Effects of ischaemia‐mimetic factors on isolated rat ventricular myocytes

Abstract

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.

Simulated ischemia-induced preconditioning of isolated ventricular myocytes from young adult and aged Fischer-344 rat hearts

“…The PO 2 value was ϳ650 mmHg in normal Tyrode buffer, and this rapidly declined by ϳ90% (to 70 mmHg) in ischemic Tyrode buffer, as previously described (43). This 90% decrease in PO2 values is greater than the 75-80% reduction in PO2 reported in other cellular models of simulated ischemia and reperfusion (35,36). A PO2 value of 70 mmHg represents hypoxia (47).…”

Extracellular proton depression of peak and late Na+ current in the canine left ventricle

“…These included hyperkalemia, acidosis, hypoxia, substrate deprivation, and lactate accumulation (7,38). Further studies have examined the various components of ischemia at the single cell level (26,28). In this study, we examined the effects of acidosis on both peak and late I Na .…”

Efficacy of selective NCX inhibition by ORM-10103 during simulated ischemia/reperfusion

“…2). Consequently, during this protocol oxidative metabolism was severely compromised, but not abolished (Lu et al, 2005). This is not surprising, since the oxygen level in the chamber was low, but not zero (32.9 7 1.6 mmHg).…”