Chronic Porcine Two-Hit Model with Hemorrhagic Shock and <i>Pseudomonas aeruginosa</i> Sepsis

Abstract

Background: Sepsis is still a major cause of death despite well-developed therapeutical strategies such as antibiotics and supportive medication. The aim of this study was to characterize the long-term effects of a two-hit porcine sepsis model with a hemorrhagic shock as ‘first hit’ followed by a Pseudomonas aeruginosa infusion as ‘second hit’. Materials and Methods: Twelve juvenile healthy pigs were anesthetized and hemodynamically monitored. The two-hit group (n = 6) underwent a hemorrhagic shock with a 50% reduction of the mean arterial pressure and/or cardiac index for 45 min, followed by resuscitation, while the control group (n = 6) received no pretreatment. All chronically catheterized conscious pigs were challenged with a P. aeruginosa infusion (1.6 × 10⁷ CFU/kg/h for the first 24 h followed by 1.6 × 10⁶ CFU/kg/h for the next 24 h) and observed for another 48 h. Results: The two-hit group showed the following significant differences to the control group: higher APACHE II scores prior to sepsis induction, increased persisting mean pulmonary arterial pressure (MPAP) and pulmonary vascular resistance index (PVRI) during bacterial challenge. In contrast, systemic vascular resistance (SVRI) was reduced at the end of the study. Throughout the observation period, the mean arterial pressure (MAP) was significantly reduced. Conclusions: The present study shows that the clinical course and hemodynamic effects of a P. aeruginosa sepsis will be aggravated by a preceding hemorrhagic shock during an oberservation period of 96 h. This two-hit model represents a valid, clinically relevant experimental protocol in sepsis research.

Iron Dysregulation Combined with Aging Prevents Sepsis-Induced Apoptosis1

“…This is complimentary to data demonstrating that the pathobiological response to two separate "hits" is dependent upon an animal's genetic background and both the timing between and specific insults used [35,[37][38][39][40]. In "two hit" models of critical illness, the body's response frequently is markedly different from what would have been predicted based upon the reaction to a single insult.…”

Whatever happened to the Shwartzman phenomenon?

“…The dermal or generalized Shwartzman-like reaction ("two hit" model) [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][56][57][58][65][66][67][68] Endotoxin tolerance (LPS reprogramming) [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][56][57][58][65][66][67][68] Overall primary mode of transmission would be an instant, international folk hero indeed. Many theories were postulated to explain the cause of the illness ranging from bad water, miasma theory (airborne mists and contaminated, dirty, living conditions), fomites (particularly bed cloths and linens) mosquitos, fungi, bacteria, or tiny filterable agents.…”

“…A summary of the advances in understanding the interactions between the coagulation system and innate immunity, differences between endotoxin priming and endotoxin tolerance are listed in Table 1. [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][65][66][67] Univisceral Shwartzman-like reaction Local Shwartzman reaction can be induced many different tissues and is not limited to the skin. 68,69 The reaction can be induced in the lung by repetitive intratracheal administration of an inoculum.…”

Porcine Models of Severe Sepsis: Emphasis on Porcine Peritonitis

“…This priming is because of alterations in neutrophil as well as macrophage immunologic function, and likely includes maladaptive and protective responses. Eissner et al (26) used hemorrhagic shock as the initial insult, and after recovery, exposed the pigs to P. aeruginosa by infusion. When compared with a control group, Pseudomonas-induced sepsis was characterized by persisting mean pulmonary artery pressure and pulmonary vascular resistance increase, whereas systemic vascular resistance was reduced, thus paralleling typical human sepsis hemodynamics.…”