Restoration Of Coronary Blood Flow Research Articles

CLINICAL ASSESSMENT OF INVASIVE TECHNOLOGY TREATMENT OF PATIENTS WITH POST-INFARCTION ANGINA

The article presents a comparative analysis of the results obtained by the invasive treatment in patients with post-infarction angina. In own clinical material authors demonstrate high efficacy of endovascular and surgical treatment carried out in persons with urgent indications Q-myocardial infarction and unstable post-infarction angina. Furthermore, analysis of the frequency and nature of the main causes of complications in various kinds of surgery has been performed. The study found that the development of the final outcome is significantly affected not only by the initial severity of the patient's condition, but also by the selection of the most adequate method of myocardial revascularization. To increase the effectiveness of invasive treatment further improvement and implementation of new technologies of the restoration of coronary blood flow in patients with acute coronary syndrome is offered.

Adjuvant cardioprotection in cardiac surgery: update.

Cardiac surgery patients are now more risky in terms of age, comorbidities, and the need for complex procedures. It brings about reperfusion injury, which leads to dysfunction and/or loss of part of the myocardium. These groups of patients have a higher incidence of postoperative complications and mortality. One way of augmenting intraoperative myocardial protection is the phenomenon of myocardial conditioning, elicited with brief nonlethal episodes of ischaemia-reperfusion. In addition, drugs are being tested that mimic ischaemic conditioning. Such cardioprotective techniques are mainly focused on reperfusion injury, a complex response of the organism to the restoration of coronary blood flow in ischaemic tissue, which can lead to cell death. Extensive research over the last three decades has revealed the basic mechanisms of reperfusion injury and myocardial conditioning, suggesting its therapeutic potential. But despite the enormous efforts that have been expended in preclinical studies, almost all cardioprotective therapies have failed in the third phase of clinical trials. One reason is that evolutionary young cellular mechanisms of protection against oxygen handling are not very robust. Ischaemic conditioning, which is among these, is also limited by this. At present, the prevailing belief is that such options of treatment exist, but their full employment will not occur until subquestions and methodological issues with the transfer into clinical practice have been resolved.

Abstract 18599: Comparison of Outcomes for Eldelry Patients Treated With Pre-Hospital Reduced Dose Fibrinolytic Followed by Urgent Percutaneous Coronary Intervention versus Percutaneous Coronary Intervention Alone for Treatment of ST-Elevation Myocardial Infarction

Background: The ultimate treatment goal in ST-elevation myocardial infarction (STEMI) is rapid restoration of coronary blood flow. In general, fibrinolysis can be initiated earlier than primary percutaneous coronary intervention (PPCI) but it could be associated with bleeding risk, especially in elderly patients. For over 7 years we have used a strategy of field evaluation for STEMI using 12 lead EKGs obtained and transmitted by emergency services (EMS) personnel with over-read by emergency center physicians. Appropriate STEMI patients receive pre-hospital reduced dose fibrinolytic (10 units reteplase) along with aspirin, clopidogrel, and heparin, and are transported to our STEMI center for urgent PCI (termed FAST-PCI strategy). Methods: We examined the data for elderly patients (≥ 75 years) treated by either a FAST-PCI strategy or conventional PPCI. We compared demographic, clinical, angiographic data and outcomes. Ischemic time was defined as time from onset of pain to device activation. Bleeding was assessed using GUSTO criteria. Results: Between February 2006 and April 2013, we treated 1323 STEMI patients of which 214 (16.2%) were ≥75 years. FAST-PCI was employed in 120 (56%) and PPCI in 94 (44%) patients. The groups were well matched for age, cardiac risk factors and ischemic time. Data are shown in the table. Conclusions: In the elderly patients, compared with a PPCI strategy, the FAST-PCI strategy was associated with earlier infarct artery patency (Less TIMI 0 flow) and reduced 30 day mortality, as well as with lower incidence of cardiogenic shock at presentation without a bleeding penalty.

Remote ischaemic conditioning: building evidence of efficacy

This editorial refers to ‘Improved long-term clinical outcomes in patients with ST-elevation myocardial infarction undergoing remote ischaemic conditioning as an adjunct to primary percutaneous coronary intervention’, by A.D. Sloth et al . doi:10.1093/eurheartj/eht369 Rapid restoration of coronary blood flow through primary percutaneous intervention (PPCI) remains the gold standard management of acute ST-elevation myocardial infarction (STEMI). As the availability of primary interventional facilities has improved, door to balloon times have fallen and this has been rewarded with concomitant reductions in mortality and morbidity.1 The question remains, however, even with PPCI and the associated evolution of optimized medical therapy, of whether we doing absolutely everything to preserve the jeopardized myocardium. In the face of improved clinical outcomes, it may be difficult to envisage where any further improvement might come from. Rapid recanalization/reperfusion of an occluded epicardial artery is a paradoxical phenomenon due to its association with reperfusion-induced injury. Reperfusion is indispensable for reviving the myocardium at risk of necrosis, but the reintroduction of oxygen leads to the generation of damaging reactive oxygen species, whereas re-energization of the processes necessary to maintain cellular ion homeostasis leads to rapid intracellular alkalization, which, combined with intracellular and mitochondrial calcium overload, represent the ‘perfect storm’ for initiation of cell death signalling cascades.2 The extension of the myocardial infarct by reperfusion is not necessarily inevitable. An intervention known as ischaemic conditioning was recognized in animal models as early as 19863 and is capable of reducing infarct size in these models by up to 50%.4 Ischaemic conditioning, whereby brief, repetitive, non-injurious ischaemia, before (pre-conditioning), during …

Association Between Intraprocedural Thrombotic Events and Adverse Outcomes After Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction (a Harmonizing Outcomes With RevasculariZatiON and Stents in Acute Myocardial Infarction [HORIZONS-AMI] Substudy)

The present study sought to determine the extent to which adverse angiographic events encountered during percutaneous coronary intervention for ST-segment elevation myocardial infarction (STEMI) are associated with adverse clinical outcomes. Patients with STEMI represent a cohort at particularly high risk of intraprocedural thrombotic events (IPTEs). The overall frequency and implications of IPTEs occurring in patients with STEMI have not been systematically quantified in previous studies. A total of 3,163 patients undergoing primary percutaneous coronary intervention with stent implantation for STEMI in the Harmonizing Outcomes with RevasculariZatiON and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial underwent detailed frame-by-frame core laboratory angiographic analysis to assess IPTEs. The clinical outcomes at 30 days were compared between the patients with and without IPTEs. IPTEs, defined as the development of new or increasing thrombus, abrupt vessel closure, no reflow, slow reflow, and distal embolization at any point during the procedure, occurred in 386 patients (12.2%). The independent predictors of IPTE were thrombus at baseline, lesion length, and randomization to bivalirudin; the patients with IPTEs were also more likely to receive bailout glycoprotein IIb/IIIa inhibitors and unplanned thrombectomy. Compared with patients without IPTEs, the patients with IPTEs had higher 30-day rates of composite major adverse cardiovascular events (death, myocardial infarction, ischemic target vessel revascularization, and stroke; 7.8% vs 4.2%, p = 0.002), major bleeding not related to coronary artery bypass grafting (11.8% vs 6.5%, p <0.001), and all-cause death (4.2% vs 1.8%, p = 0.002). On multivariate analysis, IPTEs were independently associated with 30-day major adverse cardiovascular events, major bleeding, and death. In conclusion, the development of IPTEs in patients undergoing primary percutaneous coronary intervention for STEMI was associated with subsequent adverse outcomes, including major adverse cardiovascular events, major bleeding, and death. Additional studies of strategies to decrease the occurrence of IPTEs are warranted.

Effects of Tirofiban Maintenance 24 or 48 Hours in Patients with Anterior Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention

OP-048 Percutaneous coronary intervention (PCI) does not often have optimal results despite restoration of coronary blood flow at myocardial recovery because of impaired microvascular perfusion. Previous studies have focused on the starting time and dosage of tirofiban. This study aimed to

Intracoronary bivalirudin

Intracoronary thrombi are a common finding in the setting of acute coronary syndromes and correlate with intraprocedural complications, adverse prognosis and unpredictable response to standard pharmacological and interventional treatment. Interventional cardiologists have learned to fear the so-called hostile thrombus, with its aggressive and unstable behavior often leading to abrupt and refractory vessel closure. Here we report a case series of intracoronary bivalirudin administration to treat massive intracoronary thrombi, leading to rapid clot disappearance and coronary blood flow restoration. Interventional cardiologists might consider intracoronary bivalirudin administration as a bailout strategy during unusual critical situations.

Effects of Tirofiban Maintenance Duration on Myocardial Perfusion Defect Severity in Anterior Myocardial Infarction

Percutaneous coronary intervention (PCI) does not often produce optimal results, despite restoration of coronary blood flow at myocardial recovery, because of impaired microvascular perfusion. This study aimed to investigate and evaluate with (99m)Tc-sestamibi scan whether the results of PCI can be changed by maintenance infusion of tirofiban for 24 or 48 h in patients presenting with anterior ST-elevation myocardial infarction (STEMI). The study included 84 patients with anterior STEMI who were candidates for primary PCI and whose occlusion was in the proximal or mid-left anterior descending artery. Patients were given 25 μg/kg/3 min tirofiban and randomized to receive maintenance infusion at 0.15 μg/kg/min for 24 or 48 h. A resting (99m)Tc sestamibi scan was performed on the 5th day post-procedure before discharge. The primary efficacy endpoint was a patient's score on a 5-point scoring system for perfusion defect severity. Major adverse cardiac events (MACE) were defined as death from any cause, re-infarction, and clinically driven target-vessel revascularization within the first 6 months. Baseline characteristics of the patients were similar in the two infusion groups (n = 42 per group). There was no significant difference in the symptom onset-to-presentation time or door-to-balloon time between the two groups. With the exception of basal anteroseptal and basal anterior segments, significant reductions were obtained on the 5-point scoring system for perfusion defect severity in segments and in the summed rest scores. No significant differences were observed between the two groups in the incidence of MACE at 6 months. The safety profile did not differ between 24 and 48 h infusions of tirofiban. The use of tirofiban, when administered at a high bolus dose and maintained for 48 h, was safe and significantly reduced perfusion defect severity in patients with anterior STEMI presenting early after symptom onset and undergoing primary PCI.

Protocolo terapéutico hospitalario del infarto de miocardio

The initial evaluation of patients with chest pain in emergency departments or outpatient focuses on identifying those patients with an acute coronary syndrome ST segment elevation (STEMI) to provide reperfusion therapy to the patient in the shortest time possible because this time until the restoration of coronary blood flow is the major determinant of prognosis of myocardial infarction (MI). For this we have invested much effort in developing protocols that direct care and treatment of patients with acute coronary syndrome.

Pathophysiology of Myocardial Ischemia Reperfusion Injury: A Review

Cardiovascular events are one of the leading causes of death in the world. Thrombolysis, percutaneous transluminal coronary angioplasty, and coronary bypass surgery are the general treatment strategies of cardiovascular events. All of these treatment strategies can cause a myocardial ischemia reperfusion (MI/R) injury, which is known to occur on the restoration of coronary blood flow after a period of myocardial infarction (MI). Although there is an only way to save the myocardium from necrotic and apoptotic damages, reperfusion achieved by the restoration of blood flow often aggravates cardiac dysfunction. It is believed that MI/R injury is related to the increased reactive oxygen species (ROS), calcium overloading, and the loss of membrane phospholipids especially during the reperfusion. The harmful effects of ROS on cardiac tissue during the MI/R can be prevented by endogenous antioxidant systems. Also, the complement system plays a crucial role in the inflammatory events of ischemic injury; thereupon it is important in the pathogenesis of the MI/R injury. Polymorphonuclear leukocytes in the reperfusion period are also associated with MI/R injury. Therefore these circumstances can increase the irreversible tissue damage. Although sometimes the reperfusion is provided, blood flow cannot be supplied to the myocardial tissue. This is called a no-reflow phenomenon. A lot of exogenous antioxidant agents can be used to prevent this process of injury. Due to these properties of antioxidants, a number of studies have been carried out and have been reported anywhere in the world. These studies demonstrated that these agents can be used in the MI/R-induced tissue damage and protect the heart against ROS-related myocardial injury.

Czy możliwa jest dalsza poprawa wyników leczenia ostrych zespołów wieńcowych?

Successful treatment of myocardial infarction related to early reperfusion therapy has caused growing interest in not only ischemic but also myocardial reperfusion injury. Most experimentally confirmed preservation myocardial reperfusion injury methods have failed in clinical practice. Probably one reason for their ineffectiveness was the very narrow “time window” necessitating application of protective methods before obtaining reperfusion. Reducing the myocardial necrosis and preservation of the left ventricular function are the main goals of the therapy. Experimental data suggest that up to 50% of the infarct size may be related to reperfusion injury. Function of the mitochondrial permeability transition pore (mPTP) in the inner mitochondrial membrane, being closed during myocardial ischemia and opening at the beginning of reperfusion, is the common element linking protective methods. Their opening gives rise to metabolic alterations and may lead to cardiomyocyte death (lethal reperfusion injury). That is why successful intervention, very difficult to achieve, has to take precedence over coronary blood flow restoration. Cyclosporin A, an mPTP blocker, was effective in the first small clinical trial in preservation of myocardial reperfusion injury in acute coronary syndrome intervention. Second mitochondrial injury action is related to generation of reactive oxygen species (ROS) including superoxide anions. Reactive oxygen species accumulation results in mitochondrial pH increase leading to mPTP opening. Discovery of a small molecule cationic peptide, readily penetrating cell membranes and concentrating in mitochondria, may give new therapy perspectives. Combining therapy may be possible as well.

BIOELECTRIC IMPEDANCEMETRY AS A METHOD OF ASSESSMENT OF THE MYOCARDIUM DURING OPEN-HEART SURGERY

The article analyses the possibility of using direct bioelectric impedancemetry of the right ven- tricle (RV) as an intra-operation method for evaluation of myocardial protection effectiveness in open-heart surgery. The results of intra-operation monitoring of bioelectric impedancemetry indi- cators of RV in 40 patients underwent surgical treatment with the use of cardioplegia were ana- lyzed. Bioelectrical impedance of myocardium has been studied during the whole period of artificial blood circulation. The analysis of the results showed that the bioelectric myocardium impedancemetry allows to assess the level of the interstitial space filling during the infusion of cardioplegia solution, providing an opportunity to assess the perfusion adequacy and also the level of reperfusion cells damage and myocardium swelling degree at the stage of coronary blood flow restoration. Using the method of myocardium bioelectric impedancemetry we found that blood cardioplegia with the "thermal induction" more reliably protects the myocardium in the period of anoxia in comparison with the cold cardioplegia.

Modern Management of Acute Myocardial Infarction

Disruption of intracoronary plaque with thrombus formation provides the pathophysiologic foundation for acute coronary syndromes, which comprise ST-segment myocardial infarction, non-ST-segment myocardial infarction, and unstable angina. Management differs depending on whether ST-segment elevation is present, but the general principles of timely restoration of coronary blood flow and initiation of secondary prevention strategies are applicable to all patients. The purpose of this review is to discuss first the epidemiology, pathophysiology, and diagnosis of acute myocardial infarction. Risk stratification and therapy for patients with ST-segment elevation myocardial infarction and non-ST-segment elevation acute coronary syndromes are then reviewed along with diagnosis and management of the complications of myocardial infarction.

Recommendations for an efficient and safe use of fibrinolytic agents

ST-segment myocardial infarction (STEMI) is caused by thrombotic occlusion of a major coronary artery. Rapid restoration of coronary blood flow is essential in preventing myocardial necrosis. Early reperfusion of the infarct-related artery limits infarct size and improves outcome. Achieving the shortest possible delay between symptom onset and reperfusion is therefore one of the most critical factors in the management of STEMI.

Myocardial Infarction and Protection

Cardioprotection has been defined as a therapy that limits the infarct size during an acute myocardial infarction that may lead to better clinical outcomes. Various interventions have been investigated in the past to reduce myocardial infarct size with variable success. The best strategy till date to limit infarct size has been the early restoration of coronary blood flow, with percutaneous coronary interventionwhere available. Stenting following invasive reperfusion, especially in the early hours after an infraction has been found superior to all other available modalities of therapy. Attempt to decrease time from onset of symptoms to start of reperfusion and maintaining vessel patency has been proven to yield the best outcomes. Future studies powered to better assess clinical outcomes are needed for adjunctive therapy with stem cells and hypothermia.

The coronary circulation in cardioprotection: more than just one confounder

Cardioprotection, i.e. the reduction in infarct size by pre-, post-, or remote conditioning, has originally been characterized in young and healthy experimental animals. Over the last two decades many signalling steps of cardioprotection have been identified, again in young and healthy animals. Although proof-of-concept studies unequivocally demonstrated the recruitment of all forms of cardioprotection in humans, the translation of cardioprotection to clinical routine has been poor. The apparent lack of translation has been attributed to poor design of clinical trials, but also to the neglect of confounders, such as age, sex, comorbidities, and comedications, in experimental studies. The present opinionated review focuses on the coronary circulation as a major determinant of cardioprotection. Coronary occlusion and the restoration of coronary blood flow are the causes of myocardial ischaemia and reperfusion injury from which protection is sought. On the other hand, brief cycles of coronary occlusion and reperfusion are also the stimulus for protection from myocardial ischaemia/reperfusion injury. The recruitment of collateral blood flow also contributes to protection from infarction. Finally, the coronary microcirculation is also a target of both injury by myocardial ischaemia/reperfusion and protection from it. Different manifestations of coronary artery disease, such as coronary stenosis or coronary microembolization, impact on both injury and protection.

Mitochondrial STAT3 Activation and Cardioprotection by Ischemic Postconditioning in Pigs With Regional Myocardial Ischemia/Reperfusion

Timely restoration of coronary blood flow is the only way to salvage myocardium from infarction, but reperfusion per se brings on additional injury. Such reperfusion injury and the resulting size of myocardial infarction is attenuated by ischemic postconditioning, ie, the repeated brief interruption of coronary blood flow during early reperfusion. The signal transduction of ischemic postconditioning is under intense investigation, but no signaling step has yet been identified as causal for such protection in larger mammals in situ. We have now in an in situ pig model of regional myocardial ischemia/reperfusion addressed the role of mitochondrial signal transducer and activator of transcription 3 (STAT3). We demonstrated reduction of infarct size by ischemic postconditioning (26 ± 3% of area at risk versus 38 ± 2% in controls with immediate full reperfusion) along with more markedly increased tyrosine(705) phosphorylation of STAT3 in myocardial biopsies (at 10 minutes reperfusion: 9.2 ± 3.0-fold from baseline versus 6.6 ± 2.9-fold in controls with immediate full reperfusion). Increased tyrosine(705) phosphorylation of STAT3 and better preservation of complex 1 respiration and calcium retention capacity were also present in isolated mitochondria from postconditioned myocardium in vitro. Prior janus kinase/STAT inhibition with AG490 in vivo abrogated the infarct size reduction and the better preservation of mitochondrial function, and the STAT3 inhibitor Stattic in vitro also abrogated better preservation of mitochondrial function. Our data support a causal role for mitochondrial STAT3 activation to mediate cardioprotection through better mitochondrial function.

The role of inflammatory response in myocardial ischemia reperfusion injury

Background Myocardial/ischemia reperfusion injury (I/RI) is defined as myocardial injury caused by the restoration of coronary blood flow after an ischemic episode, which leads to severe myocyte metabolic derangements and ultrastructural impairment. The I/RI also triggers the activation of an inflammatory cascade evidenced by neutrophils accumulating and inflammatory mediators releasing. Thus the inflammatory response has been recognized as one of the most important mechanisms of I/ RI. It has been identified that reperfusion -induced inflammation and excessive production of cytokines can promote myocardial damage during ischemia and reperfusion. Thus modulating the inflammatory response at the onset of reperfusion may represent a potent therapeutic strategy to attenuate the myocardial I/RI. Objective Objects of this review are to evaluate the possible roles of the inflammatory response in mechanisms of myocardial I/RI. Content The effects of inflammatory mediators including inflammatory cells and cytokines in I/RI process are in detailed introduced. Trend The inflammatory response is exactly an important mechanism in IRI, but its effects in the I/RI process are not simple. Except damages caused by the inflammatory response, it can produce benefits. For improving cardioprotection, all treatments by regulating I/RI -induced inflammation should keep the balance of its two sides. Key words: Ischemia/reperfusion injury; Inflammatory response; Reactive oxygen species; Cytokines

Coronary stents: factors contributing to perioperative major adverse cardiovascular events

Patients with coronary stents undergoing non-cardiac surgery are at increased risk of major adverse cardiovascular events perioperatively. Impeccable patient care and communication between all members of the healthcare team will minimize this risk. The dominant risk factor for stent thrombosis and major adverse cardiovascular events is the interruption of dual antiplatelet therapy (e.g. aspirin and clopidogrel). If clopidogrel therapy has to be interrupted due to increased risk of bleeding, continuation of aspirin is strongly recommended to reduce the risk of stent thrombosis. The interval between percutaneous coronary interventions and operation is the next major risk factor for stent thrombosis. The incidence of major adverse cardiovascular events is inversely related to this interval, with the highest mortality rate occurring <30 days after stent implantation. Ideally, for patients with drug-eluting stents, elective surgery should be delayed for at least 1 yr and for patients with bare-metal stents, the recommended minimum period is 6 weeks. The use of a neuraxial anaesthetic technique must be carefully considered due to the risk of an epidural haematoma. Perioperative monitoring should focus on early recognition of myocardial ischaemia, infarction, or both. If stent thrombosis is present, rapid triage to an interventional catheterization laboratory is essential for restoration of coronary blood flow.

Ischemic postconditioning: a clinical perspective

Primary percutaneous coronary intervention is the recommended therapy for patients with ST‑elevation myocardial infarction. However, restoration of coronary blood flow may lead to reperfusion injury, which has been suggested to account for 50% of the final myocardial infarct size. As an adjuvant therapy to primary percutaneous coronary intervention, ischemic postconditioning (IPost) has been shown to be safe and to underlie cardioprotection in several clinical trials. However, there remain important issues to be settled before IPost can be used routinely in patients undergoing primary percutaneous coronary intervention: first, determining which IPost protocol is the most optimal in humans; second, determining the effect of IPost on clinical outcome; third, determining in which patients should IPost be applied; and fourth, determining the effect on left ventricular function. This article discusses these issues with a clinical perspective and looks into alternative pharmacological cardioprotection.