Animal models in the study of myocardial ischaemia and ischaemic syndromes

Time for primary review 29 days. Although myocardial ischaemia has been one of the most extensively studied topics in cardiovascular research, its definition is still debated 1. In the strictest sense ‘ischaemia’ derived from the Greek words, ischo (to restrain) and haima (blood), means insufficient blood, and if we would adhere to this definition, all animal models which lack blood (e.g. isolated heart models) should by definition be termed ‘ischaemic'. Most investigators prefer to define ischaemia as an imbalance between the amount of oxygen and substrates supplied to the heart and the amount needed to perform normal function 1, 2. The rationale behind this definition is that the myocardium strongly depends on oxygen to sustain adequate oxidative phosphorylation, the only metabolic process that is capable of providing sufficient high energy phosphates to maintain normal myocardial contraction. When oxygen supply to the heart becomes impaired there will be inadequate production of high energy phosphates with a resultant decline in myocardial contractility. When this condition develops, the myocardium starts to produce some, but not sufficient, high energy phosphates by anaerobic glycolysis, and lactate which is the end-product of this process starts to accumulate in the myocardium. Myocardial ischaemia is thus viewed as a condition in which an imbalance exists between oxygen-supply and oxygen-demand, leading to anaerobic metabolism and reduced contractile function. Central to the definition of ischaemia is that coronary flow is not only insufficient to allow adequate energy production, but that the impaired flow also results in impaired removal of metabolic waste products. In the large majority of cases in man myocardial ischaemia is confined to specific regions of the myocardium (regional ischaemia), because a stenosis in a coronary artery prevents adequate perfusion of the artery's distribution area (supply ischaemia). In its early stage of development, the stenosis can … * Corresponding author. Experimental Cardiology, Thoraxcenter, Erasmus University Rotterdam, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands. Tel.: +31-10-408-8029; Fax: +31-10-436-5607; E-mail: verdouw@tch.fgg.eur.nl