Temperature Affects Human Cardiac Sarcoplasmic Reticulum Energy-mediated Calcium Transport

Hypothermic cardioplegic solutions are currently used to preserve cardiac function during transportation. However, it has been shown that end-diastolic compliance decreases in donor heart during reperfusion. Excessively cold temperatures may affect membrane-bound enzymes (CA2+ ATPase and Ca2+ uptake) which are necessary for calcium homeostasis. To study the effect of temperature on Ca2+ ATPase and Ca2+ uptake activities over the temperature range to which a donor heart is usually exposed (4°-37°C), sarcoplasmic reticulum (SR) was isolated from human atrial appendages. SR was also isolated from atrial appendages which had been stored in saline at 4°C for 4 or 24 h or 24 h in St Thomasʹ cardioplegic solution (ST). Ca2+ ATPase and Ca2+ uptake from these samples were compared with those found in the SR of unstored appendages. The activity of Ca2+ uptake and Ca2+ ATPase showed great sensitivity at assay temperatures below 22°C, while no such sensitivity was identified in SR NADPH/cytochrome C reductase (NCR). After storage of atrial appendages for only 4 h in saline at 4°C, Ca2+ uptake activity was reduced 50% in the SR when compared to unstored controls (80 ± 9.9 nmol/mg/min and 155.24 ± 2.4 nmol/mg/min, respectively; P < 0.02) whereas Ca2+ ATPase was not affected until 24 h of storage, when the activity was also decreased > 50% (P = 0.0002). However, NCR was not affected. In addition, storage at 4°C significantly decreased the SR protein yield (mg/g homogenate protein) at 4 or 24 h in saline as well as 24 h in ST. However, there was no decrease in the enzyme activities (Ca2+ ATPase, 229 ± 25.3; Ca2+ uptake, 221 ± 27.1; NCR, 24.9 ± 0.48 nmol/mg/min). Following exposure to low temperature, alteration of Ca2+ uptake and Ca2+ ATPase may result in disruption of calcium homeostasis, thereby interrupting excitation-contraction coupling and relaxation. The damaging effects of hypothermia should be taken into account when assessing the peri-operative complications and the long-term results of cardiac transplantation.