Two cases of bronchial asthma after treatment with amiodarone.

Amiodarone is a highly effective antiarrhythmic agent for the prevention of life-threatening arrhythmias. Two cases are described of patients who developed bronchial asthma after treatment with amiodarone. The bronchial asthma resolved after the dose of amiodarone was decreased in both patients. To our knowledge, an association between amiodarone and severe bronchial asthma has previously been reported only once in the medical literature. Physicians should note that amiodarone may cause bronchospasm in susceptible patients.

cis Element decoy against nuclear factor-kappaB attenuates development of experimental autoimmune myocarditis in rats.

Nuclear factor-kappaB (NFkappaB) plays a significant role in the coordinated transactivation of cytokine, inducible NO synthase (iNOS), and adhesion molecule genes. Although inflammation is an essential pathological feature of myocarditis, the role of NFkappaB in this process remains obscure. We examined the role of NFkappaB in the progression of rat experimental autoimmune myocarditis (EAM) and tested the hypothesis that NFkappaB blockade with a decoy against the cis element of NFkappaB can prevent the progression of EAM. Lewis rats were immunized with purified porcine cardiac myosin to establish EAM on day 0. NFkappaB decoy was infused into the rat coronary artery on day 0 (group NF0), 7 (group NF7), or 14 (group NF14) and harvested on day 21. Scrambled decoy was infused on day 0 (group SD0), 7 (group SD7), or 14 (group SD14) and served for control groups. The ratios of myocarditis-affected areas to the ventricular cross-sectional area of all treatment groups were significantly lower than those of the control groups (group NF0, 33+/-18% versus SD0, 53+/-14%; group NF7, 19+/-15% versus SD7, 50+/-16%; and group NF14, 34+/-10% versus SD14, 52+/-14%). Immunohistochemical and immunoblot analyses showed expression of ICAM-1, iNOS, IL-2, and TNFalpha in myocardium of scrambled decoy groups, and this expression was effectively suppressed by NFkappaB decoy treatment. Thus, we found that NFkappaB is a key regulator in the progression of EAM and that in vivo transfection of NFkappaB decoy reduces the severity of EAM.

Effects of growth hormone following chronic angiotensin-converting enzyme inhibition in chronic heart failure: their relation to infarct size.

Growth hormone (GH) has been attracted as a possible adjunctive treatment for severe heart failure. However, its treatment effects have been still controversial. To assess severity of basal cardiac disease states in which GH might be effective, we analyzed the relation of treatment effects of GH following chronic angiotensin-converting enzyme (ACE) inhibition on cardiac function and structures to infarct size in rat model of chronic heart failure after myocardial infarction. One day after coronary occlusion, rats were randomized to either an ACE inhibitor, temocapril (T) (80 mg/L in drinking water) or placebo for 12 weeks. The animals received concomitant recombinant human (rh) GH (2 mg/kg/day, SC) (T + GH) or vehicle during the final 2 weeks. Compared with the T group, the T + GH group with large MI had smaller increments of left ventricular (LV) dP/dt(max) (0 vs 17%) and cardiac output (9 vs 49%), less improvement of LV relaxation (tau) (-3 vs 29%) and systemic vascular resistance (8 vs 29%), and a greater increase in LV end-diastolic pressure (123 vs -5%) than did the T+GH group with moderate MI. In the T + GH group when compared with the T group, these functional alterations were associated with a 12% reduction in the LV capillary density and a 21% increase in hydroxyproline contents in rats with large MI, whereas a 12% increase in the density and similar collagen contents were found in rats with moderate MI. Thus, prominent beneficial cardiovascular effects of the additive short-term, high-dose GH to chronic high-dose ACE inhibition were obtained in rats with moderate MI, whereas little additional benefit or even detrimental effects of GH were found in rats with large MI. The present study may provide an insight into the therapeutic strategy of GH given late after MI in the presence of chronic ACE inhibition in congestive heart failure.

Successful prevention of recurrent ventricular fibrillation by intravenous isoproterenol in a patient with Brugada syndrome.

Intravenous administration of isoproterenol restored the ST-segment configuration to nearly normal in the right precordial leads and completely prevented spontaneous VF attacks in a patient with Brugada syndrome. The formation of a Brugada-type ECG has been attributed to the transmural dispersion of repolarization of the right ventricular epicardium and related to modulation of the autonomic nervous system. Our case may provide clues to the pathophysiological mechanism of this syndrome.

Association of matrix metalloproteinase expression and left ventricular function in idiopathic dilated cardiomyopathy.

Myocardial remodeling is an important predictor for the development of dilated cardiomyopathy (DCM). Matrix metalloproteinases (MMPs) are the family of proteins responsible for extracellular remodeling, and tissue inhibitors of metalloproteinases (TIMPs) tightly control their activity. In the present study, the expression of MMP-2, MMP-9, TIMP-1 and TIMP-2 was determined by immunohistochemistry in right ventricular endomyocardial biopsy samples from 16 patients with idiopathic DCM, and its clinical significance was evaluated by comparison with parameters of cardiac function. To obtain a semi-quantitative assessment of MMP and TIMP expression, the average number of positive cells per high power field was counted. The left ventricular ejection fraction (LVEF) significantly correlated with the expression of both MMP-2 (r=-0.68) and TIMP-2 (r=-0.58). Patients were classified into 2 groups according to the degree of MMP-2 expression: strongly positive and weakly positive. LVEF, left ventricular (LV) end-diastolic pressure, right ventricular end-diastolic pressure, pulmonary capillary wedge pressure and the plasma norepinephrine level were significantly greater in the strongly positive group (p<0.05). In conclusion, the expression of MMPs and TIMPs in the cardiac matrix of patients with idiopathic DCM is closely associated with myocardial remodeling and subsequent deterioration of LV performance. These findings suggest new therapeutic targets for patients with idiopathic DCM.