Ever D Grech

Evidence for Free Radical Generation After Primary Percutaneous Transluminal Coronary Angioplasty Recanalization in Acute Myocardial Infarction

In animal models, oxygen-derived free radicals have been found to be important mediators of reperfusion injury to ischemic but viable myocardium. However, in humans, there is no direct evidence of free radical production after the restoration of coronary artery patency in acute myocardial infarction. The purpose of this study was to quantitate and assess the time course of free radical production in coronary venous outflow in patients with acute myocardial infarction undergoing successful recanalization of the infarct-related artery by primary percutaneous transluminal coronary angioplasty (PTCA). Primary PTCA was performed in 17 patients with acute myocardial infarction of < 6 hours duration. Direct free radical production was assessed by coronary venous effluent blood sampling before PTCA and at timed intervals up to 24 hours (or 48 hours in 6 patients) after recanalization. All samples were added to the spin trapping agent alpha-phenyl N-tert butyl nitrone and analyzed by electron paramagnetic resonance spectroscopy. Vessel patency resulted in a sharp increase in free radical signal. Relative to the level before PTCA, the changes reached statistical significance after only 15 minutes (p < 0.05). Peak signals were observed between 1 1/2 and 3 1/2 hours (p < 0.001), then declined up to 5 hours. A second increase in signal level was detected between 18 and 24 hours despite no angiographic evidence of reocclusion. A gradual decline was observed after 24 hours. These findings provide the first direct and quantitative evidence of free radical production in the immediate postrecanalization phase after thrombotic occlusion of a major coronary artery in humans.

ABC of interventional cardiology: Percutaneous coronary intervention. I: History and development

The term “angina pectoris” was introduced by Heberden in 1772 to describe a syndrome characterised by a sensation of “strangling and anxiety” in the chest. Today, it is used for chest discomfort attributed to myocardial ischaemia arising from increased myocardial oxygen consumption. This is often induced by physical exertion, and the commonest aetiology is atheromatous coronary artery disease. The terms “chronic” and “stable” refer to anginal symptoms that have been present for at least several weeks without major deterioration. However, symptom variation occurs for several reasons, such as mental stress, ambient temperature, consumption of alcohol or large meals, and factors that may increase coronary tone such as drugs and hormonal change. View this table: Unequivocal indications for use of coronary stents The Canadian Cardiovascular Society has provided a graded classification of angina which has become widely used. In clinical practice, it is important to describe accurately specific activities associated with angina in each patient. This should include walking distance, frequency, and duration of episodes. In the management of chronic stable angina, there are two invasive techniques available for myocardial revascularisation: coronary artery bypass surgery and catheter attached devices. Although coronary artery bypass surgery was introduced in 1968, the first percutaneous transluminal coronary angioplasty was not performed until September 1977 by Andreas Gruentzig, a Swiss radiologist, in Zurich. The patient, 38 year old Adolph Bachman, underwent successful angioplasty to a left coronary artery lesion and remains well to this day. After the success of the operation, six patients were successfully treated with percutaneous transluminal coronary angioplasty in that year. By todays standards, the early procedures used cumbersome equipment: guide catheters were large and could easily traumatise the vessel, there were no guidewires, and balloon catheters were large with low burst pressures. As a result, the procedure was limited to patients with refractory angina, good …

Pathophysiology and investigation of coronary artery disease

In affluent societies, coronary artery disease causes severe disability and more death than any other disease, including cancer. It manifests as angina, silent ischaemia, unstable angina, myocardial infarction, arrhythmias, heart failure, and sudden death. Coronary artery disease is almost always due to atheromatous narrowing and subsequent occlusion of the vessel. Early atheroma (from the Greek athera (porridge) and oma (lump)) is present from young adulthood onwards. A mature plaque is composed of two constituents, each associated with a particular cell population. The lipid core is mainly released from necrotic “foam cells”—monocyte derived macrophages, which migrate into the intima and ingest lipids. The connective tissue matrix is derived from smooth muscle cells, which migrate from the media into the intima, where they proliferate and change their phenotype to form a fibrous capsule around the lipid core. ![][1] Progression of atheromatous plaque from initial lesion to complex and ruptured plaque ![][2] Schematic representation of normal coronary artery wall (top) and development of atheroma (bottom) When a plaque produces a >50% diameter stenosis (or >75% reduction in cross sectional area), reduced blood flow through the coronary artery during exertion may lead to angina. Acute coronary events usually arise when thrombus formation follows disruption of a plaque. Intimal injury causes denudation of the thrombogenic matrix or lipid pool and triggers thrombus formation. In acute myocardial infarction, occlusion is more complete than in unstable angina, where arterial occlusion is usually subtotal. Downstream embolism of thrombus may also produce microinfarcts. #### Priorities for cardiology referral #### Cardiovascular risk factors ##### Non-modifiable risk factors ##### Modifiable risk factors ##### Uncertain risk factors Patients … [1]: /embed/graphic-1.gif [2]: /embed/graphic-2.gif

Reperfusion injury after acute myocardial infarction.

The restoration of oxygenated blood to ischaemic myocardium—reperfusion—halts the process leading to infarction. Early reperfusion is the only way to prevent progression to myocardial necrosis and thus to limit the size of the infarct. It may also, however, injure the heart. This paradox has become clinically important with the advent of thrombolytic treatment and primary coronary angioplasty for acute myocardial infarction. Several studies have shown that there are three main components of reperfusion injury: reperfusion arrhythmias, myocardial stunning, and lethal myocyte injury. Sixty years ago Tennant and Wiggers recognised that the reintroduction of blood flow could cause arrhythmias.1 In animal experiments arrhythmias may occur within seconds of the onset of reflow.2 In humans reperfusion arrhythmias are commonly associated with intracoronary thrombolytic treatment3 and primary coronary angioplasty.4 5 They may be less common after intravenous thrombolytic treatment,6 and in these circumstances it has been proposed that they pose no additional threat to life.7 The disparity may, however, be related to the rate of recanalisation. Yamazaki et al showed that in dogs sudden reperfusion was more likely to be associated with a high frequency of arrhythmias than was staged reperfusion.8 In a randomised clinical study comparing intravenous thrombolytic treatment with primary coronary angioplasty, ventricular fibrillation was significantly more common in the angioplasty group (6.7% v 2.0%).4 These studies provided angiographic …

Free-radical activity after primary coronary angioplasty in acute myocardial infarction

Free-radical activity in coronary venous outflow was assessed before and after reperfusion in nine patients with acute infarction who had undergone successful recanalization of the infarct-related artery by primary coronary angioplasty. Free-radical activity was measured in serum samples from coronary venous outflow over a timed period of 24 hours by using (1) the percentage molar ratio (PMR) of the diene conjugate 9,11-linoleic acid, and (2) malonaldehyde concentration. Preangioplasty PMR means lay within the normal range, but showed a marked increase soon after successful recanalization. Relative to baseline, the changes over time reached statistical significance between 2 and 60 minutes. No statistically significant changes in malonaldehyde occurred over the study period. We conclude that successful recanalization of the infarct artery is associated with significantly elevated free-radical activity, as measured by the PMR of conjugated diene, in coronary venous outflow. Such patients may be at risk from free radical mediated reperfusion injury.

Practical interventional cardiology

Epidemiology and pathophysiology of coronary artery disease and restenosis PTCA single and multivessel PTCA PTCA for chronic total occlusion PTCA for saphenous vein graft and internal mammary artery graft PTCA for acute MI restenosis directional coronary atherectomy TEC atherectomy rotational coronary atherectomy laser angioplasty intercoronary stenting new technology intracroronary angioplasty intracoronary ultrasound balloon valvuloplasty paediatric interventional cardiology interventions for arrhythmia control trials assisted PTCA retrieval techniques.

Acute coronary syndrome: ST segment elevation myocardial infarction.

Acute ST segment elevation myocardial infarction usually occurs when thrombus forms on a ruptured atheromatous plaque and occludes an epicardial coronary artery. Patient survival depends on several factors, the most important being restoration of brisk antegrade coronary flow, the time taken to achieve this, and the sustained patency of the affected artery. Histological appearance of a ruptured atheromatous plaque (bottom arrow) and occlusive thrombus (top arrow) resulting in acute myocardial infarction There are two main methods of re-opening an occluded artery: administering a thrombolytic agent or primary percutaneous transluminal coronary angioplasty. Effects of treatment with placebo, thrombolytic drugs, or primary percutaneous coronary intervention (PCI) on mortality, incidence of cerebrovascular events, and incidence of non-fatal re-infarction after acute myocardial infarction in randomised studies. Of the 1% incidence of cerebrovascular events in patients undergoing primary percutaneous intervention, only 0.05% were haemorrhagic. In contrast patients receiving thrombolytic drugs had a 1% incidence of haemorrhagic cerebrovascular events (P<0.0001) and an overall 2% incidence of cerebrovascular events (P=0.0004) Although thrombolysis is the commonest form of treatment for acute myocardial infarction, it has important limitations: a rate of recanalisation (restoring normal flow) in 90 minutes of only 55% with streptokinase or 60% with accelerated alteplase; a 5-15% risk of early or late reocclusion leading to acute myocardial infarction, worsening ventricular function, or death; a 1-2% risk of intracranial haemorrhage, with 40% mortality; and 15-20% of patients with a contraindication to thrombolysis. View this table: Comparison of methods of recanalisation Primary angioplasty (also called direct angioplasty) mechanically disrupts the occlusive thrombus and compresses the underlying stenosis, rapidly restoring blood flow. It offers a superior alternative to thrombolysis in the immediate treatment of ST segment elevation myocardial infarction. …

Reappraising the role of immediate intervention following thrombolytic recanalization in acute myocardial infarction

Early studies indicated that after successful thrombolytic recanalization, adjunctive percutaneous transluminal coronary angioplasty (PTCA) was not appropriate, even when a significant residual stenosis was present. The aim of this study was to assess in-hospital clinical outcomes of patients with acute myocardial infarction (AMI) who underwent successful recanalization after thrombolytic therapy. The relation between repeat AMI/unstable angina and the severity of the stenosis, as well as other angiographic and clinical features was also examined. One hundred patients with AMI of <10 hours underwent coronary angiography 2 hours after receiving thrombolytic therapy. Salvage PTCA +/- stenting was performed if recanalization was unsuccessful (Thrombolysis In Myocardial Infarction [TIMI] trial grade 0 to 2), and no PTCA was undertaken if there was brisk anterograde flow (TIMI 3). Angiographic analysis was performed to assess the severity of the residual lesion, as well as the presence or absence of thrombus. Forty patients had unsuccessful recanalization, and of these, 36 underwent attempted PTCA. Of the 60 patients with TIMI 3 flow, 15 required repeat angiography and PTCA after repeat AMI (n = 13) or unstable angina (n = 2) within 5 days. Receiver-operating characteristic analysis indicated an optimum percent diameter stenosis predictor of 85% for repeat AMI/unstable angina. There was no additional relation to age, gender, time to thrombolysis, the infarct-related artery, or the presence of culprit lesion thrombus. After recanalization, a high-grade stenosis >85% is common (n = 25, 42.4%). This is associated with a 54% repeat AMI/unstable angina risk-a ninefold increase in the incidence of such events than in patients with lesions <85%. Thus, patients with narrowings >85% may benefit from early intervention rather than a conservative approach. Narrowings <85% have a 94% probability of no repeat AMI/unstable angina and do not require early intervention.

Differential free-radical activity after successful and unsuccessful thrombolytic reperfusion in acute myocardial infarction.

BackgroundFree-radical generation after successful thrombolysis in acute myocardial infarction may jeopardise ischaemic but viable myocardium, thus limiting the optimal benefits of reperfusion. MethodsCirculating free-radical activity was assessed in 25 consecutive patients with acute myocardial infarction. Those who successfully reperfused (Group A) were compared with those who did not (Group B). We also compared patients who had or had not developed Q waves and patients with and without previous angina or myocardial infarction. All patients presented within 6 h of the onset of chest pain and received standard intravenous streptokinase therapy. Free-radical activity in serial serum samples collected over 72 h was measured using the percentage molar ratio (PMR) of the concentrations of 9,11-linoleic acid to 9,12-linoleic acid, and malonaldehyde concentration. ResultsThroughout the study period Group A (n = 11 ) showed significantly greater change in serum PMR and malonaldehyde levels compared with Group B (n = 14) (P< 0.01). PMR differences between the two groups were most pronounced at 3 and 12 h (P< 0.001). Patients with non-Q-wave myocardial infarction (n = 5) showed significantly greater changes in serum PMR and malonaldehyde levels (P< 0.01) compared with those with Q-wave infarction (n=20). A history of previous infarction or angina had no apparent effects on the changes in serum free-radical activity. ConclusionsSuccessful early reperfusion and non-Q-wave myocardial infarction are both associated with a significantly greater increase in the levels of markers of serum free-radical activity immediately after infarction. The results support present concepts of free-radical-mediated reperfusion injury. Use of these assays may identify those patients who may be at risk from free-radical-mediated reperfusion injury.

New developments in percutaneous coronary intervention

Percutaneous coronary intervention has become a more common procedure than coronary artery bypass surgery in many countries, and the number of procedures continues to rise. In one day an interventionist may treat four to six patients with complex, multivessel disease or acute coronary syndromes. Various balloons, stents, and other devices are delivered by means of a 2 mm diameter catheter introduced via a peripheral artery. The success rate is over 95%, and the risk of serious complications is low. After a few hours patients can be mobilised, and they are usually discharged the same or the next day. Even the spectre of restenosis is now fading. The present success of percutaneous procedures is largely because of refinement of our “basic tools” (intracoronary guidewires and low profile balloons), which have greatly contributed to the safety and effectiveness of procedures. However, the greatest technological advance has been in the development of stents. These are usually cut by laser from stainless steel tubes into a variety of designs, each with different radial strength and flexibility. They are chemically etched or electropolished to a fine finish and sometimes coated. Digital angiography is a great advance over cine-based systems, and relatively benign contrast media have replaced the toxic media used in early angioplasty. Although magnetic resonance and computed tomographic imaging may become useful in the non-invasive diagnosis of coronary artery disease, angiography will remain indispensable to guide percutaneous interventions for the foreseeable future. View this table: Interventional devices and their uses Pre-eminent among new devices is the drug eluting (coated) stent, which acts as a drug delivery device to reduce restenosis. The first of these was the sirolimus coated Cypher stent. Sirolimus is one of several agents that have powerful antimitotic effects and inhibit new tissue growth inside the artery and stent. In a randomised controlled trial (RAVEL) …