Ronghua Luan

Involvement of activated astrocyte and microglia of locus coeruleus in cardiac pain processing after acute cardiac injury

Abstract Objective: It is still not known whether the glial cell activation of locus coeruleus (LC) is involved in the neurophysiologic mechanism of the acute phase of heart disease. The aim of this study was to investigate whether the glial cell activation of LC responds to acute cardiac injury (ACI). Methods: In this study, ACI was established by intramyocardial injection of formalin. Afterward, we analysed c-Fos, OX42, GFAP and P2X4R expression levels in the LC of the rats by immunofluorescence staining or Western blot analysis. Results: There was no significant difference in the levels of these markers in the LC between the normal control and the sham-operated groups. Following ACI, up-regulation of GFAP, OX42 and P2X4R expression levels were observed in locus coeruleus of the rats. The peak expression time was at hour 24. P2X4R was colocalized with OX42 in activated microglias, but not with GFAP in activated astrocytes. Compared with the control group, the ACI group showed a high expression level of c-Fos at hour 1 with a peak expression level at hour 2. Conclusion: The results showed that LC glia cells, like neurons, could sensitively respond to cardiovascular nociception induced by ACI at different time points. Results of this study may provide insights into the role of glial activation in response to ACI and may represent a potential strategy for investigation of neurophysiologic mechanism of cardiac pain.

Apelin protects sarcoplasmic reticulum function and cardiac performance in ischaemia-reperfusion by attenuating oxidation of sarcoplasmic reticulum Ca2+-ATPase and ryanodine receptor.

AIMS Apelin, an endogenous cytokine, has a number of biological effects on the cardiovascular system, including a cardioprotective effect and calcium modulation. Because the intracellular calcium abnormality is considered to play an important role in cardiac dysfunction induced by ischaemia-reperfusion (I/R), the aim of this study was to examine the effects of apelin-13 on I/R-induced changes in cardiac performance and sarcoplasmic reticulum (SR) function. METHODS AND RESULTS Isolated rat hearts were subjected to global ischaemia followed by reperfusion in the absence or presence of apelin-13 and inhibitors of some survival kinases. We found that depressed cardiac performance induced by I/R was attenuated by apelin-13. Furthermore, apelin-13 depressed oxidative stress during I/R. SR function depressed during I/R was partly reversed by apelin-13. SR oxidative modification levels were increased in I/R and reversed by apelin. Inhibitors of phosphatidylinositol-3-kinase and protein kinase C abolished the effects of apelin. Apelin-13 maintained the Ca(2+) transient against I/R in cardiomyocytes. CONCLUSION Apelin protects SR function and cardiac performance during I/R by attenuating oxidation of sarco(endo)plasmic reticulum Ca(2+)-ATPase and RyR.

Efficacy and safety of supramaximal titrated inhibition of renin-angiotensin-aldosterone system in idiopathic dilated cardiomyopathy

The optimal dosing strategies for blocking the renin‐angiotensin‐aldosterone system in idiopathic dilated cardiomyopathy (IDCM) are poorly known. We sought to determine the long‐term efficacy and safety of supramaximal titration of benazepril and valsartan in patients with IDCM.

Effect of chronic pretreatment of angiotensin-converting receptor blocker on no-reflow phenomenon in patients with acute myocardial infarction undergoing percutaneous coronary intervention.

AIMS Angiotensin receptor blockers (ARBs) exert favorable effects on the vascular system, which are not directly related to hypertension lowering function. The no-reflow phenomenon determines the prognosis in patients after acute myocardial infarction (AMI). Early ARB treatment has many beneficial effects on the prognosis after AMI. In this study, we tested the hypothesis that ARB treatment before admission would have beneficial effects on the development of the no-reflow phenomenon after infarction. METHODS We investigated 276 consecutive patients with AMI undergoing successful primary percutaneous coronary intervention (PCI). No-reflow was defined as thrombolysis in myocardial infarction (TIMI) flow grade <3, which was determined by the TIMI frame count method using angiographic images obtained just after PCI and stenting. RESULTS Compared with patients without ARB treatment, patients with ARB had more frequently hypertension and ST resolution (P < 0.05), but no significant difference was found in the other clinical characteristics (age, sex, Hyperlipidaemia, Diabetes mellitus, etc) between the two groups. A total of 51 patients receiving chronic ARB treatment before admission have lower incidence of the no-reflow phenomenon than those without chronic ARB treatment (8.7% and 26.7%, P= 0.003). However, the incidence of the no-reflow phenomenon between the patients with and without hypertension had no significant difference. Multivariable logistic regression analysis revealed that ARB pretreatment was a significant predictor of the no-reflow phenomenon, whereas blood pressure was found to be insignificant. CONCLUSION Chronic pretreatment of ARB is associated with the reduction of the no-reflow phenomenon in patients with reperfused AMI and could preserve microvascular integrity after AMI independent of blood pressure lowering, which may contribute to better functional recovery.

INITIAL AND LONG-TERM CLINICAL OUTCOMES OF UNPROTECTED LEFT MAIN STENTING USING DRUG ELUTING STENTS

Objectives To evaluate the initial and long-term clinical outcomes of patients with unprotected left main (ULM) stenosis undergoing percutaneous coronary intervention (PCI) with drug eluting stents (DES) at XiJing Hospital Centre in real world patient population. Methods After excluding acute ST-segment elevation myocardial infarction and bailout stenting, 798 patients treated for ULM disease with DES from January 2003 to December 2011 at XiJing Hospital were enrolled. The clinical outcomes of ULM treated with DES were evaluated by major adverse cardiac events (MACE) and stent thrombosis (ST) during in-hospital period and after long-term follow-up respectively. MACE was defined as cardiac death, non-fatal myocardial infarction (MI) and clinically driven target lesion revascularisation (TLR). ST was evaluated in accordance with the Academic Research Consortium (ARC) definitions. Results The mean age of study population was 62±10 years, 649 (81%) patients were male, 199 (25%) patients were diabetic, and the mean ejection fraction was 54%±11%. 71 (9%) patients had an ostial and 27 (3%) had a shaft lesion (nondistal subgroup), 700 (88%) patients had a bifurcation lesion (distal subgroup). In distal subgroup, 416 (59%) patients were treated with 1 stent (1-stent subgroup) and 284 (41%) were treated with 2 stent (2-stent subgroup). Among 2-stent subgroup, 74 (11%) patients were treated with crush (crush subgroup), 86 (12%) were treated with culotte (culotte subgroup), 43 (6%) were treated with kissing (kissing subgroup) and 81 (12%) were treated with T stenting (T subgroup). Angiographic and clinical successes of PCI were obtained in all patients. During the in-hospital period, MACE occurred in 7 (0.8%) patients including 5 (0.6%) cardiac deaths and 2 (0.2%) MIs. one patient had definite (died) and four patients had probable stent thrombosis (1 had a MI and 3 died). During the long-term follow-up duration of 27±20 months, MACE occurred in 176 (22%) patients including 25 (3%) cardiac deaths, 16 (2%) MIs and 135 (17%) TLRs. six patients had probable (died) and 12 patients had possible stent thrombosis (2 had MI and 10 died). There were no significant differences in in-hospital MACE rates between nondistal and distal subgroup, between 1-stent and 2-stent subgroup and among different 2-stent technique subgroups. After long-term follow-up, the TLR rate was significantly higher in distal subgroup than in nondistal subgroup (18% vs 9%, p<0.05), the MACE rate was significantly higher in 2-stent subgroup than in 1-stent subgroup (28% vs 20%, p<0.05), and the different 2-stent technique subgroups showed similar long-term outcomes. The total stent thrombosis rates were also no significant differences between nondistal and distal subgroup, between 1-stent and 2-stent subgroup and among different 2-stent technique subgroups. Conclusions Treatment of ULM with DES is feasible and safe with good in-hospital and acceptable long-term clinical results. Compared with ostial and shaft lesion, distal bifurcation lesion is associated with a worse long-term TLR rate. 1-stent technique had a better long-term MACE rate than 2-stent technique when distal bifurcation lesion was treated, whereas different 2-stent techniques had similar clinical outcomes.