[Effect of noradrenaline and angiotensin on blood pressure and cerebral circulation in dogs, following administration via the vertebral artery].
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Angiotensin II↗
Biomedical subjects
L Wouters
Publications and source records attributed to L Wouters.
Normothermic ischemic cardiac arrest in the isolated working rabbit heart: effects of dl-nebivolol and atenolol.
The effect of pretreatment with selective beta 1-adrenoceptor blockers (dl-nebivolol or atenolol) on myocardial mechanical activity, mitochondrial function, morphology, and calcium cytochemistry was studied during normothermic ischemic arrest and reperfusion of isolated working rabbit hearts. The hearts subjected to 25 min of ischemia followed by 30 min of post-ischemic reperfusion showed typical signs of severe myocardial ischemic damage. The ultrastructural changes showed a good relation with the changes in mechanical activity and mitochondrial function. To determine whether these changes could be prevented or reduced by beta 1-adrenoceptor blockade, dl-nebivolol or atenolol (0.62 mg/liter) was added to the perfusate 30 min before the induction of ischemia. The results showed that dl-nebivolol exerted a protective effect on recovery of mechanical activity, on mitochondrial function during reperfusion as well as on the ultrastructure as examined at the end of the reperfusion period. On the other hand, atenolol failed to protect the myocardium against ischemia-reperfusion damage in the isolated working rabbit heart.
Adrenergic beta-Antagonists↗
Sabeluzole stabilizes the neuronal cytoskeleton.
There is growing evidence that cytoskeletal instability of neuronal cells is an important step towards tangle formation and subsequent functional disconnection in the AD brain. Sabeluzole, a new drug in clinical trials for Alzheimer's disease (AD), has been shown to slow down the clinical progression of the disease. In a search for the mechanism of action of this compound, the effect of sabeluzole on the neuronal cytoskeleton was investigated. Previous studies have shown that in human TR14 neuroblastoma cells and in rat hippocampal neurons a hyperstimulating medium of kinase activators leads to induction of aberrant tau phosphorylation followed by neurotoxicity. This report documents the attenuation of this neurotoxicity by sabeluzole. By selective permeabilization procedures and quantitative immunocytochemistry we show that the compound is found to preferentially increase the fraction of polymerized tubulin. Evidence is presented that the compound differentially modulates a nocodazole-induced depolymerization in contrast to a cold-induced depolymerization. In the mouse, N4 neuroblastoma cells sabeluzole decreases the spontaneous retraction frequency of neurites and lowers the lateral mobility of the cells. We, therefore, propose that sabeluzole exerts its neuroprotective effect by a stabilization of the neuronal cytoskeleton and that this mechanism provides a completely new approach for treatment in Alzheimer's disease.
Animals↗
Long-term patency of the aortofemoral Dacron graft. A graft limb related study over a 25-years period.
Graft limb patency was studied retrospectively in a consecutive series of 912 patients (1605 limbs), who received an aorto(bi)femoral Dacron graft for occlusive disease over a 25 years period (1963-1987). The mean follow-up for the series was 5.35 years (range 1 month to 23 years) and 18.5% of the patients were followed for at least 10 years. Primary patency decreased progressively to 83% at 10 years and 77% at 15 years. It was significantly improved to 90% (at 10 years) and 84% (at 15 years) by means of operative thrombectomy (secondary patency). Factors influencing patency (univariate analysis) were (1) concomitant femoropopliteal occlusive disease, (2) the site of the femoral anastomosis and (3) the date of the operation. Multivariate analysis in relation to the femoral anastomosis stressed the importance of profunda femoris artery disease and the date of operation. It is concluded that the negative effects of concomitant superficial femoral artery disease may be completely relieved by an adequate profundaplasty. Furthermore the substantial progress, we documented over the years of the study, supports our view that aortofemoral reconstruction may also be offered as the solution of choice to patients with milder forms of claudication.
Analysis of Variance↗
Erbulozole (P.I.N.N.) (R 55 104) encapsulated into cyclodextrins: has it a combined antitumoral and radioprotective potential?
The clinically applicable formulation of the microtubule inhibitor erbulozole (R 55 104), dissolved into an aqueous hydroxypropyl-beta-cyclodextrin solution (designated as R 55 104-CYCLO), exerts a similar effect on growth delay of subcutaneous MO4 fibrosarcomas in mice, with or without 10 Gy gamma-irradiation given locally to the tumors 2 h later, compared to R 55 104 in water. The drug concentration can be reduced from 80 mg/kg to 5 mg/kg without affecting the activity of this particular drug-radiation combination. Furthermore, 80 mg/kg R 55 104-CYCLO show a radioprotective effect when given 2 h before total body irradiation of non-tumor bearing mice. A radiation dose of 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 Gy respectively was given resulting in a LD50(30) of 5.97 Gy for the irradiated mice and 7.65 Gy for the drug-radiation treated animals (Dose Effect Factor = 0.78). Therapeutic implications of both observations are discussed.
Animals↗
Beta-blockade in the ischemic reperfused working rabbit heart: dissociation of beta-adrenergic blocking and protective effects.
The cardioprotective effects of the beta-blocking drugs (dl-nebivolol, d-nebivolol, propranolol, atenolol, dilevalol and pindolol) were tested in the isolated working rabbit heart. The effects of l-nebivolol, having little beta-adrenoceptor blocking activity, were also studied. The hearts were subjected to 25 min ischemia, followed by 30 min of reperfusion. In solvent-treated hearts, ischemia resulted in a considerable loss of function. The mean functional recovery of one of the most sensitive parameters, i.e. aortic flow, was only 6%. Pretreatment either with dl-nebivolol, d-nebivolol, l-nebivolol or propranol significantly improved cardiodynamic function. Recovery after pretreatment with atenolol, dilevalol and pindolol (less than 10 mg/l) was not significantly improved when compared to solvent-treated hearts. The results suggest that the protective effects of some beta-blockers are most probably not related to beta-adrenoceptor blocking activity.
Adrenergic beta-Antagonists↗
Is the outcome of coronary artery bypass graft surgery predictable in patients with severe ventricular function impairment?
Sixty consecutive patients, with a mean ejection fraction of 31.8% underwent coronary revascularization at the K. U. Leuven (Belgium). The operative mortality was 6%. At twelve months after surgery, the total actuarial survival was 90.0%, at twenty four months the total survival was down to 77.9%. All the preoperative data were entered into a mathematical model and using the stepwise logistic regression method, the predictability of death at 18 months postoperatively was analyzed. Using only the ejection fraction the accuracy of the prediction was 83.3%, the sensitivity 36.4% and the specificity 93.9%. Combining ejection fraction and NYHA functional classification before surgery the accuracy increased to 91.7%, the sensitivity to 72.7% and the specificity to 95.9%. Ejection fraction alone is a poor predictor of late death with only 36.4% sensitivity, but combining it with other parameters it is possible to construct a formula predicting death at 18 months with an accuracy of 91.7%.
Actuarial Analysis↗