Blood pressure variability, heart functionality, and left ventricular tissue alterations in a protocol of severe hemorrhagic shock and resuscitation

Abstract

Autonomic control of blood pressure (BP) and heart rate (HR) is crucial during bleeding and hemorrhagic shock (HS) to compensate for hypotension and hypoxia. Previous works have observed that at the point of hemodynamic decompensation a marked suppression of BP and HR variability occurs, leading to irreversible shock. We hypothesized that recovery of the autonomic control may be decisive for effective resuscitation, along with restoration of mean BP. We computed cardiovascular indexes of baroreflex sensitivity and BP and HR variability by analyzing hemodynamic recordings collected from five pigs during a protocol of severe hemorrhage and resuscitation; three pigs were sham-treated controls. Moreover, we assessed the effects of severe hemorrhage on heart functionality by integrating the hemodynamic findings with measures of plasma high-sensitivity cardiac troponin T and metabolite concentrations in left ventricular (LV) tissue. Resuscitation was performed with fluids and norepinephrine and then by reinfusion of shed blood. After first resuscitation, mean BP reached the target value, but cardiovascular indexes were not fully restored, hinting at a partial recovery of the autonomic mechanisms. Moreover, cardiac troponins were still elevated, suggesting a persistent myocardial sufferance. After blood reinfusion all the indexes returned to baseline. In the harvested heart, LV metabolic profile confirmed the acute stress condition sensed by the cardiomyocytes. Variability indexes and baroreflex trends can be valuable tools to evaluate the severity of HS, and they may represent a more useful end point for resuscitation in combination with standard measures such as mean values and biological measures. NEW & NOTEWORTHY Autonomic control of blood pressure was highly impaired during hemorrhagic shock, and it was not completely recovered after resuscitation despite global restoration of mean pressures. Moreover, a persistent myocardial sufferance emerged from measured cardiac troponin T and metabolite concentrations of left ventricular tissue. We highlight the importance of combining global mean values and biological markers with measures of variability and autonomic control for a better characterization of the effectiveness of the resuscitation strategy.

Keywords: cardiovascular autonomic control; hemorrhagic shock; metabolomics; myocardial sufferance; resuscitation.

Fig. 1.

Distributions (median, 25th and 75th percentiles) of the averaged value at each time point of the following variables: mean arterial pressure (MAP), heart rate (HR), maximum of 1st derivative of left ventricular pressure over time (dP/dt_max), and right atrial pressure (RAP) for both populations of hemorrhagic shock- and sham-treated animals. Open symbols indicate values relating to each shock- or sham-treated pig. T1, baseline; T2, after development of shock; T3, after fluid and vasopressor resuscitation; T4, after blood reinfusion; bpm, beats per minute. *P < 0.05 shock- vs. sham-treated animals (Mann-Whitney U-test); ^##P < 0.01 vs. T1; §P < 0.05, §§P < 0.01 vs. T2 (Friedman test, only for shock-treated pigs).

Fig. 2.

Ratio between low-frequency (LF) absolute power of each predicted component and LF absolute power of diastolic arterial pressure (DAP) at each time point for hemorrhagic shock animals. Column height is median value for the population; black bars indicate values of 25th and 75th percentiles. T1, baseline; T2, after development of shock; T3, after fluid and vasopressor resuscitation; T4, after blood reinfusion; SAP, systolic arterial pressure; RR, R-R interval. ^#P < 0.05 vs. T1 (Friedman test).