Nicotine inhibits the production of proinflammatory cytokines of mice infected with coxsackievirus B3.

AIMS: Although excessive sympathetic activation in viral myocarditis and the protective effects of sympathetic inhibition with ß-blockers are clear, the effects of enhancing vagal tone on viral myocarditis remain unclear. In several models, vagus nerve activation with the α7 nicotinic acetylcholine receptor (α7-nAChR) agonists has been demonstrated to ameliorate inflammation. This study was therefore designed to examine the effects of cholinergic stimulation with α7-nAChR agonist nicotine in a murine model of acute viral myocarditis. MATERIALS AND METHODS: BALB/C mice were infected by an intraperitoneally injection with coxsackievirus B3. Nicotine and methyllycaconitine (an α7-nAChR antagonist) were administered at doses of 0.4mg/kg and 0.8mg/kg three times per day for 7 or 14 consecutive days, respectively. The effects of nicotine and methyllycaconitine on survival rate, myocardial histopathological changes, cardiac function, cytokine levels, viral RNA, malondialdehyde, and superoxide dismutase contents were investigated. KEY FINDINGS: Nicotine significantly increased survival rate of the infected mice, decreased myocardial inflammation, and improved the impairment of left ventricular function in murine coxsackievirus B3-induced myocarditis compared with methyllycaconitine. The proinflammatory cytokines TNF-α, IL-1ß, IL-6 and IL-17A were significantly decreased in the infected mice treated with nicotine compared with methyllycaconitine. Nicotine had no significant anti-oxidative and antiviral effects in coxsackievirus B3-infected mice. SIGNIFICANCE: The results indicate that cholinergic stimulation with nicotine significantly reduced the severity of viral myocarditis in mice. The findings suggest that alpha7 nAChR agonists may be a promising new strategy for patients with myocarditis.

Dose-dependent protective effect of nicotine in a murine model of viral myocarditis induced by coxsackievirus B3.

The alpha 7 nicotinic acetylcholine receptor (alpha7 nAChR) was recently described as an anti-inflammatory target in various inflammatory diseases. The aim of this study was to investigate the dose-related effects of nicotine, an alpha7 nAChR agonist, in murine model of viral myocarditis. BALB/C mice were infected by an intraperitoneally injection with coxsackievirus B3. Nicotine was administered at doses of 0.1, 0.2 or 0.4 mg/kg three times per day for 7 or 14 consecutive days. The effects of nicotine on survival, myocardial histopathological changes, cardiac function, and cytokine levels were studied. The survival rate on day 14 increased in a dose-dependent fashion and was markedly higher in the 0.2 and 0.4 mg/kg nicotine groups than in the infected untreated group. Treatment with high-dose nicotine reduced the myocardial inflammation and improved the impaired left ventricular function in infected mice. The mRNA expressions and protein levels of TNF-α, IL-1ß, IL-6, and IL-17A were significantly downregulated in dose-dependent manners in the nicotine treatment groups compared to the infected untreated group. Nicotine dose-dependently reduced the severity of viral myocarditis through inhibiting the production of proinflammatory cytokines. The findings suggest that alpha7 nAChR agonists may be a promising new strategy for patients with viral myocarditis.

Protective role of the cholinergic anti-inflammatory pathway in a mouse model of viral myocarditis.

BACKGROUND: Activation of the cholinergic anti-inflammatory pathway, which relies on the α7nAchR (alpha 7 nicotinic acetylcholine receptor), has been shown to decrease proinflammatory cytokines. This relieves inflammatory responses and improves the prognosis of patients with experimental sepsis, endotoxemia, ischemia/reperfusion injury, hemorrhagic shock, pancreatitis, arthritis and other inflammatory syndromes. However, whether the cholinergic anti-inflammatory pathway has an effect on acute viral myocarditis has not been investigated. Here, we studied the effects of the cholinergic anti-inflammatory pathway on acute viral myocarditis. METHODOLOGY/PRINCIPAL FINDINGS: In a coxsackievirus B3 murine myocarditis model (Balb/c), nicotine and methyllycaconitine were used to stimulate and block the cholinergic anti-inflammatory pathway, respectively. Relevant signal pathways were studied to compare their effects on myocarditis, survival rate, histopathological changes, ultrastructural changes, and cytokine levels. Nicotine treatments significantly improved survival rate, attenuated myocardial lesions, and downregulated the expression of TNF-α and IL-6. Methyllycaconitine decreased survival rate, aggravated myocardial lesions, and upregulated the expression of TNF-α and IL-6. In addition, levels of the signaling protein phosphorylated STAT3 were higher in the nicotine group and lower in the methyllycaconitine group compared with the untreated myocarditis group. CONCLUSIONS/SIGNIFICANCE: These results show that nicotine protects mice from CVB3-induced viral myocarditis and that methyllycaconitine aggravates viral myocarditis in mice. Because nicotine is a α7nAchR agonist and methyllycaconitine is a α7nAchR antagonist, we conclude that α7nAchR activation increases the phosphorylation of STAT3, reduces the expression of TNF-α and IL-6, and, ultimately, alleviates viral myocarditis. We also conclude that blocking α7nAchR reduces the phosphorylation of STAT3, increases the expression of TNF-α and IL-6, aggravating viral myocarditis.

Catheter ablation of idiopathic premature ventricular contractions and ventricular tachycardias originating from the vicinity of endocardial and epicardial mitral annulus.

BACKGROUND: Several previous reports have revealed that idiopathic ventricular arrhythmias (VAs), including premature ventricular contractions (PVCs) and ventricular tachycardias (IVTs), can originate from endocardial mitral annulus (ENDO MA). However, these data are limited to ENDO MA VAs, and little is known about the electrocardiographic (ECG) characteristics and the efficacy of radiofrequency catheter ablation (RFCA) via the coronary venous system for the VAs arising from the epicardial MA (EPI MA). METHODOLOGY/PRINCIPAL FINDINGS: Characteristics of body surface electrocardiogram and electrophysiologic recordings were analyzed in 21 patients with symptomatic PVCs/IVTs originating from the vicinity of MA. Among 597 patients with PVCs/IVTs, the incidence of VAs originating from the ENDO and EPI MA was 3.52% (21 cases). Eleven (52%) from the ENDO MA, and 10 (48%) from the EPI MA. There were different characteristics of ECG of PVCs/VT originating from the ENDO and EPI MA. The prolonged pseudodelta wave time and intrinsicoid deflection time in lead V2 and the precordial maximum deflection index reliably differentiated EPI MA VAs from ENDO MA VAs with high sensitivity and specificity. Successful RFCA in 18 patients could be achieved (85.7% acute procedural success). CONCLUSIONS/SIGNIFICANCE: ECG characteristics of PVCs/VTs originating from the different portions of the MA are different, and can help regionalize the origin of these arrhythmias. RFCA within the coronary venous system was relatively effective and safe for the PVCs/IVTs and should be seen as an alternative approach, when the MA PVCs/IVTs could not be eliminated by RFCA from the endocardium.

Catheter ablation of idiopathic premature ventricular contractions and ventricular tachycardias originating from right ventricular septum.

BACKGROUND: Idiopathic premature ventricular contractions (PVCs) and ventricular tachycardias (IVTs) originating from the subtricuspid septum and near the His bundle have been reported. However, little is known about the prevalence, distribution, electrocardiographic characteristics and the efficacy of radiofrequency catheter ablation (RFCA) for the ventricular arrhythmias arising from the right ventricular (RV) septum. This study aimed to investigate electrocardiographic characteristics and effects of RFCA for patients with symptomatic PVCs/IVTs, originating from the different portions of the RV septum. METHODOLOGY/PRINCIPAL FINDINGS: Characteristics of body surface electrocardiogram and electrophysiologic recordings were analyzed in 29 patients with symptomatic PVCs/IVTs originating from the RV septum. Among 581 patients with PVCs/IVTs, the incidence of ventricular arrhythmias originating from the RV septum was 5%. Twenty (69%) had PVCs/IVTs from the septal portion of the tricuspid valvular RV region (3 from superoseptum, 15 from midseptum, 2 from inferoseptum), and 9 (31%) from the septal portion of the basal RV (1 from superoseptum, 4 from midseptum, 4 from inferoseptum). There were different characteristics of ECG of PVCs/VT originating from the different portions of the RV septum. Twenty-seven of 29 patients with PVCs/IVTs arising from the RV septum were successfully ablated (93.1% acute success). CONCLUSIONS/SIGNIFICANCE: ECG characteristics of PVCs/VTs originating from the different portions of the RV septum are different, and can help regionalize the origin of these arrhythmias. The septal portion of the tricuspid valvular RV region was the preferential site of origin. RFCA was effective and safe for the PVCs/IVTs arising from the RV septum.

Effect of pre-procedural statin therapy on myocardial no-reflow following percutaneous coronary intervention: a meta analysis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Successful revascularization of coronary artery disease, especially ST-elevation myocardial infarction (STEMI), does not always mean optimal myocardial reperfusion in a portion of patients because of no-reflow phenomenon. We hypothesized that statins might attenuate the incidence of myocardial no-reflow when used before percutaneous coronary intervention (PCI). The purpose of this study was to summarize the evidence of pre-procedural statin therapy to reduce myocardial no-reflow after PCI.</p><p><b>METHODS</b>We searched the MEDLINE, Cochrane, and clinicaltrials.gov databases from inception to October 2012 for clinical trials that examined statin therapy before PCI. We required that studies initiated statins before PCI and reported myocardial no-reflow. A DerSimonian-Laird model was used to construct random-effects summary risk ratios.</p><p><b>RESULTS</b>In all, 7 studies with 3086 patients met our selection criteria. The use of pre-procedural statins significantly reduced post-procedural no-reflow by 4.2% in all PCI patients (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.35 to 0.90, P = 0.016), and attenuated by 5.0% in non-STEMI patients (RR 0.41, 95% CI 0.18 to 0.94, P = 0.035). This benefit was mainly observed in the early or acute intensive statin therapy populations (RR 0.43, 95% CI 0.26 to 0.71, P = 0.001).</p><p><b>CONCLUSIONS</b>Acute intensive statin therapy before PCI significantly reduces the hazard of post-procedural no-reflow phenomenon. The routine use of statins before PCI should be considered.</p>

Ischemic preconditioning attenuates myocardial no-reflow and reperfusion injury after revascularization of acute myocardial infarction by reducing myocardial edema via the protein kinase A pathway / 中华心血管病杂志

<p><b>OBJECTIVE</b>Myocardial edema plays an important role in the development of myocardial no-reflow and reperfusion injury after the revascularization of acute myocardial infarction (AMI). The present study investigated whether the effect of ischemic preconditioning (IPC) against myocardial no-reflow and reperfusion injury was related to the reduction of myocardial edema through the protein kinase A (PKA) pathway.</p><p><b>METHODS</b>Twenty-four minipigs were randomized into sham, AMI, IPC, and IPC + H-89 (PKA inhibitor, 1.0 µg · kg(-1) · min(-1)) groups. The area of no-reflow (ANR), area of necrosis (AN), and water content in left ventricle and ischemic-myocardium and non-ischemic area were determined by pathological studies. Microvascular permeability was determined by FITC-labeled dextran staining. Cardiomyocyte cross-sectional area (CSA) and mitochondria cross-sectional area (MSA) were evaluated by histological analysis. Myocardial expression of aquaporins (AQPs) was detected by Western blot.</p><p><b>RESULTS</b>Compared with the MI group, the sizes of no-reflow and infarct were reduced by 31.9% and 46.6% in the IPC group (all P < 0.01), water content was decreased by 5.7% and 4.6% in the reflow and no-reflow myocardium of the IPC group (all P < 0.05), microvascular permeability and cardiomyocytes swelling in the reflow area were inhibited by 29.8% and 21.3% in the IPC group (all P < 0.01), mitochondrial water accumulation in the reflow and no-reflow areas of the IPC group were suppressed by 45.5% and 34.8% respectively (all P < 0.01), and the expression of aquaporin-4, -8, and -9 in the reflow and no-reflow myocardium were blocked in the IPC group. However, these beneficial effects of IPC were partially abolished in the IPC + H-89 group.</p><p><b>CONCLUSIONS</b>The cardioprotective effects of IPC against no-reflow and reperfusion injury is partly related to the reduction of myocardial edema by inhibition of microvascular permeability and aquaporins up-regulation via PKA pathway.</p>

Pretreatment with Tongxinluo protects porcine myocardium from ischaemia/reperfusion injury through a nitric oxide related mechanism / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The traditional Chinese medicine Tongxinluo can protect myocardium against ischaemia/reperfusion injury, but the mechanism of its action is not well documented. We examined the involvement of nitric oxide in the protective role of Tongxinluo.</p><p><b>METHODS</b>Miniswine were randomized to four groups of seven: sham, control, Tongxinluo and Tongxinluo coadministration with a nitric oxide synthase inhibitor N(omega)-nitro-L-arginine (L-NNA, 10 mg/kg i.v.). Three hours after administration of Tongxinluo, the animals were anaesthetised and the left anterior descending coronary artery ligated and maintained in situ for 90 minutes followed by 3 hours of reperfusion before death. Area of no reflow and necrosis and risk region were determined pathologically by planimetry. The degree of neutrophil accumulation in myocardium was obtained by measuring myeloperoxidase activity and histological analysis. Myocardial endothelial nitric oxide synthase activity and vascular endothelial cadherin content were measured by colorimetric method and immunoblotting analysis respectively.</p><p><b>RESULTS</b>Tongxinluo significantly increased the local blood flow and limited the infarct and size of no reflow. Tongxinluo also attenuated myeloperoxidase activity and neutrophil accumulation in histological sections and maintained the level of vascular endothelial cadherin and endothelial nitric oxide synthase activity in the reflow region when compared with control group. The protection of Tongxinluo was counteracted by coadministration with L-NNA.</p><p><b>CONCLUSIONS</b>Tongxinluo may limit myocardial ischaemia and protect the heart against reperfusion injury. Tongxinluo regulates synthesis of nitric oxide by altering activity of endothelial nitric oxide synthase.</p>

Effect of arotinolol on left ventricular function in patients with idiopathic dilated cardiomyopathy / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of long-term treatment with arotinolol in patients with idiopathic dilated cardiomyopathy (IDCM).</p><p><b>METHODS</b>Sixty-three patients with IDCM were evaluated at baseline and after 12-month therapy with arotinolol. The conventional therapy for congestive heart failure was continued throughout the study with arotinolol as the only beta-blocker. Left ventricular function was assessed with the New York Heart Association functional class and two-dimensional echocardiography.</p><p><b>RESULTS</b>After 12-month arotinolol treatment, there was a significant improvement in left ventricular systolic function. Left ventricular end-systolic dimension significantly decreased from 59.52 +/- 8.83 mm to 50.89 +/- 8.17 mm (P < 0.001). Left ventricular ejection fraction significantly increased from 27.39% +/- 7.94% to 41.13% +/- 9.45% ( P < 0.001). Left ventricular mass index decreased from 150.47 +/- 42.42 g/m2 to 141.58 +/- 34.36 g/m2 (P < 0.01). No adverse events leading to premature discontinuation of study drug occurred.</p><p><b>CONCLUSION</b>In this preliminary study, 12-month arotinolol treatment has a favorable effect on left ventricular function in patients with IDCM, and it is safe and well tolerated.</p>

Effect of adenosine on endothelin-1 in the infarcted reflow and no-reflow myocardium of mini-swine / 中国医学科学院学报

<p><b>OBJECTIVE</b>To evaluate the effect of adenosine on endothelin-1 (ET-1) after acute myocardial infarction (AMI) and reperfusion and explore the possible mechanism of no-reflow.</p><p><b>METHODS</b>Twenty-four mini-swine were randomized into three study groups: control group (n=8), adenosine treated group (n=8), and sham-operated group (n=8). The mini-swine in the groups were subjected to 3 hours of coronary occlusion, followed by 60 minutes of reperfusion except those in the sham-operated group. The levels of ET-1 in blood sample, normal, infracted reflow and no-reflow myocardium were evaluated by radioimmuno-assay (RIA). The gene expressions of ET-1 in normal, infracted reflow and no-reflow myocardium were quantified by reverse transcription-polymerase chain reaction.</p><p><b>RESULTS</b>In both control group and adenosine group, compared with that at the baseline, ET-1 in blood sample significantly increased at 5 minutes and 180 minutes of left anterior descending coronary artery occlusion, as well as 5 and 60 minutes of reperfusion (all P < 0.01). In adenosine group, the levels of ET-1 were significantly lower than those in the control group (P < 0.05, P < 0.01). In both control group and adenosine group, compared with that in normal myocardium, ET-1 levels in both infarcted reflow and no-reflow myocardium significantly increased (both P < 0.01), with the level of ET-1 in no-reflow myocardium significantly higher than that in infarcted reflow myocardium (P < 0.01). In adenosine group, the level of ET-1 in infarcted reflow myocardium was significantly lower than that in the control group (P < 0.01). In both control and adenosine groups, compared with that in normal myocardium, the gene expression of ET-1 in infarcted reflow myocardium was significantly up-regulated (P < 0.01), while that of ET-1 in. no-reflow myocardium significantly down-regulated (P < 0.01). In adenosine group, the level of ET-1 in infarcted reflow myocardium was significantly lower than that in the control group (P < 0.01).</p><p><b>CONCLUSION</b>The endothelium injury may be one of the important mechanisms for no-reflow phenomenon. Adenosine cay prevent endothelium from injury to reduce no-reflow.</p>

Effect of tongxinluo on endothelin-1 in the mini-swine model of acute myocardial infarction and reperfusion / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To evaluate the change of endothelin-1 (ET-1) in the mini-swine model of acute myocardial infarction (AMI) and reperfusion and the effect of Tongxinluo (TXL) on it, and to explore the possible mechanism of no-reflow.</p><p><b>METHODS</b>Forty mini-swines were randomized into 5 groups: the model group, the small,middle and large dose of TXL groups and the sham-operated group, 8 in each group. The AMI reperfusion model was established by coronary ligation for 3 hrs followed with relaxation for 1 hr. Plasma ET-1 content before and after AMI, and after reperfusion was determined respectively by radioimmunoassay. The ET-1 mRNA expression in myocardial tissue of normal, ischemic and no-reflow area were respectively quantified by reverse transcription-polymerase chain reaction.</p><p><b>RESULTS</b>(1) Compared with before AMI, levels of plasma ET-1 at the time points of 5 min and 3 hrs after AMI, 5 min and 1 hrs after reperfusion in the model group were significantly raised, showing an increasing tendency (all P < 0.01). But the increment in the middle and large dose of TXL groups were all lower than that in the model group (P < 0.05). (2) In the model and the TXL groups, levels of ET-1 in myocardial tissue of ischemic and no-reflow area were significantly higher than those in the normal area, and the increment in no-reflow area was higher than that in ischemic area (all P < 0.01). Compared with the model group, significant lowering of ET-1 in ischemic area was only shown in the middle and large dose of TXL groups (P < 0.01). (3) In the model and the TXL groups, ET-1 mRNA expression in ischemic area was significantly higher (all P < 0.01), while it in no-reflow area was significantly lower than that in the normal area respectively (all P < 0.01). The raised ET-1 mRNA expression in the middle and large dose TXL groups was significantly lowered when compared with that in the model group (P < 0.01).</p><p><b>CONCLUSION</b>The endothelium injury might be one of the important mechanisms for no-reflow phenomenon. TXL might reduce the no-reflow by protecting endothelium cells. was significantly higher (all P < 0.01), while it in no-reflow area was significantly lower than that in the normal area respectively (all P < 0.01). The raised ET-1 mRNA expression in the middle and large dose TXL groups was significantly lowered when compared with that in the model group (P < 0.01). Conclusion The endothelium injury might be one of the important mechanisms for no-reflow phenomenon. TXL might reduce the no-reflow by protecting endothelium cells.</p>

Beneficial effects of ischemic preconditioning on myocardial no-reflow in a mini-swine model of acute myocardial infarction and reperfusion / 中国医学科学院学报

<p><b>OBJECTIVE</b>To evaluate the effects of ischemic preconditioning (IPC) on myocardial no-reflow in a mini-swine model of acute myocardial infarction (AMI) and reperfusion.</p><p><b>METHODS</b>Twenty-four mini-swines were randomized into 3 study groups: 8 in control, 8 in IPC and 8 in sham-operated. Animals in the former two groups were subjected to 3 hours of coronary occlusion followed by 1 hour of reperfusion. Data on hemodynamics and coronary blood flow volume (CBV) were collected, and the area of no-reflow (ANR) was evaluated with both myocardial contrast echocardiography (MCE) in vivo and pathological means. Necrosis area (NA) was measured with triphenyltetrazolium chloride (TTC) staining.</p><p><b>RESULTS</b>In control group, left ventricular systolic pressure (LVSP), the maximum change rate of left ventricular pressure rise and fall (+/-dp/dtmax) and cardiac output (CO) significantly declined (P < 0.05, P < 0.01), while left ventricular end-diastolic pressure (LVEDP) significantly increased at the end of 3 hours of left anterior descending coronary artery occlusion (both P < 0.01), with +/-dp/dtmax further significantly declined (both P <0.05) at 1 hour of reperfusion. In IPC group, LVSP, +/-dp/dtmax, CO and LVEDP significantly recovered at 1 hour of reperfusion, compared with those in control group. In IPC group, the coronary ligation area was similar on both MCE in vivo and pathological evaluation (P > 0.05), and ANR was both also similarly as high as (16.4 +/- 2.24) % and (17.5 +/- 2.87) %, respectively, with final necrosis area (NA) reaching (78.4 +/- 3.62) %. In IPC group, ANR and final NA were significantly lower than those in control group (P < 0.05, P < 0.01). In the control group, coronary blood flow volumn immediately after release of 3 hours occlusion and at 1 hour of reperfusion were significantly lower than the baseline (both P < 0.01). In IPC group, coronary blood flow volumn were significantly higher than those in the control group (both P < 0.01).</p><p><b>CONCLUSION</b>IPC is effective to prevent myocardial no-reflow, improve left ventricular function and decrease infarct area.</p>

Beneficial effects of adenosine on myocardial no-reflow in a mini-swine model of acute myocardial infarction and reperfusion / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the beneficial effects of adenosine on myocardial no-reflow in a mini-swine model of acute myocardial infarction (AMI) and reperfusion.</p><p><b>METHODS</b>Twenty-four animals were randomly assigned to 3 groups: 8 in controls, 8 in adenosine-treated and 8 in sham-operated. The groups were subjected to 3 hours of coronary occlusion followed by 60 minutes of reperfusion except the sham-operated group. Data on hemodynamics and coronary blood flow volume (CBV) were collected. The area of no-reflow was evaluated by both myocardial contrast echocardiography (MCE) in vivo and histopathological means and necrosis area was measured with triphenyltetrazolium chloride staining.</p><p><b>RESULTS</b>(1) In control group, systolic and diastolic blood pressure (SBP and DBP), left ventricular systolic pressure, maximal rate of increase and decline in left ventricular pressure (+/- dp/dtmax) and cardiac output significantly declined (P < 0.05-0.01), while left ventricular end-diastolic pressure (LVEDP) and pulmonary capillary wedge pressure (PCWP) significantly increased at the end of 3 hours of LAD occlusion (both P < 0.01), with +/- dp/dtmax further significantly declined (both P < 0.05) at 60 minutes of reperfusion. In adenosine treated group, the changes of SBP and DBP, left ventricular systolic pressure, +/- dp/dtmax, cardiac output, LVEDP and PCWP were the same as those in the control group after AMI and reperfusion, while left ventricular systolic pressure, +/- dp/dtmax, cardiac output, LVEDP and PCWP recovered significantly at 60 minutes of reperfusion compared with those at 6 hours AMI. (2) In control group, the coronary ligation areas (LA) were similar (P > 0.05) detected by MCE in vivo and histopathological evaluation, and the areas of no-reflow were both as high as 67.5% and 69.3%, respectively. The final necrosis area reached 99% of LA. Compared with those in the control group, there was no significant difference in LA on both MCE and histopathological evaluation in the adenosine-treated group, though the areas of no-reflow on both methods were significantly decreased to 21% and 22% (both P < 0.01) and final necrosis area was also significantly decreased to 75% of LA (P < 0.05). (3) In the control group, CBV were significantly declined to 45.8% and 50.6% of the baseline at immediately after release of 3 hours occlusion and at 60 minutes of reperfusion, respectively (both P < 0.01). In the adenosine-treated group, CBV were also significantly declined at immediately after release of 3 hours occlusion, and at 60 minutes of reperfusion (both P < 0.05), though significantly increased to 79.5% and 79.9% of the baseline which were both significantly higher than those in the control group.</p><p><b>CONCLUSION</b>Adenosine has an effective role in preventing myocardial no-reflow, improving left ventricular function and reducing infarct area during AMI and reperfusion in mini-swine.</p>

Beneficial effects of fosinopril on myocardial no-reflow in a mini-swine model of acute myocardial infarction and reperfusion / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the effects of fosinopril on myocardial no-reflow in a mini-swine model of acute myocardial infarction and reperfusion.</p><p><b>METHODS</b>Twenty-four mini-swines were randomized into 3 study groups: 8 in control group, 8 in fosinopril-treated group (1 mg.kg(-1).d(-1)) and 8 in sham-operated group. Animals in the former two groups were subjected to 3 hours of coronary occlusion followed by 60 minutes of reperfusion. Data on haemodynamics and coronary blood flow volume (CBV) were collected, and the area of no-reflow was evaluated with both myocardial contrast echocardiography (MCE) in vivo and pathological means. Necrosis area was measured with triphenyltetrazolium chloride (TTC) staining.</p><p><b>RESULTS</b>(1) In the control group, systolic and diastolic blood pressure (SBP and DBP), left ventricular systolic pressure (LVSP), maximal rate of increase and decrease in left ventricular pressure (+/- dp/dt(max)) and cardiac output (CO) significantly declined (P < 0.05-0.01), while left ventricular end-diastolic pressure (LVEDP) and pulmonary capillary wedge pressure (PCWP) significantly increased at the end of 3 hours occlusion of left anterior descending artery (both P < 0.01). Compared with those at the end of 3 hours of occlusion, +/- dp/dt(max) further significantly declined (P < 0.05) at 60 minutes of reperfusion. In the fosinopril group, the changes of SBP and DBP, LVSP, +/- dp/dt(max), CO, LVEDP and PCWP were similar as those in the control group after 3 hours of acute myocardial infarction. In contrast, LVSP, +/- dp/dt(max), CO, LVEDP and PCWP recovered significantly at 60 minutes of reperfusion. (2) In the control group, the coronary ligation area was similar on both MCE in vivo and pathological evaluation, and the area of no-reflow was similarly as high as 78.5% and 82.3%, respectively, with final necrosis area reaching 99% of ligation area. In the fosinopril group, there was no significant difference in ligation area on both MCE and pathological evaluations between the fosinopril and control groups, although the area of no-reflow on both methods was significantly decreased to 24.5% and 25.2%, respectively, (P < 0.01) with final necrosis area of pathological evaluation being also significantly decreased to 88.9% of LA (P < 0.05). (3) In the control group, CBV was significantly declined to 45.8% and 50.6% from at baseline, immediately after release of occlusion (3 hours) and at 60 minutes of reperfusion (P < 0.01). In the fosinopril group, CBV was also significantly declined immediately after release of occlusion (3 hours), and at 60 minutes of reperfusion (P < 0.05), but significantly increased to 69.1% and 72.1% from at baseline, that were significantly greater than those in the control group (both P < 0.01).</p><p><b>CONCLUSION</b>Fosinopril is effective in preventing myocardial no-reflow, improving left ventricular function, and reducing infarct area during acute myocardial infarction and reperfusion in mini-swine.</p>