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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A highly-standardized plate method was used to study fibrinolytic profiles in 14 patients with essential hypertension and 245 normotensive healthy control subjects. Compared with the normotensive group, the group with essential hypertension showed a defect in fibrinolysis, as evidenced by a significant increase in the mean level of inhibitor of plasminogen activation, and a subset of the hypertensive patients also showed a significant decrease in the mean level of vascular plasminogen activator. There were no significant differences between the two groups in relation to plasma fibrinogen level, total fibrinolytic activity and plasmin inhibitor. The alterations in inhibitor of plasminogen activation and vascular plasminogen activator in the patients with essential hypertension may reflect a defect in the fibrin-clearing mechanism and, perhaps, contribute to the vascular complications of hypertension.
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PMID:Abnormalities of fibrinolysis in essential hypertension. 624 55

The distribution of mRNA coding for the members of the wide-spectrum proteinase scavenging system of the alpha-2-macroglobulin family was examined in the mouse: Alpha-2-macroglobulin (MAM), the murinoglobulins (MUG), the alpha-2-macroglobulin receptor (alpha 2MR) and the receptor associated protein, the heparin binding protein-44 (alpha 2MRAP/HBP-44), a component of unknown function. The results demonstrate that MAM is expressed in the mouse embryo exclusively in the liver and not before day 13 of gestation. MUG mRNA was never detected during embryogenesis. On the other hand, both the alpha 2MR and the alpha 2MRAP/HBP-44 messages were present throughout all embryonal stages examined. The distribution of the alpha 2MR mRNA was widespread in most tissues, with stronger signals observed in developing mouse brain, in whisker follicles and in the perifollicular mesenchyme, in lung, liver, kidney, intestine and placenta. The alpha 2MRAP/HBP-44 mRNA was detected predominantly in brain, lung, liver, kidney and placenta. Interestingly, within each tissue the cellular distribution of the alpha 2MR and alpha 2MRAP/HBP-44 mRNA was quite different with the most remarkable extremes observed in kidney and in placenta. The implication of these observations for receptor expression and function are discussed. Northern analysis of adult tissues extended these observations: major signals for MAM and MUG were seen only in liver, while the expression of the alpha 2MR and the alpha 2MRAP/HBP-44 was widespread with highest levels of the 15-kb alpha 2MR mRNA in liver. Kidney was the most abundant source of alpha 2MRAP/HBP-44 mRNA with the 1.8- and 3.6-kb mRNAs, derived from the same gene by alternative mRNA splicing, present in nearly constant ratios in most tissues, except in testis. The notable absence of expression of MAM in the first half of gestation indicates that during this period the receptor is scavenging for proteinases complexed to MAM derived from the maternal circulation or is being used for endocytosis of the other documented ligands, such as plasminogen activator complexes or apolipoprotein E-containing lipoprotein particles.
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PMID:Distribution of mRNA coding for alpha-2-macroglobulin, the murinoglobulins, the alpha-2-macroglobulin receptor and the alpha-2-macroglobulin receptor associated protein during mouse embryogenesis and in adult tissues. 751 54

Among endothelial secretogogues prostacyclin (PGI2), nitric oxide (NO) and tissue plasminogen activator (t-PA) play a crucial role in maintaining thromboresistance, tone and structure of the vascular wall. Most receptor agonists, such as B2 kinin receptor agonists, or shear force produce a coupled release of all three secretogogues, and therefore interactions between them are to be expected. Essentially, PGI2 is a platelet suppressant, NO a vasodilator and t-PA a fibrinolytic agent. These and other properties of endothelial secretogogues supplement each other in protecting the cardiovascular system from injuries. It is not surprising that disturbances of the secretory function of endothelial cells are associated with atherosclerosis, diabetes, thrombosis or hypertension. Traditionally, PGI2, NO, t-PA or their substitutes are used individually for the treatment of peripheral arterial disease, angina pectoris or acute myocardial infarction. In light of recent findings, their joint administration can be advocated. For instance, NO donors will potentiate platelet-suppressant action of PGI2 analogues, whereas exogenous PGI2 or TXA2 synthase inhibitors (i.e. following increase in endogenous PGI2) will abolish a paradox of prothrombotic action of t-PA or streptokinase. The replacement therapy with PGI2, NO or t-PA should match as closely as possible the physiologically coupled release of these secretogogues.
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PMID:Interactions between endothelial secretogogues. 754 32

Despite effective antihypertensive therapy, essential hypertension is still associated with considerable residual risk of cardiovascular complications. The aim of the present study was to investigate the state of the endogenous fibrinolytic system in young subjects with borderline hypertension. Thirty-nine young (age, 24 to 34 years) male subjects with borderline hypertension (systolic BP [SBP] 140 to 160 mm Hg and/or diastolic BP [DBP] 85 to 95 mm Hg) and 17 normotensive control subjects (age, 22 to 31 years; SBP 110 to 130 and DBP 60 to 80 mm Hg) were recruited from a population screening. Plasma levels of tissue-type plasminogen activator (t-PA) antigen and activity and plasminogen activator inhibitor 1 (PAI-1) antigen were determined at rest and in response to a venous occlusion test. Borderline-hypertensive subjects had metabolic and anthropometric characteristics similar to normotensive individuals. In comparison with normotensive subjects, borderline-hypertensive subjects had higher plasma concentration of t-PA antigen both at rest and after venous occlusion but similar levels of t-PA activity or PAI-1 antigen. The increase in t-PA antigen and activity in response to venous occlusion was significantly greater in borderline-hypertensive subjects than in normotensive control subjects (P < .0001 and P = .003, respectively). In stepwise regression analyses, 24-hour mean arterial pressure emerged as the single most powerful predictor of t-PA antigen levels, but body mass index was the most important determinant of t-PA activity and PAI-1 antigen. However, PAI-1 was explained by both body mass index (partial r = .48, P < .001) and 24-hour mean arterial pressure (partial r = .29, P < .05). Thus, early hypertension may be associated with significant alterations in endogenous fibrinolysis.
Hypertension 1995 Nov
PMID:Enhanced levels of tissue-type plasminogen activator in borderline hypertension. 759 Oct 20

Ten days after surgical treatment of a gastric perforation a 70-year-old woman developed progressive dyspnoea and hypertension without any signs of deep vein thrombosis. Emergency echocardiography revealed acute cor pulmonale with a dilated right atrium and ventricle, as well as paradoxical ventricular septal motion. In addition it demonstrated an elongated, extremely mobile thrombus stuck in a patent foramen ovale with most of it floating in the right atrium, the remainder in the left atrium. Within 2 hours of the ultrasound examination she went into fulminant pulmonary embolism with circulatory arrest and paradoxical embolization from the atria to the brain, after which the intraatrial thrombus was no longer detectable. She was successfully resuscitated and thrombolysis was immediately started with tissue-plasminogen activator (100 mg over 90 min), with ensuing stabilization of the circulation. The patient was gradually weaned off the ventilator over the following few days, but she died 10 days after the resuscitation from the severe cerebral damage.
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PMID:[Transient thrombus in patent foramen ovale with pulmonary and paradoxical embolization]. 824 45

Spontaneous coronary artery dissection is a rare cause of acute myocardial infarction. It usually occurs in relatively young patients and is frequently found at autopsy. Because of the low incidence, the treatment of choice for spontaneous coronary artery dissection is still not settled. Here the authors report a sixty-six-year-old woman with coronary lesions judged as spontaneous coronary artery dissection. She presented with chest pain. Under diagnosis of acute inferior myocardial infarction, she was treated with recombinant tissue-type plasminogen activator. Coronary arteriography performed two weeks later revealed a dissection involving a long segment of right coronary artery. The left coronary arteries and uninvolved portion of right coronary artery were smooth and patent. She suffered no hypertension and gave no definite history of trauma. This patient was treated medically with aspirin, isosorbide dinitrate, and metoprolol and remained in stable condition after a follow-up period of six months.
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PMID:Spontaneous coronary artery dissection in an elderly woman with acute inferior myocardial infarction. A case report. 766 90

Parenchymatous intracerebral hemorrhage (ICH) is a serious, infrequent complication of thrombolytic therapy for acute myocardial infarction. We studied the clinical and radiologic features, manner of presentation, associated factors, and temporal course in 23 patients with ICH associated with 150 mg or 100 mg recombinant tissue-type plasminogen activator (rt-PA) and heparin therapy for acute myocardial infarction in the Thrombolysis in Myocardial Infarction (TIMI) II Pilot and Randomized Clinical Trial. In TIMI II, 13 of the 23 ICH patients developed or maintained systolic blood pressure > or = 160 mm Hg or diastolic blood pressure > or = 90 mm Hg during the rt-PA infusion and before the onset of neurologic symptoms. Six patients (26%) had life-threatening ventricular arrhythmias, five before onset of neurologic symptoms. A decreased level of consciousness was the earliest neurologic abnormality in 15 (65%) and the most common initial physical finding (in 19, or 82%). Onset was usually gradual (70%), but time to maximal deficit was frequently (61%) within 6 hours of onset. The locations of the primary ICH sites were lobar in 16 (70%), thalamic in four (17%), and brainstem-cerebellum in three (13%), but the putamen was never the primary site. Multiple lobar hemorrhages occurred in six cases (26%). The timing and size of ICH was similar among patients treated with 150 mg rt-PA and 100 mg rt-PA. Brain CT demonstrated an arteriovenous malformation in one case. Four patients had hypofibrinogenemia, which was profound in three patients. Pathologic findings were available for five patients. Of these, three patients had cerebral amyloid angiopathy, and one had hemorrhagic transformation of an ischemic cerebral infarction found at autopsy. We conclude that ICH following rt-PA and heparin therapy for acute myocardial infarction presents as a distinctive clinical syndrome. Intracerebral bleeding after combined thrombolytic and antithrombotic therapy may be associated with cerebral amyloid angiopathy and other vascular lesions. Acute or persistent hypertension before or during rt-PA infusion, life-threatening ventricular arrhythmias, and hypofibrinogenemia, either alone or in combination, may play roles in some cases. Care should be exercised when considering thrombolytic therapy for patients with risk factors for ICH.
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PMID:Clinical features and pathogenesis of intracerebral hemorrhage after rt-PA and heparin therapy for acute myocardial infarction: the Thrombolysis in Myocardial Infarction (TIMI) II Pilot and Randomized Clinical Trial combined experience. 772 50

At 12 centers, 395 patients, including 288 men (73%) and 107 women (27%) with acute myocardial infarction (AMI), were prospectively randomized to treatment with tissue plasminogen activator (t-PA) or primary percutaneous transluminal coronary angioplasty (PTCA). Compared with men, women were older (65.7 vs 57.7 years, p < 0.0001), more often had diabetes mellitus (19% vs 10%, p = 0.03), systemic hypertension (54% vs 39%, p = 0.005), prior congestive heart failure (5% vs 0%, p = 0.002), and presented later after symptom onset (229 vs 174 minutes, p = 0.0004). The in-hospital mortality in women was 3.3-fold higher than men (9.3% vs 2.8%, p = 0.005). After adjustment for comorbid baseline characteristics, however, only advanced age independently correlated with mortality. Among t-PA-treated patients, mortality was significantly higher in women than in men (14.0% vs 3.5%, p = 0.006). Intracranial hemorrhage after t-PA was also more common in women than in men (5.3% vs 0.7%, p = 0.037). In contrast, women and men had similar in-hospital mortality after primary PTCA (4.0% vs 2.1%, respectively, p = 0.46). No intracranial bleeding occurred in PTCA-treated patients. A univariate trend was present for reduced in-hospital mortality in women treated with PTCA rather than t-PA (4.0% vs 14.0%, p = 0.07). By multiple logistic regression analysis of 15 clinical variables, treatment with PTCA rather than t-PA, as well as younger age, were independently predictive of in-hospital survival in women.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of in-hospital outcome in men versus women treated by either thrombolytic therapy or primary coronary angioplasty for acute myocardial infarction. 774

We have recently shown that mental stress increases local net release of tissue-type plasminogen activator (t-PA) across the forearm vascular bed. However, the mechanisms responsible for the t-PA release in man during stress are undefined. To study the effects of endothelial cell receptor stimulation and fluid shear stress we used the perfused forearm model to characterize the in vivo tissue plasminogen activator (t-PA) response in man to methacholine (Mch) and sodium nitroprusside (SNP), at doses calculated to cause similar degrees of vasodilation. The study was performed in 7 healthy young men (age 22-24 yrs) without hypertension, diabetes mellitus, or hypercholesterolemia. Each subject received double-blind step-wise i. a. infusions of Mch (0.1-0.8-4.0 micrograms/min) and SNP (0.5-2.5-10 micrograms/min) in randomized order. Each dose step was infused for 5 min. Forearm blood flow was assessed by plethysmography. Net release/uptake was expressed as the product of arterio-venous concentration gradient and forearm plasma flow. At pre-infusion baseline, there was a significant net release of t-PA antigen of approximately 0.9 ng x min-1 x 100 ml-1 and t-PA activity of 3.5 fmol x min-1 x 100 ml-1 across the forearm. I.a. infusion of Mch and SNP increased forearm blood flow from 1.9 to 14.9 and from 1.8 to 12.1 ml x min-1 x 100 ml-1, respectively (Mch vs SBP N.S.).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Release of tissue-type plasminogen activator in response to muscarinic receptor stimulation in human forearm. 787 38

Thrombolytic therapy improves outcome in patients with myocardial infarction but is associated with an increased risk of intracranial haemorrhage. For some patients, this risk may outweigh the potential benefits of thrombolytic treatment. Using data from other studies, we developed a model for the assessment of an individual's risk of intracranial haemorrhage during thrombolysis. Data were available from 150 patients with documented intracranial haemorrhage and 294 matched controls. 49 patients with intracranial haemorrhage and 122 controls had been treated with streptokinase, whereas 88 cases and 148 controls had received alteplase. By multivariate analysis, four factors were identified as independent predictors of intracranial haemorrhage; age over 65 years (odds ratio 2.2 [95% Cl 1.4-3.5]), body weight below 70 kg (2.1 [1.3-3.2]), hypertension on hospital admission (2.0 [1.2-3.2]), and administration of alteplase (1.6 [1.0-2.5]). If the overall incidence of intracranial haemorrhage is assumed to be 0.75%, patients without risk factors who receive streptokinase have a 0.26% probability of intracranial haemorrhage. The risk is 0.96%, 1.32%, and 2.17% in patients with one, two, or three risk factors, respectively. We present a model for individual risk assessment that can be used easily in clinical practice.
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PMID:Individual risk assessment for intracranial haemorrhage during thrombolytic therapy. 790 5


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