enalapril and Endomyocardial-Fibrosis

Echocardiography was used in the study of 40 patients with stage IIA-IVB lymphogranulomatosis. In 2-6 years before the study all patients had been treated with combination radio- (36-44 Gy) and chemotherapy. Echocardiography revealed endomyocardial fibrosis and signs of cardiac remodeling (reduced left ventricular dimensions and volumes, decreased myocardial mass and impaired diastolic function). The patients were divided into 2 groups. Patients of group 1 were given enalapril (5-10 mg/day), of group 2 - potassium and magnesium aspartate and inosine. In 2 months 68% of patients in group 1 demonstrated improvement of structural and functional state of the heart, no such changes occurred in group 2.

Topics: Adolescent; Adult; Angiotensin-Converting Enzyme Inhibitors; Enalapril; Endomyocardial Fibrosis; Female; Hodgkin Disease; Humans; Male; Middle Aged; Radiotherapy

Patients with renal failure develop cardiovascular alterations which contribute to the higher rate of cardiac death. Blockade of the renin angiotensin system ameliorates the development of such changes. It is unclear, however, to what extent ACE-inhibitors can also reverse existing cardiovascular alterations. Therefore, we investigated the effect of high dose enalapril treatment on these alterations.. Male Sprague Dawley rats underwent subtotal nephrectomy (SNX, n = 34) or sham operation (sham, n = 39). Eight weeks after surgery, rats were sacrificed or allocated to treatment with either high-dose enalapril, combination of furosemide/dihydralazine or solvent for 4 weeks. Heart and aorta were evaluated using morphometry, stereological techniques and TaqMan PCR.. After 8 and 12 weeks systolic blood pressure, albumin excretion, and left ventricular weight were significantly higher in untreated SNX compared to sham. Twelve weeks after SNX a significantly higher volume density of cardiac interstitial tissue (2.57±0.43% in SNX vs 1.50±0.43% in sham, p<0.05) and a significantly lower capillary length density (4532±355 mm/mm(3) in SNX vs 5023±624 mm/mm(3) in sham, p<0.05) were found. Treatment of SNX with enalapril from week 8-12 significantly improved myocardial fibrosis (1.63±0.25%, p<0.05), but not capillary reduction (3908±486 mm/mm(3)) or increased intercapillary distance. In contrast, alternative antihypertensive treatment showed no such effect. Significantly increased media thickness together with decreased vascular smooth muscles cell number and a disarray of elastic fibres were found in the aorta of SNX animals compared to sham. Both antihypertensive treatments failed to cause complete regression of these alterations.. The study indicates that high dose ACE-I treatment causes partial, but not complete, reversal of cardiovascular changes in SNX.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Cardiomyopathies; Enalapril; Endomyocardial Fibrosis; Male; Nephrectomy; Rats; Rats, Sprague-Dawley; Treatment Outcome; Uremia

A 34-year-old previously healthy woman was admitted to another hospital because of abdominal pain, cough and dyspnea. Peripheral eosinophilia was present. Two months later she was admitted to the cardiology department with signs of mitral regurgitation. Dyspnea, fatigue, skin rashes with pruritus and a systolic murmur were noted.. Laboratory tests showed 11.4/nl leukocytes (normal range 4.8-10.8/nl) with an eosinophilia of 19% (normal range < 4%) corresponding to 2.2/nl. Cardiac magnetic resonance imaging revealed endomyocardial fibrosis involving the posterior mitral leaflet with resulting valvular regurgitation. Doppler ultrasound showed restrictive heart failure. DIAGNOSIS, THERAPY AND FURTHER COURSE: The diagnosis of idiopathic hypereosinophilia most likely as part of hypereosinophilic syndrome with cardiac involvement was made. The patient was treated with digitalis, diuretics and peptidyl dipeptidase (PDP) inhibitor. The treatment with glucocorticoids and cytotoxic agent to achieve a reduction of eosinophil count was ended by the patient a few weeks later.. The hypereosinophilic syndrome with endomyocardial fibrosis is rare, and its prognosis is grave. The pathophysiological mechanisms are not entirely clear, nearly 70 years after Löffler first described fibrous endocarditis with eosinophilia. Patients receive symptomatic medical therapies. Additional surgical treatment has been reported,. Antihypereosinophilic therapy is used to control the disease.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Cardiomyopathy, Restrictive; Cardiotonic Agents; Diagnosis, Differential; Digoxin; Diuretics; Drug Therapy, Combination; Echocardiography, Doppler; Enalapril; Endomyocardial Fibrosis; Female; Humans; Hypereosinophilic Syndrome; Magnetic Resonance Imaging; Mineralocorticoid Receptor Antagonists; Mitral Valve Insufficiency; Patient Compliance; Prognosis; Spironolactone; Sulfonamides; Torsemide

Angiotensin-converting enzyme inhibitors have been shown to reduce morbidity and mortality in patients with heart failure. The angiotensin type-1 blocking and cardioprotective properties of perindopril and enalapril were studied in a rat model of dilated cardiomyopathy after autoimmune myocarditis. Enalapril at 20 mg/kg showed the same angiotensin type-1 blocking action as perindopril at 2 mg/kg in rats with heart failure. Twenty-eight days after immunization, surviving Lewis rats (90/120 = 75%) were divided into six groups and administered perindopril at 0.02, 0.2 and 2 mg/kg per day (Groups P0.02, P0.2 and P2), enalapril at 2 and 20 mg/kg per day (Groups E2 and E20) or vehicle alone (Group V, all groups n = 15). After oral administration for 1 month, four of 15 (27%) rats in Group V, and two (13%) in Groups P0.02 and E2 died. None of the animals in Groups P0.2, P2 and E20, or normal rats (Group N) died. Although both angiotensin-converting enzyme inhibitors improved ventricular function in a dose-dependent manner, the left ventricular end-diastolic pressure and area of myocardial fibrosis were lower, and +/- dP/dt was higher in Group P2 (4.9 +/- 0.6 mmHg, 7.5 +/- 1.4% and +2651 +/- 254/-2622 +/- 189 mmHg/s, respectively) than in Group V (16.7 +/- 1.3, 36 +/- 2.6 and +2659 +/- 176/-2516 +/- 205, respectively) and Group E20 (7.5 +/- 2.5, 15.6 +/- 2.0 and +2018 +/- 110/-2097 +/- 102, respectively). Although the expression levels of transforming growth factor-beta1 and collagen-III mRNA in Group V (36.3 +/- 5.7 and 157.6 +/- 12.7%) were significantly higher than those in Group N (19.6 +/- 3.0 and 65.2 +/- 1.5%, both p < 0.01), they were reduced in Group P2 (21.4 +/- 5.9 and 75.2 +/- 9.3%, both p < 0.01). These results suggest that although enalapril can block increases in blood pressure caused by circulating angiotensin type-1, perindopril at 2 mg/kg may confer greater protection than enalapril at 20 mg/kg against injury from the renin-angiotensin system in heart failure.

Topics: Administration, Oral; Angiotensin I; Animals; Cardiomyopathy, Dilated; Collagen Type III; Disease Models, Animal; Dose-Response Relationship, Drug; Enalapril; Endomyocardial Fibrosis; Gene Expression; Heart Failure; Hemodynamics; Hypertension; Infusions, Intravenous; Male; Pericardial Effusion; Perindopril; Rats; Rats, Inbred Lew; RNA, Messenger; Survival Rate; Time Factors; Transforming Growth Factor beta; Transforming Growth Factor beta1; Ventricular Dysfunction, Left; Ventricular Pressure

Atrial structural remodeling creates a substrate for atrial fibrillation (AF), but the underlying signal transduction mechanisms are unknown. This study assessed the effects of ACE inhibition on arrhythmogenic atrial remodeling and associated mitogen-activated protein kinase (MAPK) changes in a dog model of congestive heart failure (CHF).. Dogs were subjected to various durations of ventricular tachypacing (VTP, 220 to 240 bpm) in the presence or absence of oral enalapril 2 mg. kg(-1). d(-1). VTP for 5 weeks induced CHF, local atrial conduction slowing, and interstitial fibrosis and prolonged atrial burst pacing-induced AF. Atrial angiotensin II concentrations and MAPK expression were increased by tachypacing, with substantial changes in phosphorylated forms of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p38-kinase. Enalapril significantly reduced tachypacing-induced changes in atrial angiotensin II concentrations and ERK expression. Enalapril also attenuated the effects of CHF on atrial conduction (conduction heterogeneity index reduced from 3.1+/-0.4 to 1.9+/-0.2 ms/mm, P<0.05), atrial fibrosis (from 11.9+/-1.1% to 7.5+/-0.4%, P<0.01), and mean AF duration (from 651+/-164 to 218+/-75 seconds, P<0.05). Vasodilator therapy of a separate group of VTP dogs with hydralazine and isosorbide mononitrate did not alter CHF-induced fibrosis or AF promotion.. CHF-induced increases in angiotensin II content and MAPK activation contribute to arrhythmogenic atrial structural remodeling. ACE inhibition interferes with signal transduction leading to the AF substrate in CHF and may represent a useful new component to AF therapy.

Topics: Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Atrial Fibrillation; Dogs; Electrophysiology; Enalapril; Endomyocardial Fibrosis; Heart Atria; Heart Failure; Hemodynamics; Hydralazine; Isosorbide Dinitrate; Mitogen-Activated Protein Kinases; Renin-Angiotensin System; Signal Transduction; Tachycardia, Ventricular

To determine whether antihypertensive treatment could alter hypertension and age-related progressive impairment of coronary hemodynamics and cardiac fibrosis in aged spontaneously hypertensive rats (SHR).. Old SHR were given their respective therapy for 3 months. To differentiate between hypertension and age-related changes, a comparison was made between left and right ventricular indices since the right ventricle was not exposed to pressure overload.. Male, 65-week-old spontaneously SHR were divided into three groups and were given either vehicle, felodipine (30 mg/kg per day) or enalapril (30 mg/kg per day). After 12 weeks of the respective treatments, systemic and coronary hemodynamics (radionuclide-labelled microspheres), right and left ventricular and aortic mass indices, and right and left ventricular hydroxyproline concentrations (an estimate of collagen) were determined.. Arterial pressure and total peripheral resistance were reduced to the same extent in SHRs treated with either felodipine or enalapril; however, compared to the control rats, enalapril was more effective in reducing left ventricular and aortic mass indices. Both agents also improved coronary hemodynamics of both ventricles in aged SHR but enalapril was more effective as indicated by a greater increase in coronary flow reserve and a greater decrease in minimal coronary vascular resistance. Furthermore, enalapril but not felodipine reduced left ventricular hydroxyproline concentration; and right ventricular hydroxyproline concentration increased with felodipine but remained unchanged with enalapril.. Both enalapril and felodipine ameliorated adverse cardiovascular effects of hypertension in the aged SHRs within 12 weeks, as demonstrated by reduced arterial pressure, diminished left ventricular mass, and improved coronary hemodynamics. Enalapril also decreased aortic mass and left ventricular collagen concentration and appeared to be more effective in improving coronary hemodynamics than felodipine, possibly as a result, in part, of reduced myocardial fibrosis.

Topics: Aging; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Body Weight; Calcium Channel Blockers; Cardiovascular System; Collagen; Enalapril; Endomyocardial Fibrosis; Felodipine; Hemodynamics; Hydroxyproline; Hypertension; Male; Myocardium; Rats; Rats, Inbred SHR

6 hours after the second dose (5 mg) of enalapril 9 males and 6 females (mean age 34.93 +/- 1.03 years) with endomyocardial fibrosis (EMF) underwent ECG and pulsed Doppler echocardiography to study enalapril effect on cardiohemodynamics. As shown by ventricular diastolic function and systolic flow in the pulmonary artery with estimation of mean pressure in the pulmonary artery according to Kitabatake, enalapril (renitek) affects positively cardiohemodynamics of EMF patients: improvement of ventricular diastolic function occurred in line with a significant fall in the pulmonary artery pressure. It is noted that application of Doppler echocardiography is essential for detection of restriction syndrome.

Topics: Adult; Analysis of Variance; Cardiomyopathy, Restrictive; Drug Evaluation; Echocardiography; Electrocardiography; Enalapril; Endomyocardial Fibrosis; Female; Hemodynamics; Humans; Male; Syndrome

To evaluate the effects of hypertension on cardiac hypertrophy, on myocardial structure, and on ventricular arrhythmias, 27 3-month-old spontaneously hypertensive rats were treated with enalapril (10 mg/kg) daily for 11 months and compared with 26 untreated control rats. Systolic arterial pressure was significantly decreased in treated rats, and at the end of the experiment, it was 199 +/- 3 mm Hg (treated) versus 237 +/- 3 mm Hg (controls) (p less than 0.001). At this time, spontaneous arrhythmias and induced arrhythmias either by programmed electrical stimulation (train of stimuli +1 or 2 extrastimuli) or by trains of eight stimuli at decreasing coupling intervals were observed in isolated heart preparations. Comparing enalapril-treated and control rats, spontaneous arrhythmias (9 of 27 versus 20 of 26, respectively; p less than 0.01), programmed stimulation-induced arrhythmias (3 of 26 versus 12 of 23, respectively; p less than 0.01), and trains of stimuli-induced arrhythmias (4 of 26 versus 14 of 19, respectively, p less than 0.001) were less frequent in the enalapril group. Left ventricular weight was decreased in treated rats by 18% (p less than 0.001). Enalapril administration diminished the fraction of myocardium occupied by foci of replacement fibrosis normally occurring in control rats by 59% (p less than 0.001). Finally, a significant correlation was found between left ventricular weight, the extent of myocardial fibrosis, and the occurrence of ventricular fibrillation. It was concluded that chronic treatment with enalapril, which resulted in attenuation of systemic arterial pressure by limiting cardiac hypertrophy and myocardial fibrosis, decreases the propensity of the heart of hypertensive rats to arrhythmogenesis.

Topics: Analysis of Variance; Animals; Arrhythmias, Cardiac; Blood Flow Velocity; Blood Pressure; Electrocardiography; Enalapril; Endomyocardial Fibrosis; Heart Rate; Heart Ventricles; Hypertension; Male; Rats; Rats, Inbred SHR; Ventricular Fibrillation