Omachi Akira, Sharma Avadhesh C, Alden Kris J, Sam Albert D, Ferguson James L
Department of Physiology and Biophysics, University of Illinois, College of Medicine, Chicago 60612, USA.
Shock. 2002 Mar;17(3):193-8. doi: 10.1097/00024382-200203000-00006.
The present study was designed to test the hypothesis that induction of chronic peritoneal sepsis in rats would produce a more severe calcium paradox-mediated myocardial injury in isolated heart preparation than is seen in normal hearts, and that this would be inhibited by sucrose as in normal hearts. Male Sprague-Dawley rats were made septic using 200 mg of cecal material (obtained from a donor rat) suspended in 5 mL of 5% dextrose in sterile water D5 W/kg. In septic animals, the cecal material was injected in the peritoneum, while sham-septic animals received only D5 W/kg (5 mL/kg). A third group consisting of normal rats (no surgery) group was also included. Hearts were harvested from all three groups and were subjected to a calcium paradox-mediated injury in an isolated heart preparation. Hearts were perfused with Krebs-Henseleit (KH) medium and were allowed to stabilize, followed by a perfusion with Ca2+-free KH for 10 min. After this 10-min Ca2+-free KH perfusion, rats were reperfused with KH medium for 60 min. Ca2+-free KH medium was used in control experiments, while sucrose experiments were conducted with the same medium except that 150 mM sucrose replaced 75 mM NaCl. A marked decrease in ATP and phosphocreatine occurred during Ca2+ reperfusion in all hearts in absence of sucrose. In the presence of the disaccharide, no change in high-energy phosphate (HEP) levels was observed in normal hearts, while lower ATP concentrations were seen in sham and septic hearts. Thus, sucrose did not inhibit cellular injury in sham and septic hearts as it did in normal hearts, and this might be due to a smaller HEP availability. Control studies with normal, sham, and septic hearts exhibited cessation of contractions in the absence of Ca2+, and appearance of large amounts of cytosolic protein in the effluent perfusate during Ca2+ reperfusion. With normal hearts, perfusion with sucrose caused a 96% inhibition of the total creatine kinase (CK) release observed in control experiments. With sham hearts, 32% of CK release was inhibited by sucrose, while 68% of the CK release was attributed to stress associated with surgery performed in the sham-septic group. In septic hearts, only 8% of the CK release was inhibited by sucrose, suggesting that more severe myocardial injury occurs when septic hearts are subjected to a calcium paradox as compared to other groups. It is evident that sucrose can inhibit a small fraction of the CK release from septic hearts during the calcium paradox as compared to the large CK loss associated with sham sepsis. We have concluded that induction of sepsis made the heart more susceptible to a calcium paradox-mediated myocardial injury.
与正常心脏相比，诱导大鼠发生慢性腹膜败血症会在离体心脏制备中导致更严重的钙反常介导的心肌损伤，且蔗糖会如在正常心脏中一样抑制这种损伤。使用悬浮于5 mL无菌水中的5%葡萄糖（D5W）/kg的200 mg盲肠内容物（取自供体大鼠）使雄性斯普拉格-道利大鼠发生败血症。在败血症动物中，将盲肠内容物注入腹膜，而假败血症动物仅接受D5W/kg（5 mL/kg）。还包括由正常大鼠（未手术）组成的第三组。从所有三组中采集心脏，并在离体心脏制备中使其遭受钙反常介导的损伤。心脏先用克雷布斯-亨塞尔特（KH）培养基灌注并使其稳定，然后用无钙KH灌注10分钟。在这10分钟的无钙KH灌注后，用KH培养基对大鼠再灌注60分钟。对照实验使用无钙KH培养基，而蔗糖实验使用相同的培养基，只是用150 mM蔗糖替代75 mM氯化钠。在无蔗糖的情况下，所有心脏在钙再灌注期间ATP和磷酸肌酸均显著降低。在存在二糖的情况下，正常心脏中高能磷酸（HEP）水平未见变化，而假手术和败血症心脏中的ATP浓度较低。因此，蔗糖在假手术和败血症心脏中并未如在正常心脏中那样抑制细胞损伤，这可能是由于HEP可用性较小。对正常、假手术和败血症心脏的对照研究显示，在无钙时收缩停止，在钙再灌注期间流出的灌注液中出现大量胞质蛋白。对于正常心脏，用蔗糖灌注可使对照实验中观察到的总肌酸激酶（CK）释放抑制96%。对于假手术心脏，蔗糖抑制了32%的CK释放，而68%的CK释放归因于假败血症组手术相关的应激。在败血症心脏中，蔗糖仅抑制了8%的CK释放，这表明与其他组相比，败血症心脏在遭受钙反常时会发生更严重的心肌损伤。显然，与假败血症相关的大量CK损失相比，蔗糖在钙反常期间可抑制败血症心脏中一小部分CK释放。我们得出结论，败血症的诱导使心脏更容易受到钙反常介导的心肌损伤。
