前列腺素对肾性高血压兔颈动脉窦压力感受器反射的影响

孤离颈动脉窦．记录腰交感神经活动．研究前列腺素对肾性高血压兔颈动脉窦压力感受器反射的影响。结果表明：①环加氧酶抑制剂消炎痛可使正常动物窦反射明显减弱，而对高血压动物却无明显作用。提示内源性前列腺素对正常动物窦反射起增强作用，而在高血压动物，这种作用缺失。②与正常动物相同．外源性前列环素（ＰＧＩ２）也使高血压动物窦反射明显增强，提示高血压动物动脉压力感受器对前列腺素的反应性仍保持正常，内源性前列腺素对高血压动物窦压力感受器反射无明显调制作用，主要可能由于内源性前列腺素（如ＰＧＩ２）缺乏所致。     

Mechanisms underlying the renoprotective effect of GABA against ischaemia/reperfusion‐induced renal injury in rats

Excitation of the renal sympathetic nervous system is important for the development of ischaemic acute kidney injury (AKI) in rats. We reported that intravenous treatment with GABA has preventive effects against ischaemia/reperfusion (I/R)‐induced renal dysfunction with histological damage in rats; however, the mechanisms underlying these effects on renal injury remain unknown. Thus, the aim of the present study was to clarify how GABA mechanistically affects ischaemic AKI in rats. Ischaemic AKI was induced in rats by clamping the left renal artery and vein for 45 min and then reperfusing the kidney to produce I/R‐induced injury. Treatment with the GABA_B receptor antagonist CGP52432 (100 nmol/kg, i.v., or 1 nmol/kg, i.c.v.) abolished the suppressive effects of 50 μmol/kg, i.v., GABA on enhanced renal sympathetic nerve activity (RSNA) during ischaemia, leading to elimination of the renoprotective effects of GABA. Intracerebroventricular treatment with 0.5 μmol/kg GABA or i.v. treatment with 1 μmol/kg baclofen, a selective GABA_B receptor agonist, prevented the I/R‐induced renal injury equivalent to i.v. treatment with GABA. Conversely, i.v. treatment with 10 μmol/kg bicuculline, a GABA_A receptor antagonist, failed to affect the preventive effects of GABA against ischaemic AKI. We therefore concluded that GABA_B receptor stimulation in the central nervous system, rather than peripheral GABA_B receptor stimulation, mediates the preventive effect of GABA against ischaemic AKI by suppressing the enhanced RSNA induced by renal ischaemia.     

Effects of direct cedrol inhalation into the lower airway on autonomic nervous activity in totally laryngectomized subjects

Aims

Previous studies reported that Cedrol (odorant) inhalation (CI) induced changes in autonomic balance and baroreceptor sensitivity (BRS) in both healthy subjects and anosmic patients. This suggests that Cedrol may act on the lower airway, and that the pulmonary system may exert an inhibitory influence on the cardiovascular system.

Method

To test the above possibility, vaporized Cedrol (64.0 ± 7.7 10⁻⁹m) or blank air was directly inhaled through the lower airway from a hole in the trachea, but not through the upper airway, using totally laryngectomized subjects. During the experiment, ECG, systolic (SBP) and diastolic (DBP) blood pressures were measured. Sympathetic and parasympathetic nervous activity was estimated by spectral analyses of variability in these parameters (heart rate variability (HRV), SBP variability (SBPV) and DBP variability (DBPV)). BRS was computed from transfer gain between SBP and the R-R interval of the ECG.

Results

SBP and DBP significantly decreased during CI, although there were no significant differences in HR and respiratory rate. BRS significantly increased during CI. The low frequency components of SBPV and DBPV (indices for sympathetic activity) significantly decreased during CI, while high frequency components of HRV (an index for parasympathetic activity) significantly increased.

Conclusions

The present experiment using totally laryngectomized patients replicated the similar results in healthy subjects who inhaled Cedrol through the nose, suppression of sympathetic outflow and increase in parasympathetic outflow. These results demonstrated that Cedrol acts on the lower airway and pulmonary system, and suggest a new target for drug therapy of hypertension.

What is already known about this subject

• Relationships between smell sensation and autonomic changes have been studied extensively.
• However, the possibility that odorants may also act on the lung and lower airway remains unknown.

What this study adds

• The present results provide the first evidence that the lung and lower airway exert an inhibitory influence on the cardiovascular system in response to Cedrol (odorant) in the air under physiological conditions.

     

Angiotensin II modulation of the arterial baroreflex: role of the area postrema

1. Resetting the operating point of the arterial baroreflex appears to be an important factor involved in determining the level of sympathetic outflow. 2. Substantial data indicate that circulating angiotensin (Ang)II can reset the arterial baroreflex to higher operating pressures. 3. This action of AngII to increase the level of sympathetic nervous system outflow relative to blood pressure may contribute to elevated mean arterial pressure (MAP) during AngII hypertension, as well as to the maintenance of MAP during low sodium states. 4. In most instances, the resetting observed during elevated peripheral AngII is dependent on the area postrema (AP). 5. Although the central mechanisms by which the arterial baroreflex resets to different operating pressures remain to be completely defined, the AP may provide a separate mechanism whereby humoral factors can modulate the operating point of the arterial baroreflex.     

脂质体携载前列腺素E_1抗心肌缺血再灌注损伤

目的　研究脂质体携载前列腺素E1(Lipo PGE1)减轻心肌再灌注损伤的机理。方法　 2 4只家兔随机分成Lipo PGE1组 ,PGE1组及对照组 ,每组 8只。以家兔左冠脉前降支 (LAD)结扎 6 0min ,再灌注 12 0min为缺血再灌注模型 ,于再灌注前 10min分别自耳缘静脉静注Lipo PGE1(2 μg·kg-1PGE1) ,PGE1(2 μg·kg-1)及等容量的脂肪乳剂 (Lipo PGE1的溶剂 ) ,以Evans蓝及氯化三苯基四氮唑 (TTC)双重染色确定缺血心肌及梗塞心肌范围 ,通过测定心肌组织髓过氧化物酶 (MPO)活性反应缺血心肌中性粒细胞浸润程度。结果　Lipo PGE1组梗塞心肌占危险区心肌重量百分比(32 2 0 %± 4 70 % )比较对照组 (44 5 7%± 5 46 % )及PGE1(42 0 9%± 6 93% )降低 (P <0 0 1) ;Lipo PGE1治疗组缺血区心肌组织MPO活性〔(1 9± 1 2 )U·g-1〕较对照组〔(5 3± 2 4)U·g-1〕及PGE1组〔(4 2± 2 0 )U·g-1〕均降低 ,边缘区心肌组织MPO活性〔(1 4± 1 1)U·g-1〕较对照组〔(3 3± 1 5 )U·g-1〕也降低 (P <0 0 5 )。结论　Lipo PGE1能有效抑制再灌注心肌中性粒细胞的浸润 ,减轻心肌再灌注损伤。     

含血停搏液对未成熟心肌缺血-再灌注损伤的实验研究

目的观察冷血浆停搏液对未成熟心肌缺血-再灌注损伤的保护作用。方法选择14～26日龄日本大耳白兔20只,建立Langendorff离体心脏灌注模型。随机抽取4只作为正常对照组(C组),其余16只随机均分为冷血浆组(P组)和冷血组(B组)。C组灌注10minK-H液终止灌注,取右室心肌做检测用。P组、B组降温同时开始分别灌注冷血浆停搏液和冷血停搏液(4℃)15mL/kg,低温(10℃)停搏30min开始复温,再灌注37℃K-H液10min后,采集、处理和保存右室心肌标本。TUNEL法测定心肌细胞凋亡。RT-PCR检测Bcl-2mRNA,行半定量分析。结果C组心肌组织凋亡率为0,P组和B组均出现心肌细胞凋亡,P组凋亡率低于B组(P<0.05)。缺血-再灌注损伤可以使心肌组织中Bcl-2mRNA表达减弱,B组Bcl-2mRNA表达减弱更为明显,P组、B组分别与对照组比较,有显著性差异(P<0.05,P<0.01)。结论未成熟心肌缺血-再灌注伴有细胞凋亡。冷血停搏液、冷血浆停搏液对未成熟心肌缺血均具有保护作用,而冷血浆停搏液作用更为明显。     

Effects of defibrotide,a novel oligodeoxyribonucleotide,on ischaemia and reperfusion injury of the rat liver

1. The purpose of this study was to investigate the protective effects of defibrotide, a single-stranded polydeoxyribonucleotide, on ischaemia-reperfusion injury to the liver using a rat model. 2. Ischaemia of the left and median lobes was created by total inflow occlusion for 30 min followed by 60 min of reperfusion. Hepatic injury was assessed by the release of liver enzymes (alanine transferase, ALT and lactic dehydrogenase, LDH). Hepatic oxidant stress was measured by superoxide production, lipid peroxidation and nitrite/nitrate formation. Leukocyte-endothelium interaction and Kupffer cell mobilization were quantified by measuring hepatic myeloperoxidase (MPO), polymorphonuclear leukocyte adherence to superior mesenteric artery (SMA) and immunostaining of Kupffer cell. 3. Defibrotide treatment resulted in a significant inhibition of postreperfusion superoxide generation, lipid peroxidation, serum ALT activity, serum LDH activity, MPO activity, serum nitrite/nitrate level, leukocyte adherence to SMA, and Kupffer cell mobilization, indicating a significant attenuation of hepatic dysfunction. 4. A significant correlation existed between liver ischaemia/reperfusion and hepatic injury, suggesting that liver ischaemia/reperfusion injury is mediated predominantly by generation of oxygen free radicals and mobilization of Kupffer cells. 5. We conclude that defibrotide significantly protects the liver against liver ischaemia/reperfusion injury by interfering with Kupffer cell mobilization and formation of oxygen free radicals. This study provides strong evidence that defibrotide has important beneficial effects on acute inflammatory tissue injury such as that occurring in the reperfusion of the ischaemic liver.     

早期应用替罗非班对急诊冠脉介入术后心肌微循环再灌注的影响

目的:探讨早期应用替罗非班对直接经皮冠脉介入术(PCI)术后心肌微循环再灌注的影响。方法:初发ST段抬高急性心肌梗死(STEMI)拟行直接PCI术病人131例,A组(n=32,阿司匹林、氯吡格雷和替罗非班),B组(n=99,阿司匹林和氯吡格雷)。全部病人即刻嚼服阿司匹林300 mg,后100 mg·d~(-1);口服氯吡格雷300 mg,后75 nag·d~(-1)。A组再给予替罗非班注射液10μg·kg~(-1)负荷剂量,推注3 min,而后0．15μg·kg~(-1)·min~(-1)持续静脉滴注48 h。入选后即刻测定血小板聚集率、活化状态及心电图,24 h和72 h复查。结果:入选24 h后,A组血小板聚集率及活化状态较B组明显下降(P＜0．05),ST段完全回落率明显高于B组(P＜0．05)。与B组相比,A组梗死相关动脉(IRA)狭窄程度较轻[(69±s 11)％vs (87±8)％,P=0．03]。PCI术后心肌梗死溶栓试验(TIMI),血流3级A组高于B组(97％vs 82％, P=0．045),TIMI血流灌注分级(TMPG),3级A组高于B组(63％vs 42％,P=0．048)。治疗期间轻度血小板减少和出血A组高于B组(9％vs 1％,P=0．045)。随访30 d,2组死亡率无差异,但主要不良心脏事件(MACE)发生率A组低于B组(6％vs 27％,P=0．013),进一步分析A组严重心绞痛(6％vs 21％,P＜0．05)及靶血管再次血运重建术(6％vs 25％,P=0．021)较B组显著降低。结论:在阿司匹林和氯吡格雷基础上早期应用替罗非班,可进一步抑制血小板功能,减少STEMI再灌注后无再流或慢血流的发生,改善心肌微循环再灌注及病人预后。     

Mechanisms of sympathetic activation in heart failure

1. Heart Failure (HF) is a serious, debilitating condition with poor survival rates and an increasing level of prevalence. A characteristic of HF is a compensatory neurohumoral activation that increases with the severity of the condition. 2. The increase in sympathetic activity may be beneficial initially, providing inotropic support to the heart and peripheral vasoconstriction, but in the longer term it promotes disease progression and worsens prognosis. This is particularly true for the increase in cardiac sympathetic nerve activity, as shown by the strong inverse correlation between cardiac noradrenaline spillover and prognosis and by the beneficial effect of beta-adrenoceptor antagonists. 3. Possible causes for the raised level of sympathetic activity in HF include altered neural reflexes, such as those from baroreceptors and chemoreceptors, raised levels of hormones, such as angiotensin II, acting on circumventricular organs, and changes in central mechanisms that may amplify the responses to these inputs. 4. The control of sympathetic activity to different organs is regionally heterogeneous, as demonstrated by a lack of concordance in burst patterns, different responses to reflexes, opposite responses of cardiac and renal sympathetic nerves to central angiotensin and organ-specific increases in sympathetic activity in HF. These observations indicate that, in HF, it is essential to study the factors causing sympathetic activation in individual outflows, in particular those that powerfully, and perhaps preferentially, increase cardiac sympathetic nerve activity.     

丙泊酚对大鼠心肌缺血再灌注损伤的保护作用

目的 探讨异丙酚的心肌保护作用及机制.方法 阻断大鼠左冠状动脉前降支30 min,再灌注2 h引起心肌缺血再灌注(I/R)损伤.缺血前10 min分别灌注异丙酚3,6及12 mg·kg-1至再灌12 h后实验结束.记录心率和平均动脉压,并计算心率-血压指数;光镜电镜观察心肌组织的形态学变化;原位末端标记检测心肌细胞凋亡...     

Intrathecal neurotensin is hypotensive, sympathoinhibitory and enhances the baroreflex in anaesthetized rat

BACKGROUND AND PURPOSE

The neuromodulatory effects of the gut-neuropeptide neurotensin on sympathetic vasomotor tone, central respiratory drive and adaptive reflexes in the spinal cord, are not known.

EXPERIMENTAL APPROACH

Neurotensin (0.5 µM–3 mM) was administered into the intrathecal (i.t.) space at the sixth thoracic spinal cord segment in urethane-anaesthetized, paralysed, vagotomized male Sprague–Dawley rats. Pulsatile arterial pressure, splanchnic sympathetic nerve activity (sSNA), phrenic nerve activity, ECG and end-tidal CO₂ were recorded.

KEY RESULTS

Neurotensin caused a dose-related hypotension, sympathoinhibition and bradycardia. The maximum effects were observed at 3000 µM, where the decreases in mean arterial pressure (MAP), heart rate (HR) and sSNA reached −25 mmHg, −26 beats min⁻¹ and −26% from baseline, respectively. The sympathetic baroreflex was enhanced. Changes in central respiratory drive were characterized by a fall in the amplitude of the phrenic nerve activity. Finally, administration of SR 142948A (5 mM), a potent, selective antagonist at neurotensin receptors, caused a potent hypotension (−35 mmHg), bradycardia (−54 beats min⁻¹) and sympathoinhibition (−44%). A reduction in the amplitude and frequency of the phrenic nerve activity was also observed.

CONCLUSIONS AND IMPLICATIONS

The data demonstrate that neurotensin plays an important role in the regulation of spinal cardiovascular function, affecting both tone and adaptive reflexes.     

Effects of prostaglandins and nitric oxide on the renal effects of angiotensin II in the anaesthetized rat

1. The potential influences of nitric oxide (NO) and prostaglandins on the renal effects of angiotensin II (Ang II) have been investigated in the captopril-treated anaesthetized rat by examining the effect of indomethacin or the NO synthase inhibitor, N^ω-nitro-L-arginine methyl ester (L-NAME), on the renal responses obtained during infusion of Ang II directly into the renal circulation.
2. Intrarenal artery (i.r.a.) infusion of Ang II (1–30 ng kg⁻¹ min⁻¹) elicited a dose-dependent decrease in renal vascular conductance (RVC; −38±3% at 30 ng kg⁻¹ min⁻¹; P<0.01) and increase in filtration fraction (FF; +49±8%; P<0.05) in the absence of any change in carotid mean arterial blood pressure (MBP). Urine output (Uv), absolute (UNaV) and fractional sodium excretion (FENa), and glomerular filtration rate (GFR) were unchanged during infusion of Ang II 1–30 ng kg⁻¹ min⁻¹ (+6±17%, +11±17%, +22±23%, and −5±9%, respectively, at 30 ng kg⁻¹ min⁻¹). At higher doses, Ang II (100 and 300 ng kg⁻¹ min⁻¹) induced further decreases in RVC, but with associated increases in MBP, Uv and UNaV.
3. Pretreatment with indomethacin (10 mg kg⁻¹ i.v.) had no significant effect on basal renal function, or on the Ang II-induced reduction in RVC (−25±7% vs −38±3% at Ang II 30 ng kg⁻¹ min⁻¹). In the presence of indomethacin, Ang II tended to cause a dose-dependent decrease in GFR (−38±10% at 30 ng kg⁻¹ min⁻¹); however, this effect was not statistically significant (P=0.078) when evaluated over the dose range of 1–30 ng kg⁻¹ min⁻¹, and was not accompanied by any significant changes in Uv, UNaV or FENa (−21±12%, −18±16% and +36±38%, respectively).
4. Pretreatment with L-NAME (10 μg kg⁻¹ min⁻¹ i.v.) tended to reduce basal RVC (control −11.8±1.4, +L-NAME −7.9±1.8 ml min⁻¹ mmHg⁻¹×10⁻²), and significantly increased basal FF (control +15.9±0.8, +L-NAME +31.0±3.7%). In the presence of L-NAME, renal vasoconstrictor responses to Ang II were not significantly modified (−38±3% vs −35±13% at 30 ng kg⁻¹ min⁻¹), but Ang II now induced dose-dependent decreases in GFR, Uv and UNaV (−51±11%, −41±14% and −31±17%, respectively, at an infusion rate of Ang II, 30 ng kg⁻¹ min⁻¹). When evaluated over the range of 1–30 ng kg⁻¹ min⁻¹, the effect of Ang II on GFR and Uv were statistically significant (P<0.05), but on UNaV did not quite achieve statistical significance (P=0.066). However, there was no associated change in FENa observed, suggesting a non-tubular site of interaction between Ang II and NO.
5. In contrast to its effects after pretreatment with L-NAME alone, Ang II (1–30 ng kg⁻¹ min⁻¹) failed to reduce renal vascular conductance in rats pretreated with the combination of L-NAME and the selective angiotensin AT₁ receptor antagonist, {"type":"entrez-nucleotide","attrs":{"text":"GR117289","term_id":"238364164","term_text":"GR117289"}}GR117289 (1 mg kg⁻¹ i.v.). This suggests that the renal vascular effects of Ang II are mediated through AT₁ receptors. Over the same dose range, Ang II also failed to significantly reduce GFR or Uv.
6. In conclusion, the renal haemodynamic effects of Ang II in the rat kidney appear to be modulated by cyclooxygenase-derived prostaglandins and NO. The precise site(s) of such an interaction cannot be determined from the present data, but the data suggest complex interactions at the level of the glomerulus.

     

Effects of optic tract stimulation on baroreflex vagal bradycardia in rats

1. Arterial baroreflexes are suppressed in stressful conditions. Intense visual stimuli can cause a threatening sensation and produce defensive reactions. 2. The present study was designed to determine whether and how electrical stimulation of the optic tract (OT) affects arterial baroreflexes, especially the heart rate component, baroreflex vagal bradycardia (BVB), in rats. In chloralose- urethane anaesthetized, beta-adrenoceptor-blocked rats, BVB was evoked by electrical stimulation of the aortic depressor nerve. 3. Electrical stimulation of the OT was found to not only increase blood pressure and heart rate, but also to inhibit BVB. To determine whether these responses were mediated by the lateral genticulate body and/or the superior colliculus, which are major target sites to which the OT projects, each was activated with electrical and chemical stimulation. 4. The lateral genticulate body did not respond to either electrical or chemical stimulation, whereas the superior colliculus increased blood pressure and heart rate while suppressing BVB following electrical stimulation. Essentially similar responses were observed following microinjection of the GABA antagonist bicuculline methiodide. 5. Optic tract-induced inhibition of BVB was abolished by bilateral destruction of the superior colliculus. Furthermore, this inhibition was also largely attenuated by destruction of the midbrain periaqueductal grey (PAG). 6. In conclusion, electrical stimulation of the OT increases blood pressure, heart rate and inhibits BVB. These responses are not mediated by the lateral genticulate body but are mediated by the superior colliculus. The PAG may participate in the subsequent mediation of the responses to electrical stimulation of the OT and the OT-induced inhibition of BVB may contribute to expression of a light-induced defence reaction.     

Nicorandil suppressed myocardial purine metabolism during exercise in patients with angina pectoris

To elucidate the effect of Nicorandil on myocardial energy metabolism and myocardial sympathetic activity, we administered Nicorandil orally to eight patients with angina pectoris prior to exercise testing. Arterial and coronary sinus levels of lactate, ammonia, hypoxanthine (HX), adrenaline and noradrenaline were measured during exercise in order to determine the irrespective myocardial extraction ratios (MER). Compared to placebo, Nicorandil increased the time to development of significant ST depression (322 vs 390 s) while decreasing the maximum amplitude of ST depression (0.244 vs 0.216 mV). Heart rate, systolic blood pressure, and the rate pressure product during exercise were not significantly affected. The MER of lactate, measured during exercise, was significantly higher after Nicorandil than placebo (13.6 vs 27.9). Similarly, the MERs of ammonia and HX were significantly higher after Nicorandil (-46.0 vs 7.4% and –47.0 vs 9.9% respectively). Nicorandil, had no apparent effect on myocardial sympathetic activity as the MERs of adrenaline and noradrenaline were essentially unaffected. We conclude that Nicorandil decreased myocardial ischaemia and suppressed myocardial accelerated purine metabolism (a marker of cellular energy metabolism) during exercise in patients with angina pectoris. This effect appears not to be related to myocardial sympathetic activity.     

Effects of bepridil and lidocaine on the intravenctricular conduction in acutely ischaemic and infarcted canine myocardium

Summary Effects of bepridil, an antiarrhythmic and antianginal drug, on intraventricular conduction in acutely ischaemic and infarcted myocardium were examined in anaesthetized dogs, and compared with those of lidocaine. Bepridil at doses of 2 and 5 mg/kg markedly prolonged the conduction time of a premature excitation induced by a ventricular stimulation in the infarcted zone. The effect of bepridil was dependent on a coupling time of the stimulation. Bepridil showed a marked effect at a coupling time of 150 ms, while it showed no significant effect at a prolonged coupling time of 1 s. In other words, the effect of bepridil was interval-dependent. Lidocaine showed a similar interval-dependent effect, but the effect of lidocaine at a longer coupling time was less than that of bepridil. The premature stimulation produced severely delayed conduction which resulted in reentrant beats. Bepridil blocked these conductions, thereby preventing reentrant beats. In contrast to the depressant effect of bepridil in the infarcted myocardium, bepridil prevented the prolongation of conduction time during acute ischaemia. The alternation of the ST-T complex during acute ischaemia which is also an important arrhythmogenic factor was also attenuated by bepridil. Contrary to bepridil, lidocaine significantly enhanced the conduction delay and the alternation in the ST-T complex. In conclusion, bepridil as well as lidocaine showed an interval-dependent depression of the conduction in the infarcted zone of the heart, whereas during acute ischaemia bepridil in contrast to lidocaine attenuated the conduction delay and ST-T alternans. Send offprint requests to H. Hashimoto at the above address     

Acute administration of cannabidiol in vivo suppresses ischaemia-induced cardiac arrhythmias and reduces infarct size when given at reperfusion

Background and purpose:

Cannabidiol (CBD) is a phytocannabinoid, with anti-apoptotic, anti-inflammatory and antioxidant effects and has recently been shown to exert a tissue sparing effect during chronic myocardial ischaemia and reperfusion (I/R). However, it is not known whether CBD is cardioprotective in the acute phase of I/R injury and the present studies tested this hypothesis.

Experimental approach:

Male Sprague-Dawley rats received either vehicle or CBD (10 or 50 µg·kg⁻¹ i.v.) 10 min before 30 min coronary artery occlusion or CBD (50 µg·kg⁻¹ i.v.) 10 min before reperfusion (2 h). The appearance of ventricular arrhythmias during the ischaemic and immediate post-reperfusion periods were recorded and the hearts excised for infarct size determination and assessment of mast cell degranulation. Arterial blood was withdrawn at the end of the reperfusion period to assess platelet aggregation in response to collagen.

Key results:

CBD reduced both the total number of ischaemia-induced arrhythmias and infarct size when administered prior to ischaemia, an effect that was dose-dependent. Infarct size was also reduced when CBD was given prior to reperfusion. CBD (50 µg·kg⁻¹ i.v.) given prior to ischaemia, but not at reperfusion, attenuated collagen-induced platelet aggregation compared with control, but had no effect on ischaemia-induced mast cell degranulation.

Conclusions and implications:

This study demonstrates that CBD is cardioprotective in the acute phase of I/R by both reducing ventricular arrhythmias and attenuating infarct size. The anti-arrhythmic effect, but not the tissue sparing effect, may be mediated through an inhibitory effect on platelet activation.     

The opposite effects of nitric oxide donor,S‐nitrosoglutathione,on myocardial ischaemia/reperfusion injury in diabetic and non‐diabetic mice

Nitric oxide is a potent anti‐apoptotic and cardioprotective molecule in healthy animals. However, recent study demonstrates that overexpression of eNOS exacerbates the liver injury in diabetic animals. whether diabetes may also alter NO's biologic activity in ischaemic/reperfused heart remains unknown. The present experiment was designed to determine whether the nitric oxide donor, S‐nitrosoglutathione, may exert different effects on diabetic and non‐diabetic myocardial ischaemia/reperfusion (MI/R) injury. Diabetic state was induced in mice by multiple intraperitoneal injections of low‐dose streptozotocin (STZ). The control or diabetic mice were subjected to 30 minutes ischaemia and 3 or 24 hours reperfusion. At 10 minutes before reperfusion, diabetic and non‐diabetic mice were received an intraperitoneal injection of S‐nitrosoglutathione (GSNO, a nitric oxide donor, 1 μmol/kg). GSNO attenuated MI/R injury in non‐diabetic mice, as measured by improved cardiac function, reduced infarct size and decreased cardiomyocyte apoptosis. In contrast, GSNO failed to attenuate but, rather, aggravated the MI/R injury in diabetic mice. Mechanically, the diabetic heart exhibited an increased nitrative/oxidative stress level, as measured by peroxynitrite formation, compared with non‐diabetic mice. Co‐administration of GSNO with EUK134 (a peroxynitrite scavenger) or MnTE‐2‐PyP5 (a superoxide dismutase mimetic) or Apocynin (a NADPH oxidase inhibitor) 10 minutes before reperfusion significantly decreased the MI/R‐induced peroxynitrite formation and the MI/R injury. Collectively, the present study for the first time demonstrated that diabetes may cause superoxide overproduction, increase NO inactivation and peroxynitrite formation, and thus convert GSNO from a cardioprotective molecule to a cardiotoxic molecule.     

Drug-induced changes in blood flow in the acutely ischaemic canine myocardium; relationship to subendocardial driving pressure

SUMMARY 1. The effects of various drugs have been studied on blood flow and oxygen handling (availability, extraction and consumption) in both normal and acutely ischaemic regions of the canine myocardium. Ischaemia was produced by the acute ligation of the anterior descending branch of the left coronary artery.
2. Lidoflazine, like other coronary vasodilator drugs, increases blood flow in the normal myocardium, but does not increase flow through the ischaemic region. Drugs of this type may, in addition, open up 'shunt' vessels within the ischaemic region.
3. Of three cardiac stimulants studied, only oxyfedrine consistently increases blood flow through the ischaemic region; isoprenaline and glucagon do not.
4. Noradrenaline causes marked increases in flow through the ischaemic region: its effect is associated with an increase in coronary pressure in the artery distal to the ligature.
5. Evidence is put forward that the critical factor determining flow through ischaemic regions of the myocardium is the transventricular driving pressure. When the effects of various drugs on flow and driving pressure are analysed and compared, the only drugs that increase flow in an ischaemic region are those that increase the pressure gradient across the wall of the left ventricle.     

Anti-inflammatory actions of aprotinin provide dose-dependent cardioprotection from reperfusion injury

BACKGROUND AND PURPOSE: Myocardial injury following ischaemia and reperfusion has been attributed to activation and transmigration of polymorphonuclear leukocytes (PMNs) with release of mediators including oxygen-derived radicals and proteases causing damage. EXPERIMENTAL APPROACH: We studied the serine protease inhibitor aprotinin in an in vivo rabbit model of 1 h of myocardial ischaemia followed by 3 h of reperfusion (MI+R). Aprotinin (10,000 Ukg(-1)) or its vehicle were injected 5 min prior to the start of reperfusion. KEY RESULTS: Myocardial injury was significantly reduced with aprotinin treatment as indicated by a reduced necrotic area (11+/-2.7% necrosis as percentage of area at risk after aprotinin; 24+/-3.1% after vehicle; P<0.05) and plasma creatine kinase activity (12.2+/-1.5 and 17.3+/-2.3 IU g(-1) protein in aprotinin and vehicle groups, respectively, P<0.05). PMN infiltration (assessed by myeloperoxidase activity) was significantly decreased in aprotinin-treated animals compared to vehicle (P<0.01). Histological analysis also revealed a substantial increase in PMN infiltration following MI+R and this was significantly reduced by aprotinin therapy (44+/-15 vs 102+/-2 PMN mm2 in aprotinin vs vehicle-treated animals, P<0.05). In parallel in vitro experiments, aprotinin inhibited neutrophil-endothelium interaction by reducing PMN adhesion on isolated, activated aortic endothelium. Finally, immunohistochemical analysis illustrated aprotinin significantly reduced myocardial apoptosis following MI+R. CONCLUSIONS AND IMPLICATIONS: Inhibition of serine proteases by aprotinin inhibits an inflammatory cascade initiated by MI+R. The cardioprotective effect appears to be at least partly due to reduced PMN adhesion and infiltration with subsequently reduced myocardial necrosis and apoptosis.     

原花青素对大鼠心肌缺血-再灌注损伤的保护作用

目的探讨原花青素对大鼠心肌缺血-再灌注损伤引起的氧化应激损伤的保护作用。方法建立心肌缺血-再灌注模型。再灌注结束后采血,测定丙二醛(MDA)、超氧化物歧化酶(SOD)、天冬氨酸转氨酶(AST)、乳酸脱氢酶(LDH),测量心肌梗死面积。结果原花青素能明显降低血浆中MDA、AST和LDH的含量(P<0.05),提高SOD活性(P<0.05),减少心肌梗死面积(P<0.05)。结论原花青素对大鼠心肌缺血-再灌注损伤引起的氧化应激损伤的有保护作用。