Oxidative stress and myocardial damage during elective percutaneous coronary interventions and coronary angiography. A comparison of blood-borne isoprostane and troponin release

The role of oxidative stress in clinical cardiology is still controversial. The aims of the present study were to examine if minor ischaemic episodes as may occur during elective percutaneous coronary intervention (PCI) induce oxidative stress and, eventually, if oxygen stress correlates with myocardial injury. Thirty eight and nine patients underwent PCI and diagnostic coronary angiography, respectively. Peripheral blood was sampled at different time points for plasma analyses of: 8-iso-PGF2alpha (free radical-mediated oxidative stress); 15-keto-dihydro-PGF2alpha (cyclooxygenase-mediated inflammation); troponin-T (myocardial injury); hsCRP, vitamin A and vitamin E; and, total antioxidants status (TAS). In both groups 8-iso-PGF2alpha increased transiently by approximately 80% (p < 0.001) during the procedure. There was a minor troponin-T release (p < 0.001) after PCI, but no correlation with 8-iso-PGF2alpha. Troponin-T did not increase after angiography. 15-keto-dihydro-PGF2alpha decreased by 50% after ended procedure, but increased by 100% after 24 h compared to baseline. hsCRP increased significantly (p < 0.001) from baseline to the next day in the PCI-group, but not in the angiography group. Vitamins and TAS decreased slightly after the procedures. It is concluded that a moderate oxidative stress was induced by both elective PCI and coronary angiography but that no correlation was found between oxidative stress and myocardial injury in this setting. This indicates that other mechanisms than ischaemia-reperfusion episodes caused an elevation in plasma isoprostane such like the injury at a vascular site mutual for both procedures. A secondary finding from the study was elevated markers of early inflammatory response, not only after PCI, but also after angiography.     

Prospective register of primary percutaneous coronary interventions in patients with acute myocardial infarction

The present study has evaluated the immediate angiographic results of primary percutaneous interventions (PCI) in patients with acute myocardial infarction, as well as hospital and 6-month clinical outcomes. The analysis covered a total of 265 patients (females (23%) and males (77%)); their mean age was 57+/-11 years. The mean time before the first balloon dilatation during PCI was 278+/-135 minutes after the development of the pain syndrome or 109+/-94 minutes after hospital admission. PCI proved to be effective in 96% of the patients, as evidenced by angiography. TIMI 3 blood flow was achieved in 83% of cases during PCI. After primary PCI, hospital mortality was 98.9% and 95% survived 6 months. At 6-month follow-up, 22% patients had positive exercise tests, recurrent angina pectoris and/or more than 50% luminal stenosis of the infarct-related artery. Control angiography made less than 6 months later showed 11% restenosis. This prospective study has demonstrated the high immediate and long effectiveness and safety of primary interventions in acute myocardial infarction.     

Oxidative stress parameters in erythrocytes of post-reperfused patients with myocardial infarction

The effect of reperfusion of patients with myocardial infarction on the levels of some anti-oxidant enzymes, total thiols, malondialdehyde formation in erythrocytes and plasma ascorbate levels have been investigated. Significantly decreased activities of catalase and superoxide dismutase and decreased levels of total thiols in RBC's and ascorbic acid in plasma suggest that reperfusion of the infarcted myocardium leads to oxidative stress conditions wherein anti-oxidant mechanisms become less effective in coping with the oxidative insult. This view is further supported by the observation that in the post reperfused patients there is a highly significant enhancement in the levels of malondialdehyde.     

Oxidative stress reversibly inactivates myocardial enzymes during cardiac arrest

Oxidative stress during cardiac arrest may inactivate myocardial enzymes and thereby exacerbate ischemic derangements of myocardial metabolism. This study examined the impact of cardiac arrest on left ventricular enzymes. Beagles were subjected to 5 min of cardiac arrest and 5 min of open-chest cardiac compressions (OCCC) before epicardial direct current countershocks were applied to restore sinus rhythm. Glutathione/glutathione disulfide redox state (GSH/GSSG) and a panel of enzyme activities were measured in snap-frozen left ventricle. To test whether oxidative stress during arrest inactivated the enzymes, metabolic (pyruvate) or pharmacological (N-acetyl-l-cysteine) antioxidants were infused intravenously for 30 min before arrest. During cardiac arrest, activities of phosphofructokinase, citrate synthase, aconitase, malate dehydrogenase, creatine kinase, glucose-6-phosphate dehydrogenase, and glutathione reductase fell by 56, 81, 55, 34, 42, 55, and 45%, respectively, coincident with 50% decline in GSH/GSSG. OCCC effected full recovery of glutathione reductase and partial recovery of citrate synthase and aconitase, in parallel with GSH/GSSG. Phosphofructokinase, malate dehydrogenase, creatine kinase, and glucose-6-phosphate dehydrogenase recovered only after cardioversion. Antioxidant pretreatments augmented phosphofructokinase, aconitase, and malate dehydrogenase activities before arrest and enhanced these activities, as well as those of citrate synthase and glucose-6-phosphate dehydrogenase, during arrest. In conclusion, cardiac arrest reversibly inactivates several important myocardial metabolic enzymes. Antioxidant protection of these enzymes implicates oxidative stress as a principal mechanism of enzyme inactivation during arrest.     

Early interventions in the management of acute uncomplicated myocardial infarction.

The demonstration that the vast majority of acute transmural myocardial infarctions are caused by an occlusive thrombus in the coronary artery, together with the concept that myocardium can be salvaged for a period of time after the onset of such occlusion, has heralded a new era of management of this disorder. This involves an aggressive interventional approach aimed at restoring coronary artery patency early while decreasing myocardial oxygen demands. Abundant data show that coronary flow can be reestablished using either intravenous chemical thrombolytic agents (tissue-type plasminogen activator and streptokinase), percutaneous transluminal coronary angioplasty, or coronary artery bypass grafting. Conjunctive aspirin or heparin therapy (or both) is effective in maintaining vessel patency once perfusion is restored. Myocardial oxygen demand can be reduced, where feasible, by pharmacotherapy and control of the patient''s associated pain and anxiety. The beta-adrenergic blockers and nitrates are particularly suitable in this regard, and angiotensin-converting enzyme inhibitors favorably affect infarct expansion and ventricular remodeling. With such an approach, infarct size can be reduced, leading to improved left ventricular function--the prime determinant of morbidity and mortality in patients with acute infarction. The in-hospital mortality has fallen from about 30% three decades ago to less than 8% in many coronary care units.     

Electrophoresis of serum isoenzymes and proteins following acute myocardial infarction

The clinical significance of the serum enzymes creatine kinase (CK, EC 2.7.3.2), lactate dehydrogenase (LD, EC 1.1.1.27) and aspartate aminotransferase (EC 2.6.1.1), and the isoenzymes CK 1–3 and LD 1–5, in acute myocardial infarction (AMI) is reviewed. Particular attention is given to electrophoretic analysis of the isoenzymes (and the CK isoforms/subforms) following AMI and thrombolytic therapy. Other protein markers for the monitoring of AMI, including myoglobin and muscle contractile proteins, are also discussed and the potential for the detection of new marker proteins using high-resolution two-dimensional electrophoretic methods is demonstrated. Whilst emphasis is placed upon electrophoretic methods the value of complementary immunoassays is acknowledged in order to maintain a balanced perspective.     

Role of coronary artery bypass grafting during the acute and subacute phase of ST-elevation myocardial infarction

Background/Objectives. We aimed to investigate the incidence and clinical outcome of coronary artery bypass grafting (CABG) performed in contemporary patients with ST-elevation myocardial infarction (STEMI) within 30 days after presentation. Methods. All 1071 patients enrolled in the Thrombus Aspiration during Percutaneous coronary intervention in Acute myocardial infarction Study (TAPAS) were included in this analysis. CABG was indicated for both ischaemic and anatomical reasons according to the current treatment guidelines for STEMI. For all surgical as well as non-surgical patients, clinical outcome was assessed at both 30 days and one year. Results. CABG was performed within 30 days of presentation in 59/1071 (5.5%) patients, in 13 (22%) within 24 hours, in eight (14%) between one and three days, and in 38 (64%) between four and 30 days. Compared with non-surgical patients, surgical patients required more initial intra-aortic balloon pump support (33 vs. 5%, p<0.001) and more often had multi-vessel disease (p<0.001). Overall, rethoracotomy was performed in 9/59 (15%) patients. In patients operated within three days, the rethoracotomy rate was markedly higher than after three days (33 vs. 5%, p=0.004). Cardiac mortality at 30 days and one year was 1.7% in the surgical group and 3.2 and 5.3%, respectively, in the non-surgical group. Conclusion. STEMI patients treated with CABG within three days after presentation are at increased risk of rethoracotomy. However, despite this higher incidence of surgical complications and multiple high-risk features at presentation, surgical management during the acute and subacute phase is associated with excellent 30-day and one-year survival. (Neth Heart J 2010;18:348-54.)     

The state of the coronary arteries during balloon dilatation following thrombolytic therapy of acute myocardial infarction (a quantitative angiographic study)

The paper is concerned with the investigation of 52 patients who received i.v. thrombolytic therapy and "delayed" balloon dilatation of the coronary arteries in the first hours of acute myocardial infarction for the first 6 days. The investigation was repeated 6 mos after the onset of disease. Analysis of the coronaroventriculography results has shown that a combined use of i.v. thrombolytic therapy and delayed balloon dilatation of the coronary arteries results in a considerable and prolonged improvement of vascular permeability attended by a significant improvement of left ventricular local function and a decrease in the number of reocclusions. Infarction-related artery restenosis after combined therapy has little influence on left ventricular function which can be probably associated with a slow rate of its formation. Infarction-related vascular reocclusion leads to marked impairment of left ventricular total and local function.     

Prolactin is involved in the systemic inflammatory response in myocardial infarction

Prolactin may contribute to an atherogenic phenotype. Furthermore, previous studies have shown that prolactin levels increase in situations of acute stress and inflammation. We therefore aimed to investigate the relationship between prolactin, acute stress and inflammation in patients with myocardial infarction. We performed a case-control study in 40 patients with myocardial infarction and 39 controls, aged 41-84 years. Blood for assessment of prolactin and high sensitive C-reactive protein (hsCRP) was drawn at inclusion, that is, during the acute phase of the event, and 2-3 weeks later. Unexpectedly, prolactin levels at inclusion did not differ between cases and controls (7.0 ng/ml and 6.0 ng/ml, respectively, p=0.28). 2-3 weeks later prolactin levels in cases had not decreased. However, univariate regression analysis indicated that hsCRP is associated with prolactin levels (regression coefficient β 0.11; [95% CI 0.01; 0.21]; p=0.03) in cases during the acute phase of myocardial infarction. Our findings may suggest that prolactin is involved in the systemic inflammatory response, which takes place during myocardial infarction; however, this association may not be strong enough to induce higher prolactin levels in patients with myocardial infarction.     

Daylight saving time does not seem to be associated with number of percutaneous coronary interventions for acute myocardial infarction in the Netherlands

BackgroundIn multiple studies, the potential relationship between daylight saving time (DST) and the occurrence of acute myocardial infarction (MI) has been investigated, with mixed results. Using the Dutch Percutaneous Coronary Intervention (PCI) registry facilitated by the Netherlands Heart Registration, we investigated whether the transitions to and from DST interact with the incidence rate of PCI for acute MI.MethodsWe assessed changes in hospital admissions for patients with ST-elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI) undergoing PCI between 1 January 2015 and 31 December 2018. We compared the incidence rate of PCI procedures during the first 3 or 7 days after the transition with that during a control period (2 weeks before transition plus second week after transition). Incidence rate ratio (IRR) was calculated using Poisson regression. Potential gender differences were also investigated.ResultsA total of 80,970 PCI procedures for STEMI or NSTEMI were performed. No difference in incidence rate a week after the transition to DST in spring was observed for STEMI (IRR 0.95, 95% confidence interval (CI) 0.87–1.03) or NSTEMI (IRR 1.04, 95% CI 0.96–1.12). After the transition from DST in autumn, the IRR was also comparable with the control period (STEMI: 1.03, 95% CI 0.95–1.12, and NSTEMI: 0.98, 95% CI 0.91–1.06). Observing the first 3 days after each transition yielded similar results. Gender-specific results were comparable.ConclusionBased on data from a large, nationwide registry, there was no correlation between the transition to or from DST and a change in the incidence rate of PCI for acute MI.     

Thrombolytic therapy for acute myocardial infarction

A retrospective analysis of 4,094 deliveries among Navajo Indian women was carried out to determine the prevalence of gestational diabetes mellitus and diabetes antedating pregnancy. Three data sources--a local prenatal registry, a delivery room log, and hospital discharge records--were evaluated for their usefulness as surveillance systems for gestational diabetes. In all, 177 cases of gestational diabetes and 13 cases of preexisting diabetes were identified, giving a prevalence of maternal diabetes in pregnancy of 4.6%. When women with preexisting diabetes or documented gestational diabetes during a previous pregnancy were excluded, the prevalence of gestational diabetes during the study period was 3.4%. Although each data source used separately failed to identify 20% to 40% of diabetic pregnancies, more than 97% of cases were identified using a combination of the prenatal registry and the delivery log.     

Increased release of beta thromboglobulin during acute myocardial infarction

Beta thromboglobulin (betaTG) is a platelet-specific protein released during platelet aggregation. To classify the role of platelet aggregation in acute myocardial infarction (AMI), betaTG levels were measured by means of a specific and highly sensitive radioimmunoassay in patients admitted to the Coronary Care Unit for the evaluation of acute chest pain. These levels were compared to creatine phosphokinase (CPK) values and the percentage of myocardial fraction (MB), as well as electrocardiographic criteria for AMI. Beta thromboglobulin was considered elevated when it was greater than 132 micro/1. The CPK and MB fraction were considered to indicate AMI if there was an increase of MB fraction greater than 5% of the total CPK and a progressive increase of the total CPK and MB fraction during the course of the disease. Ten patients were compared to 28 control subjects. Seven patients had electrocardiographic evidence of AMI in addition to CPK and MB criteria. Six of these patients also had elevated betaTG values, whereas one did not. This patient was admitted late during his clinical course, as evidenced by the CPK-MB curve. Of the three patients without clinical evidence of AMI, two had normal betaTG levels, whereas the third patient had one normal betaTG level and one mildly elevated level. This study implicates the role of platelet aggregation in AMI and suggests its potential usefulness as a diagnostic aid in evaluating acute chest pain.     

Improved myocardial performance induced by clofibrate during reperfusion after acute myocardial infarction

The increase of cellular fatty acids appears to be one of the causes of the myocardial injury during ischemia and reperfusion. This study was designed to examine whether a hypolipidemic drug such as clofibrate can reduce the myocardial injury during ischemia and reperfusion. Clofibrate was fed to experimental pigs for 9 days. Isolated in situ hearts from both experimental and control pigs were subjected to 60 min of regional ischemia induced by occluding the left anterior descending coronary artery, followed by 60 min of global ischemia by hypothermic cardioplegic arrest and 60 min of reperfusion. The clofibrate feeding resulted in the better cardiac performance as judged by increased coronary blood flow, improved left ventricular function, and reduced myocardial injury as judged by creatine kinase release. Although the clofibrate-fed animals contained higher levels of thiobarbituric reactive materials, the free fatty acid levels of plasma and myocardium were much lower compared with control animals. The clofibrate feeding was also associated with increased peroxisomal catalase and beta-oxidation of fatty acids. These results suggest that decreased levels of free fatty acids in the plasma and the myocardium and increased catalase activity induced by antilipolytic therapy appear to provide beneficial effects to the myocardium during ischemia and reperfusion.     

Cardiac cholinergic NO-cGMP signaling following acute myocardial infarction and nNOS gene transfer

Myocardial infarction (MI) is associated with oxidative stress, which may cause cardiac autonomic impairment. We tested the hypothesis that acute MI disrupts cardiac cholinergic signaling by impairing nitric oxide (NO)-cGMP modulation of acetylcholine (ACh) release and whether the restoration of this pathway following cardiac neuronal NO synthase (nNOS) gene transfer had any bearing on the neural phenotype. Guinea pigs underwent four ligature coronary artery surgery (n = 50) under general anesthesia to induce MI or sham surgery (n = 32). In a separate group, at the time of MI surgery, adenovirus encoding nNOS (n = 29) or enhanced green fluorescent protein (eGFP; n = 30) was injected directly into the right atria, where the postganglionic cholinergic neurons reside. In vitro-evoked right atrial [3H]ACh release, right atrial NOS activity, and cGMP levels were measured at 3 days. Post-MI 24% of guinea pigs died compared with 9% in the sham-operated group. Evoked right atrial [3H]ACh release was significantly (P < 0.05) decreased in the MI group as was NOS activity and cGMP levels. Tetrahydrobiopterin levels were not significantly different between the sham and MI groups. Infarct sizes between gene-transferred groups were not significantly different. The nNOS transduced group had significantly increased right atrial [3H]ACh release, right atrial NOS activity, cGMP levels, and decreased cAMP levels. Fourteen percent of the nNOS transduced animals died compared with 31% mortality in the MI + eGFP group at 3 days. In conclusion, cardiac nNOS gene transfer partially restores the defective NO-cGMP cholinergic pathway post-MI, which was associated with a trend of improved survival at 3 days.