Invited commentary

Abstract

It is a privilege to review and comment on this interesting article. The experimental study presented by Dr Suematsu and coworkers demonstrates the beneficial effects of chronic administration of Nipradilol, a nitric oxide-releasing beta-adrenergic blocker, on myocardial injury following ischemic injury using an isolated rat heart model. The authors have postulated that chronic pretreatment with Nipradilol may attenuate the ischemic myocardial injury by enhancing coronary endothelial nitric oxide (NO) production and reducing lipid-peroxidation, and the results were mostly supportive of this hypothesis. This important work, after their previous work with short-term treatment with nipradilol, may differentiate a possible mechanism for Nipradilol protection of the myocardium against ischemic injury from the mechanism of NO production and lipid peroxidase inhibition. The conclusions are sound and mostly acceptable, however, there are some concerns about the interpretation of results. The following issues should be discussed to verify the conclusions derived from this study.The result from combined pretreatment with Nipradilol and ischemic preconditioning raises concerns, because the combination almost abolished the beneficial effects of Nipradilol pretreatment or produced worse results compared to the group with ischemic preconditioning alone. This may be a unique finding; however, the result might have been different if the authors had chosen a different time course for ischemic preconditioning. As the authors mentioned, the time protocol for the ischemic preconditioning employed here may not be optimal for a maximal protective effect. The optimal time protocol for ischemic preconditioning is still controversial, but an appropriate protocol is mandatory in this study to examine protective behavior against ischemic injury with and without Nipradilol.The result also introduces a problem in the clinical setting. If patients have been pretreated with a beta-blocker, is ischemic preconditioning not recommended during intervention or surgery? The effect of ischemic preconditioning in this study should be clearly described and more detailed data may be required. Since the mechanism of the ischemic preconditioning is thought to include ATP sensitive K+ channels, endogenous NO synthesis, adenosine metabolism and more, further investigation to examine the protective mechanism of Nipradilol using possible modifications of these mechanisms is necessary in future.In summary, although the study design and the results have some controversial points, the authors deserve congratulations for their sitmulating work in pharmacological myocardial protection and its mechanism from the standpoint of ischemic preconditioning and endogenous NO synthesis. It is a privilege to review and comment on this interesting article. The experimental study presented by Dr Suematsu and coworkers demonstrates the beneficial effects of chronic administration of Nipradilol, a nitric oxide-releasing beta-adrenergic blocker, on myocardial injury following ischemic injury using an isolated rat heart model. The authors have postulated that chronic pretreatment with Nipradilol may attenuate the ischemic myocardial injury by enhancing coronary endothelial nitric oxide (NO) production and reducing lipid-peroxidation, and the results were mostly supportive of this hypothesis. This important work, after their previous work with short-term treatment with nipradilol, may differentiate a possible mechanism for Nipradilol protection of the myocardium against ischemic injury from the mechanism of NO production and lipid peroxidase inhibition. The conclusions are sound and mostly acceptable, however, there are some concerns about the interpretation of results. The following issues should be discussed to verify the conclusions derived from this study. The result from combined pretreatment with Nipradilol and ischemic preconditioning raises concerns, because the combination almost abolished the beneficial effects of Nipradilol pretreatment or produced worse results compared to the group with ischemic preconditioning alone. This may be a unique finding; however, the result might have been different if the authors had chosen a different time course for ischemic preconditioning. As the authors mentioned, the time protocol for the ischemic preconditioning employed here may not be optimal for a maximal protective effect. The optimal time protocol for ischemic preconditioning is still controversial, but an appropriate protocol is mandatory in this study to examine protective behavior against ischemic injury with and without Nipradilol. The result also introduces a problem in the clinical setting. If patients have been pretreated with a beta-blocker, is ischemic preconditioning not recommended during intervention or surgery? The effect of ischemic preconditioning in this study should be clearly described and more detailed data may be required. Since the mechanism of the ischemic preconditioning is thought to include ATP sensitive K+ channels, endogenous NO synthesis, adenosine metabolism and more, further investigation to examine the protective mechanism of Nipradilol using possible modifications of these mechanisms is necessary in future. In summary, although the study design and the results have some controversial points, the authors deserve congratulations for their sitmulating work in pharmacological myocardial protection and its mechanism from the standpoint of ischemic preconditioning and endogenous NO synthesis.