enalapril and Myocarditis

We have previously demonstrated that angiotensin-converting enzyme (ACE) inhibition with enalapril produces persistent effects that protect against future nitric oxide synthase (NOS) inhibitor (L-arginine methyl ester, L-NAME)-induced cardiac dysfunction and outer wall collagen deposition in spontaneously hypertensive rats (SHR). In the present study, we dissect the cytokine/chemokine release profile during NOS inhibition, its correlation to pathological cardiac remodeling and the impact of transient ACE inhibition on these effects. Adult male SHR were treated with enalapril (E+L) or tap water (C+L) for 2 weeks followed by a 2-week washout period. Rats were then subjected to 0, 3, 7 or 10 days of L-NAME treatment. The temporal response to NOS inhibition was evaluated by measuring arterial pressure, cardiac remodeling and cytokine/chemokine levels. L-NAME equivalently increased blood pressure and myocardial and vascular injury in C+L and E+L rats. However, pulse pressure (PP) was only transiently altered in C+L rats. The levels of several inflammatory mediators were increased during L-NAME treatment. However, interleukin-6 (IL-6) and IL-10 and monocyte chemoattractant protein-1 were uniquely increased in C+L hearts; whereas IL-4 and fractalkine were only elevated in E+L hearts. By days 7 and 10 of L-NAME treatment, there was a significant increase in the cardiac density of macrophages and proliferating cells, respectively only in C+L rats. Although myocardial injury was similar in both treatment groups, PP was not changed and there was a distinct cardiac chemokine/cytokine signature in rats previously treated with enalapril that may be related to the lack of proliferative response and macrophage infiltration in these hearts.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Arterial Pressure; Cell Proliferation; Chemokine CCL2; Chemokines; Cytokines; Disease Progression; Enalapril; Enzyme Inhibitors; Interleukin-10; Interleukin-6; Macrophages; Male; Myocarditis; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; Rats; Rats, Inbred SHR

The combination of ventricular tachycardia (VT) and severe left ventricular dysfunction presents a serious challenge in management of acute fulminant myocarditis (AFM). We report a case of a 17-month-old girl with AFM, presented with hypotension and VT, successfully treated with respiratory and inotropic support, high-dose intravenous immunoglobulin, and amiodarone. The myocardial function improved significantly within 2 weeks of treatment. The clinical course was complicated by significant amiodarone-induced hepatotoxicity, disseminated intravascular coagulation, and deep-vein thrombosis. She was later diagnosed with congenital dysfibrinogenemia and treated with chronic Lovenox therapy.

Topics: Acute Disease; Amiodarone; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Drug Therapy, Combination; Electrocardiography; Enalapril; Female; Follow-Up Studies; Humans; Immunoglobulins, Intravenous; Immunologic Factors; Infant; Myocarditis; Tachycardia, Ventricular; Ventricular Function, Left

Losartan, a recently developed nonpeptide angiotensin II (AII) receptor antagonist, was orally administered for 14 days to mice with viral myocarditis, beginning 7 days after encephalomyocarditis virus inoculation. The angiotensin-converting enzyme inhibitors (ACEI) captopril and enalapril were also administered in the same manner to compare the therapeutic effects of these three drugs on the degree of myocarditis, acute heart failure, and left ventricular (LV) hypertrophy. Heart weight and the heart weight/body weight ratio were reduced by losartan (60 mg/kg/day) and captopril (7.5 mg/kg/day), but not by enalapril (1 mg/kg/day). LV wall thickness and cavity dimension were decreased in the losartan and captopril groups. Captopril reduced both myocardial necrosis and inflammation, whereas enalapril reduced myocardial necrosis but not inflammation. However, none of the studied losartan doses (1.2, 12, 60 mg/kg/day) influenced myocardial necrosis and inflammation resulting from viral infection. Thus, specific blockade of AII is beneficial in congestive heart failure (CHF) and LV hypertrophy but is not effective in viral-evoked inflammation and injury.

Topics: Acute Disease; Administration, Oral; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Biphenyl Compounds; Body Weight; Captopril; Cardiovirus Infections; Enalapril; Encephalomyocarditis virus; Female; Heart; Heart Failure; Hypertrophy, Left Ventricular; Imidazoles; Injections, Intraperitoneal; Losartan; Mice; Mice, Inbred C3H; Myocarditis; Myocardium; Organ Size; Random Allocation; Tetrazoles; Therapeutic Equivalency

Eight infants aged between 4 days and 12 weeks with severe heart failure that was refractory to optimal conventional treatment with diuretics were treated with enalapril. The starting dose was 0.1 mg/kg/day, increasing according to response to 0.12-0.43 mg/kg/day. One infant with severe myocarditis did not tolerate enalapril because of hypotension and later died of intractable heart failure. Six of the remaining patients had congenital systemic to pulmonary shunts and one had a simple aortic coarctation. Two weeks after starting enalapril the clinical features of heart failure had improved in all the infants, the mean (SEM) plasma sodium concentration had increased from 129 (2.4) to 136 (1.1) mmol/l and plasma urea concentration had fallen from 7.0 (0.85) to 2.9 (0.85) mmol/l. These data suggest that enalapril is a potentially useful treatment for severe heart failure in infancy.

Topics: Dose-Response Relationship, Drug; Enalapril; Heart Defects, Congenital; Heart Failure; Humans; Infant; Infant, Newborn; Myocarditis; Sodium; Urea