'Low T3syndrome' in a pig model of cardiopulmonary resuscitation - the time-course of changes in thyroid hormones and plasma catecholamines

Abstract

Objective: To investigate the time-course of changes in thyroid hormone and plasma catecholamine levels after administration of epinephrine, norepinephrine or vasopressin in a pig model of cardiopulmonary resuscitation (CPR). Design: Prospective, randomised controlled study. Setting: Animal care facility, Department of Experimental Anaesthesia. Subjects: A total of 21 pigs. Interventions: The pigs were randomly allocated to receive either 45 μg/kg epinephrine (epi, n=7), 45 μg/kg norepinephrine (norepi, n=7), or 0.8 IU/kg vasopressin (vaso, n=7) after 4 minutes of ventricular fibrillation and 3 minutes of open chest CPR. Measurements and main results: Arterial blood samples were obtained before CPR (pre-arrest), during mechanical CPR, ie before drug administration (DA), 5 minutes after DA and 60 and 180 minutes after restoration of spontaneous circulation (ROSC) for radioimmunological detection of iodothyronine serum concentration (total triiodothyronine TT3 ng/dl, thyroxine TT4 μg/dl, reverse triiodothyronine rT3 ng/dl, free unbound thyroxine fT4 ng/dl [equilibrium dialysis]). At the same time-points plasma catecholamine levels were measured by high pressure liquid chromatography (HPLC). Short-term ROSC was accomplished with epinephrine, norepinephrine or vasopressin in all animals. Even during CPR, all animals exhibited a rapid decrease of TT3. Irrespective of the drug given for CPR, the animals demonstrated a significant and sustained disappearance of TT3 180 minutes after ROSC (pre-arrest: epi group 55±10.7, norepi group 67±14.6, vaso group 42±6.4; 180 minutes after ROSC: epi group 14±3.4*, norepi group 18±5.6*, vaso group 14±3.4* ng/dl, *p<0.05). This was accompanied by a significant increase of rT3 180 minutes after ROSC (pre-arrest: epi group 22.5±2.2, norepi group 24±5.0, vaso group 23±1.7; 180 minutes after ROSC: epi group 52±7.3*, norepi group 45±8.8*, vaso group 43±5.8* ng/dl, *p<0.05). Vasopressin-treated animals exhibited significantly lower plasma levels of epinephrine and norepinephrine after drug administration. However, these differences in plasma catecholamines during CPR influenced neither the time-course nor the extent of change in thyroid hormone indices during and after CPR. Conclusions: Our data demonstrate the rapid development of a low T3 and high rT3 syndrome in a pig model of CPR within 3 hours following cardiac arrest and successful ROSC. Thyroid hormone metabolism is rapidly involved in the endocrine response to maximal stress during and after cardiac arrest. Neither the drug treatment during CPR nor the different plasma catecholamines concentrations affected the time-course and extent of changes in thyroid hormone status in this animal model.