PubMed · 9766175
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1998. After your heart attack.. https://pubmed.ncbi.nlm.nih.gov/9766175/
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Arrhythmic death can be reduced by antiarrhythmic drugs to a range of 24%. Electrophysiologic study by testing noninducibility of ventricular arrhythmia represents the classic method for evaluating the effectiveness of drug therapy. Several clinical studies have shown thaat sotalol suppresses VT induction and prevents arrhythmias recurrences at long term follow-up in 23% to 67% of patients. The efficacy of sotalol EP guided therapy in preventing VT/VF is not necessarily related to prevention of sudden death. In the ESVEM study the superiority of d,l-sotalol to other antiarrhythmic drugs was confirmed. The response to programmed ventricular stimulation was found to be strongly predictive for arrhythmia free state while the failure of sotalol therapy to suppress VT at the EP study was associated with an high recurrence rate (40%). However, EP study failes to predict freedom from sudden death. The beta-blocking activity of racemic sotalol may account for some of the observed survival benefit.Beta-blockers therapy reduces mortality in patients after myocardial infarction primarily by a reduction of sudden death. A reduction of death, worsening heart failure and life threatening ventricular arrhythmias was shown in a recent study on carvedilol. In the prospective study of Steinbeck the EP guided-therapy did not improve the overall outcome when compared to metoprolol. Suppression of inducible arrhythmias by antiarrhythmic drugs was associated with a better outcome. The effectiveness of defibrillator therapy in reducing overall mortality, has been uncertain since great clinical trials have been concluded. MADIT, AVID and CASH trials confirmed the superiority of ICD therapy over antiarrhythmic drugs therapy: ICD should be considered the first choice therapy in post-cardiac arrest patients. The ongoing BEST Trial will give us further responses about the interaction between EP study and metoprolol effect compared to ICD in patients post myocardial infarction also focusing on tolerability and compliance of the beta-blocking therapy in patients with low ejection fraction. In this study will be useful to optimize therapy in patients at high risk of sudden death.
Heart failure is one of the commonest debilitating conditions of industrialized society, with mortality and morbidity comparable with that of the common neoplastic diseases. The role of antagonists of the adrenergic beta-receptor (beta-blockers) in heart failure has been the subject of debate for many years. Data from studies of the therapeutic use of beta-blockers in patients following acute myocardial infarction suggest that in this circumstance these agents confer at least as much benefit to patients with heart failure as they do to those without. Similarly retrospective analysis of a number of the studies of angiotensin converting enzyme (ACE) inhibitors in heart failure suggest a greater effect of the combination of beta-blocker with ACE inhibitor compared with ACE inhibitor alone. The results of recent prospective, placebo-controlled studies of the addition of beta-blocker to standard therapy in patients with chronic heart failure have confirmed a significant beneficial effect. beta-blocker therapy in these studies was well tolerated and in addition to improved mortality, beta-blocker therapy is associated with improved morbidity in terms of progressive heart failure and numbers of hospitalizations. Initiation of beta-blocker therapy in heart failure may be associated with deterioration of cardiac function in the short term. Treatment should be started at a low dose of beta-blocker with slow up-titration in a number of steps over several weeks. In spite of the established benefits of ACE inhibition in patients with heart failure, this treatment is under-utilized. Part of this shortfall is due to physicians' perceptions regarding potential unwanted effects of ACE inhibition. Perceptions regarding unwanted effects of beta-adrenoceptor blocker therapy are likely to be at least as great. While beta-blockade represents a welcome addition to the therapeutic armoury of physicians caring for patients with heart failure, initiation and stabilization of beta-adrenoceptor blocker therapy should be undertaken under specialist supervision.
We previously reported that prostaglandin F(2alpha) (PGF(2alpha)) activates both phosphoinositide-hydrolyzing phospholipase C and phosphatidylcholine-hydrolyzing phospholipase D in osteoblast-like MC3T3-E1 cells and then induces the activation of protein kinase C (PKC). In this study, we investigated the effect of PGF(2alpha) on the induction of heat shock protein 27 (HSP27), a low-molecular-weight heat shock protein, in these cells. PGF(2alpha) significantly induced the accumulation of HSP27 dose-dependently within the range of 10 nM to 10 microM. PGF(2alpha) stimulated the increase in the levels of mRNA for HSP27. A total of 10 nM 12-O-tetradecanoylphorbol-13-acetate (TPA), an activator of PKC, induced the accumulation of HSP27. The stimulative effect of PGF(2alpha) was reduced in the PKC down-regulated cells. Calphostin C, a specific inhibitor of PKC, suppressed the PGF(2alpha)-induced HSP27 accumulation as well as that induced by TPA. HSP27 induction by PGF(2alpha) was reduced by U-73122, a phospholipase C inhibitor, or propranolol, a phosphatidic acid phosphohydrolase inhibitor. PGF(2alpha) and TPA stimulated p42/p44 mitogen-activated protein (MAP) kinase. PD98059, an inhibitor of the upstream kinase that activates p42/p44 MAP kinase, suppressed the induction of HSP27 stimulated by PGF(2alpha) or TPA. PD98059 and calphostin C reduced the levels of mRNA for HSP27 increased by PGF(2alpha). These results indicate that PGF(2alpha) stimulates the induction of HSP27 via p42/p44 MAP kinase activation, which depends on upstream PKC activation in osteoblasts.