Restoration Of Coronary Blood Flow Research Articles

The effect of intravenous administration of erythropoietin on the infarct size in primary percutaneous coronary intervention

BackgroundAfter an acute myocardial infarction, the early restoration of coronary blood flow is mandatory for reducing infarct size. However, the process of reperfusion itself may also cause irreversible myocardial injury and contribute to the final infarct size. Recent animal studies have suggested that erythropoietin could protect the myocardium when administered after the onset of reperfusion. We investigated whether the administration of erythropoietin at the time of PCI would limit the size of the infarct during acute myocardial infarction by analysis of MRI and cardiac enzymes in this pilot study. MethodsWe randomly assigned 57 patients with acute, anterior wall ST-elevation myocardial infarction who were presented within 12h after the onset of chest pain to one group which was given an intravenous bolus of recombinant human erythropoietin (rhEPO, 50U/kg) immediately before undergoing PCI or the control group without the IV treatment before PCI. Infarct size was assessed by measuring the release of cardiac enzymes (CK, CK-MB) and by performing MRI on day 4 after infarction. ResultsThe injection of erythropoietin did not result in thrombotic or hypertensive complications. The release of cardiac enzyme was not different between two groups. On day 4, the absolute infarct volume of the area of hyperenhancement on MRI did not differ between two groups (EPO group 52.4±23.6cm3 vs. control group 54.8±28.6cm3, p=0.74). Two groups did not differ in the percentage of total infarct volume over left ventricle volume (EPO group 34.4±11.7% vs. 37.0±13.8%, p=0.50). ConclusionsIntravenous administration of erythropoietin was safe and was not associated with thrombotic or hypertensive side effects. However, it did not reduce the infarct size when assessed by MRI and cardiac enzyme. Further studies about the dose or routes of administration of EPO are needed (ClinicalTrials.gov Identifier NCT00882466).

Flutningstími og gæði meðferðar hjá sjúklingum með ST-hækkunar hjartadrep á Norður- og Austurlandi

A good outcome of patients presenting with STEMI (ST-Segment Elevation Myocardial Infarction) depends on early restoration of coronary blood flow. Pre-hospital fibrinolysis is recommended if primary percutaneous coronary intervention (PPCI) cannot be performed within 90 minutes of first medical contact (FMC). The purpose of this study was to study transport times for patients with STEMI who were transported with air-ambulance from the northern rural areas of Iceland to Landspitali University Hospital in Reykjavík, and to assess if the medical management was in accordance with clinical guidelines. Retrospective chart review identified 33 patients with STEMI who were transported with air-ambulance to Landspitali University Hospital in Reykjavík during the years 2007 and 2008. The total time from first medical contact to arrival at Landspitali University Hospital emergency room was 3 hours and 7 minutes (median). All patients received aspirin and 26 (78.8%) received clopidogrel and enoxaparin. 16 patients (48.5%) received thrombolytic therapy in median 33 minutes after FMC and 15 patients had PPCI performed in median 4 hours and 15 minutes after FMC. Estimated PCI related delay was 3 hours and 42 minutes (median). One patient died and one was resuscitated within 30 hospital days. Mean hospital stay was 6.0 days. First medical contact to balloon time of less than 90 minutes is impossible for patients with STEMI transported from the northern rural areas to Landspitali University Hospital in Reykjavík. Medical therapy was in many cases suboptimal and PCI related delay too long.

Myocardial Stunning After Electroconvulsive Therapy in Patients With an Apparently Normal Heart

Myocardial stunning refers to contractile dysfunction that persists after an ischemic episode and restoration of coronary blood flow. In this article, 2 cases of myocardial stunning after electroconvulsive therapy in patients with an apparently normal heart are presented. The incidence of this condition is unknown. It is observed that this condition seems to occur in females and in the obese and is generally associated with rapid recovery. This occurrence seems to be brought about by autonomic changes that occur during electroconvulsive therapy. Several drugs have been used to ameliorate the condition, although studies were limited to establish efficacy of regimens.

Abstract: P1244 HIGHLY SENSITIVE C-REACTIVE PROTEIN AND THE FRAMINGHAM RISK SCORE ARE ASSOCIATED WITH CORONARY DISEASE SEVERITY IN PATIENTS WITH METABOLIC SYNDROME

Streptokinase is an effective thrombolytic agent which, with early restoration of coronary blood flow, has the potential for limiting infarct size. Distinct from thrombolysis, we studied the effects of streptokinase on reperfusion coronary blood flow and infarct size. Open-chest anesthetized canines underwent a 90 minute snare occlusion of the left circumflex coronary artery followed by release and reperfusion through a critical stenosis for 6 hours. The animals were assigned randomly to two groups. Intracoronary streptokinase [group 1 (n = 8): 6000 IU/kg in 3 ml of saline] or saline [group 2 (n = 8): 3 ml of saline] was infused at 0.05 ml/min for 60 minutes beginning 30 minutes before reperfusion. Coronary blood flow was stable in group 1 during reperfusion, while in group 2 it fell during 6 hours of reperfusion (30 ± 4 ml/min to 18 ± 2 ml/min, P = 0.05). The ST-segment elevation on the limb lead II electrocardiogram 15 minutes after coronary artery occlusion was similar in both groups (group 1: 3.9 ± 0.6 mV, group 2: 2.3 ± 0.5 mV), suggesting the extent of myocardial ischemia was also similar in both groups. The infarct sizes were similar when expressed both as a percent of the total left ventricular mass [(IZLV) group 1: 17 ± 2.5%, group 2: 17.5 ± 2.5%] or as a percent of the area at risk of infarction [(IZAR) group 1: 39 ± 6%, group 2: 39 ± 5%]. In both groups, the mass of left ventricle dependent on the blood flow distribution of the left circumflex coronary artery was similar when compared to total left ventricular mass [(ARLV) group 1: 41 ± 3%, group 2: 44 ± 4%]. These results demonstrate that streptokinase maintains reperfusion coronary blood flow through a critical stenosis at a rate similar to baseline levels. Despite the fact that coronary blood flow remained stable with streptokinase during reperfusion, infarct size was not limited after 90 minutes of fixed coronary artery occlusion in this canine model of myocardial injury.

Carbon‐coated Stents in Patients with Acute Coronary Syndromes

For patients with ST elevation myocardial infarction (STEMI) or non-ST elevation myocardial infarction (NSTEMI), rapid restoration of coronary blood flow is the primary therapeutic goal. Because of the acute nature of this clinical presentation, bleeding risks may not be adequately evaluated, limiting the use of drug-eluting stents, since premature discontinuation of antiplatelet therapy strongly predicts stent thrombosis. We evaluated angiographic and clinical results of non-drug-eluting carbon-coated stents. In this prospective observational study, angiographic and clinical 6-mo results of a carbon-coated stent for treatment of acute lesions in native coronary arteries were evaluated. Angiographic main outcome measures included in-stent late loss and binary restenosis rate. Major adverse cardiac events (MACEs) were defined as any death, Q-wave myocardial infarction (MI), and target lesion revascularization. We included 320 patients with STEMI (n = 205) or NSTEMI (n = 115) with 360 lesions. Reference vessel diameter was 2.93 +/- 0.53 mm and stented length 22.7 +/- 13.8 mm. Angiographic follow-up was available in 220 of 360 lesions (61%). In-stent late loss was 0.69 +/- 0.75 mm, with a binary restenosis rate of 19.1%. For the total segment late loss was 0.74 +/- 0.77 mm and binary restenosis rate 21.4%. Clinical follow-up for 97.4% of discharged patients was available. Hierarchical MACEs were death in 14 patients (4.4%), Q-wave MI in 3 patients (0.9%), and target lesion revascularization in 39 patients (12.2%). In this prospective, observational study, the use of a carbon-coated stent for treatment of lesions in patients with STEMI or NSTEMI was associated with a low late loss, translating into a low binary angiographic restenosis rate within a 6-mo follow-up.

Pathophysiologie des myokardialen Reperfusionsschadens

Rapid interventional restoration of coronary blood flow is the most effective therapy to limit infarct size in today}s cardiology. The early phase of reperfusion represents, however, a window of therapeutic opportunities largely unused in the clinic. Experimentally it has been clearly shown that the modalities of reperfusion have a substantial impact on infarct size, since reperfusion itself can damage the myocardium (reperfusion injury). The major cause for acute injury of the cardiomyocytes in reperfusion is their hypercontracture. Cytosolic Ca (2+) overload and malfunction of cell organelles, i. e. sarcoplasmic reticulum and mitochondria, determine the pathophysiology of reperfusion injury. The underlying mechanisms can be influenced in the first minutes of reperfusion by activation of protective signalling pathways (reperfusion therapy). First clinical studies confirm the efficacy of acute reperfusion therapy.

Non-invasive treatment of ST elevation myocardial infarction

There is good evidence that timely restoration of coronary blood flow in obstructed infarct related arteries is a significant determinant of both short and long term mortality and morbidity. This...

Surgical treatment of myocardial bridging: report of 31 cases

Myocardial bridging (MB) is usually considered a benign condition but may result in myocardial ischemia, myocardial infarction (MI), exercise-induced tachycardia, atrioventricular conduction block or even sudden cardiac death. This retrospective study summarizes our operative methods and outcomes for treatment of 31 cases of MB. From January 1997 to December 2006, 31 consecutive patients (24 men and 7 women; aged 35 - 67 years; mean 52.3 years) with MB underwent surgical treatment. Thirteen patients had MB only and 18 patients had MB associated with other heart diseases. In preoperative cardiac function grading, 5 patients were in NYHA class I and 18 in NYHA class II and 8 in NYHA class III. Among them, 15 underwent myotomy and 16 underwent coronary artery bypass grafting (CABG). All patients survived and recovered uneventfully. Neither hospital or late death nor major complications occurred. Postoperative exercise testing in all patients failed to reveal any persistent ischemia. Follow-up time was 3 - 115 months (mean 31 months). Follow-up angiographic studies in 21 patients (68%) demonstrated restoration of coronary blood flow and myocardial perfusion without significant residual compression of the artery. All patients were symptom-free and currently in NYHA class I - II. The patients who are refractory to medication should actively undergo the surgical procedures such as myotomy and CABG. Myotomy should be advocated as the first choice because of its safety and satisfactory results.

Exercise‐Induced ST‐Segment Elevation in Patients with a Recent Acute Myocardial Infarction Treated by Primary Percutaneous Coronary Intervention

To get insight in the mechanism of exercise-induced ST-segment elevation (STE) in patients with Q/QS waves at the electrocardiogram (ECG). We performed exercise stress test in 13 patients with anterior acute myocardial infarction treated by successful primary percutaneous coronary intervention (PCI). Compared to rest, an additional STE > or = 1 mm in one or more precordial ECG leads during exercise occurred in nine patients (69%), in the absence of symptoms. In acute myocardial infarction (MI) patients, treated by primary PCI and showing optimal coronary blood flow restoration at angiography, STE can still be induced by exercise in Q/QS wave ECG leads. This finding lends further support to the theory that exercise-induced STE in this clinical context is unlikely to represent by itself transient myocardial ischemia or viability.

Myocardial Reperfusion Injury

Lethal reperfusion injury is a paradoxical type of myocardial injury caused by the restoration of coronary blood flow after an ischemic episode. This review focuses on the mechanisms of the injury, on attempts to protect the heart against it, and on promising new approaches to cardioprotection during percutaneous coronary intervention.

Arterial coronary–coronary conduit over single, distal left anterior descending coronary artery lesion: 3.5 years afterward

Arterial coronary–coronary conduit over single, distal left anterior descending coronary artery lesion: 3.5 years afterward

THROMBOLYTIC THERAPY OF ACUTE MYOCARDIAL INFARCTION

Importance of thrombolytic therapy for restoration of coronary blood flow in acute myocardial infarction is emphasized. Indications and contraindications, advantages and disadvantages for thrombolysis therapy are discussed. The ways of different thrombolytics implementation, efficacy criteria and possible side effects are also presented.

THROMBOLYTIC THERAPY OF ACUTE MYOCARDIAL INFARCTION

Importance of thrombolytic therapy for restoration of coronary blood flow in acute myocardial infarction is emphasized. Indications and contraindications, advantages and disadvantages for thrombolysis therapy are discussed. The ways of different thrombolytics implementation, efficacy criteria and possible side effects are also presented.

Anaphylactic shock: The advantages of intra aortic balloon counter pulsation for the treatment of heart failure

The authors report a patient with a history of angina pectoris who developed anaphylactic shock that was complicated by a heart failure due to focal heart ischaemia. Early coronary angiography confirmed the diagnosis of localised coronary hypoperfusion. Intra aortic balloon counter pulsation succeeded in the restoration of coronary blood flow and haemodynamic stability. The authors discuss the opportunity of such treatment when a focal coronary hypoperfusion is diagnosed.

Impacts of Glycoprotein IIb/IIIa Inhibition on QT Dispersion After Successful Percutaneous Coronary Intervention

Coronary ischemia augments inhomogeneity in ventricular repolarization. Decrease in the QT dispersion (QTd) following restoration of coronary blood flow to the ischemic myocardium by successful percutaneous coronary intervention (PCI) is an expected outcome. The purpose of the study was to seek whether glycoprotein IIb/IIIa (GP IIb/IIIa) inhibition has additional beneficial effects on QT dispersion after angiographically successful PCI. The study involved 111 consecutive patients scheduled for elective coronary balloon angioplasty with or without stent implantation. Sixty patients (mean age 58 +/-9) were randomized to receive standard therapy including preprocedural aspirin, ticlopidine, and IV heparin, and 51 patients (mean age 54 +/-10) were randomized to receive additional IV tirofiban infusion before the lesion was crossed with the guidewire. Standard 12-lead simultaneous ECG recordings for the measurement of QTd and corrected QTd (QTcd) (calculated by using Bazett's formula) were obtained before and immediately after the procedure, and at the 6th, and 24th hours. Blood samples for detection of postprocedural myocardial damage (CK-MB and cTn-I) were taken before and immediately after the procedure, at the 6th, 12th, and 24th hours. In total, 128 stenoses were treated with PCI. Seventy of these lesions were in the standard therapy group and 58 in the tirofiban group. QTd and QTcd were not statistically different between the 2 groups before and immediately after the procedure and at the 6th hours, but at the 24th hour QTd and QTcd were significantly longer in the standard therapy group (p=0.047 and p=0.001, respectively). Postprocedural troponin-I elevation (B=0.692, p=0.037), maximum inflation pressure (B=0.182, p=0.001), and previous myocardial infarction (MI) (B=0.885, p=0.004) were defined as the predictors of the final QT dispersion at the 24th hour. QT dispersion significantly decreased after successful percutaneous coronary intervention. GP IIb/IIIa inhibition therapy was not superior by means of recovery of increased QT dispersion during the early hours of the intervention, but it prevented minor myocardial necrosis and provided more long-lasting recovery in QT dispersion as compared with heparin therapy. This impact of GP IIb/IIIa receptor inhibition on QTd may be a possible mechanism by which these drugs reduce cardiovascular events after PCI.

Transient and reversible deoxyribonucleic acid damage in human left ventricle under controlled ischemia and reperfusion

ObjectivesWe sought to describe the sequence of molecular events during ischemia and reperfusion of the human heart and to determine the activation of stress kinases and deoxyribonucleic acid (DNA) damage response elements on apoptosis in ischemia or reperfusion of the human heart. BackgroundBrief ischemia is tolerated by cardiac myocytes, but it determines immediate metabolic changes and block of contraction. Prompt restoration of coronary blood flow is inexorably associated with a slow recovery of myocardial contractile function. The prolonged, postischemic contractile dysfunction in the viable tissue is called myocardial stunning. The molecular mechanisms underlying myocardial stunning and ischemia-reperfusion injury are still poorly understood. Their elucidation would be valuable in order to identify novel therapeutic strategies. MethodsWe examined human left ventricular samples taken from 20 patients undergoing elective valve surgery before aortic cross-clamping, 20 ± 2 min (brief ischemia), 58 ± 5 min after the cross-clamping period (prolonged ischemia), and 21 ± 4 min after reconstitution of coronary blood flow (reperfusion). Stress kinases and DNA damage sensor proteins (ATM, H2AX, p53) were determined by immunoblotting with specific antibodies. Electron microscopy analysis was carried out on ischemic and reperfused samples. ATP content, reactive oxygen species (ROS) levels, and cytochrome oxidase activity were determined by biochemical assays. ResultsIschemia caused accumulation of ROS, reduction of cytochrome C oxidase and ATP, and activation of stress kinases p38 and Jun terminal kinase. Electron microscopy showed significant mitochondrial swelling in the majority of cells, but no appreciable apoptosis of cardiomyocytes. During ischemia, myocytes were intensely stained by TUNEL, and many cells showed proliferative cell nuclear antigen-positive nuclei. Finally, we found in ischemic tissues increased p53/p21WAFlevels and phosphorylation of histone H2AX, a substrate of ATM kinase, which marks double-strand DNA breaks. Reperfusion caused a robust extracellular signal-regulated kinase-1/2 activation, a marked reduction of TUNEL staining, and persistent activation of ATM checkpoint. ConclusionsThese data indicate that ischemia induces extensive DNA damage and activation of ATM checkpoint. Reperfusion allows the repair of the DNA lesions and salvage of ischemic cells.

The dilemma of skeletonized internal thoracic artery sequential bypass versus proximal pedicled in situ internal thoracic artery plus coronary-coronary free internal thoracic artery bypass for multiple lesions of the left anterior descending coronary artery

The dilemma of skeletonized internal thoracic artery sequential bypass versus proximal pedicled in situ internal thoracic artery plus coronary-coronary free internal thoracic artery bypass for multiple lesions of the left anterior descending coronary artery

In situ pedicle graft and coronary-coronary bypass grafting using internal thoracic artery in management of multiple lesions of the left anterior descending coronary artery

Nowadays, coronary-coronary bypass grafting (CCBG) has been applied in patients with heavily calcified ascending aorta or due to lack of graft material. We describe a case in which the patient's large left anterior descending (LAD) coronary artery, running well over the cardiac apex, presented with proximal and distal stenosis. Although the pedicled left internal thoracic artery (ITA) graft is sometimes too short for sequential bypass in cases of distal stenosis of the LAD coronary artery, we used a free, short segment of the pedicled left ITA for coronary-coronary bypass grafting. The in situ remnant of the left pedicled ITA was used to bypass the proximal LAD stenosis. The patient's postoperative course was uneventful. Predischarge angiogram (on the 9th postoperative day) showed an in situ left ITA graft as well as afree coronarycoronary ITA graft. The patient had a regularfollow-up after 3 months, and was classified as New York Heart Association (NYHA) class I. Primarily used in aorto-coronary bypass surgery (termino-terminal interposition of the saphenous vein between two parts of a resected coronary artery), CCBG was revised latter on, and from hemodynamic point of view the physiologic restoration of coronary blood flow has been confirmed CCBG might be an attractive approach for bypassing distal lesions of large coronary arteries (combined with arterial or venous grafting of targeted arteries, if proximal stenoses are also present). The proximal remnant of ITA can be used as an in situ or free graft.

Platelet glycoprotein IIb/IIIa inhibitors: recognition of a two-edged sword?

Glycoprotein (GP) IIb/IIIa antagonists are potent inhibitors of platelet aggregation that provide marked protection from ischemic events in patients undergoing percutaneous coronary intervention (PCI).1,2⇓ Abciximab, the prototypic GP IIb/IIIa inhibitor, has been studied in >8000 patients undergoing elective or high-risk PCI.2,3,4⇓⇓ In these patients, it produces a consistent 35% to 56% reduction in ischemic end points at 30 days, with a significant 22% reduction in the risk of death, as shown in a combined analysis of long-term (3-year minimum) follow-up of the Evaluation of 7E3 for the Prevention of Ischemic Complications (EPIC), Evaluation in PTCA to Improve Long-term Outcome with abciximab GP IIb/IIIa blockade (EPILOG), and Evaluation of Platelet IIb/IIIa Inhibitor for Stenting (EPISTENT) trials.5 Similar results, albeit of a smaller magnitude, have been seen with the small-molecule antagonists tirofiban and eptifibatide, with a 16% to 35% reduction in ischemic events in patients undergoing PCI.1,6⇓ Attempts to expand the therapeutic indication of GP IIb/IIIa antagonists to other conditions associated with platelet-mediated thrombosis, however, have been less fruitful than expected. Instead of reducing major ischemic events, long-term oral GP IIb/IIIa inhibitor therapy7 has uniformly increased the fatality rate. Furthermore, the overall efficacy of a number of the intravenous antagonists in non–ST-segment elevation acute coronary syndromes (ACS), or in combination with thrombolysis in ST-segment elevation myocardial infarction (MI), has been less than anticipated.8 Of particular concern is the fact that there has been a paradoxical increase in adverse events in 2 of the trials of intravenous therapy in ACS.9,10⇓ Platelets are known to play an important role in the pathogenesis of ACS, yet the high levels of platelet inhibition attainable with GP IIb/IIIa antagonists have failed to dramatically improve clinical outcomes outside of PCI. In this article, we discuss these …

Amelioration of microvascular myocardial ischemia by gene transfer of vascular endothelial growth factor in rabbits

Objectives: Restoration of coronary blood flow by angiogenesis may offer a new approach to intractable ischemic heart disease. In the present study, we investigated the angiogenic effects of gene transfer of vascular endothelial growth factor 165 on microvascular myocardial ischemia. Methods: A rabbit model of microvascular myocardial ischemia was created by plugging coronary microvessels with microspheres (15 μm in diameter, 2.8 × 105/kg, n = 29). Gene transfer was performed by semi-selective intracoronary injection of recombinant adenovirus expressing vascular endothelial growth factor 165 forty minutes after microsphere injection (n = 9). Results: Microsphere injection reduced myocardial perfusion (78% ± 9% of baseline tissue flow) and diminished myocardial contraction (61% ± 12% of the baseline ejection fraction) and cardiac performance (elevated left ventricular end-diastolic pressure and decreased systemic flow) in the acute phase. At 17 ± 3 days, gene transfer of vascular endothelial growth factor 165 had had the following effects: (1) promoted coronary angiogenesis as evidenced by myocardial flow above the baseline (121% ± 24%), (2) increased vascular density revealed by synchrotron radiation microangiography and histologic analysis, (3) ameliorated the degree of myocardial ischemia as evidenced by myocardial lactate content and the extent of histologic necrosis, and (4) restored heart function as evidenced by increased ejection fraction (95% ± 10%), reduced left ventricular end-diastolic pressure, and restored body weight. Conclusions: In vivo vascular endothelial growth factor 165 gene transfer promoted angiogenesis and was an effective approach to treating microvascular myocardial ischemia. (J Thorac Cardiovasc Surg 2000;120:720-8)