Elsevier

Vascular Pharmacology

Volume 52, Issues 3–4, March–April 2010, Pages 131-137
Vascular Pharmacology

Review
Thyroid hormone in cardiac surgery

https://doi.org/10.1016/j.vph.2009.11.004Get rights and content

Abstract

Thyroid hormone has a wide range of cardiovascular effects which are mediated at both genomic and non-genomic levels. As a stress response to surgery, the non-thyroidal illness syndrome or euthyroid sick syndrome occurs in the post-operative period following cardiac surgery. There remains debate about the potential benefits of the treatment of the non-thyroidal illness syndrome in this setting with acute thyroid hormone supplementation. This review article sets out to discuss the potential benefits of thyroid hormone supplementation and the results from trials relating to both adult and paediatric cardiac surgical population as well as in the setting of brain stem death to optimise the potential cardiac donor.

Introduction

Clinical and experimental studies performed in states of thyroid hormone (TH) deficiency, excess or exogenous administration have demonstrated that THs have a range of direct and indirect cardiovascular effects. Moreover, thyroid hormonal status may also affect the recovery of post-ischaemic myocardial function. Patients undergoing cardiac surgery experience two phenomena that could be directly influenced by thyroid hormone administration. Firstly, cardiac surgery is associated with reductions in the levels of the circulating biologically active TH, triiodothyronine (T3) and it has been postulated that correction of this low T3-state could be beneficial to cardiovascular performance. Secondly, as cardiac surgery is associated with episodes of global or regional ischaemia, exogenous TH administration may affect post-ischaemic myocardial recovery.

This review sets out to discuss; the effects of pre-operative thyroid status in patients undergoing cardiac surgery, the occurrence of the low T3 state associated with cardiac surgery and the use of T3 as both an inotropic and myocardial protective agent in the post-ischaemic period in adult and paediatric cardiac surgery as well as the use of TH supplementation in the brain stem dead (BSD) cardiac donor.

Section snippets

The cardiovascular effects of thyroid hormone

Thyroid hormone has a number of different effects on the heart and vascular system (Klein & Danzi, 2007, Klein & Ojamaa, 2001a, Klein & Ojamaa, 2001b, Klein & Ojamaa, 2001c, Ojamaa et al., 1993, Park et al., 1997). Hyperthyroidism results in a high cardiac output state secondary to increased heart rate and contractility with reduced systemic vascular resistance (SVR) and hypothyroidism has the opposite effects (Dillmann, 1993, Klein & Danzi, 2007, Klein & Danzi, 2008).

The effects of TH on the

Peripheral haemodynamic changes

Reduction in systemic vascular resistance is one of the earliest changes that occur to patients on administration of TH (Klein, 1990, Schmidt et al., 2002). This may in part be due to the release of local vasodilators that are liberated as a result of increasing metabolic activity and oxygen consumption. This reduction in systemic vascular resistance decreases afterload and leads to an increase in cardiac output. The subsequent increase in cardiac output leads to an increased oxygen delivery to

Hyperthyroidism and the heart

Hyperthyroidism is well known to have cardiovascular consequences. Hyperthyroid patients commonly have a resting tachycardia. They may present with a number of cardiac rhythm disturbances (most commonly supraventricular) such as atrial fibrillation and complications of this including thromboembolism and heart failure. Cardiac output can be between 50 and 300% higher than in normal subjects. This is due to increase in heart rate, left ventricular contraction, blood volume and a decrease in SVR (

Hypothyroidism and the heart

Hypothyroid patients may have many of the symptoms or signs associated with heart failure including dyspnoea, oedema, cardiomegaly and effusions. Low cardiac output in these patients is due to decreased heart rate, reduction in ventricular filling and decreased myocardial contractility. Hypothyroidism is a risk factor for coronary artery disease (Auer et al., 2003), however, these patients tend to have a lower incidence of angina and myocardial infarction, perhaps secondarily to the reduction

Non-thyroidal illness syndrome

In response to severe physiological stress such as starvation, illness or surgery (including cardiac surgery), changes in the circulating concentrations of T3, thyroxine (T4) and thyrotrophin (TSH) are noted. These changes reflect changes in both peripheral TH metabolism and changes in the hypothalamic–pituitary–thyroid axis (Fliers et al., 2001). In the situation of severe physical stress, circulating levels of triiodothyronine (T3) decrease within two hours and this is thought to reflect a

Thyroid hormone changes in cardiac surgery

In cardiac surgery, concentrations of free T3 decline slowly prior to institution of cardiopulmonary bypass (CPB) with a much more dramatic decline once CPB is established (Bremner et al., 1978). The NTIS has been demonstrated to occur within the context of both adult and paediatric cardiac surgery (Klemperer et al., 1995a, Murzi et al., 1995). The response of a decline in circulating T3 does not appear to be related specifically to the phenomenon of CPB. Recently published studies measuring TH

Acute T3 administration in animal models of myocardial ischaemia

A number of animal studies were performed in the late 1980s and early 1990s investigating the potentially beneficial effects of TH supplementation following myocardial ischaemia.

In a porcine model, animals underwent two or three hour periods of ischaemia whilst on CPB at moderate hypothermia (26 °C) with cardioplegia at half-hourly intervals. Half of these were administered systemic T3 (6 μg) at removal of the aortic cross clamp (AXC), all were rewarmed to 37 °C and CPB discontinued. In the group

Adult cardiac surgery

Novitzky performed two small randomised blinded trials assessing the administration of T3 in patients undergoing coronary artery bypass graft surgery (CABG) (Novitzky et al., 1989). In the first of these trials 24 patients with left ventricular ejection fraction (LVEF) < 30% were administered either placebo or T3 (n = 12) at AXC removal and at pre-defined intervals post-operatively. In the T3 group, inotrope and diuretic requirements were reduced. In the second study (n = 24) of this series T3 was

Paediatric cardiac surgery

The majority of studies involving the use of TH supplementation and the paediatric population are small and involve a heterogeneous group of pathologies, temperature strategies and age ranges.

In a randomised double-blind placebo controlled trial of 40 paediatric patients undergoing a variety of procedures, subjects were randomised to receive either T3 (2 μg kg− 1 on first post-operative day, followed by 1 μg kg− 1 on subsequent days) or placebo for up to 12 days following surgery. Serum circulating TH

Thyroid hormone and myocardial protection

In addition to the beneficial haemodynamic effects seen with T3 administration, recent animal and clinical data has suggested that T3 may have a positive influence on protecting the myocyte following ischaemia. Sustained activation of the p38 mitogen activated protein kinase (MAPK) following ischaemia is associated with increased cell death. Long-term administration of T4 (two weeks) followed by ischaemia and reperfusion in an isolated rodent heart model has been demonstrated to improve

Management of the brain stem dead cardiac donor

Following BSD, a number of hormonal and haemodynamic changes occur that are potentially deleterious to the cardiovascular function of the BSD cardiac donor. This includes a low T3 state (Powner et al., 1990). Within 24 h of BSD, T3 concentrations fall to approximately 50% of normal, stabilising to approximately 40% over the next two to seven days (Taniguchi et al., 1992). T4 levels remain in the normal range. Administration of T3 has been demonstrated to correct this deficiency (Taniguchi et

Conclusions

The use of thyroid hormone therapy in cardiac surgery still remains one of debate (Burman, 1996, Utiger, 1995). Replacement with T3 therapy is able to correct the NTIS that occurs in connection with the severe stress responses associated with cardiac surgery and can be administered without any adverse side effects. However, despite a number of studies noting potential improvements in haemodynamic performance and reduced inotrope requirements, investigators have been unable to demonstrate any

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