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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Calcium channel blockade provides a logical approach to the treatment of pulmonary hypertension because these drugs exert direct vasodilator effects in the highly constricted pulmonary circulation. To determine the effectiveness of verapamil in the treatment of primary pulmonary hypertension the haemodynamic effects of the drug were evaluated in seven patients with this disorder; 10 mg was given intravenously to six patients and 120 mg orally to one patient. Verapamil produced a 20% decline in pulmonary vascular resistance and a 27% decrease in mean pulmonary arterial pressure without significant changes in systemic vascular resistance. One patient who received verapamil 480 mg orally daily for three months showed sustained haemodynamic and clinical improvement. Concomitant with its beneficial effects on the pulmonary circulation, however, verapamil produced a pronounced decrease in right ventricular stroke work index (42%) and increase in right ventricular filling pressure (50%), indicating a direct depressant effect of the drug on right ventricular function. In one patient these cardiodepressant effects were sufficiently pronounced to produce severe hypotension and cardiac arrest. In conclusion, although verapamil appears to exert preferential vasodilator effects on the pulmonary circulation, its negative inotropic effects may be particularly detrimental to patients with primary pulmonary hypertension who have pre-existing right ventricular dysfunction; hence, treatment with verapamil is not recommended in such cases.
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PMID:Detrimental effects of verapamil in patients with primary pulmonary hypertension. 674 18

Clinical experience with calcium antagonists in congestive heart failure has, to date, been mainly restricted to the use of nifedipine but there is either no or only a limited extent of information available on diltiazem and verapamil. In patients with acute and chronic congestive heart failure, single-dose administration of nifedipine was seen to lead to a decrease in systemic vascular resistance, left ventricular filling pressure and ventricular volumes as well as to an increase in stroke volume, ejection fraction and mean velocity of circumferential fiber shortening. These favorable effects could not be detected in eight patients during a three-week treatment phase with 80 mg nifedipine daily: resting blood pressure, cardiac volumes, echocardiographically-dimensions and exercise tolerance were unchanged as compared with placebo. In patients with ischemic heart disease and impaired ventricular function, in addition to an improvement in systolic function, single-dose nifedipine administration led to favorable effects on diastolic function with a shift of the diastolic pressure-volume relationship downward and to the diastolic pressure-volume relationship downward and to the left. In patients with severe aortic regurgitation, the observed increase in effective cardiac output affected by nifedipine was primarily attributable to an increase in heart rate. In the presence of an initially-elevated systemic vascular resistance, the regurgitation fraction decreased. In pulmonary hypertension, favorable hemodynamic effects have been reported after acute administration of verapamil as well as diltiazem and nifedipine. In individual cases, promising results in patients with primary pulmonary hypertension have been reported during long-term therapy with nifedipine provided that a favorable initial response could be documented.
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PMID:Calcium antagonists in heart failure. 685 66

Progressive dyspnea and syncope occurred in a young woman with primary pulmonary hypertension despite therapy with hydralazine. Abnormal pulmonary artery reactivity was documented by an additional increase in pulmonary artery pressure and pulmonary vascular resistance during exercise and after an episode of hydralazine-induced hypotension. Nifedipine reduced rest and exercise pulmonary artery pressure, pulmonary vascular resistance and right ventricular stroke work, and increased cardiac output and markedly improved exercise capacity. Reevaluation after 6 months showed persistence of the favorable hemodynamic and clinical effects. Vasodilator therapy, potentially hazardous because of effects on systemic vascular resistance, can be evaluated safely only with hemodynamic monitoring. Nifedipine may be a useful drug in selected patients with primary pulmonary hypertension.
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PMID:Hemodynamic effects of nifedipine in primary pulmonary hypertension. 685 10

The effort limitation in primary pulmonary hypertension (PPH) is thought to result from an inability to increase cardiac output with exercise. The precise mechanism, however, is unknown. We studied right ventricular (RV) and left ventricular (LV) function and interactions in 16 patients with PPH with electron beam computed tomography (EBCT) at rest and during supine bicycle exercise. RV and LV volumes and masses were measured at systole and diastole, and ejection fraction and cardiac index computed. Resting RV end-diastolic volume (215 +/- 72 ml) and mass (110 +/- 45 g) were increased, whereas stroke volume (65 +/- 26 ml) and ejection fraction (31 +/- 8%) were decreased. LV end-diastolic volume (80 +/- 31 ml) was decreased, whereas ejection fraction remained normal (66 +/- 9%). Cardiac index was at the lower limit of normal (2.26 +/- 0.72 L/min/m2). During exercise, RV end-diastolic volume was unchanged (196 +/- 63 ml, p = NS) but stroke volume (52 +/- 29 ml, p < 0.05) and ejection fraction (26 +/- 10%, p = 0.08) decreased. LV end-diastolic (52 +/- 22 ml, p < 0.001), end-systolic (17 +/- 8 ml, p < 0.001), and stroke volumes (35 +/- 20 ml, p < 0.001) decreased, whereas ejection fraction (65 +/- 15%, p = NS) and cardiac index remained unchanged (2.17 +/- 0.93 L/min/m2, p = NS). the ratio of RV/LV stroke volume at rest (1.21 +/- 1.06) increased with exercise (1.74 +/- 1.13, p = 0.09).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Understanding right and left ventricular systolic function and interactions at rest and with exercise in primary pulmonary hypertension. 785 31

The aims of this study were first to analyze pulmonary flow differences between patients with primary pulmonary hypertension (PPH) and volunteers, and second to determine whether magnetic resonance (MR) 3D Fourier encoding velocity imaging is capable of assessing hemodynamics in PPH. Pulmonary and aortic flows were quantified with MR imaging in 13 patients with PPH confirmed by right heart catheterization (RHC) within the same week and in 10 volunteers. MR pulmonary antegrade velocities, acceleration time (defined as the time from the onset of flow to the peak velocity), and arterial distensibility (maximal surface-minimal surface/minimal surface) were significantly different in patients (p < 0.05). MR pulmonary and aortic flow volumes correlated well with each other in the two populations (r = 0.98). Agreement between MR and RHC data was low: for the right cardiac output (mean difference) the 95% confidence interval was -0.88 to -0.22 L/min and for the right stroke volume 2.83 to 9.71 ml. However, the high coefficient correlations found between the two techniques showed that MR data could be used as indicators of right hemodynamics. 3D Fourier encoding-velocity sequence is a reliable noninvasive flow measurement method for the quantification of right hemodynamics in patients with PPH.
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PMID:Quantification of hemodynamics in primary pulmonary hypertension with magnetic resonance imaging. 792 39

To ascertain the role of invasive investigations in the diagnosis of primary pulmonary hypertension (PPH), 12 PPH patients underwent catheterization of the left and right heart compartments, contrast right and left ventriculography and oximetry. Compared to control values, the patients had high pressure in the pulmonary artery and right ventricle. Some of them exhibited elevated pressure in the right atrium. Pulmonary artery wedge pressure, left ventricular end-diastolic and systolic, diastolic pressure in the aorta did not differ significantly from those in the controls. Right and left ventriculography revealed an increase in the end-systolic and end-diastolic volumes of the right ventricle which diminished its stroke index and ejection fraction. The latter two were reduced in the left ventricle also. Because the procedure was well tolerated by the patients, it is recommended for PPH diagnosis and follow-up.
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PMID:[The results of catheterization and the x-ray angiographic assessment of cardiac contractility and volume in primary pulmonary hypertension]. 794 Mar 43

The neuroprotective actions of the anticonvulsant phenytoin (diphenylhydantoin, PHT) were evaluated using 3 week old primary hippocampal cultures derived from 19 day embryonic rat. When added to the culture medium prior to a hypoxic insult, PHT increased neuronal viability two-fold. Doubling extracellular Mg2+ concentration was similarly neuroprotective. In contrast, PHT was unable to protect against hypoxia-induced death in one week old cultures, nor was PHT protective against N-methyl-D-aspartate (NMDA)-induced neurotoxicity in cultures of either age. These findings suggest that non-NMDA receptor mechanisms are important in hypoxia-induced neuronal death, and may have important implications for the treatment of stroke.
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PMID:Phenytoin protects against hypoxia-induced death of cultured hippocampal neurons. 797 Feb 3

Endothelins are ubiquitously produced 21-amino-acid peptides that were discovered as an endothelial product and may play important roles in cardiovescular physiology and pathophysiology. The main endothelin produced by the endothelium is endothelin-1. The vasoconstrictor role of endothelins may participate in blood pressure elevation and vascular hypertrophy in salt-dependent models of hypertension (deoxycorticosterone acetate-salt hypertensive rats, spontaneously hypertensive rats treated with deoxycorticosterone, acetate and salt, and Dehl salt-sensitive rats), and in stroke-prone spontaneously hypertensive rats. In humans, endothelins may play important roles in moderate to severe essential hypertension, and in the hypertension of African-Americans. Endothelins may be involved in cardiac hypertrophy, and there is increasing evidence of their participation in heart failure, in which acute endothelin antagonism in humans exerts beneficial effects. Endothelin expression is enhanced in smooth muscle cells migrating into the intima of arteries in atherosclerosis, suggesting a role in atherogenesis. Endothelin may participate as a vasoconstrictor in coronary artery disease, and as a contributor to intimal proliferation in restenosis after coronary angioplasty. In patients with myocardial infarction, cardiac production of endothelin is increased, particularly in those with cardiogenic shock. There is a potential for participation of endothelins in vasospasm accompanying stroke or subarachnoid hemorrhage: in the latter, endothelin antagonism has shown beneficial effects in experimental models. In neonatal and in primary pulmonary hypertension, endothelin expression is enhanced, and in experimental models endothelin antagonism resulted in favorable responses. Systemic sclerosis is another, peripheral, form of vascular disease in which endothelin may play a role and in which endothelin antagonism may be an interesting therapeutic alternative. The pathophysiologic role of endothelins is becoming increasingly apparent in cardiovascular disease, generating interesting potential therapeutic targets for the use of endothelin antagonists or endothelin-converting enzyme inhibitors.
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PMID:Clinical significance of endothelin in cardiovascular disease. 926 47

Adrenomedullin, a potent hypotensive peptide, reduces blood pressure and pulmonary vascular resistance, and increases pulmonary blood flow. The mRNA for adrenomedullin and its receptor is highly expressed in the lung, suggesting a regulatory role for adrenomedullin in the pulmonary circulation. To investigate the clinical significance of adrenomedullin in patients with pulmonary hypertension, we studied the relationship between plasma levels of adrenomedullin and pulmonary haemodynamics. Venous, arterial and pulmonary arterial blood samples were obtained during cardiac catheterization and plasma levels of adrenomedullin were measured by specific radioimmunoassay in 33 consecutive patients with severe pulmonary hypertension (12 cases of primary pulmonary hypertension, 21 with chronic thromboembolic pulmonary hypertension; age 49+/-16 years, mean pulmonary arterial pressure 50+/-15mmHg). In addition, plasma levels of adrenomedullin were measured before and after acute nitric oxide inhalation. The changes in plasma adrenomedullin during the follow-up period of 10.3+/-4.3 months were also evaluated (n=5). Sixty-two healthy subjects served as the control group. Adrenomedullin was measured in an antecubital vein in the controls. Plasma levels of adrenomedullin were significantly higher in the patients with pulmonary hypertension than in the control subjects (10.1+/-8.7 versus 4.9+/-1.1pmol/l, P<0.01). Plasma levels of adrenomedullin, expressed as their natural logarithm, were significantly correlated with mean right atrial pressure (r=0.71, P<0.01), stroke volume (r=-0.63, P<0.01), total pulmonary resistance (r=0.60, P<0.01), mean pulmonary arterial pressure (r=0.37, P<0.05), and the natural logarithm of plasma atrial natriuretic peptide (r=0. 63, P<0.01). Plasma levels of adrenomedullin did not change significantly after nitric oxide inhalation, but significantly increased in association with the elevation of the total pulmonary resistance during the long-term follow-up period. These results suggest that plasma levels of adrenomedullin increase in proportion to the extent of pulmonary hypertension.
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PMID:Increased plasma levels of adrenomedullin in patients with pulmonary hypertension. 985 4

The endothelins (ET) are potent 21-amino-acid vasoconstrictor peptides produced in many different tissues, particularly in the endothelium of blood vessels. ET-1 is the main endothelin secreted by the endothelium, and acts in a paracrine or autocrine fashion on blood vessels by interacting with ETA or ETB receptors on smooth muscle to stimulate contraction or on ETB receptors on endothelial cells to induce the release of vasorelaxants (nitric oxide and prostacyclin). Production of ET-1 is enhanced in several experimental models of hypertension in the rat, such as sodium-sensitive forms, e.g. deoxycorticosterone acetate (DOCA)-salt hypertensive, DOCA-salt-treated spontaneously hypertensive rats (SHR) and Dahl salt-sensitive rats, as well as other models such as stroke-prone SHR, angiotensin II-infused rats and fructose-fed rats, and possibly 1-K 1C Goldblatt hypertensive rats. In contrast, SHR, 2-K 1C Goldblatt hypertensive rats and nitric oxide-deficient (L-NAME-treated) hypertensive rats do not exhibit an ET-1 component. Endothelin dependency is manifested by excessive vascular growth, particularly in small arteries, and blood pressure lowering and regression of vascular growth after treatment with endothelin antagonists. The latter may be combined ETA/ETB or selective ETA antagonists, of which several are orally active and already in clinical development. In humans, endothelin-dependent vascular tone has been shown in studies of forearm blood flow. Enhanced expression of ET-1 mRNA has been demonstrated in the endothelium of small arteries of patients with moderate to severe hypertension. In a 4-week trial the combined ETA/ETB antagonist bosentan reduced the blood pressure of essential hypertensive patients equally to enalapril. Bosentan improved hemodynamics in patients with heart failure in acute and 2-week-long studies. Endothelin antagonists also offer promise in a rapidly fatal condition, primary pulmonary hypertension. Thus, the endothelin system appears to be involved in different forms of cardiovascular disease in experimental animals and humans, and its interruption offers great promise as a new therapeutic intervention in hypertension, heart failure and other diseases.
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PMID:Endothelin and endothelin antagonists in hypertension. 988 74


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