ABSTRACT
BACKGROUND: Lower liver transplant success is observed when the donor is female. Intracellular acidosis during ischemia is proposed to contribute to the injury sustained by the transplanted organ and its role in livers obtained from nonheartbeating donors is unclear. Research has shown that livers of female rats develop a greater degree of intracellular acidosis during ischemia than males. This work explores the role of sex hormones in mediating this sex difference. METHODS: Subgroups of neutered female rats were given 17 beta-estradiol (E), progesterone (P), or combination (E+P). To compare the effects of female sex hormones in males, subgroups of intact and castrated males received 17 beta-estradiol. In vivo and ischemic liver biopsies were taken and analyzed for lactate and H. RESULTS: Although there was no effect of hormone therapy on baseline metabolic parameters, during ischemia compared to neutered females, livers from E females significantly (P<0.01) increased lactate by 56% and H+ by 71%, while E+P significantly increased only lactate (39%; P<0.05). Livers from neutered males given 17 beta-estradiol showed significantly greater (P<0.001) accumulation of lactate (80%) and H+ (79%). This was even shown in intact males, where despite a blunted response, 17 beta-estradiol, significantly (P<0.05) increased lactate by 39% and H+ by 25%. CONCLUSION: This study illustrates the mechanisms for the sex difference in the liver's metabolic response to ischemia are estrogen mediated, which is seen even in the presence of male hormones, thus offering one explanation for the lower liver transplant success when the donor is female.
Subject(s)
Acidosis, Lactic/metabolism , Estradiol/metabolism , Gonadal Steroid Hormones/metabolism , Liver/metabolism , Progesterone/metabolism , Reperfusion Injury/metabolism , Acidosis, Lactic/etiology , Animals , Estradiol/pharmacology , Female , Gonadal Steroid Hormones/pharmacology , Hydrogen/metabolism , Lactic Acid/analysis , Liver/drug effects , Male , Progesterone/pharmacology , Rats , Rats, Sprague-Dawley , Reperfusion Injury/complications , Sex FactorsABSTRACT
The testes of Wistar Kyoto (WKY) and Spontaneously Hypertensive (SHR) rats have been shown to have differences in regional vascular resistance. In addition, myocardial hypertrophy tends to be more pronounced and occur more frequently in WKY and SHR female rats than in their male counterparts. Therefore, we sought to determine whether hypertension had any effect on reproductive organs and whether this effect was the same among strains. We removed the testes or uterus from Sprague Dawley (SD; n = 30 male and 30 female), WKY (n = 23 male and 16 female), and SHR (n = 27 male and 34 female) rats, weighed these animals and organs, and calculated the reproductive organ:body weight ratio (mean +/- 1 standard deviation x 10-3 g). The testes:body weight ratio of WKY (6.5 +/- 0.8) animals was significantly (P= 0.05) less than those of SD (7.6 +/- 1.1) and SHR (8.0 +/- 0.5) rats. The uterus:body weight ratio of the SD rats (1.7 +/- 0.4) was significantly (P = 0.05) less than those of WKY (2.4 +/- 0.6) and SHR (2.3 +/- 0.6) rats. Compared with WKY rats, male SD rats had a higher testes:body weight ratio whereas female SD rats had a lower uterus: body weight ratio. Whereas the SHR testes:body weight ratio was significantly higher than that of WKY rats, this effect was not seen for the uterus: body weight ratio. The effect of hypertension on reproductive organs should be taken into consideration when choosing a species, gender, or organ for study. As well, data compared across genders or strains must be evaluated carefully to ensure valid comparisons.
Subject(s)
Body Weights and Measures , Genitalia/physiopathology , Hypertension/complications , Animals , Female , Male , Rats , Rats, Mutant Strains , Rats, WistarABSTRACT
A multiple in vivo liver biopsy technique was developed to measure labile metabolites (creative phosphate [CP], ATP, lactate) without interfering with normal perfusion and metabolism. Anesthetized rats (n = 7) had a midline abdominal incision done to expose the liver. Four biopsies were taken across 20 min. Bleeding was controlled by a small, nontraumatic clamp proximal to the biopsy. Prefrozen dressing forceps grasped the liver and scissors cut the biopsy, which was frozen in liquid nitrogen. Bleeding was minimal and hemodynamic stability was preserved. This technique has few complications, bleeding is easily controlled, and it allows for large multiple biopsies, which give reliable metabolic data and can be consistently taught.