Effect of triiodothyronine administration on the kidney during haemorrhagic shock and resuscitation

Abstract

Objective: Apoptosis, measured via caspase activity, can be used to assess renal tissue damage in haemorrhagic shock. We investigated whether Triiodothyronine could attenuate apoptosis and protect against haemorrhagic shock-induced renal injury. Methods: Haemorrhagic shock was induced in swine until the mean arterial pressure (MAP) was 35–40 mmHg for 40 minutes. Animals were randomly assigned to a control group (n=5), Group-F (Fluid resuscitation, n=6), and Group-T3 (Fluid plus Triiodothyronine, n=6). The swine were resuscitated for 1 hour aiming to MAP restoration (±10% from baseline) and were followed up for another 360 minutes. Haemodynamic parameters, fluids, acid-base status, plasma urea nitrogen, creatinine levels and caspase activity in the kidney were measured. Results: Haemodynamic parameters did not differ significantly amongst the three groups. Group-T3 required less normal saline (Group-T3: 1083±204 mL versus F: 2500±547 mL, p=0.001) and hydroxyethyl starch (Group-T3: 558±102 mL versus F: 916±204 mL, p=0.004) during resuscitation. Additionally, Group-T3 swine experienced less acidosis following haemorrhage/resuscitation with a pH of 7.39 versus a pH of 7.26 in Group-F (p=0.004) at 360 minutes. Urea remained within normal limits in all groups, but creatinine levels were elevated at 6 hours in Group-F as compared to Group-T3 (p=0.019). Apoptosis, assessed by renal caspase-3 activity, was increased in Group-T3 (132±174 pmol minute−1 g−1) and reduced in Group-F (32±18 pmol minute−1 g−1) as compared to the control group, but without statistical significance (p=0.245 between Group-T3 and Group-F). Conclusion: Administration of Triiodothyronine in a swine model of haemorrhagic shock seems to interfere with renal cell apoptosis. The exact mechanism needs to be further investigated in future research.