Richmond Pharmacology Ltd., St George's University of London, Cranmer Terrace, London, UK.
Cardiovascular and Cell Sciences Research Institute, St George's University of London, London, UK.
J Clin Pharmacol. 2019 Jun;59(6):799-810. doi: 10.1002/jcph.1374. Epub 2019 Jan 11.
Meal intake leads to a significant and prolonged increase in cardiac output to supply the splanchnic vasculature. A meal is associated with sympathetic activation of the cardiovascular system, and food ingestion is correlated with an increase in heart rate, an increase in cardiac stroke volume, and QTc interval shortening for up to 7 hours. Given the complexity of the system, one or several of many mechanisms could explain this observation. The shortening of the QTc interval was correlated with a rise of C-peptide following food ingestion, but the mechanisms by which C-peptide may be involved in the modulation of cardiac repolarization are still unknown. This shortening of the myocardial action potential caused by the ingestion of food was further investigated in the present study by measuring the QRS, J-T , and T -T intervals in search of further clues to better understand the underlying mechanisms. A retrospective analysis was conducted based on data collected in a formal thorough QT/QTc study in which 32 subjects received a carbohydrate-rich "continental" breakfast, moxifloxacin without food, and moxifloxacin with food. We assessed the effect of food on T-wave morphology using validated algorithms for measurement of J-T and T -T intervals. Our findings demonstrate that a standardized meal significantly shortened J-T for 4 hours after a meal and to a much lesser extent and shorter duration (up to 1 hour) prolonged the T -T and QRS intervals. This suggests that the QTc shortening occurs mainly during phase 2 of the cardiac action potential. As there was no corresponding effect on T -T beyond the first hour, we conclude that a meal does not interfere with the outward correcting potassium channels but possibly with Ca currents. An effect on mainly Ca aligns well with our understanding of physiology whereby an increase in stroke volume, as observed after a meal, is associated with changes in Ca cycling in and out of the sarcoplasmic reticulum during cardiac myocyte contraction.
进食会导致心输出量显著且持续增加，以供应内脏血管系统。进食会引起心血管系统的交感神经激活，与心率增加、心搏量增加和 QT 间期缩短相关，最长可达 7 小时。鉴于系统的复杂性，许多机制中的一个或几个可能解释这一观察结果。QTc 间期缩短与进食后 C 肽升高相关，但 C 肽如何参与心脏复极化的调节机制尚不清楚。本研究通过测量 QRS、J-T 和 T-T 间期，进一步研究了进食引起的心肌动作电位缩短，以寻找更好地理解潜在机制的进一步线索。本研究对一项正式的全面 QT/QTc 研究中收集的数据进行了回顾性分析，该研究中 32 名受试者接受了富含碳水化合物的“欧式”早餐、空腹莫西沙星和进食后莫西沙星。我们使用 J-T 和 T-T 间期测量的验证算法评估了食物对 T 波形态的影响。我们的研究结果表明，标准化餐显著缩短了 J-T，在餐后 4 小时内，并且在较小程度和较短时间内（最长 1 小时）延长了 T-T 和 QRS 间期。这表明 QTc 缩短主要发生在心脏动作电位的第 2 阶段。由于在第一个小时之后 T-T 没有相应的变化，我们得出结论，进食不会干扰外向纠正钾通道，但可能会干扰 Ca 电流。对 Ca 电流的主要影响与我们对生理学的理解一致，即餐后观察到的心搏量增加与心肌细胞收缩时肌浆网内外 Ca 循环的变化有关。
