The correlation of cardiac mass with arterial haemodynamics of resistive and capacitive load in rats with normotension and established hypertension

In hypertensive animals and humans, cardiac hypertrophy may occur as a consequence of an external load on the heart. Several studies have suggested that the non-pulsatile components of arterial haemodynamics, such as arterial pressure and vascular resistance, do not adequately represent the ventricular afterload and are not well correlated with the degree of cardiac hypertrophy (CH). The present study was undertaken to analyse the correlation between the degree of CH and various haemodynamic parameters in the spontaneously hypertensive rat (SHR) with established hypertension. A total of 36 SHRs (6–8 months) with a tail-cuff pressure above 190 mm Hg were used. Control data were obtained from 32 age-matched normotensive Wistar Kyoto rats (WKY). Animals were anaesthetized with pentobarbitone sodium (40 mg/kg i.p.) and artificially ventilated with a respirator. A Millar catheter with a high-fidelity pressure sensor was used to record the aortic pressure and an electromagnetic flow transducer to monitor the aortic flow. The pressure and flow signals were subjected to Fourier transformation for the analysis of the arterial impedance spectrum. The left ventricular weight-to-body weight ratio (LVW/BW) was taken as a measure of the degree of CH. The measured haemodynamic parameters in these anaesthetized, open-chest SHRs were systolic pressure (SP) (mean ± SE) 172±4 mm Hg, diastolic pressure (DP), 120±3 mm Hg, pulse pressure (PP) 52±2 mm Hg, peripheral resistance (R _p) 344,032±8,012 dyne · s · cm^–5, characteristic impedance (Z_c) 6,442±313 dyne · s · cm^–5, the impedance modulus at the first harmonic (Z1) 26,611±1,061 dyne · s · cm^–5, mean arterial compliance (C _m) 0.87 ±0.04 l/mm Hg and LVW/BW 3.092±0.026 mg/g. These parameters were significantly greater than the corresponding values in WKY, except that C _m was much decreased. In SHR, the LVW/BW was not significantly correlated with the SP, DP, R _p and steady external power. In contrast, the degree of CH was positively correlated with Z_c (r=0.66, P<0.001), Z1 (r=0.62, P<0.001) and pulsatile external work (r=0.41, P<0.05). It was also positively correlated with the backward pressure wave (r=0.42, P<0.05) and negatively correlated with C _m (r=-0.72, P<0.01). Such correlations of LVW/BW with pulsatile haemodynamics were not found in the normotensive WKY. The results indicate that the degree of cardiac hypertrophy in hypertensive rats, with a high blood pressure and increased stiffness of the arterial tree, is more closely related to pulsatile arterial haemodynamics than to the nonpulsatile components.     

Effect of whole-body mild-cold exposure on arterial stiffness and central haemodynamics: a randomised, cross-over trial in healthy men and women

Aortic pulse wave velocity (PWV) and augmentation index (AIx) are independent predictors of cardiovascular risk and mortality, but little is known about the effect of air temperature changes on these variables. Our study investigated the effect of exposure to whole-body mild-cold on measures of arterial stiffness (aortic and brachial PWV), and on central haemodynamics [including augmented pressure (AP), AIx], and aortic reservoir components [including reservoir and excess pressures (P _ex)]. Sixteen healthy volunteers (10 men, age 43 ± 19 years; mean ± SD) were randomised to be studied under conditions of 12 °C (mild-cold) and 21 °C (control) on separate days. Supine resting measures were taken at baseline (ambient temperature) and after 10, 30, and 60 min exposure to each experimental condition in a climate chamber. There was no significant change in brachial blood pressure between mild-cold and control conditions. However, compared to control, AP [+2 mmHg, 95 % confidence interval (CI) 0.36–4.36; p = 0.01] and AIx (+6 %, 95 % CI 1.24–10.1; p = 0.02) increased, and time to maximum P _ex (a component of reservoir function related to timing of peak aortic in-flow) decreased (?7 ms, 95 % CI ?15.4 to 2.03; p = 0.01) compared to control. Yet there was no significant change in aortic PWV (+0.04 m/s, 95 % CI ?0.47 to 0.55; p = 0.87) or brachial PWV (+0.36 m/s; ?0.41 to 1.12; p = 0.35) between conditions. We conclude that mild-cold exposure increases central haemodynamic stress and alters timing of peak aortic in-flow without differentially affecting arterial stiffness.     

Effects of chronic exposure to cold or hypoxia on ventricular weights and ventricular myoglobin concentrations in guinea pigs during growth

Male guinea pigs were exposed continuously to 5°C for 2–18 weeks (BW=239–1074 g) or to an ambientPO₂=80 mm Hg for 2–14 weeks (BW=244–965g). Control guinea pigs were kept at 22°C and an average ambientPO₂ of 133 mm Hg.The right and the left ventricular free walls were separated from the septum and weighed (RVW and LVW). Myoglobin concentrations [Mb] of the right and the left ventricles were measured. In all animals, total heart weights (THW), RVW and LVW were linearly related to BW. In the control animals, ventricular [Mb] increased with BW for 2–3 weeks after birth but remained unchanged thereafter. In the 5°C animals, after 4 weeks of exposure, [Mb] in the right and the left ventricles was significantly higher than that of the controls. THW also was significantly higher in the 5°C animals. Furthermore, this cold-induced cardiac hypertrophy was due to both right and left ventricular hypertrophy. In hypoxia-acclimated animals, after 14 weeks of exposure toPO₂=80 mm Hg, the [Mb] of the RV was significantly higher than that of the controls, whereas there was no significant difference between the [Mb] of the LV of the control and hypoxic animals. THW was significantly higher in the hypoxic guinea pigs than in the controls or the 5°C animals. The hypoxia-induced cardiac hypertrophy was due to a marked right ventricular hypertrophy while LVW was significantly lower in the hypoxic animals than in the controls     

Haemodynamic changes induced by short- and long-term sodium chloride or sodium bicarbonate intake in deoxycorticosterone-treated rats

The contribution of chloride to the haemodynamic changes of salt-dependent deoxycorticosterone (DOC) hypertension was studied in young Wistar rats subjected to dietary loading with sodium chloride (NaCl) or sodium bicarbonate (NaHCO₃). Mean arterial pressure (MAP), cardiac output, systemic resistance (TPR) and arterial rigidity (estimated from pulse pressure/stroke volume ratio, PP/SV) were determined in conscious chronically cannulated rats. DOC-induced increase of MAP and TPR appeared earlier in NaCl-loaded than in NaHCO₃-loaded rats. After 4–6 weeks of hypertensive treatment MAP, TPR and PP/SV ratio were higher in DOC-treated rats fed NaCl diet than in those fed NaHCO₃ diet. In contrast, after a long-term hypertensive regimen (lasting for 7–9 weeks) there was no significant difference in either MAP or TPR between rats loaded with NaCl or NaHCO₃. On the other hand, DOC hypertension induced by a long-term feeding of NaHCO₃ diet was not associated with an increase of arterial rigidity which was characteristic for DOC-NaCl hypertensive rats. Thus, a sufficiently long selective dietary sodium loading is capable to increase the systemic resistance but not to alter the arterial rigidity. This was also confirmed by a comparison of blood pressure-matched DOC hypertensive rats fed NaCl or NaHCO₃ diets. These animals did not differ in the degree of systemic resistance elevation but the arterial rigidity was increased only in NaCl-loaded rats.     

扎考比利改善压力超负荷致大鼠心室重构的作用

目的:研究扎考比利(zacopride,ZAC)对腹主动脉缩窄所致大鼠压力超负荷性心室重构的改善作用。方法:通过腹主动脉缩窄构建大鼠压力超负荷心室重构模型,预防性给予ZAC、氯喹(chloroquine,Chlor)及ZAC+Chlor。连续给药8周,超声心动图评价心功能;计算心重/体重比(HW/BW)和左心室/体重比(LVW/BW);左心室心肌组织HE染色;透射电镜观察心肌细胞超微结构;Western blot检测大鼠心肌组织内向整流钾通道(IK1)蛋白表达;RT-PCR法检测心肌组织Kir2.1的mRNA表达。结果:与模型(vehicle)组相比,ZAC组大鼠心功能明显改善,LVEDS和LVEDD明显降低(P 0.05),LVEF和LVFS显著升高(P 0.01),HW/BW和LVW/BW显著降低(P 0.05),心肌肥大程度降低,心肌细胞横断面积明显减小(P 0.01),心肌超微结构明显改善。Chlor明显阻断了ZAC对腹主动脉缩窄所致压力超负荷大鼠心室重构的保护作用。与vehicle组相比,ZAC组大鼠心肌组织IK1蛋白表达和Kir2.1的mRNA显著升高(P 0.01)。结论:心肌IK1激动剂ZAC显著减轻大鼠左心室压力超负荷诱发的心室重构。     

长期TCV116干预对心肌梗死后心室重塑及心功能的影响

目的:研究长期新型血管紧张素Ⅱ1型受体阻断剂TCV116干预对心肌梗死(MI)后心肌重塑及心功能的影响。方法:通过结扎冠状动脉左前降支复制大鼠MI模型,1周后将大鼠随机分为:(1)MI对照组;(2)MITCV116治疗组(2mg.kg^-1·d^-1):另设假手术组及假手术TCV116组。22周后检测:(1)血流动力学参数如平均动脉压(MAP)、左室收缩压(LVSP)、室内压最大上升和下降速率(dp／dt_max)和左室舒张末压(LVEDP)及心脏形态学指标如左室相对重量(LVW／BW)和左室腔相对面积(LVCA／BW);(2)室间隔存活心肌中β肌球蛋白重链(βMHC)、B型钠尿肽(BNP)、转化生长因子β₁(TGF-β₁)、I型和III型胶原(collagenI、III)基因的mRNA表达;(3)存活率。结果:MI对照组与MITCV116治疗组间总体MI范围无显著差异(34%±14％vs33%±13%,P>0.05)。MI对照组LVW／BW和LVCA／BW显著高于假手术组(P<0.01),βMHC、BNP、TGF-β₁、collagenI和III基因的mRAN表达显著大于假手术组(P<0.01);同时MAP、LVSP、dp／dt_max显著低于和LVEDP显著高于假手术组(P<0.01),也伴随着生存时间显著缩短(P<0.05)。TCV116治疗组,LVW／BW和LVCA／BW与MI对照组比无显著差异,βMHC、BNP、TGF-β₁、collagenI和III基因的mRNA表达低于MI对照组(P<0.05或P<0.01);与此同时,MAP、LVSP、dp／dt_max显著高于及LVEDP显著低于MI对照组(P<0.05或P<0.01),并伴随着生存时间的延长(P<0.05)。结论:长期血管紧张素II1型受体阻断剂干预能显著改善心肌梗死后大鼠心室重塑及心功能。     

Cardiac angiotensin II type I and type II receptors are increased in rats submitted to experimental hypothyroidism

This study assessed the behaviour of angiotensin II (Ang II) receptors in an experimental hypothyroidism model in male Wistar rats. Animals were subjected to thyroidectomy and resting for 14 days. The alteration of cardiac mass was evaluated by total heart weight (HW), right ventricle weight (RVW), left ventricle weight (LVW), ratio of HW, RVW and LVW to body weight (BW) and atrial natriuretic factor (ANF) expression. Cardiac and plasma Ang II levels and serum T₃ and T₄ were determined. The mRNA and protein levels of Ang II receptors were investigated by RT-PCR and Western blotting, respectively. Functional analyses were performed using binding assays. T₃ and T₄ levels and the haemodynamic parameters confirmed the hypothyroid state. HW/BW, RVW/BW and LVW/BW ratios and the ANF expression were lower than those of control animals. No change was observed in cardiac or plasma Ang II levels. Both AT1/AT2 mRNA and protein levels were increased in the heart of hypothyroid animals due to a significant increase of these receptors in the RV. Experiments performed in cardiomyocytes showed a direct effect promoted by low thyroid hormone levels upon AT1 and AT2 receptors, discarding possible influence of haemodynamic parameters. Functional assays showed that both receptors are able to bind Ang II. Herein, we have identified, for the first time, a close and direct relation of elevated Ang II receptor levels in hypothyroidism. Whether the increase in these receptors in hypothyroidism is an alternative mechanism to compensate the atrophic state of heart or whether it may represent a potential means to the progression of heart failure remains unknown.     

长期甲状腺素刺激对大鼠心肌Ca /钙调蛋白依赖性蛋白激酶Ⅱ的影响

目的: 通过观察长期甲状腺素刺激对心肌Ca²⁺/钙调蛋白依赖性蛋白激酶Ⅱ(CaMKII)的影响,探讨CaMKII是否参与甲亢性心脏病的发生发展。方法: 将20只SD大鼠随机分为甲状腺素刺激组和对照组,每组各10只。以0.2 mg·kg^-1·d^-1的剂量腹腔注射甲状腺素或等体积生理盐水3个月(每次给药前称体重),造模后3个月处死大鼠。以心重(HW)、心重与体重之比(HW/BW)、左心室重与体重之比(LVW/BW)及心肌细胞直径大小反映心肌肥厚;以心肌血管周围胶原面积(PVCA)/血管腔面积(VA)的比值反映心肌纤维化。用实时定量RT-PCR和Western blotting分别从mRNA水平和蛋白表达水平反映CaMKII的变化。结果: 造模3个月后与对照组相比,甲状腺素刺激组的HW/BW、LVW/BW、心肌细胞直径大小和心肌纤维化程度(PVCA/VA)均明显高于对照组,分别是对照组的1.87、1.84、2.15和1.94倍,差异均显著(P<0.05,P<0.01);甲状腺素刺激组心肌细胞中CaMKII mRNA表达水平、蛋白含量与对照组相比均降低,分别是对照组的40%和79%,但CaMKII的活性较对照组增加1.58倍,其差异均显著(P<0.05)。结论: 长期甲状腺素刺激诱导大鼠心肌肥厚模型中,甲状腺素降低心肌CaMKII的表达,但心肌CaMKII的活性增加,CaMKII可能参与甲状腺素诱导的甲亢性心脏病的发生发展。     

Circadian systemic haemodynamics in borderline and mild hypertension.

Circadian variations in blood pressure (BP), stroke volume (SV), heart rate (HR), cardiac output (CO) and total peripheral resistance (TPR) were determined by a pulse contour method from the intra-arterial pulse wave in 32 normotensive (NT), 32 borderline hypertensive (BHT) and 31 hypertensive (HT) middle-aged men. Daytime averages were used as the reference levels. The nocturnal decrease in BP and HR were similar in the three groups. In the night, SV did not change in the NT group, but was increased in the BHT and HT groups. The nocturnal increase in SV may reflect reduced venous capacity causing increased cardiac filling. As a consequence of the difference in SV, the nocturnal CO fall was diminished in the HT group as compared with the NT group. Moreover, TPR had a tendency to decrease in the HT group, which may be considered as a baroreflex response to buffer the expected rise in BP. Five years later, 25 NT, 24 BHT and 19 HT subjects were reassessed using casual BP measurements. In the NT and BHT groups, six and 17 subjects, respectively, had progressed to hypertension. In a logistic regression model for those who became HT, the nocturnal increase in SV was a significant predictor for future hypertension. In conclusion, the results suggest that circadian systemic haemodynamics may be altered before BP is markedly elevated, and that haemodynamic studies might be useful in predicting the development of sustained hypertension.     

缓激肽在依那普利对心肌梗死大鼠心肌肥厚及心功能影响中的作用

目的:探讨依那普利(enalapril)对大鼠心肌梗塞(M1)后心肌肥厚及心功能的影响是否与其抑制缓激肽(BK)降解的途径有关。方法:将大鼠随机分为:①假手术对照组(sham-operated control),②心肌梗死组(MI),③依那普利干预组(MI+enalapril),④依那普利和BKB₂受体阻断剂Hoe-140共同干预组(MI+enalapril+Hoe-140),⑤血管紧张素ⅡⅠ型受体阻断剂losartan干预组(Ml+losartan)。3个药物干预组从MI术后第3d开始给药,持续4周,然后测定左心室舒张末压(LVEDP)、+dp/dt_max及左心室重/体重(LVW/BW)、左心室非梗死区组织的平均(每核)心肌细胞体积,并进行组间比较。结果:3个药物干预组的LVEDP、LVW/BW及V(m)n均低于MI组(均Pp/dt_max和MI组相比无显著差别。3个药物干预组之间平均动脉压(MAP)无明显差异,但Ml+enalapril+Hoe-140组的LVW/BW及V(m)n的值却高于MI+enalapril组。结论:Enalapril可阻抑大鼠MI后的心肌肥厚并改善左心室功能,这种作用的部分机制是由于其促使了心肌组织BK的积累,即BK参与了enalapril阻抑心肌肥厚及改善心功能的作用,且这些作用不依赖于血压的影响。     

The perinatal rat: body weight, hematocrit and regional changes in heart weight and lactate dehydrogenase isozyme composition and activity

Body weight (BW), hematocrit (Hct), heart weight (HW) and cardiac lactate dehydrogenase (LDH) activity and isozyme pattern were studied in the perinatal rat. BW increased linearly, from 5 days before birth till 10 days after birth, while Hct increased from 30 to 34% within 1 day of birth. HW increased in step with BW. However, the relative contribution to total HW of right ventricle (RV), interventricular septum (S) and atria declined relative to the left ventricle free wall (LVW) beginning 2 to 3 days before birth. RV/LVW declined steadily throughout the study period. LDH specific activity in LVW, RV, S and atria increased greatly prior to birth and less so afterwards, with atria showing the lowest values throughout the study. Total LDH activity in each portion of the heart paralleled the respective regional weight changes. LDH isozyme composition (percent M subunit) declined at the time of birth in LVW, RV and S from 63 to 43%; change in atrial M subunit was smaller. The change in LDH isozyme composition could be accounted for in LVW, RV and S by increasing H subunit activity alone. In atria, both M and H subunit activity increased.     

Development of a patient-specific simulation tool to analyse aortic dissections: Assessment of mixed patient-specific flow and pressure boundary conditions

Aortic dissection has high morbidity and mortality rates and guidelines regarding surgical intervention are not clearly defined. The treatment of aortic dissection varies with each patient and detailed knowledge of haemodynamic and mechanical forces would be advantageous in the process of choosing a course of treatment. In this study, a patient-specific dissected aorta geometry is constructed from computed tomography scans. Dynamic boundary conditions are implemented by coupling a three element Windkessel model to the 3D domain at each outlet, in order to capture the essential behaviour of the downstream vasculature. The Windkessel model parameters are defined based on clinical data. The predicted minimum and maximum pressures are close to those measured invasively. Malperfusion is indicated and complex flow patterns are observed. Pressure, flow and wall shear stress distributions are analysed. The methodology presented here provides insight into the haemodynamics in a patient-specific dissected aorta and represents a development towards the use of CFD simulations as a diagnostic tool for aortic dissection.     

Arterial and left ventricular pressures illude transient alternans of contractility during postextrasystolic potentiation

We have previously found that the postextrasystolic (PES) potentiation (PESP) of the left ventricular (LV) contractility (Emax) decays typically in transient alternans even in the normally ejecting canine heart. This contradicted the general expectation that arterial pressure (AP) and LV pressure (LVP) usually decay exponentially during PESP. We hypothesized this contradiction to be due to the different cardiodynamic behaviors of AP and LVP from LV Emax during PESP. We tested this hypothesis by measuring AP, LVP, LV volume, Emax, effective arterial elastance (Ea) as an index of afterload, and pulse pressure (PP) during PESP in eight anesthetized open-chest dogs by using the conductance catheter system. We changed Ea by changing the total peripheral resistance (TPR) with methoxamine hydrochloride (iv) and repeated the measurements. Although the Emax alternans patterns during PESP were comparable between the normal and high afterloads, LVP and PP were slightly potentiated and alternated under the normal afterload, whereas LVP and PP were obviously potentiated and alternated under the high afterload. We also simulated the effects of Ea/Emax on the transient alternans of AP and LVP on a computer. Despite the same alternans pattern of Emax, a higher Ea/Emax, which is typical in heart failure, caused a larger PP alternans, whereas a lower Ea/Emax, which is typical in normal hearts, almost eliminated it. These results suggest that a transient alternans of LV contractility during PESP could be overlooked when AP and LVP are monitored in in situ normal hearts.     

Surgical Outcomes and Post-Operative Changes in Patients with Significant Aortic Stenosis and Severe Left Ventricle Dysfunction

Little is known regarding long-term survival and changes in systolic function following surgery after the occurrence of a severe left ventricular (LV) dysfunction in patients with severe aortic stenosis. Inclusion criteria were an aortic valve area less than 1 cm² and an LV ejection fraction (EF) less than 35%. Between January 1990 and July 2007, 41 (male: 30) patients were identified. The pre-operative mean EF and mean aortic valve area were 26.7±6.1% and 0.54±0.2 cm², respectively. Concomitant coronary artery bypass surgery was performed in 8 patients (19.6%). Immediate post-operative echocardiogram showed to be much improved in LV EF (27.2±5.5 vs. 37.4±11.3, P<0.001), LV mass index (244.2±75.3 vs. 217.5±71.6, P=0.006), and diastolic LV internal diameter (62.5±9.3 vs. 55.8±9.6, P<0.001). Post-operative LV changes were mostly complete by 6 months, and were maintained thereafter. There was one in-hospital mortality (2.4%) and 12 late deaths including one patient diagnosed with malignancy in whom LV function was normal. Multivariate analysis showed pre-operative atrial fibrillation and NYHA FC IV to be significant risk factors for cardiac-related death. Aortic valve replacement in patients with significant aortic stenosis and severe LV dysfunction showed acceptable surgical outcomes. Moreover, LV function improved significantly in many patients.     

Sex Differences in the Relation of Body Composition to Cardiovascular Parameters and Functions in Korean Adolescents: A School-Based Study

ObjectiveObesity in adolescence is associated with increased cardiovascular risk. The patterns of obesity and body composition differ between boys and girls. It is uncertain how body composition correlates with the cardiovascular system and whether such correlations differ by sex in adolescents.MethodsBody composition (fat-free mass (FFM), adipose mass, waist circumference (WC)) and cardiovascular parameters and functions were studied in 676 healthy Korean adolescents aged 12-16 years. Partial correlation and path analyses were done.ResultsWC correlated with stroke volume (SV) and cardiac output (CO), systolic blood pressure (SBP) and pulse pressure (PP), cardiac diastolic function (ratio of early to late filling velocity (E/A ratio)), and vascular function (pulse wave velocity (PWV)) in boys. Adipose mass was related to SV, CO, SBP, PP, left ventricular mass (LVM), and PWV in girls – and to E/A ratio in both sexes. FFM affected SV, CO, SBP, and PP in both sexes and LVM in boys. Cardiac systolic functions had no relation with any body composition variable in either sex.ConclusionIn adolescence, the interdependence of the cardiovascular system and the body composition differs between sexes. Understanding of those relations is required to control adolescent obesity and prevent adult cardiovascular disease.Key Words: Adolescent, Body composition, Cardiac output, Blood pressure, Pulse wave velocity     

Hormone replacement therapy improves arterial stiffness in normotensive postmenopausal women

Objectives: Aortic stiffness, determined by the pulse wave velocity (PWV), is an independent marker of cardiovascular risk. PWV is mainly influenced by age-associated alterations of arterial wall structure and blood pressure (BP). To determine the impact of hormone replacement therapy (HRT) on arterial compliance in normotensive, postmenopausal women, we examined the effects of HRT on PWV. Methods: Fifty-six postmenopausal women aged 50–70 years were recruited into the present retrospective study from the patients visiting our menopause clinic. Twenty-seven women who were prescribed HRT (14 on estrogen alone and 13 on estrogen plus progestogen) for several months to 6 years and an age-matched group of 29 women not on HRT were studied (Study 1). Nine postmenopausal women were also studied before and at 4 weeks of the treatment of estrogen replacement therapy (ERT) (Study 2). Brachial to ankle PWV (baPWV), which is correlated with aortic PWV, was determined using an automatic device, BP-203PRE. Results: In Study 1, PWV was significantly correlated with age in both groups (controls: r=0.392, P=0.035; HRT group: r=0.471, P=0.013), and HRT significantly lowered the PWV value at all ages examined (Mean±S.D. of baPWV in controls: 1382.2±114.1; HRT: 1245.3±124.8, P=0.0001). In Study 2, baPWV decreased significantly after ERT (P<0.05), without a significant change in systolic BP (P=0.851). Conclusions: Estrogen appears to improve arterial compliance independently of BP within 4 weeks.     

三七总皂苷对异丙肾上腺素所致大鼠心肌肥厚和纤维化的影响

目的：研究三七总皂苷（PNS）对异丙肾上腺素所致大鼠心肌肥厚和纤维化的保护作用。方法： 用异丙肾上腺素（ISO）5 mg·kg^-1·d^-1,sc,连续7 d，建立大鼠心肌肥厚和纤维化模型。造模第2 d开始给大鼠腹腔注射PNS 25和50 mg· kg^-1·d^-1,连续14 d，测定全心重量指数（HW/BW）、左心室重量指数（LVW/BW即LVI）；采用试剂盒用分光光度法检测左心室心肌组织中羟脯氨酸（Hyp）、丙二醛（MDA）、一氧化氮（NO）含量和超氧化物歧化酶（SOD）、谷光苷肽过氧化酶（GSH-Px）、一氧化氮合酶（NOS）活性；用放免分析法检测左心室心肌组织中血管紧张素Ⅱ（AngⅡ）含量。结果： ISO模型组大鼠的HW/BW、LVI、左心室HyP、AngⅡ、MDA含量和诱生型NOS(iNOS)活性显著高于生理盐水对照组，SOD、GSH-Px及结构型NOS(cNOS)活性和NO含量明显比生理盐水对照组低；PNS治疗组左心室心肌组织中NO含量、cNOS 、SOD和GSH-Px活性明显高于ISO模型组；MDA和AngⅡ含量及iNOS活性和心脏重量指数比ISO模型组低。结论： PNS有抗心肌肥厚和纤维化作用，该作用与清除氧自由基及升高NO含量有关。     

不同年龄高血压大鼠心肌中MKP-1的表达及对心肌肥厚的影响

目的：研究不同年龄的自发性高血压大鼠（SHR）和Wistar Kyoto大鼠（WKY）心室肌组织中丝裂原活化蛋白激酶（MAPK）及其磷酸酶（MKP-1）的表达以及与心肌肥厚的关系。方法： 用左心室重量与体重的比值作为心肌肥大指数并以此指标反映心肌肥厚；分别用Western blotting方法和RT-PCR法半定量测定心室肌组织中磷酸化细胞外信号调节激酶（p-ERK）的蛋白表达和MKP-1 mRNA的含量。结果： （1）SHR的血压自8周龄起明显高于WKY（P<0.01），心肌肥大指数明显大于WKY（P<0.05），ERK和MKP-1的表达均比WKY高（P<0.05）；（2）SHR的血压随年龄增长而升高（P<0.05），至14周趋于稳定，心肌肥大指数则在24周时出现激增（P<0.01）；（3）p-ERK随年龄增长呈递增趋势，而MKP-1呈递减趋势，且与心肌肥大指数和ERK的表达呈负相关（P<0.01）。结论： MKP-1在高血压大鼠随年龄和血压增加的心肌肥厚过程中起重要作用，其表达逐渐下降可能是导致ERK激活增加，进而引起心肌细胞肥大的重要原因。     

Continuous monitoring of haemodynamic parameters in humans during the early phase of simulated diving with and without breathholding

This study examined the integrative changes of blood pressure (BP) and stroke volume (SV) leading to the initial biphasic heart rate (f _c) response (first 15 s) in simulated diving manoeuvres with and without breathholding (BH). Simulated diving was studied in ten young healthy volunteers by application of a gel-filled pack at 0°C and 18°C on the forehead with and without BH. Beat-by-beat and second-to-second f _c, BP, SV, and total peripheral vascular resistance (TPR) were followed by continuous non-invasive monitoring. In all conditions (BH with forehead cooling at 0° and 18°C) there was an early rise in BP triggering the first tachycardial response (f _c acceleration) which was immediately counteracted by the concurrent further increase of SV leading to the second phase of early bradycardic response (f _c deceleration). Furthermore, the continuous beat-by-beat and second-to-second monitoring allowed the documentation of a highly significant increase of TPR within the first few seconds of the manoeuvres. Our data further indicated that the differences in haemodynamics observed during the stimuli at different temperatures was overruled by BH. Detailed comparisons of the beat-by-beat and second-to-second analyses were unable to show that one method was better than the other. Using continuous non-invasive monitoring of haemodynamic variables during simulated diving manoeuvres it was possible to provide better insights into the physiological principles and meaning of the diving reflex in humans. Accepted: 2 September 1999     

氯沙坦逆转高血压大鼠心肌重塑的实验研究

目的探讨氯沙坦对自发性高血压大鼠(SHR)心肌重塑的影响。方法16周龄雄性SHR20只,随机分为氯沙坦治疗组和SHR对照组。同龄雄性WKY鼠10只作为正常对照组。给予氯沙坦每天30mg/kg溶于饮水灌胃治疗17周。测定动脉收缩压、左心室壁的厚度、左心室重量与体重之比(LVW/BW)。透射电镜评估左心室肥厚(LVH)的程度。用真彩色图像分析系统计算左心室胶原容积分数。结果氯沙坦治疗组血压、LVW/BW、左室壁厚度与SHR对照组相比明显降低,但与WKY相比有所升高。透射电镜下氯沙坦治疗组心肌的超微结构与WKY相似,SHR的结构有异常改变。与SHR对照组相比,氯沙坦治疗组左心室胶原容积分数下降。结论氯沙坦能有效地降低SHR的血压、逆转高血压左室重塑。