Raheja Rashmi, Gupta Hemlata, Pandey Uma, Deshpande Shripad B
Department of Physiology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, India.
Department of Obstetrics & Gynecology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, India.
Life Sci. 2017 Dec 1;190:52-57. doi: 10.1016/j.lfs.2017.09.042. Epub 2017 Sep 29.
Lignocaine is used during intrapartum and postpartum period but there are conflicting reports regarding the effect of lignocaine on uterine contractility. Therefore, this study was undertaken to delineate the effect of lignocaine on uterine contractility and the underlying mechanisms.
The in vitro contractions were recorded from the uterine segments obtained from adult rats (in estrous phase) and also from human myometrial tissue. Effect of lignocaine on spontaneous uterine contractions was recorded in the absence or presence of antagonists. Effect of sodium nitroprusside (SNP, NO donor) on uterine contractility was assessed. The NO was assayed (indicator of NO activity) from the supernatant after exposing the myometrial tissue to lignocaine in the absence or the presence of L-NAME or hemoglobin.
Lignocaine (100μM) increased the amplitude of uterine contractions by 75% with no alterations in frequency. Similar magnitude of increase was seen with human myometrial tissue also. The spontaneous activities were absent in Ca-free or in nifedipine (10μM) containing medium. Heparin (IP blocker, 10IU/ml), but not the indomethacin (10μM) blocked the lignocaine-induced augmentation. L-NAME (NOS inhibitor, 10μM) or methylene blue (guanylyl cyclase inhibitor, 100μM) partially blocked the lignocaine-induced augmentation. SNP (30μM) increased the amplitude of spontaneous uterine contractions. Lignocaine increased the NO content (indicator of NO activity) of uterine tissue and the increase was blocked by L-NAME or hemoglobin.
Present observations indicate that lignocaine augments the amplitude of uterine contractions via Ca-dependent mechanisms involving NO-G cyclase-dependent mechanisms.
利多卡因在分娩期和产后使用，但关于利多卡因对子宫收缩力的影响存在相互矛盾的报道。因此，本研究旨在阐明利多卡因对子宫收缩力的影响及其潜在机制。
记录成年大鼠（发情期）子宫段以及人子宫肌层组织的体外收缩情况。在不存在或存在拮抗剂的情况下记录利多卡因对子宫自发收缩的影响。评估硝普钠（SNP，一氧化氮供体）对子宫收缩力的作用。在不存在或存在L-精氨酸甲酯（L-NAME）或血红蛋白的情况下，将子宫肌层组织暴露于利多卡因后，从上清液中检测一氧化氮（一氧化氮活性指标）。
利多卡因（100μM）使子宫收缩幅度增加75%，频率无变化。人子宫肌层组织也出现了类似程度的增加。在无钙或含有硝苯地平（10μM）的培养基中未观察到自发活动。肝素（IP阻断剂，10IU/ml）可阻断利多卡因诱导的增强作用，而吲哚美辛（10μM）则不能。L-精氨酸甲酯（一氧化氮合酶抑制剂，10μM）或亚甲蓝（鸟苷酸环化酶抑制剂，100μM）部分阻断了利多卡因诱导的增强作用。硝普钠（30μM）增加了子宫自发收缩的幅度。利多卡因增加了子宫组织中一氧化氮的含量（一氧化氮活性指标），L-精氨酸甲酯或血红蛋白可阻断这种增加。
目前的观察结果表明，利多卡因通过涉及一氧化氮-鸟苷酸环化酶依赖性机制的钙依赖性机制增强子宫收缩幅度。
