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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Experimental myocardial infarction is a model of cardiac overload due to amputation of part of the cardiac muscle. The development of cardiac failure depends on the size of the infarct and the time factor. This model of overload is associated with changes of the phenotype of the remaining healthy muscle and with peripheral vascular modifications partially dependent of the activation of pressor and/or deactivation of dilator systems. These changes are proportional to the size of the infarction at a given time after induction of the model. The degree of right ventricular hypertrophy and the decrease in blood pressure reflect the severity of infarction and the deterioration of the remaining myocardial function, affecting the haemodynamics both before and after the left ventricle. The increases in the 1/3 forms of isomyosins, the amount of subendocardial collagen, the biosynthesis, stocking and secretion of ANF are related to the infarct size and degree of overload. Similarly, the concentration of cyclic GMP is proportional to the infarct size. These parameters reflect ventricular overload, the increase of stress and energy deprivation of the remaining healthy muscle. The activation of peripheral pressor systems is also dependent on the infarct size reflects the effect of cardiac pump dysfunction on the kidney, liver, brain and endothelium. Large infarcts are associated with increased circulating renin and renal concentrations, with a decrease in angiotensinogen levels related to its consumption by the renin and to reduced hepatic synthesis and also with increased secretion and biosynthesis of vasopressin by the hypothalamus. In this model, Perindopril is beneficial by decreasing the cardiac load. It reduces the blood pressure, causes regression of bi-auricular and right ventricular hypertrophy. Changes in myosin isoenzyme configuration regress and subendocardial fibrosis and ANF concentrations are normalised. The effects of ACE inhibitors in this context, though very beneficial, are limited by the impossibility of normalising cardiac load and stress when the initial amputation of cardiac contractile mass exceeds 40%.
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PMID:[Experimental myocardial infarction in the rat. Effect of perindopril]. 166 27

The acute systemic and regional hemodynamic responses to a single oral dose (4 mg) of the angiotensin converting enzyme inhibitor perindopril were investigated in 10 patients with severe congestive heart failure. Perindopril produced significant and long-lasting decreases in systemic vascular resistance (-18%), right atrial pressure (-60%), and mean pulmonary capillary wedge pressure (-28%), whereas it significantly increased cardiac index (+ 12%). Brachial (+ 130%, pulsed Doppler technique) and renal (+ 34%) blood flows were also significantly increased whereas hepatic blood flow remained unchanged. Brachial flow/cardiac output and renal flow/cardiac output ratios increased significantly from 0.8 to 1.6 and from 13.2 to 16.5, respectively. The maximal decreases in forearm and renal (but not in systemic) vascular resistances were correlated with the basal plasma norepinephrine concentrations but not plasma epinephrine concentrations or plasma renin activity. We conclude that in severe heart failure (a) perindopril considerably improves systemic hemodynamics and exerts an inhomogeneous vasodilating effect, resulting in a redistribution of flows toward the forearm and renal territories, (b) norepinephrine is a major determinant of the arteriolar tone in these two vascular beds, and (c) the pulsed Doppler is a particularly suitable method to non-invasively detect and assess hemodynamic improvements in heart failure patients.
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PMID:Systemic and regional hemodynamic effects of perindopril in congestive heart failure. 169 80

Haemodynamic studies performed in patients with cardiac failure have shown that perindopril decreases right and left ventricular filling pressures, systemic blood pressure and peripheral resistances, slightly reduces the heart rate and increases cardiac output. Flammang showed that these haemodynamic changes are sustained after 12 months' treatment. A randomised double blind multicenter trial versus placebo was carried out over 3 months following a 15 days pre-inclusion period in 125 patients with NYHA Stage II and III cardiac failure stabilised by digitalis and diuretic therapy. Perindopril was administered at a dosage of 2 or 4 mg according to initial systolic blood pressure and efficacy was evaluated at 1 and 3 months according to the NYHA classification, a score of clinical severity, the duration of two exercise stress tests on a bicycle ergometer or treadmill and the cardiothoracic ratio. There were no cases of cardiac decompensation (NYHA Stage IV) in the group of perindopril whilst 3 cases were observed in the placebo group. Significant improvements in the clinical scores and effort capacity were observed in the perindopril group. The duration of exercise on the treadmill was 778 seconds with perindopril compared to 544 seconds in the placebo group. Systolic blood pressure did not change and there was a slight decrease in standing diastolic pressures. No significant increases in blood urea or creatinine levels were observed. To study the effects on blood pressure, a major factor in the management of a patient with cardiac failure, McFadyen compared the changes in blood pressure after a single dose of perindopril, enalapril, captopril and placebo.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Perindopril and chronic heart failure]. 179 31

Perindopril is a non-sulphydryl, pro-drug, ACE inhibitor. Following oral dosing, peak concentrations of the active moiety, perindoprilat, are achieved after 2-3 hours and perindoprilat is barely detectable by 24 hours. In contrast, maximal ACE inhibition is observed 4-6 hours after oral dosing and substantial inhibition persists beyond 24 hours. Inhibition of ACE is dose-dependent over the range 1-16 mg perindopril orally, and is mirrored by elevation of plasma renin activity and falls in aldosterone concentrations. Blood pressure reductions have been confirmed in normotensive and hypertensive subjects with maximal effect 6-10 hours after dosing and adequate antihypertensive activity at 24 hours. Blood pressure reductions are greater in the elderly than in young subjects due to pharmacokinetic differences. Dose reduction is required in elderly subjects and those with renal impairment. The antihypertensive efficacy of perindopril 4-8 mg once daily, is comparable to that of atenolol 50-100 mg once daily, captopril 25-50 mg twice daily or a hydrochlorothiazide/amiloride combination. Reduction in heart failure severity has also been reported. Perindopril appears to be a safe and effective agent for use in hypertension.
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PMID:Clinical pharmacology of perindopril. 228 58

Perindopril is an orally active, non-thiol angiotensin-converting enzyme (ACE) inhibitor, which in doses of 4 to 8mg is effective in the control of essential hypertension. As monotherapy it is as effective as once-daily atenolol and possibly more effective than twice-daily captopril. A synergistic response has been noted when perindopril is combined with a thiazide diuretic. Maximal pharmacodynamic effects (ACE inhibition, increase in plasma renin activity and angiotensin I, reduction in aldosterone and angiotensin II and blood pressure) are seen 4 to 6 hours after dosing, with substantial effects still present at 24 hours. Perindopril is a prodrug which requires de-esterification to perindoprilat for useful ACE inhibition. Maximal plasma perindoprilat concentrations are reached 2 to 6 hours after oral administration of perindopril, and 70% of the active metabolite is cleared by the kidneys. The other major metabolite of perindopril is an inactive glucuronide. Ageing is associated with increased serum perindoprilat concentrations, which are probably caused by a combination of enhanced conversion to the active metabolite and diminished renal clearance. Compensated cirrhosis does not appear to have an independent effect. There is little published experience of the use of perindopril in patients with cardiac failure or other cardiac disease, but preliminary evidence would support the general value of this class of agent as adjunctive therapy.
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PMID:Perindopril. A review of its pharmacokinetics and clinical pharmacology. 240 93

Right cardiac catheterization studies have demonstrated an improvement in cardiac hemodynamics in patients with heart failure following the administration of perindopril (per): reduction in ventricular filling pressures (pulmonary capillary wedge pressure, right atrial pressure) and systemic resistance and an increase in cardiac output. The intensity and duration of these modifications were frequently insufficient after 2 mg, but were significant over 24 hours after 4 mg. A randomized, double-blind multicenter study versus placebo (pla) was conducted for 3 months, following a preinclusion period of 15 days, in 103 heart failure patients (stages II and III of the NYHA classification) treated with diuretic +/- digitalis. The following parameters were evaluated before (be), after 1 month (1m) and after 3 months (3 m) treatment: duration of stress test (DST) (sec), clinical severity score (SS), cardiothoracic ratio (CTR), serum creatinine (Cr) (mumol/l), systolic blood pressure (SBP) (mm Hg) in the supine (s) and erect (e) positions. 50 patients received per and 53 received pla; 46 patients in each group completed the double-blind period. Perindopril was administered at doses of 2 mg (n = 6) and 4 mg (n = 40). The following results were obtained: (table; see text) Three cases of acute heart failure occurred in the placebo group compared with none in the peridopril group. The efficacy of perindopril in heart failure was demonstrated by the improvement in effort capacity and severity score and by the reduction in cardiothoracic ratio. The variation in SBP and serum creatinine, in particular, reflected the good safety.
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PMID:Value of perindopril in the treatment of chronic congestive heart failure. Multicenter double-blind placebo-controlled study. 269 Nov 30

1. Left ventricular myocardial infarction was induced in female Wistar rats by ligation of the left anterior descending coronary artery. 2. One month following operation, rats with infarcts developed marked cardiomegaly compared to sham operated rats, indicating the presence of chronic left ventricular failure. 3. The ratio of the noradrenaline metabolite 3,4-dihydroxyphenylethylene glycol (DHPG) to noradrenaline (NA) was elevated in the right ventricle of rats with heart failure one month following infarction, suggesting a chronic increase in cardiac sympathetic activity. 4. Perindopril therapy for one month commenced 4 weeks after infarction returned cardiac weights to normal and significantly reduced right ventricular DHPG/NA ratios. 5. The results suggest that ACE inhibition with perindopril reduces elevated levels of cardiac sympathetic activity in rats with chronic left ventricular failure and leads to regression of cardiomegaly.
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PMID:Cardiac 3,4-dihydroxyphenylethylene glycol (DHPG) and catecholamine levels during perindopril therapy of chronic left ventricular failure in rats. 272 98

To explain how converting enzyme inhibition could improve the prognosis in cardiac insufficiency, the effect of converting enzyme inhibition (CEI) by S9490-3 (Perindopril) treatment for 2 months (treated infarctions, n = 18) on hormonal plasma variables and the quantitative and qualitative changes in myocardium were studied in an experimental model of left ventricular infarction in rats (untreated infarctions, n = 18) and compared to a sham-operated control group (n = 15). Induction of myocardial infarction was associated with a transient decrease in blood pressure. CEI treatment maintained a lower blood pressure throughout the experimental period. Plasma renin concentration was not significantly increased in the untreated infarct group (155.4 +/- 136.7 ng AI/ml/hr) as compared to the sham-operated group (47.6 +/- 15.9 ng AI/ml/hr). Plasma aldosterone did not change in the three experimental groups. The plasma level of immunoreactive atrial natriuretic factor increased in the untreated infarct group (185 +/- 245 pg/ml) as compared with the control group (76 +/- 40 pg/ml) and was normalized by CEI (66 +/- 60 pg/ml). Body weight was slightly decreased in both treated and untreated infarct groups, whereas the heart weight was significantly increased in the untreated group (1,540 +/- 310 mg) and normalized by treatment (1,145 +/- 180 mg) as compared with sham-operated controls (1,071 +/- 80 mg). The combined atria and right ventricular mass was significantly increased in the untreated infarct group (660 +/- 210 mg) and decreased by treatment (443 +/- 106 mg) but was not completely normalized (controls, 343 +/- 40 mg). Left ventricular isomyosin profiles were modified by myocardial infarction as compared with controls: V1 form decreased from 62.4 +/- 9.4% in the sham-operated group to 41.6 +/- 13.4% in the infarct group, and the V3 form increased from 13.0 +/- 4.7% in sham-operated animals to 27.4 +/- 11.8% in untreated infarct animals. CEI treatment partially, but significantly, reversed this modification of the isomyosin profile (V1, 53.0 +/- 14.4%; V3, 17.5 +/- 8.0%). Volume density of collagen was significantly increased in the untreated infarct rats (4.14 +/- 0.81% versus 2.68 +/- 0.49% in controls), and this was reversed by treatment (2.95 +/- 0.66%). Messenger RNA encoding for atrial natriuretic factor, measured by dot blot hybridization, was significantly increased in both the atria and the ventricles in the untreated infarct group, and treatment by CEI partially reversed this increase. Thus, myocardial infarction profoundly modified several variables of peripheral circulation and quantitative and qualitative myocardial protein expression.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Hormonal and cardiac effects of converting enzyme inhibition in rat myocardial infarction. 296 44

Systemic vasoconstriction due to stimulation of the sympathetic and renin-angiotensin-aldosterone systems is a hallmark of heart failure and this is accompanied by impaired endothelium-dependent relaxations at the level of large arteries. This study investigated, in a rat model of heart failure, whether such an endothelial dysfunction also exists at the level of the resistance artery, and whether this is associated with morphologic changes, as well as the effects of chronic treatment with the angiotensin-converting enzyme inhibitor perindopril (2 mg/kg/day). After 12 months, arterial pressure, left ventricular (LV) end diastolic pressure (LVEDP), and LV dP/dt were measured in anesthetized rats. Responses to acetylcholine and nitroprusside were determined in isolated and perfused mesenteric artery segments (diameter: 280 +/- 15 microns). After fixation, vessel diameter, media cross-sectional area, and media collagen and elastin densities were measured by image analysis. After 12 months, untreated rats showed signs of heart failure, i.e., reduced LV dP/dt, and increased LVEDP, heart weight/body weight, LV cavity circumference, and myocardial collagen density. In mesenteric vessels the endothelium-dependent vasodilator response to acetylcholine was impaired, whereas the response to the nitric oxide donor nitroprusside was unaffected. Heart failure did not affect vascular morphological parameters. Perindopril decreased blood pressure and LVEDP without any modification of LV dP/dt, and prevented cardiac remodeling. At the vascular level, perindopril improved the response to acetylcholine and reduced media cross-sectional area and collagen density without affecting internal vessel diameter or elastin density. Thus, heart failure decreases endothelium-dependent vasodilator response to acetylcholine without modification of vessel structure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Vascular and myocardial protective effects of converting enzyme inhibition in experimental heart failure. 748 84

Chronic heart failure (CHF) impairs endothelium-dependent vasodilatation of large conductance arteries. We investigated whether a similar reduction also occurs in small arteries, and whether such a reduction can be prevented by the angiotensin converting enzyme inhibitor perindopril (P) in a rat model of CHF (left coronary artery ligation). After 1 month treatment with placebo or P (2 mg/kg/day), rats were anesthetized and arterial pressure, left ventricular end-diastolic pressure, and central venous pressure were measured with a micromanometer. Segments of aorta and mesenteric artery (mean diameter, 281 +/- 8 microns) were then isolated, cannulated, and perfused at constant pressure using an arteriograph. Responses to increasing concentrations of acetylcholine (Ach), nitroprusside, and to 10(-4) mol/L NG-nitro-L-arginine methyl ester (L-NAME) were studied after preconstriction by phenylephrine. Heart failure resulted in a decrease in systolic and diastolic pressures, an increase in left ventricular end-diastolic and central venous pressures, and a significant depression of Ach-induced dilatation of the mesenteric artery (maximal dilatation, from 90 +/- 4% to 63 +/- 4%, P < .05) but not of the aorta (from 56 +/- 8% to 45 +/- 5%, NS) without any modification in the endothelium-independent vasodilatation induced by nitroprusside. In the group treated by the angiotensin converting enzyme (ACE) inhibitor perindopril, systolic and diastolic pressures were slightly decreased, whereas left ventricular end diastolic, central venous pressures, and the endothelium-dependent vasodilating response to Ach were normalized. Responses to L-NAME were not affected by CHF or perindopril. Perindopril also decreased hypertrophy, as evidenced by a significantly lower heart weight in treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prevention of endothelial dysfunction in small and large arteries in a model of chronic heart failure. Effect of angiotensin converting enzyme inhibition. 764 44


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