Effects of ischaemia-mimetic factors on isolated rat ventricular myocytes

Conventional ischaemia-mimetic solutions contain several key components for inducing hypoxia, glucose deficiency, acidosis, lactate accumulation and hyperosmosis. The effect of each component on myocyte contractility during cardiac ischaemia was investigated in this study. A video-based edge-detection system was used to monitor single ventricular myocytes isolated from the rat. The effect of each factor was compared by preparing the following ischaemia-mimetic solutions: solution A, containing all of the above-mentioned factors; and solutions B, C, D, E and F, each with one of the factors excluded. The solutions that contained lactate severely reduced the contractility of the cardiomyocytes, but cell contraction did not differ significantly between the cardiomyocytes in these solutions. The effect of the solution without the acidosis-inducing component was weaker than that of the conventional ischaemia-mimetic solution. The solution lacking lactate produced the least depression of cell contractility. Lactate impaired cardiomyocyte contractility in a concentration-dependent manner. Our observations suggest that lactate is the main contributor to cardiac ischaemic injury and that its effects are attributable to acidosis and are concentration dependent. Imposition of hypoxia, glucose deficiency and hyperosmosis had little impact on the cardiomyocytes.