血压平逆转2K1C肾性高血压大鼠左室重构的作用及其机理的研究

目的:研究血压平逆转二肾一夹肾性高血压大鼠左室重构的作用及其机理。方法:建立2K1C肾性高血压大鼠(RHR)模型,术后8周40只RHR随机分为5组,每组8只,分为:血压平大、中、小剂量组(73、36.5、18.25g·kg-1·d-1);依那普利组(10g·kg-1·d-1);模型组,另取8只大鼠作为假手术对照组。模型组和假手术组灌服等容量水,疗程8周。手术前及术后每周测血压1次,给药第8周末,各组测量大鼠体重(BW),眼眶放血2ml,断头处死大鼠,迅速取出心脏,去除心房、右室游离壁,左室及室间隔称重(LVW),计算LVW/BW之比。采用放免法检测血清PCⅢ,心肌组织石蜡切片HE染色及SP免疫组化染色高清晰度图像分析系统测量心肌细胞形态参数及原癌基因cmyc和cfos表达阳性细胞的平均光密度值。结果:血压平降低血压,降低左室重量(LVW)、左室重量指数(LVW/BW)、心肌细胞体积及血清PCⅢ含量,抑制原癌基因cmyc和cfos的表达,血压平大、中剂量组LVW、LVW/BW及血清PCⅢ含量明显低于模型组(P<0.01),图像分析心肌细胞形态参数(面积、周长、平均直径、长径及短径)及cmyc、cfos表达阳性的心肌细胞平均光密度值明显低于模型组(P<0.01),与假手术组接近(P>0.05)。结论:复方中药血压平具有逆转2K1C肾性高血压大鼠左室重构的作用,其降低血压和血清PCⅢ含量、抑制Ⅲ型胶原合成、防治心肌纤维化及降低原癌基因cmyc和cfos的表达、抑制心肌细胞肥大、减轻左心室肥厚是其逆转二肾一夹肾性高血压大鼠左室重构的部分机制。     

The hedonic impact and intake of food are increased by midazolam microinjection in the parabrachial nucleus

Benzodiazepines have been reported to induce eating when administered into the brainstem of rats (either the fourth ventricle or the parabrachial nucleus). Benzodiazepines in the brainstem also have been reported to enhance the hedonic impact of taste, as measured by hedonic/aversive taste reactivity patterns, when administered to the fourth ventricle. The present study examined whether the parabrachial nucleus in particular is a brainstem site of the benzodiazepine-produced enhancement of eating and palatability. Food intake (cereal mash) was measured after brainstem microinjections of midazolam or vehicle (0.0, 7.5, and 15.0 microg) into the parabrachial nucleus, the nucleus of the solitary tract, the pedunculopontine tegmental nucleus, or the fourth ventricle (60 microg). We used the taste reactivity paradigm to measure hedonic/aversive affective reactions elicited from rats by oral infusions of a bittersweet solution (7% sucrose-0.01% quinine). Positive hedonic reactions and negative aversive reactions to sucrose-quinine were also measured after microinjections of midazolam (0.0, 7.5, and 15 microg) into the parabrachial nucleus. Midazolam increased food intake and selectively enhanced positive hedonic taste reactivity patterns to the bittersweet solution when microinjections were delivered to the parabrachial nucleus. When administered to the other brainstem sites at the same doses, however, midazolam had no effect. We therefore conclude that the parabrachial nucleus can mediate the benzodiazepine-induced enhancement of the hedonic impact of taste as well as mediating the enhancement of eating behavior.     

Cytoarchitectonic Basis for Safe Entry Into the Brainstem

This work is a continuation of the anatomical study in which safe approach zones through the floor of the fourth ventricle--infrafacial and suprafacial--were morphologically and morphometrically defined (Acta Neurochir (1997) 139: 1014-1019). The purpose of cytoarchitectonic study was to analyze correlation between morphometry of the facial colliculus and hypoglossal triangle and localization of the corresponding cranial nerves nuclei in the brainstem tegmentum in order to verify morphometrical borders of the previously defined zones. Morphometrical evaluation of the fourth ventricle floor of 10 examined brainstems was initially performed. Distances from obex to the rostral portion of hypoglossal triangle and facial colliculus were determined. Then a series of axial sections of each specimen, stained for Nissl substance, were analyzed to define the distance from obex to the rostral portion of the hypoglossal and abducens nuclei. Distances of motor trigeminal and facial nuclei from the midline sagittal plane were also measured. The obtained results allowed morphometrical determination of the infra-abducental and supra-abducental region of safe entry into the brainstem tegmentum. Infra-abducental region corresponds to infrafacial safe approach zone and supra-abducental to suprafacial zone. The distance of the rostral portion of facial colliculus from obex was longer than the distance of the rostral pole of abducens nucleus from obex in every examined specimen (by 0.7 mm on average). A very similar correlation between the distance of the rostral margin of hypoglossal triangle and localization of the rostral pole of hypoglossal nucleus was found. The rostral portion of hypoglossal triangle was longer by 1.5 mm on average. The obtained results show that previously defined infrafacial and suprafacial safe approach zones via the fourth ventricle floor correspond morphometrically to tegmental regions of safe entry--infra-abducental and supra-abducental respectively. It suggests that morphometrical evaluation of the fourth ventricle floor proposed by the authors could be useful in the intra-operative determination of safe entry via the rhomboid fossa into the brainstem tegmentum.     

培哚普利对急性心肌梗死后心肌纤维化的血清指标影响

目的 :观察冠心病急性心肌梗死患者心肌纤维化的血清指标变化和血管紧张素转换酶抑制剂对心肌纤维化及心室重构的逆转作用 ,探讨血清指标作为临床判断心肌纤维化与心室重构及其逆转的临床价值。方法 :正常对照组20例 ,心肌梗死组44例 ,心肌梗死后应用培哚普利治疗12周 ,用放射免疫分析法测定血清指标PCⅢ (Ⅲ型前胶原 )、LN(层粘连蛋白 )、HA(透明质酸 )。结果 :心肌梗死2周后较正常对照组血清PCⅢ、LN、HA明显增高 (P<0 01) ,培哚普利治疗12周后血清PCⅢ、LN、HA明显下降 (P<0 01)。结论 :血清PCⅢ、LN、HA可以作为心肌梗死后心肌纤维化与心室重构的间接观察指标。     

A paradigm for awake intraoperative memory mapping during forniceal stimulation

We report the case of a chess player with superior premorbid cognitive function who presented to the Cognitive Disorders clinic at the National Hospital for Neurology and Neurosurgery with a 2-year history of symptoms of possible memory loss. Initially the MRI scan appearance was within normal limits and his cognitive scores inside the normal range; subsequently his cognitive function deteriorated and he fulfilled criteria for Mild Cognitive Impairment (MCI) two years later. Unexpectedly he died of an unrelated illness seven months later and post mortem examination of the brain was carried out, revealing advanced Alzheimer’s disease (CERAD definite and NIA-Regan Institute high likelihood).

This case highlights the difficulties encountered in assessing patients with superior premorbid function in the early stages of Alzheimer’s disease, and reveals the value of serial MRI and neuropsychological assessment in detecting and monitoring early neurodegenerative disease.     

Right Ventricular Function Predicts Clinical Response to Specific Vasodilator Therapy in Patients with Pulmonary Hypertension

Introduction: We followed patients with pulmonary arterial hypertension (PAH) receiving specific vasodilator therapy and tested for predictors of clinical outcome. Methods: Thirty‐two patients (mean age 39 ± 15 years, 22 women, diagnosed with pulmonary hypertension; PH): 29 with PAH and 3 patients with inoperable chronic thromboembolic PH received therapy with either bosentan, sildenafil, or both and were evaluated with clinical parameters, biomarkers (B‐type natriuretic peptide values), and echocardiography before receiving specific medication and every 3 months thereafter. A right heart catheterization was performed at baseline. A composite endpoint of death, worsening of functional class, or the need of a second vasodilator agent was used to define the clinical nonresponders. Results: Patients were followed for 14 months (7.5–21). The endpoint was reached by 15 patients: four patients died (two idiopathic PAH and two PAH in context of Eisenmenger syndrome), seven patients showed 1 functional class worsening, and four patients needed to be switched to combination therapy. Patients who remained clinically stable or improved had at baseline a better cardiac output with a less remodeled right ventricle (RV) and better functioning RV (all P < 0.05). A RV fractional area change (RVFAC) lower than 25.7% and a RV global strain value higher than ?13.4% predict with 87% sensitivity and 83% specificity (AUC 87.3%, P = 0.001) and 73% sensitivity and 91% specificity (AUC 84.2%, P = 0.003), respectively, patients who will deteriorate clinically under specific vasodilator therapy. A multivariate model showed RVFAC to be the only independent predictor of the endpoint with a HR of 0.87 (0.8–0.96), P = 0.007. Conclusions: Over an average period of 1 year, almost half of patients showed signs of clinical deterioration despite specific vasodilator therapy. Parameters of right ventricular morphology and function had prognostic value in these patients.     

Effect of variable annular reduction on functional tricuspid regurgitation and right ventricular dynamics in an ovine model of tachycardia-induced cardiomyopathy

ObjectiveTo investigate the effect of variable tricuspid annular reduction (TAR) on functional tricuspid regurgitation (FTR) and right ventricular (RV) dynamics in ovine tachycardia-induced cardiomyopathy.MethodsNine adult sheep underwent implantation of a pacemaker with an epicardial lead and were paced at 200 to 240 bpm until the development of biventricular dysfunction and functional TR was noted. During reoperation on cardiopulmonary bypass, 6 sonomicrometry crystals were placed around the tricuspid annulus (TA) and 14 were placed on the RV epicardium. Annuloplasty suture was placed around the TA and externalized to an epicardial tourniquet. After weaning from cardiopulmonary bypass, echocardiographic, hemodynamic, and sonomicrometry data were acquired at baseline and during 5 progressive TARs achieved with suture cinching. TA area and RV free wall strains and function were calculated from crystal coordinates.ResultsAfter pacing, changes in left ventricular (LV) ejection fraction and RV fractional area decreased significantly. Mean TA diameter increased from 25.1 ± 2.9 mm to 31.5 ± 3.3 mm (P = .005), and median TR (range, 0-3+) increased from 0 (0) to 3 (2) (P = .004). Progressive suture cinching reduced the TA area by 18 ± 6%, 38 ± 11%, 56 ± 10%, 67 ± 9%, and 76 ± 8%. Only aggressive annular reductions (67% and 76%) decreased TR significantly, but these were associated with deterioration of RV function and strain. A moderate annular reduction of 56% led to a substantial reduction of TR with little deleterious effect on regional RV function.ConclusionsA moderate TAR of approximately 50% may be most advantageous for correction of functional TR and simultaneous maintenance of regional RV performance. Additional subvalvular interventions may be needed to achieve complete valvular competence.