Prolonged protective effects following propranolol withdrawal against isoproterenol-induced myocardial infarction in normotensive and hypertensive rats

Young adult, male and female, normotensive Sprague-Dawley (S-D) and spontaneously hypertensive rats (SHR) were injected with propranolol three times daily for 3 weeks. None of the animals manifested signs of withdrawal when the injections were terminated. Seven days later, the animals were challenged with a dose of isoproterenol which would produce massive myocardial infarction and 50-60% mortality in non-treated animals. The propranolol pretreatment caused marked tranquilizing and blood pressure lowering effects in SHR exclusively. Despite the 7-day propranolol withdrawal period, very few animals died and myocardial damage was minimal. However, blood pressure levels dropped to shock-like levels, blood CPK and LDH levels showed dynamic increases, there was marked hypertriglyceridaemia, and plasma corticosterone rose to supranormal levels. Microscopically, the hearts of the propranolol pretreated animals showed little evidence of necrosis but the SHR hearts manifested large atrial and ventricular thrombi. It is suggested that in the rat, propranolol treatment causes positive myocardial protective effects mediated through hormonal and metabolic changes and propranolol withdrawal does not lead to hypersensitivity to catecholamines. In fact, the beta-blocking effects of propranolol remain effective for some time after withdrawal.     

Prolonged protective effects following propranolol withdrawal against isoproterenol-induced myocardial infarction in normotensive and hypertensive rats.

Young adult, male and female, normotensive Sprague-Dawley (S-D) and spontaneously hypertensive rats (SHR) were injected with propranolol three times daily for 3 weeks. None of the animals manifested signs of withdrawal when the injections were terminated. Seven days later, the animals were challenged with a dose of isoproterenol which would produce massive myocardial infarction and 50-60% mortality in non-treated animals. The propranolol pretreatment caused marked tranquilizing and blood pressure lowering effects in SHR exclusively. Despite the 7-day propranolol withdrawal period, very few animals died and myocardial damage was minimal. However, blood pressure levels dropped to shock-like levels, blood CPK and LDH levels showed dynamic increases, there was marked hypertriglyceridaemia, and plasma corticosterone rose to supranormal levels. Microscopically, the hearts of the propranolol pretreated animals showed little evidence of necrosis but the SHR hearts manifested large atrial and ventricular thrombi. It is suggested that in the rat, propranolol treatment causes positive myocardial protective effects mediated through hormonal and metabolic changes and propranolol withdrawal does not lead to hypersensitivity to catecholamines. In fact, the beta-blocking effects of propranolol remain effective for some time after withdrawal.     

Hormonal and metabolic changes during acute myocardial infarction in normotensive vs hypertensive rats.

Male and female, normotensive, Sprague-Dawley (S-D) rats, and spontaneously hypertensive rats (SHR) were subjected to acute and massive myocardial infarction with isoproterenol. Some of the animals were pre-treated (7 days) with the prolactin-lowering drug, bromocryptine. SHR survived in greater numbers than S-D but developed massive congestive heart failure of late onset. The adrenal glands and hearts became greatly hypertrophied in parallel with severely involuted thymus glands. ECG tracings demonstrated intense tachycardia and myocardial ischaemia. Bromocryptine reduction of prolactin (PRL) showed no effect on ECG tracings but reduced triglyceride, free fatty acid, total cholesterol and glucose levels. Isoproterenol caused dynamic increase in glucose, free fatty acids and triglycerides. CPK levels demonstrated greater cardiac damage in S-D vs SHR; greatly elevated SGOT and SGPT levels confirmed the presence of fatty liver in S-D and SHR. Myocardial infarction caused marked increase in circulating PRL in females only and sustained increases in aldosterone and corticosterone. SHR survivors had a high incidence of atrial and ventricular thrombi, left ventricular aneurysms, and intense fibroplasia and cartilaginous metaplasia in areas adjacent to damaged myocardium. It is suggested that adrenal steroidogenesis during an acute myocardial infarct favours survival and more complete myocardial repair in females vs males, and preexisting hypertension in SHR is associated with hormonal and metabolic response patterns different from normotensive S-D rats.     

Social stress, myocardial damage and arrhythmias in rats with cardiac hypertrophy.

In rat models of cardiac hypertrophy (moderate aortic coarctation: ACm, n=18; severe aortic coarctation: ACs, n=27; aging: OLD, n=25; spontaneous chronic hypertension: SHR, n=18) and properly matched control animals (C(ACm), n=17; C(ACs), n=19; C(OLD), n=24; C(SHR), n=22), we investigated the relative contribution of intense autonomic activity and cardiac structural damage to ventricular arrhythmogenesis. We used an "in vivo" to tissue level approach, by correlating in the same animal: (i) social stress-induced ventricular arrhythmias, telemetrically recorded, and (ii) left ventricular weights (LVW) and amount and geometrical properties of myocardial fibrosis (MF). Arterial blood pressure was significantly higher in ACm (+11%), ACs (+28%) and SHR (+34%) than in controls. LVW were approximately 20% greater in ACm, ACs and OLD and 50% greater in SHR. MF was about twice as great and characterized by more frequent occurrence of microscopic scarring in ACm and ACs, and eight times greater and associated with both a higher number and a larger size of fibrotic foci in OLD and SHR compared to controls. Social stress increased ventricular arrhythmia vulnerability in all models of cardiac hypertrophy, as well as in controls. The arrhythmogenic action of stress was facilitated in ACs, OLD and SHR. A correlation between structural cardiac remodeling and ventricular arrhythmias was found only in SHR and OLD, which exhibited the greatest increase in LVW and/or MF. Social stress proved to be a valuable tool for analyzing the combined effects of autonomic stimulation and altered myocardial substrate on the genesis of potentially life-threatening arrhythmias in social animals.     

Effects of a diet rich in Q-3 fatty acids on left ventricular geometry and dynamics in spontaneously hypertensive rats

Summary The aim of the present study was to investigate the chronic effects of a dietetic antihypertensive treatment on blood pressure, ventricular dynamics and geometry of the pressure loaded heart. Spontaneously hypertensive rats (SHR) received a standard diet enriched with 10% mackerel oil, containing 30% polyunsaturated Q-3 fatty acids, over a period of 70 days. As described previously the diet reduced blood pressure permanently by 40-50 mm Hg. Despite this reduction, the degree of left ventricular hypertrophy was only slightly (statistically insignificantly) reduced. This was probably a result of an increase in sympathetic tone as indicated by a raised pulse rate. On the other hand, the treatment prevented the development of eccentric hypertrophy, typical to the SHR, without changing the elastic material properties of the myocardium. Since the age-matched controls did not show significant degenerative alterations, protective effects at the level of myocardial tissue could not be demonstrated. Furthermore, future investigations need to investigate why myocardial contractility of the treated animals diminishes as observed in this study.     

加味镇眩颗粒对高血压大鼠心肌基质金属蛋白酶-2和微血管密度的影响

目的观察加昧镇眩颗粒对自发性高血压大鼠（SHR）血浆血管紧张素Ⅱ（AngⅡ）、心肌基质金属蛋白酶-2（MMP-2）表达水平和微血管密度（MVD）的影响。方法将50只SHR大鼠随机分为加味镇眩颗粒高剂量组、加味镇眩颗粒中剂量组、加味镇眩颗粒低剂量组、卡托普利组、SHR对照组,经过12周的干预,分别测定动物血压变化,血浆AngⅡ含量、免疫组织化学法检测心肌MMP-2蛋白表达水平、心肌微血管密度。结果治疗组均可降低SHR血压、血浆AngⅡ含量、心肌MMP-2蛋白表达水平,增加SHR心肌微血管密度,与SHR组相比差异具有统计学意义（P〈0．05）,中药组中,加味镇眩颗粒高剂量组效果最好。与卡托普利组相比,高剂量组在12周末降压效果相当（P〉0．05）,且更能降低心肌MMP-2蛋白表达水平（P〈0．05）,增加SHR心肌微血管密度（P〈0．05）。结论加味镇眩颗粒可降低SHR血压,可能与降低血浆血管紧张素Ⅱ含量．下调心肌MMP-2蛋白表达水平,改善SHR大鼠心肌微血管稀疏的作用有关。     

Ameliorative effects of adrenalectomy on the hyperphagia,hyperlipidaemia, hyperglycaemia and hypertension of obese,spontaneously hypertensive rats (Obese/SHR).

Genetically obese and hypertensive rats (Obese/SHR) were subjected to sham or bilateral adrenalectomy at 4-5 weeks of age with the onset of hyperphagia. The sham-operated Obese/SHR ate voraciously and by 180 days of age males weighed 700 g and females 590 g. The adrenalectomized Obese/SHR ate much less and weighed 325 and 225 g. The systolic blood pressure of the intact Obese/SHR ranged from 160 to 170 mmHg, whereas the blood pressure of the adrenalectomized animals ranged from 108 to 110 mmHg. The thymi of the intact Obese/SHR were massive compared to those of the adrenalectomized rats. Adrenalectomy effectively reduced the hyperinsulinaemia, adiposity, hyperlipidaemia, hyperglycaemia, and elevated BUN levels of the obese rats. Several obese rats had old or new myocardial infarcts, fatty livers, giant-sized islets of Langerhans, nodular and hyperaemic adrenal glands, narrow zona glomerulosa devoid of lipid, vacuolated inner cortical zones, foci of intimal fibrinohyalin deposits in mesenteric arteries, early glomerulosclerosis, and large, rounded bladder calculi. The adrenalectomized Obese/SHR displayed none of these stigmata. It is suggested that the genetically programmed obesity and hypertension in these SHR are mediated by abnormal activity of the hypothalamic-pituitary-adrenal-gonadal axis, may be likened to Cushing''s disease in the human, and is associated with accelerated ageing.     

Intravenous administration of vascular endothelial growth factor improves cardiac performance and inhibits cardiomyocyte apoptosis

This study investigated the effects of vascular endothelial growth factor (VEGF) intravenous administration on cardiac performance and cardiomyocyte apoptosis in a rat model of acute myocardial infarction. Left coronary artery ligation produced extensive myocardial infarction in 48 rats and sham operated in 24 animals. Twenty-four hours after surgery, the rats were randomized to receive VEGF165-heparin (treated group) or heparin-saline (control group) treatment. The sham-operated animals were also to receive VEGF165-heparin (sham group) treatment. VEGF165 (2 microg/ml) with heparin (50 U) or heparin-saline (50 U/ml) was administered daily via the tail vein for 7 and 14 days. Fifty-eight rats survived and included in the study. There were not significant effects of VEGF on hemodynamic parameters in sham animals. As compared with control animals at 9 days after ligation (with 10 rats for each group), rats treated with VEGF had significantly higher maximum rate of left ventricular pressure rise (+ dP/dtmax) or fall ( - dP/dtmax) and microvessel counts, and significantly lower left ventricular end-diastolic pressure (LVEDP) and infarct size. At 16 days after surgery (12, 7 and 9 rats in sham, control and treated groups; respectively), VEGF treatment significantly increased mean arterial pressure (MAP), left ventricular systolic pressure (LVSP), +/- dP/dtmax and microvessel counts, and significantly decreased LVEDP and infarct size. VEGF treatment significantly inhibited cardiomyocyte apoptosis and the expression of p53, Fas and Bax protein, and increased the expression of Bcl-2 protein in myocardium at 9 days after myocardial infarction.     

Effect of chemical sympathectomy on cardiac hypertrophy and hemodynamics following myocardial infarction in the rat

The effects of sympathectomy on cardiac structure and function were studied in an animal model of myocardial infarction. Ninety-six rats were double randomized to control or infarction disease state and to placebo or chemical sympathectomy (guanethidine, 30 mg/kg daily, intraperitoneal). Five weeks after anterior infarction, there was hypertrophy in placebo-treated animals in myocardial fibers remote from the infarct (9.8 +/- 1.8 microns in infarction vs 8.1 +/- 1.0 microns in control, p less than 0.05). However, myocardial hypertrophy was not present in guanethidine-treated animals (8.6 + 1.6 microns in infarction vs 8.0 + 0.6 microns in control, p = N.S.). Guanethidine treatment caused significant reductions in systolic arterial blood pressure and indices of left ventricular contractility and relaxation (p less than 0.05), but these effects were not different between infarct and control treatments (p = N.S.). Although both effects of guanethidine treatment (sympathectomy and hemodynamic) were correlated with myocardial fiber diameter by univariate analysis, only sympathectomy was significant by stepwise regression analysis (p less than 0.05). Therefore, the cardiac sympathetic nerves have important effects on the development of hypertrophy after myocardial infarction, and sympathectomy alters this process in the rat model.     

钩藤碱对自发性高血压大鼠心室重构过程中TGF-β_1/Smad通路的影响

目的:观察钩藤碱对自发性高血压大鼠血压、心肌肥厚及心肌纤维化的影响并探讨其可能的作用机制。方法:32只自发性高血压大鼠随机分为模型组、钩藤碱高(10 mg·kg-1·d-1)、低(2.5 mg·kg-1·d-1)剂量组、卡托普利组(17.5 mg·kg-1·d-1),每组8只。另设8只Wistar-Kyoto大鼠作为正常对照组。分别于给药前和给药后每2周测量尾动脉收缩压(SBP)。治疗10周后处死大鼠,取其心脏计算全心重量指数和左心室重量指数;检测心肌中羟脯氨酸(HYP)及血浆中血管紧张素Ⅱ(AngⅡ)的含量;HE染色观察心肌病理学变化,Masson染色观察心肌胶原纤维变化;免疫组化法和Western blot法测心肌组织转化生长因子-β1(TGF-β1)和Smad3蛋白的表达。结果:与模型组相比,钩藤碱能明显降低自发性高血压大鼠的血压(P0.05),降低心肌HYP含量及血浆AngⅡ的含量(P0.05),减轻心肌组织的病理损伤和胶原纤维沉积,下调TGF-β1和Smad3蛋白的表达(P0.01)。结论:钩藤碱能降低自发性高血压大鼠的血压、调节改善自发性高血压大鼠的心室重构,其机制可能与其影响TGF-β1/Smad通路以及降低AngⅡ含量有关。     

Functional and stereologic estimations of myocardial capillary exchange capacity in treated and untreated spontaneously hypertensive rats.

Myocardial capillary exchange capacity was investigated by stereologic and functional techniques in parallel during pressure-overload cardiac hypertrophy and after long-term antihypertensive therapy with the vasodilator felodipine. In 26-week-old female spontaneously hypertensive rats (SHR) blood pressure increased by 25% and left ventricular weight (LVW/BW) increased by 18% compared to Wistar-Kyoto rats (WKY). Myocardial capillary surface and volume densities normalized for organ weight were similar in both ventricles for both strains. Moreover, capillary surface density was higher sub-epicardially (EPI) than in the subendocardium (ENDO) in the left ventricle of SHR. Thirteen weeks of felodipine-therapy (SHR-Felo) normalized blood pressure without affecting LVW/BW although a transition from concentric to eccentric hypertrophy is known to occur. Myocardial capillary surface and volume densities and the left ventricular ENDO-EPI-gradient in surface density were similar to untreated SHR. However, felodipine-treatment increased right ventricular weight and capillary volume density. Functional capillary exchange was estimated in terms of permeability surface area products (PS) for Cr-EDTA and vitamin B12 and normalized for organ weight. PSCr-EDTA, PSB12 and the ratio PSCr-EDTA/PSB12 (an index of capillary permeability) were similar in SHR and WKY. Furthermore, the relation between functional and stereological indices of exchange capacity was investigated in a multiple linear regression analysis. However, no significant correlation between PS and neither capillary surface nor volume density was found. In conclusion, myocardial capillary exchange capacity was well adapted to the pressure overload cardiac hypertrophy present in female SHR. Despite induction of right ventricular hypertrophy, felodipine-treatment did not affect capillary exchange capacity. Furthermore, when functional and stereologic estimates were performed in parallel, the importance of dynamic factors for myocardial capillary exchange capacity (e.g. heterogeneity) was illustrated.     

Utility of a population-based case-control study model with a limited number of patients in estimating risks of hypertension

A population-based case-control study of the risks of hypertension was carried out in a primary care district where data on all patients have been registered in out- and in-patient computer schemes and where extensive studies and treatment programs regarding blood pressure have been performed for more than a decade. The results of the study, which comprised a limited number of patients, accord with those of more extensive and prospective studies. The hypertensives had high risks of developing myocardial infarction and stroke even though they were treated according to internationally accepted norms regarding blood pressure. The estimated population-attributable risk of hypertension in men was 30% with regard to myocardial infarction and 68% with regard to stroke. Smoking and hypertension were found to be independent risk indicators of myocardial infarction in men and hypertension was a strong risk indicator of stroke. Thus, a case-control study carried out in this way in a primary care district gives valid results regarding the efficacy of an antihypertensive treatment program and may therefore serve as a model for future studies in primary health care.     

阿托伐他汀对自发性高血压大鼠心室重塑的作用及机制

目的：研究阿托伐他汀对自发性高血压大鼠（SHR）心室重塑的作用及机制。方法：雄性SHR 12只，随机分为2组（每组6只）：阿托伐他汀组（阿托伐他汀50 mg·kg^-1·d^-1）和SHR（0.5%阿拉伯胶浆10 mL·kg^-1·d^-1）组；另选WKY大鼠6只（0.5%阿拉伯胶浆10 mL·kg^-1·d^-1）作为正常对照组。实验6周后，称取大鼠全心重量及左心室重量，计算左心室重量指数；同时检测心肌羟脯氨酸、胶原蛋白含量；大鼠血清C反应蛋白含量；免疫组化检测心肌血管细胞黏附分子(VCAM)的表达；原位杂交测定心肌细胞NF-κB的表达；透射电镜观察心肌的超微结构。结果：SHR组心肌NF-κB的表达和心肌VCAM的表达强于WKY组；阿托伐他汀组大鼠的心脏重量、心肌羟脯氨酸、胶原蛋白和大鼠血清C反应蛋白的含量低于SHR组；同时心肌NF-κB的表达和心肌VCAM的表达低于SHR组。透射电镜显示：阿托伐他汀组细胞核膜不完整，肌原纤维排列紊乱，横纹不清，间质胶原纤维增生等病理改变轻于SHR组。结论：阿托伐他汀具有改善SHR心室重塑的作用，其分子机制可能下调SHR心肌NF-κB的表达和心肌VCAM的表达，抑制心肌的慢性炎症有关。     

2-Methoxyestradiol attenuates hypertension and coronary vascular remodeling in spontaneously hypertensive rats

ObjectivesAccumulating data provide evidence that some metabolites of 17β-estradiol are biologically active and mediate multiple effects on the cardiovascular and renal systems. We investigated the effect of 2-methoxyestradiol (an active metabolite of estradiol with non-feminizing activity) on the development of hypertension and myocardial vascular remodeling in male and female ovarectomized SHR.MethodsRats were divided into five groups: intact females, ovarectomized (OVX), OVX+ 2-methoxyestradiol (2ME), control males, and male + 2ME. Systolic blood pressure was determined from 10 to 18 weeks. Structural changes in coronary vessels were quantified by an image analyzer. Immunoblotting of phosphorylated ERK1/2 and NADPH oxidase activity were performed on mesenteric arteries.ResultsTreatment with 2ME reduced the increase in systolic blood pressure in male and ovarectomized rats to values not different from those obtained in intact females. Myocardial arterioles and small arteries showed significant increases in wall-to-lumen ratio and perivascular fibrosis in male and ovarectomized rats when compared with intact females. NADPH oxidase activity was increased in mesenteric arteries from males and ovarectomized females as compared with intact females. Finally, the expression of phosphorilated ERK1/2 were significantly higher in mesenteric arteries from male and ovariectomized animals than in those from intact females. Those effects of ovarectomy and gender differences were totally or partially prevented by treatment with 2-methoxyestradiol.ConclusionsThese data demonstrate that 2-methoxyestradiol protects the vasculature from hypertension-induced myocardial arterial remodeling in male and ovarectomized SHR, and that might be in part related to decreased superoxide generation and ERK1/2 activation.     

Diastolic properties of the hypertrophied left ventricle in spontaneously hypertensive rats

The influence of myocardial hypertrophy on left ventricular volume compliance was studied in vitro in isolated hearts of 4 and 19 month old spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). In both SHR groups diastolic volume compliance was similar to that in the controls, despite the presence of left ventricular hypertrophy. This seems to be mainly due to an altered geometric situation, since with increased wall thickness to internal radius ratio (w/ri), which was at hand, the less are outer myocardial layers stretched at a given increase in ventricular volume. This may imply that these layers will only little interfere with luminal distension (and thereby with diastolic volume compliance) in SHR. It was also observed that the progressive increase of ventricular hypertrophy from 4 to 19 months of age did not further increase w/ri in SHR, indicating an increase in overall ventricular size with age. Left ventricular end diastolic pressure (LVEDP) was also measured in conscious 5 week and 4 month old SHR compared with matched controls. LVEDP increased with the development of hypertension and was significantly elevated in 4 month old SHR. This will increase also the average diastolic pre-stretch of the SHR left ventricle and mobilize the "Starling mechanism" to maintain a normal stroke volume against the increased afterload for the heart in established hypertension. This seems particularly important since the hypertrophic w/ri increase (about 20%) is smaller than the great elevation of mean arterial pressure (40-50%) in SHR.     

Functional and stereologic estimations of myocardial capillary exchange capacity in treated and untreated spontaneously hypertensive rats

Myocardial capillary exchange capacity was investigated by stereologic and functional techniques in parallel during pressure-overload cardiac hypertrophy and after long-term antihypertensive therapy with the vasodilator felodipine. In 26-week-old female spontaneously hypertensive rats (SHR) blood pressure increased by 25 % and left ventricular weight (LVW/BW) increased by 18% compared to Wistar-Kyoto rats (WKY). Myocardial capillary surface and volume densities normalized for organ weight were similar in both ventricles for both strains. Moreover, capillary surface density was higher sub-epicardially (EPI) than in the subendocardium (ENDO) in the left ventricle of SHR. Thirteen weeks of felodipine-therapy (SHR-Felo) normalized blood pressure without affecting LVW/BW although a transition from concentric to eccentric hypertrophy is known to occur. Myocardial capillary surface and volume densities and the left ventricular ENDO-EPI-gradient in surface density were similar to untreated SHR. However, felodipine-treatment increased right ventricular weight and capillary volume density. Functional capillary exchange was estimated in terms of permeability surface area products (PS) for Cr-EDTA and vitamin B₁₂ and normalized for organ weight. PS_cr-EDTA, PS_B12 and the ratio PS_cr-EDTA/PS_B12 (an index of capillary permeability) were similar in SHR and WKY. Furthermore, the relation between functional and stereological indices of exchange capacity was investigated in a multiple linear regression analysis. However, no significant correlation between PS and neither capillary surface nor volume density was found. In conclusion, myocardial capillary exchange capacity was well adapted to the pressure overload cardiac hypertrophy present in female SHR. Despite induction of right ventricular hypertrophy, felodipine-treatment did not affect capillary exchange capacity. Furthermore, when functional and stereologic estimates were performed in parallel, the importance of dynamic factors for myocardial capillary exchange capacity (e.g. heterogeneity) was illustrated.     

Effect of spontaneous running on blood pressure, heart rate and cardiac dimensions in developing and established spontaneous hypertension in rats

The effect of chronic voluntary exercise on resting blood pressure and heart rate was measured in two different age groups of spontaneously hypertensive rats (SHR). In the younger group, left ventricular dimensions were also measured. The younger group was 9 weeks old at the start of the experiment and was in a period of rapid blood-pressure rise. The older group, 13 weeks old at the start of the experiment, already had established hypertension. During a period of 6 weeks, the animals ran spontaneously in wheels mounted in their cages and reached a maximum of 6-7 km per 24 h. Age-matched, sedentary SHR were used as controls. Both groups of runners showed a decrease in body weight in comparison to controls. The younger runners exhibited a delayed onset of hypertension. They also showed a significantly increased left ventricular (LV) end-diastolic volume for every measured end-diastolic pressure between 7.5 mmHg and 20 mmHg (P less than 0.05). This suggests the development of a structural growth-dependent increase of the internal LV radius while LV weight and wall-to-lumen ratio were largely unaltered in younger runners compared with controls. In SHR with established hypertension, physical training did not reduce arterial blood pressure but heart rate was significantly lower than in the controls. These results thus indicate that an early onset of physical exercise in SHR may delay the development of hypertension. In addition, a more favourable cardiac design could also be seen.     

苯那普利对自发性高血压大鼠心肌缺血-再灌注心功能、氧自由基和肌浆网Ca2+-ATP酶的影响

目的:探讨血管紧张素转换酶抑制剂(ACEI)对自发性高血压大鼠(SHR)心肌缺血-再灌注心功能、氧自由基和肌浆网Ca²⁺-ATP酶的影响。方法:30只10周龄雌性SHR分为2组,SHR对照组(SHR)、SHR+B组(每日10mg/kg苯那普利);另15只同周龄、同性别Wistar大鼠作为对照组(Wistar)。治疗12周后,每组大鼠结扎左冠状动脉前降支30min,再灌注30min,观察血流动力学参数,左室心肌丙二醛(MDA)含量、超氧化物岐化酶(SOD)活性及肌浆网(SR)Ca²⁺-ATP酶活性。结果:与Wistar组比较,SHR组血压、左心室重/体重较高,左心功能损害程度较重,心肌MDA含量较高,SOD活性和SRCa²⁺-ATP酶活性较低;SHR+B组血压、左心室重/体重、左心功能损害程度,SRCa²⁺-ATP酶活性无显著性差异,但心肌MDA含量较低,SOD活性较高。结论:苯那普利可逆转SHR左室肥厚,促进缺血-再灌注心肌SRCa²⁺-ATP酶活性的恢复和减少氧自由基损害,从而减轻缺血-再灌注心功能损伤。     

Effect of a flexible ventricular restraint device on cardiac remodeling after acute myocardial infarction

The effects of a flexible ventricular restraint device on left ventricular (LV) dilatation and hypertrophy after transmural infarction are examined in an ovine model. Left ventricular remodeling and dilatation occurs after extensive myocardial infarction. A flexible ventricular restraint made from a nitinol mesh was evaluated in adult female sheep (n=14). Cardiac magnetic resonance imaging scans and hemodynamic measurements were completed before and 6 weeks after anterior myocardial infarction. Treatment animals (n=7) received passive ventricular restraint concurrently with LV infarction; the others (n=7) served as controls. Increases in LV end-diastolic volume index were significantly less in the restraint group than in controls (0.20+/-0.41 vs 0.83+/-0.50 ml/kg, p<0.03). End-systolic volumes increased less in treatment animals (0.43+/-0.28 vs 0.90+/-0.38 ml/kg, p<0.03). Control hearts showed an increase in LV mass after infraction, whereas LV mass decreased in restrained hearts (0.14+/-0.19 vs -0.25+/-0.36 g/kg, p<0.03). Hemodynamic studies showed similar changes after infarction for the control and the device group. Gross and microscopic examination showed no device-induced epicardial injury. A flexible ventricular restraint device attenuated remodeling after acute myocardial infarction in sheep.     

Comparative effects of cortisone,dianabol and enovid on isoprenaline-induced myocardial infarction in arteriosclerotic vs nonarteriosclerotic rats.

Male and female nonarteriosclerotic (virgin) and arteriosclerotic (breeder) Sprague-Dawley rats were subjected to acute myocardial infarction with isoprenaline. When myocardial necrosis was most intense, animals were given cortisone (high and low doses), Dianabol, or Enovid. Animals receiving large doses of cortisone manifested the best survival rate during the early stages of myocardial infarction. Although their serum enzyme levels were least elevated and their hearts showed tha least amount of damage, these animals had undergone the most intense body weight loss and began to die suddenly during the later stages of the experiment. These animals also manifested hyperlipidaemia, hyperglycaemia, septicaemia, severe disuse atrophy of their adrenal glands, and reduced Cmpd. B production. Animals treated with low doses of cortisone or with the anabolic and androgenic steroid, Dianabol, manifested none of the myocardial pretective effects of the larger dose of cortisone. These animals displayed a high incidence of left ventricular aneurysm formation concomitant with extensive cartilaginous metaplasia within the aneurysmal sites. Treatment with the contraceptive drug, Enovid, caused body weight loss, hyperlipidaemia, hyperglycaemia, gonadal atrophy and reduction of Cmpd. B production. Although the high dose of cortisone exercised definite salutary effects during early myocardial infarction, chronic treatment led to adrenal disuse atrophy and hypoadrenocorticism associated with sudden death during the later stages of myocardial repair. These findings indicate that proper adjustment of the dose and chronicity of corticosteroids used for treating the crisis of acute myocardial infarction must be made in order to provide effective protection against untoward pathophysiological conditions, acceleration of myocardial repair, but without suppression of adrenal function.