Routine early coronary angioplasty versus ischaemia-guided angioplasty after thrombolysis in acute ST-elevation myocardial infarction: a meta-analysis.

AIMS: Prompt coronary reperfusion following acute ST-segment elevation myocardial infarction is pivotal to survival. Primary angioplasty is the gold standard in restoring reperfusion, but thrombolysis needs consideration when optimal call to balloon time is not feasible. Following lysis and with evolving pharmacoinvasive therapies, the advantage of routine, early percutaneous coronary intervention (PCI) over standard ischaemia-guided PCI remains debatable. We meta-analysed studies comparing these two interventional strategies. METHODS AND RESULTS: A MEDLINE search for randomized control studies was performed using the search terms 'coronary, thrombolysis, early or immediate stenting, and acute ST-elevation myocardial infarction'. Further, relevant studies were identified from global cardiovascular scientific sessions/congresses. Two interventional strategies were studied in 3195 patients in eight trials and meta-analysed using a random effects model. The combined endpoint of 30-day mortality, re-infarction, and ischaemia was reached in 106/1487 (7.3%) patients in the routine early PCI group and in 199/1470 (13.5%) patients in the ischaemia-guided PCI group following lysis with odds ratio (OR) 0.47 [95% confidence interval (CI), 0.32-0.68, P < 0.0001] favouring routine early PCI, driven by significant reduction in both re-infarction OR 0.62 (95% CI, 0.42-0.90, P < 0.011) and ischaemia OR 0.21 (95% CI, 0.10-0.47, P < 0.001). Thirty-day mortality or major bleeding rates between strategies were not significantly different. CONCLUSION: Where primary PCI is not feasible, our meta-analysis favours routine early PCI within 24 h of thrombolysis for acute ST-elevation myocardial infarction-a strategy that is safe and a time-target that is easily achievable. Early PCI is associated with reduced recurrence of ischaemia and re-infarction, but at no increased risk of major haemorrhage.

Autocrine and paracrine actions of natriuretic peptides in the heart.

The natriuretic peptides, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP), are a family of polypeptide mediators exerting numerous actions in cardiovascular homeostasis. ANP and BNP are cardiac derived, being secreted and up-regulated in myocardium in response to many pathophysiological stimuli. CNP is an endothelium-derived mediator. The classical endocrine effects of ANP and BNP on fluid homeostasis and blood pressure, especially in conditions characterised by left ventricular dysfunction, are well recognised and extensively researched. However, there is accumulating evidence that, in addition to endocrine actions, ANP and BNP exhibit important autocrine and paracrine functions within the heart and coronary circulation. These include regulation of myocyte growth, inhibition of fibroblast proliferation and extracellular matrix deposition, a cytoprotective anti-ischaemic (preconditioning-like) function, and influences on coronary endothelium and vascular smooth muscle proliferation and contractility. Most if not all of these actions can be ascribed to particulate guanylyl cyclase activation because the ANP/BNP receptor, natriuretic peptide receptor (NPR)-A, has an intracellular guanylyl cyclase domain. Subsequent elevation of the intracellular second messenger cGMP may exert diverse physiological effects through activation of cGMP-dependent protein kinases (cGK), predominantly cGK-I. However, there appear to be other contributory mechanisms in several of these actions, including the augmentation of nitric oxide synthesis. These diverse actions may represent counterregulatory mechanisms in the pathophysiology of many cardiovascular diseases, not just those typified by left ventricular dysfunction. Ultimately, insights from the autocrine/paracrine actions of natriuretic peptides may provide routes to therapeutic application in cardiac diseases of natriuretic peptides and drugs that modify their availability.

B-type natriuretic peptide limits infarct size in rat isolated hearts via KATP channel opening.

B-type natriuretic peptide (BNP) has been reported to be released from the myocardium during ischemia. We hypothesized that BNP mediates cardioprotection during ischemia-reperfusion and examined whether exogenous BNP limits myocardial infarction and the potential role of ATP-sensitive potassium (K(ATP)) channel opening. Langendorff-perfused rat hearts underwent 35 min of left coronary artery occlusion and 120 min of reperfusion. The control infarct-to-risk ratio was 44.8 +/- 4.4% (means +/- SE). BNP perfused 10 min before ischemia limited infarct size in a concentration-dependent manner, with maximal protection observed at 10(-8) M (infarct-to-risk ratio: 20.1 +/- 5.2%, P < 0.01 vs. control), associated with a 2.5-fold elevation of myocardial cGMP above the control value. To examine the role of K(ATP) channel opening, glibenclamide (10(-6) M), 5-hydroxydecanoate (5-HD; 10(-4) M), or HMR-1098 (10(-5) M) was coperfused with BNP (10(-8) M). Protection afforded by BNP was abolished by glibenclamide or 5-HD but not by HMR-1098, suggesting the involvement of putative mitochondrial but not sarcolemmal K(ATP) channel opening. We conclude that natriuretic peptide/cGMP/K(ATP) channel signaling may constitute an important injury-limiting mechanism in myocardium.