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Biomedical subjects

B Dupuis

Publications and source records attributed to B Dupuis.

At least 37 records · Page 2Linked to original sources
PubMed1998

[Electrophysiologic effects and arrhythmogenic potential of diphemanil methylsulfate on rabbit purkinje fibers. Correlations with clinical observations of QT prolongation in pediatrics].

Serious undesirable cardiac side effects have been reported with treatment with diphemanil methylsulfate (Prantal) in premature babies or neonates. To understand the origin of this problem, the authors undertook an electrophysiological study of the effects of this product in vitro on rabbit Purkinje fibres. In three separate series (N = 5 to N = 8), the effects of increasing concentrations (0.1 microM-30 microM) of diphemanil methylsulfate, different frequencies of stimulation (0.2 Hz, 1 Hz, 2 Hz) and duration of exposition (60 min followed by 120 min washout) were observed on the properties of the action potential. The results show a clearcut antiarrhythmic Class III type action characterised by a concentration-dependent prolongation of the action potential duration with an inverse frequency dependency without significant changes of the other parameters. During stimulation at 0.2 Hz, early post-depolarizations and induced activity were observed in 3/8 of the fibres exposed to 10 microM and 8/8 fibres exposed to 30 microM. The effect did not attain a steady state after 60 min of exposition. It was not reversed by 120 min of washout of the preparation. These results were compatible with the reported cardiac arrhythmic effects of prolongation of the QT interval and torsades de pointe.

Action Potentials↗
PubMed1997

Endothelial derived vasorelaxation is impaired in human APO A-I transgenic rabbits.

Endothelium-derived relaxing factor (nitric oxide: NO) may provide an endogenous defence against atherosclerosis which impairs endothelium-dependent vascular relaxation. Atherosclerosis development is inhibited in cholesterol fed human apo A-I transgenic rabbits (Duverger, N., Circulation, 1996, 94, 713-717). We investigated if endothelium-dependent vascular relaxation is modified in human apo A-I transgenic rabbits by testing in vitro endothelium-dependent receptor-dependent vascular relaxation to acetylcholine and endothelium-dependent receptor-independent vascular relaxation to A23187 of abdominal aorta, precontracted with phenylephrine, in human apo A-I transgenic rabbits (n=4) versus non transgenic littermates (n=4). Endothelium-independent vascular relaxation was investigated with sodium nitroprusside. Vascular precontraction to phenylephrine was significantly increased in human apo A-I transgenic rabbits (p<0.05) while endothelium-independent vascular relaxation to nitroprusside was similar between human apo A-I transgenic rabbits and control rabbits. Endothelium-dependent receptor-dependent and receptor-independent vascular relaxations were reduced in human apo A-I transgenic rabbits (p<0.05). Maximum endothelium-dependent receptor-dependent vascular relaxation was negatively correlated with HDL-cholesterol and total apo A-I (rabbit+ human) plasma levels (r=0.87 and 0.86, p=0.01, respectively) but not with atherogenic plasma lipid (VLDL-cholesterol, LDL-cholesterol, VLDL+LDL cholesterol, triglycerides, apolipoprotein B) levels. These results suggest that the transgenesis of human apo A-I in rabbits impairs signal transduction of endothelial NO synthesis.

Acetylcholine↗
PubMed1997

ACE inhibition accelerates endothelial regrowth in vivo: a possible explanation for the benefit observed with ACE inhibitors following arterial injury.

Recent in vitro studies suggest that angiotensin converting enzyme (ACE) inhibitors stimulate endothelial cell proliferation and migration. The present study was designed to test the hypothesis that an ACE inhibitor may accelerate endothelial regrowth in vivo. Twenty eight New Zealand White rabbits were randomized to receive placebo or the ACE inhibitor perindopril and underwent iliac balloon denudation. Endothelial regrowth, quantified 28 days after injury using Evans blue, was significantly greater in perindopril-treated animals than in controls (131 +/- 9 mm2 vs 69 +/- 8 mm2; P < .001). These results were confirmed by scanning electron microscopy and by specific immunostaining for endothelial cells. These data provide the first in vivo demonstration that ACE inhibitors accelerate endothelial regrowth after arterial injury. This effect may contribute to the benefit observed with ACE inhibition following arterial injury.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Effect of ramipril on heart rate variability in digitalis-treated patients with chronic heart failure.

The aim of this study was to evaluate the effect of an angiotensin-converting enzyme (ACE) inhibitor, ramipril, on heart rate variability in patients with heart failure simultaneously treated with digitalis. This study was a multicentric, randomized, double-blind, placebo-controlled study including 50 patients with chronic heart failure (CHF). All patients were in NYHA functional class II and III. The etiology of CHF was mainly idiopathic dilated cardiomyopathy and ischemic heart disease. After a 4-week placebo run-in period with digoxin and diuretics, patients were randomized to receive additional ramipril or placebo. To assess heart rate variability (HRV) and arrhythmias, 24-hour ECGs were recorded at the end of the placebo run-in period, 8 and 24 weeks after randomization. Spectral analysis of HRV was performed during one diurnal and one nocturnal 5-minute time period. No statistically significant differences in HRV within low-, high-, and total-frequency bands were induced by ramipril in either the diurnal or nocturnal periods, both at 8 and 24 weeks after randomization. Ramipril produced a significant decrease in nonsustained ventricular tachycardia at 24 weeks of treatment (p = 0.01). These results run against previous observations showing an increase in parasympathetic tone with ACE inhibitors in heart failure. The present study thus suggests that the effects of ACE inhibitors in CHF are variable and depend on the patient and concomitant treatment that might influence HRV such as digoxin treatment.

Adult↗
PubMed1997

Comparative efficacy of the intravenous administration of linsidomine, a direct nitric oxide donor, and isosorbide dinitrate in severe unstable angina. A French multicentre study. French Group of Investigators.

AIMS: Although linsidomine shares common properties with nitrovasodilators, it releases nitric oxide directly without catalytic involvement by thiols. We conducted a prospective, randomized, multicentre, parallel group, single-blind study to compare the efficacy of intravenous administration of linsidomine with that of isosorbide dinitrate in unstable angina. METHODS AND RESULTS: Between November 1990 and July 1992, 568 patients with suspected unstable angina (class IIIB of the Braunwald classification) received a continuous infusion of either linsidomine (1 mg.h-1 on average) or isosorbide dinitrate (2.5 mg.h-1 on average) for 72 h. All patients received concomitant aspirin and intravenous heparin, 81% beta-blockers and 38% calcium antagonists. Holter monitoring was performed in all patients and analysed blindly. Only 25% of the patients had at least one episode of chest pain during the study (24.6% vs 25.8% in the linsidomine and isosorbide dinitrate groups, P = 0.74), of which 12% were associated with ECG changes. Holter criteria yielded similar results in both groups: 33% of patients presented episodes of myocardial ischaemia (32.6% vs 33.9% in the linsidomine and isosorbide dinitrate groups, P = 0.74), while 45% showed episodes of ventricular arrhythmia (43.5% vs 46.5% in the linsidomine and isosorbide dinitrate groups, P = 0.48). The incidence of serious clinical events at 72 h (death, myocardial infarction or myocardial revascularization) was 6.5% (5% vs 8% in the linsidomine and isosorbide dinitrate groups, P = 0.17). CONCLUSION: Intravenous linsidomine is at least as efficacious as isosorbide dinitrate in the stabilization of patients with severe unstable angina.

Aged↗
PubMed1997

Dobutamine improves gastrointestinal mucosal blood flow in a porcine model of endotoxic shock.

OBJECTIVE: To test the hypothesis that saline solution plus dobutamine increases gastrointestinal mucosal perfusion better than saline solution alone in a model of endotoxic shock. DESIGN: Prospective, randomized, unblinded study. SETTING: Animal research laboratory affiliated with a university teaching hospital. SUBJECTS: Twelve female pigs, weighing 30 to 32 kg. INTERVENTIONS: Animals were anesthetized, and their lungs were mechanically ventilated. Catheters were inserted into the right atrium, pulmonary artery, and carotid artery for blood sampling and blood pressure and cardiac output measurements. A tonometer and a laser Doppler probe were placed in the lumen of the stomach and the ileum for determination of mucosal acid-base status and measurement of mucosal blood flow. Group 1 animals (n = 6) received an infusion (T = 0 min) of 150 mcirog/kg Escherichia coli endotoxin and normal saline solution (0.3 mL/kg/min). Group 2 animals (n = 6) received an infusion of endotoxin and were resuscitated with the same method as used in group 1, but an infusion of dobutamine (5 microg/kg/min) was begun at T = 60 mins, and continued for the duration of the experiment. MEASUREMENTS AND MAIN RESULTS: Both experimental regimens produced shock, with decreased mean arterial pressure and systemic vascular resistance, without change in cardiac output and oxygen delivery. Endotoxin plus saline infusion decreased gastrointestinal mucosal blood flow to <60% of baseline and decreased gastrointestinal pH. In contrast, gastrointestinal mucosal blood flow returned to baseline values, and intramucosal pH tended to normalize by the end of the saline solution plus dobutamine resuscitative protocol. CONCLUSION: Compared with saline solution alone, saline solution plus dobutamine increased blood flow to the gastrointestinal mucosa, and may have partially improved oxygenation.

Animals↗
PubMed1997

bFGF restores endothelium-dependent responses of hypercholesterolemic rabbit thoracic aorta.

In animal models, a hypercholesterolemic diet induces areas of deendothelialization and impairs endothelium-dependent vasorelaxation. Angiogenic growth factors increase endothelial cell growth in vivo. This study was thus designed to test the hypothesis that chronic administration of basic fibroblast growth factor (bFGF) in hypercholesterolemic rabbits might restore normal physiological responses to endothelium-dependent agonists. After feeding on a 2% cholesterol diet for 6 wk, 14 New Zealand White rabbits received twice-weekly intravenous boluses of either 2.5 microg bFGF (hypercholesterolemic bFGF group, n = 6) or placebo (hypercholesterolemic control group, n = 8) for 3 wk and were killed for assessment of in vitro vasoreactivity and for histological analysis. Six animals fed with standard rabbit diet were used to assess normal responses. Endothelium-dependent responses to acetylcholine and to the calcium ionophore A-23187 were reduced in the hypercholesterolemic control group compared with normal rabbits. Hypercholesterolemic animals treated with bFGF had significantly better endothelium-dependent responses than hypercholesterolemic rabbits not treated with bFGF. Endothelium-independent responses did not differ significantly among the three groups. A similar degree of plaque formation was observed in control- and bFGF-treated hypercholesterolemic rabbits. These results show that, in this model of atherosclerosis, bFGF has a highly beneficial effect on the functional responses of atherosclerotic vessels and does not have a deleterious effect on the degree of plaque formation.

Acetylcholine↗
PubMed1996

Role of endothelial cells in restenosis after coronary angioplasty.

Percutaneous transluminal coronary angioplasty (PTCA) is today a procedure of choice in many patients with atherosclerotic coronary artery disease. Despite high rates of initial success, restenosis, occurring in 30 to 40 percent of patients within the first six months, remains the major problem limiting the long-term efficacy of the procedure. Animal models have enhanced our knowledge in the understanding of the mechanisms involved in the restenotic process after experimental angioplasty. In fact, the two known determinants of restenosis are the proliferative and migrative response of underlying smooth muscle cells with production of extracellular matrix and the recently highlighted vascular remodeling. Endothelium, which regenerates from the leading edge of the de-endothelialized area within the weeks following arterial injury, is of particular interest in the modulation of the healing process after the procedure. Endothelial dysfunction, as an imbalance between relaxing and contracting factors, between anti- and pro-coagulant mediators or growth-inhibiting and growth-promoting factors, occurs at sites of regenerating endothelium. Experimental studies, using drugs that enhance endothelium-derived relaxing factors release or drugs that diminish endothelium-derived contracting factors production, have often been shown to be effective in the restenosis prevention. Thus, impairment in endothelial cell function may be considered as one of the major regulatory element in the restenotic process. This review discusses the interactions between endothelial and smooth muscle cells and has for aim to point out the major role of endothelial cells in the development of neointimal thickening and arterial remodeling.

Angioplasty, Balloon, Coronary↗
PubMed1996

The arterial wall: a new pharmacological and therapeutic target.

In recent years, two key concepts having numerous interrelationships were advanced for the understanding of various cardiovascular diseases: the "endothelial dysfunction" and the "arterial remodelling". Both endothelial dysfunction and arterial remodelling occur in various pathologies including essential hypertension, heart failure, atherosclerosis, restenosis after angioplasty, and pulmonary hypertension, and have modified the therapeutic approach by offering new pharmacological targets: specific receptors not only at the site of the vascular smooth muscle cells but also on the endothelial cells, growth factors that stimulate proliferation of smooth muscle, and receptors and enzymes of the extra-cellular matrix. Among the various substances under research, the present review will discuss angiotensin II receptor antagonists, endothelin receptor antagonists, nitrates-NO donors, potassium channel activators, and substances interfering with proteoglycans and other components of the extra-cellular matrix.

Angiotensin Receptor Antagonists↗
PubMed1996

NO synthesis is involved in structural and functional effects of ACE inhibitors in injured arteries.

Angiotensin-converting enzyme (ACE) inhibitors reduce intimal hyperplasia after balloon injury. A role for nitric oxide (NO) has been suggested in this effect. Because recent data suggest that NO may modulate some features of endothelial cells and because endothelial cells are involved in the control of intimal hyperplasia, we investigated the role of NO synthesis in the effect of an ACE inhibitor, perindopril, on neoendothelial dysfunction and intimal hyperplasia in a rabbit model of unilateral iliac balloon injury. New Zealand White male rabbits received placebo, perindopril, or cotreatment with perindopril and NG-nitro-L-arginine methyl ester (L-NAME) and were evaluated 4 wk after the injury. Fifteen rabbits (5 in each group) were used to assess in vitro vasoreactivity and twenty-four (8 in each group) for morphometric analysis. In injured vessels, neoendothelium-dependent relaxation in ACE inhibitor-treated animals was improved compared with placebo (P < 0.05) and restored to the level of noninjured vessels (NS). The improvement observed with ACE inhibitor was abolished by cotreatment with L-NAME (P < 0.05). In the same vessels, no effect was observed on neoendothelium-independent vasoreactivity. The improved neoendothelial dysfunction with ACE inhibitor was associated with a 66% reduction in intimal thickening (P < 0.01). The effect was also reversed by cotreatment with L-NAME (P < 0.01). In noninjured vessels, treatment did not alter vasoreactivity or morphology of the vessel wall. These results suggest that NO synthesis may play a key role in the improvement of vascular function seen with ACE inhibitor in balloon-injured vessels.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1995

Restenosis after coronary angioplasty.

The major disadvantage of using percutaneous transluminal coronary angioplasty to treat patients with atherosclerotic coronary disease is the frequent occurrence of restenosis after an initially successful procedure. Studies in animals and histological observations in man have demonstrated that restenosis is characterized by neointimal hyperplasia due to smooth muscle cell proliferation and to the synthesis of extracellular matrix. Improvements in technology or pharmacological interventions have had no significant impact on the rate of restenosis. In spite of our increased understanding of the molecular mechanisms of restenosis. no effective treatment is available at the present time. Gene therapy, which has produced encouraging initial results in experimental models, may provide a solution in the medium term.

Angioplasty, Balloon, Coronary↗
PubMed1995

Angiotensin converting enzyme inhibition prevents proto-oncogene expression in the vascular wall after injury.

OBJECTIVES: Angiotensin converting enzyme (ACE) inhibitors reduce neointimal hyperplasia after balloon denudation, but the mechanisms are not completely understood. It has been demonstrated that nuclear oncogenes are induced in the vascular wall in the hours immediately after injury, and that the same genes are induced by angiotensin II in vascular smooth muscle cells. It has therefore been suggested that the effects of ACE inhibitors on the response of the vessel wall could be mediated by an inhibition of proto-oncogene expression. METHODS AND RESULTS: Sixteen New Zealand White rabbits were randomly assigned for histologic analysis to receive placebo (n = 9) or 1 mg/kg per day perindopril (n = 7). After treatment for 7 days balloon aortic injury was performed. The treatment was continued and the rabbits were killed 28 days after injury. In the perindopril group the neointimal cross-sectional area was significantly smaller than in the control group. Six untreated rabbits were used to assess the time course of proto-oncogene expression in the aortic wall after injury in the present model. After extraction, total aortic RNA was hybridized with myc, fos and jun probes. Based on the results, the effects of ACE inhibition on proto-oncogene expression were tested 1 h after balloon denudation. Accordingly, 24 rabbits were randomly assigned to pretreatment for 7 days with placebo or with 1 or 10 mg/kg per day perindopril (n = 8, for each group) and were killed 1 h after injury. Expression of c-myc was not altered by pretreatment. However, 1 mg/kg per day perindopril induced significant reductions of 50% in c-jun and 45% in c-fos expression compared with control. No additional effect was obtained with the higher dose. CONCLUSION: The effect of ACE inhibition on intimal hyperplasia is associated with a reduction in early cellular events such as c-fos and c-jun expression. These results suggest that potent ACE inhibition at the time of vascular injury may be required to limit the hyperplastic response of the vessel wall.

Animals↗
PubMed1995

Neointimal thickening after balloon denudation is enhanced by aldosterone and inhibited by spironolactone, and aldosterone antagonist.

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 micrograms.kg-1.d-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.

Aldosterone↗
PubMed1994

Angiopeptin inhibits oncogene induction in rabbit aorta after balloon denudation.

BACKGROUND: Angiopeptin, a synthetic cyclic octapeptide analogue of somatostatin, reduces neointimal hyperplasia after balloon denudation of rabbit aorta if administered before injury. The aim of this study was to analyze the effect of angiopeptin pretreatment on the level of expression of the c-fos and c-jun protooncogenes, early markers of smooth muscle cell proliferation, after balloon denudation of rabbit aorta. METHODS AND RESULTS: For histological analysis of the effect of angiopeptin on neointimal thickening after aortic balloon denudation, rabbits were randomized into three groups: group 1 (controls), twice-daily injections of saline begun 24 hours before balloon denudation (n = 9); group 2, twice-daily injections of angiopeptin 10 micrograms/kg begun 24 hours before balloon denudation (n = 9); and group 3, twice-daily injections of angiopeptin 10 micrograms/kg begun 1 hour after balloon denudation (n = 7). The degree of neointimal thickening 28 days after balloon denudation was significantly less in group 2 than in group 1 (neointimal area: group 1, 0.59 +/- 0.11 mm2; group 2, 0.22 +/- 0.05 mm2; P < .05. Neointima/media: group 1, 0.85 +/- 0.17; group 2, 0.23 +/- 0.05; P < .05). When angiopeptin was started 1 hour after denudation (group 3), however, the neointimal area (0.52 +/- 0.09 mm2) and the neointima/media ratio (0.76 +/- 0.10) were not statistically different from the control group. For analysis of protooncogene induction, rabbits received twice-daily subcutaneous injections of saline (n = 7), angiopeptin 10 micrograms/kg (n = 8), or angiopeptin 100 micrograms/kg (n = 4) begun 24 hours before balloon denudation. The animals were killed 30 minutes after balloon denudation, and total aortic RNA was hybridized with fos and jun probes. Expression of c-fos and c-jun was detected 30 minutes after injury; angiopeptin pretreatment at 20 micrograms.kg-1.d-1 induced a 41% reduction in c-fos expression and a 42% reduction in c-jun expression compared with control animals. The inhibitory effect at the higher dose of angiopeptin was similar. CONCLUSIONS: Our results show that the inhibitory effect of angiopeptin on neointimal thickening is related to events that occur very early after injury and suggest that the inhibition of smooth muscle cell activation may be responsible, at least in part, for this effect.

Animals↗
PubMed1994

Long-term oral administration of L-arginine reduces intimal thickening and enhances neoendothelium-dependent acetylcholine-induced relaxation after arterial injury.

BACKGROUND: Nitric oxide (NO), in addition to its potent vasorelaxant properties, may participate in growth regulation of cultured smooth muscle cells. It was recently demonstrated that in vivo endothelial injury induces the production of NO from L-arginine in the arterial wall. METHODS AND RESULTS: We studied the effects of long-term administration of L-arginine, the precursor of NO, on neointimal thickening and on neoendothelium-dependent vasorelaxation 4 weeks after balloon denudation of normocholesterolemic rabbit iliac arteries. Rabbits were fed with either a standard diet or a diet supplemented with L-arginine (2.25%) in their drinking water 3 days before and during 4 weeks after balloon denudation. The effectiveness of L-arginine supplementation was confirmed by measurement of plasma arginine levels. L-Arginine had no effect on hemodynamic parameters. All animals were killed 4 weeks after balloon denudation, and a digital histomorphometric analysis of three serial nonconsecutive histological cross sections per iliac artery was performed. Intimal thickening was reduced (P < .05) from 0.43 +/- 0.08 (SE) mm2 in controls (n = 8) to 0.24 +/- 0.02 mm2 in treated animals (n = 8). Ten animals (n = 5 in each group) were used for in vitro vasoreactivity assessment 4 weeks after balloon denudation. Neoendothelium-dependent acetylcholine-induced relaxation (10(-8) mol/L to 3.10(-5) mol/L) in treated animals (Emax = -24.1 +/- 5.5%) was significantly greater than in controls (Emax = -8.9 +/- 2.2%). Endothelium-independent relaxation did not differ between groups (Emax = -58.1 +/- 6.5% in L-arginine-supplemented animals versus -52.9 +/- 6.8% in controls). CONCLUSIONS: Our results demonstrate that L-arginine, a precursor of NO, reduces neointimal thickening after balloon denudation and improves neoendothelial-dependent acetylcholine-induced relaxation.

Acetylcholine↗
PubMed1993

Heparin does not inhibit oncogene induction in rabbit aorta following balloon denudation.

OBJECTIVE: Smooth muscle 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.

Animals↗
PubMed1993

Effects of acute and chronic administration of acebutolol on the right ventricular effective refractory period in conscious dogs.

beta-Adrenergic blocking drugs are effective in reducing sudden cardiac death after acute myocardial infarction but the precise mechanism of this effect is unclear. We investigated the acute and chronic effects of acebutolol, a beta-adrenergic blocker, on electrocardiographic parameters, diastolic excitability threshold (DET), and right ventricular effective refractory period (RVERP) in chronically instrumented conscious dogs. These parameters were determined during spontaneous sinus rhythm and at a fixed pacing rate (200 beats/min). Acebutolol (0.5, 1, and 5 mg/kg i.v.) decreased the heart rate (HR) (by 23, 26, and 24%, respectively) without effects on any electrocardiographic parameters or on the DET. The maximal increases in ERP were 4.7, 7, and 7.8%, respectively, during pacing and 8.5, 13.3, and 10.3%, respectively, during sinus rhythm. Acebutolol, 10 mg/kg/day P.O. for 6 weeks, reduced the HR from the third day onward without altering the PR, QRS, QT, or QTc intervals or the DET. The increase in ERP was significant from the third day (14%) during pacing and from the seventh day (15.5%) during sinus rhythm. The degree of prolongation of the ERP subsequently remained stable during the 6 weeks of treatment. The ERP returned to the baseline value 7 days after acebutolol withdrawal. This increase in ERP, which was more marked during chronic oral treatment, could contribute to the documented protective effect of the beta-blocking drugs against sudden cardiac death after myocardial infarction.

Acebutolol↗