NMDA receptor-driven calcium influx promotes ischemic human cardiomyocyte apoptosis through a p38 MAPK-mediated mechanism.

N-methyl-D-aspartate receptor (NMDAR) activity plays a key role in cerebral ischemia. Although NMDAR is also expressed in cardiomyocytes, little research has been performed on NMDAR activity in myocardial ischemia. Here, using an in vitro oxygen-glucose deprivation (OGD) cardiomyocyte model, we evaluated the effects of NMDAR activity upon calcium influx, viability, apoptosis, and investigated the roles of several key mitogen-activated protein kinases (MAPKs). Primary human neonatal cardiomyocytes were cultured under OGD conditions to mimic in vivo ischemic conditions. Enhancing NMDAR activity via NMDA significantly promoted calcium influx, decreased cell viability, increased apoptosis, and enhanced p38 MAPK phosphorylation in OGD cardiomyocytes (all P < 0.05). These effects were rescued by several calcium-channel blockers (ie, MK-801, La3+ , Gap26 peptide, 18ß-glycyrrhetinic acid) but most potently rescued via the NMDAR-specific antagonist MK-801 or removal of extracellular free calcium (all P < 0.05). Knocking-down p38 MAPK activity by small-molecule inhibition or genetic methods significantly increased cell viability and reduced apoptosis (all P < 0.05). Enhancing p38 MAPK activity abolished MK-801's apoptosis-reducing effects in a p38 MAPK-dependent manner. In conclusion, NMDAR-driven calcium influx promotes apoptosis in ischemic human cardiomyocytes, an effect which can be attributed to enhanced p38 MAPK activity.

N-Methyl-D-Aspartate Receptor-Driven Calcium Influx Potentiates the Adverse Effects of Myocardial Ischemia-Reperfusion Injury Ex Vivo.

BACKGROUND: Despite the adverse effects of N-methyl-D-aspartate receptor (NMDAR) activity in cardiomyocytes, no study has yet examined the effects of NMDAR activity under ex vivo ischemic-reperfusion (I/R) conditions. Therefore, our aim was to comprehensively evaluate the effects of NMDAR activity through an ex vivo myocardial I/R rat model. METHODS: Isolated rat hearts were randomly segregated into 6 groups (n = 20 in each group): (1) an untreated control group; (2) a NMDA-treated control group; (3) an untreated I/R group; (4) an I/R+NMDA group treated with NMDA; (5) an I/R+NMDA+MK-801 group treated with NMDA and the NMDAR inhibitor MK-801; and (6) an I/R+NMDA+[Ca]-free group treated with NMDA and [Ca]-free buffer. The 4 I/R groups underwent 30 minutes of ischemia followed by 50 minutes of reperfusion. Left ventricular pressure signals were analyzed to assess cardiac performance. Myocardial intracellular calcium levels ([Ca]i) were assessed in isolated ventricular cardiomyocytes. Creatine kinase, creatine kinase isoenzyme MB, lactate dehydrogenase, cardiac troponin I, and cardiac troponin T were assayed from coronary effluents. TTC and TUNEL staining were used to measure generalized myocardial necrosis and apoptosis levels, respectively. Western blotting was applied to assess the phosphorylation of PKC-δ, PKC-ε, Akt, and extracellular signal-regulated kinase. RESULTS: Enhanced NMDAR activity under control conditions had no significant effects on the foregoing variables. In contrast, enhanced NMDAR activity under I/R conditions produced significant increases in [Ca]i levels (∼1.2% increase), significant losses in left ventricular function (∼5.4% decrease), significant multi-fold increases in creatine kinase, creatine kinase isoenzyme MB, lactate dehydrogenase, cardiac troponin I, and cardiac troponin T, significant increases in generalized myocardial necrosis (∼36% increase) and apoptosis (∼150% increase), and significant multi-fold increases in PKC-δ, PKC-ε, Akt, and extracellular signal-regulated kinase phosphorylation (all P < 0.05). These adverse effects were rescued by the NMDAR inhibitor MK-801 or [Ca]-free buffer (all P < 0.05). CONCLUSIONS: NMDAR-driven calcium influx potentiates the adverse effects of myocardial I/R injury ex vivo.

Pyriform sinus localization-assisted blind intubation: comparison with laryngoscopic intubation.

BACKGROUND: Conventional endotracheal intubation requires laryngoscopy for a direct view of the glottis. However, laryngoscopy is associated with many potential complications. The aim of the present study was to compare the efficacy and safety of pyriform sinus localization-assisted blind orotracheal intubation with those of conventional laryngoscopic orotracheal intubation. MATERIAL AND METHODS: A randomized, patient-blind, prospective study of 300 patients who underwent various operations was performed. One hundred patients were assigned to the laryngoscopic intubation group (laryngoscopy group), and 200 patients were assigned to the blind intubation group (blind group). RESULTS: The total intubation success rate in the blind group was similar to that in the laryngoscopy group (100% vs. 99%, respectively; p=0.33). Oxygen saturation by pulse oximetry in both groups was maintained at >98%. The intubation time was significantly shorter in the blind group than in the laryngoscopy group (9.7±3.4 s vs. 23.0±5.8 s, respectively; p<0.001). Postoperative complication rates were significantly lower in the blind group than in the laryngoscopy group. Recovery time from these symptoms was significantly shorter in the blind group than in the laryngoscopy group (p=0.004). CONCLUSIONS: Pyriform sinus localization-assisted blind orotracheal intubation was shown to be more effective than conventional laryngoscopic orotracheal intubation in terms of success rate, intubation time, and postoperative complication rate. Moreover, it is less affected by common risk factors; thus, this method may be more beneficial in patients with difficult airways.