Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During the acute phase of myocardial infarction, the generation of thrombin is reflected in the sudden rise of fibrinopeptide A (FPA) and the thrombin-antithrombin III (TAT) complex in blood. We have systematically determined the FPA and TAT plasma concentrations over a period of 14 days after acute myocardial infarction in 100 patients. Mean levels of both thrombin markers were the highest on admission, remained elevated over the following few days, and then gradually declined after day 5. Still, by the end of the first week two thirds of the patients had distinctly elevated TAT and FPA levels, and by the end of the second week such an abnormality was present in half of them. Continuous intravenous heparin infusion at a dose of 20,000 units/day, administered for 1 week to patients who had either received (n = 21) or not received (n = 17) streptokinase, led to a significant depression (p less than 0.05) of thrombin markers over the first 48 hours, an effect that did not persist over the subsequent days of treatment. In patients not assigned to heparin treatment, those in heart failure had significantly (p less than 0.05) higher mean TAT and FPA values on days 3, 5, and 7 compared with patients in whom heart failure was absent. Infarct extension, pulmonary embolism, and death were also associated with a rise in one or both thrombin markers, often preceding the onset of clinical symptoms. Thrombinogenesis was not accompanied by changes in mean plasma concentrations of prothrombin, antithrombin III, or alpha 2-macroglobulin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Persistent generation of thrombin after acute myocardial infarction. 157 16

The hemostatic alterations in two adult patients who were supported by left ventricular assist devices (LVADs) because of postcardiotomy heart failure were evaluated. In both patients, fibrinopeptide A and thrombin-antithrombin III complex increased markedly during the first several days, and thereafter decreased moderately but remained above normal over the entire procedure. Furthermore, fibrinopeptide B beta 15-42 and alpha 2 plasmin inhibitor-plasmin complex were also markedly increased over the entire course of LVAD treatment. These data show that the LVAD system strongly activates both the coagulation and the fibrinolytic system, even when thromboembolic or bleeding complications are not clinically evident. Furthermore, the decrease in physiological coagulation inhibitors, especially protein C, indicates that these factors are activated and consumed during LVAD treatment. Because protein C is important in regulating the coagulation cascade during LVAD treatment, exhaustion of this system might result in thromboembolic complications during LVAD treatment.
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PMID:Hemostatic alterations caused by ventricular assist devices for postcardiotomy heart failure. 199 93

Serial pulmonary angiography with videodensitometry was performed in 18 rats with pulmonary damage caused by administration of a fibrinolysis inhibitor, tranexamic acid (200 mg/kg body weight injected intraperitoneally) and bovine thrombin (500 NIH/kg body weight injected into the right femoral vein). The mean transit time (MTT) was calculated from videodensitometry, the observed area of interest consisting of approximately one-third of the right lung, including both central and peripheral parts. The impact of the pulmonary damage was analysed by morphologic methods and correlated to MTT. Although a pressure rise presumably occurred in the pulmonary circulation, no change in MTT was found after induction of pulmonary damage, indicating opening of actual and potential anastomoses between pulmonary arterioles and venules to serve as by-pass portions and as a safety-valve mechanism for the capillary bed and the right heart, respectively. Another explanation to unchanged MTT may be opening of resting capillary beds. Two rats with very severe pulmonary damage showed prolonged MTT. These rats may have suffered from cardiac failure.
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PMID:Videodensitometry in rats with pulmonary damage due to microembolism. 408 73

The Gaboon viper has acquired an impressive reputation which is at least partly unfounded. This handsome animal with such striking features is undoubtedly docile which accounts for the very low incidence of bite amongst humans. There are only six detailed clinical reports on the effect of bite and these are summarized in the review. The viper does indeed produce prodigious amounts of venom, but the toxicity, weight for weight, is rather low compared to other poisonous snakes. Venom extractions have been carried out on four snakes over a 13-year-period and the effects of this venom have been studied in a variety of experimental animals. Systemic envenomation is characterized by immediate abrupt hypotension, subsequent cardiac damage and dyspnoea. The individual venom components responsible for these effects have not been isolated but it seems likely that the two enzymes which have been studied extensively (phospholipase A2 and the thrombin-like enzyme, gabonase) do not contribute significantly to lethality. We propose three principal activities which give rise to the major signs of systemic envenomation. Haemorrhagin; causing widespread damage to microvasculature which leads to the pulmonary oedema and hence dyspnoea, and locally causes blistering. Cardiotoxin; a long-acting material causing cardiac muscle damage, arrhythmia and ultimately cardiac failure. Peripheral vasodilator; a short acting effect, operating either locally via bradykinin formation and/or unknown peptides or centrally on the vasomotor centre.
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PMID:The Gaboon viper (Bitis gabonica): its biology, venom components and toxinology. 639 43

The myocardium of 37 rabbits with a fulminant (Group 1) and acute (Group 2) course of experimental acute pulmonary heart of vascular genesis produced by intravenous administration of thrombin in subcutaneous administration of histamine was studied. The control consisted of 9 hearts of rabbits sacrificed by intravenous novocain injection. Combined methods were used to examine the myocardium, including special staining methods suitable for detection of early cardiomyocyte damage, polarization and electron microscopy, histoenzymological methods, and histostereometry. The volumetric density of focal alterations in comparison of the results between groups both for the heart as a whole and for both its parts was found to be statistically significantly higher than that in the controls. Similar results were obtained in the right to left ventricle ratio. No significant differences in the values compared were found in the controls. The volumetric density of focal lesions reached the maximum values in Group 2 by 24 hours in the right parts. The results indicate that the alterative form of cardiac insufficiency underlies sudden death in acute pulmonary heart of the vascular genesis.
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PMID:[Structural and metabolic changes in the contractile myocardium in experimental acute pulmonary heart disease of vascular origin]. 715 37

The authors have previously demonstrated that urotensin I, a peptide derived from the urophysis of bony fish, reduced arterial blood pressure of anesthetized dogs by selective dilation of the mesenteric vascular bed. In the present experiments, intravenous infusions of urotensin I produced a sustained increase in cardiac output and decrease in peripheral resistance. The magnitude of the hypotensive response and of reflex effects on the heart appeared to be limited quantitatively by the unique mechanism of action. Coronary artery flow was maintained in spite of a decrease in coronary filling pressure, presumably as a consequence of coronary autoregulation and the increased cardiac output. No direct cardiac effects were observed on close-arterial injection into a coronary artery. An agent with these characteristics which will decrease left ventricle afterload is of interest in the management of myocardial failure and possibly of cardiogenic shock. In dogs in which minimal myocardial injury was produced by injection of thrombin into a coronary artery, intravenous infusions of urotensin I restored minimal but statistically significant elevations in right and left ventricular end-diastolic pressures to preinsult levels.
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PMID:Use of a specific mesenteric vasodilator peptide, urotensin I, to reduce afterload in the dog. 723 39

Endothelins (ET) are a family of peptides with potent biological properties. Endothelial cells produce exclusively ET-1 while other tissues produce ET-2 and ET-3. The production of ET requires an increase in intracellular Ca2+. This increase can be induced by physical chemicals (i.e. hypoxia) or receptor-operated stimuli (i.e. thrombin, angiotensin II, arginine vasopressin, transforming growth factor beta 1, interleukin-1). Most of ET is released abluminally towards vascular smooth muscle and less luminally. The main vascular effect of ET are vasodilation (transient), profound and sustained vasoconstriction as well as proliferation of vascular smooth muscle. These biological effects are mediated by distinct receptors. Three ET receptors have been cloned, i.e. ETA-, ETB- and ETC-receptors. In vascular tissue ETA-receptors are expressed on vascular smooth muscle and responsible for vasoconstriction. ETB-receptors are expressed on endothelium and linked to nitric oxide and/or prostacyclin release. Activation of these receptors explains the transient vasodilation with intraluminal application of ET. Vascular smooth muscle cells can express ETB-receptors which contribute to ET-induced vasoconstriction particularly at lower concentrations. The role of the recently cloned ETC-receptor in the vasculature is still uncertain. ET production is increased (as judged from circulating plasma levels) in vascular disease and atherosclerosis in particular, in myocardial infarction and heart failure, pulmonary hypertension and renal disease. ET production is increased in arterial hypertension remains controversial. Non-peptidic ET antagonists have been developed which either block ETA- receptors or ETA- and ETB-receptors simultaneously. The advantage of ETA-receptors is that they leave the endothelium-dependent vasodilation to ET (via ETB-receptor) intact. However, ETB-mediated contraction remains unaffected by these antagonists. In contrast ETA-/ETB-antagonists fully prevent ET-induced vasoconstriction, however, they also inhibit the endothelial effects of the peptide. ET antagonists interfere with the effects of ET in isolated vascular tissue (including that obtained from humans) as well as in vivo. In humans, ETA as well as ETA-/ETB-antagonists inhibit endothelin-induced vasoconstriction. Hence in summary ET are a family of potent peptides with profound effects in the vasculature. Several studies suggest a role of ET in cardiovascular disease. The newly developed ET-antagonists are potent and selective tools to delineate the (patho-)physiological roles of ET and may become a new class of cardiovascular drugs.
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PMID:Endothelin and endothelin antagonists: pharmacology and clinical implications. 771 86

Assays which detect the release of platelet-specific proteins and of peptides during thrombogenesis and are considered markers of activation of platelets and the coagulation system have recently been developed. This study was designed to utilize these haemostasis-related markers to test the hypothesis that a prethrombotic state is related to the presence, aetiology and severity of heart failure. Seventy patients with heart failure were evaluated and data were compared with 36 normal volunteers and 41 patients with coronary artery disease without heart failure (CAD). Thrombogenesis was documented using assays which measure platelet function, thrombin activity and fibrinolysis. Platelet function was measured by determining plasma concentrations of platelet factor 4 (PF4) and beta-thromboglobulin (BTG). Thrombin-antithrombin III complexes (TAT) and fibrinopeptide A (FPA) were determined to evaluate thrombin activity. Fibrinolytic activity was assessed by measuring D-Dimer levels. Patients with heart failure, when compared to normals, had increased plasma levels of BTG (89 +/- 62 IU.ml-1 vs 50 +/- 59 IU.ml-1, P < 0.01), TAT (4.6 +/- 4.3 micrograms.l-1 vs 2.3 +/- 0.64 micrograms.l-1, P < 0.005), and D-Dimer levels (506 +/- 444 IU.ml-1 vs 191 +/- 144 IU.ml-1, P < 0.0001). Patients with heart failure, when compared to the CAD group, had increased plasma levels of D-Dimer (506 +/- 444 ng.ml-1 vs 191 +/- 144 ng.ml-1, P < 0.05). Aetiology of heart failure did not affect these measurements. Patients with severe heart failure, as determined by high plasma norepinephrine concentration or low ejection fraction, were more likely to have activation of platelets and the coagulation system.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Platelet function, thrombin and fibrinolytic activity in patients with heart failure. 844 96

Endothelin-1 is a recently discovered peptide mainly released from endothelial cells. Hypoxia and ischemia as well as numerous factors such as angiotensin 11, thrombin and transforming growth factor beta 1 stimulate the formation of the peptide. On the other hand the synthesis of endothelin is inhibited by nitric oxide and atrial natriuretic peptide via the formation of cyclic guanosine monophosphate. Released from endothelial cells endothelin-1 mediates transient vasodilation followed by a profound and longlasting vasoconstriction. Endothelin is also a mitogen for smooth muscle proliferation. Endothelins exert their biological effects via activation of specific receptors. Two different receptors have been cloned from mammalian tissues (ET(A) and ET(B) receptors). On vascular smooth muscle cells both receptors mediate contractions. Endothelial cells only express ET(B) receptors linked to the formation of nitric oxide and/or prostacyclin formation. Increased plasma concentrations of endothelin-1 have been described in a variety of diseases such as pulmonary hypertension, arteriosclerosis, renal failure, acute coronary syndromes, heart failure, migraine and vascular diseases. Recently an increasing number of endothelin receptor antagonists have been synthetized, which have been shown to inhibit endothelin-mediated vasoconstriction. Clinical studies are now ongoing to elucidate the pathophysiologic role of endothelin and the potential benefit of the blockade of the system in different disease states.
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PMID:Endothelin and endothelin antagonists: potential role in cardiovascular and renal disease. 873 56

Left ventricular assist devices have provided successful supportive therapy for patients awaiting cardiac transplantation for extended periods of time. Although thromboembolic events have complicated support with these devices, the HeartMate left ventricular assist device developed by Thermo Cardiosystems, Inc., Woburn, Massachusetts, was specifically designed with a textured blood-contacting surface to minimize this risk. Clinical experience with this device has been encouraging, inasmuch as minimal thromboembolic complications have occurred despite the absence of anticoagulation. The coagulation and fibrinolytic pathways in these individuals were investigated to better understand the hematologic status of patients treated with the Thermo Cardiosystems device. Despite apparently normal prothrombin and activated partial thromboplastin times, as well as platelet counts, evidence of significant thrombin generation and fibrinolysis was present. To eliminate underlying cardiac failure as the responsible factor for these abnormalities, we made similar measurements in patients with end-stage heart failure who were not supported by an assist device or anticoagulation. These measurements revealed no evidence of thrombin generation or fibrinolysis. These data demonstrate that patients supported with a left ventricular assist device, while successfully sustained without systemic anticoagulation, nevertheless have evidence of activation of coagulation. These phenomena appear to be related to the presence of the device rather than to the underlying cardiac abnormalities. Although procoagulant and fibrinolytic pathways are apparently balanced in these patients, these data underscore the potential for the development of bleeding or thrombosis in clinically relevant settings.
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PMID:Activation of coagulation and fibrinolytic pathways in patients with left ventricular assist devices. 887 37


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