Endotoxic shock model with fluid resuscitation in Macaca mulatta

Abstract

These studies established a macaque model of early-phase endotoxic shock, and investigated the resuscitation effects of three different solutions. Twenty-four macaques were assigned to four groups. Nineteen animals were given an intravenous dose of 2.8 mg/kg lipopolysaccharide (LPS). At 60 min after LPS challenge, the animals were given (i) 5 mL/kg normal saline (Ns group, n=6), (ii) 5% of 5 mL/kg sodium bicarbonate (Sb group, n=6), (iii) hypertonic 3.5% sodium chloride of 5 mL/kg (Hs group, n=7). The control group (Co group, n=5) was first injected with 1 mL/kg Ns and with 5 mL/kg Ns 60 min later. Haemodynamic parameters and blood gases were measured during the experiment, and myocardial morphology was examined on termination of the experiment. Administration of LPS caused hypotension and decreases of the left ventricular work index (LVWI). In the Sb group, mean arterial pressure, cardiac index, systemic vascular resistance index, LVWI and right ventricular work index were significantly higher than those of the Ns group. Pathological changes of myocardium were identified in all of the LPS groups. The studies suggest that macaques are suitable models for studying endotoxic shock and potential fluid therapies.

Early-phase Endotoxic Shock-induced Myocardial Injury Increases iNOS and Selectin Expression in Macaque Primate

“…6,8,9 The hearts and plasma used in the present study were obtained from the same macaques in our recent study. 8 In order to clearly illustrate the experimental process, the experiment procedure is described below.…”

“…6 An exaggerated release of cytokines resulted in harmful effects in macaque models, such as abnormal haemodynamics, reduction of the density of ryanodine receptor/calcium release-channel in cardiac myocytes, and myocardial damage which may be observed by electron microscopy. [7][8][9] The dilation of the sarcoplasmic reticulum and myofilament destruction in myocardium and epithelial injury in capillaries were obvious in macaques, and in rabbits, too. 10 However, the mechanism of myocardial injury in macaques with early-phase endotoxic shock is obscure.…”

“…In the investigations of solution resuscitation during septic shock, 5% sodium bicarbonate treatment worsened the states of rats or rabbits, 11,12 whereas perfusion of sodium bicarbonate improved the physiological parameters of macaques. 8,9 Primates, including humans, demonstrate similar physiological functions and anatomical features, especially cardiovascular functions. Macaques, non-human primate animals, may be used to monitor haemodynamic parameters and to investigate the effects of therapy, and macaque models may mimic clinical situation of early-phase septic shock in humans.…”

“…8 Dilation of the sarcoplasmic reticulum, myofilament fracture, myofilament contractures and nuclear damage was shown in the degenerative myocardium. The myofilament bundles sometimes were broken into many pieces between two contracture zones.…”

Decrease in toll-like receptors 2 and 4 in the spleen of mouse with endotoxic tolerance

“…Some non-human primates, such as baboons and rhesus macaques, shared similar LPS sensitivity with rodents [12,13]. In macaques, 2.8 mg/kg LPS [14,15] or 3.0 mg/kg LPS [16] were needed to induce cytokine release and shock. Macaque sensitization to LPS is less strong than human sensitization.…”