Weidong Pei

Remote periconditioning reduces myocardial no-reflow by the activation of KATP channel via inhibition of Rho-kinase

UNLABELLED Remote periconditioning is induced by brief cycles of ischemia and reperfusion of a remote organ applied during sustained myocardial ischemia. It remains unknown whether the remote periconditioning reduces myocardial no-reflow. The adenosine triphosphate-sensitive potassium (K(ATP)) channel opening and inhibition of Rho-kinase may be the important mechanism of protection against myocardial no-reflow. Therefore, this study was sought to assess the effect of remote periconditioning on myocardial no-reflow and explore the possible mechanism. METHODS Coronary ligation area and area of no-reflow were determined with pathological means in 58 mini-swines randomized into 7 study groups: 9 controls, 8 in remote periconditioning, 8 in hydroxyfasudil (a specific inhibitor of Rho-kinase)-treated, 9 in glibenclamide (K(ATP) channel blocker)-treated, 8 in remote periconditioning and glibenclamide, 8 in hydroxyfasudil and glibenclamide and 8 sham-operated. The ischemia and reperfusion model was created with 3 h of left anterior descending artery occlusion followed by 2 h of reperfusion. RESULTS Compared with the control group, remote periconditioning decreased Rho-kinase activity (P<0.01), increased coronary blood volume (P<0.05), decreased area of no-reflow (from 82.3+/-3.9% to 45.5+/-5.7% of ligation area, P<0.01) and reduced necrosis size (from 98.5+/-1.3% to 74.7+/-6.3% of ligation area, P<0.05). Hydroxyfasudil had the same effect on the above parameters as remote periconditioning. Glibenclamide abrogated the effect of remote periconditioning or hydroxyfasudil on area of no-reflow and necrosis area, but not Rho-kinase activity. CONCLUSION Remote periconditioning can reduce myocardial no-reflow after ischemia and reperfusion. This beneficial effect could be due to its activation of K(ATP) channel via inhibition of Rho-kinase.

The Effect of Statins on the No-Reflow Phenomenon : An Observational Study in Patients with Hyperglycemia before Primary Angioplasty

BACKGROUND An association between admission plasma glucose levels and an increased risk of no-reflow has been well documented. Although HMG-CoA reductase inhibitor (statin) therapy can reduce no-reflow, little is known about its effect on no-reflow in patients with hyperglycemia. In the present study, we investigated whether pretreatment with a statin could reduce no-reflow in patients with hyperglycemia, who underwent primary coronary intervention for acute myocardial infarction (AMI). METHODS A total of 259 consecutive patients who underwent primary angioplasty for a first AMI were studied. Blood glucose and creatinine kinase levels were measured on admission. All patients underwent 2-dimensional echocardiography and electrocardiographic analysis just after admission. No-reflow was defined as a Thrombolysis in Myocardial Infarction (TIMI) flow grade <3. Hyperglycemia was defined as a blood glucose level >or=10 mmol/L. Statin administration prior to admission was determined by detailed interview or information in the medical records. RESULTS Hyperglycemia was diagnosed in 154 patients on admission. The no-reflow phenomenon was found in 31 of the 154 patients with hyperglycemia. The incidence of no-reflow was significantly greater in patients with hyperglycemia compared with no hyperglycemia. A multivariable logistic regression analysis showed that hyperglycemia on admission was an independent predictor of no-reflow. Among the 154 patients with hyperglycemia, there were no significant differences in baseline clinical characteristics between patients who received statin pretreatment and those who did not; however, hyperlipidemia occurred in a greater number of the patients who did not receive statin pretreatment. The 40 patients with hyperglycemia who received statins before admission had a lower incidence of no-reflow than those who did not receive statin pretreatment (5% and 25.4%; p < 0.05). Multivariable logistic regression analysis revealed that absence of statin pretreatment was a significant predictor of no-reflow in patients with hyperglycemia, along with ejection fraction on admission, initial TIMI 0 flow, number of Q waves, and anterior AMI. CONCLUSION The results of our study show that pretreatment with statins could attenuate no-reflow after AMI in patients with acute hyperglycemia.

Chronic pretreatment of metformin is associated with the reduction of the no-reflow phenomenon in patients with diabetes mellitus after primary angioplasty for acute myocardial infarction.

INTRODUCTION Metformin is one of the most commonly prescribed antihyperglycemic agents for the treatment of type 2 diabetes. However, little is known about the effect of metformin on no-reflow in diabetic patients. AIM In this study, we investigated retrospectively whether chronic pretreatment with metformin was associated with no-reflow in diabetic patients who underwent primary coronary intervention for acute myocardial infarction (AMI). RESULTS A total of 154 consecutive diabetic patients who underwent primary angioplasty for a first ST-segment elevation myocardial infarction were studied. No-reflow was defined as a final TIMI flow of ≤2 or final TIMI flow of 3 with a myocardial blush grade of <2. The no-reflow phenomenon was found in 53 of 154 patients. There were no significant differences in clinical characteristics between the patients with and without metformin pretreatment. However, the 65 patients receiving chronic metformin treatment before admission had lower incidence of the no-reflow than those without it (4.2 and 14.6%, P < 0.05). Multivariable logistic regression analysis revealed that absence of metformin pretreatment was a significant predictor of the no-reflow along with high-burden thrombus, ejection fraction on admission and anterior AMI. CONCLUSION These results suggested that chronic pretreatment with metformin may be associated with the reduction of the no-reflow phenomenon in patients with diabetes mellitus after primary angioplasty for AMI.

The Effect of Statins on the No-Reflow Phenomenon

BackgroundAn association between admission plasma glucose levels and an increased risk of no-reflow has been well documented. Although HMG-CoA reductase inhibitor (statin) therapy can reduce no-reflow, little is known about its effect on no-reflow in patients with hyperglycemia. In the present study, we investigated whether pretreatment with a statin could reduce no-reflow in patients with hyperglycemia, who underwent primary coronary intervention for acute myocardial infarction (AMI).MethodsA total of 259 consecutive patients who underwent primary angioplasty for a first AMI were studied. Blood glucose and creatinine kinase levels were measured on admission. All patients underwent 2-dimensional echocardiography and electrocardiographic analysis just after admission. No-reflow was defined as a Thrombolysis in Myocardial Infarction (TIMI) flow grade <3. Hyperglycemia was defined as a blood glucose level ≥10 mmol/L. Statin administration prior to admission was determined by detailed interview or information in the medical records.ResultsHyperglycemia was diagnosed in 154 patients on admission. The no-reflow phenomenon was found in 31 of the 154 patients with hyperglycemia. The incidence of no-reflow was significantly greater in patients with hyperglycemia compared with no hyperglycemia. A multivariable logistic regression analysis showed that hyperglycemia on admission was an independent predictor of no-reflow. Among the 154 patients with hyperglycemia, there were no significant differences in baseline clinical characteristics between patients who received statin pretreatment and those who did not; however, hyperlipidemia occurred in a greater number of the patients who did not receive statin pretreatment. The 40 patients with hyperglycemia who received statins before admission had a lower incidence of no-reflow than those who did not receive statin pretreatment (5% and 25.4%; p < 0.05). Multivariable logistic regression analysis revealed that absence of statin pretreatment was a significant predictor of no-reflow in patients with hyperglycemia, along with ejection fraction on admission, initial TIMI 0 flow, number of Q waves, and anterior AMI.ConclusionThe results of our study show that pretreatment with statins could attenuate no-reflow after AMI in patients with acute hyperglycemia.