Heart Attack Treatment Research Articles

Angioplasty to replace thrombolysis as first-line treatment for heart attack

Angioplasty is to become the first-line treatment for heart attack after the publication last month of a report by the National Infarct Angioplasty Project (NIAP).

Primary angioplasty the new first-line heart attack treatment in UK

Primary angioplasty the new first-line heart attack treatment in UK

Colombistatin: a disintegrin isolated from the venom of the South American snake (Bothrops colombiensis) that effectively inhibits platelet aggregation and SK-Mel-28 cell adhesion

Snake venoms are complex mixtures of proteins, which affect the vital biologic systems of prey, as well as humans. Envenomation leads to immobilization by paralysis, cardiac, and circulatory failure. These same venom proteins that cause havoc in the physiologic system could be used as therapeutic agents. Disintegrins and disintegrin-like proteins are molecules found in the venom of four snake families (Atractaspididae, Elapidae, Viperidae, and Colubridae). The disintegrins are non-enzymatic proteins that inhibit cell-cell interactions, cell-matrix interactions, and signal transduction. These proteins may have potential in the treatment of strokes, heart attacks, cancers, osteoporosis, and diabetes. The present study describes the isolation and characterization of a disintegrin (colombistatin) found in the venom of the Venezuelan snake mapanare (Bothrops colombiensis). Colombistatin was purified by a two-step high-performance liquid chromatography procedure, which included reverse phase C18 and size exclusion protein Pak 60. Colombistatin inhibited ADP-induced platelet aggregation, human urinary (T24) and skin melanoma (SK-Mel-28) cancer cell adhesion to fibronectin, and cell migration. Colombistatin contained 72 amino acids with a mass of 7.778 kDa as determined by mass spectrometry. Colombistatin could be used as a therapeutic tool in the treatment of melanoma cancers and also thrombotic diseases.

Primary angioplasty the new first-line heart attack treatment in UK

Primary angioplasty the new first-line heart attack treatment in UK

Venom variation in hemostasis of the southern Pacific rattlesnake ( Crotalus oreganus helleri): Isolation of hellerase

Envenomations by the southern Pacific rattlesnake ( Crotalus oreganus helleri) are the most common snakebite accidents in southern California. Intraspecies venom variation may lead to unresponsiveness to antivenom therapy. Even in a known species, venom toxins are recognized as diverse in conformity with interpopulational, seasonal, ontogenetic and individual factors. Five venoms of individual C. oreganus helleri located in Riverside and San Bernardino counties of southern California were studied for their variation in their hemostatic activity. The results demonstrated that Riverside 2 and San Bernardino 1 venoms presented the highest lethal activity without hemorrhagic activity. In contrast, San Bernardino 2 and 3 venoms had the highest hemorrhagic and fibrinolytic activities with low lethal and coagulant activities. Riverside 1, Riverside 2 and San Bernardino 1 venoms presented a significant thrombin-like activity. San Bernardino 2 and 3 venoms presented an insignificant thrombin-like activity. In relation to the fibrinolytic activity, San Bernardino 3 venom was the most active on fibrin plates, which was in turn neutralized by metal chelating inhibitors. These results demonstrate the differences amongst C. oreganus helleri venoms from close localities. A metalloproteinase, hellerase, was purified by anionic and cationic exchange chromatographies from San Bernardino 3 venom. Hellerase exhibited the ability to break fibrin clots in vitro, which can be of biomedically importance in the treatment of heart attacks and strokes.

Improving the care of heart attack patients

The emergency treatment of heart attacks in the UK, or what is known as ST elevation myocardial infarction (STEMI), has undergone substantial change in recent years, with the use of both pharmacological treatment administered before the patient is admitted to hospital (pre-hospital thrombolysis (PHT)), mechanical intervention and primary percutaneous coronary intervention (PPCI), increasing rapidly.

Peptides Inhibitors of F11R/JAM‐A Adhesion Molecules

F11‐R receptor was characterized as an adhesion protein, called also aka JAM‐A (or JAM‐1), which under normal physiological conditions is expressed constitutively on the surface of the platelets and localized within tight junctions of endothelial cells (EC). The utilization of specific F11R/JAM‐A peptide antagonists and recombinant proteins supported the role of F11R/JAM‐A in the process of platelets adhesion to inflamed endothelial cells and identified plaque formation leading to inflammatory thrombosis and atherosclerosis where the platelets have a critical influence in the progression and development of the cardiovascular disease. Thus, the development of new drugs antagonizing the F11R/JAM‐A function could evolve as an effective strategy for the treatment of atherosclerosis, heart attacks and stroke. We present one of the first trials toward development of peptide‐based inhibitors of F11R/JAM‐A function. Among many trials, the peptide D‐Lys‐Ser‐Val‐Ser‐D‐Arg‐Glu‐Asp‐Thr‐Gly‐Thr‐Tyr‐Thr‐Cys‐CONH2 proved to be a potent inhibitor of human platelets aggregation in vitro. Further molecular docking experiments showed that this peptide makes favorable hydrophobic and electrostatic interactions within the proposed binding site of JAM‐1 (X‐Ray structure 1nbq.pdb was used as template).

Is Human Hibernation Possible?

The induction of hypometabolism in cells and organs to reduce ischemia damage holds enormous clinical promise in diverse fields, including treatment of stroke and heart attack. However, the thought that humans can undergo a severe hypometabolic state analogous to hibernation borders on science fiction. Some mammals can enter a severe hypothermic state during hibernation in which metabolic activity is extremely low, and yet full viability is restored when the animal arouses from such a state. To date, the underlying mechanism for hibernation or similar behaviors remains an enigma. The beneficial effect of hypothermia, which reduces cellular metabolic demands, has many well-established clinical applications. However, severe hypothermia induced by clinical drugs is extremely difficult and is associated with dramatically increased rates of cardiac arrest for nonhibernators. The recent discovery of a biomolecule, 5'-AMP, which allows nonhibernating mammals to rapidly and safely enter severe hypothermia could remove this impediment and enable the wide adoption of hypothermia as a routine clinical tool.

Structures of potent selective peptide mimetics bound to carboxypeptidase B

This article reports the crystal structures of inhibitors of the functional form of thrombin-activatable fibrinolysis inhibitor (TAFIa). In vivo experiments indicate that selective inhibitors of TAFIa would be useful in the treatment of heart attacks. Since TAFIa rapidly degrades in solution, the homologous protein porcine pancreatic carboxypeptidase B (pp-CpB) was used in these crystallography studies. Both TAFIa and pp-CpB are zinc-based exopeptidases that are specific for basic residues. The final development candidate, BX 528, is a potent inhibitor of TAFIa (2 nM) and has almost no measurable effect on the major selectivity target, carboxypeptidase N. BX 528 was designed to mimic the tripeptide Phe-Val-Lys. A sulfonamide replaces the Phe-Val amide bond and a phosphinate connects the Val and Lys groups. The phosphinate also chelates the active-site zinc. The electrostatic interactions with the protein mimic those of the natural substrate. The primary amine in BX 528 forms a salt bridge to Asp255 at the base of the S1' pocket. The carboxylic acid interacts with Arg145 and the sulfonamide is hydrogen bonded to Arg71. Isopropyl and phenyl groups replace the side chains of Val and Phe, respectively. A series of structures are presented here that illustrate the evolution of BX 528 from thiol-based inhibitors that mimic a free C-terminal arginine. The first step in development was the replacement of the thiol with a phosphinate. This caused a precipitous drop in binding affinity. Potency was reclaimed by extending the inhibitors into the downstream binding sites for the natural substrate.

Public knowledge of heart attack symptoms in Beijing residents

Definitive treatment for heart attack is early reperfusion with either angioplasty or thrombolytic therapy, and the benefit is strictly time-dependent. Patient outcomes are improved with either therapy when initiated as soon as possible. Recognition of heart attack symptoms is logically tied to taking action to receive prompt emergency care. Inadequate knowledge of heart attack symptoms may prolong delay. The purpose of this study was to document knowledge about heart attack symptoms in Beijing residents and to identify the characteristics associated with increased knowledge of heart attack. A structured survey was conducted in 18 communities in Beijing from March 1 through June 10 in 2006. Addresses and participants were selected randomly following a stratification. The survey was designed to collect knowledge of heart attack symptoms from sampled adults in each community. A total of 4627 respondents completed the questionnaires correctly, and 50.29% of them were female. Totally 64.15% of the respondents reported chest pain or discomfort (common symptoms) as a symptom of heart attack; 75.38% reported at least one of the following eight symptoms as a symptom of heart attack: back pain, shortness of breath, arm pain or numbness, nausea or vomiting, neck, jaw or shoulder pain, epigastric pain, sweating, weakness (less common symptoms); 20.36% correctly reported four or more heart attack symptoms, only 7.4% knew all the correct heart attack symptoms, and 28.94% knew about reperfusion therapy for heart attack; 31.7% reported to call 120 or 999 while having a heart attack themselves; however 89.6% reported to call 120 or 999 when someone else is suffering from a heart attack. Very old persons and those with health insurance coverage, high education level, high household income, longer living in Beijing and previous experience with heart disease had greater knowledge of heart attack symptoms. Public knowledge of common heart attack symptoms as well as less common heart attack symptoms is deficient in Beijing residents. But their knowledge of calling emergency medical services when someone is having a heart attack is relatively adequate. Public health efforts are needed to increase the recognition of the major heart attack symptoms in both the general public and groups at high risk for an acute cardiac event, especially in socioeconomically disadvantaged subgroups, including persons with low education level, low household income, and no health insurance coverage.

Are Health Care Prices Rising When Adjusted for Outcomes? Evidence from Heart Attack Treatments in Ontario

Increase in medical spending is an issue in all the developed countries and particularly in Canada. However, given that medical technology is evolving rapidly, we do not know whether price or quantity/quality of services is responsible for more of this increase. The objective of this study is to address the issue of measuring health care price in Canada. We estimate two types of price indices: a service price index (SPI), which prices specific medical services without any adjustment for health outcomes, and a cost-of-living index (COLI), which measures an outcome- adjusted cost of treating a specific health problem. These indices are applied to Acute Myocardial Infarction (AMI - or heart attack) treatment for the period 1995/96 and 2001/02, with cost data provided by the Ontario Case Costing Initiative (OCCI) and mortality data obtained from the Discharge Abstract Database. While we estimate a positive real annual change in AMI treatment price for the SPI, the real COLI fell about 1.0 percent per year under our benchmark assumption on the value of life, without even considering the quality of life of AMI patients.

Non-invasive low frequency vibration as a potential emergency adjunctive treatment for heart attack and stroke. An in vitro flow model

Myocardial infarction and stroke (arterial thrombosis) comprise the leading killers and sources of disability in the developed world, and incomplete thrombolysis along with high bleeding rates (plus late presentations to cathlabs) have prompted an intensive search for alternative or adjunctive emergency therapies. Transcutaneous ultrasound has been studied in remediation of thrombosis, but has been problematic due to poor penetration, risk of arterial damage, plus the apparent need for a highly skilled approach. Surprisingly there has been no reported studies on the much simpler application of transcutaneous low frequency vibration (well known for its superior penetration and flow enhancing characteristics) to assist arterial thrombolysis. The aim of our experiment therefore was to test the hypothesis whether vibration (i.e. approximately 100 Hz, 0.5 mm), when applied across an attenuating barrier, would assist recanulization of a thrombosed flow system held at arterial like pressure. A teddy bear with a 2 cm slab of New York Steak placed upon its chest surface was used as a test subject with an in-dwelling catheter (approximately 4.0 mm lumen) cannulated through the bear's thorax. In a series of test runs (n=30), a 2 h old (or older) blood clot was injected into the catheter such as to occlude it at a stenosis site (approximately 90% luminal narrowing) created by a clamp placed along the catheter within the teddy's chest region. A pressurized heparinized IV system was in all cases connected to the catheter such as to yield an "arterial like" lumen pressure proximal the obstruction. For each test run, after a twenty minute observation period to confirm stability of the occlusion, test groups where randomized to receive vibration to the slab of steak upon the teddy's "chest wall" (generally overlying the site of the thrombotic obstruction), or no vibration for an evaluation period of up to 45 min. Catheter reflow occurred rapidly (median reflow-time 90 s) in the vibration groups within the evaluation period (i.e. 15/17), while the system remained otherwise blocked in the control groups receiving no vibration (i.e. 0/13). The difference in flow system patency rate for the vibration groups vs. the control groups was statistically significant (P=0.0000009). The frequent and generally rapid re-establishment of flow in vibration groups compared to the complete absence of reflow in control groups confirms the hypothesis that vibration applied across a physical barrier assists clearance of a blood clot in a stenosed flow system under systemic levels of pressure. We studied the incidence of clearance of a blood clot within a stenosed, heparanized catheter system held at arterial like pressure that was treated with externally delivered low frequency vibration (applied proximate the thrombotic occlusion across an attenuating medium--a 2 cm thick slab of New York Steak--at approximately 100 Hz, 0.5 mm), versus no vibration. Reflow in test runs incorporating vibration occurred faster, and resulted in significantly greater recanulization rates in the catheter system versus test runs without vibration (P=0.0000009). Non-invasive vibration holds potential as an adjunct to pharmacologic therapy in treatment of acute arterial thrombosis. Further study of this technique appears warranted in live animal models.

Productivity Spillovers in Health Care: Evidence from the Treatment of Heart Attacks

A large literature in medicine documents variation across areas in the use of surgical treatments that is unrelated to outcomes. Observers of this phenomena have invoked "flat of the curve medicine" to explain these facts, and have advocated for reductions in spending in high-use areas. In contrast, we develop a simple Roy model of patient treatment choice with productivity spillovers that can generate the empirical facts. Our model predicts that high-use areas will have higher returns to surgery, better outcomes among patients most appropriate for surgery, and worse outcomes among patients least appropriate for surgery, while displaying no relationship between treatment intensity and overall outcomes. Using data on treatments for heart attacks, we find strong empirical support for these and other predictions of our model, and reject alternative explanations such as waste or supplier induced demand, for geographic variation in medical care.

The F11 receptor (F11R/JAM-A) in atherothrombosis: Overexpression of F11R in atherosclerotic plaques

F11R is the gene name for an adhesion protein, called the F11-receptor, aka JAM-A, which under normal physiological conditions is expressed constitutively on the surface of platelets and localized within tight junctions of endothelial cells (EC). Previous studies of the interactions between human platelets and EC suggested that F11R/JAM-A plays a crucial role in inflammatory thrombosis and atherosclerosis. The study reported here obtained in-vivo confirmation of this conclusion by investigating F11R/JAM-A protein and mRNA in patients with aortic and peripheral vascular disease and in an animal model of atherosclerosis. Molecular and immunofluorescence determinations revealed very high levels of F11R/JAM-A mRNA and F11R/JAM-A protein in atherosclerotic plaques of cardiovascular patients. Similar results were obtained with 12-week-old atherosclerosis-prone apoE-/- mice, an age in which atherosclerotic plaques are well established. Enhanced expression of the F11R/JAM-A message in cultured EC from human aortic and venous vessels was observed following exposure of the cells to cytokines. Determinations of platelet adhesion to cultured EC inflamed by combined cytokine treatment in the presence of F11R/JAM-A - antagonists provided data indicating that de novo expression of F11R/JAM-A on the luminal surface of inflamed EC has an important role in the conversion of EC to a thrombogenic surface. Further studies of these interactions under flow conditions and under in-vivo settings could provide a final proof of a causal role for F11R/JAM-A in the initiation of thrombosis. Based on our in-vitro and in-vivo studies to date, we propose that therapeutic drugs which antagonize the function of F11R/JAM-A should be tested as novel means for the prevention and treatment of atherosclerosis, heart attacks and stroke.

The Return on Investment in Health Care: From 1980 to 2000

Objective To estimate the return on US investment (ROI) in overall health as well as four specific conditions. Methods The study utilized three distinct approaches to “triangulate” the evidence as related to ROI in health care: 1) an estimation of the average ROI in additional health-care service expenditures in the United States for the year 2000 compared with the year 1980, based on US summaries of health expenditures and health outcomes; 2) an estimate of the ROI in Medicare services for the period from 1985 to 2000 for treatment of heart attack, stroke, type 2 diabetes, and breast cancer, based on National Long-term Care Survey data and Medicare claims; and 3) an estimate of the ROI for selected major treatment innovations for the same four conditions during the period from 1975 to 2000. Results We calculated that each additional dollar spent on overall health-care services produced health gains valued at $1.55 to $1.94 under our base case assumptions. The return on health gains associated with treatment for heart attack, stroke, type 2 diabetes, and breast cancer were $1.10, $1.49, $1.55, and $4.80, respectively, for every additional dollar spent by Medicare. The ROI for specific treatment innovations ranged from both savings in treatment costs and gains in health to gains in health valued at $1.12 to $38.00 for every additional dollar spent. Conclusion The value of improved health in the US population in 2000 compared with 1980 significantly outweighs the additional health-care expenditures in 2000 compared with 1980.

Heart cells keep the rhythm

Cytokine therapy post–heart attack restores the expression of gap junction proteins and thus restores electrical connections between heart cells, according to a new study by Kuhlmann and colleagues (page 87). These heart cells, with better electrical connections, are able to pump with a more normal rhythm. Figure 1 G-CSF treatment restores the expression of connexin 43 on cardiomyocytes near areas of heart attack–induced damage (arrows). Restoring the function of damaged heart tissue is a new approach to the treatment of myocardial infarctions, or heart attacks. The scar tissue from heart attacks creates a roadblock for electrical conduction and can cause the heart to beat erratically. Indeed, erratic heartbeats—or arrhythmias—are the primary cause of death in patients who have had heart attacks. Heart attack treatments range from blood-thinning and cholesterol-lowering drugs, which reduce the likelihood of developing blocked arteries, to implanted defibrillators that shock erratically beating hearts into line. But the idea of repairing damaged heart tissue is new. One promising repair approach involves the intravenous injection of two cytokines—G-CSF (granulocyte colony-stimulating factor) and SCF (stem cell factor)—which mobilize stem cells from the bone marrow (BM). Early studies suggested that these stem cells travel to the damaged heart and differentiate into functional heart cells called cardiomyocytes. Other studies, however, found no evidence that stem cells can become cardiomyocytes. Kuhlmann and colleagues now confirm that G-CSF/SCF treatment in mice with heart damage causes BM-derived cells to enter the heart, but they show that virtually none of these cells become bona fide heart cells. The benefit of this treatment—which improved the heart's pump function and protected against induced arrhythmias—instead correlated with enhanced expression of the gap junction protein connexin 43 on the surface of heart cells adjacent to the injured tissue. The expression of connexin 43, which provides the electrical connection between neighboring cells, is decreased after heart injury, thus reducing the conductive capacity between cells. The connexin-inducing effect of G-CSF might be direct, as cardiomyocyte expression of the G-CSF receptor was increased in response to injury. But this possibility is difficult to test in vitro, as mouse cardiomyocytes grow poorly in culture. The authors are also investigating G-CSF–independent signaling pathways that induce the expression of connexin 43 in other cell types.

Isolation and characterization of two disintegrins inhibiting ADP-induced human platelet aggregation from the venom of Crotalus scutulatus scutulatus (Mohave Rattlesnake)

Disintegrins and disintegrin-like proteins are molecules found in the venom of four snake families (Atractaspididae, Elapidae, Viperidae, and Colubridae). The disintegrins are nonenzymatic proteins that inhibit cell-cell interactions, cell-matrix interactions, and signal transduction, and may have potential in the treatment of strokes, heart attacks, cancers, and osteoporosis. Prior to 1983, the venom of Crotalus scutulatus scutulatus (Mohave Rattlesnake) was known to be only neurotoxic; however, now there is evidence that these snakes can contain venom with: (1) neurotoxins; (2) hemorrhagins; and (3) both neurotoxins and hemorrhagins. In this study, two disintegrins, mojastin 1 and mojastin 2, from the venom of a Mohave rattlesnake collected in central Arizona (Pinal County), were isolated and characterized. The disintegrins in these venoms were identified by mass-analyzed laser desorption ionization/time-of-flight/time-of-flight (MALDI/TOF/TOF) mass spectrometry as having masses of 7.436 and 7.636 kDa. Their amino acid sequences are similar to crotratroxin, a disintegrin isolated from the venom of the western diamondback rattlesnake (C. atrox). The amino acid sequence of mojastin 1 was identical to the amino acid sequence of a disintegrin isolated from the venom of the Timber rattlesnake (C. horridus). The disintegrins from the Mohave rattlesnake venom were able to inhibit ADP-induced platelet aggregation in whole human blood both having IC50s of 13.8 nM, but were not effective in inhibiting the binding of human urinary bladder carcinoma cells (T24) to fibronectin.

Biomedicine: Heart attack treatment: Better late than never

Science NewsVolume 167, Issue 26 p. 413-413 Of Note Biomedicine: Heart attack treatment: Better late than never First published: 25 September 2009 https://doi.org/10.1002/scin.5591672614AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume167, Issue2625 June 2005Pages 413-413 RelatedInformation

How to Clean the Dirtiest Place in the Cell: Cationic Antioxidants as Intramitochondrial ROS Scavengers

Membrane-penetrating triphenyl alkyl phosphonium cations have been suggested for many years in our group as having the ability to measure mitochondrial potential were recently used by Murphy as vehicles to specifically target CoQ to mitochondria. As was shown in our group, the phosphonium derivative of CoQ (MitoQ) easily penetrates a planar bilayer phospholipid membrane as a cation, generating 60 mV electric potential (Deltapsi) per a 10-fold MitoQ gradient. This means that MitoQ should be unequally distributed across the inner mitochondrial membrane, the intramitochondrial [MitoQ] = extramitochondrial [MitoQ] x 10(3) at 180 mV Deltapsi. In line with such a calculation, Murphy and his colleagues reported that antioxidant efficiency of MitoQ added to mitochondria or cells appears to be very much higher than of CoQ. It was found that H2O2-induced apoptosis (Murphy) and the H2O2-mediated bystander killing of the cultivated cells (our group) are completely arrested by pretreatement of the cells with 10(-10) - 10(-8) M MitoQ. These effects indicate that MitoQ and similar compounds may be promising in treatment of heart attack, stroke and other diseases accompanied by massive apoptosis in the injured tissue. The very fact that: (i) MitoQ is not only accumulated by mitochondria but also can be regenerated in its reduced form by mitochondrial respiratory chain, (ii) it is the mitochondrial interior that produces a large portion of reactive oxygen species (ROS) in our body, and (iii) the most sensitive ROS targets are localized in the mitochondrial matrix suggest the MitoQ-like compounds are promising tools of molecular therapy of aerobic cells. In line with this suggestion, we found that addition of MitoQ strongly improves structural and biochemical parameters of cultivated cells. As to cationic tetrapeptides, recently advertised as mitochondrially-targeted Deltapsi-independent antioxidants, their effect is most probably mediated by an opioid activity inherent in some of these substances.

1138 Use of nonpharmacological measures in the treatment and prevention of stroke and heart attack

Stroke and heart attack rank high on the morbidity and mortality scale both in Croatia and worldwide. As these are diseases from which a part of patients die, a part have lower or higher degree of disability and only a minor part recover completely, the problem of treatment and prevention of these diseases is in the very focus of interest of a large number of researchers. New potential risk factors for cerebrovascular and cardiovascular diseases are discovered on an almost daily basis. It seems that more effort has been invested in the detection of risk factors than in the use of efficient measures for their removal or control. It is by no means infrequently that individuals with a history of stroke or heart attack after the early phase of recovery, resume of smoking habit, fail to follow the principles of healthy nutrition, neglect light physical activity, unnecessarily get exposed to stressful situations or those than cannot be avoided tend to solve in an inappropriate manner, and eventually sustain recurrent stroke or heart attack in spite of regular use of pharmacological agents. Therefore, during patient hospitalization and post hospital follow-up, in addition to the usual control neurological and cardiologic examinations, patients should be provided appropriate assistance in the process of lifestyle modification, in cooperation with their family members, in order to reduce the possibility of the disease recurrence. The professionally justifiable, available and cost-effective non-pharmacological measures that are relevant for both prevention and efficient therapy of Cerebrovascular and cardiovascular diseases are discussed.