ABSTRACT
Heat shock proteins (HSPs) are an important family of protective proteins. They are involved actively in an array of cellular processes, including protective effects on the cardiovascular system in response to various stimuli. Increasing evidence shows that pharmacologic interventions that induce expression of HSPs may be a novel approach for the treatment of cardiovascular diseases. However, agents that induce expression of HSPs used previously are toxic or have harmful side effects, which limit their clinical application. Geranylgeranylacetone (GGA) is not only a widely used antiulcer agent in Asia, but also a nontoxic inducer of HSPs expression. It increases the expression of HSPs rapidly in the presence of ischemia, anoxia, oxidative stress, and toxicants, thereby having significant protective effects. The cardioprotective effects of GGA have been corroborated by experiments in vivo and in vitro. Importantly, several derivatives of GGA have been synthesized that have improved pharmaco-chemical and HSPs-boosting properties. In this review, the current knowledge and potential cardioprotective mechanisms of GGA are summarized comprehensively. We discuss the protective effects of GGA in cardiovascular diseases and myocardial injury induced by physical or chemical injury. Currently available information suggests that GGA could be employed as a novel pharmacologic intervention against cardiovascular disease.
Subject(s)
Cardiovascular Agents/therapeutic use , Cardiovascular Diseases/drug therapy , Cardiovascular System/drug effects , Diterpenes/therapeutic use , Animals , Anti-Arrhythmia Agents/therapeutic use , Apoptosis/drug effects , Arrhythmias, Cardiac/drug therapy , Arrhythmias, Cardiac/metabolism , Arrhythmias, Cardiac/physiopathology , Cardiovascular Agents/adverse effects , Cardiovascular Agents/pharmacokinetics , Cardiovascular Diseases/metabolism , Cardiovascular Diseases/pathology , Cardiovascular Diseases/physiopathology , Cardiovascular System/metabolism , Cardiovascular System/pathology , Cardiovascular System/physiopathology , Diterpenes/adverse effects , Diterpenes/pharmacokinetics , Endothelium, Vascular/drug effects , Endothelium, Vascular/metabolism , Endothelium, Vascular/physiopathology , Heat-Shock Proteins/metabolism , Humans , Insulin Resistance , Myocardium/metabolism , Myocardium/pathology , Oxidative Stress/drug effects , Treatment OutcomeABSTRACT
OBJECTIVE: To explore the efficacy and safety of radiofrequency catheter ablation (RCA) for ventricular premature beats originating from left coronary sinus under the guidance of 3-dimensional mapping system (CARTO). METHODS: A total of 15 patients with premature ventricular contractions (PVCs) originating from left coronary sinus underwent CARTO-guided RCA. Anatomical structures were constructed and three-dimension (3D) electrical activation sequence was plotted for left ventricle and aortic sinus. The distance of earliest activation point of PVCs and origin of left coronary artery were surveyed after left coronary arteriography. RESULTS: The electrocardiogram (ECG) results showed that R-wave was upward in leads II, III and avF, QRS waves in lead I was mainly of rS, rs and rsr types, QS type in lead avL, RS, Rs and rS type in lead V(1), RS type in lead V(3) and absence of S wave in lead V(5)/V(6). Intraoperative mapping detected the earliest activation point on the posterior-inferior origin of left coronary artery (LMCA) ostium (n = 7), on the anterio-inferior of LMCA ostium (n = 3) and on the inferior of LMCA ostium (n = 5). The earliest activation point (local activation time) was shorter 86 - 120 ms than surface electrocardiogram QRS wave, discharge melting on the earliest activation point and nearby succeeded. PVCs disappeared, PVCs failed to be induced under similar preoperative conditions (aleudrin intravenous) and no complication occurred intraoperatively and postoperatively. CONCLUSION: The CARTO-guided RCA is a safe and effective in the treatment of PVCs originating from left coronary sinus.
