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The efficiency of basic fibroblast growth factors (bFGF) in restoring the normal physiological responses thoracic aorta to endothelium-dependent agonist was analyzed in hypercholesterolemic rabbits. Administration of bFGF in hypercholesterolemic rabbits improved endothelium-dependent responses and enhanced the responses of denuded arterial segments to endothelium-dependent vasodilators. Furthermore, bFGF improved reendothelialization without altering neointimal formation in hypercholesterolemic rabbits.

Nitric oxide synthesis affects the angiotensin-converting enzyme's (ACE) inhibitory effect on the abnormal functioning of neoendothelial cells and intimal hyperplasia in a rabbit model with injured arteries. Long-term administration of an ACE inhibitor, perindopril, improves neoendothelial dysfunction and reduces the intimal hyperplasia. The continuous release of NO in the iliac arterial walls influences the ACE inhibition effects.

Objective: Growth regulatory properties of nitric oxide (NO) in cultured endothelial cells is controversial. The aim of our study was to investigate the effect of l-arginine, the endogenous NO precursor, and l-NAME, an inhibitor of NO synthase on the reendothelialization process after angioplasty. Methods: Fifty-five New Zealand White rabbits underwent denudation of the left iliac artery. After injury the rabbits were randomized in three groups: l-arginine 2.25% (l-arginine, n=19); NG-nitro-l-arginine methyl ester 15 mg/kg/day (l-NAME, n=19); and placebo (controls, n=17). Treatment was solubilized in drinking water. Reendothelialization was evaluated at 4 weeks by macroscopic evaluation of Evans blue staining and endothelial-specific immunostaining (CD-31) on cross sections. Intimal hyperplasia was evaluated by morphometric analysis. Results: Despite a significant increase in plasma arginine (P=0.001) and a reduction in intimal hyperplasia (P=0.003) with l-arginine, neither agent had a significant effect on reendothelialization at 4 weeks (controls=36±4%, l-arginine=43±3%, l-NAME=33±4%; NS). Conclusion: These results suggest that, in spite of previously demonstrated effects on neointimal hyperplasia, the NO pathway does not influence the regrowth of macrovascular endothelial cells in vivo. [ABSTRACT FROM PUBLISHER]

Objective: Non-uniform drug-induced prolongation of repolarization predominating in the midmyocardial (M) cell layers has been shown to be responsible for perpetuation of reentry, giving rise to torsade de pointes. However, the absence of M cells in immature animals, especially the pig, suggests other possible underlying mechanisms. We sought to examine, in this species, the effects of predisposing factors to torsade de pointes on the dispersion of epicardial repolarization and their contribution to arrhythmogenesis. Methods: Computerized mapping of repolarization and activation was conducted on the epicardial surface in 29 Langendorff-perfused hearts of eight-week-old pigs. Activation–recovery intervals were measured simultaneously from 128 unipolar electrograms. Results: Baseline iso-interval maps were dipolar (41%) or multipolar (59%). Dispersion of repolarization was reverse frequency-dependent but was unaffected by lowering [K+]o. dl-Sotalol (0.1 mmol/l) reinforced local gradients and thus increased epicardial dispersion, whereas intramural recordings did not demonstrate any predominant effect in midmyocardial layers. Phenylephrine (1 μmol/l) notably augmented dl-sotalol effects. After [Mg++]o lowering, although dispersion was not significantly increased, dl-sotalol was associated with the spontaneous occurrence of polymorphic ventricular tachycardia in seven out of nine experiments. When maps of repolarization of escape beats were compared with activation maps of first arrhythmic beats, an arc of functional dissociation was observed in the vicinity of a steep gradient of repolarization in two out of nine tachycardias. Conclusion: Epicardial dispersion of repolarization is increased by slow rates, dl-sotalol and phenylephrine but is not the only requirement for initiation of polymorphic ventricular tachycardia. In combination with other factors, it helps continuation of the arrhythmia in this model. [ABSTRACT FROM PUBLISHER]

Objective: The aim was to examine the effects of aldosterone and of an aldosterone antagonist, spironolactone, on neointimal thickening in a rabbit model of balloon injury. Methods: Eighteen rabbits underwent aortic and iliac balloon injury and were randomised to subcutaneous infusion of aldosterone (70 μg·kg−1·d-t-1) or vehicle solution for 28 d. Eighteen other rabbits were randomised to receive daily subcutaneous injections of spironolactone (50 mg·kg−1·d−1) or of vehicle for 7 d before injury and for 28 d after the procedure. All animals were then killed just after measurement of plasma renin activity and of arterial pressure. Vessels were fixed and five cross sections were analysed per rabbit (three aortic; two from iliac artery). Mean values of neointimal area and of the neointimal area/medial area ratio were calculated. Results: Aldosterone treatment was associated with a decrease in renin activity and a non-significant increase in mean arterial pressure. Aldosterone significantly augmented the neointimal thickening in the iliac artery [0.42(SEM 0.07) v 0.24(0.03) mm2, P < 0.05]but not in the aorta [0.63(0.08) v 0.59(0.12) mm2, NS]. Spironolactone significantly inhibited intimal thickening, both in the iliac artery [0.09(0.02) v 0.29(0,01) mm2, P < 0.001]and in the aorta [0.31(0.03) v 0.59(0.06) mm2, P < 0.001]. Spironolactone administration was associated with an increase in renin activity and a decrease in mean arterial blood pressure. Conclusions: Aldosterone administration enhances neointimal thickening after injury and spironolactone, an aldosterone antagonist, is a potent inhibitor of neointimal thickening in the same model. This suggests a role for aldosterone in the pathophysiology of neointimal proliferation after balloon injury and for aldosterone antagonists in its prevention. [ABSTRACT FROM PUBLISHER]

Objective: Smooth musle cell proliferation and migration are the predominant responses to intimal and medial injury after percutaneous transluminal coronary angioplasty. The in vivo inhibitory effect of heparin on these responses is well documented. To test the hypothesis that the antiproliferative effect of heparin in vivo may be related to an inhibition of proto-oncogene expression, the effects of pretreatment with heparin on the expression of the c-myc, c-fos and c-jun proto-oncogenes were examined in a rabbit model of balloon denudation. Methods: Animals were randomised 5 h before balloon denudation to receive a subcutaneous injection of unfractionated heparin (7500 IU·kg−1, n=7) or saline (n=6). Total RNA extracted from the aorta 1 h after balloon denudation was analysed by northern blot technique. A histological study was also performed in saline treated (n=4) and heparin treated (n=4) animals 28 d after balloon denudation. Results: The histological study showed that the degree of neointimal thickening was significantly less in heparin treated animals. However, the level of expression of the proto-oncogenes we studied was similar in both groups. Conclusions: Heparin inhibits neointimal thickening after balloon denudation. This inhibition is not associated with an overall decrease in the level of expression of the c-myc, c-fos, or c-jun proto-oncogenes in the arterial wall, suggesting that the antiproliferative effect of heparin may be due to an effect on other events in the cell cycle.Cardiovascular Research 1993;27:1209-1213 [ABSTRACT FROM PUBLISHER]

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In earlier open studies, β-blockers were found to be effective in the treatment of neuroleptic-induced akathisia. In the present study, 16 patients with severe neuroleptic-induced akathisia successively received low doses of three β-blockers--propranolol, sotalol, and betaxolol. There was rapid and complete improvement in seven of 16 patients (and partial improvement in three patients) treated with propranolol and in all four patients treated with betaxolol. The efficacy of propranolol and betaxolol and failure of sotalol in treating neuroleptic-induced akathisia suggest a central mechanism of action. [ABSTRACT FROM AUTHOR]