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BACKGROUND: To be listed for heart transplantation (HTx), optimization of the dosage of angiotensin converting enzyme (ACE) -inhibitors is recommended worldwide even though this issue has not been thoroughly investigated in the pre-transplantation cohort. OBJECTIVE: The aim of this database study was to analyze the prognostic impact of a pre-defined high vs a low ACE inhibitor dose range at the time of listing for elective HTx in addition to various previously established prognostic factors. METHODS: Medical records from 237 patients (84% male, mean age 54 years) admitted between January 1995 and January 1998 from 25 different centers in Austria were reviewed. Forty-seven percent were taking > or =75 mg captopril, > or =20 mg enalapril, > or =20 mg lisinopril or > or =5 mg ramipril daily ("high-dose" group) and 53% received smaller doses ("low-dose" group). RESULTS: No significant differences between groups were detected at baseline except that patients with higher ACE inhibitor doses were more likely to take nitrates, beta-blockers and amiodarone, received higher furosemide doses and had higher serum gamma-glutamyl transferase levels. Follow-up was 328 days (248 SD) with 16% deaths in the "high-dose" group vs 288 days (270 SD) with 25% deaths in the "low-dose" group. Kaplan-Meier survival curves demonstrated a significant difference over time between the two treatment groups (P = 0.03). Furthermore, dichotomized ACE inhibitor treatment at the time of listing was the strongest independent single predictor of mortality (P = 0.01) with only blood pressure (P = 0.02), alanine transaminase (P = 0.02) and left ventricular end diastolic diameter (P = 0.02) providing additional prognostic information. To explain these findings several factors have to be considered a) greater benefit with higher ACE inhibitor doses b) sicker patients receiving lower ACE inhibitor doses and c) more experienced heart failure care of the "high-dose" group. CONCLUSIONS: Heart transplantation candidates who, for whatever reason, receive ACE-inhibitors below the recommended dosages, are at increased mortality risk and thus merit greater scrutiny.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10703687&dopt=Abstract
Clin Exp Hypertens A. 1988;10(6):1259-70.
Local inhibition of angiotensin II formation and bradykinin degradation in isolated hearts.
Scholkens BA, Linz W.
Hoechst AG, Frankfurt, (Main), FR Germany.
The interaction of the converting enzyme (CE)-inhibitor ramipril and the bradykinin (BK)-antagonist D-Arg-[Hyp2, Thi5,8, D-Phe7]BK with angiotensin I (ANG), ANG II and BK were studied in isolated hearts of rats and guinea pigs. In isolated working rat hearts perfusion with ANG I and ANG II reduced cardiac function and coronary flow, increased the activities of lactate dehydrogenase (LDH) and creatine kinase (CK) in the perfusate, decreased high-energy rich phosphates and glycogen in the myocardium and increased duration and incidence of post-ischemic reperfusion arrhythmias. BK on the other hand reduced LDH and CK activities, improved metabolic parameters in the myocardium and reduced reperfusion arrhythmias. In isolated rat hearts pretreatment with ramipril protected against reperfusion arrhythmias and reduced enzyme activities of LDH and CK in the coronary effluent. Cardiodynamic parameters and coronary flow improved and myocardial tissue levels of glycogen, ATP and creatine phosphate (CP) were elevated. Almost identical changes were seen during perfusion with BK. The cardioprotective effects produced by both, the CE-inhibitor and BK, were completely abolished when the BK-antagonist was added to the perfusate, while a smaller inhibition was obtained by indomethacin perfusion. In isolated guinea pig hearts BK increased coronary flow. Single-dose oral pretreatment with ramipril potentiated, whereas perfusion with the BK-antagonist abolished this effect. These data add support to the hypothesis that local inhibition of CE = kininase II contributes to the beneficial effects of CE-inhibitors in the heart.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2975971&dopt=Abstract
Probl Tuberk. 1999;(6):42-4.
[Efficiency of ramipril treatment in patients with chronic obstructive bronchitis complicated by chronic cor pulmonale]
[Article in Russian]
Butorov IV, Vatulin VN, Bodrug NI, Fudulei RF, Matkovskii SK, Butorova VG.
The supplementation of the angiotensin-converting enzyme inhibitor ramipril to combined therapy in patients with chronic obstructive bronchitis complicated by chronic cor pulmonale resulted in positive central, pulmonary, and peripheral hemodynamic changes, improved peripheral tissue oxygenation, by exerting beneficial effects on the course of the disease.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10715959&dopt=Abstract
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