Myocardial Cell Damage and Breakdown of Cation Homeostasis During Conditions of Ischaemia and Reperfusion, the Oxygen Paradox, and Reduced Extracellular Calcium

Abstract

Enzyme release from perfused rat heart was determined under various conditions of injury. In analogous experiments, intracellular cation concentrations were measured using ion-selective microelectrodes. Under appropriate conditions, the inhibition of mitochondrial and/or glycolytic ATP production led to a decrease in the release of enzymes. During ischaemia or the oxygen paradox, the sarcosolic Ca 2+ concentration was highly elevated; reperfusion or reoxygenation was followed by a drastic enzyme release. This was also found to be true under the conditions of an increased permeability brought about by a reduced extracellular Ca 2+ concentration of 0.1 mmol/1. The intracellular pH under all conditions of injury was only moderately decreased. The sarcosolic Na + concentration was markedly increased whereas the K + concentration was decreased. The critical Ca 2+ concentration of the sarcosol beyond which cell damage and enzyme release are inducible was assumed to be in the range between 10 and 32 μιηοΐ/ΐ. The driving force of the Na + /Ca 2+ exchange reaction of the sarcolemma is discussed in relation to recovery from hypoxic injury and the potential for avoiding cell damage.

Warm blood cardioplegia reduces the fall in the intracellular concentration of taurine in the ischaemic/reperfused heart of patients undergoing aortic valve surgery

“…Data was expressed per wet weight (A) and per protein content (B). **Significantly different for biopsy 3 vs. biopsies 1 and 2 (P < 0.05) via the Na+/H + result in an accumulation of [Na+]~ (Diederichs et al, 1990;Tani, 1990;Suleiman, 1994). As hypothermia inhibits the Na-pump (Suleiman and Chapman, 1990), a further rise in [Na+]i is expected during hypothermic ischaemia.…”

Characteristics of l -alanine transport in cardiac sarcolemmal vesicles and into isolated cardiac myocytes

“…Under normal conditions, the large inwards Na + gradient and the negative membrane potential would favour influx, though the high tissue content coupled with any further production may also stimulate efflux. However, under ischaemic conditions, the efflux pathway would be greatly enhanced due to the higher rate of alanine synthesis [21], the decrease in ATP production [18,19], increase in the intracellular Na + concentration and membrane depolarisation [4]. This would then favour the continuous utilisation of glutamate for the purpose of anaerobic energy production during ischaemia.…”

Cardioprotection requires flipping the ‘posttranslational modification’ switch

“…In order to understand the nature of how PTMs generate cardioprotection, the detrimental cellular processes occurring during the injury must be understood. In general, ischemia reperfusion (I/R) causes cellular necrosis characterized by cellular and organelle swelling, denaturation and coagulation of cytoplasmic proteins, breakdown of cell organelles, depletion of ATP, loss of calcium homeostasis, and defects in membrane permeability (Lamers and Ruigrok, 1983;Diederichs et al, 1990;Gottlieb et al, 1996;Halestrap et al, 2007); all of these effects can lead to reduced cardiovascular function and impair recovery.…”