**1. Introduction**

264 Perioperative Considerations in Cardiac Surgery

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> Thyroid hormones (THs) are key regulators of metabolism. The thyroid gland produces both thyroxine (T4) and triiodothyronine (T3). T4 is the main product and is converted in the periphery via deiodination to T3 which is the main biologically active TH. The production of THs is regulated by thyrotrophin (TSH) in response to TSH releasing hormone (TRH). This, in turn, is regulated by a negative feedback mechanism related to serum levels of free T3 and T4 (fT3 and fT4). Binding of T3 to TH receptors (TR) followed by binding of T3-TR complex to thyroid response elements within TH responsive genes leads to changes in gene transcription. These effects of TH are present through a wide number of tissues and organ systems including the cardiovascular system.

#### **2. Thyroid hormone and its actions on the cardiovascular system**

The effects of TH on both the heart and peripheral vascular system have been well documented1-9. In states of TH excess (hyperthyroidism) a high cardiac output state secondary to increased heart rate and contractility with a reduction in systemic vascular resistance (SVR) is seen. In hypothyroidism, the reciprocal effects are observed. The reduction that is seen in SVR is an early response to TH administration10, 11. This may be partly due to the release of local vasodilators liberated as a result of increasing metabolic activity and oxygen consumption. The effects of TH on vascular tone may also be attributable to its direct effects on arteriolar smooth muscle. Intracoronary administration of TH in Langendorff preparations has been demonstrated to lead to coronary vasodilatation within 15 seconds12 and in normal human subjects reductions in SVR are seen within minutes of administration11, with this effect lasting for several hours when administered intra-operatively13.

TH is able to manifest its effects on the cardiovascular system at both a genomic and nongenomic level; this means that with administration of TH there are immediate nongenomic cardiovascular consequences6, 11, 14, followed by later genomic alterations which include alterations in the expression of the beta one adrenergic receptor (ADRB1). However, despite increasing receptor expression, there is a paucity of evidence that T3 administration increases sensitivity to catecholamines15, 16. TH also acts upon the expression of calcium handling proteins within the myocyte including the sarcoplasmic reticulum calcium ATPase (SERCA) and its negative regulator phospholamban (PLB). Administration of T3 increases the level of SERCA mRNA and protein and also lowers phospholamban levels and increases its phosphorylation state, which enhances the activity of SERCA17-22. The combined effect of these changes is an increase in the force of contraction and speed of diastolic relaxation.
