Treatment Of No-reflow Research Articles

The Immediate and Short-Term Outcomes of Patients with ST Elevation Myocardial Infarction with High Thrombus Burden Receiving Intracoronary Verapamil versus Epinephrine during Primary Percutaneous Coronary Intervention

Abstract Background When total coronary artery occlusion was found in the early hours of transmural myocardial infarction, most of our research interest and treatment strategies focused on epicardial coronary arteries. Little attention, however, is paid to the coronary microvasculature. When a coronary artery is occluded, detrimental changes occur in the cardiac capillaries and arterioles. After relief of the occlusion, blood flow to the ischemic tissue may still be impeded, a phenomenon known as no reflow. This abstract attempt to provide an in-depth understanding of this phenomenon and comparative review of two intracoronary agents used in no reflow settings. Aim of the Study This study is a comparative prospective study designed to compare between two agents‟ verapamil and adrenaline in treatment of no reflow in patients presenting with STEMI (ST elevation myocardial infarction) and a high thrombus burden developing no reflow during PPCI. Patients and Methods This study is a comparative prospective clinical trial designed to compare between two agents‟ verapamil and adrenaline in treatment of no reflow in patients presenting with STEMI and a high thrombus burden developing no reflow during PPCI. Results We have compared two of the proposed agents adrenaline and verapamil in the management of CNF and found out that verapamil is better in terms of improving LV functions but not the coronary flow. This further supported the consideration that MVO and CNF are two different entities and that we should be fully satisfied with restoration of coronary flow however all possible solutions should be spent to achieve adequate coronary perfusion so as not to give any change to MVO and microvascular dysfunction. We need a better understanding of the pathology of CNF and MVO for better solutions. It is time that we include agents more concerned with the ischemic reperfusion injury, looking at it not solely as a mechanical issue but also as an inflammatory and cellular pathology. Fighting the No reflow should be broad spectrum until such time we have a deep insight to the main pathology behind it. Conclusion The study concluded that the verapamil and adrenaline were not superior the standard treatment in term of TFG, but the verapamil was superior to both groups in improving the MBG while the adrenaline was not superior to the control group. The short-term outcomes were better in verapamil group than the adrenaline and control group who were equivocal.

Treatment of Refractory No-Reflow in Cardiac Catheterization Laboratory; Role of Intracoronary Verapamil (A Case Report)

The no reflow phenomenon is a feared complication in Percutaneous Coronary Intervention (PCI) procedures including elective as well as primary PCI (Percutaneous Coronary Intervention), and results in worse prognosis. A number of etiological factors are involved in pathogenesis of no reflow phenomenon. These include distal athero embolization, ischemic and reperfusion injury, microvascular spasm and endothelial dysfunction. The treatment of no reflow depends on underlying mechanism and includes pharmacological as well as non-pharmacological interventions. Pharmacological agents include vasodilators like adenosine, sodium nitroprusside, verapamil, in addition to adrenaline (intracoronary) and, GpIIa/IIIb inhibitors. Non pharmacological measures include mechanical thrombus aspiration. Among pharmacological agents, Verapamil is usually the least preferred agent because of its negative ionotropic effect. Here, we describe a case of refractory no reflow in a patient undergoing primary PCI to right coronary artery (RCA), which was treated with a no. of pharmacological agents as well as aspiration thrombectomy but without much success and finally responded to intracoronary verapamil.

Effectiveness of Intra-Coronary Injection of Sodium Nitroprusside for the Treatment of Coronary No-Reflow through Punctured Coronary Balloon

Rapid restoration of thrombolysis in myocardial infarction III in case of no-reflow during percutaneous coronary intervention is imperative. Application of punctured coronary balloon intracoronary injection of sodium nitroprusside is a prompt, safe and effective method. To investigate the effectiveness of intracoronary injection of sodium nitroprusside via punctured coronary balloon in the treatment of no-reflow in coronary artery is the main objective of the study. We retrospectively analyzed 76 patients treated with intracoronary injection of sodium nitroprusside via punctured coronary balloon for coronary no-reflow. All 76 patients successfully completed intracoronary injection of sodium nitroprusside with the improvement of no-reflow in coronary artery for thrombolysis in myocardial infarction grade III in 74 patients. There were two complications which occurred in the early application of this technique. One was a punctured coronary balloon fracture left in the distal coronary artery and the other was a difficult pullback of the punctured coronary balloon catheter. After improving the application method, later no more complications occurred in 67 patients and no complications such as coronary guide wire pulling out of the coronary artery, coronary artery dissection, coronary artery perforation and coronary artery air embolism occurred. Coronary no-reflow treatment with intracoronary injection of sodium nitroprusside via punctured coronary balloon is safe and effective when properly applied.

Unmet goals in the treatment of Acute Myocardial Infarction: Review.

Reperfusion therapy decreases myocardium damage during an acute coronary event and consequently mortality. However, there are unmet needs in the treatment of acute myocardial infarction, consequently mortality and heart failure continue to occur in about 10% and 20% of cases, respectively. Different strategies could improve reperfusion. These strategies, like generation of warning sign recognition and being initially assisted and transferred by an emergency service, could reduce the time to reperfusion. If the first electrocardiogram is performed en route, it can be transmitted and interpreted in a timely manner by a specialist at the receiving center, bypassing community hospitals without percutaneous coronary intervention capabilities. To administer thrombolytic therapy during transport to the catheterization laboratory could reduce time to reperfusion in cases with expected prolonged transport time to a percutaneous coronary intervention center or to a center without primary percutaneous coronary intervention capabilities with additional expected delay, known as pharmaco-invasive strategy. Myocardial reperfusion is known to produce damage and cell death, which defines the reperfusion injury. Lack of resolution of ST segment is used as a marker of reperfusion failure. In patients without ST segment resolution, mortality triples. It is important to note that, until recently, reperfusion injury and no-reflow were interpreted as a single entity and we should differentiate them as different entities; whereas no-reflow is the failure to obtain tissue flow, reperfusion injury is actually the damage produced by achieving flow. Therefore, treatment of no-reflow is obtained by tissue flow, whereas in reperfusion injury the treatment objective is protection of susceptible myocardium from reperfusion injury. Numerous trials for the treatment of reperfusion injury have been unsuccessful. Newer hypotheses such as “ controlled reperfusion”, in which the interventional cardiologist assumes not only the treatment of the culprit vessel but also the way to reperfuse the myocardium at risk, could reduce reperfusion injury.

Abstract 248: Prolonged Adult Cardiac Arrest With Enhanced Cardiopulmonary Resuscitation and Sodium Nitroprusside: A Case Series

Introduction: Sudden cardiac death remains the leading cause of death in the United States, and overall survival with good neurological function nationally is about 8%. Prolonged refractory cardiac arrest requires an efficient method to maintain viability to the vital organs until a reversible cause, if present, can be treated. Sodium Nitroprusside Enhanced CPR, or SNPeCPR, is a new form of CPR consisting of active compression-decompression (ACD), impendence threshold device (ITD), abdominal binding, and large doses of sodium nitroprusside. We present here a series of 6 patients in whom these methods were utilized in the setting of cardiac arrest in the cardiac catheterization laboratory. Methods: 6 patients who suffered cardiac arrest (5 VT/VF and 1 PEA) and were treated for an average time of 32±12 minutes before arrival to the cardiac catheterization laboratory. Utilizing a LUCAS® device in combination with an ITD allowed for prolonged periods of CPR during which time percutaneous coronary intervention was performed to re-establish coronary blood flow. Abdominal binding was performed, and finally, alternating boluses of 2 and 1 mg of sodium nitroprusside for a total of 4 doses were given as treatment for no reflow in the coronary vascular bed throughout the duration of CPR. The etiology of the cardiac arrest was ostial LAD occlusion (4 cases), left main occlusion (1) contrast induced anaphylactic reaction and PEA (1). Results: Six patients were successfully treated with SNPeCPR. The mean time of CPR was 58±17 minutes. Hemodynamic measurements during CPR approached pre-arrest physiologic levels (mean±STD SBP/DBP was 88±23/38±12) . 5/6 patients survived to hospital discharge. All survivors had normal neurological function at hospital discharge and 1-month clinic follow up Cerebral Performance Category score of 1. Average LVEF at hospital discharge was 48±18 % . 4/5 survivors were alive at one year follow up. Conclusions: Sodium nitroprusside, in combination with mechanical adjuncts to CPR, is a safe and effective method of prolonged resuscitation. Further prospective studies will be required to further assess the efficacy of SNPeCPR in cases of prolonged cardiac arrest.

TREATMENT OF REPERFUSION INJURY WITH RECOMBINANT ADAMTS13 IN A PORCINE MODEL OF ACUTE MYOCARDIAL INFARCTION

Background: No reflow and decreased microvascular perfusion after percutaneous coronary intervention increase morbidity and mortality in ST-elevation myocardial infarction (STEMI) patients. No reflow may be mediated by platelet vessel wall interaction that is governed by von Willebrand factor. ADAMTS13 is a metalloprotease that cleaves von Willebrand factor, thereby reducing its prohemostatic properties. There is considerable evidence that ADAMTS13 levels decrease and von Willebrand factor levels increase in STEMI patients. Recombinant ADAMTS13 has been effective in reducing cerebral infarct size in a murine model of stroke. Aims: In this study recombinant ADAMTS13 was tested as a potential treatment of no reflow in a porcine model of cardiac ischemia and reperfusion. Methods: In 23 female swine (median age 83 days, median weight 30 kg) a balloon was inflated in the circumflex coronary artery for 75 min. Fifteen minutes after reperfusion, an intracoronary bolus of either recombinant ADAMTS13 (400 U/kg, Baxter Innovations Vienna, Austria) or vehicle was given. Results: ADAMTS13 activity significantly increased in treated pigs (from median 18%, IQR 14.5-24.0 to median 324%, IQR 117.0- 384.0, P = 0.003) whereas no change was observed in the control group. Animals were sacrificed 7 days later for histopathology. There was no difference in the size of myocardial necrosis as assessed with plasma Troponin T measurements, continuous 12 leads ECG, macroscopical infarct analysis, and histopathology using phosphotungstic acid-hematoxylin staining. Microvascular obstruction as estimated by staining with anti-CD31/Hematoxylin and counting of vessels and microthrombi was similar for both groups. Conclusions: Intracoronary treatment with recombinant ADAMTS13 did not prevent formation of microthrombi and did not decrease infarct size in this porcine coronary model of ischemia and reperfusion.

Prevention and treatment of no-reflow

No-reflow phenomenon occurs frequently during primary percutaneous coronary intervention for ST-segment elevation myocardial infarction and it has a strong negative impact on outcome. Prevention of no-reflow has to be defined as any attempt to prevent its occurrence prior to or during the recanalization procedure. Strategy of prevention may be pharmacological or device based. Among drugs, abciximab is indicated by European Society of Cardiology (ESC) guidelines for prevention of no-reflow (class of recommendation IIa and level of evidence B). Among devices used for preventing no-reflow, manual thrombus aspiration only has been associated with a reduction of no-reflow and lower mortality at follow-up and is currently indicated in the ESC guidelines (class IIa of recommendation and level B of evidence). Treatment of no-reflow has to be defined as any attempt to treat its occurrence after coronary recanalization. Strategy of treatment may be pharmacological or device based. Adenosine and verapamil are indicated by ESC guidelines for treatment of no-reflow (class of recommendation IIb and level of evidence B and C, respectively). Serial assessment of myocardial perfusion showed that in up to 50% of patients no-reflow is spontaneously reversible. This finding may open new scenarios, as mechanisms of reversibility may become future therapeutic targets.

Percutaneous Cardiopulmonary Support in Refractory No-Reflow with Cardiogenic Shock after Coronary Stenting in Acute Myocardial Infarction

Coronary no-reflow is defined as inadequate myocardial perfusion of a given coronary segment without angiographic evidence of mechanical vessel obstruction. No-reflow is visualized angiographically as a reduction in thrombolysis in myocardial infarction (TIMI) flow grade and is typically accompanied by chest pain, electrocardiographic changes with ST-segment shift and possible hemodynamic compromise. No-reflow during primary percutaneous coronary intervention (PCI) results in increasing mortality and morbidity. Therefore, treatment of noreflow is associated with improved clinical outcomes. Generally, the treatment of no-reflow is based on pharmacotherapy. In this case, despite maximal pharmacotherapy and intraaortic balloon pump (IABP), refractory no-reflow accompanied with cardiogenic shock was successfully treated with percutaneous cardiopulmonary support (PCPS).

Therapy for replenishing qi, nourishing yin and promoting blood circu-lation in patients with acute myocardial infarction undergoing percu-taneous coronary intervention: a randomized controlled trial

No-reflow phenomenon after reperfusion treatment of acute myocardial infarction (AMI) is becoming more recognized today. The effective treatment for no-reflow has not been reported. To observe the effects of traditional Chinese medicine (TCM) therapy for replenishing qi, nourishing yin, and promoting blood circulation on AMI patients undergoing percutaneous coronary intervention (PCI). This study was conducted from January 2005 to March 2006 using a double-blinded, randomized method. Thirty-five AMI patients (Killip I-II) were first diagnosed as ST segment elevation AMI and obtained primary PCI. They were recruited from People's Hospital, Peking University. All patients' symptoms accorded with qi-yin deficiency syndrome and blood stasis syndrome. They were randomly and double blindly divided into control group (18 cases) and treatment group (17 cases). The patients in the control group received Western medicine treatment, and the patients in the treatment group were treated with Western medicine plus American ginseng and Salviae miltiorrhizae preparations. They were all treated for 3 months. Before and after 3-month treatment, the TCM symptoms were observed and scored. At the state of baseline and dobutamine stress, left ventricular ejection fraction (LVEF), wall motion score (WMS), WMS index and normal cardiac muscle percentage (NCMP), and the myocardial contrast echocardiography index k, which reflects myocardium microcirculation perfusion, were detected. After 3-month treatment, the TCM symptoms in the treatment group were improved as compared with the control group (X(2)=4.118, P=0.042). At the state of dobutamine stress, LVEF in the treatment group after treatment was higher than those in the control group (t=2.130, P=0.041) and before treatment (t=2.345, P=0.032). Although the number of the segments with increased k value was more than that in the control group, there was no significant difference. TCM therapy for replenishing qi, nourishing yin and promoting blood circulation can improve the clinical symptoms and quality of life of the AMI patients undergoing PCI, and is beneficial to myocardium microcirculation. Thus, it may be an alternative cardioprotective treatment strategy for successful myocardial microcirculation in AMI patients after reperfusion.

The pathogenesis and treatment of no-reflow occurring during percutaneous coronary intervention

No-reflow is one of the major causes of postinterventional rise of cardiac enzyme and myocardial infarction (MI). This complication is associated with substantial morbidity and mortality after percutaneous coronary intervention (PCI). During and after a no-reflow episode, the patient can suffer from severe chest pain, hypotension, bradycardia, hemodynamic collapse, MI, congestive heart failure, and death. Every effort should be taken to reduce the incidence of this complication. The distal embolic protection device has been shown to decrease this risk in saphenous vein graft (SVG) interventions but not in native coronaries. On the other hand, the use of glycoprotein IIb/IIIa receptor antagonists have been effective in reducing the occurrence of no-reflow during PCI of native coronaries but not during SVG interventions. The treatment of no-reflow is based on the intracoronary administrations of medications that induce maximal vasodilatation in small distal coronary vasculature. The most commonly used drugs in this setting are adenosine, nitroprusside, and verapamil. The goal of this study was to review the pathogenesis and treatment of no-reflow in patients undergoing PCI.

Pharmacological Management of No Reflow During Percutaneous Coronary Intervention

Angiographic no reflow is a recognized phenomenon during percutaneous coronary intervention (PCI). It usually follows successful lesion dilation and, by definition, it represents a reduction in epicardial coronary blood flow in the absence of identifiable dissection, obstruction or distal vessel cut off (indicative of distal embolisation). No reflow appears to be more commonly associated with PCI for acute myocardial infarction and PCI for saphenous vein graft occlusions. While the exact mechanism of no reflow is unknown, theoretical causes include local humoral and microembolic effects leading to microcirculatory dysfunction. As the process is multifactorial, various therapeutic strategies are required in different situations. The present day pharmacological management involves the use of vasodilators including nitrates, verapamil, papaverine, adenosine, nicardipine and sodium nitroprusside, but interestingly a vasoconstrictor like epinephrine may also have a role. Glycoprotein IIb/IIIa platelet receptors antagonist have shown a powerful de-thrombotic effect, and the intracoronary administration appears to be particularly promising. We review the pathogenesis of a reduced epicardial flow during PCI and focus on those drugs that have been studied for the treatment of no reflow. Although no double blind, randomized trial has been conducted to assess any of these agents, or to determine the appropriate dosage, we try to identify some useful conclusions from the published evidence.

Effects of the Nitric Oxide Donor Nitroprusside on No-Reflow Phenomenon During Coronary Interventions for Acute Myocardial Infarction

We tested the effects of the nitric oxide donor nitroprusside as treatment for no reflow in 23 consecutive patients who underwent coronary angioplasty for acute myocardial infarction. No reflow was defined as a decrease of >/=1 Thrombolysis In Myocardial Infarction (TIMI) trial flow grade occurring after successful initial coronary recanalization. Nitroprusside induced a significant improvement in coronary flow, with an increase in TIMI flow grade from 1.5 +/- 0.8 to 2.9 +/- 0.3 (p <0.0001) and in TIMI frame count from 46 +/- 25 to 16 +/- 5 (p <0.0001). There were no significant adverse effects apart from transient hypotension. Intracoronary nitroprusside should be considered as a treatment of no reflow occurring in acute myocardial infarction.

Continuous postoperative intra-arterial urokinase infusion in the treatment of no reflow following revascularization of the acutely ischemic limb.

The loss of distal tissue perfusion sufficient for limb salvage following restoration of inflow to an acutely ischemic extremity has been referred to as the "no-reflow" phenomenon. We hypothesized that patients with no reflow and limb-threat ischemia might benefit from prolonged postoperative intra-arterial infusion of the thrombolytic agent urokinase (UK). Twelve patients with arteriographic and clinical evidence of no reflow following a lower extremity arterial thrombectomy and/or bypass procedure were treated with a continuous intra-arterial UK infusion in the immediate postoperative period. The mean duration of UK infusion was 47 hours (range 15 to 112 hours). The mean rate of infusion was 58,000 units/hr (range 30,000 to 100,000 units/hr). Seven patients required transfusion for bleeding from the treated extremity (mean 3.4 units packed cells) and one required reoperation for a groin hematoma. Plasma fibrinogen levels remained within the normal range in all patients, and no systemic bleeding complications were encountered. The intra-arterial UK infusion resulted in limb salvage in 7 of 12 patients. Six patients have viable, functional extremities at a mean follow-up interval of 24.9 months (range 6.4 to 49.7 months). One patient required below-knee amputation 6 months after treatment for progressive ischemia. The other five patients required below-knee amputation during the same hospitalization after UK failed to restore distal perfusion. The postoperative period is widely considered to be a contraindication to thrombolytic therapy. Our experience indicates that while UK may cause bleeding from the treated extremity, which in some cases requires transfusion, there is no evidence of systemic fibrinolysis or systemic hemorrhage.(ABSTRACT TRUNCATED AT 250 WORDS)