Grape Seed Extract-Cardiac Impact and Drug Interaction

描述(申请人提供)：商业报道称抗氧化剂可以减缓心脏病的进展或严重程度。因此，许多传统医疗保健的患者正在服用来自维生素、矿物质和植物药的抗氧化剂补充剂。然而，人们对其潜在的作用机制知之甚少，混淆了安全性和有效性评估。植物药是一种复杂的植物化学混合物，其中任何一种都可能与处方的药物方案相互作用，并改变其生物效果。在某些疾病状态或医疗干预中，这些相互作用可能对患者健康和治疗有害。心脏病通常涉及心脏缺血/再灌注损伤。缺血/再灌注损伤发生在心脏首先被剥夺，然后重新供氧时，产生破坏性的活性氧物种(ROS)。缺血/再灌注损伤发生在心脏病的整个过程中--以充血性心力衰竭的微妙、慢性方式发生，或以心脏外科手术那样的急性方式发生。缺血/再灌流损伤 通过短暂的缺氧期或用阿片类药物进行预适应而降低。阿片类止痛药用于急诊和外科手术。阿片类心脏保护的一种机制涉及产生低水平的预适应ROS。因此，ROS猝灭抗氧化剂可能改变阿片类心脏保护。合成抗氧化剂已经被证明可以实验地减少阿片类药物对心脏的保护，但还没有发表的研究调查饮食中补充抗氧化剂的潜在影响。我们的研究将使用一种标准化的葡萄籽提取物IH636，它含有丰富的抗氧化剂原花青素。使用兔心肌细胞和全心手术，我们将确定补充三周的IH636是否影响心脏应激防御蛋白的表达或抗氧化储备。我们还将测定心肌膜完整性、细胞代谢、心脏功能和总体生存能力。同时，我们将使用相同的终点评估IH636在缺血/再灌注条件下的心脏效应。最后，利用阿片类药物机制的知识，我们拟议的研究将评估IH636补充是否与阿片类药物心脏保护相互作用，以及这种相互作用的性质。对于葡萄籽提取物补充剂，作用机制和阿片类药物相互作用目前尚不清楚。考虑到这种植物提取物的使用越来越多，提高安全性和有效性的知识势在必行。

DESCRIPTION (provided by applicant): Antioxidants are commercially reported to slow the advance or severity of heart disease. As such, many patients of conventional health care are consuming antioxidant supplements from vitamins, minerals, and botanicals. However, little is understood of their potential mechanisms of action, confounding safety and efficacy evaluations. Botanicals represent a complex blend of phytochemicals, any of which may interact with prescribed drug regimens and alter their biological effects. In certain diseased states or medical interventions, these interactions could be deleterious to patient health and treatment. Heart disease commonly involves cardiac ischemia/reperfusion damage. Ischemia/reperfusion damage occurs when the heart is first denied then re-supplied with oxygen, generating damaging reactive oxygen species(ROS). Ischemia/reperfusion injury occurs across the span of heart disease - in a subtle, chronic fashion with congestive heart failure, or in an acute fashion as with cardiac surgical procedures. Ischemia/reperfusion damage is lowered through preconditioning, which occurs through brief periods of oxygen deprivation or through pretreatment with drugs such as opioids. Opioid pain-killers are used in emergent and surgical settings. One mechansism of opioid cardioprotection involves the generation of low levels of preconditioning ROS. Thus, ROS-quenching antioxidants may alter opioid cardioprotection. Synthetic antioxidants have been shown to experimentally decrease opioid cardioprotection, but no published studies have investigated the potential impact of dietary antioxidant supplementation. Our studies will utilize a standardized grape seed extract IH636, rich in antioxidant proanthocyanidins. Using rabbit cardiac myocyte and whole heart procedures, we will determine if three weeks of IH636 supplementation affects the expression of cardiac stress defense proteins or antioxidant reserve. We will also determine cardiac membrane integrity, cellular metabolism, heart function, and overall viability. In concert, we will evaluate cardiac effects of IH636 under ischemia/reperfusion conditions using the same endpoints. Finally, using knowledge of opioid mechansisms, our proposed studies will evaluate if IH636 supplementation interacts with opioid cardioprotection, and the nature of this interaction. For grape seed extract supplementation, both mechanisms of action and opioid interaction are currently unknown. Considering the increasing use of this botanical extract, improved knowledge of safety and efficacy is imperative.