Persistent endothelial dysfunction in calcified aortic stenosis beyond valve replacement surgery.
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Aortic Valve Stenosis↗
Biomedical subjects
T F Luscher
Publications and source records attributed to T F Luscher.
[Molecular mechanisms of endothelial dysfunction in diabetes].
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Animals↗
Renal function: the Cinderella of cardiovascular risk profile.
The presence of an altered renal function in essential hypertension, advanced heart failure (HF) and after a myocardial infarction (MI) is associated with higher cardiovascular morbidity and mortality. Indices of altered renal function (e.g., microalbuminuria, increased serum creatinine concentrations, decrease in estimated creatinine clearance or overt proteinuria) are independent predictors of cardiovascular morbidity and mortality in any of the three clinical situations. These parameters should then be routinely evaluated in clinical practice. These facts have several therapeutic implications. First, although there is no evidence-based information on the level of blood pressure that confers optimal renal protection, levels substantially lower than past recommendations are advisable. Second, hypertensive kidney damage should be prevented by early treatment of hypertensive patients, particularly those with microalbuminuria. Finally, to avoid further aggravation of high cardiovascular risk, antihypertensive agents devoid of unwanted metabolic side effects should be used for the treatment of hypertensive vascular damage. In HF, the combination of an angiotensin-converting enzyme (ACE) inhibitor and a beta-blocker seem to be the most renoprotective. Renal outcome is also improved by ACE inhibition after an MI. Finally, renal and cardiovascular outcome seem to run in parallel in all these situations.
Angiotensin-Converting Enzyme Inhibitors↗
Endothelin antagonists for hypertension and renal disease.
The endothelin system has been implicated in the pathogenesis of arterial hypertension and renal disorders. Endothelin-1, the predominant isoform of the endothelin peptide family, regulates vasoconstriction and cell proliferation in tissues both within and outside the cardiovascular system through activation of Gi-protein-coupled ET(A) and ET(B) receptors. Endothelin synthesis is regulated through autocrine mechanisms by endothelin converting enzymes, chymases, and non-endothelin converting enzyme metalloproteases. In-vitro experiments have demonstrated that endothelin-1 stimulates growth in vascular smooth muscle and in the kidney. Recent studies indicate that endothelin mRNA and protein are also increased in vivo in the kidney and vasculature in hypertension and renal disease. Studies using molecular or pharmacological inhibition of the endothelin system demonstrate that endothelin-1 contributes to the functional and structural changes associated with arterial hypertension and glomerulosclerosis, and that these effects are only in part dependent on blood pressure. These experimental studies and first clinical trials suggest that endothelin antagonists may offer therapeutic potential to reduce end-organ damage in diseases associated with vascular remodeling and renal injury.
Amino Acid Sequence↗
Doppler characterization of left ventricular diastolic function in cardiac amyloidosis.
Sixty-four patients with primary systemic amyloidosis-53 with two-dimensional echocardiographic features of cardiac involvement (Group I) and 11 without cardiac involvement (Group II)--underwent Doppler echocardiographic assessment of left ventricular diastolic function. Pulsed wave Doppler recordings of left ventricular inflow velocities and pulmonary vein flow velocities with respiratory monitoring in these patients were compared with findings in a normal group. Patients in Group I showed striking abnormalities of left ventricular diastolic filling when classified into subgroups by mean left ventricular wall thickness: early greater than 12 but less than 15 mm; advanced greater than or equal to 15 mm. In early amyloidosis, relaxation was abnormal, with decreased peak early velocity (75 +/- 20 versus 86 +/- 16 cm/s; p less than 0.01), increased late velocity (71 +/- 22 versus 56 +/- 13 cm/s; p less than 0.01), decreased early to late velocity ratio (1.2 +/- 0.6 versus 1.6 +/- 0.5; p less than 0.01) and prolonged isovolumic relaxation time (87 +/- 15 versus 73 +/- 13 ms; p less than 0.01) compared with normal values. In advanced amyloidosis, there was a restrictive filling pattern with a markedly shortened deceleration time (148 +/- 50 versus 199 +/- 32 ms; p less than 0.001), decreased pulmonary vein peak systolic flow velocity (34 +/- 16 versus 54 +/- 12 cm/s; p less than 0.01) and increased diastolic flow velocity (55 +/- 20 versus 44 +/- 12 cm/s; p less than 0.01) compared with normal values. Group and the subgroup with early amyloidosis had similar flow velocity patterns. Thus, this study documents that in cardiac amyloidosis, a spectrum of diastolic filling abnormalities exists; the restrictive filling pattern is seen only in the advanced stages.
Amyloidosis↗
Endothelium-dependent responses in human blood vessels.
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Blood Vessels↗
Serotonin reduces coronary flow in the isolated heart of the spontaneously hypertensive rat.
Serotonin may cause vasodilatation or vasoconstriction. In hypertension the vasoconstrictor effects of serotonin predominate. Experiments were designed to study the effects of serotonin on coronary flow in isolated hearts of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. The hearts were paced at constant rate and perfused by the Langendorff technique at constant pressure (75 cmH2O). In WKY rats serotonin (10-9 to 10-5 mol/l) caused concentration-dependent increases in coronary flow and a decrease in cardiac performance. In SHR, the monoamine caused concentration-dependent, partially reversible decreases in coronary flow, and a marked decrease in cardiac performance. The inhibitor of cyclo-oxygenase indomethacin prevented the decrease in coronary flow and cardiac performance caused by serotonin in SHR, but did not affect the increase in coronary flow in WKY rats. These experiments suggest that in the coronary circulation of SHR the response to serotonin is shifted from vasodilatation to vasoconstriction. The mediator of this vasoconstriction is probably a product of cyclo-oxygenase.
Animals↗
Autoregulation and vascular reserve in the coronary circulation of the spontaneously hypertensive rat.
Hypertension causes structural and functioning changes in blood vessels. Experiments were performed in isolated hearts of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats perfused by the Langendorff technique. Spontaneously hypertensive rats had significantly higher left heart to body weight ratios than WKY rats, indicating left ventricular hypertrophy. Coronary flow per unit cardiac mass was lower and vascular resistance was higher at 75 cm H2O perfusion pressure in SHR. This difference was maintained during maximal vasodilatation. In WKY rats, but not in SHR, autoregulation of flow was observed in the pressure range 75-150 cm H2O due to an increase in coronary vascular resistance. After maximal vasodilatation the pressure-flow relationship was linear in SHR and WKY rats, but less steep and shifted to the right in SHR. We conclude that structural adaptations of the coronary circulation in SHR lead to decreased coronary vascular reserve and a loss of autoregulation in the normal blood pressure range.
Animals↗