Captopril fails to reverse hypertrophy of the left ventricle induced by aortic insufficiency in rabbits

Angiotensin converting enzyme (ACE) inhibition has been reported to induce regression of hypertrophy in several models of hemodynamic pressure overload. The aim of the present study was to determine whether the ACE inhibitor captopril can reduce hypertrophy of the left ventricle induced by a chronic volume overload and modify collagen composition of the hypertrophied myocardium. Rabbits with four months lasting aortic insufficiency were divided into two groups: treated with captopril (20 mg/kg/day) for five weeks and treated with placebo. The respective control groups were represented by sham-operated animals. Aortic insufficiency induced a decrease of diastolic pressure, an increase of systolic and pulse pressure, hypertrophy of the left and right ventricle, and an increase of hydroxyproline content in the left ventricle without a change of hydroxyproline concentrations in either ventricle. Captopril treatment further enhanced pulse pressure by decreasing diastolic blood pressure. Hypertrophy of the left ventricle, hydroxyproline content and concentration in both ventricles were unaffected by captopril treatment. It is concluded that ACE inhibition did not reverse the left ventricular hypertrophy developed as a result of overload induced by aortic insufficiency. We suggest that mechanisms different from activation of the renin-angiotensin system may play a decisive role in the maintenance of hypertrophy in this particular model of volume hemodynamic overload.     

Echocardiographic evaluation of delayed outcome of artificial valve implantation in patients with aortic semilunar valve insufficiency]

An average follow-up period of 16 patients was 28 months following an implantation of the artificial aortic valve for its insufficiency. In 10 operated patients who were able to continue their occupation exercise tolerance increased by two classes, according to NYHA. Blood pressure gradient decreased significantly from 61.8 to 37.5 mmHg, cardiac volume index decreased from 639 to 602 ml/m2. Echocardiographically measured muscle mass of the left ventricle, end-diastolic and end-systolic volumes, and the left atrial dimensions decreased significantly following surgery. A significance of the relation of the left ventricle volume to its mass <4 as a prognostic factor in aortic valve replacement has also been confirmed.     

Treatment of aortic insufficiency with a descending aortic valvular homograft: 19-year follow-up and historical perspective

This case report and 19-year follow-up concerns a patient with aortic insufficiency who was one of the first to undergo surgical treatment with a descending aortic valvular homograft. The historical perspective afforded here may stimulate ideas concerning advances in future methods and materials to be used in cardiac surgery.     

Parameters of tubulo-glomerular function in anesthetized rabbits with acute kidney insufficiency

We have induced acute renal failure (ARF) in barbiturate anesthetized rabbits, through warm ischaemia of 30 or 60 min duration caused by transient bilateral occlusion of renal arteries. In this model we have monitored some renal performance parameters, before and 4 hours after reperfusion, aiming to characterize ARF in this animal species. Glomerular filtration rate (determined by the inulin clearance technique) was of 9.74 +/- 0.48 ml min-1 in 4 rabbits before injury and declined by 91% (60 min ischemia) during the first reperfusion hour. In 6 rabbits undergoing 30 min occlusion, pre-ARF values of 10.70 +/- 0.98 ml min-1 declined by 47%. In both groups no recovery was observed in the following hours. Tubular enzymes (alanine-amino-peptidase, AAP and N-acetyl-beta-glucosaminidase, NAG) were released into urines before injury at the rate of 1.11 +/- 0.18 and 1.32 +/- 0.41 mU min-1, respectively, in the 30 min model (3 animals/group). During ARF, maximal AAP output was five-fold increased (5.83 +/- 0.35 mU min-1), whereas NAG was unmodified. On the other hand, renal haemodynamics in 5 rabbits did not change after the ischaemic procedure: total renal blood flow (44 +/- 5 ml min-1) and renal vascular resistances (225 +/- 26 Pa ml-min) displayed less than 10% variations throughout the reperfusion period. We concluded that ARF in rabbits can be reliably and reproducibly monitored and that the pathogenesis of the disease, in our situation, is attributable mainly to tubular cell damage and not to impairment of the vascular component of renal performance.     

Hypoglycaemic, antioxidative and nephroprotective effects of taurine in alloxan diabetic rabbits

The therapeutic potential of taurine was investigated under diabetic conditions. Alloxan diabetic rabbits were treated daily for three weeks with 1% taurine in drinking water. The following parameters were measured: 1) serum glucose, urea, creatinine and hydroxyl free radical (HFR) levels; 2) blood glutathione redox state; 3) urine albumin concentration; 4) hepatic and renal HFR levels, GSH/GSSG ratios and the activities of catalase, superoxide dismutase and the enzymes of glutathione metabolism; 5) renal NADPH oxidase activity; 6) the rates of renal and hepatic gluconeogenesis. Histological studies of kidneys were also performed. Taurine administration to diabetic rabbits resulted in 30% decrease in serum glucose level and the normalisation of diabetes-elevated rate of renal gluconeogenesis. It also decreased serum urea and creatinine concentrations, attenuated diabetes-evoked decline in GSH/GSSG ratio and abolished hydroxyl free radicals accumulation in serum, liver and kidney cortex. Animals treated with taurine exhibited elevated activities of hepatic gamma-glutamylcysteine syntetase and renal glutathione reductase and catalase. Moreover, taurine treatment evoked the normalisation of diabetes-stimulated activity of renal NADPH oxidase and attenuated both albuminuria and glomerulopathy characteristic of diabetes. In view of these data, it is concluded that: 1) diminished rate of renal gluconeogenesis seems to contribute to hypoglycaemic effect of taurine; 2) taurine-induced increase in the activities of catalase and the enzymes of glutathione metabolism is of importance for antioxidative action of this amino acid and 3) taurine nephroprotective properties might result from diminished renal NADPH oxidase activity. Thus, taurine seems to be beneficial for the therapy of both diabetes and diabetic nephropathy.     

Proteolytic activity in brains of rabbits treated with aluminum

Aluminum injection in rabbits leads to neurofibrillary changes which are at light microscopic level similar to those found in Alzheimer's disease. We used this animal model to see whether changes in proteolytic activity occur that may affect protein degradation in the altered neurofibrillary structure. Rabbits were injected via the cisterna magna with aluminum chloride, and after ten days tissue was excised from the spinal cord, hippocampus, occipital lobe, and cerebellum. Sections from the hippocampus and spinal cord were examined for neurofibrillary changes; enzyme activity was measured in all four areas. The enzymes studied were cathepsins A, B, and D, and the angiotensin-converting enzyme. No significant differences could be established in enzymatic activity in aluminum-injected animals compared to controls. However, a significant decrease in Triton-soluble proteins was observed in the treated animals, which correlated with changes in neurofibrillary structure. This decrease was most noticeable in the spinal cord (from 16.6 to 12.5 mg/g).     

The ethanol-induced open-field activity in rodents treated with isethionic acid, a central metabolite of taurine.

The effect of isethionic acid, a central metabolite of taurine, on ethanol-induced locomotor activity was investigated in rodents. Ten minutes following an (i.p.) simultaneous administration of ethanol (0.0, 1.5, 2.0, 2.5, 3.0, 3.5 g/kg) and isethionic acid (0.0, 22.5, 45.0, 90.0, 180.0 mg/kg), mice were placed in the open-field chambers and locomotor activity was measured during a ten-minute testing period. A significant interaction was found between isethionic acid and ethanol. Isethionic acid pre-treated mice (45.0, 90.0 and 180.0 mg/kg) showed a higher locomotor activity than the saline group at 2.5 and 3 g/kg of ethanol. In a second study, isethionic acid (45 mg/kg) and ethanol (1 g/kg) were simultaneously injected to rats. Ten minutes after the two treatments, rats were placed in the open-field chamber for a 30-minute period. The depressant effects that ethanol produced on rat locomotion were amplified by the same dose of isethionic acid as it affected ethanol-induced locomotion in mice (45 mg/kg). However, isethionic acid did not change the spontaneous locomotion at any of the doses tested in mice or rats. Since no differences in blood ethanol levels were detected in both mice and rats, the interaction between isethionic acid's action and ethanol-related locomotion does not seem to be due to different rates of absorption of ethanol or any other pharmacokinetic process related to ethanol levels. The current study displayed that isethionic acid, administered intraperitoneally, behaves in a similar way to its immediate precursor, taurine, by amplifying ethanol-induction of the locomotor activity.     

Atrial natriuretic peptide messenger RNA and peptide in rats with aortic valve insufficiency

To investigate ANP gene expression in diseased hearts of animals without genetic defects, immunoreactive ANP (IR-ANP) and ANP mRNA were measured in a rat with aortic valve insufficiency (AI), which was produced by puncturing one of the aortic valve leaflets with a plastic rod. Plasma IR-ANP concentration was higher in AI rats than in sham rats (p less than 0.05). Decreased atrial concentration of IR-ANP (p less than 0.05) and unchanged atrial ANP mRNA concentration were shown in AI rats. The ventricular concentrations of IR-ANP and ANP mRNA in AI rats were 5.4 and 2.4 times higher than those in sham rats (p less than 0.05, respectively). These results demonstrate that gene expression of ventricular ANP is markedly increased in AI rats while that of atrial ANP is not changed.     

抗生素联合卡介苗治疗结核病的动物模型评价

目的用豚鼠模型初步评价抗生素联合卡介苗治疗结核病的可行性。方法用高剂量Mtb皮下攻击豚鼠2周后,将重组ESAT6-CFP10(EC)变态反应原皮试阳性的豚鼠随机分成4组:NS组、BCG组、抗生素组、抗生素+BCG组。抗生素+BCG组接受异烟肼(isoniazid,INH)和利福喷丁(rifapentine,RFT)的联合化疗,1次/周,共3次,给药结束后,每只豚鼠皮下免疫1/10人用剂量BCG;BCG组每只豚鼠仅皮下免疫1/10人用剂量BCG;抗生素组仅给药INH和RFT,1次/周,共3次;NS组给予生理盐水作为阴性对照。全部豚鼠于攻毒13周后安乐死解剖,评价肝、脾、肺的脏器综合病变指数,计算脾脏活菌载量(lg CFU),并对肝、脾、肺脏器做组织病理检查。结果 NS组、BCG组、抗生素组和抗生素+BCG组的脏器评分分别为83±8、81±10、45±28和33±14。其中,BCG组与NS组差异无统计学意义;抗生素组和抗生素+BCG组与NS组差异均有统计学意义(分别q=6.84,P0.001;q=9.02,P0.001),两组与BCG组比较,差异也均有统计学意义(q=6.44,P0.001;q=8.63,P0.001);但抗生素组与抗生素+BCG组差异无统计学意义。抗生素+BCG组豚鼠的脾脏活菌载量为(3.62±1.13)lg CFU,与NS组的(4.92±0.52)lg CFU和BCG组的(5.20±0.43)lg CFU比较,差异均有统计学意义(q=5.54,P0.01;q=6.72,P0.001)。抗生素组脾脏活菌载量为(4.39±0.50)lg CFU,与其他各组的差异均无统计学意义。病理组织切片显示各组病变程度由重到轻依次为BCG组NS组抗生素+BCG组≈抗生素组。结论化疗后免疫1针BCG的治疗效果较差,多针次的BCG免疫效果还需进一步研究。