Heart-rate variability depression in porcine peritonitis-induced sepsis without organ failure

Abstract

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.

Esmolol indirectly stimulates vagal nerve activity in endotoxemic pigs

“…In addition to this, the SDNN power is relatively low in all the animal groups as reported in other studies [ 28 ]. This gives a strong importance to the spectral variations observed during the endotoxemic aggression.…”

SOFA Score, Hemodynamics and Body Temperature Allow Early Discrimination between Porcine Peritonitis-Induced Sepsis and Peritonitis-Induced Septic Shock

“…In general, the vascular smooth muscle tone is a product of intensive crosstalk of local (humoral) regulatory mechanisms and of central regulatory mechanisms of the autonomic nervous system, dominantly the sympathetic branch. Analysis of heart rate variability, in agreement with our previous studies [14,26], revealed a shift of the sympathovagal balance toward sympathetic dominance (increase in LF component, decrease in HF component) in both groups to a similar extent. However, the increased sympathetic drive, in the group of septic shock even with further support of therapeutic administration of norepinephrine, did not override (peripheral) vasodilatory mechanism, and consequently, it did not prevent a marked reduction of the systemic vascular resistance.…”

“…In short, autologous feces (1 g/kg for inducing septic shock or 0.5 g/kg for inducing sepsis) were inoculated in the abdominal cavity after short cultivation (10 h, isotonic saline, 37 • C). The selection of doses was based on earlier studies of our group [11][12][13][14]. The high dose (1 g/kg) was sufficient in our experimental setting for the development of irreversible septic shock with sustained vasopressor support within 20-22 h. The low dose (0.5 g/kg) invariably did not induce septic shock within 24 h (no sustained vasopressor support, low plasma levels of lactate).…”

Rethinking animal models of sepsis – working towards improved clinical translation whilst integrating the 3Rs

“…Interdisciplinary collaboration with bioengineering, statistics and mathematics can help to make more of the data acquired. For example, the extraction of heart rate variability or other detailed cardiovascular changes [103][104][105][106][107] can be generated from preclinical blood pressure or ECG waveforms and can be combined with inflammatory biomarkers, to build a more detailed picture of the physiological status of the animal. Reassuringly, such interdisciplinary analytical approaches have already led to the successful development of early alert systems in patients [108].…”