Department of Pharmacology, Institute of Clinical Medicine, University of Oslo and Oslo University Hospital , Oslo , Norway.
Center for Heart Failure Research, Faculty of Medicine, University of Oslo and Oslo University Hospital , Oslo , Norway.
Am J Physiol Heart Circ Physiol. 2018 Nov 1;315(5):H1137-H1147. doi: 10.1152/ajpheart.00208.2018. Epub 2018 Jul 13.
Targeted temperature management is part of the standardized treatment for patients in cardiac arrest. Hypothermia decreases cerebral oxygen consumption and induces bradycardia; thus, increasing the heart rate may be considered to maintain cardiac output. We hypothesized that increasing heart rate during hypothermia would impair diastolic function. Human left ventricular trabeculae obtained from explanted hearts of patients with terminal heart failure were stimulated at 0.5 Hz, and contraction-relaxation cycles were recorded. Maximal developed force (F), maximal rate of development of force [(dF/d t)], time to peak force (TPF), time to 80% relaxation (TR80), and relaxation time (RT = TR80 - TPF) were measured at 37, 33, 31, and 29°C. At these temperatures, stimulation frequency was increased from 0.5 to 1.0 and to 1.5 Hz. At 1.5 Hz, concentration-response curves for the β-adrenergic receptor (β-AR) agonist isoproterenol were performed. F, TPF, and RT increased when temperature was lowered, whereas (dF/d t) decreased. At all temperatures, increasing stimulation frequency increased F and (dF/d t), whereas TPF and RT decreased. At 31 and 29°C, resting tension increased at 1.5 Hz, which was ameliorated by β-AR stimulation. At all temperatures, maximal β-AR stimulation increased F, (dF/d t), and maximal systolic force, whereas resting tension decreased progressively with lowering temperature. β-AR stimulation reduced TPF and RT to the same extent at all temperatures, despite the more elongated contraction-relaxation cycle at lower temperatures. Diastolic dysfunction during hypothermia results from an elongation of the contraction-relaxation cycle, which decreases the time for ventricular filling. Hypothermic bradycardia protects the heart from diastolic dysfunction and increasing the heart rate during hypothermia should be avoided. NEW & NOTEWORTHY Decreasing temperature increases the duration of the contraction-relaxation cycle in the human ventricular myocardium, significantly reducing the time for ventricular filling during diastole. During hypothermia, increasing heart rate further reduces the time for ventricular filling and in some situations increases resting tension further impairing diastolic function. Modest β-adrenergic receptor stimulation can ameliorate these potentially detrimental changes during diastole while improving contractile force generation during targeted temperature management.
目标温度管理是心脏骤停患者标准化治疗的一部分。低温可降低脑氧耗并诱导心动过缓；因此，可考虑增加心率以维持心输出量。我们假设在低温时增加心率会损害舒张功能。从终末期心力衰竭患者心脏移植中获得的人心室小梁，在 0.5 Hz 下受到刺激，并记录收缩-舒张循环。在 37、33、31 和 29°C 下测量最大发展力（F）、最大力发展速率[(dF/d t)]、达到最大力的时间（TPF）、达到 80%松弛的时间（TR80）和松弛时间（RT=TR80-TPF）。在这些温度下，刺激频率从 0.5 增加到 1.0 和 1.5 Hz。在 1.5 Hz 时，进行了β肾上腺素能受体（β-AR）激动剂异丙肾上腺素的浓度-反应曲线。当温度降低时，F、TPF 和 RT 增加，而(dF/d t)降低。在所有温度下，增加刺激频率都会增加 F 和(dF/d t)，而 TPF 和 RT 则会降低。在 31 和 29°C 时，1.5 Hz 时静息张力增加，β-AR 刺激可改善这种情况。在所有温度下，最大β-AR 刺激均增加 F、(dF/d t)和最大收缩力，而静息张力随温度降低而逐渐降低。β-AR 刺激在所有温度下均将 TPF 和 RT 降低到相同程度，尽管在较低温度下收缩-舒张循环更长。低温时的舒张功能障碍是由于收缩-舒张循环的延长，这会减少心室充盈的时间。低温性心动过缓可保护心脏免受舒张功能障碍的影响，并且应避免在低温时增加心率。新意和值得注意的地方：在人心室心肌中，降低温度会增加收缩-舒张循环的持续时间，从而显著减少舒张期心室充盈的时间。在低温时，增加心率会进一步减少心室充盈时间，在某些情况下会进一步增加静息张力，从而进一步损害舒张功能。适度的β肾上腺素能受体刺激可以在舒张期改善这些潜在的有害变化，同时在目标温度管理期间改善收缩力产生。
