The increasing availability of mice with gene supplementation (transgenic), site-specific inactivation mutations (gene "knock-outs"), or site-specific genetic modification mutations (gene "knock-ins") has spurred interest in the development of murine
trauma models. In this study, C57 BL/6 mice (28 g) were given a cutaneous
burn over 40% total body surface area by applying
brass probes (1 x 2 x 0.003 cm) heated to 100 degrees C in boiling water to the animals side and back for 5 s. Shams received
anesthesia alone and not
burn. Mice were killed 24 h post-
burn to determine presence of partial-thickness or full-thickness
burn injury, cardiac contractile function (Langendorff perfusion, n = 7 or 8 mice/group) or to examine cardiac myocyte
cytokine secretion in isolated cardiomyocytes (
collagenase perfusion, n = 4 or 5 mice/group). All mice were killed 24 h post-
burn for subsequent cardiac or cardiomyocyte studies. Our studies confirm that this murine model of
burn trauma produced mixed partial- or full-thickness
burn injury, whereas there was no
necrosis or
inflammation in
sham burn mice. Baseline hematocrits were similar in all mice (44+/-1) but decreased after
burn trauma (37+/-1), likely because of the volume of fluid
resuscitation and
hemodilution.
Burn trauma impaired cardiac contraction and relaxation as indicated by the lower left ventricular pressure (LVP) measured in
burn (56+/-4) compared to that measured in shams (84+/-1 mmHg, P < 0.001), a lower rate of LVP rise (+dP/dt max, 1393+/-10 vs. 2000+/-41 mmHg/s, P < 0.002), and reduced LVP fall (-dP/dt max, 1023 - 40 vs. 1550+/-50, P < 0.001). These differences occurred despite similar coronary perfusion pressures and heart rates in both
sham and
burn mice. Ventricular function curves were shifted downward in the
burn mice in the direction of contractile failure; in addition, hearts from
burn mice had reduced LVP and +dP/dt responses to increases in coronary flow rate, increases in perfusate Ca2+, and to
isoproterenol challenge (P < 0.05).
Burn trauma promoted cardiac myocyte secretion of
tumor necrosis factor (
TNFalpha) (175+/-6 pg/mL) compared to that measured in shams (72+/-9 pg/mL, P < 0.05);
burn trauma also increased cardiac myocyte secretion of
interleukin 1beta (IL-1beta) (
sham: 2+/-0.5;
burn: 22+/-1 pg/mL, P < 0.05) and
IL-6 (
sham: 70+/-6;
burn: 148+/-16 pg/mL, P < 0.05). Anti-
TNFalpha strategies prevented
burn-mediated cardiac contractile deficits.
Burn trauma altered Ca2+ homeostasis in murine cardiomyocytes (
Fura-2 AM loading). [Ca2+]i in myocytes from
burns (185+/-4 nM) was higher than values measured in myocytes from shams (86+/-nM, P < 0.05). These data confirm that the murine
burn model provides a reasonable approach to study the molecular and cell biology of
inflammation in organ dysfunction after
burn trauma.