Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151814 (coronary occlusion)
 3,687 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Heparin has been labeled with [99mTc] pertechnetate and its ability to image damaged coronary vessels and myocardium during and following myocardial ischemia has been studied in experimental animals. The data obtained indicate that Tc-99m heparin localizes in damaged myocardium and coronary vessels in canine models of temporary myocardial ischemia and reperfusion and in damaged myocardium during fixed coronary occlusion. Scintigraphic detection of damaged myocardium was possible in both models, but the highest levels of Tc-99m heparin in damaged myocardial tissue were found in those dogs with temporary coronary occlusion and reflow. The data suggest that Tc-99m heparin may be of value as a positive imaging agent when coronary arteries or myocardium are injured and either reperfusion is allowed and/or significant blood flow persists in the damaged area.
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PMID:Technetium-labeled heparin: preliminary report of a new radiopharmaceutical with potential for imaging damaged coronary arteries and myocardium. 66 Feb 85

Heparin in large doses significantly improved epicardial electrocardiographic findings and preserved myocardial tissue and creatine phosphokinase (CPK) after coronary ligation in the dog. Epicardial S-T segment elevation 15 minutes after occlusion was lowered 84% (from 64.5 + 8.5 [standard error of the mean] to 10.4 +/- 3.0 mv) by heparin infusions of 60,000 units. Myocardial creatine phosphokinase depletion was reduced from 39 to 24% at comparable levels of S-T segment elevation. Histologic evidence of necrosis decreased 32%. It is concluded that heparin can reduce the extent of ischemic injury after acute coronary occlusion in the dog. These results may lend insight into the factors responsible for ischemic injury.
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PMID:Effects of heparin in large doses on the extent of myocardial ischemia after acute coronary occlusion in the dog. 125 97

Myocardial infarction (MI) is the result of acute coronary occlusion and the prognosis depends on the infarct size. In experimental studies, infarct size is reduced by early coronary reperfusion which may be obtained by intravenous thrombolytic therapy. This simple, rapid and widely used technique is the clinical treatment of choice. The diagnosis of MI must be confirmed by clinical and electrocardiographic findings. The clinical history is important because the value of reperfusion when started after the 6th hour after the onset of chest pain is questionable. However, it is often difficult to determine the beginning of MI when preceded by unstable angina. Contraindications to thrombolytic therapy must be carefully excluded irrespective of the thrombolytic agent because of the risk of haemorrhage. This must be weighed up against the risk of the MI itself. Therefore, age is not a systematic exclusion criterion. The choice of thrombolytic is based on the efficacy, mode of administration and cost. Heparin therapy at effective doses is associated in all cases to prevent reocclusion. Aspirin is given orally. The association of a calcium inhibitor or a betablocker may also be considered. Reperfusion and ischaemia may give rise to arrhythmias and haemodynamic changes which have to be rapidly corrected. Haemorrhagic complications during thrombolysis are treated according to the severity and time of onset by blood transfusion sometimes associated with a plasmin inhibitor. Reocclusion is an indication for emergency coronary angioplasty but in some cases repeat thrombolytic therapy may be beneficial. When the MI is extensive, rapid transfer to a cardiological centre with catheter facilities is advisable.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Thrombolytic therapy of myocardial infarction: practical management]. 153 Apr 12

The efficacy and safety of intravenous administration of recombinant tissue-type plasminogen activator (rt-PA, made by Boehringer Ingelheim Corp.) was investigated in 10 patients with acute myocardial infarction (AMI). The rt-PA was given as a bolus dose of 10 mg followed by an infusion of 50 mg, 20 mg and 20 mg in successive hours. Heparin and aspirin were given to all the patients. The time interval from the onset of chest pain to thrombolysis was from 2.3 to 6.1 h with mean of 3.9 h. Coronary angiography, performed before administration of rt-PA and every 30 minutes thereafter, demonstrated total coronary occlusion (grade O) in 9 patients and grade 1 in 1 at baseline study. The infarct-related coronary artery were LAD in 5, RCA in 3 and LCX in 2. At 90 minutes after infusion of rt-PA reperfusion of the infarct-related artery was observed in 7 patients, the success rate was 70%. In one case the infarct-related LCX was not opened at 90 minutes, but it was reperfused at 170 minutes, after intracoronary administration of 10 mg of rt-PA. The total dose in this case was 130 mg. During 30 days of hospitalization death occurred in only one case with cardiogenic shock, in whom the infarct-related RCA was not reperfused by rt-PA but was successfully recanalized by PTCA. The patient died from rupture of the left ventricle on the 4th day. No patient had clinical evidence of reinfarction. Follow-up angiography in 2 patients showed that the arteries reperfused initially were patent.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Intravenous recombinant tissue-type plasminogen activator in acute myocardial infarction]. 181 88

Bovine testicular hyaluronidase (BTH) reduces experimental myocardial infarct size and ameliorates electrocardiographic signs of ischemia. This study was done to determine if heparin, an in vitro inhibitor of hyaluronidase activity, blocks the action of BTH in the myocardium of dogs after coronary artery occlusion. BTH was administered intravenously as 5,000 NF units/kg at 0.5 and 2.5 hours after coronary occlusion. Heparin was administered intravenously as a 150-unit/kg loading dose, followed by 10 units/kg per hour i.v., beginning 15 minutes before coronary occlusion. The area of myocardial ischemia at risk was assessed by a radiolabeled microsphere technique; the area that developed necrosis was assessed by a histochemical technique. In vivo activity of BTH was assessed by a colorimetric analysis of the BTH substrate, i.e., hyaluronic acid (HA), extracted from myocardial tissue. For biochemical analysis of HA, the heart was divided into anterior myocardium, which included ischemic tissue and posterior nonischemic myocardium. The myocardial HA content of dogs treated with BTH plus heparin (anterior, 3.44 +/- 0.40 micrograms HA/mg protein; posterior, 3.69 +/- 0.33 micrograms HA/mg protein) was not significantly different from control (anterior, 3.61 +/- 0.29 micrograms HA/mg protein; posterior, 3.55 +/- 0.23 micrograms HA/mg protein). In contrast, BTH lowered myocardial HA content (anterior, 2.16 +/- 0.21 micrograms HA/mg protein; posterior, 2.08 +/- 0.14 micrograms HA/mg protein) compared with either BTH plus heparin or control groups in both anterior myocardium (p = 0.006) and posterior myocardium (p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Heparin inhibits bovine testicular hyaluronidase activity in myocardium of dogs with coronary artery occlusion. 670 49

Heparin is a highly sulfated polysaccharide consisting of a repeating disaccharide structure as found in other glycosaminoglycanes. The intravenous and subcutaneous formulation of the drug is routinely used for its well-known, time-honored antithrombotic effect. However, available evidences linking heparin to angiogenesis raise the possibility of a therapeutically relevant antiischemic effect of the drug. Molecular biology data show that in a hypoxic milieu heparin could facilitate angiogenesis through interactions with a family of polypeptide growth factor mitogens that stimulate endothelial cell proliferation. Experimental data suggest that heparin can augment collateral circulation when combined with other potentially angiogenetic factors, such as repeated ischemia, coronary occlusion, or physical exercise. Clinical data, although very initial, encompassing a total of only 41 heparin-treated patients with coronary artery disease, suggest that heparin facilitates collateral development stimulated by exercise-induced myocardial ischemia in humans. According to the heparin-collateral hypothesis, the mechanism of action of heparin as an antiischemic medication would be independent of its anticoagulant action. The molecular targets of heparin are Factor Xa and IIa for antithrombotic action, heparin-binding growth factors (including fibroblast growth factor and vascular endothelial growth factor) for angiogenesis. The antithrombotic effect is not linked to a cellular target, whereas the angiogenetic effect directly stimulates endothelial cells. The molecular cofactor required for effect is antithrombin III for antithrombosis, and possibly endogenous adenosine for angiogenesis. The therapeutic effect is achieved within minutes or hours for antithrombosis, and within weeks or months for angiogenesis.
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PMID:The coronary angiogenetic effect of heparin: experimental basis and clinical evidence. 937 49

We studied the presence of collagen degrading enzymes (matrix metalloproteinases, MMPs) in porcine myocardium following ischemia and late reperfusion. In nine pigs, left anterior descending coronary artery was occluded for 6 h followed by reperfusion for 3 h. Six pigs without coronary occlusion served as controls. After the reperfusion period, transmural biopsies from the anterior (ischemic zone) and posterior wall (non-ischemic myocardium) in the left ventricle were obtained and extracted. Heparin-Sepharose isolated components in extracts were analysed for collagenase (triple-helical collagen degradation) and gelatinase activity (zymography). Immunohistochemistry using anti-human (MMP-1, MMP-2, MMP-9, and fibronectin) antibodies was performed on additional biopsies. Collagenase (MMP-1) and gelatinases (MMP-2, MMP-9) could be demonstrated in the extracts of non-ischemic myocardium from ischemic/reperfused as well as control pigs and MMP-1 and MMP-9 activity was found to be increased in ischemic/reperfused myocardium compared with non-ischemic myocardium. In ischemic/reperfused myocardium from live pigs investigated, myocyte necrosis could be confirmed by fibronectin immunoreaction in myocytes and MMP-1 and MMP-9 immunoreactions were increased. MMP-9 was present in cells likely to be infiltrating leukocytes in a patchy distribution throughout the ischemic myocardium. Quite coincident with MMP-9 positive cells, MMP-1 immunoreaction appeared in necrotic myocytes, in addition to reactions observed in vessel walls, endo- and epicardium, and extracellular matrix in non-ischemic myocardium. Thus, the results showed increased amounts of collagenase (MMP-1) and gelatinase (MMP-9) in ischemic/ reperfused myocardium, indicating the appearance of increased amounts of collagen degrading enzymes very early following ischemia and late reperfusion.
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PMID:Increased amounts of collagenase and gelatinase in porcine myocardium following ischemia and reperfusion. 971 Aug 10

Patients with unstable angina have an increased activation of the coagulation system. Aspirin and ticlopidine given in combination may potentiate each other by the combination of different action mechanisms and may reduce the risk of coronary occlusion and clinical instability. Plasma tissue factor (TF) levels collected into the stenotic coronary artery may be an index of TF expression within the vasculature. In 160 patients undergoing angioplasty for a 81+/-5% coronary lesion, we measured TF in blood samples collected from a vein and from the coronary ostium. Immediately after and 10 minutes after the dilation procedures the samples were withdrawn also beyond the lesion. Heparin 150 U/kg was given as an anticoagulant. All patients were pretreated with 250 mg/day of aspirin. One hundred twenty patients were randomly assigned to receive 24, 48, or 72 hours of ticlopidine treatment (250 mg/twice daily). TF levels did not increase during angioplasty but there was a significantly higher TF expression in unstable than in stable patients, irrespective of the invasiveness of debulking procedures. When ticlopidine was given for 72 hours, TF levels were similar to normal laboratory values both in stable and unstable patients. This combined antiplatelet pretreatment may be of benefit in unstable angina patients, with a favorable cost/benefit ratio.
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PMID:Effect of aspirin and ticlopidine on plasma tissue factor levels in stable and unstable angina pectoris. 1107 61

The electrocardiogram (ECG) can be used for determining the presence, location and extent of jeopardized myocardium during acute coronary occlusion. Accordingly, the ECG has become essential in the treatment of patients with acute coronary syndrome (ACS). This thesis aims at optimizing the decision support, provided by the ECG, for choosing the best treatment strategy in the individual patient with ST-segment elevation acute myocardial infarction (STEMI). ECG recorded in the prehospital setting has become the standard of care in many communities, but to achieve the full advantage of this early approach it is important that the ECG is recorded from accurately placed electrodes to produce an ECG that resembles the standard 12-lead ECG. Accurate electrode placement is difficult especially in the acute setting, and we investigated an alternative lead system with fewer electrodes in easily identified positions. We showed that the system produced waveforms similar to the standard 12-lead ECG. However, occasional diagnostic errors were seen, compromising general acceptance of the system. Once the ECG has been recorded a decision regarding triage must be made on the basis of a correct ECG diagnosis. We found that trained paramedics can diagnose STEMI correctly in patients without ECG confounding factors, while the presence of ECG confounding factors decreased their ability substantially. Consequently, since many patients do present with ECG confounding factors, transmission to an on-call cardiologist for an early correct diagnosis is needed. We showed that time to pPCI was reduced by more than 1 hour by transmitting prehospital ECG to a cardiologist's handheld device for diagnosis, triage, and activation of the catheterization laboratory when needed. The optimal treatment strategy is dependent on the duration of ischemia however patient information is often inaccurate. Accordingly, it would be advantageous if the first available ECG can help identify patients who will benefit greatly from acute reperfusion therapy versus patients with modest effect. We showed that by recognizing the acuteness of the infarction process the initial ECG can identify a group of patients with no potential for myocardial salvage despite short symptom duration. Urgent transport for pPCI may then not be necessary in this group of patients, and conservative treatment may be an option. Conversely, we also identified a group of patients with a large potential for myocardial salvage with acute reperfusion therapy despite long symptom duration. We also investigated whether ST-segment elevation on the initial ECG could provide prognostic information and thereby decision support for appropriate triage. All patients regardless of ST-segment elevation seemed to have most clinical benefit from pPCI. However, only patients with the greatest amount of ST-segment elevation had a reduced mortality rate with pPCI suggesting that patients with minor infarcts may achieve similar benefit from fibrinolysis followed by transfer to angiography and PCI. Once the triage decision is settled, STEMI patients must undergo ECG monitoring and receive antithrombotic therapy for optimal prehospital care. STEMI patients transported over even short distances are in danger of developing arrhythmic complications, but appropriate treatment is available when primary ambulances are supported by physician-manned ambulances in urban areas. Prehospital antithrombotic therapy must be effective in preparing the patient for pPCI without causing bleeding. Heparin is currently the standard therapy, but we showed that the direct thrombin inhibitor bivalirudin may be an attractive alternative by causing less bleeding events, and a higher frequency of preprocedure thrombolysis in myocardial infarction (TIMI) 3 flow. After reperfusion therapy a decision regarding the need for further treatment is desirable. By determining ST-segment resolution in the post-reperfusion ECG we showed that the degree of ST-segment resolution at 90 minutes and 4 hours is important for risk stratification after fibrinolysis, but not after pPCI. Interestingly, we found that patients with compete ST-segment resolution treated with fibrinolysis had the highest risk of reinfarction. Consequently, transfer to a PCI-facility should be considered in all patients treated with fibrinolysis as the initial reperfusion therapy. Based on the findings in the present thesis we conclude that the ECG is an important tool for decision support in every step from symptom onset to post-reperfusion therapy in STEMI patients.
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PMID:The ECG as decision support in STEMI. 2238 Oct 96

Cardiovascular diseases, among all diseases, are taking the most victims worldwide. Coronary artery occlusion, takes responsibility of about 30% of the yearly global deaths in the world (Heart Disease and Stroke Statistics 2017 At-a-Glance, 2017), raising the need for viable substitutes for cardiovascular tissues. Depending on a number of factors, blocked coronary arteries are now being replaced by autografts or stents. Since the autografts, as the gold standard coronary artery replacements, are not available in adequate quality and quantity, the demand for small diameter vascular substitute comparable to native vessels is rapidly growing. Synthetic grafts have been successfully approved for developing vascular replacements but regarding the special conditions in small-caliber vessels, their use is limited to large-diameter vascular tissue engineering. The major problems associated with the vascular tissue engineered grafts are thrombosis and intimal hyperplasia. Heparin, a negatively charged natural polysaccharide has been used in fabricating vascular grafts since it prevents protein fouling on the surfaces and most importantly, impeding thrombosis. Herein, we focused on heparin, as a multifunctional bioactive molecule that not only serves as an anticoagulant with frequent clinical use but also acts as an anti-inflammatory and angiogenic regulatory substance. We summarized heparin incorporation into stents and grafts and their applicability to restrain restenosis. Also, the applications of heparinzation of biomaterials and heparin mimetic polymers and different approaches invoked to improve heparin bioactivity have been reviewed. We summarized the methods of adding heparin to matrices as they were explained in the literature. We reviewed how heparin influences the biocompatibility of the scaffolds and discussed new advances about using heparin in small-diameter vascular tissue engineering.
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PMID:The applications of heparin in vascular tissue engineering. 3250 10


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