Early immunoneutralization of calcitonin precursors attenuates the adverse physiologic response to sepsis in pigs

Kristin E. Wagner, Jose M Martinez, Steven D. Vath, Richard H. Snider, Eric S. Nylén, Kenneth L. Becker, Beat Müller, Jon C. White

Research output: Contribution to journalArticle

83 Citations (Scopus)

Abstract

Objective: The 116 amino acid prohormone procalcitonin and some of its component peptides (collectively termed calcitonin precursors) are important markers and mediators of sepsis. In this study, we sought to evaluate the effect of immunoneutralization of calcitonin precursors on metabolic and physiologic variables of sepsis in a porcine model. Design: A prospective, controlled animal study. Setting: A university research laboratory. Subjects: 30-kg Yorkshire pigs. Interventions: Sepsis was induced in 15 pigs by intraperitoneal instillation of a suspension of cecal content (1 g/kg animal body weight) and a toxinogenic Escherichia coli solution (2 × 1011 colony-forming units). During induction of sepsis, seven pigs received an intravenous infusion of purified rabbit anfiserum, reactive to the aminoterminal portion of porcine prohormone procalcitonin. Another eight control pigs received an intravenous infusion of purified non-reactive rabbit antiserum. For all 15 animals, physiologic data (urine output, core temperature, arterial pressure, heart rate, cardiac index, and stroke volume index) and metabolic data (serum blood urea nitrogen and creatinine, arterial lactate, and pH) were collected or recorded hourly until death at 15 hrs. Measurements and Main Results: In this large-animal model of rapidly lethal peritonitis, serum calcitonin precursors were significantly elevated. Amino-prohormone procalcitonin-reactive antiserum administration resulted in a significant improvement or a beneficial trend in a majority of the measured physiologic and metabolic derangements induced by sepsis. Specifically, arterial pressure, cardiac index, stroke volume index, pH, and creatinine were all significantly improved, while urine output and serum lactate had beneficial trends. Treated animals also experienced a statistically significant increase of short-term survival. Conclusions: These data from a large-animal model with polymicrobial sepsis demonstrate the salutary effect of early immunoneutralization of calcitonin precursors on physiologic and metabolic variables. Immunologic blockade of calcitonin precursors may offer a novel therapeutic approach to human sepsis.

Original languageEnglish
Pages (from-to)2313-2321
Number of pages9
JournalCritical Care Medicine
Volume30
Issue number10
StatePublished - Oct 1 2002
Externally publishedYes

Fingerprint

Calcitonin
Sepsis
Swine
Intravenous Infusions
Stroke Volume
Immune Sera
Lactic Acid
Creatinine
Arterial Pressure
Animal Models
Serum
Urine
Rabbits
Cardiac Volume
Blood Urea Nitrogen
Peritonitis
Suspensions
Stem Cells
Heart Rate
Body Weight

Keywords

  • Calcitonin gene related peptide
  • Calcitonin precursors
  • Cardiac index
  • Immunoneutralization
  • Lactate
  • Peritonitis
  • PH
  • Procalcitonin
  • Renal function
  • Sepsis

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Wagner, K. E., Martinez, J. M., Vath, S. D., Snider, R. H., Nylén, E. S., Becker, K. L., ... White, J. C. (2002). Early immunoneutralization of calcitonin precursors attenuates the adverse physiologic response to sepsis in pigs. Critical Care Medicine, 30(10), 2313-2321.

Early immunoneutralization of calcitonin precursors attenuates the adverse physiologic response to sepsis in pigs. / Wagner, Kristin E.; Martinez, Jose M; Vath, Steven D.; Snider, Richard H.; Nylén, Eric S.; Becker, Kenneth L.; Müller, Beat; White, Jon C.

In: Critical Care Medicine, Vol. 30, No. 10, 01.10.2002, p. 2313-2321.

Research output: Contribution to journalArticle

Wagner, KE, Martinez, JM, Vath, SD, Snider, RH, Nylén, ES, Becker, KL, Müller, B & White, JC 2002, 'Early immunoneutralization of calcitonin precursors attenuates the adverse physiologic response to sepsis in pigs', Critical Care Medicine, vol. 30, no. 10, pp. 2313-2321.
Wagner, Kristin E. ; Martinez, Jose M ; Vath, Steven D. ; Snider, Richard H. ; Nylén, Eric S. ; Becker, Kenneth L. ; Müller, Beat ; White, Jon C. / Early immunoneutralization of calcitonin precursors attenuates the adverse physiologic response to sepsis in pigs. In: Critical Care Medicine. 2002 ; Vol. 30, No. 10. pp. 2313-2321.
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AU - Wagner, Kristin E.

AU - Martinez, Jose M

AU - Vath, Steven D.

AU - Snider, Richard H.

AU - Nylén, Eric S.

AU - Becker, Kenneth L.

AU - Müller, Beat

AU - White, Jon C.

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N2 - Objective: The 116 amino acid prohormone procalcitonin and some of its component peptides (collectively termed calcitonin precursors) are important markers and mediators of sepsis. In this study, we sought to evaluate the effect of immunoneutralization of calcitonin precursors on metabolic and physiologic variables of sepsis in a porcine model. Design: A prospective, controlled animal study. Setting: A university research laboratory. Subjects: 30-kg Yorkshire pigs. Interventions: Sepsis was induced in 15 pigs by intraperitoneal instillation of a suspension of cecal content (1 g/kg animal body weight) and a toxinogenic Escherichia coli solution (2 × 1011 colony-forming units). During induction of sepsis, seven pigs received an intravenous infusion of purified rabbit anfiserum, reactive to the aminoterminal portion of porcine prohormone procalcitonin. Another eight control pigs received an intravenous infusion of purified non-reactive rabbit antiserum. For all 15 animals, physiologic data (urine output, core temperature, arterial pressure, heart rate, cardiac index, and stroke volume index) and metabolic data (serum blood urea nitrogen and creatinine, arterial lactate, and pH) were collected or recorded hourly until death at 15 hrs. Measurements and Main Results: In this large-animal model of rapidly lethal peritonitis, serum calcitonin precursors were significantly elevated. Amino-prohormone procalcitonin-reactive antiserum administration resulted in a significant improvement or a beneficial trend in a majority of the measured physiologic and metabolic derangements induced by sepsis. Specifically, arterial pressure, cardiac index, stroke volume index, pH, and creatinine were all significantly improved, while urine output and serum lactate had beneficial trends. Treated animals also experienced a statistically significant increase of short-term survival. Conclusions: These data from a large-animal model with polymicrobial sepsis demonstrate the salutary effect of early immunoneutralization of calcitonin precursors on physiologic and metabolic variables. Immunologic blockade of calcitonin precursors may offer a novel therapeutic approach to human sepsis.

AB - Objective: The 116 amino acid prohormone procalcitonin and some of its component peptides (collectively termed calcitonin precursors) are important markers and mediators of sepsis. In this study, we sought to evaluate the effect of immunoneutralization of calcitonin precursors on metabolic and physiologic variables of sepsis in a porcine model. Design: A prospective, controlled animal study. Setting: A university research laboratory. Subjects: 30-kg Yorkshire pigs. Interventions: Sepsis was induced in 15 pigs by intraperitoneal instillation of a suspension of cecal content (1 g/kg animal body weight) and a toxinogenic Escherichia coli solution (2 × 1011 colony-forming units). During induction of sepsis, seven pigs received an intravenous infusion of purified rabbit anfiserum, reactive to the aminoterminal portion of porcine prohormone procalcitonin. Another eight control pigs received an intravenous infusion of purified non-reactive rabbit antiserum. For all 15 animals, physiologic data (urine output, core temperature, arterial pressure, heart rate, cardiac index, and stroke volume index) and metabolic data (serum blood urea nitrogen and creatinine, arterial lactate, and pH) were collected or recorded hourly until death at 15 hrs. Measurements and Main Results: In this large-animal model of rapidly lethal peritonitis, serum calcitonin precursors were significantly elevated. Amino-prohormone procalcitonin-reactive antiserum administration resulted in a significant improvement or a beneficial trend in a majority of the measured physiologic and metabolic derangements induced by sepsis. Specifically, arterial pressure, cardiac index, stroke volume index, pH, and creatinine were all significantly improved, while urine output and serum lactate had beneficial trends. Treated animals also experienced a statistically significant increase of short-term survival. Conclusions: These data from a large-animal model with polymicrobial sepsis demonstrate the salutary effect of early immunoneutralization of calcitonin precursors on physiologic and metabolic variables. Immunologic blockade of calcitonin precursors may offer a novel therapeutic approach to human sepsis.

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KW - Renal function

KW - Sepsis

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