ramipril and Cardiomyopathies

We tested the hypothesis that renin-angiotensin system inhibition could reverse left ventricular diastolic dysfunction in patients with type 2 diabetes.. Forty asymptomatic patients with type 2 diabetes were recruited in this double-blind cross-over trial. Left ventricular diastolic function was assessed at baseline with Doppler echocardiography; ratios of early to late peak flow velocity through the mitral orifice (E/A) and velocity time integral of early to late transmitral diastolic flow (VTIE/VTIA) were evaluated. In addition, plasma brain natriuretic peptide (BNP) was measured. Patients received randomly either ramipril (2.5 mg/day), or telmisartan (40 mg/day) or their combination for 3 months. Subsequently, every patient was crossed over to alternative regimens after a 2-week washout period. Measurements were repeated at the end of each treatment period. Both E/A and VTIE/VTIA ratios were increased (29 and 20% with ramipril, 25 and 23% with telmisartan and 36 and 28% with combination treatment, respectively, p < 0.001), whereas plasma BNP levels were significantly reduced with all 3 regimens (9% with ramipril, 25% with telmisartan and 36% with combination, p < 0.001).. Both ramipril and telmisartan improve echocardiographic left ventricular diastolic indices and reduce plasma BNP levels in diabetic patients; their combination yields an even better therapeutic effect.

Topics: Analysis of Variance; Angiotensin-Converting Enzyme Inhibitors; Benzimidazoles; Benzoates; Blood Flow Velocity; Cardiomyopathies; Cross-Over Studies; Diabetes Complications; Double-Blind Method; Echocardiography, Doppler; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Ramipril; Statistics, Nonparametric; Telmisartan; Treatment Outcome

We hypothesized that peroxisome proliferator-activated receptors (PPARs) might be involved in a complex protective action of ACE inhibitors (ACEi) in anthracyclines-induced cardiomyopathy. For purpose of study, we compared effects of ramipril on cardiac dysfunction, cardiac failure markers and PPAR isoforms in moderate and severe chronic daunorubicin-induced cardiomyopathy. Male Wistar rats were administered with a single intravenous injection of daunorubicin: 5mg/kg (moderate cardiomyopathy), or 15mg/kg (severe cardiomyopathy) or co-administered with daunorubicin and ramipril (1mg/kg/d, orally) or vehicle for 8 weeks. Left ventricular function was measured invasively under anesthesia. Cardiac mRNA levels of heart failure markers (ANP, Myh6, Myh7, Myh7b) and PPARs (alpha, beta/delta and gama) were measured by qRT-PCR. Protein expression of NADPH subunit (gp91phox) was measured by Western blot. Moderate cardiomyopathy exhibited only minor cardiac dysfunction what was corrected by ramipril. In severe cardiomyopathy, hemodynamic dysfunction remained unaltered upon ramipril although it decreased the significantly up-regulated cardiac ANP mRNA expression. Simultaneously, while high-dose daunorubicin significantly decreased PPARbeta/delta and PPARgama mRNA, ramipril normalized these abnormalities. Similarly, ramipril reduced altered levels of oxidative stress-related gp91phox. On the other hand, ramipril was unable to correct both the significantly decreased relative abundance of Myh6 and increased Myh7 mRNA levels, respectively. In conclusion, ramipril had a protective effect on cardiac function exclusively in moderate chronic daunorubicin-induced cardiomyopathy. Although it normalized abnormal PPARs expression and exerted also additional protective effects also in severe cardiomyopathy, it was insufficient to influence impaired cardiac function probably because of a shift in myosin heavy chain isoform content.

Topics: Angiotensin-Converting Enzyme 2; Animals; Anthracyclines; Cardiomyopathies; Gene Expression Regulation; Heart; Male; Myosin Heavy Chains; NADPH Oxidases; Nitric Oxide; Peptidyl-Dipeptidase A; Peroxisome Proliferator-Activated Receptors; PPAR delta; PPAR gamma; PPAR-beta; Ramipril; Rats; Rats, Wistar; Receptor, Angiotensin, Type 1; RNA, Messenger; Signal Transduction

A 27-year-old woman was admitted to the emergency room because of dyspnoea. Two months earlier she had given birth to a healthy young boy via cesarean section.. Computed tomography showed acute embolism in both pulmonary arteries. Chest X-ray and echocardiography revealed an enlarged left ventricle, a highly reduced left ventricular function and thrombosis in the left ventricle.. The patient was treated with extensive medical heart failure therapy, and also with bromocriptine for eight weeks. Six months later, left ventricular ejection fraction had significantly improved.. Peri- or postpartum cardiomyopathy (PPCM) is a rare, potentially life-threatening heart disease, which is characterized by sudden onset of heart failure between the final weeks of pregnancy and up to six months after childbirth. Early diagnosis is crucial for the patient's prognosis. Recent pilot studies on the effect of adding bromocriptine to standard heart failure therapy indicated an improvement of prognosis and myocardial function. In this case significant improvement of left ventricular function was thus achieved.

Topics: Adrenergic beta-1 Receptor Antagonists; Adult; Angiotensin-Converting Enzyme Inhibitors; Anticoagulants; Antihypertensive Agents; Bisoprolol; Bromocriptine; Cardiomyopathies; Female; Heparin, Low-Molecular-Weight; Humans; Mineralocorticoid Receptor Antagonists; Postpartum Period; Radiography; Ramipril; Risk Factors; Spironolactone; Sulfonamides; Torsemide; Treatment Outcome

The case of a 66-year-old male with heart failure and cardiorenal syndrome is presented. The patient had normal renal function before intensive treatment with diuretics and ACE inhibitor. Shortly after the ACE inhibitor was stopped and diuretics were either stopped or reduced in dosage, his renal function normalized. Suggestions are presented for follow-up after initiation of ACE inhibitor treatment.

Topics: Angiotensin-Converting Enzyme Inhibitors; Cardiomyopathies; Diuretics; Furosemide; Heart Failure; Humans; Kidney; Male; Metolazone; Middle Aged; Ramipril; Spironolactone; Uremia

Ac-SDKP (N-acetyl-seryl-aspartyl-lysyl-proline) is a physiological tetrapeptide hydrolysed by ACE (angiotensin-converting enzyme). In experimental models of hypertension, Ac-SDKP has antifibrotic effects in the heart; however, the role of Ac-SDKP in diabetic cardiomyopathy is currently unknown. The aim of the present study was to evaluate the effect of Ac-SDKP on cardiac systolic and diastolic function, and interstitial and perivascular fibrosis in the heart of diabetic rats.Diabetes was induced in 55 Sprague-Dawley rats by streptozotocin injection. Control rats (n=18)underwent only buffer injection.Out of the 55 diabetic rats, 19 were chronically treated with insulin and 13 with the ACEI (ACE inhibitor) ramipril (3 mg x kg(-1 )of body weight x day(-1)). At 2 months after the onset of diabetes, Ac-SDKP (1 mg x kg(-1) of body weight x day(-1)) was administered by osmotic minipumps for 8 weeks to eight control rats, 13 diabetic rats, seven diabetic rats treated with ramipril and nine insulin-treated diabetic rats. Diabetic rats had a significant increase in blood glucose levels. Left ventricular interstitial and perivascular fibrosis, and TGF-beta1 (transforming growth factor-beta1) protein levels were increased in diabetic rats, but not in insulin-treated diabetic rats and ramipril-treated diabetic rats, compared with control rats. Ac-SDKP administration significantly reduced left ventricular interstitial and perivascular fibrosis in diabetic rats and in diabetic rats treated with ramipril. This was accompanied by a significant reduction in active TGF-beta1 and phospho-Smad2/3 protein levels in myocardial tissue of diabetic rats. Echocardiography showed that diabetes was associated with increased end-systolic diameters, and depressed global systolic function and diastolic dysfunction, as assessed by transmitral Doppler velocity profile. These changes were completely reversed by insulin or ramipril treatment. Ac-SDKP treatment partially restored diastolic function in diabetic rats. In conclusion, Ac-SDKP administration in diabetic rats reduces left ventricular interstitial and perivascular fibrosis, active TGF-beta1 and phospho-Smad2/3levels, and improves diastolic function. Taken together, these findings suggest that, by inhibiting theTGF-beta/Smad pathway, Ac-SDKP protects against the development of diabetic cardiomyopathy

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Cardiomyopathies; Diabetes Complications; Diabetes Mellitus, Experimental; Fibrosis; Heart Ventricles; Hypoglycemic Agents; Insulin; Male; Myocardium; Oligopeptides; Ramipril; Rats; Rats, Sprague-Dawley; Smad Proteins; Transforming Growth Factor beta1

We investigated the role of kinin and nitric oxide (NO) in the modulation of cardiac O(2)consumption in Syrian hamsters with overt heart failure (HF) and age-matched normal hamsters. Using echocardiography, the hamsters with heart failure had reduced ejection fraction [31(+/-8) v 76(+/-5)%] and LV dilation [4.9(+/-0. 2) v 5.7(+/-0.3) mm, both P<0.05 from normal]. O(2)consumption in the left ventricular free wall was measured using a Clark-type O(2)electrode in an air-tight chamber, containing Krebs solution buffered with Hepes (37 degrees C, pH 7.4). Concentration response curves to bradykinin (BK), ramiprilat (RAM), amlodipine (AMLO) and the NO donor, S -nitroso- N -acetyl-penicillamine (SNAP) were performed. Basal myocardial O(2)consumption was lower in the HF group compared to normal [316(+/-21) v 404(+/-36) nmol O(2)/min/g, respectively, P<0.05]. In the hearts from normal hamsters BK (10(-4)mol/l), RAM (10(-4)mol/l), and AMLO (10(-5)mol/l) all significantly reduced myocardial O(2)consumption by 42(+/-6)%, 29(+/-7)% and 27(+/-5)% respectively. This reduction was attenuated in the presence of N -nitro- l -arginine methyl ester (l -NAME) [BK: 3.3(+/-1.5)%, RAM: 3.3(+/-1.2)%, AMLO: 2.3(+/-1.2)%, P<0.05]. Interestingly in the hearts from HF group, BK, RAM and AMLO caused a significantly smaller reduction in myocardial O(2)consumption [10(+/-2)%, 2.5(+/-1.3)%, 6.3(+/-2.3)%, P<0.05]. In contrast, the NO donor SNAP reduced myocardial O(2)consumption in both groups and all those responses were not affected by l -NAME. These data indicate that endogenous NO production through the kinin-dependent mechanism is impaired at end-stage heart failure. The loss of kinin and NO control of mitochondrial respiration may contribute to the pathogenesis of heart failure.

Topics: Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Animals; Body Weight; Bradykinin; Cardiomyopathies; Cricetinae; Dose-Response Relationship, Drug; Echocardiography; Enzyme Inhibitors; Kinins; Male; Mesocricetus; Muscles; Myocardium; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Donors; Organ Size; Oxygen; Oxygen Consumption; Penicillamine; Ramipril; Vasodilator Agents

Experimental uremia is known to cause cardiac hypertrophy. In the present study we examined the effect of uremia with or without concomitant treatment of hypertension by the converting enzyme Ramipril (125 micrograms/day) on micromorphometric indices of cardiac interstitium at the light microscopical and ultrastructural level. In male SD rats, 21 days of uremia caused an increase of total heart weight (1040 +/- 73 mg wet wt vs. 871 +/- 81 in controls, P less than 0.05) with an increase of both right and left ventricular weight. This was accompanied by reduction of capillary cross-sectional area despite unchanged capillary length. The volume density (cm3/cm3) of cardiomyocytes was unchanged (0.881 +/- 0.01 vs. 0.871 +/- 0.016 in controls), but volume density of interstitial tissue (excluding capillary lumen) was significantly increased (0.042 +/- 0.011 cm3 interstitial tissue/cm3 total heart tissue vs. 0.019 +/- 0.007 in controls). This was associated with signs of activation of interstitial cells, that is, increased volume of interstitial cell nuclei and interstitial cell cytoplasm. Concomitantly, a significant increase of volume density of non-cellular interstitial ground substance was found which was not normalized by antihypertensive treatment using Ramipril. After three months of uremia, electron microscopy showed collagen fiber deposition in the interstitium. Comparable interstitial fibrosis was not observed in hearts of rats with renovascular (one clip-two kidney) hypertension. It is concluded that uremia increases myocardial interstitial ground substance by mechanisms independent of hypertension. The data may be relevant for recent findings of diastolic heart malfunction secondary to impaired compliance in uremic patients.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Bridged Bicyclo Compounds; Cardiomyopathies; Fibrosis; Hypertension; Male; Nephrectomy; Ramipril; Rats; Rats, Inbred Strains; Uremia