Adrenomedullin limits reperfusion injury in experimental myocardial infarction

Adrenomedullin (AM) is a vascular–derived polypeptide that exerts numerous actions in cardiovascular homeostasis. Recent studies have demonstrated a cytoprotective action of exogenously applied or genetically over–expressed AM in experimental myocardial infarction. The present studies were undertaken to test the hypothesis that AM exerts its effects through direct augmentation of NO generation in the myocardium during early reperfusion. Rat isolated hearts underwent 35 min left coronary artery occlusion followed by 120 min reperfusion. Infarct size (as percentage of ischaemic riskzone) was determined by Evans’ blue and tetrazolium double staining. AM 1 nM administered 5 min prior to and during the first 15 min of ischaemia did not significantly influence infarct size. However, the same concentration of AM given during the last 5 min ischaemia and first 15 min of reperfusion significantly limited infarct size (AM reperfusion 15.9 ± 3.5% vs control 31.4 ± 2.1%, P < 0.01). AM at reperfusion improved coronary flow and LV contractility. The protective effects of adrenomedullin were abolished in the presence of the NO synthase inhibitor, L–NAME 100 µM (infarct size 24.6 ± 5.7%, P > 0.05 vs control). AM treatment at reperfusion was associated with augmented phosphorylation of the pro–survival kinase, Akt, determined by immunoblotting of tissue sampled 30 min following reperfusion. These studies provide the first evidence that AM exerts its cytoprotective action specifically during early reperfusion through a NO–dependent mechanism.     

Reduction in reperfusion injury by blood-free reperfusion after experimental myocardial infarction

Because myocardial reperfusion injury may be caused by various blood constituents, a transient period of blood-free reperfusion was evaluated in closed chest dogs subjected to a 90 min angioplasty balloon occlusion of the left anterior descending coronary artery. In the treated group (n = 13), the balloon remained inflated for an additional 15 min while the infarct vessel was perfused with an acellular oxygenated perfluorochemical emulsion (Fluosol). The balloon was then deflated, permitting blood reperfusion. In the control group (n = 13), the balloon was deflated after 90 min of coronary occlusion. One week after infarction, the area at risk was defined in vivo by monastral blue dye staining, and the area of myocardial necrosis was assessed using triphenyltetrazolium chloride staining with histologic confirmation. Major determinants of infarct size, including rate-pressure product, area at risk and severity of myocardial ischemia (assessed by the extent of ST segment elevation during coronary occlusion), were not significantly different in the two groups. Treated dogs demonstrated a 47% reduction in infarct size expressed as a percent of the area at risk compared with control dogs (27.0 +/- 4.4% versus 50.8 +/- 4.4%, p less than 0.01). Treated dogs also demonstrated a superior global left ventricular ejection fraction (57.5 +/- 2.5% versus 51.0 +/- 2.2%, p less than 0.05) and anterolateral (regional) ejection fraction (32.6 +/- 3.6% versus 19.8 +/- 3.9%, p less than 0.05) compared with values in control dogs assessed by contrast ventriculography after 1 week of reperfusion. It is concluded that a transient period of blood-free reperfusion with an oxygenated perfluorochemical reduces reperfusion injury in a canine model of myocardial infarction.     

ST-segment dynamics during reperfusion period and the size of myocardial injury in experimental myocardial infarction

Background

Exacerbation of ST elevation associated with reperfusion has been reported in patients with myocardial infarction. However, the cause of the “reperfusion peak” and relation of its magnitude to the size of myocardial damage has not been explored. The aim of our study was to assess the correlation between the ST-dynamics during reperfusion, the myocardium at risk (MaR), and the infarct size (IS).

Methods

Infarction was induced in 15 pigs by a 40-minute-long balloon inflation in the left anterior descending coronary artery. Tetrofosmin Tc 99m was given intravenously after 20 minutes of occlusion, and ex vivo single photon emission computed tomography was performed to assess MaR. Maximal ST elevation in a single lead and maximal sum of ST deviations in 12 leads were measured before, during, and after occlusion from continuous 12-lead electrocardiographic monitoring. A gadolinium-based contrast agent was given intravenously 30 minutes before explantation of the heart. Final IS was estimated using ex vivo cardiac magnetic resonance imaging.

Results

All pigs developed an anteroseptal infarct with MaR = 42% ± 9% and IS = 26% ± 7% of left ventricle. In all pigs, reperfusion was accompanied by transitory exacerbation of ST elevation that measured 1300 ± 500 μV as maximum in a single lead compared with 570 ± 220 μV at the end of occlusion (P < .001). The transitory exacerbation of ST elevation exceeded the maximal ST elevation during occlusion (920 ± 420 μV, P < .05). The ST elevation resolved by the end of the reperfusion period (90 ± 30 μV, P < .001). Exacerbation of ST elevation after reperfusion correlated with the final IS (r = 0.64, P = .025 for maximal ST elevation in a single lead and r = 0.80, P = .002 for sum of ST deviations) but not with MaR (r = 0.43, P = .17 for maximal ST elevation in a single lead and r = 0.49, P = .11 for sum of ST deviations). The maximal ST elevation in a single lead and the sum of ST deviations during occlusion did not correlate with either MaR or final IS.

Conclusion

In the experiment, exacerbation of ST elevation is common during restoration of blood flow in the occluded coronary artery. The magnitude of the exacerbation of ST elevation after reperfusion in experimentally induced myocardial infarction in pigs is associated with infarct size but not with MaR.     

Reperfusion and reperfusion injury in acute myocardial infarction

Recognition of the clinical markers of reperfusion and comprehension of the effects of reperfusion injury in acute myocardial infarction provide a unique challenge for today's critical care nurse. In this article we will explore the processes of reperfusion injury. A review of relevant literature and presentation of a clinical case study and care plan will enable the critical care nurse to construct a larger knowledge base and assist in the nursing management of patients with acute myocardial infarction. Evaluation and treatment of reperfusion and reperfusion injury remains under investigation, but through the skills of assessment, planning, and intervention the critical care nurse can coordinate prompt and appropriate care to the patient with an acute myocardial infarction.     

Magnesium, acute myocardial infarction and reperfusion injury

Coronary artery disease (CAD) ranks top with respect to morbidity and mortality in humans. Development of high-tech diagnostic and therapeutic strategies has greatly improved the prognosis of CAD and acute myocardial infarction (AMI) over the past decade. Data from experimental and clinical research have provided important information on the role of magnesium in CAD and AMI. In relation to duration and severity of CAD, an adrenaline induced systemic stress arises, which provokes enhanced magnesium requirements, because magnesium is the co-factor in ATP dependent myocardial metabolism. The success of pharmacological or mechanical intervention in AMI can be compromised by reperfusion injury, which is probably caused by myocardial calcium accumulation. Since magnesium blocks myocardial calcium influx, reperfusion injury might be diminished or even prevented by magnesium application. Thus, the common procedure of invasive cardiac intervention and intravenous magnesium administration before reperfusion could become the gold standard in treatment of AMI.     

Effect of echinochrom on experimental myocardial reperfusion injury]

Echinochrom, a new antioxidant of the polyhydroxynaphthaquinone class, was tested for its cardioprotective activity in a model of occlusive reperfusion myocardial infarction (90-min occlusion and 4-hour reperfusion) in the acute experiments with open-chest dogs. The bolus intravenous injection of echinochrom in a dose of 1 mg/kg 5 min before reperfusion caused a significant (over 40%) reduction in the size of a necrotic focus. A supplementary administration of echinochrom 5 min after the onset of ischemia failed to contribute to a significant enhancement of its protective effect, suggesting that there is no substantial effect of the agent on ischemic lesion. The efficacy of echinochrom given after prolonged ischemia, low effective doses, and no adverse effects create prerequisites for using the drug in the clinical setting.     

急性心肌梗塞再灌注损伤临床表现及分析

目的:对急性心肌梗塞(AMI)再灌注后出现的特殊临床表现进行分析。方法:对50例AMI患者静脉溶栓后冠状动脉造影(显示为TIMI血流3级)的资料进行分析。结果:再灌注后有48例胸痛迅速缓解,有2例患者在再灌注后胸痛突然加重;有44例患者出现心律失常;40例出现一过性低血压;8例出现一过性ST段抬高。结论:冠脉血管再通后绝大部分患者胸痛迅速缓解,但大多有心律失常发生,一过性低血压,少数患者可出现ST段一过性胸痛加重;故溶栓后应进行持续心电图和血压监测。     

急性心肌梗死再灌注损伤临床表现及分析

目的对急性心肌梗死再灌注后出现的特殊临床表现进行分析。方法50例急性心肌梗死患者经静脉溶栓后行冠状动脉造影显示TIMI血流3级。结果再灌注后48例胸痛迅速缓解,2例患者在再灌注后胸痛突然加重;44例患者出现心律失常;40例出现一过性低血压;8例出现一过性ST段抬高。结论冠脉血管再通后绝大部分患者胸痛迅速缓解,且有心律失常发生,一部分患者可出现一过性胸痛加重;一过性低血压也比较常见,可能与多种因素有关;ST段反常性抬高可能是心肌再灌注的指标;溶栓后应进行持续心电和血压监测。     

Lornoxicam for prevention of myocardial injury during acute ST-elevation myocardial infarction

10% of patients with acute ST-elevation myocardial infarction (STEMI) treated with reperfusion therapy fail to develop an enzyme rise, but do exhibit transient ECG changes, which are consistent with an aborted myocardial infarction. Following reperfusion by primary PCI in STEMI, oxidative stress and an inflammatory response are induced immediately. Inflammation is a critical component of STEMI. Both COX isoforms are involved in reperfusion and ischemic myocardial injury. To evaluate the effectiveness of lornoxicam - nonselective NSAID, in decrease of myocardial injury during acute ST-elevation myocardial infarction. We analyzed 22 patients with STEMI, 14 of them received 16 mg and 8 mg lornoxicam after 20 min and 8 hours, respectively, after arrival to hospital. 12 f them received alteplase, 10 patients with cardiac pain up to 24 hours from the beginning, did not receive reperfusion therapy. All patients received anticoagulants, antiplatlet therapy, -blockers. The primary end point was all-cause mortality by the day 30 and hospitalization due to congestive heart failure by the 1st year. There was no difference in mortality and heart failure by the 30 day and 1st year respectively, between the patients with STEMI treated with lornoxicam or placebo. Randomized controlled trials are needed to explore potential cardioprotective effects of lornoxicam in patients with acute STEMI.     

重组人脑利钠肽对心肌梗死再灌注损伤的实验研究

目的通过构建急性心肌梗死(Acute myocardial infarction,AMI)再灌注兔子模型,观察重组人脑利钠肽(Lyophiluzed Re-combinant Human Brain Natriuretic Peptide,rhBNP)对兔子心肌梗死再灌注损伤的保护作用。方法制备实验性心肌梗死再灌注损伤模型,随机分为 3 组 :A 组 :假手术组、B 组 :模型组、C 组 :rhBNP 组(治疗前组和治疗后组)。测定心肌酶学(血清天冬氨酸氨基转移酶AST、乳酸脱氢酶 LDH、磷酸肌酸激酶 CK)、超氧化物酶(supemxide dismutase,SOD)活性、髓过氧化物酶(myeloperoxidase,MPO)活性、丙二醛(malonaldehyde,MDA)含量以及治疗前后 N 端脑钠素前体(N-terminal pro-brain natriuretic peptide,NT-proBNP)、超敏 C反应蛋白(high-sensitivity CRP,hs-CRP ,hs-CRP)水平变化。结果与 A 组相比,B 组兔子的 SOD 活性明显下降,MDA 及 MPO 含量均明显增加(P<...     

Effects of edaravone on reperfusion injury in patients with acute myocardial infarction

This clinical pilot study was a randomized, controlled, open-label study in 80 patients with acute myocardial infarction and was designed to examine the effects of a novel free radical scavenger, edaravone. Administration of edaravone before myocardial reperfusion was associated with smaller enzymatic infarcts and better clinical outcome.     

The role of myocardial reperfusion and hypertrophy in the development of heart rupture in experimental myocardial infarction

Balloon dilatation was used to explore the strength of the left ventricular wall in rats. The rupture pressure of the left ventricle was 645 +/- 22 mm Hg and that of the right ventricle was 247 +/- 15 mm Hg in intact animals. Left ventricular hypertrophy induced by 50% ascending aortic stenosis increased rupture pressure proportionally to the degree of hypertrophy. In transmural myocardial infarction occupying 40-55% of the left ventricular wall volume, the rupture pressure within 10 days of myocardial infarction was the same as that in the intact myocardium. Following 24 hours of ischemia, myocardial reperfusion produced no effects, but after 2 or 4 hours of ischemia it reduced the strength of the heart wall by 50%. It was concluded that early thrombolytic therapy might be a risk factor for cardiac rupture in myocardial infarction.     

Coronary reperfusion by thrombolysis and early beta-adrenergic blockade in acute experimental myocardial infarction

The effects of beta-adrenergic blockade, thrombolysis and their combination on infarct size and left ventricular function were investigated in a canine model of thrombotic occlusion of the left anterior descending coronary artery. Metoprolol was administered intravenously (0.5 mg/kg) over 10 min, starting 15 min after occlusion. Recombinant human tissue-type plasminogen activator (rt-PA) was given intravenously 1 h after occlusion for clot lysis. Anatomic infarct size was measured as a percent of perfusion area and ventricular mass. Left ventricular function was assessed by ejection fraction and the centerline method. Groups 1, 3, 5 and 7 were evaluated after 24 h and received, respectively, metoprolol plus rt-PA, rt-PA, metoprolol and no treatment; groups 2, 4, 6 and 8 were studied after 1 week and treated, respectively, as groups 1, 3, 5 and 7. Metoprolol did not influence infarct size and global or regional ventricular function after 24 h and 1 week. Thrombolysis reduced infarct size from 69.5 +/- 3.4% (24 h) and 76.6 +/- 1.8% (1 week) in the control group to, respectively, 44.1 +/- 11.6% and 39.5 +/- 10.5% (p greater than 0.05), did not influence left ventricular function after 24 h and was accompanied after 1 week by a definite recovery of global and regional left ventricular function when compared with findings in control dogs. Metoprolol plus rt-PA further reduced infarct size (percent perfusion area) to 20.4 +/- 3.7% and 19.9 +/- 8.1% after 24 h and 1 week, respectively (p = NS versus rt-PA).(ABSTRACT TRUNCATED AT 250 WORDS)     

腺苷对急性心肌梗死病人PCI术后心肌再灌注损伤的临床观察

目的观察腺苷对急性心肌梗死(AM I)患者行PC I后再灌注损伤心肌的保护作用。方法AM I患者分为腺苷组和生理盐水组,行PC I时一组冠脉内推注腺苷,一组推注生理盐水,并测定血浆SOD、MDA、CK-MB峰值。结果腺苷组MDA较生理盐水组低(5.01±0.80 vs 6.97±0.86,P<0.05),腺苷组SOD较生理盐水组高(80.70±3.23 vs 61.63±3.49,P<0.05),腺苷组CK-MB峰值较生理盐水组明显降低(123.6±84.3 vs186.1±92.2,P<0.05)。结论AM I患者行急诊PC I术时冠脉内应用腺苷能减轻心肌再灌注损伤。     

Opioids and myocardial reperfusion injury

It is well-established that reperfusion is the major method of salvaging ischemic myocardium following prolonged coronary artery occlusion, although the idea of reperfusion injury remains controversial. Moreover, more recent evidence strongly suggests that reperfusion per se is thought to result in further damage to the myocardium and blood vessel endothelium by various biochemical and physical factors including a burst of oxygen-derived free radicals (ROS), cellular or mitochondrial calcium overload and shear stress, to name a few. This has been termed lethal reperfusion injury. It has become increasingly evident that strategies in which interventions are administered during the early stages of reperfusion produce a reduction in reperfusion-mediated damage primarily by reducing massive calcium overload or by altering the intracellular milieu (pH, osmotic stress, etc.) and ROS release upon reperfusion. Furthermore, it is apparent that activation of blood borne elements such as neutrophils and macrophages and factors released by these cells such as cytokines may be responsible for a continuing expansion of infarction in the hours or even days following timely reflow and that inhibiting these factors may attenuate reperfusion injury. The present review will focus on the effect of endogenous and exogenous opioids on ischemic and reperfusion injury since these compounds are routinely used in the surgical arena and may have unappreciated cardioprotective effects in this subset of patients. Particular emphasis will be on the role of opioids in reperfusion injury and their relationship to the newly discovered phenomenon of postconditioning.