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。     

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。     

Changes in myocardial capillary diffusion capacity during infusion of vasoactive drugs

The present study investigated how variations in coronary vascular resistance and metabolic demand affected myocardial capillary diffusion capacity. Hearts from Wistar rats were perfused with Krebs-Henseleit-albumin buffer in a Langendorff preparation, where heart rate (HR), contractility (dP/dt_max) and myocardial oxygen consumption (MVO₂) were recorded continuously. Myocardial capillary diffusion capacity was measured as the permeability surface area product (PS) for Cr-EDTA and vitamin B₁₂ by the single injection colorimetric indicator dilution method. After base-line recordings without drugs, angiotensin II + arginine-vasopressin was infused, which increased coronary vascular resistance by 90%, stimulated HR by 11%, decreased dP/dt_max by 21% and reduced MVO₂ by 4%. PS_Cr-EDTA and PS_B12, decreased by 24 and 27%, respectively, leaving the ratio PS_Cr-EDTA/PS_B12 unchanged indicating unaltered capillary permeability. Moreover, the reductions in MVO₂ and PS correlated significantly. During vasodilation: (1) nitroprusside-NA stimulated HR by 7% and decreased dP/dt_max by 14%; (2) adenosine reduced dP/dt_max by 37% and decreased MVO₂ by 9%; and (3) isoproterenol increased HR, dP/dt_max and MVO₂ by 53, 76 and 9%, respectively. However, all three vasodilators reduced PS_Cr-EDTA and PS_B12 in parallel by 7–25% leaving PS_Cr-EDTA/PS_B12 unchanged. Thus, maximal estimated diffusion capacities were obtained during spontaneous coronary vascular tone, most likely reflecting maximal capillary recruitment in the Krebs-Henseleit-albumin perfused heart. The derecruiting effects of the vasoconstrictors were partly overridden by metabolic factors, while the reductions of PS after vasodilation more likely were due to increased heterogeneity in coronary flow.     

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.     

Role of aspirin in modulating myocardial ischemic reperfusion injury

The role of low-dose aspirin (3 mg/kg, i.v.) in attenuating ischemic reperfusion injury was studied in a canine model. Regional ischemia for 40 min was produced by temporary occlusion of the left anterior descending coronary artery and thereafter reperfusion instituted for 3 h. Mean arterial pressure (MAP), heart rate (HR), left ventricular end diastolic pressure (LVEDP), positive (+) LV dP/dt _max and negative (–) LV dP/dt _max were monitored alongwith myocardial adenosine triphosphate (ATP), creatine phosphate (CP), glycogen and lactate. Following reperfusion, there was a significant fall in (i) MAP, (ii) (+) LV dP/dt _max and (iii) (–) LV dP/dt _max. LVEDP was corrected after about 2h of reperfusion. Replenishment of only myocardial CP occurred, without any change in ATP and glycogen, although lactate accumulation was corrected.Aspirin administered 15 min before reperfusion (posttreatment) caused normalisation of LVEDP within 15 min and prevented any deterioration in (–) LV dP/dt _max, although it had no effect on MAP and (+) LV dP/dt _max. After 3h of reperfusion (post-treatment), myocardial ATP, CP, glycogen and lactate contents became normal. The number of premature ventricular complexes was significantly reduced after aspirin treatment. The present study indicates that low-dose aspirin post-treatment can ameliorate at least some of the deleterious consequences of reperfusion injury of the myocardium.     

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 μg/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/dt_max) or fall ( ? dP/dt_max) 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/dt_max 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.     

Relative roles of vagal and sympathetic effector mechanisms in the baroreflex control of myocardial contractility in conscious rabbits

The relative roles of vagal and sympathetic effector mechanisms in the baroreflex control of myocardial contractility have been assessed in the conscious normotensive and hypertensive rabbit. Graded increases in mean arterial pressure (MAP) were produced by inflation of a balloon occluder around the abdominal aorta. Stimulus response curves relating the change in MAP to the induced change in peak rate of change of left ventricular pressure (peak LVdP/dt) were produced when heart rate was allowed to change and when it was held constant by atrial pacing. These curves were repeated after sympathetic blockade with propranolol, vagal blockade with methylscopolamine and combined blockade with the two drugs together.Increase in MAP produced a reflex fall in peak LVdP/dt which was due to two components. There was a reflex negative inotropic effect which was independent of heart rate, occurring in animals in whom heart rate was held constant by atrial pacing, and there was also a reduction in peak LVdP/dt which was caused by the reflex bradycardia when the heart rate was allowed to change. Both sympathetic and vagal efferents contributed to the reflex fall in peak LVdP/dt seen after elevation of MAP, the sympathetic being primarily responsible for the direct negative inotropic effect and the vagus for the bradycardia and hence the secondary effects on peak LVdP/dt.The slope of the stimulus response curves relating the fall in peak LVdP/dt to the increase in MAP was similar in intact normotensive and hypertensive rabbits, both with and without atrial pacing. This indicates that the sensitivity of the baroreceptor-myocardial contractility reflex was not impaired in the hypertensive animals, 6 weeks after renal wrapping, even though reflex control of heart rate is blunted at this time. Furthermore, the relative contribution of the vagus and the sympathetic to the control of contractility was similar in normotensive and hypertensive animals when heart rate was allowed to change. On the other hand, when the heart rate was held constant with atrial pacing, vagal blockade with methyl scopolamine revealed a contribution of the vagus to the reflex negative inotropic effect in hypertensive rabbits that was not evident in normotensive animals.     

Superiority of developed over total pressure for heart contractility indices in dogs

Summary The independence of indices of contractility to Starling effects was tested in 6 closed-chest dogs. After vagal and beta-receptors blockade, indices calculated with total left ventricular isometric pressure (TP), were shown to be strongly dependent of rises in end-diastolic pressure (LVEDP) induced by dextran infusion. At LVEDP of 14.6±1.5, 22.2±1.1 and 32.8±1.5 mm Hg (±SEM), the peak value of velocity of the contractile elements calculated with total pressure (peak V_{CE, TP}) diminished by 21, 40 and 50%, and the extrapolated value of V_{CE, TP} at zero total pressure (V_{max, TP}) diminished by 15, 30 and 44%. In contrast, indices calculated with developed pressure (DP=TP-LVEDP) at the same LVEDP were much less influenced, particularly the extrapolated value of V_{CE, DP} at zero DP (V_{max, DP5}) and (peakdP/dt)/DP did not significantly change.During angiotensin infusion, expected decreases in TP indices secondary to LVEDP rises were partially masked by simultaneous increases in contractility, and DP indices tended to rise. On the other hand, with minimal changes in LVEDP, as during calcium injection and paired stimulation, increases in TP and DP indices demonstrate inotropic effects equally well.Our study also shows that, besides V_max calculated with DP, the instantaneous ratio of peakdP/dt and DP can also be proposed as a simpler and thus more convenient index of contractility independent of volume changes.This work was supported in part by Grant 20022 from the Fonds de la Recherche Scientifique Médicale.     

Parameters of ventricular contractility in mice: influence of load and sensitivity to changes in inotropic state

We examined the relative usefulness of parameters to determine left ventricular contractility in mice invasively. The optimal parameter must be sensitive to changes in inotropy and insensitive to changes in loading. Furthermore, it should be able to confirm or reject the hypothesis of altered myocardial contractility after a limited number of experiments. Left ventricular function was assessed in closed-chest mice using a microtip pressure-conductance catheter at baseline and after increases in preload, afterload, or contractility. The parameters are differentially influenced by loading conditions and inotropic state. Only those parameters that could differentiate between basal and increased contractility with a power of 0.85 in ten or less experiments were considered useful. Ejection fraction, preload-recruitable stroke work (PRSW), and dP/dt_max/V _ed could demonstrate the smallest changes in contractility. Stroke work, maximal power and dP/dt_max were most influenced by preload. End-systolic elastance, ejection fraction, and stroke work were afterload-dependent. Dividing the magnitude of the effect of inotropic stimulation to that of load changes gives an index for the usefulness for each parameter. A high ratio indicates that the change in parameter reflects inotropic rather than load change. This ratio was highest for PRSW, which seems to be the best parameter for judging contractility differences in mice.     

八肽胆囊收缩素逆转内毒素休克大鼠心功能降低的实验研究

目的: 观察八肽胆囊收缩素(CCK-8)改善内毒素休克(ES)大鼠心功能的变化,探讨CCK-8抗ES的作用及机制。方法: 实验分对照组、脂多糖(LPS)组、CCK组及CCK+LPS组;监测左室内收缩压(LVP)、左室收缩与舒张期内压变化的最大速率、心率(HR)和平均动脉压(MAP)的动态变化;分别测定2h血清、心肌组织中超氧化物歧化酶(SOD)活性、丙二醛(MDA)和一氧化氮(NO)含量的变化。结果: 静脉注射CCK-8(40μg·kg^-1),引起短时间心率减慢,轻度MAP、LVP和±LVdp/dt_max上升;静脉注时LPS(8mg·kg^-1),引起HR生快后慢双向改变MAP、LVP和±LVdp/dt_max快速持续下降;整体预先注射CCK-8,可明显缓解ES大鼠HR的快速变化,逆转MAP、LVP和±LVdp/dt_max下降,但未恢复至正常水平。CCK-8可提高ES大鼠血清、心肌组织中SOD活性,降低MDA和NO含量。结论: CCK-8可引起短时间心率减慢、轻度MAP上升和心肌收缩力增强;预先应用CCK-8可以减轻ES大鼠心肌氧化损伤,减少NO合成,恢复心肌收缩力,逆转心功能降低及顽固性低血压,是其发挥抗ES的重要机制之一。     

Altered melusin pathways involved in cardiac remodeling following acute myocardial infarction

BackgroundMelusin, a muscle-specific integrin-linked protein, has been reported to be a biomechanical sensor and to protect the heart from pressure overload. In the present study, we investigated the possible role that melusin plays during cardiac remodeling after myocardial infarction (MI).MethodsWe constructed a heart failure model of rats induced by left anterior descending coronary artery ligation. At different time points (1, 2, 3, 4, 6, and 8 weeks) following the operation, cardiac function was monitored by echocardiography and hemodynamic assessment; cardiac morphology was measured using hematoxylin–eosin-stained sections. Melusin expression, as well as p-Akt, Akt, and one of the Rho small GTPase family members, CDC42, was determined dynamically by Western blotting analysis during the postinfarction cardiac remodeling.ResultsProgressive increase in left ventricular (LV) end-systolic dimension and LV end-diastolic dimension and decrease in percent LV fractional shortening (%FS) and LVdp/dt_max demonstrated gradually deteriorated cardiac function in rats following MI operation. Morphological analysis revealed cardiac remodeling in MI animals, including increased LV diameter and decreased border zone thickness. We also showed a dynamic change in melusin during heart failure progression; it had an initial decline which was evident at 3 weeks and increased subsequently, reaching peak levels at 6 weeks. This dynamic change in melusin was significantly correlated with %FS and LVdp/dt_max. p-Akt/Akt and CDC42 protein expression was correlated with melusin content.ConclusionsThe altered melusin pathways and CDC42 parallel the cardiac function progression during cardiac remodeling post-MI. The dynamic change of them during this procedure may represent an important molecular mechanism underlying postinfarction cardiac remodeling and provide potential therapeutic targets.     

保心胶囊对实验性犬心肌缺血血流动力学的影响

目的:观察保心胶囊对结扎犬心肌缺血时心脏血流动力学的影响。 方法:实验分假手术对照组,缺血组,缺血+地奥组,缺血+保心低剂量组,缺血+保心中剂量组,各组犬连续灌胃(生理盐水或药物)三天后,结扎犬心脏冠脉左前降支复制急性心肌缺血模型,测定犬不同时点的血压、血流量及左室等容期压力最大变化速率的变化。结果:保心中剂量组对血压、血流量及左室等容期压力最大变化速率的作用与缺血组比较有显著差异(P＜0.05)。结论:保心胶囊具有改善心肌缺血、增强心肌舒缩能力的作用。     

Albumin decreases hydrogen peroxide and reperfusion injury in isolated rat hearts

Perfusion with human serum albumin decreased myocardial hydrogen peroxide (H₂O₂) levels (as assessed by inactivation of myocardial catalase activities following ammotriazole pretreatment) and increased myocardial ventricular developed pressures (DP), contractility (+dP/dt) but not relaxation rate (-dP/dt) in isolated crystalloid perfused rat hearts subjected to normothermic global ischemia (20 min) and then reperfusion (40 min). Albumin also decreased H₂O₂ concentrations in vitro. The findings support the possibility that albumin may act as a protective O₂ metabolite scavenger in vivo.     

Inotrope Wirkungen des Nervus Vagus am Hundeventrikel in situ

Zusammenfassung Der Einfluß efferenter Vagusreizung auf die Kontraktilität des linken und rechten Ventrikels, in situ wurde an Hunden in Morphin-Urethan-Narkose untersucht. Bei Konstanz der Herzfrequenz (Schrittmacherelektroden am Vorhof, AV-Knoten, oder Ventrikel) wurde nach beidseitiger Vagotomie bei auxotonischen und isometrischen Kontraktionsformen der rechte periphere Vagusstumpf gereizt und Änderungen der maximalen Druckanstiegsgeschwindigkeit (dP/dt _max ) und der maximalen Strömungsgeschwindigkeit (dV/dt _max ) in der Aorta ascendens in Abhängigkeit vom enddiastolischen Druck verfolgt. Bei Frequenzen um 120/min gingdP/dt _max um 7–10% unddV/dt _max um 5–8% zurück während der enddiastolische Druck im Mittel leicht anstieg. Nach Ausschluß von methodisch bedingten Fehlermöglichkeiten (Kontraktionsrückstände, Störungen der Vorhof-Kammer-Koordination), reflektorischen Einflüssen, Änderungen der Coronardurchblutung und der Erregungsausbreitung im Ventrikel trat eine geringe negativ inotrope Vaguswirkung auf. Die beschriebenen Veränderungen konnten jedoch nur bei intensiver und langdauernder Vagusreizung beobachtet werden und waren bei hohen Schrittmacherfrequenzen besonders ausgeprägt. Verglichen mit Amphibienherzen wird die biologische Bedeutung vagaler Efferenzen auf die (frequenzbezogene) Kontraktionskraft des Hundeventrikels daher als unbedeutend angesehen.Mit dankenswerter Unterstützung der Deutschen Forschungsgemeinschaft     

曲古抑菌素A对心衰大鼠心脏促炎细胞因子及心功能的影响

目的: 观察组蛋白脱乙酰化酶抑制剂曲古抑菌素A(TSA)对心肌梗死后心衰(HF)大鼠心脏肿瘤坏死因子(TNF-α)、白细胞介素-1β(IL-1β)和诱导型一氧化氮合酶(iNOS)及心功能的影响。方法: 采用冠状动脉左前降支结扎术致心肌梗死制备大鼠HF模型和假手术模型(sham),给予TSA或vehicle处理。给药4周后,测定血流动力学参数,应用免疫组织化学和ELISA检测左室心肌TNF-α、IL-1β和iNOS的水平,并测定右室/体重(RV/BW)、肺重/体重(LW/BW)。结果: 与HF+vehide组相比,给予TSA后可使HF大鼠心肌组织内增高的TNF-α、IL-1β和iNOS含量明显降低(P<0.05),左室舒张末压(LVEDP)和LW/BW降低(P<0.05);降低的左室内压最大上升速率(+dp/dt_max)和左室内压最大下降速率(-dp/dt_max)明显升高(P<0.05)。结论: 组蛋白脱乙酰化酶抑制剂TSA抑制心肌梗死后HF大鼠心肌组织TNF-α、IL-1β及iNOS的产生,并且可能通过该抑制作用改善HF大鼠的心功能,减轻肺淤血。     

Increased cardiac sympathetic nerve activity following acute myocardial infarction in a sheep model

The time course of cardiac sympathetic nerve activity (CSNA) following acute myocardial infarction (MI) is unknown. We therefore undertook serial direct recordings of CSNA, arterial blood pressure (MAP) and heart rate (HR) in 11 conscious sheep before and after MI, and compared them with 10 controls. Conscious CSNA recordings were taken daily from electrodes glued into the thoracic cardiac nerves. Infarction was induced under pethidine and diazepam analgesia by applying tension to a coronary suture. MI size was assessed by left ventricular planimetry (%) at postmortem, peak troponin T and brain natriuretic peptide levels (BNP). Baroreflex slopes were assessed daily using phenylephrine-nitroprusside ramps. The mean infarcted area was 14.4 ± 2.9%, troponin T 1.88 ± 0.39 μg l⁻¹ and BNP 8.4 ± 1.3 pmol l⁻¹. There were no differences in haemodynamic parameters or CSNA between groups at baseline. MAP and HR remained constant following MI. CSNA burst frequency increased from baseline levels of 55.8 ± 7.1 bursts min⁻¹ to levels of 77.5 ± 8.7 bursts min⁻¹ at 2 h post-MI, and remained elevated for 2 days ( P < 0.001). CSNA burst area also increased and was sustained for 7 days following MI ( P = 0.016). Baroreflex slopes for pulse interval and CSNA did not change. CSNA increases within 1 h of the onset of MI and is sustained for at least 7 days. The duration of this response may be longer because the recording fields decrease with time. This result is consistent with a sustained cardiac excitatory sympathetic reflex.     

An autologous platelet-rich plasma hydrogel compound restores left ventricular structure,function and ameliorates adverse remodeling in a minimally invasive large animal myocardial restoration model: A translational approach: Vu and Pal “Myocardial Repair: PRP,Hydrogel and Supplements”

AimsCell-based myocardial restoration has not penetrated broad clinical practice yet due to poor cell retention and survival rates.In this study, we attempt a translational, large-scale restorative but minimally invasive approach in the pig, aiming at both structurally stabilizing the left ventricular (LV) wall and enhancing function following ischemic injury.Methods and resultsA myocardial infarction (MI) was created by permanent ligation of left circumflex coronary artery through a small lateral thoracotomy. Thirty-six Yorkshire pigs were randomized to receive transthoracic intramyocardial injection into both infarct and border zone areas with different compounds: 1) Hyaluronic acid-based hydrogel; 2) autologous platelet-rich plasma (PRP); 3) ascorbic acid-enriched hydrogel (50 mg/L), combined with IV ibuprofen (25 mg/kg) and allopurinol (25 mg/kg) (cocktail group); 4) PRP and cocktail (full-compound); or 5) saline (control). The latter two groups received daily oral ibuprofen (25 mg/kg) for 7 days and allopurinol (25 mg/kg) for 30 days, postoperatively. Hemodynamic and echocardiographic studies were carried out at baseline, immediately after infarction and at end-point. Eight weeks after MI, the full-compound group had better LV fractional area change, ejection fraction and smaller LV dimensions than the control group. Also, dp/dt_max was significantly higher in the full-compound group when the heart rate increased from 100 bpm to 160bpm in stress tests. Blood vessel density was higher in the full-compound group, compared to the other treatment groups.ConclusionsA combination of PRP, anti-oxidant and anti-inflammatory factors with intramyocardial injection of hydrogel has the potential to structurally and functionally improve the injured heart muscle while attenuating adverse cardiac remodeling after acute myocardial infarction.     

Validation of a novel method to determine non-invasively the rate of central aortic pressure changes

Introduction: One of the most sensitive indices of myocardial contractility is represented by the rate of increase of intraventricular pressure during isovolumetric contraction (dP/dt) and (dP/dt_ejc), which represents the rate of change of pressure during ejection. Today these parameters can be obtained only by invasive catheterization methods. We developed a novel technique that leads to the non-invasive reconstruction of the central aortic pressure. The technique is based on the concept of applying multiple successive occlusive pressures on the brachial artery from peak systole to diastole using an inflatable cuff and plotting the values against time intervals. The hypothesis is that the time intervals required for the aortic pressure wave to overcome a given occlusive brachial pressure applied by a sphyngomanometer on the arm are equal to time needed to reach the same pressure in the central aorta plus the propagation time to the brachial point, which is constant in the same patient throughout the measurements.

Methods and results: We tested the hypothesis using an animal experiment. The new non-invasive device was mounted on the left forelimb of the animal. A Millar pressure transducer catheter was inserted to the aorta and the aorta pressure was recorded at time intervals of 1 ms. A second catheter was inserted into the coronary arteries and used to create controlled occlusion of the arteries using a balloon inflated to 10 atm. Measurements were obtained before the intervention was started, and throughout the sequence of repeated occlusions and deflations. At the end of the sequence, IV dobutamine was administered and results were monitored for 10 min while the heart rate and blood pressure were rising. Non-invasive dP/dt_ejc was reduced typically by 20% in response to balloon inflation. In long occlusion periods, stabilization and sometimes recovery of dP/dt_ejc is observed. By plotting dP/dt_ejc measured by the new non-invasive device versus catheter measurements a correlation factor of 0.843 was found.

Conclusion: A newly developed method of non-invasive measurement of central dP/dt has been found to correlate to invasive measurements in an animal model.     

Ventricular remodeling after myocardial infarction and effects of ACE inhibition on hemodynamics and scar formation in SHR.

The effect of ACE inhibition after myocardial infarction (MI) on MI healing and remodeling in the presence of hypertension is not exactly known. Therefore, the effect of quinapril on scar formation, remodeling and hemodynamics was studied in spontaneously hypertensive rats (SHR). Nine weeks after moderate and large MI, left ventricular end-diastolic pressure (LVEDP) and passive pressure-volume relations were similar in 28-week-old hypertensive and normotensive rats. Chronic therapy with quinapril (6 mg/kg/day, started 30 min post-MI) reduced LVEDP and LV to body weight ratio, yet did not affect pressure-volume relations. Quinapril increased MI size and reduced the content and brightness of collagen fibers in the scar examined by polarized light microscopy. In conclusion, ventricular dilatation after MI was not accelerated in SHR, probably due to LV hypertrophy. Quinapril produced beneficial hemodynamic effects similar to that observed in the normotensive rat model. The significance and timing of ACE inhibitor-induced impairment of scar formation need further evaluation.     

非兴奋性电刺激对正常及心肌梗死兔心功能的影响及其作用的局部性

目的:观察于绝对不应期发放电刺激对正常和心肌梗死(MI)兔在体心脏心功能的影响及其对心肌作用的局部性。方法:64只家兔随机分为正常组和MI组两大组,每组又分为前壁和后壁两组。复制MI模型,4周后每组开胸,窦性心律下,分别于前壁组和后壁组的左心室前壁和后壁,发放绝对不应期方波电刺激(CCM)。观察左心室收缩压(LVSP)左心室舒张末压(LVEDP)及其微分(±dp/dt_max)的变化。结果:正常组前壁和后壁CCM刺激时LVSP及+dp/dt_max均显著大于刺激前(P<0.05),LVEDP低于、-dp/dt_max负值大于刺激前(P<0.05),且不同部位的CCM刺激对心功能的影响不同,左心室前壁的上述作用大于后壁(P<0.05);MI组前壁和后壁CCM刺激时LVSP及+dp/dt_max亦大于刺激前(P<0.05),LVEDP低于、-dp/dt_max负值亦大于刺激前(P<0.05),但前后壁两组之间无显著差别(P＞0.05)。结论:于绝对不应期发放电刺激能明显增强正常和MI后心肌的收缩和舒张功能,CCM刺激对心肌的作用是局部性的。