The evaluation of pituitary damage associated with cardiac arrest: An experimental rodent model

Yu Okuma,Tomoaki Aoki,Lance B Becker,Santiago J Miyara,Junhwan Kim,Tai Yin,Mitsuaki Nishikimi,Koichiro Shinozaki,Ryosuke Takegawa,Kei Hayashida

doi:10.1038/s41598-020-79780-3

Abstract

The pituitary gland plays an important endocrinal role, however its damage after cardiac arrest (CA) has not been well elucidated. The aim of this study was to determine a pituitary gland damage induced by CA. Rats were subjected to 10-min asphyxia and cardiopulmonary resuscitation (CPR). Immunohistochemistry and ELISA assays were used to evaluate the pituitary damage and endocrine function. Samples were collected at pre-CA, and 30 and 120 min after cardio pulmonary resuscitation. Triphenyltetrazolium chloride (TTC) staining demonstrated the expansion of the pituitary damage over time. There was phenotypic validity between the pars distalis and nervosa. Both CT-proAVP (pars nervosa hormone) and GH/IGF-1 (pars distalis hormone) decreased over time, and a different expression pattern corresponding to the damaged areas was noted (CT-proAVP, 30.2 ± 6.2, 31.5 ± 5.9, and 16.3 ± 7.6 pg/mg protein, p < 0.01; GH/IGF-1, 2.63 ± 0.61, 0.62 ± 0.36, and 2.01 ± 0.41 ng/mg protein, p < 0.01 respectively). Similarly, the expression pattern between these hormones in the end-organ systems showed phenotypic validity. Plasma CT-proAVP (r = 0.771, p = 0.025) and IGF-1 (r = −0.775, p = 0.024) demonstrated a strong correlation with TTC staining area. Our data suggested that CA induces pathological and functional damage to the pituitary gland.

Highlights

The pituitary gland plays an important endocrinal role, its damage after cardiac arrest (CA) has not been well elucidated
Induced massive and gradual damage exhibited at Triphenyltetrazolium chloride (TTC) staining through 2 h of resuscitation
Dynamic quantitative levels of high mobility group box 1 (HMGB-1) in the pituitary revealed that HMGB-1 immediately increased after resuscitation (Fig. 1)

Summary

Introduction

The pituitary gland plays an important endocrinal role, its damage after cardiac arrest (CA) has not been well elucidated. The pituitary gland, consisting of the anterior (pars distalis) and posterior (pars nervosa) lobes, plays an important endocrinal role exerting significant influence over cardiovascular h omeostasis[4]. The anterior pituitary gland is responsible for the production of hormones, including adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone, growth hormone (GH), follicle-stimulating hormone, luteinizing hormone, and prolactin These hormones modulate downstream effects through the hypothalamic-pituitary-target organ axis. Compelling data from clinical and preclinical studies have revealed the association between post-CA adrenal insufficiency and increased risk of mortality and morbidity of CA patients[8,11] None of these studies focused on the broad spectrum of the pituitary gland system, including vasopressin and other anterior pituitary gland hormones. In order to evaluate the time-dependent transportation of these hormones and their effects on the end-organs, we measured hormonal levels at several time points and in several samples

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