Background Our previous studies have demonstrated that Tongxinluo （TXL）, a traditional Chinese medicine, can protect hearts against no-reflow and reperfusion injury in a protein kinase A （PKA）-dependent manner. Th...Background Our previous studies have demonstrated that Tongxinluo （TXL）, a traditional Chinese medicine, can protect hearts against no-reflow and reperfusion injury in a protein kinase A （PKA）-dependent manner. The present study was to investigate whether the PKA-mediated cardioprotection of TXL against no-reflow and reperfusion injury relates to the inhibition of myocardial inflammation, edema, and apoptosis. Methods In a 90-minute ischemia and 3-hour reperfusion model, minipigs were randomly assigned to sham, control, TXL （0.05 g/kg, gavaged one hour prior to ischemia）, and TXL ＋ H-89 （a PKA inhibitor, intravenously and continuously infused at 1.0 μg/kg per minute） groups. Myocardial no-reflow, necrosis, edema, and apoptosis were determined by pathological and histological studies. Myocardial activity of PKA and myeloperoxidase was measured by colorimetric method. The expression of PKA, phosphorylated cAMP response element-binding protein （p-CREB） （Ser133）, tumor necrosis factor a （TNF-a）, P-selectin, apoptotic proteins, and aquaporins was detected by Western blotting analysis. Results TXL decreased the no-reflow area by 37.4% and reduced the infarct size by 27.0% （P〈0.05）. TXL pretreatment increased the PKA activity and the expression of Ser133 p-CREB in the reflow and no-reflow myocardium （P 〈0.05）. TXL inhibited the ischemia-reperfusion-induced elevation of myeloperoxidase activities and the expression of TNF-a and P-selectin, reduced myocardial edema in the left ventricle and the reflow and no-reflow areas and the expression of aquaporin-4, -8, and -9, and decreased myocytes apoptosis by regulation of apoptotic protein expression in the reflow and no-reflow myocardium. However, addition of the PKA inhibitor H-89 counteracted these beneficial effects of TXL. Conclusion PKA-mediated cardioprotection of TXL against no-reflow and reperfusion injury relates to the inhibition of myocardial inflammation, edema, and apoptosis in the reflow and no-reflow myocardium.展开更多
Objectire This study compares the effects of small dose of recombinant tissue - type plasminogenactivator (tPA) with those of conventional dose of urokinase (UK) and assesses the influence of different modes ofintrave...Objectire This study compares the effects of small dose of recombinant tissue - type plasminogenactivator (tPA) with those of conventional dose of urokinase (UK) and assesses the influence of different modes ofintravenous UK administration in patients with acute myocardial infarction (AMI). Methods Eighty patientswith AMI were randomized to 50mg of tPA (Group Ⅰ, n=26) using an accelerating approach or to 1.0-1.5 millionU of UK (Group Ⅱ, n=54). UK was administered as a single bolus injection of whole dose (GrouP Ⅱa, n=26) orhalf dose bolus injection followed by half dose infusion (Group Ⅱb, n=28). All patients underwent coronaryartsriogrophy 90min after the initiation of intravenous thrombolysis, and the infarct - related coronary artery (IRA)patency was evaluated. Cardiac events during hospitalization were recorded and predischarge left ventricularfunction was determined by two - dimensional echocardiography. Results The IRA patency rate was significantlyhigher in Group Ⅰ (88.4%) than in Group Ⅱ (53.7%) (P<0.01). Group Ⅰ patients had less cardiac events duringhospitalization (11.5% vs 33.3%) and greater improvement in left ventricular function than group Ⅱ patients.However, these angiogrophic, left ventricular functional and prognostic parameters did not significantly differbetween Group Ⅱa and Group Ⅱb. Conclusion Thrombolysis after AMI with small dose of intravenous tPAexerts better angiographic and clinical effects than that with conventional dose of UK. The thrombolytic effects ofUK were not affected by different modes of intravenous administration of the agent.展开更多
文摘Background Our previous studies have demonstrated that Tongxinluo （TXL）, a traditional Chinese medicine, can protect hearts against no-reflow and reperfusion injury in a protein kinase A （PKA）-dependent manner. The present study was to investigate whether the PKA-mediated cardioprotection of TXL against no-reflow and reperfusion injury relates to the inhibition of myocardial inflammation, edema, and apoptosis. Methods In a 90-minute ischemia and 3-hour reperfusion model, minipigs were randomly assigned to sham, control, TXL （0.05 g/kg, gavaged one hour prior to ischemia）, and TXL ＋ H-89 （a PKA inhibitor, intravenously and continuously infused at 1.0 μg/kg per minute） groups. Myocardial no-reflow, necrosis, edema, and apoptosis were determined by pathological and histological studies. Myocardial activity of PKA and myeloperoxidase was measured by colorimetric method. The expression of PKA, phosphorylated cAMP response element-binding protein （p-CREB） （Ser133）, tumor necrosis factor a （TNF-a）, P-selectin, apoptotic proteins, and aquaporins was detected by Western blotting analysis. Results TXL decreased the no-reflow area by 37.4% and reduced the infarct size by 27.0% （P〈0.05）. TXL pretreatment increased the PKA activity and the expression of Ser133 p-CREB in the reflow and no-reflow myocardium （P 〈0.05）. TXL inhibited the ischemia-reperfusion-induced elevation of myeloperoxidase activities and the expression of TNF-a and P-selectin, reduced myocardial edema in the left ventricle and the reflow and no-reflow areas and the expression of aquaporin-4, -8, and -9, and decreased myocytes apoptosis by regulation of apoptotic protein expression in the reflow and no-reflow myocardium. However, addition of the PKA inhibitor H-89 counteracted these beneficial effects of TXL. Conclusion PKA-mediated cardioprotection of TXL against no-reflow and reperfusion injury relates to the inhibition of myocardial inflammation, edema, and apoptosis in the reflow and no-reflow myocardium.
文摘Objectire This study compares the effects of small dose of recombinant tissue - type plasminogenactivator (tPA) with those of conventional dose of urokinase (UK) and assesses the influence of different modes ofintravenous UK administration in patients with acute myocardial infarction (AMI). Methods Eighty patientswith AMI were randomized to 50mg of tPA (Group Ⅰ, n=26) using an accelerating approach or to 1.0-1.5 millionU of UK (Group Ⅱ, n=54). UK was administered as a single bolus injection of whole dose (GrouP Ⅱa, n=26) orhalf dose bolus injection followed by half dose infusion (Group Ⅱb, n=28). All patients underwent coronaryartsriogrophy 90min after the initiation of intravenous thrombolysis, and the infarct - related coronary artery (IRA)patency was evaluated. Cardiac events during hospitalization were recorded and predischarge left ventricularfunction was determined by two - dimensional echocardiography. Results The IRA patency rate was significantlyhigher in Group Ⅰ (88.4%) than in Group Ⅱ (53.7%) (P<0.01). Group Ⅰ patients had less cardiac events duringhospitalization (11.5% vs 33.3%) and greater improvement in left ventricular function than group Ⅱ patients.However, these angiogrophic, left ventricular functional and prognostic parameters did not significantly differbetween Group Ⅱa and Group Ⅱb. Conclusion Thrombolysis after AMI with small dose of intravenous tPAexerts better angiographic and clinical effects than that with conventional dose of UK. The thrombolytic effects ofUK were not affected by different modes of intravenous administration of the agent.
