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H Wesseling - One of the best experts on this subject based on the ideXlab platform.
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clinical and neurohumoral differences between Spirapril and captopril in mild to moderate chronic congestive heart failure
Journal of Cardiac Failure, 1997Co-Authors: Stan A J Van Den Broek, Hans L Hillege, H Wesseling, Pieter A De Graeff, Wiek H Van Gilst, Dirk J Van Veldhuisen, Ki LieAbstract:Abstract Background: This study was done to determine whether the difference in duration of action of the long-acting angiotensin-converting enzyme (ACE) inhibitor Spirapril compared with the short-acting ACE inhibitor captopril affects clinical efficacy in patients with congestive heart failure. Methods and Results: The effects on exercise capacity, neurohumoral status, and quality of life were studied in 20 patients with mild to moderate congestive heart failure in a double-blind, randomized, comparative study in parallel groups with a duration of 12 weeks. All assessments during the study were performed in the morning, before intake of the study medication, to avoid the expected peak effect of the ACE inhibitors used. Mean peak oxygen consumption (peak Vo 2 ) was 17.4 mL/min/kg (range, 14.2–19.9 mL/min/kg) and mean left ventricular ejection fraction was 28% (range, 13–40%). Exercise duration in the captopril group showed a significant increase after 12 weeks ( P P Conclusions: This study showed that the effects of the ACE inhibitors Spirapril and captopril on exercise capacity are not related to the degree of inhibition of serum ACE activity.
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effects of Spirapril and captopril on regional blood flow in chronic congestive heart failure a comparison between a short and a long acting angiotensin converting enzyme inhibitor
Journal of Cardiovascular Pharmacology, 1995Co-Authors: Stan A J Van Den Broek, Hans L Hillege, H Wesseling, Pieter A De Graeff, Andries J Smit, Armand R J Girbes, Louis Journee, Wiek H Van Gilst, Dirk J Van Veldhuisen, Ki LieAbstract:Spirapril is a new angiotensin-converting enzyme (ACE) inhibitor with a long duration of action. To determine whether duration of inhibition of serum ACE activity may affect regional blood flow (RBF), we compared Spirapril with captopril, an ACE inhibitor with a short duration of action. Both the short- and long-term effects were studied in patients with mild to moderate congestive heart failure (CHF). Calf, renal, and hepatic BF measurements were performed in the morning before intake of the study medication; 24 h after the previous dose of Spirapril (n = 9 patients) and 12 h after the previous dose of captopril (n = 9 patients). Serum ACE activity after 1, 6, and 12 weeks was significantly reduced in patients receiving Spirapril, but not in those receiving captopril. The decrease in mean arterial pressure (MAP) was more pronounced in the Spirapril group. Calf BF showed a slight but not significant increase in both Spirapril- and captopril-treated patients. Effective renal BF increased significantly only in patients treated with Spirapril. Although filtration fraction (FF) tended to decrease in the Spirapril group, the decrease was significant only in the captopril group. No changes were observed in hepatic BF. Cerebral BF (CBF) measurements were performed after intake of the first dose of study medication and after 12 weeks, immediately after drug intake. Significant reduction in MAP in the two treatment groups both after the first dose and after 12 weeks did not affect CBF. Despite a significantly prolonged decrease in MAP and serum ACE activity in Spirapril-treated patients, no marked differences in RBF were noted between the two ACE inhibitors.
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converting enzyme inhibition after experimental myocardial infarction in rats comparative study between Spirapril and zofenopril
Cardiovascular Research, 1991Co-Authors: J Van Wijngaarden, Y M Pinto, W K Van Gilst, P A De Graeff, C D J De Langen, H WesselingAbstract:Study objective — The aim was to compare the effects of two novel angiotensin converting enzyme (ACE) inhibitors, Spirapril and zofenopril, on cardiac remodelling in rats with congestive heart failure after myocardial infarction. Spirapril contains no sulphydryl group, whereas zofenopril is a sulphydryl containing ACE inhibitor. Design — Experimental myocardial infarction was induced by ligation of the left coronary artery. Sham operated animals served as controls. Treatment with Spirapril (2-2.5 mg·kg−1·d−1) or zofenopril (12-15 mg·kg−1·d−1) added to the drinking water was started immediately after myocardial infarction or sham operation and continued for six weeks. After the treatment period, all rats were killed. The heart was rapidly removed and perfused as described by Langendorff. Heart rate and left ventricular pressure were measured both at baseline and during stimulation with isoprenaline (6 nM). Heart and lung weights were determined. Subjects — Normotensive male Wistar rats (220-240 g) were used. Measurements and main results — Experimental myocardial infarction considerably increased left ventricular cavity volume. Chronic treatment with either Spirapril or zofenopril significantly attenuated this increase in volume. In infarcted rats, the increase in total heart and lung weight was also significantly reduced by chronic treatment with Spirapril and zofenopril, indicating that these compounds reduce cardiac mass and pulmonary congestion in congestive heart failure due to myocardial infarction. There were no significant differences between treatment with Spirapril and zofenopril. In the isolated and perfused rat heart, myocardial infarction significantly decreased both heart rate and left ventricular pressure. Converting enzyme inhibition only affected heart rate. Heart rate was significantly higher in infarcted animals treated with Spirapril and zofenopril than in untreated infarcted animals. Conclusions — Both Spirapril and zofenopril attenuated ventricular enlargement and cardiac hypertrophy in rats with congestive heart failure after myocardial infarction when treatment was started in the acute phase of myocardial infarction. No additional role could be attributed to the sulphydryl moiety of zofenopril. It is also suggested that these two ACE inhibitors modify cardiac sympathetic activity in rats with congestive heart failure, but more studies are needed to confirm these findings.
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the acute hemodynamic hormonal and pharmacokinetic properties of oral Spirapril in patients with moderate to severe heart failure
Journal of Cardiovascular Pharmacology, 1991Co-Authors: Saj Vandenbroek, A Vanbruggen, Pa Degraeff, Hans L Hillege, Wh Vangilst, H Wesseling, Ki LieAbstract:The acute hemodynamic, hormonal, and pharmacokinetic responses to the oral angiotensin-converting enzyme (ACE) inhibitor Spirapril were studied in 15 patients with moderate to serve congestive heart failure in a baseline controlled dose-ranging study. Doses of 0.3, 1.0, 1.5, 3.125, and 6.25 mg were investigated for 24 h in three groups of five patients each. All doses demonstrated a significant reduction in serum ACE, even after 24 h. Significant reductions in mean arterial pressure, systemic vascular resistance, and pulmonary capillary wedge pressure were observed with doses > 1.0 mg Spirapril. Maximal significant hemodynamic effects occurred approximately 4-6 h after drug administration. The plasma concentrations of Spirapril and its metabolite Spiraprilate were dose-dependent. After administration of Spirapril, the quick rise to the peak level of Spiraprilate suggests rapid metabolism of Spirapril into Spiraprilate and a slow elimination of this metabolite. No severe hypotension or other serious side effects occurred in the patients studied. The results indicate that Spirapril may be expected to be an effective drug in the treatment of congestive heart failure. From our findings we conclude that 1.5 mg Spirapril is an optimal starting dose in patients with moderate to severe congestive heart failure.
Ki Lie - One of the best experts on this subject based on the ideXlab platform.
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clinical and neurohumoral differences between Spirapril and captopril in mild to moderate chronic congestive heart failure
Journal of Cardiac Failure, 1997Co-Authors: Stan A J Van Den Broek, Hans L Hillege, H Wesseling, Pieter A De Graeff, Wiek H Van Gilst, Dirk J Van Veldhuisen, Ki LieAbstract:Abstract Background: This study was done to determine whether the difference in duration of action of the long-acting angiotensin-converting enzyme (ACE) inhibitor Spirapril compared with the short-acting ACE inhibitor captopril affects clinical efficacy in patients with congestive heart failure. Methods and Results: The effects on exercise capacity, neurohumoral status, and quality of life were studied in 20 patients with mild to moderate congestive heart failure in a double-blind, randomized, comparative study in parallel groups with a duration of 12 weeks. All assessments during the study were performed in the morning, before intake of the study medication, to avoid the expected peak effect of the ACE inhibitors used. Mean peak oxygen consumption (peak Vo 2 ) was 17.4 mL/min/kg (range, 14.2–19.9 mL/min/kg) and mean left ventricular ejection fraction was 28% (range, 13–40%). Exercise duration in the captopril group showed a significant increase after 12 weeks ( P P Conclusions: This study showed that the effects of the ACE inhibitors Spirapril and captopril on exercise capacity are not related to the degree of inhibition of serum ACE activity.
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effects of Spirapril and captopril on regional blood flow in chronic congestive heart failure a comparison between a short and a long acting angiotensin converting enzyme inhibitor
Journal of Cardiovascular Pharmacology, 1995Co-Authors: Stan A J Van Den Broek, Hans L Hillege, H Wesseling, Pieter A De Graeff, Andries J Smit, Armand R J Girbes, Louis Journee, Wiek H Van Gilst, Dirk J Van Veldhuisen, Ki LieAbstract:Spirapril is a new angiotensin-converting enzyme (ACE) inhibitor with a long duration of action. To determine whether duration of inhibition of serum ACE activity may affect regional blood flow (RBF), we compared Spirapril with captopril, an ACE inhibitor with a short duration of action. Both the short- and long-term effects were studied in patients with mild to moderate congestive heart failure (CHF). Calf, renal, and hepatic BF measurements were performed in the morning before intake of the study medication; 24 h after the previous dose of Spirapril (n = 9 patients) and 12 h after the previous dose of captopril (n = 9 patients). Serum ACE activity after 1, 6, and 12 weeks was significantly reduced in patients receiving Spirapril, but not in those receiving captopril. The decrease in mean arterial pressure (MAP) was more pronounced in the Spirapril group. Calf BF showed a slight but not significant increase in both Spirapril- and captopril-treated patients. Effective renal BF increased significantly only in patients treated with Spirapril. Although filtration fraction (FF) tended to decrease in the Spirapril group, the decrease was significant only in the captopril group. No changes were observed in hepatic BF. Cerebral BF (CBF) measurements were performed after intake of the first dose of study medication and after 12 weeks, immediately after drug intake. Significant reduction in MAP in the two treatment groups both after the first dose and after 12 weeks did not affect CBF. Despite a significantly prolonged decrease in MAP and serum ACE activity in Spirapril-treated patients, no marked differences in RBF were noted between the two ACE inhibitors.
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the acute hemodynamic hormonal and pharmacokinetic properties of oral Spirapril in patients with moderate to severe heart failure
Journal of Cardiovascular Pharmacology, 1991Co-Authors: Saj Vandenbroek, A Vanbruggen, Pa Degraeff, Hans L Hillege, Wh Vangilst, H Wesseling, Ki LieAbstract:The acute hemodynamic, hormonal, and pharmacokinetic responses to the oral angiotensin-converting enzyme (ACE) inhibitor Spirapril were studied in 15 patients with moderate to serve congestive heart failure in a baseline controlled dose-ranging study. Doses of 0.3, 1.0, 1.5, 3.125, and 6.25 mg were investigated for 24 h in three groups of five patients each. All doses demonstrated a significant reduction in serum ACE, even after 24 h. Significant reductions in mean arterial pressure, systemic vascular resistance, and pulmonary capillary wedge pressure were observed with doses > 1.0 mg Spirapril. Maximal significant hemodynamic effects occurred approximately 4-6 h after drug administration. The plasma concentrations of Spirapril and its metabolite Spiraprilate were dose-dependent. After administration of Spirapril, the quick rise to the peak level of Spiraprilate suggests rapid metabolism of Spirapril into Spiraprilate and a slow elimination of this metabolite. No severe hypotension or other serious side effects occurred in the patients studied. The results indicate that Spirapril may be expected to be an effective drug in the treatment of congestive heart failure. From our findings we conclude that 1.5 mg Spirapril is an optimal starting dose in patients with moderate to severe congestive heart failure.
Gottfried Weidinger - One of the best experts on this subject based on the ideXlab platform.
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impact of a low dose combination of isradipine sro and Spirapril on left ventricular mass and left ventricular performance in patients with hypertension and left ventricular hypertrophy
Clinical Drug Investigation, 2002Co-Authors: David Pittrow, Gottfried Weidinger, Thomas Stoerk, Hermann EichstaedtAbstract:Objective This study investigated the effects of a low-dose fixed combination of the ACE inhibitor isradipine SRO (slow-release oral) and the calcium antagonist Spirapril on left ventricular hypertrophy (LVH) in patients with mild to moderate hypertension and LVH.
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Evaluation of the Efficacy and Tolerability of a Low-Dose Combination of Isradipine and Spirapril in the First-Line Treatment of Mild to Moderate Essential Hypertension
Cardiovascular Drugs and Therapy, 1997Co-Authors: David Bernhard Pittrow, Astrid Antlsperger, Dieter Welzel, Gerhard Wambach, Wolfgang Schardt, Gottfried WeidingerAbstract:To investigate the concept of initiating therapy with low doses of a calcium antagonist and an ACE inhibitor, a fixed combination of isradipine 2.5 mg plus the ACE inhibitor Spirapril 3 mg was compared with its components, with the full-dose monotherapies (isradipine 5 mg or Spirapril 6 mg), and with placebo. After a 2-week wash out phase in pretreated patients and a subsequent 2-week placebo period, 405 patients with a diastolic blood pressure (DBP) between 100 and 114 mmHg were randomly allocated to 12-week once-daily double-blind treatment in one of the six treatment arms. In patients whose blood pressure was not normalized (defined as DBP≤90 mmHg) after 6 weeks of treatment, the dosage of either medication was doubled or, in the placebo group, was switched to the fixed combination. After week 6, the mean reductions from baseline in sitting systolic/diastolic blood pressure 24 hours after dosing (trough) for the fixed combination or the monotherapies isradipine 5 mg, isradipine 2.5 mg, Spirapril 6 mg, Spirapril 3 mg, and placebo were10.4/8.7, 10.0/9.4, 6.5/6.7, 10.0/8.3, 7.0/5.8, and 2.2/4.7 mmHg, respectively. The blood pressure changes obtained with the low-dose fixed combination were essentially identical to those observed with the full-dose monotherapies, thus showing an additive effect of low-dose isradipine and Spirapril. In terms of tolerability, the lowest rate of any adverse events was found in the combination group. In this group, typical adverse events of calcium antagonists, such as headache, flushing, ankle edema, or palpitations, were observed only in 5%, 2%, 1%, and 0%, respectively, dry cough, considered typical for ACE inhibitors, was observed in only 1% of the combination group. In conclusion, the low-dose components isradipine 2.5 mg and Spirapril 3 mg were shown to have an additive effect when combined, exerting a blood pressure–lowering effect comparable with the full doses and a trend to a better tolerability profile in comparison with the standard doses. Thus, low-dose combination therapy with these drugs appears to be a rational alternative to conventional monotherapy in the first-line treatment of hypertension.
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influence of isradipine and Spirapril on left ventricular hypertrophy and resistance arteries
Hypertension, 1996Co-Authors: Petra A Thurmann, Gottfried Weidinger, Nicola Stephens, A M Heagerty, Peter Kenedi, Norbert RietbrockAbstract:Left ventricular hypertrophy is a common clinical feature in hypertensive patients and may be associated with structural changes in vessel morphology. In an open prospective trial, we evaluated 14 patients with previously untreated hypertension (163±2/104±2 mm Hg) and an echocardiographically determined left ventricular mass index of 141.6±5.2 g/m 2 , indicating left ventricular hypertrophy. We obtained a gluteal skin biopsy sample before starting treatment to investigate subcutaneous small-artery (approximately 200 to 400 μm diameter) morphology and function. Patients then received antihypertensive treatment with a combination of Spirapril (3 or 6 mg) and isradipine (2.5 or 5 mg). Echocardiographic recordings were made after 6 months and 1 year, and a final biopsy was taken after 1 year. After 1 year, blood pressure was significantly reduced to 142±3/90±1 mm Hg ( P 2 ( P
C Guitard - One of the best experts on this subject based on the ideXlab platform.
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comparison of efficacy of Spirapril and enalapril in control of mild to moderate hypertension
Cardiovascular Drugs and Therapy, 1997Co-Authors: C Guitard, F W Lohmann, R Alfiero, M Ruina, V AlvisiAbstract:The efficacy of Spirapril, 6 mg once daily, was compared with enalapril, 5-20 mg once daily, in the control of mild-to-moderate hypertension in a placebo-controlled, parallel-group study. A total of 251 patients participated in the study, all of whom underwent a 4-week washout period on placebo. Thereafter, 100 patients were randomized to Spirapril, 6 mg once daily, 101 patients to enalapril, 5-20 mg once daily, and 50 patients remained on placebo. Sitting diastolic blood pressure (DBP) and systolic blood pressure (SBP) were measured at 2-weekly clinic visits. Blood pressure profiles during peak and trough plasma drug concentrations (2-4 hours and 24-26 hours postdose, respectively) were determined at baseline and 4 and 8 weeks after starting the double-blind phase. Compared with placebo, treatment with both Spirapril and enalapril resulted in significant reductions (p < 0.001) in DBP and SBP. DBP was reduced to a greater extent with Spirapril than with enalapril both at peak (-17.4 mmHg vs. -14.8 mmHg) and trough (-14.7 mmHg vs. -12.4 mmHg). Thus, although the trough/peak DBP ratios for Spirapril and enalapril were very similar (84% vs. 82%), actual reductions in DBP were different. Spirapril and enalapril treatment resulted in similar reductions in SBP at both peak and trough levels. Both drugs were well tolerated, and there were very few adverse events or changes in hematological or biochemical parameters during the study. In conclusion, Spirapril, 6 mg once daily, as the initial and maintenance dose, is at least as effective and well tolerated as enalapril individually titrated.
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placebo controlled comparison of Spirapril at 6 12 and 24 mg day in mild to severe essential hypertension
Blood pressure. Supplement, 1994Co-Authors: C Guitard, E Maibach, J Franck, G Cocco, G Boxho, B Mellein, R WaiteAbstract:In a double-blind, parallel-group study, 260 patients with mild to severe essential hypertension were randomized to treatment with placebo or Spirapril at 6, 12 or 24 mg once daily for 6 weeks. When blood pressures were measured at the end of the dosing interval (trough), all Spirapril regimens had produced similar reductions in sitting systolic and diastolic blood pressures (siSBP/siDBP) which were significantly greater than those observed in placebo-treated patients. There were no relevant changes in resting heart rate in any of the study groups. At the study endpoint, the mean reductions in siSBP/siDBP were 14.9/11.5 mmHg with Spirapril at 6 mg, 15.4/12.0 mmHg with Spirapril at 12 mg and 17.8/12.4 mmHg with Spirapril at 24 mg/day vs. 3.1/3.6 mmHg with placebo. In a subgroup of 122 patients, blood pressure was recorded at the end of the dosing interval and during the 8 hours immediately postdose to monitor the peak effects on blood pressure. All Spirapril dosages produced similar reductions at peak with a mean decrease of siDBP of approximately 20 mmHg in comparison to baseline values vs 6-7 mmHg with placebo. The trough:peak ratios for 6, 12 and 24 mg all lay between 60% and 90% for siSBP and siDBP, indicating that most of the peak effect was maintained at trough. Spirapril was well tolerated; the adverse event profile was not different from that with placebo, and no dose-related adverse events were observed.(ABSTRACT TRUNCATED AT 250 WORDS)
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placebo controlled crossover comparison of Spirapril at 3 6 12 and 24 mg once daily in mild to severe essential hypertension
Blood pressure. Supplement, 1994Co-Authors: C Guitard, P Sassano, C Tzincoca, J Duchiez, M E SafarAbstract:In a randomized, double-blind, crossover study, 20 patients with mild to severe essential hypertension received 3 weeks of treatment with each of four dosages of Spirapril (3, 6, 12 and 24 mg once daily) or placebo. Standing and supine blood pressures were measured by use of both an automatic oscillometric instrument (Dinamap) and a mercury sphygmomanometer over a 24-hour period. Spirapril at 6, 12 and 24 mg once daily produced similar reductions in systolic and diastolic blood pressure. At most time points, there was a statistically significant difference between the reductions with Spirapril compared with placebo. Spirapril at 3 mg once daily was less effective than the higher dosages, producing a lower mean blood pressure reduction and a shorter duration of antihypertensive action, mainly as regards systolic pressure. Spirapril was well tolerated and no patients withdrew from the study because of adverse effects. These data suggest that, although all four evaluated Spirapril dosages effectively lowered supine and standing blood pressure in patients with mild to severe hypertension, the blood pressure-lowering effect of the 3 mg/day regimen was less than optimal. There were only minor variations in efficacy between dosages > or = to 6 mg/day, which may be attributable to the variability of blood pressure. Further investigations of larger numbers of patients are required to verify these results.
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pharmacokinetics of Spirapril in renal impairment
Blood pressure. Supplement, 1994Co-Authors: P A Meredith, P Grass, C Guitard, H L ElliottAbstract:The pharmacokinetics of Spirapril and its active diacid metabolite Spiraprilat were characterized in four groups of patients categorized on the basis of their renal function. No statistically significant effects of renal impairment upon the disposition of Spirapril were detected. In contrast, there were significant perturbations in the pharmacokinetics of Spiraprilat: The maximum plasma concentration (Cmax) values in the severely renally impaired group were 2-3 times those in the group of patients with normal renal function whereas the corresponding area under the curve (AUC) values were 5-6 times higher. However, there was no evidence of accumulation of Spiraprilat in any of the groups as determined by the pharmacokinetic parameters derived after single and multiple doses. Thus, despite the evidence of a significant influence of renal impairment upon the disposition of Spiraprilat, the lack of accumulation during the translation from single to multiple doses indicates that there is a considerable margin of safety for Spirapril in renal impairment.
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24 hour ambulatory blood pressure monitoring and Spirapril in mild to severe essential hypertension a randomized dose comparison
Blood pressure. Supplement, 1994Co-Authors: G Vreugdenhil, C Guitard, B Mellein, M C Jacobs, D P Veerman, T ThienAbstract:This was a multicentre randomized, double-blind, parallel-group study to compare the antihypertensive efficacy of Spirapril at 3 mg with 12 mg once daily, as determined by 24-hour ambulatory blood pressure monitoring (ABPM), in patients with mild to severe essential hypertension. Following a 4-week placebo run-in phase, 52 male and female outpatients, aged 23-67 years with mild to severe essential hypertension [diastolic blood pressure (DBP) > or = 100 mmHg and or = 10 mmHg) was the same in both groups (32% and 37%). There were mean decrease in both systolic blood pressure (SBP) and DBP at trough with both 3 mg and 12 mg doses: -9/-7 mmHg and -12/-7 mmHg, respectively. The rate of normalization (trough DBP < or = 90 mmHg) was 12% and 30% with the 3 mg and 12 mg doses, respectively. Of the 44 patients whose daytime ABPM could be compared, one of 20 patients taking 3 mg of Spirapril, and 9 of 24 taking 12 mg of Spirapril achieved a DBP < or = 90 mmHg for all time intervals while awake. The differences in blood pressure-lowering were significant with both SBP and DBP during the day and at the end of the dosing interval (p < 0.001 and p < 0.01, respectively). The changes from baseline at 24 hours postdose for SBP/DBP were -3/-6 mmHg with 3 mg and -14/-12 mmHg with 12 mg of Spirapril.(ABSTRACT TRUNCATED AT 250 WORDS)
Robert P Hof - One of the best experts on this subject based on the ideXlab platform.
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time course of Spirapril induced structural and functional changes after myocardial infarction in rats followed with magnetic resonance imaging
Journal of Cardiovascular Pharmacology, 1993Co-Authors: W Zierhut, Markus Rudin, D Novosel, E Robertson, H G Zerwes, J P Evenou, R Stirnimann, Robert P HofAbstract:Structural alterations after myocardial infarction (MI) in rats are usually examined only after death of the experimental animal. Magnetic resonance imaging (MRI) allows repeated and noninvasive measurements of important structural [left ventricular (LV) mass, LV wall thickness, LV chamber radius] as well as function [LV end-systolic and LV end-diastolic volume, stroke volume (SV), ejection fraction (EF)] parameters for a prolonged period. We describe our experience in a series of experiments in rats. Three weeks after MI, infarct size (IS) was determined by MRI and the rats were divided into two groups with equal IS. Three weeks later, treatment with the angiotensin-converting enzyme (ACE) inhibitor Spirapril (10 mg/kg in food) or placebo was started. In both groups, the first MRI scan taken before the treatment showed moderately dilated left ventricles and signs of impaired LV function, i.e., an increase in LV end-systolic and end-diastolic volume and decreased EF. After 3-week treatment, no significant differences with respect to heart structure and function were detected as compared with those of untreated animals. Prolonged treatment for 10 weeks with Spirapril resulted in significant reduction of LV dilatation, LV mass, and LV end-systolic and end-diastolic volume, which was accompanied by improved EF. Hemodynamic examinations after treatment for 6 months showed, in contrast to control animals, no increase in right ventricular systolic pressure in animals receiving Spirapril. Furthermore, histologic examination of perfusion-fixed hearts at the end of the study demonstrated more pronounced LV dilatation in control animals, thus confirming the in vivo MRI data. Delayed treatment with Spirapril proved to have beneficial effects on structure and function of infarcted hearts within 10 weeks. Spirapril limited LV dilatation, reduced LV weight and LV end-systolic and end-diastolic volumes, and improved EF.
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Spirapril and cilazapril inhibit neointimal lesion development but cause no detectable inhibition of lumen narrowing after carotid artery balloon catheter injury in the rat
Blood Pressure, 1993Co-Authors: Nigel S Cook, Markus Rudin, Hansgunter Zerwes, Charles Pally, Robert P HofAbstract:Five groups of 12 rats were subject to balloon lesion of the left carotid artery and neointimal thickening was measured histologically 2 weeks after injury. Rat groups received either Spirapril (3, 10 or 30 mg/kg/day, administered throughout the study in the food), cilazapril (10 mg/kg/day) or placebo. Spirapril caused a dose-dependent inhibition of the neointimal thickening of the rat carotid artery. The degree of inhibition with 10 mg/kg/d Spirapril and cilazapril was similar (-44% and -42% respectively). The carotid lumen area was measured in vivo by nuclear magnetic resonance (NMR) imaging both before and 2 weeks after balloon injury and also postmortem by histological techniques. Two weeks after injury, the lumen area of the left carotid artery was significantly reduced following balloon injury, as measured by both techniques. Treatment did not detectably modify this stenosis process despite the use of two independent methods for assessing lumen size, even though neointimal thickening was strongly at...
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effect of Spirapril on left ventricular hypertrophy due to volume overload in rats
Journal of Cardiovascular Pharmacology, 1992Co-Authors: K Umemura, W Zierhut, Markus Rudin, D Novosel, E Robertson, B Pedersen, Robert P HofAbstract:The effect of the angiotensin-converting enzyme (ACE) inhibitor Spirapril on structural and functional parameters of volume-overloaded rat hearts was evaluated in a time-course study. Left ventricular hypertrophy (LVH) was induced by graded disruption of the aortic valve in male Wistar rats. Four weeks later, structural (LV mass and LV wall thickness) as well as functional parameters [LV end-systolic and end-diastolic volumes, stroke volume (SV), ejection fraction (EF)] were determined in anesthetized animals by magnetic resonance imaging (MRI). The rats were then divided into two groups, one of them receiving Spirapril (10 mg/kg/day) in food. LV parameters were evaluated by MRI at 4, 18, 25, and 32 days after treatment was started. MRI analysis before the start of treatment showed that both groups had developed a similar degree of eccentric LV hypertrophy. Similarly, LV wall thickness, end-systolic and end-diastolic volumes, SV, and EF did not differ between the groups. Treatment with Spirapril resulted in stable LV weight during the follow-up period of 32 days, whereas the untreated group showed a significant steady increase in heart weight. LV end-diastolic volume, LV end-systolic volume, and SV were smaller in the Spirapril group when measured after 25 and 32 days, but only the difference in end-diastolic volume reached statistical significance. LV wall thickness and EF were not affected by Spirapril. After the last MRI determinations, blood pressure (BP) and the response to angiotensin I (ANGI) were measured in conscious animals. Systolic BP (SBP) and mean arterial pressure (MAP) were significantly lower in Spirapril-treated rats, and the dose-response curve to ANGI was shifted to the right.(ABSTRACT TRUNCATED AT 250 WORDS)