year recurrence-free survival rate was 94 per cent for T1 and 84 per cent for T2. The ultimate tumour control (taking into account four cases of total laryngectomy) was 94 per cent for T1 and 93 per cent for T2. Primary surgery by CHEP therefore appears to be a good option for early glottic carcinomas. The main problem remains that voice recovery is mediocre in one quarter of patients.

Transport of uterine PGF2 alpha to the ovaries by systemic circulation and local lymphovenous-arterial diffusion during luteolysis in sheep.

The theory of countercurrent vascular transfer of PGF2 alpha during luteolysis was examined. In the first experiment, pulmonary clearance of PGF2 alpha was determined to re-examine whether the total amount of PGF2 alpha was degraded in the lungs after one passage. Cardiac output was measured by the Fick method and PGF2 alpha by radio-immunoassay before and after vascular lung supply, using pulmonary catheterization and the interventional radiology method in ten anaesthetized ewes on day 16 of the oestrous cycle. Cardiac output remained stable (7156 +/- 439 ml min-1). Infusion of 5 iu oxytocin resulted in an increase in plasma PGF2 alpha concentrations at 30 min in the uterine vein and the pulmonary and femoral arteries (3811 +/- 806, 224 +/- 55 and 18 +/- 4 pg ml-1, respectively). The PGF2 alpha concentrations decreased exponentially and the half-time decreases were 27 (r = 0.99), 16 (r = 0.99) and 18 (r = 0.98) min, respectively. Pulmonary clearance of PGF2 alpha was estimated at 6338 +/- 451 ml min-1. In a second experiment, an arterio-arterial gradient of plasma PGF2 alpha concentrations was analysed between the proximal and distal segments of the ovarian artery to verify whether the total amount of PGF2 alpha flowing to the ovary was from the local venous-arterial countercurrent pathway. Surgical catheterization techniques were performed on 11 ewes on day 16 of the oestrous cycle. The ovarian arterial blood flow was measured by the implantable Doppler method (8 +/- 1 ml min-1). The maximum plasma PGF2 alpha concentrations in the femoral and distal ovarian arteries were 23 +/- 6 and 42 +/- 11 pg ml-1 (P < 0.05), respectively. Plasma PGF2 alpha decreased exponentially in the femoral artery and the half-time decrease was 26 min (r = 0.98), and in the distal ovarian artery close to the ovary PGF2 alpha decreased linearly and the half-time decrease was 108 min (r = 0.96). Consequently, the arterio-arterial diffusion gradient of PGF2 alpha concentrations was extended to 3 h. These experiments showed that the PGF2 alpha flow rate in the pulmonary artery was 42.275 +/- 10.793 micrograms per 150 min (n = 10) and the systemic arterial PGF2 alpha flow rate was 5.359 +/- 1.658 micrograms per 150 min (n = 10). Therefore, 12% of the PGF2 alpha was not oxidized by the lungs. The proximal ovarian PGF2 alpha flow rate was 6.909 +/- 2.341 ng per 150 min, while the distal flow rate was 21.003 +/- 5.703 ng per 150 min (n = 11). Thus, 33% of the PGF2 alpha was transported rapidly to the ovary via the systemic route, while 67% was transported by slow local countercurrent diffusion, which extended the duration of luteolytic activity to four times that of the PGF2 alpha surge. These results indicate both rapid systemic transport of PGF2 alpha to the ovaries and a slower buffer mechanism involving a local diffusion pathway, rather than a direct countercurrent system.

[Hypopharyngeal sarcomatoid carcinoma with one time sarcomatous recurrence. A case report]. / Récidive sarcomateuse monophasique d'un carcinome sarcomatoïde hypopharyngé. A propos d'un cas.

We report case of a patient with hypopharyngeal biphasic sarcomatoid carcinoma, with two tumor cell component, epidermoid and spindle cells, treated by surgery only. Two years later, recurrence is noted with totally different histologic form, sarcomatous monophasic, with spindle tumor cells and smooth muscle phenotype with immunohistochemistry, looking like primitive leiomyosarcoma of high malignancy degree. Such monophasic sarcomatous forms of sarcomatoid carcinoma, without epithelial tumor component, are deceptive and can be mistaken with primitive sarcoma. That is why discovery of epithelial differenciation signs, with immunohistochemistry or electronic microscopy, is very important. In our case, while the epithelial differenciation in the recurrent tumor is away, previous history of true biphasic sarcomatoid carcinoma in the same anatomic location, allows to assert recurrence of the same tumor with monophasic sarcomatous expression and smooth muscle phenotype in this case. Therefore in front of "sarcoma of the upper aerodigestive tract", of any immunohistochemical phenotype, monophasic sarcomatous form of epidermoid sarcomatoid carcinoma have always to be evocated and searched.

Role of the hematocrit in a rabbit model of arterial thrombosis and bleeding.

BACKGROUND: A decrease in hematocrit lengthens bleeding time. The authors studied the role of hematocrit variations in an experimental model of arterial thrombosis and bleeding. METHODS: The Folts model was used in 24 rabbits. After anesthesia was induced and common monitors were positioned, the right common carotid artery was exposed and a 60% stenosis was induced. A compression injury of the artery was then produced, which triggered a series of cyclic episodes of thrombosis and clot lysis (cyclic flow reductions [CFRs]). After counting the number of CFRs that occurred in 20 min (CFR1), the animals were assigned randomly to one of three groups (n = 8 in each group): control, hemodilution with rabbit homologous platelet-rich plasma, and hemodilution with gelatin solution and then reinfusion of the shed blood. The effect of hemodilution with replacement by platelet-rich plasma or by colloid was observed by recording the number of CFRs during another 20-min period (CFR2). A third period of observation (CFR3) followed shed blood reinfusion in the gelatin solution group. Ear immersion bleeding time was recorded after each CFR period. RESULTS: In the two experimental groups, the decrease in hematocrit (from 36 +/- 3% to 23 +/- 2% and from 38 +/- 3% to 23 +/- 2%, respectively; mean +/- SD) abolished CFRs (from a median of 4 to 0 and 7 to 0, respectively) and significantly lengthened bleeding time (from 76 +/- 24 s to 114 +/- 36 s and from 84 +/- 37 s to 127 +/- 29 s, respectively). Blood reinfusion in the group that received the gelatin solution caused CFR to reappear (CFR3 = 4). CONCLUSIONS: Decreases in hematocrit reduced the cyclic arterial thrombosis rate and increased the bleeding time in the rabbits in this study. Hematocrit normalization caused thrombosis to reappear.

Ketorolac and enoxaparin affect arterial thrombosis and bleeding in the rabbit.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) may interfere with hemostasis during the perioperative period, and the combination of NSAID and enoxaparin could increase this effect. The aim of this prospective, blinded experimental study was to assess these effects using a model of arterial thrombosis and bleeding in the rabbit. METHODS: After anesthesia was induced and monitors placed, the common carotid arteries were exposed, and 60% stenosis of the right common carotid artery was produced. Twenty minutes later, a compression injury of the artery was produced that triggered a series of cyclic episodes of thrombosis and clot lysis. This was manifested as cyclic flow reductions (CFR; measured with an electromagnetic flow meter). After the first flow reduction was noted, the rabbits were immediately and randomly assigned to one of four groups (n = 10 each) that received intravenous infusions: control, ketorolac (2 mg/kg), enoxaparin (0.5 mg/kg), and ketorolac plus enoxaparin (2 mg/kg and 0.5 mg/kg, respectively). The number of CFRs that occurred in the subsequent 20-min period was used as a measure of treatment effect. The contralateral common carotid artery was exposed, and both stenosis and injury were produced. The ability of the administered drug to prevent thrombosis was assessed as the number of CFRs that occurred during the first 20-min period after vessel injury. In addition, both before and after group assignment and drug injection, bleeding times were noted and a platelet aggregation test was performed. Laparotomy was followed by a spleen section, and the extent of the wound and the amount of splenic bleeding were measured. RESULTS: The treatment effect was indicated by the median number of CFRs, which was 5.5 in the control group, 1 in the ketorolac group, 2 in the enoxaparin group, and 0 in the ketorolac + enoxaparin group. The prevention effect was indicated by the median number of CFRs, which was 4 in the control group, 0 in the ketorolac group, 2 in the enoxaparin group, and 0.5 in the ketorolac + enoxaparin group. Bleeding time was significantly lengthened in the enoxaparin and in the ketorolac + enoxaparin groups. Splenic and wound bleeding was greater in the ketorolac group. Platelet aggregation was completely inhibited in the ketorolac and the ketorolac + enoxaparin groups. CONCLUSIONS: Ketorolac had an important antithrombotic activity. The association of enoxaparin with ketorolac seemed to lengthen the bleeding time observed with ketorolac.