Acute Myocardial Infarction - Science topic

Out-of-hospital cardiac arrest (OHCA) due to acute myocardial infarction (AMI) and traumatic intracranial hemorrhage (TBI-related ICH) presents a complex resuscitation challenge. The approach to intervention must balance the need for cardiopulmonary resuscitation (CPR) while considering the risks of worsening intracranial bleeding.

Addressing AMI (Suspected STEMI/NSTEMI)

Would you like a more detailed breakdown of any aspect?

You have to continue Clipidogrel, and pause ASA. I do not see the reason to give Heparin with DAPT after PCI. If you don't give Clipidogrel, you will have a patent with STEMI along with SAH, and studies have shown that mostly major bleeding with DAPT are from ASA and multiple studies are prooving benefit with Clipidogrel and ASA for 7 days, and than only Clipidogrel. So.. To be short, in no circumstances you can not "pause" Clipidogrel, but ASA you can, and Heparin has no benefit after PCI.

Best regards

In order for a patient to be diagnosed with a myocardial infarction, they must have at least two of the following three criteria, according to the World Health Organization:

Clinical history of chest discomfort consistent with ischemia, such as crushing chest pain

An elevation of cardiac markers in blood (Troponin-I, CK-MB, Myoglobin)

Characteristic changes on electrocardiographic tracings taken serially

As to the last point, comparing the patient’s current ECG within old ECG is an important part of diagnosis. On the other hand, particularly worrisome changes by ECG should still be treated presumptively if the prior ECG is not available.

To help you with :

Thank you Renee

Hi, for you to increase survival rate , there should reduced time of ligation and the positioning of the tie along the LAD.

Check this link

regards

Adverse post-MI LV remodeling can be evaluated at different levels:

- Anatomical level: LV dilatation (increase in LV end-diastolic volume and LV end-systolic volumes), LV hypertrophy (increase in LV mass), architectural / geometrical remodeling (the LV loses its usual elongated, gullet-like shape and acquires a more spherical configuration, you can use sphericity index for this)

- Neurohormonal level: Sympathetic system overdrive (increase in adrenaline/noradrenaline levels), enhancement of RAAS system (higher levels of angiotensin II or aldosterone), raise in BNP (neurohormone marking LV dilatation)

- Histological level in the remote non-infarcted tissue: Cardiomyocyte hypertrophy (using staining for vinculin or wheat hemagglutinin), interstitial fibrosis (staining for picrosirius red), capillary paucity (staining for CD31 or isolectin)

- Molecular level: Activation (phosphorylation) of Akt/ERK/p38 (which drive cardiomyocyte hypertrophy), molecular markers of fibrosis (collagen I/III, CTGF, TGF-beta)

- Metabolism/energetic levels: Healthy myocardium predominantly consumes free fatty acid to generate ATP. There is a shift, however, in cardiac metabolism in remodeled myocardium towards mainly using glucose instead of free fatty acids

After MI, Fb are activated throughout the LV, presumably through TGF-β1 in response to increased wall stress and/or inflammation. Additional regional specific signaling leads to interstitial fibrosis via collagen cross-linking in MIadjacent. Local LOX activity could be stimulated by higher mechanical load imposed by tethering to the infarct or signals could diffuse from the scar. Identifying specific signaling cues to maintain the mature state of MyoFb phenotype in the scar tissue may open new perspectives in targeting the MyoFb reversibility in interstitial fibrosis without damaging existing scar tissue.

Yes, the intra peritoneal good is an alternative. Also you can use a catheter or water bottle to feed test group of rats.

The outcome of coronary artery occlusions is age-, species, severity of occlusion, duration, coronary collateral blood flow during ischemia (compared to baseline), operator and drugs used to support and stabilize hemodynamic.

In experimental models, regional ischemia is complicated by the above-mentioned factors and contributes to lack of reproducibility in the same laboratory and in literature.

It is seldom to see authors report complications, arrhythmia, fibrillation and mortality that why young investigators waste time and resources by following prior publications that do not report pitfalls of their studies. Swine model lacks coronary collateral, that is why pigs die with small risk areas (occlusion close to the apex) from arrhythmia and cardiac arrest not from infarction. Investigators treat all groups with lidocaine to attenuate arrhythmia and ventricular fibrillation, yet some more lidocaine and other inotropic drugs are used to minimize mortality.

Unlike regional ischemia, global ischemia and measuring load-independent indices of cardiac performance and correlating that to myocardial bioenergetics, marker enzymes of ischemia and infarction and the end-point of infarct size.

To obtain reproducible studies and results you must design experiments that have clinical relevance and try to minimize variations within same group and amongst other groups and time. GOOD LUCK

Dear Dr. Gennadiy

I truly appreciate your kind help.

Best wishes to you for success in your career and life!

Olá! Obrigada pela literatura recomendada. Olharemos!!!!!

I believe that the permanent artery ligation model is the most used, not only because the repercussions of acute myocardial infarction, its physiology, its implications and its repercussion on myocardial dynamics can be more definitively observed, since in the ischemia model -reperfusion in which the artery is occluded and open, if the period is less than 20 minutes, we will only have transient alterations (stunning model), which is completely different from the infarct model, so if it is to study the infarct and its consequences the most suitable model is permanent vessel occlusion.

What was the evidence for the AMI? What did the angio show? What's his LV like now? But this is a curable tumour so the risks of treatment will have to be balanced very carefully against the risks of not treating.

Yes, hypotension is a known risk factor for poor outcome not only in cardiovascular diseases. But whats about the hypertension. Were you able to make similar or even inverse experience here, like it shown in nearly all risk models for the mortality after MI?

All the best for planning to perform such experiments. Good luck

Yes that sounds right, you will need the probe for the ultrasound.

LAD ligation is good for inducing local ischemia, I have not seen it being used for HF but it does require great surgical ability with a stereoscope. I think it would be too detrimental for a survival surgery but its definitely possible. You should try RAP , rapid atrial pacing as its probably better than drug induction.

The most important to give at once is a chewable aspirin 300 mg tab.  it has a high mortality benifit.

GTN Spray even better than sublingual GTN but only for symptomatic relief. no mortality benefit.

guide for lvef and segment strain..

I use the effect of drinking a glass of water. If pain increases befor wanishing after à transitory blockade of water, it's absolutely specific.  Frequently, these criteria are not all present.

Greetings dear colleague:

Sent this interesting article. I hope you find it useful for their research.

We send you a warm greeting from Havana. Cuba.

I am performing MCAO on SD rats and I have 1 in 5 deaths but its because of jugular vein injection after MCAO. So there are various possibilities:

1) Amount of time for Surgery?

2)Check charcoal filters if Isoflrane is not being absorbed by the filters then animals might die.

3)Vagus nerve should not be damaged.

4)Make sure you add food and hydrogel in the cage.

5)When I insert  filament its around 30mm in the internal, one possible problem would be your filament is going in pterigopalatine and it advances only 20mm there. So make sure your filament when you insert through external immediately place forcep below the ECA and push filament in ICA. It should definitely advance 30mm.

Rat:280-330

Coating diameter: 0.37, 0.39

Bare filament: 5-0, 4-0

Search  “037”, “039”

Hope this helps.

Thank you for your contribution to my question.

Thanks Dr Kumar and Sandip. 

Hi everybody!

Excellent question, outstanding answers and comments!

I posed this same question to my ex-associates when introducing the first Chest Pain Unit in Brazil in 1996, and then at the Abstract Sessions of the American College of Emergency Physicians congress in 1999, again at the European Society of Cardiology congress in 1999 and 2000, and again at the American College of Cardiology congress in 2002. At that time we only used CKMB as a necrosis marker.

As we can see almost 2 decades later, and approprietely mentioned by all of you, there is no definite answer for this practical and very important question.

The introduction of high-sensitive troponins brought this questioning again but made things even more difficult (not to say, worse...) in the decision-making process in the ER.

I cannot agree more with Will's last paragraph but how to achieve that is the one-million dollar answer! 

You may want to contact my colleague here, Dr. Arkady Pertsov at

How to determine if ischemic hearts have irreversible ischemia_And How to treat them? Answer from a Clinical and Physiology investigator

First, assuming that severe ischemia or infarction occur as consequence of coronary obstruction or occlusion (clot) usually shows large number of coronary collateral anastomosis (inter/Intra artery anastomosis) along with precise natural bypass in the site of the major obstruction (Baroldi G et al, Circulation Res. 1956, Cardiovasc. Ultrasound 2005. His book is available from Internet, 2002): Macrovascular CHD. In these patients is better to assume that myocardial in “bypassed artery” has reversible options. In effect, ECG are reversed or returned to normal, under a novel therapeutic approach (Brief discussed at the end).

Second, assuming that severe ischemia or infarction occur in presence of “normal selective coronary arteriogram” (Likoff W et al, NEJM 1967), “a changing Philosophy“(Bugiardini R, Mertz BCN, JAMA 2005) implies that other critical factors, as the microvascular blood flow and O2 delivery are missing: Microvascular CHD.

However, in any scenario the incontrovertible fact is that O2 delivery occurs at the cellular level and involves a critical role of red-cell K-dependent ATP synthesis and release in presence of low pH or low PO2 (Ellsworth ML. Physiology, Bethesda 2009). Therefore, impaired capillary vasodilation instead of blood flow of the conductive coronary arteries) appears to be a major factor in the pathogenesis of CHD (Research Gate: Delgado-Almeida. Am Coll Cardiology Dec 2014, Figure).

This critical role in red-cell K-dependent function includes the K-activation of O2 binding by human hemoglobin (Delgado-Almeida A. FASEB J, 2012), suggesting that an enhanced hemoglobin O2-binding in the lung capillary bed is a required step for anti-anginal effects of nitrates or any other drugs, while explaining the failure of intracoronary administration of nitroglycerin to relieve angina induced by pacing, rapidly reversed by intravenous or sublingual doses (Ganz W, Marcus HS. Circulation 1972).

Third, how to determine if ischemia is irreversible or reversible damage? And How to treat them

a) Clinical and ECG serial evaluations and others as Echoc.

b) BOLD analysis (intra capillary levels of deoxyhemoglobin, MRI) documenting that reduced coronary perfusion in CHD does not always implies deoxygenation, opening a new way to assess myocardial ischemia (Karamitsos TD, Circ. Cardiovasc. Imaging 2010).

c) Improving the inherited effect in Red-Blood-Cell Potassium Content recorded in hypertensive and half of their normotensive offspring, as reported by our laboratory, confirmed to be a critical factor in vascular, renal function and total body water and K content (Delgado-Almeida A. Circulation. Abstract, AHA 2013).

d) Preserving the impaired RBC-K uptake related to drugs, particularly Diuretics and β-blockers (Oski FA et al, Science 1972, Agostoni A et al, Science 1973, both with propranolol) inducing abrupt K-efflux from RBC-K and disturbed oxygen affinity to hemoglobin.

e) Finally, a Physiological and Therapeutic approach addressing the defective RBC-K content and functions in CHD, by a novel composition of Amiloride HCl Dihydrate, allowing to improve Central Aortic BP and systolic pulse waveform reflection (type II-IV), reversing ischemic ECG with normal ECG in half of angina patients (in 6-months) and inducing electrical regeneration in previous areas of old infarcts (Delgado-Almeida A et al. Recent Pat on Cardiovasc Drug Discov.2010 and 2012).

Although these paragraphs might support myocytes regeneration of adult human heart by resident or bone marrow stems cells, the fact is that collateral anastomosis recorded by angiography are clear angiogenesis evidences in ischemic hearts. These peripheral and capillary support in CHD may explain innate regeneration of the heart and isolated living cells surrounded by large infarction (Anversa P, Leri A. Mayo Clin Proc. 2013).

Of note, that the role of stem cells in human biology might be recognized and traced as far as two centuries ago in different tissues and organs: Bones (bone reparation in fractures, cited in NEJM 1800’s), Liver (Donor and receptor of hepatic lobule, leading to almost normal anatomy by MRI and function in 3-4 months), Heart (collateral anastomosis and electrical regeneration of the heart in CHD). References for Bone and Liver Regeneration in PubMed.

FIGURE: Erythrocyte K-dependent ATP Synthesis-Function (See Delgado-Almeida A. β-blockers in Angina. J Am Coll Cardiol. Dec 2004; 64:2710-12).

FIGURE LEGEND: Electron microscopy views at the myocardial capillary net, in which diameters and blood flow is tightly controlled by a RBC-K dependent enzyme (pyruvate kinase activity) required for ATP synthesis and ATP release in the presence of low pH or PO2 (See, References 11-13, 38).

In myocardial cell, RBC release 1 mmol of O2 and 0.7 mmol of K from Oxyhemoglobin, in exchange for protons and CO2 from the myocardium; the reverse of K and O2-binding occurs at the lung capillary beds, as documented in our laboratory by in vitro studies in human venous blood samples (FASEB J 2012, Delgado-Almeida A).

An anatomical aspect is well evident in this picture, the larger RBC diameter (7±0.5 µ) versus 3.5-5.0 µ for most microvascular lumen (purple arrows). However, despite narrower capillary diameters, the flow velocity of these cells in healthy subject is 300-400 µ/sec, critically dependent of RBC-K dependent Pyruvate Kinase activity for ATP synthesis and release, the most powerful regulator of capillary vasodilatation and blood flow. Therefore, impaired vasodilatation and longer RBC transit time, instead of arterial vasoconstriction appears to be the most critical factor in essential hypertension and CHD, and probably represent a novel paradigm in the therapeutic management of these cardiovascular diseases.

Ok Sanjay good but only Sokolow-Lyon over thickness don't answer completely ESC post about this.

Great your post

Thanks

For me Time AT obtention TIMI 3 whatever the tool!!!

philippe BRUNELBRUNEL

Hi Narendra.

Heart lysates in RIPA buffer should normally work for MPO assay. However, it depends on the kit. We have tried ELISA with tissue lysate in RIPA buffer and it worked always.

Alternative strategies depends on your aim. If you want to measure MPO activity, then MPO assay kits or ELISA are the best option. If you are interested in MPO mass, then immunoblot of MMP2/9 or MPO should be sufficient. 

For activity measurements, I would suggest to go for ELISA than colorimetric assays.

All the best,

Chintan

i think reproducability of DT will be a issue ..so it wont be a reliable parameter.

According to the European Society of Cardiology (and other societies) universal definition of myocardial infarction, there are five type of MI. Type 1 is your conventional MI related to plaque erosion or rupture leading to thrombus formation. Type 3 is defined by the circumstance of sudden death, but could also be related to thrombus formaiton. Type 4a is MI related to PCI and Type 5 is MI related to CABG. Type 4b is the detection of stent thrombosis. All types are related to thrombosis except type 2. Type 2 is MI secondary to ischemia due to increased oxygen demand or decreased supply (e.g. coronary artery spams, coronary embolism, anaemia, arrhythmias, hypertension or hypotension.

So in conclusion, a type 2 MI occurs without thrombosis.

Reference attached

Yes, the procedure of MI in small size rat is the same as in mice. For detail please check my two papers.

erhe

Dear Colleagues,

NGF and BDNF may also be considered in coronary atherosclerosis, attached is our related paper on ACS...

George

What are the possible explanations by which HDL dysfunctional causes lower flow-mediated dilation and reduces production of nitric oxide in the setting of acute myocardial infarction?

Dear Anil,

First of all, BNP is clearly associated with incident acute myocardial infarction. In a study published in the Journal of the American Heart Association in November 2013, Matsuzawa et al. demonstrated that BNP is an independent cardiovascular event predictor, hazard ratio 1.019 (CI95% 1.002-1.037, p<0.023) for 0.1 increase of the natural logarithm of BNP [1]. Also, Kara et al. just published (February 2014) in the Clinical Research Cardiology their conclusion obtained from a BNP-normal sub-sample (n = 1639) that the gender-specific 90th percentile of BNP (31 pg/ml for males and 45 pg/ml for females) is associated with incident major cardiovascular and coronary events with a hazard ratio of 1.86 (CI 95% 1.37-2.53, p <0.0001) [2]. Other older publications also state that BNP can predict CAD and LVH in the general population [3-5].

Regarding to the physiological basis, BNP is one of the earliest responses to hemodynamic pressure overload and is elevated in patients with left ventricular hypertrophy, both risk factors for MI [6]. BNP is synthesized in and secreted from the cardiac ventricle, and is released primarily from the left ventricle in response to increased wall stress. The augmented production of BNP in the hypertrophied myocardium can be considered as a compensation mechanism against ventricular overload, since BNP serves to reduce both cardiac preload and afterload by its natriuretic, diuretic and vasodilatory effect [7].

Hoping to have been of help,

Best Regards,

1. Matsuzawa Y, et al. Peripheral endothelial function and cardiovascular events in high-risk patients. J Am Heart Assoc. 2013 Nov 25;2(6):e000426. doi: 10.1161/JAHA.113.000426.

2. Kara K, et al. B-type natriuretic peptide: distribution in the general population and the association with major cardiovascular and coronary events-The Heinz Nixdorf Recall Study. Clin Res Cardiol. 2014 Feb;103(2):125-32. doi: 10.1007/s00392-013-0628.

3. Foote R, et al. Detection of exercise-induced ischemia by changes in B-type natriuretic peptides. J Am Coll Cardiol. 2004;44:1980-1987.

4. Uusimaa P, et al. Plasma B-type natriuretic peptide reflects left ventricular hypertrophy and diastolic function in hypertension. Int J Cardiol. 2004;97:251-256.

5. Munagala VK, et al. The natriuretic peptides in cardiovascular medicine. Curr Probl Cardiol. 2004;29:707-769.

6. Kohno M, et al. Brain natriuretic peptide as a cardiac hormone in essential hypertension. Am J Med. 1992;92(1):29-34.

7. Nakagawa O, et al. Rapid transcriptional activation and early mRNA turnover of brain natriuretic peptide in cardiocyte hypertrophy. Evidence for brain natriuretic peptide as an “emergency” cardiac hormone against ventricular overload. J Clin Invest 1995;96:1280-7.

The answer is more complex than has been discussed. There is usually chest pain, but the nature of the chest pain is variable, and elusive. My grandfather was perfectly healthy walking every day, but when he went to Case-Westyrn Reserve ER, he was sent home because maybe he had tightness in the chest. My aunt knew that that was really atypical and he was brought back. Lee Goldman somewhat resolved the problem in his algorithm - STABBING excludes MI (not always). Crushing, tightness, difficulty breathing, are in, and radiation to the left arm is additionally helpful. It may present as a "gallbladder attack" because of the innervation by the vagus nerve.

The second feature that is important, but not always helpful is the EKG. ST elevation is diagnostic. Q-wave is pathognomonic if not preiously known. ST depression is a red flag, and T-wave inversion can't be discarded. Normal sinus rhythm might exclude MI, and perhaps atypical EKG abnormalities that are not the above.

The third part of the discussion is the use mof cardiac biomarkers. The original test was SGOT (AST) that was introduced by Arthur Karmen, a medical student at Albert Einstein. There may also be a neutrophil elevation because of the inflammatory response. Then came LAH and CK, followed by LD isonzyme 1 and CK isoenzyme MB. They have a characteristic rise to peak and decline. The introduction of troponins T and then I, changed the landscape. Then the troponins were made ultrasensitve, so that minor elevations were identified from ischemia, but then we have type 1 and type 2 infarcts. The type 1 infarct is associated with plaque rupture. It is a slam dunk. The type 2 is below level of the original diagnostic cutoff based on ROC curve analysis. A major confounder can be chroni kidney disease.

Than you again Dr Hany.