Feng J, Li H, Rosenkranz E R
Division of Cardiothoracic Surgery, Children's Hospital of Buffalo, Buffalo, New York 14222, USA.
J Surg Res. 2000 May 15;90(2):131-7. doi: 10.1006/jsre.2000.5865.
Activating ATP-sensitive potassium (K(ATP)) channels improves ischemia tolerance of adult rabbit hearts. We hypothesize that (a) endogenous activation of the K(ATP) channel accounts for better ischemia tolerance of neonatal hearts and (b) exogenous K(ATP) channel activation with pinacidil further improves the neonatal heart's tolerance to cardioplegic ischemia.
Study 1: Seven (control) neonatal rabbits received intraperitoneal saline, whereas five others (Glib) received 0.3 mg/kg glibenclamide 10 min before sacrifice. They were perfused on Langendorff with Krebs-Henseleit buffer (KHB). Baseline left ventricle (LV) performance and coronary flow (CF) were measured. After 20 min of 37 degrees C ischemia and 10 min of reperfusion, recovery was measured. Study 2: Ten (control) neonatal hearts underwent 90 min of normothermic ischemia with St. Thomas' cardioplegia (STCP) solution administered every 30 min. Ten others were pretreated with a 10-min infusion of 1 microM pinacidil in KHB and received 1 microM pinacidil-enriched STCP. Recovery of LV performance and CF were measured after 60 min of reperfusion.
Study 1: Glib significantly reduced preischemia LV performance by 28%* compared to control hearts. Recovery of Glib-treated hearts was significantly less (67%) than controls (81%). Study 2: Pinacidil-treated hearts had significantly better recovery of LV performance (39%) and CF (78%) compared to 23 and 52%, respectively, in untreated controls (*P < 0.05 vs control hearts).
Endogenous K(ATP) channel activation in neonatal hearts contributes to their better tolerance to ischemia. Exogenous K(ATP) channel activation by pinacidil pretreatment and cardioplegic enrichment significantly improved the neonatal rabbit heart's tolerance to cardioplegic ischemia. This may be an important addition to myocardial protection during pediatric cardiac surgery.
激活三磷酸腺苷敏感性钾（K(ATP)）通道可提高成年兔心脏的缺血耐受性。我们假设：（a）K(ATP)通道的内源性激活是新生儿心脏具有更好缺血耐受性的原因；（b）用吡那地尔进行外源性K(ATP)通道激活可进一步提高新生儿心脏对心脏停搏性缺血的耐受性。
研究1：7只（对照组）新生兔在处死前10分钟腹腔注射生理盐水，另外5只（格列本脲组）注射0.3mg/kg格列本脲。用克雷布斯-亨塞尔特缓冲液（KHB）对其进行Langendorff灌注。测量基础左心室（LV）功能和冠状动脉血流量（CF）。在37℃缺血20分钟和再灌注10分钟后，测量恢复情况。研究2：10个（对照组）新生心脏接受90分钟的常温缺血，每30分钟给予圣托马斯心脏停搏液（STCP）。另外10个心脏先用10分钟KHB中1μM吡那地尔灌注预处理，然后接受富含1μM吡那地尔的STCP。再灌注60分钟后测量LV功能和CF的恢复情况。
研究1：与对照心脏相比，格列本脲组显著降低缺血前LV功能28%。格列本脲处理组心脏的恢复情况明显低于对照组（67%对比81%）。研究2：与未处理的对照组分别为23%和52%相比，吡那地尔处理组心脏的LV功能（39%）和CF（78%*）恢复情况明显更好（*与对照心脏相比，P<0.05）。
新生儿心脏中K(ATP)通道的内源性激活有助于其更好地耐受缺血。通过吡那地尔预处理和心脏停搏液富集进行外源性K(ATP)通道激活可显著提高新生兔心脏对心脏停搏性缺血的耐受性。这可能是小儿心脏手术中心肌保护的一项重要补充。
