Left ventricular function during porcine-resuscitated septic shock with pre-existing atherosclerosis.
BACKGROUND
Reversible, depressed cardiac function is frequently encountered during septic shock and commonly called septic cardiomyopathy. Previous studies demonstrated reduced ejection fraction and left ventricular dilatation in both humans and animal models. However, the majority of the studies in humans excluded pre-existing cardiac disease and animal studies were performed on healthy specimen and/or without vasopressor support during sepsis. In order to more closely mimic the actual patients' conditions on intensive care units and to assess the influence of both cardiac comorbidity and vasopressor support on septic cardiomyopathy, we evaluated the left ventricular function in a porcine model of resuscitated septic shock with pre-existing atherosclerosis.


METHODS
Hypercholesterolaemic, atherosclerotic pigs due to homozygous low-density lipoprotein receptor mutation and high-fat diet were anaesthetised and surgically instrumented. Faecal peritonitis was induced by inoculation of autologous faeces into the peritoneal cavity in n = 8 animals; n = 5 pigs underwent sham procedure. Sepsis resuscitation included administration of fluids and noradrenaline. Left ventricular function was analysed via pressure-conductance catheters before, 12 and 24 h after the induction of sepsis.


RESULTS
The main findings were impaired ventricular dilatation (no significant change in the left ventricular end-diastolic volume) and unchanged ejection fraction in septic pigs with pre-existing atherosclerosis. The relaxation time constant τ decreased while dp/dtmax increased. Cardiac nitrotyrosine formation increased while expression of the endogenous hydrogen sulphide (H2S)-producing enzyme cystathionine γ-lyase (CSE) decreased.


CONCLUSIONS
The data of the present study are in conflict with previously published data from healthy animal models, most likely as a result of ongoing resuscitation including noradrenaline treatment or intrinsic pathophysiologic processes of the pre-existing atherosclerosis. Moreover, increased nitrotyrosine formation and decreased expression of CSE suggest the implication of augmented oxidative/nitrosative stress and/or reduced bioavailability of nitric oxide as well as diminished endogenous H2S release in the pathophysiology of septic cardiomyopathy.
Klinik für Anästhesiologie, Universitätsklinik Ulm, Ulm, Germany. benedikt.nussbaum@uni-ulm.de.|Institut für Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Universitätsklinik Ulm, Helmholtzstraße 8/1, 89081, Ulm, Germany. benedikt.nussbaum@uni-ulm.de.
Benedikt L
BL
Nußbaum
Institut für Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Universitätsklinik Ulm, Helmholtzstraße 8/1, 89081, Ulm, Germany.
Oscar
O
McCook
Klinik für Anästhesiologie, Universitätsklinik Ulm, Ulm, Germany.|Institut für Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Universitätsklinik Ulm, Helmholtzstraße 8/1, 89081, Ulm, Germany.
Clair
C
Hartmann
Institut für Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Universitätsklinik Ulm, Helmholtzstraße 8/1, 89081, Ulm, Germany.
José
J
Matallo
Klinik für Anästhesiologie, Universitätsklinik Ulm, Ulm, Germany.|Institut für Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Universitätsklinik Ulm, Helmholtzstraße 8/1, 89081, Ulm, Germany.
Martin
M
Wepler
Department of Surgical Sciences and Integrated Diagnostics, IRCCS San Martino IST, University of Genova, Genova, Italy.
Elena
E
Antonucci
Klinik für Unfall-, Hand-, Plastische- und Wiederherstellungschirurgie, Universitätsklinik Ulm, Ulm, Germany.
Miriam
M
Kalbitz
Klinik für Unfall-, Hand-, Plastische- und Wiederherstellungschirurgie, Universitätsklinik Ulm, Ulm, Germany.
Markus
M
Huber-Lang
Klinik für Anästhesiologie, Universitätsklinik Ulm, Ulm, Germany.
Michael
M
Georgieff
Institut für Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Universitätsklinik Ulm, Helmholtzstraße 8/1, 89081, Ulm, Germany.
Enrico
E
Calzia
Institut für Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Universitätsklinik Ulm, Helmholtzstraße 8/1, 89081, Ulm, Germany.
Peter
P
Radermacher
Klinik für Anästhesiologie, Universitätsklinik Ulm, Ulm, Germany.|Institut für Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Universitätsklinik Ulm, Helmholtzstraße 8/1, 89081, Ulm, Germany.
Sebastian
S
Hafner
Atherosclerosis; CSE; Comorbidity; Left ventricular function; Nitrotyrosine; Septic cardiomyopathy; Septic shock; Ventricular dilatation