Wallen W Jack, Belanger Michael P, Wittnich Carin
Department of Physiology and The Cardiovascular Sciences Collaborative Program, University of Toronto, Toronto, ON M5S IA8, Canada.
Can J Physiol Pharmacol. 2003 Jan;81(1):40-7. doi: 10.1139/y03-018.
Compared with normal hearts, those with pathology (hypertrophy) are less tolerant of metabolic stresses such as ischemia. Pharmacologic intervention administered prior to such stress could provide significant protection. This study determined, firstly, whether the pentose sugar ribose, previously shown to improve postischemic recovery of energy stores and function, protects against ischemia when administered as a pretreatment. Secondly, the efficacy of this same pretreatment protocol was determined in hearts with pathology (hypertrophy). For study 1, Sprague-Dawley rats received equal volumes of either vehicle (bolus i.v. saline) or ribose (100 mg/kg) before global myocardial ischemia. In study 2, spontaneously hypertensive rats (SHR; blood pressure approximately 200/130) with myocardial hypertrophy underwent the same treatment protocol and assessments. In vivo left ventricular function was measured and myocardial metabolites and tolerance to ischemia were assessed. In normal hearts, ribose pretreatment significantly elevated the heart's energy stores (glycogen), and delayed the onset of irreversible ischemic injury by 25%. However, in vivo ventricular relaxation was reduced by 41% in the ribose group. In SHR, ribose pretreatment did not produce significant elevations in the heart's energy or improvements in tolerance to global ischemia, but significantly improved ventricular function (maximal rate of pressure rise (+dP/dt(max)), 25%; normalized contractility ((+dP/dt)/P), 13%) despite no change in hemodynamics. Thus, administration of ribose in advance of global myocardial ischemia does provide metabolic benefit in normal hearts. However, in hypertrophied hearts, ribose did not affect ischemic tolerance but improved ventricular function.
与正常心脏相比，有病变（肥大）的心脏对诸如局部缺血等代谢应激的耐受性较低。在这种应激之前进行药物干预可以提供显著的保护作用。本研究首先确定，先前已证明能改善缺血后能量储备和功能恢复的戊糖核糖，作为预处理给药时是否能预防局部缺血。其次，在有病变（肥大）的心脏中确定相同预处理方案的疗效。在研究1中，斯普拉格-道利大鼠在全心肌缺血前接受等量的载体（静脉推注生理盐水）或核糖（100毫克/千克）。在研究2中，患有心肌肥大的自发性高血压大鼠（SHR；血压约为200/130）接受相同的治疗方案和评估。测量体内左心室功能，并评估心肌代谢物和对缺血的耐受性。在正常心脏中，核糖预处理显著提高了心脏的能量储备（糖原），并将不可逆缺血损伤的发生延迟了25%。然而，核糖组的体内心室舒张功能降低了41%。在SHR中，核糖预处理并未使心脏能量显著升高，也未改善对全心缺血的耐受性，但尽管血流动力学无变化，却显著改善了心室功能（最大压力上升速率（+dP/dt(max)）提高了25%；标准化收缩性（(+dP/dt)/P）提高了13%）。因此，在全心肌缺血前给予核糖确实能给正常心脏带来代谢益处。然而，在肥大心脏中，核糖并未影响缺血耐受性，但改善了心室功能。
