Murine in Vivo Myocardial Contractile Dysfunction After Burn Injury Is Exacerbated by Pneumonia Sepsis

Abstract

We evaluated hemodynamic and cardiac contractile dysfunction in a murine model of 40% contact burn complicated by Streptococcus pneumoniae (1 x 10(5) CFU) sepsis. Male, 9- to 10-week-old C57/BL6 mice were divided into the following groups: sham burn, sham sepsis; 24 h after burn alone; 24 h after sepsis alone; 7 days after burn alone; and 7 days after burn followed by pneumonia sepsis. Hemodynamic and cardiac contractile function was assessed with carotid artery cannulation and left ventricular pressure-volume analysis. At 24 h after burn, there were significant decreases in all load-insensitive contractility variables including the end-systolic pressure volume relationship, preload-recruitable stroke work, and maximum elastance, but there were no changes in global hemodynamics. Twenty-four hours after sepsis, there was similar cardiac contractile dysfunction, along with a decrease in cardiac output, but mean arterial pressure was maintained with an increase in systemic vascular resistance. Late burn (7 days) was associated with a recovery of all contractility variables except the end-systolic pressure volume relationship. However, sepsis induced during the late burn period was associated with a significant decrease in heart rate and cardiac output, but mean arterial pressure was still maintained with increased systemic vascular resistance. With burn complicated by sepsis, all cardiac contractility variables showed profound contractile dysfunction. Our data indicate that burn complicated by sepsis is associated with more pronounced cardiac contractile dysfunction than burn alone or sepsis alone.

Role of interleukin-6 in cardiac inflammation and dysfunction after burn complicated by sepsis

“…Although IL-6 is increased as part of the acute phase reaction, its role in mediating myocardial depression after acute injuries is not as clearly defined as the roles of TNF-␣ and IL-1␤. We focused on the role of IL-6 in cardiac inflammation and function after burn plus sepsis as a clinically relevant model of injury where our laboratory has repeatedly shown that myocardial depression after this two-hit injury is exaggerated compared with burn alone or sepsis alone (33,38,42,43).…”

“…Seven days after burn, mice were anesthetized again with isoflurane, and 1 ϫ 10 5 colony forming units of S. pneumoniae were instilled into the trachea. Sepsis was confirmed by positive blood cultures 24 h after bacterial instillation (38).…”

“…We used our previously established model of 40% total body surface area (TBSA) contact burn followed by Streptococcus pneumoniae sepsis induced at 7 days after the initial burn (38,43). We used this model because our institutional data showed most infectious complications occurred between 4 and 7 days after burn injury (9), and our experimental data showed a maximum myocardial depression after this injury model of burn complicated by sepsis (38,43). The total body weight (TBW) of each mouse was obtained before the injury.…”

“…Variables obtained during IVC occlusion included LV end-systolic pressure-volume relationship (ESPRV), preload-recruitable stroke work (PRSW), and time-varying maximum elastance (E max). All data were analyzed with pressure-volume analysis software (PVAN version 3.1; Millar Instruments) (38).…”

“…Whereas many studies suggest an active role of this cytokine in acute inflammation (32), others indicate its role as a marker (31), or even as an anti-inflammatory mediator (44). The complex roles of IL-6 in mediating essential cell function and the inflammatory response after burn and sepsis prompted the present study examining the effects of IL-6 on cardiac inflammation and function using our clinically relevant model of burn complicated by sepsis (burn plus sepsis) (38,43). On the basis of our previous findings (24), we hypothesize that IL-6 mediates myocardial dysfunction after burn plus sepsis.…”