Poly (ADP-ribose) polymerase inhibitor reduces heart ischaemia/reperfusion injury via inflammation and Akt signalling in rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Poly (ADP-ribose) polymerase (PARP) has been proposed to play an important role in the pathogenesis of heart ischaemia/reperfusion (I/R) injury. 3,4-dihydro-5-[4-(1-piperidinyl)butoxy]-1(2H)-isoquinolinone (DPQ), a potent PARP inhibitor, has cardiac protective effects. Because the underlying mechanisms are not understood, we investigated the effect of DPQ on heart I/R injury and its mechanisms.</p><p><b>METHODS</b>Studies were performed with I/R rats' hearts. DPQ was used to inhibit the activation of PARP. Cardiac function and cellular apoptosis were assessed. The activation of PARP, transcription factor nuclear factor-kappaB (NF-κB), intercellular adhesion molecule-1 (ICAM-1), cyclooxygenase-2 (COX-2) and matrix metalloproteinase-9 (MMP-9) were evaluated. We also evaluated expression of Akt and two of its downstream targets, glycogen synthase kinase-3β (GSK-3β) and forkhead transcription factor FOXO3a.</p><p><b>RESULTS</b>Administration of DPQ significantly decreased the activation of PARP and cellular apoptosis from (35 ± 5)% to (20 ± 4)% and simultaneously improved the cardiac function. DPQ reduced the expressions of NF-κB, ICAM-1, COX-2 and MMP-9 in rat heart and facilitated the activations of phosphor-Akt, phosphor-GSK-3β and phosphor-FOXO3a.</p><p><b>CONCLUSION</b>The protective effects of DPQ were associated with the suppression of inflammation and the activation of the Akt signalling pathways suggesting that the inhibition of poly (ADP-ribose) polymerase reduced heart I/R injury in rats.</p>

Poly (ADP-ribose) polymerase contributes myocardial ischemia-reperfusion of rats by regulating Akt signaling pathway / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effect of poly (ADP-ribose) polymerase (PARP) in heart ischemia and reperfusion (I/R) injury in rat and on Akt mediated signaling pathway.</p><p><b>METHOD</b>Rats were divided into sham, I/R, I/R+3,4-dihydro-5-[4-(1-piperidinyl)butoxy]-1(2H)- isoquinolinone (DPQ, 10 mg/kg, i.p.), an inhibitor of PARP, I/R + DPQ + Akt inhibitor LY294002, 10 mg/kg (n = 12 each). Cardiac function, apoptosis of the cardiomyocytes were measured, myocardial expression of PARP, Akt, glycogen synthase kinase-3β (GSK-3β) and forkhead transcription factor FOXO3a were detected.</p><p><b>RESULTS</b>(1) The expression of PARP were significantly upregulated in I/R group compared to sham group which was significantly attenuated in I/R + DPQ group (P < 0.05 vs. I/R group). (2)PARP inhibition significantly reduced cardiomyocyte apoptosis from (34.0 ± 6.2)% to (23.0 ± 3.8)% (P < 0.05). The LVDP, +dp/dt and -dp/dt were significantly higher in I/R + DPQ group compared to I/R group (all P < 0.05). (3) The expression of Akt, GSK-3β and FOXO3a were significantly upregulated in I/R + DPQ group compared to I/R group (P < 0.05) which were significantly attenuated in I/R + DPQ + LY294002 group compared to I/R + DPQ group (all P < 0.05).</p><p><b>CONCLUSION</b>PARP activation contributes to myocardial I/R injury in rats by modulating Akt mediated signaling pathway.</p>

Poly (ADP-ribose) polymerase inhibition attenuates ischemia/reperfusion induced myocardial injury in rat via reducing myocardial nuclear factor κB activity / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effect of Poly (ADP-ribose) polymerase (PARP) inhibition on ischemia/reperfusion (I/R) induced myocardial injury in rat and related mechanisms.</p><p><b>METHOD</b>Adult Wistar rats were randomly divided into sham-control (n = 18), I/R (60 min ischemia followed by 180 min reperfusion, n = 18) and I/R + PARP inhibitor 3,4-dihydro-5-[4-(1-piperidinyl)butoxy]-1(2H)-isoquinolinone (DPQ), 10 mg/kg, i.p. injection at 1 h before I/R (n = 18). Myocardial expression of PARP, infarct size, and cardiomyocytes apoptosis were determined. Additionally, myocardial NF-κB activity and the myocardial expressions of ICAM-1, COX-2 and MMP-9 at protein and mRNA level were detected.</p><p><b>RESULT</b>(1) Myocardial expression of PARP was significantly upregulated in I/R group compared to sham-control group, which could be significantly reduced by pretreatment with DPQ (P < 0.05 vs. I/R group). (2) Infarct size [(31.45 ± 5.54)% vs. (45.97 ± 4.22)%] and cardiomyocytes apoptosis [(23.0 ± 3.8)% vs. (34.0 ± 6.2)%] were significantly reduced by pretreatment with DPQ (all P < 0.05 vs. I/R group). (3) Pretreatment with DPQ also significantly decreased the NF-κB activity and the myocardial expressions of ICAM-1, COX-2 and MMP-9 at both protein and mRNA level (all P < 0.05).</p><p><b>CONCLUSION</b>The expression of PARP, NF-κB activity and the myocardial expressions of ICAM-1, COX-2 and MMP-9 are upregulated in I/R induced myocardial injury. PARP inhibitor DPQ could attenuate I/R induced myocardial injury through reducing NF-κB activity and the myocardial expressions of ICAM-1, COX-2 and MMP-9.</p>

Effect of Chinese guidelines issued in 2001 on in-hospital management and prognosis of patients with acute myocardial infarction / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the effect of Chinese guidelines issued on December 2001 on in-hospital management and prognosis of patients with acute myocardial infarction.</p><p><b>METHODS</b>A retrospective study was carried out in patients hospitalized in our hospital with acute myocardial infarction from January 1994 to December 2004.</p><p><b>RESULTS</b>There were 1783 patients enrolled in our study. Reperfusion therapy was undergone in 21.7% of patients hospitalized between 1994 and 2001, and in 35.8% of patients hospitalized between 2002 and 2004 (P < 0.001). Beta-blockers, ACE inhibitors and/or angiotensin receptor blockers, lipid regulating agents and antithrombins were used more extensively between 2002 and 2004 than before (all P < 0.001). There were no significant differences in the usage of nitrates and antiplatelets before and after the guidelines was issued (98.8% vs 97.9%, P = 0.172; 97.4% vs 98.6%, P = 0.113 respectively). After the guidelines issued, the incidence of angina pectoris, heart failure and death in hospital were lower than before (32.2% vs 41.2%, P < 0.001; 17.2% vs 26.2%, P < 0.001; 6.4% vs 9.4%, P = 0.038).</p><p><b>CONCLUSIONS</b>Chinese guidelines issued on December 2001 have great effect on the management and prognosis of patients with acute myocardial infarction. After the guidelines was issued the management became more standardized and the incidence of in-hospital complications was lower than before.</p>

A randomized clinical trial on comparison of weight-adjusted dose with low dose recombinant tissue-type plasminogen activator on Chinese patients with acute myocardial infarction / 中华心血管病杂志

<p><b>OBJECTIVE</b>The aim of the study was to quest appropriate dose of recombinant tissue-type plasminogen activator (rt-PA) on Chinese patients with acute myocardial infarction.</p><p><b>METHODS</b>All enrolled patients were randomized into weight-adjusted dose or low dose rt-PA group, and received a basal treatment with aspirin and heparin. Additionally, after an intravenous bolus of 8 mg rt-PA, patients in weight-adjusted dose group (n = 93) were given an intravenous infusion of 42-92 mg rt-PA (1 mg/kg body weight), while patients in the low dose group (n = 91) were treated with an intravenous infusion of 42 mg rt-PA over 90 minutes. The observational endpoint included reperfusion rate of the infarct-related artery by clinical criteria, left ventricular ejection fraction and major adverse cardiovascular events within 30 days in the two groups.</p><p><b>RESULTS</b>There were 74 patients diagnosed reperfusion by clinical criteria in weight-adjusted dose group and 59 patients in low dose group (79.6% vs 64.8%, P = 0.026). The left ventricular ejection fraction seemed to be better in weight-adjusted dose group than in low dose group (P = 0.259). The major adverse cardiovascular events within 30 days were less in weight-adjusted dose group than in low dose group (P < 0.05).</p><p><b>CONCLUSION</b>There was statistical significant superiority of weight-adjusted dose over low dose rt-PA in the treatment of Chinese patients with acute myocardial infarction.</p>