Jarkovska Dagmar, Valesova Lenka, Chvojka Jiri, Benes Jan, Danihel Vojtech, Sviglerova Jitka, Nalos Lukas, Matejovic Martin, Stengl Milan
1 Biomedical Center, Faculty of Medicine in Pilsen, Charles University, 32300 Pilsen, Czech Republic.
2 Department of Physiology, Faculty of Medicine in Pilsen, Charles University, 32300 Pilsen, Czech Republic.
Exp Biol Med (Maywood). 2017 May;242(9):1005-1012. doi: 10.1177/1535370217700521. Epub 2017 Mar 17.
Depression of heart-rate variability (HRV) in conditions of systemic inflammation has been shown in both patients and experimental animal models and HRV has been suggested as an early indicator of sepsis. The sensitivity of HRV-derived parameters to the severity of sepsis, however, remains unclear. In this study we modified the clinically relevant porcine model of peritonitis-induced sepsis in order to avoid the development of organ failure and to test the sensitivity of HRV to such non-severe conditions. In 11 anesthetized, mechanically ventilated and instrumented domestic pigs of both sexes, sepsis was induced by fecal peritonitis. The dose of feces was adjusted and antibiotic therapy was administered to avoid multiorgan failure. Experimental subjects were screened for 40 h from the induction of sepsis. In all septic animals, sepsis with hyperdynamic circulation and increased plasma levels of inflammatory mediators developed within 12 h from the induction of peritonitis. The sepsis did not progress to multiorgan failure and there was no spontaneous death during the experiment despite a modest requirement for vasopressor therapy in most animals (9/11). A pronounced reduction of HRV and elevation of heart rate developed quickly (within 5 h, time constant of 1.97 ± 0.80 h for HRV parameter TINN) upon the induction of sepsis and were maintained throughout the experiment. The frequency domain analysis revealed a decrease in the high-frequency component. The reduction of HRV parameters and elevation of heart rate preceded sepsis-associated hemodynamic changes by several hours (time constant of 11.28 ± 2.07 h for systemic vascular resistance decline). A pronounced and fast reduction of HRV occurred in the setting of a moderate experimental porcine sepsis without organ failure. Inhibition of parasympathetic cardiac signaling probably represents the main mechanism of HRV reduction in sepsis. The sensitivity of HRV to systemic inflammation may allow early detection of a moderate sepsis without organ failure. Impact statement A pronounced and fast reduction of heart-rate variability occurred in the setting of a moderate experimental porcine sepsis without organ failure. Dominant reduction of heart-rate variability was found in the high-frequency band indicating inhibition of parasympathetic cardiac signaling as the main mechanism of heart-rate variability reduction. The sensitivity of heart-rate variability to systemic inflammation may contribute to an early detection of moderate sepsis without organ failure.
在系统性炎症状态下，患者和实验动物模型均已显示出心率变异性（HRV）降低，并且HRV已被认为是脓毒症的早期指标。然而，HRV衍生参数对脓毒症严重程度的敏感性仍不清楚。在本研究中，我们对临床上相关的腹膜炎诱导脓毒症猪模型进行了改良，以避免器官衰竭的发生，并测试HRV对这种非严重状态的敏感性。在11只麻醉、机械通气并安装仪器的雌雄家猪中，通过粪便性腹膜炎诱导脓毒症。调整粪便剂量并给予抗生素治疗以避免多器官衰竭。从脓毒症诱导开始对实验对象进行40小时的筛查。在所有脓毒症动物中，腹膜炎诱导后12小时内出现了伴有高动力循环和炎症介质血浆水平升高的脓毒症。脓毒症未进展为多器官衰竭，并且尽管大多数动物（9/11）对血管加压药治疗有适度需求，但实验期间没有自发死亡。脓毒症诱导后，HRV迅速显著降低且心率升高（在5小时内，HRV参数TINN的时间常数为1.97±0.80小时），并在整个实验过程中维持。频域分析显示高频成分减少。HRV参数的降低和心率升高比脓毒症相关的血流动力学变化提前数小时（全身血管阻力下降的时间常数为11.28±2.07小时）。在无器官衰竭的中度实验性猪脓毒症情况下，HRV出现了显著且快速的降低。脓毒症中HRV降低的主要机制可能是副交感神经心脏信号传导的抑制。HRV对全身炎症的敏感性可能有助于早期检测无器官衰竭的中度脓毒症。影响声明 在无器官衰竭的中度实验性猪脓毒症情况下，心率变异性出现了显著且快速的降低。在高频带中发现心率变异性主要降低，表明副交感神经心脏信号传导的抑制是心率变异性降低的主要机制。心率变异性对全身炎症的敏感性可能有助于早期检测无器官衰竭的中度脓毒症。
