A Heartbreaking Renal Transplantation: Is Norepinephrine the Culprit to Blame?

INTRODUCTION: Takotsubo cardiomyopathy (TCM), also known as "broken heart syndrome," "apical ballooning syndrome," and "stress-induced cardiomyopathy," was first described in Japanese patients in 1990 by Sato et al. TCM is an increasingly recognized syndrome characterized by transient and reversible systolic dysfunction of the apical and middle segments of the left ventricle. This syndrome resembles acute myocardial infarction in the absence of evident coronary artery occlusion. Herein, we present a case of a 51-year-old male who underwent his second deceased-donor renal transplantation for end-stage-renal-disease due to a work-related accident. Perioperatively, initiation of continuous infusion of noradrenaline was decided to achieve adequate graft perfusion due to persistently low blood pressure. On the second postoperative day, the patient experienced tachycardia and atypical angina-like chest pain. Electrocardiogram (ECG) showed signs of myocardial infarction and elevated troponin levels were observed. Urgent coronary angiography was normal and transthoracic echocardiography (TEE) was indicative for Takotsubo cardiomyopathy. DISCUSSION: Although, the precise pathophysiology of Takotsubo cardiomyopathy is still unknown, it seems that it is associated with excessive sympathetic stimulation, microvascular dysfunction, coronary artery vasospasm, and abnormal myocardial tissue metabolism. The development of patient's symptoms after the initiation of norepinephrine along with their immediate resolution after the discontinuation of the drug might suggest a causal relationship. This is the first time that TCM after renal transplantation is thought to be linked with the administration of exogenous catecholamines.

Pharmacological inhibition of TRalpha1 receptor potentiates the thyroxine effect on body weight reduction in rats: potential therapeutic implications in controlling body weight.

It has been previously reported that thyroid hormone receptor alpha1 (TRalpha1) is involved in the regulation of food intake and heart rhythm. Herein, we show that pharmacological inhibition of TRalpha1 by dronedarone, an amiodarone like compound (shown to antagonize thyroid hormone binding to TRalpha1), prevented the thyroid hormone induced increase in food intake and heart rate acceleration in rats. This resulted in a marked reduction in body weight. It is likely that thyroid analogs may prove potential therapeutic agents for controlling body weight.

Hyperthyroid hearts display a phenotype of cardioprotection against ischemic stress: a possible involvement of heat shock protein 70.

Hyperthyroid hearts are shown to display a phenotype of cardioprotection against ischemic stress, but the underlying signaling mechanisms remain largely unknown. The present study investigated the possible relation of HSP70 to the thyroid hormone induced cardioprotection. HSP70 is a redox-regulated molecular chaperone, and enhances cell survival under stress. Thyroxin (25 microg/100 g body weight) was administered to Wistar male rats for four days (THYR-4d) and two weeks (THYR-14d), respectively, while untreated animals served as controls (CON-4d, CON-14d). Isolated hearts from control and thyroxin treated rats were subjected to 20 min zero-flow ischemia followed by 45 min of reperfusion (I/R). The amount of HSP70 in the myocardium for THYR-14d was 1.85 times the levels of CON-14d (p < 0.05). The levels of HSP70 expression were no different between THYR-4d and CON-4d, p > 0.05. This was only accompanied by an increase in MDA levels (used as an index of oxidative stress) in THYR-14d compared to untreated hearts. These changes corresponded to a differential response of the heart to I/R; post-ischemic recovery of function was significantly increased in THYR-14d compared to CON-14d, and was no different between the THYR-4d and CON-4d hearts. In conclusion, long-term thyroxin administration results in increased tolerance of the myocardium to I/R and enhances the expression of HSP70 which may, at least in part, account for this response.

Thyroid hormone receptors alpha1 and beta1 are downregulated in the post-infarcted rat heart: consequences on the response to ischaemia-reperfusion.

There is accumulating evidence that thyroid hormone metabolism is altered after myocardial infarction (AMI) but its physiological relevance remains largely unknown. The present study investigated the possible role of thyroid hormone signaling in the response of the post-infarcted heart to ischaemia-reperfusion. Wistar rats were subjected to left coronary artery ligation (AMI), or sham operation (SHAM). After 8 weeks, hearts from AMI and SHAM rats were perfused in Langendorff mode and subjected to 20 min of zero-flow global ischaemia (I) and 45 min of reperfusion (R); AMI(I/R), n = 7 and SHAM(I/R), n = 7. Basal left ventricular pressure (LVDP), +dp/dt, and -dp/dt were significantly reduced. Left ventricular weight of the viable myocardium was increased by 14% in the AMI as compared to SHAM hearts, P < 0.05. T(3) and T(4) plasma levels in nM were 1.83 (0.08) and 53.3 (2.9) for SHAM and 1.76 (0.06) and 59.4 (5.2) for AMI rats, respectively, P > 0.05. TRalpha1 and TRbeta1 expression levels were 1.3- and 1.8-fold less in AMI than in SHAM hearts, P < 0.05. Furthermore, SERCA and NHE1 expression levels were 2.1- and 1.8-fold less in AMI than in SHAM, P < 0.05. PKCepsilon was 1.35-fold more in AMI compared to SHAM, P < 0.05. Myocardial glycogen content (in micromol/g) was 7.8 (1.2) in AMI as compared to 4.4 (0.5) for SHAM hearts, P < 0.05. After I/R, left ventricular end-diastolic pressure at 45 min of R (LVEDP45 in mmHg) was 20.3 (3.2) for AMI(I/R) vs 50.6 (4.8) mmHg for SHAM(I/R), P < 0.05. LDH release per gram of tissue was 251 (103) for AMI(I/R) and 762 (74) for SHAM(I/R), P < 0.05. In conclusion, TRalpha1 and TRbeta1 are downregulated after myocardial infarction and this was associated with altered expression of thyroid hormone responsive genes and increased tolerance of the post-infarcted heart to ischaemia-reperfusion injury.

Blockade of angiotensin II type 1 receptor diminishes cardiac hypertrophy, but does not abolish thyroxin-induced preconditioning.

Growth and stress seem to share common intracellular pathways and activation of growth signaling can increase resistance to stress. Thyroid hormone induces cardiac hypertrophy and preconditions the myocardium against ischemia reperfusion injury. The present study investigated whether this response is mediated by renin-angiotensin system (RAS). RAS is shown to be activated in hyperthyroidism and is involved in the development of cardiac hypertrophy. Male Wistar rats were treated with L-thyroxin (25 microg/100 g, sc, od) for fourteen days, while normal rats served as controls. In addition, irbesartan (150 mg/kg po), a potent blocker of angiotensin II type 1 receptor (AT1), was given with L-thyroxin for fourteen days. Isolated hearts were perfused in Langendorff mode; after stabilization, they were subjected to 20 min zero-flow global ischemia and 45 min of reperfusion. Thyroxin induced cardiac hypertrophy, which was diminished with irbesartan administration. Post-ischemic recovery of function was increased in thyroxin-treated hearts as compared to controls while ischemic contracture was accelerated and intensified. Irbesartan did not abolish this response. In conclusion, blockade of angiotensin II type 1 receptor with irbesartan preserves thyroxin-induced cardioprotection while diminishing cardiac hypertrophy. It is likely that thyroxin-induced cardioprotection is due to a direct effect of thyroid hormone.