Endothelial and smooth muscle properties of coronary and mesenteric resistance arteries in spontaneously hypertensive rats compared to WKY rats

Summary— To investigate if the functional alterations observed in resistance arteries of spontaneously hypertensive rats (SHRs) were also present at the coronary level, in vitro experiments were performed in mesenteric resistance arteries (MRA) and in right (RIC) and left interventricular coronary (LIC) arteries taken from 15–25-week-old SHR and age-matched Wistar Kyoto rats WKYs. Using a passive extension protocol, internal diameters corresponding to 100 mmHg intraluminal pressure (D₁₀₀) were determined and vessels were set up to a normalized internal diameter (0.9 D₁₀₀). SHR mesenteric resistance arteries had a significantly smaller diameter compared to WKY arteries, whereas both types of SHR coronary arteries had a greater diameter compared to those of WKY rats. In arteries in the absence of contracting agonist, nitro-L-arginine (NOLA, 100 μM) induced a progressive rise in basal tone, which could be reversed by subsequent addition of L-arginine (100 μM) but not D-arginine (100 μM). When expressed as percent of maximal contractions induced by agonists (noradrenaline, NA [10 μM] in MRA; serotonin, 5-HT [10 μM], in RIC and LIC), these contractions were significantly stronger in WKY compared to SHR coronary and mesenteric resistance arteries. In NA-precontracted MRA and 5HT-precontracted coronary arteries in the presence of indomethacin (10 μM), the magnitude of acetylcholine-induced maximal relaxations (expressed as percent of maximal contractions induced by agonists) was greater in WKY compared to SHR arteries. After a 30-min incubation period, NOLA (100 μM) completely inhibited relaxations induced by acetylcholine (0.01–10 μM) in all types of precontracted arteries. Subsequent additions of sodium nitroprusside, (SNP, 10 μM) induced complete relaxations in all preparations. These results show that a basal release of NO or NO-like compound by endothelial cells is present in isolated mesenteric resistance and coronary arteries of WKY rats and SHRs. The contribution of endothelium-derived relaxing factor-nitric oxide (EDRF-NO) to arterial tone was lower in MRA compared to coronary arteries in both strains and in SHR compared to WKY arteries. In the SHR preparations, the impaired relaxation induced by acetylcholine appeared to be due to a functional alteration of the endothelium in the presence of normal reactivity of the smooth muscle cells.     

表小檗碱对α受体的作用

表小檗碱(epiberberine,EB)是从湖北产黄连(Coptis chinensis Franch)中提取的一种生物碱,属苯喹嗪类原小檗碱,对其药理作用的研究资料甚少,未见其对α肾上腺素体作用的报道。资料表明,许多原小檗碱类化合物有α受体阻滞作用,为从该类化合物中选择     

Prevention of postischemic ventricular fibrillation late after right or left stellate ganglionectomy in dogs

To gain insight into the differences in antiarrhythmic potential of right vs left stellate ganglionectomy, 72 dogs were randomized to either unilateral stellectomy or second intercostal space thoracotomy and left circumflex coronary arteriovenous pedicle occlusion was performed, without vagotomy, a mean of 8 weeks later under anesthesia. The type and timing of ventricular ectopic beats, including both nonsustained and sustained ventricular tachycardia and ventricular fibrillation, were investigated. Several covariates, including postischemic electrocardiographic changes, were considered. Both right and left stellate ganglionectomy reduced the incidence of early (0 to 10 min) (p = .004 and p = .001, respectively) and total (0 to 60 min) (p = .009 and p = .008, respectively) ischemia-induced ventricular fibrillation, and improved outcome (p = .0013 and p = .0012, respectively). Early sustained ventricular tachycardia was similarly reduced (p = .02) in both stellectomized groups. By contrast, neither the type nor the time distribution of the other forms of ventricular arrhythmias differed significantly among the randomized groups. The multivariate Cox's regression model showed that ST segment elevation at 3 min postocclusion, unilateral stellate ganglionectomy (either right or left), sex, and weight were significant independent predictors of the incidence of ventricular fibrillation during the occlusion period. Lower ST segment elevation and reduced incidence of sustained ventricular tachycardia in the early postischemic period might explain improved outcome in stellectomized dogs by Cox analysis. The side of intervention (either stellectomy or sham operation) did not influence survival; however, left-sided interventions were more effective than right-sided ones. These results confirm the previously reported antifibrillatory effect of left and indicate like effects of right stellate ganglionectomy in a randomized experimental study.     

Role of neoadjuvant chemotherapy in the treatment of advanced head and neck tumors. Results of two randomized therapeutical trials conducted at the Institut Curie on 208 patients]

From March 1983 to December 1989, 208 patients with locally advanced squamous cell carcinoma of the head and neck were successively included into two trials randomizing induction chemotherapy versus no pre-irradiation treatment. The chemotherapy regimen of the first trial, which included 100 patients, consisted of two cycles of a combination of cisplatin, bleomycin, vindesine, mitomycin C; while that of the second trial, which included 108 patients, consisted of three cycles of a combination cisplatin, 5-fluorouracil (continuous infusion) and vindesine. Local treatment was the same in two trials: 'primary' radiotherapy in all patients. The response was then evaluated at 55 Gy; in the case of poor response, surgery was performed, otherwise radiotherapy was continued to full doses (possibly followed by salvage surgery). The tumor and lymph node responses to chemotherapy (complete and partial response) were higher in the second trial and in the first one: 70% versus 50% for primary lesions, 47% versus 25% for lymph nodes. The toxicity of the two chemotherapy regimens was minimal. In the two trials, an initial major response to chemotherapy predicted subsequent efficacy of irradiation in 80% of the patients. Complete response rate at the end of irradiation correlates with the previous response to the chemotherapy. With a median follow-up of 60 months with the first chemotherapy regimen and 30 months with the second, overall survival and disease-free interval did not significantly differ in the two groups of patients, with or without chemotherapy. The incidence of distant metastasis was significantly reduced (P < 0.03) in the chemotherapy arms. This negative trial encourages the design of new chemotherapy protocols according to new schemes of treatment. For advanced stages of head and neck cancers (T3, T4, N2, N3), we recently launched a pilot study combining platinum and irradiation, but according to a concomitant schedule.     

Decreased serum levels of nutritional biochemical indices in healthy children with marginally delayed physical growth

Biochemical markers of nutritional status (albumin, transthyretin, insulin-like growth factor-I and zinc) were measured in slowly growing two- to five-year-old, low-income Parisian children whose weight-for-height or height-for-age z scores (WHZ or HAZ) were between — 1 and — 2 SD of the NCHS median. The results were compared to controls who were matched for age, sex, and ethnic origin with WHZ and HAZ between — 1 and + 2 SD. Mean serum levels of transthyretin, albumin and insulin-like growth factor-I and mean plasma zinc concentrations were significantly lower in the growth-impaired children than in the controls ( p = 0.002, p = 0.006, p = 0.015, and p = 0.035, respectively). While the height-retarded children had low mean serum insulin-like growth factor-I values, the weight-retarded subjects had decreased levels of albumin, transthyretin and zinc when compared to controls. Lower mean levels of nutritional markers in healthy, slowly growing children suggest that inadequate dietary intakes of zinc, protein and/or energy may result in marginal delays in weight and height gains.     

Early changes in hemoglobin and hematocrit levels after packed red cell transfusion in patients with acute anemia

BACKGROUND: Equilibration of hemoglobin concentration after transfusion has been estimated to take about 24 hours, but some studies have shown that earlier measurements reflect steady-state values in persons who have not bled recently. This study was aimed at assessing the changes over time in hemoglobin concentration after transfusion in acutely anemic patients because of recent bleeding. STUDY DESIGN AND METHODS: Thirty-two normovolemic patients recovering from an acute bleeding episode who were no longer thought to be bleeding and who received a 2- unit red cell transfusion were studied. At baseline and 15, 30, 60, and 120 minutes and 24 hours after transfusion, hemoglobin concentration and hematocrit values were measured. RESULTS: The administration of 2 units of packed red cells elicited a 24-hour increase of 22.4 +/− 6.8 g per L in hemoglobin concentration. Hemoglobin values were not different at any of the defined posttransfusion times. Hematocrit levels experienced similar changes over time. Agreement between 15-minute and 24-hour values was excellent, as only 6 percent of patients exhibited a clinically significant difference (> 6 g/L) between the hemoglobin measurements. CONCLUSION: Hemoglobin and hematocrit values rapidly equilibrate after transfusion in normovolemic patients who are recovering from an acute bleeding episode. This fact would allow a rapid assessment of the effects of transfusion and of the recurrence of bleeding in patients remaining at risk.