Preischemic administration of ribose to delay the onset of irreversible ischemic injury and improve function: studies in normal and hypertrophied hearts

• Published in: Canadian journal of physiology and pharmacology 2003-01, Vol.81 (1), p.40-47
• Main Authors: Wallen, W Jack, Belanger, Michael P, Wittnich, Carin
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphate - metabolism; Anaerobic Threshold - drug effects; Anaerobic Threshold - physiology; Animals; Biological and medical sciences; Cardiotonic Agents - administration & dosage; Cardiotonic Agents - metabolism; Cardiovascular system; Disease Models, Animal; Drug Administration Schedule; Glycogen - metabolism; Heart disease; Hypertension - complications; Hypertension - physiopathology; Hypertrophy, Left Ventricular - complications; Hypertrophy, Left Ventricular - drug therapy; Hypertrophy, Left Ventricular - physiopathology; Injections, Intravenous; Male; Medical sciences; Miscellaneous; Myocardial Ischemia - physiopathology; Myocardial Ischemia - prevention & control; Myocardium - metabolism; Pharmacology. Drug treatments; Phosphocreatine - metabolism; Physiological aspects; Rats; Rats, Sprague-Dawley; Ribose - administration & dosage; Ribose - metabolism; Structure-Activity Relationship; Sugar; Treatment; Ventricular Function, Left - drug effects; Ventricular Function, Left - physiology; Ventricular Function, Right - drug effects; Ventricular Function, Right - physiology
• ISSN: 0008-4212; 1205-7541
• 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 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 hemody na mics. 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.Key words: ribose, SHR, ischemia, ventricular function, metabolism.