Preinduction of heat shock proteins protects cardiac and hepatic functions following trauma and hemorrhage

Abstract

Although studies have shown that induction of the heat shock proteins (HSPs), such as HSP-70, has various beneficial effects after ischemia-reperfusion, it remains unknown whether prior induction of HSP-70 has any salutary effects on cardiovascular and hepatocellular functions after trauma-hemorrhage and resuscitation. Male rats were exposed to heat stress (41 degrees C, 15 min) and then allowed to recover for 24 h at room temperature (21 degrees C). The rats then underwent laparotomy (i.e., trauma induced) and were bled to and maintained at a mean arterial pressure of 40 mmHg until 40% of the maximal shed blood volume was returned in the form of Ringer lactate. Animals were then resuscitated with four times the volume of shed blood with Ringer lactate over 60 min. The maximal rate of the left ventricular pressure increase or decrease was measured up to 4 h after resuscitation. Cardiac output, hepatocellular function, plasma levels of tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) were determined at 4 h after resuscitation. Cardiac and hepatic tissue were examined for HSP-70 by Western blot analysis. Left ventricular performance, cardiac output, and hepatocellular function decreased significantly following trauma-hemorrhage. Plasma levels of TNF-alpha and IL-6 were also significantly increased. However, prior heat stress attenuated cardiovascular and hepatocellular dysfunction, decreased circulating levels of proinflammatory cytokines following trauma-hemorrhage, and was associated with an increased abundance of HSP-70 in the heart and liver. Our data, therefore, suggest that preinduction of HSP-70 protects cardiovascular and hepatocellular functions following trauma-hemorrhage and resuscitation.

Mechanism of cardiac depression after trauma-hemorrhage: increased cardiomyocyte IL-6 and effect of sex steroids on IL-6 regulation and cardiac function

“…The present results also showed that the mortality rate was 22% in male rats 2 h after trauma-hemorrhage and resuscitation; however, all castrated and E 2 -treated males were alive 2 h after traumahemorrhage and resuscitation. Furthermore, previous studies showed that the mortality rate was 30% in the vehicle-treated hemorrhaged group and 11% in the E 2 -treated group (33). In view of this information, it would appear that the observed salutary effects of E 2 do not appear to be short term.…”

“…Although we have not measured survival rates in this study, our previous results showed that if an agent had a salutary effect early after trauma-hemorrhage and resuscitation, the beneficial effects were sustained for longer periods of time and they also resulted in improved survival rates of animals (33). The present results also showed that the mortality rate was 22% in male rats 2 h after trauma-hemorrhage and resuscitation; however, all castrated and E 2 -treated males were alive 2 h after traumahemorrhage and resuscitation.…”

“…Moreover, it has been shown that estradiol attenuates cytokine production by inhibiting the transcription factor NF-B and inducing expression of the 90-kDa heat shock protein (HSP)-90 in various tissues (10). Our previous studies also showed that induction of HSPs was associated with protective effects under adverse circulatory conditions (33). Thus the normalized organ function after trauma-hemorrhage in E 2 -treated males may be also due to induction of HSP-90.…”

Inducible heat shock protein 70 kD and inducible nitric oxide synthase in hemorrhage/resuscitation-induced injury

“…A variety of biomolecules is known to be involved in this response. In rodents, increases in HSP-70i by heat stress limit tissue injury such as tissue integrity, polymorphonuclear neutrophil (PMN) infiltration and leukotriene B 4 (LTB 4 ) generation caused by ischemia reperfusion [3,4], hemorrhage [5], or hemorrhage plus resuscitation [6]. In transgenic mice expressing HSP-70i, protection against myocardial dysfunction after a brief ischemia was reported [7].…”

“…For example, TNF-α overexpression caused by sepsis, endotoxemia, hemorrhagic shock, and ischemia/ reperfusion [52,53,65] has been found. In vitro induction of HSP-70i in moncytes or macrophages inhibits TNF-α production following bacteria lipopolysaccharide stimulation, and in vivo induction of HSP-70i down-regulates tissue TNF-α production following an injurious insult [5,52,53,66]. The underlying mechanism of the inhibitory action of HSP-70i on TNF-α over-production induced by sepsis, endotoxemia, hemorrhagic shock, or ischemia/reperfusion is not clear.…”