Heart failure represents the end point of a variety of cardiovascular diseases.It is a growing health burden and a leading cause of death worldwide.To date,limited treatment options exist for the treatment of heart fa...Heart failure represents the end point of a variety of cardiovascular diseases.It is a growing health burden and a leading cause of death worldwide.To date,limited treatment options exist for the treatment of heart failure,but exercise has been well-established as one of the few safe and effective interventions,leading to improved outcomes in patients.However,a lack of patient adherence remains a significant barrier in the implementation of exercise-based therapy for the treatment of heart failure.The insulin-like growth factor 1(IGF1)phosphoinositide 3-kinase(PI3K)pathway has been recognized as perhaps the most critical pathway for mediating exercisedinduced heart growth and protection.Here,we discuss how modulating activity of the IGF1PI3K pathway may be a valuable approach for the development of therapies that mimic the protective effects of exercise on the heart.We outline some of the promising approaches being investigated that utilize PI3K-based therapy for the treatment of heart failure.We discuss the implications for cardiac pathology and cardiotoxicity that arise in a setting of reduced PI3K activity.Finally,we discuss the use of animal models of cardiac health and disease,and genetic mice with increased or decreased cardiac PI3K activity for the discovery of novel drug targets and biomarkers of cardiovascular disease.展开更多
目的探讨艾司洛尔对脓毒性休克患者的心脏保护作用。方法选取浙江省立同德医院收治的44例脓毒性休克患者,采用随机数字表法分为对照组(22例)和治疗组(22例)。治疗组在常规治疗基础上静脉泵入艾司洛尔,对照组持续静脉泵入等渗NaCl溶液。...目的探讨艾司洛尔对脓毒性休克患者的心脏保护作用。方法选取浙江省立同德医院收治的44例脓毒性休克患者,采用随机数字表法分为对照组(22例)和治疗组(22例)。治疗组在常规治疗基础上静脉泵入艾司洛尔,对照组持续静脉泵入等渗NaCl溶液。记录两组患者入组后0、24、48、72、96 h时的心率、中心静脉压(CVP)、平均动脉压(MAP)、每搏量指数(SVI)、心脏指数、全心舒张末期血容积指数(GEDVI)、左室射血分数(LVEF)、二尖瓣口舒张早晚期血流峰值流速比值(E/A)、心肌肌钙蛋白I(cTnI)、脑钠尿肽、血乳酸和ScvO_2表达水平,比较两组患者的28 d病死率。结果两组患者各时间点心率、心脏指数、GEDVI、E/A、cTnI及脑钠尿肽表达水平比较,差异均有统计学意义(F=58.045、11.102、7.132、7.136、2.970、3.006,P均<0.05)。进一步两两比较发现,治疗组患者24、48、72及96 h心率和心脏指数较对照组同时间点及治疗组0 h均显著降低(P均<0.05);治疗组患者48、72及96 h GEDVI及E/A水平较对照组同时间点及治疗组0 h均显著升高(P均<0.05);治疗组患者48、72及96 h cTnI和脑钠尿肽表达水平均较对照组同时间点显著降低(P均<0.05);治疗组患者72及96 h cTnI和脑钠尿肽表达水平均较同组0 h显著降低(P均<0.05)。且对照组及治疗组患者28 d病死情况比较,差异无统计学意义(7/22 vs. 5/22,χ~2=0.458,P=0.498)。结论艾司洛尔可减轻脓毒性休克患者心肌损伤,改善心肌舒张功能,对循环、组织灌注及氧代谢无影响,对预后无显著改变。展开更多
基金All authors are supported by the Victorian Government’s Operational Infrastructure Support ProgramSBS is supported by a joint Baker Heart and Diabetes Institute-La Trobe University doctoral scholarshipRM is supported by a National Health and Medical Research Council Senior Research Fellowship(Grant No.1078985).
文摘Heart failure represents the end point of a variety of cardiovascular diseases.It is a growing health burden and a leading cause of death worldwide.To date,limited treatment options exist for the treatment of heart failure,but exercise has been well-established as one of the few safe and effective interventions,leading to improved outcomes in patients.However,a lack of patient adherence remains a significant barrier in the implementation of exercise-based therapy for the treatment of heart failure.The insulin-like growth factor 1(IGF1)phosphoinositide 3-kinase(PI3K)pathway has been recognized as perhaps the most critical pathway for mediating exercisedinduced heart growth and protection.Here,we discuss how modulating activity of the IGF1PI3K pathway may be a valuable approach for the development of therapies that mimic the protective effects of exercise on the heart.We outline some of the promising approaches being investigated that utilize PI3K-based therapy for the treatment of heart failure.We discuss the implications for cardiac pathology and cardiotoxicity that arise in a setting of reduced PI3K activity.Finally,we discuss the use of animal models of cardiac health and disease,and genetic mice with increased or decreased cardiac PI3K activity for the discovery of novel drug targets and biomarkers of cardiovascular disease.
文摘目的探讨艾司洛尔对脓毒性休克患者的心脏保护作用。方法选取浙江省立同德医院收治的44例脓毒性休克患者,采用随机数字表法分为对照组(22例)和治疗组(22例)。治疗组在常规治疗基础上静脉泵入艾司洛尔,对照组持续静脉泵入等渗NaCl溶液。记录两组患者入组后0、24、48、72、96 h时的心率、中心静脉压(CVP)、平均动脉压(MAP)、每搏量指数(SVI)、心脏指数、全心舒张末期血容积指数(GEDVI)、左室射血分数(LVEF)、二尖瓣口舒张早晚期血流峰值流速比值(E/A)、心肌肌钙蛋白I(cTnI)、脑钠尿肽、血乳酸和ScvO_2表达水平,比较两组患者的28 d病死率。结果两组患者各时间点心率、心脏指数、GEDVI、E/A、cTnI及脑钠尿肽表达水平比较,差异均有统计学意义(F=58.045、11.102、7.132、7.136、2.970、3.006,P均<0.05)。进一步两两比较发现,治疗组患者24、48、72及96 h心率和心脏指数较对照组同时间点及治疗组0 h均显著降低(P均<0.05);治疗组患者48、72及96 h GEDVI及E/A水平较对照组同时间点及治疗组0 h均显著升高(P均<0.05);治疗组患者48、72及96 h cTnI和脑钠尿肽表达水平均较对照组同时间点显著降低(P均<0.05);治疗组患者72及96 h cTnI和脑钠尿肽表达水平均较同组0 h显著降低(P均<0.05)。且对照组及治疗组患者28 d病死情况比较,差异无统计学意义(7/22 vs. 5/22,χ~2=0.458,P=0.498)。结论艾司洛尔可减轻脓毒性休克患者心肌损伤,改善心肌舒张功能,对循环、组织灌注及氧代谢无影响,对预后无显著改变。
