Apyrase treatment of myocardial infarction according to a clinically applicable protocol fails to reduce myocardial injury in a porcine model

<p>Abstract</p> <p>Background</p> <p>Ectonucleotidase dependent adenosine generation has been implicated in preconditioning related cardioprotection against ischemia-reperfusion injury, and treatment with a soluble ectonucleotidase has been shown to reduce myocardial infarct size (IS) when applied prior to induction of ischemia. However, ectonucleotidase treatment according to a clinically applicable protocol, with administration only after induction of ischemia, has not previously been evaluated. We therefore investigated if treatment with the ectonucleotidase apyrase, according to a clinically applicable protocol, would reduce IS and microvascular obstruction (MO) in a large animal model.</p> <p>Methods</p> <p>A percutaneous coronary intervention balloon was inflated in the left anterior descending artery for 40 min, in 16 anesthetized pigs (40-50 kg). The pigs were randomized to 40 min of 1 ml/min intracoronary infusion of apyrase (10 U/ml, n = 8) or saline (0.9 mg/ml, n = 8), twenty minutes after balloon inflation. Area at risk (AAR) was evaluated by <it>ex vivo </it>SPECT. IS and MO were evaluated by <it>ex vivo </it>MRI.</p> <p>Results</p> <p>No differences were observed between the apyrase group and saline group with respect to IS/AAR (75.7 ± 4.2% vs 69.4 ± 5.0%, p = NS) or MO (10.7 ± 4.8% vs 11.4 ± 4.8%, p = NS), but apyrase prolonged the post-ischemic reactive hyperemia.</p> <p>Conclusion</p> <p>Apyrase treatment according to a clinically applicable protocol, with administration of apyrase after induction of ischemia, does not reduce myocardial infarct size or microvascular obstruction.</p

Prospects for Creation of Cardioprotective and Antiarrhythmic Drugs Based on Opioid Receptor Agonists

It has now been demonstrated that the μ, δ(1), δ(2), and κ(1) opioid receptor (OR) agonists represent the most promising group of opioids for the creation of drugs enhancing cardiac tolerance to the detrimental effects of ischemia/reperfusion (I/R). Opioids are able to prevent necrosis and apoptosis of cardiomyocytes during I/R and improve cardiac contractility in the reperfusion period. The OR agonists exert an infarct‐reducing effect with prophylactic administration and prevent reperfusion‐induced cardiomyocyte death when ischemic injury of heart has already occurred; that is, opioids can mimic preconditioning and postconditioning phenomena. Furthermore, opioids are also effective in preventing ischemia‐induced arrhythmias

Thrombolysis in Patients With Unstable Angina Improves the Angiographic But Not the Clinical Outcome - Results of Unasem, a Multicenter, Randomized, Placebo-controlled, Clinical-trial With Anistreplase

Background. The value of thrombolytic therapy in unstable angina is unclear. Methods and Results. To study this problem, 159 patients were studied in a double-blind, placebo-controlled multicenter trial. Patients without a previous myocardial infarction, with a typical history of unstable angina, and ECG abnormalities indicative of ischemia were included. After baseline angiography, study medication (anistreplase or placebo) was given. Angiography was repeated after 12-28 hours. A significant decrease occurred in diameter stenosis between the first and second angiogram in the anistreplase group compared with the placebo group (11% versus 3%, p=0.008). This difference was caused by reopening of occluded vessels in the thrombolytic group. However, no beneficial clinical effects of thrombolytic treatment were found. Bleeding complications were significantly higher in patients who received thrombolytic therapy (21 versus seven patients, p=0.001). Conclusions. Thus, angiographic but no clinical improvement after thrombolytic treatment with anistreplase was found in patients with unstable angina with an excess of bleeding complications. Therefore, thrombolytic treatment cannot be recommended in patients diagnosed as having unstable angina until proven otherwise

A comparison of systematic stenting and conventional balloon angioplasty during primary percutaneous transluminal coronary angioplasty for acute myocardial infarction

AbstractOBJECTIVESIn a multicenter, randomized trial, systematic stenting using the Wiktor stent was compared to conventional balloon angioplasty with provisional stenting for the treatment of acute myocardial infarction (AMI).BACKGROUNDPrimary angioplasty in AMI is limited by in-hospital recurrent ischemia and a high restenosis rate.METHODSA total of 211 patients with AMI <12 h from symptom onset, with an occluded native coronary artery, were randomly assigned to systematic stenting (n = 101) or balloon angioplasty (n = 110). The primary end point was the binary six-month restenosis rate determined by core laboratory quantitative angiographic analysis.RESULTSAngiographic success (Thrombolysis in Myocardial Infarction [TIMI] flow grade 3 and residual diameter stenosis <50%) was achieved in 86% of the patients in the stent group and in 82.7% of those in the balloon angioplasty group (p = 0.5). Compared with the 3% cross-over in the stent group, cross-over to stenting was required in 36.4% of patients in the balloon angioplasty group (p = 0.0001). Six-month binary restenosis (≥50% residual stenosis) rates were 25.3% in the stent group and 39.6% in the balloon angioplasty group (p = 0.04). At six months, the event-free survival rates were 81.2% in the stent group and 72.7% in the balloon angioplasty group (p = 0.14), and the repeat revascularization rates were 16.8% and 26.4%, respectively (p = 0.1). At one year, the event-free survival rates were 80.2% in the stent group and 71.8% in the balloon angioplasty group (p = 0.16), and the repeat revascularization rates were 17.8% and 28.2%, respectively (p = 0.1).CONCLUSIONSIn the setting of primary angioplasty for AMI, as compared with a strategy of conventional balloon angioplasty, systematic stenting using the Wiktor stent results in lower rates of angiographic restenosis