Low Thyroid Function Leads to Cardiac Atrophy With Chamber Dilatation, Impaired Myocardial Blood Flow, Loss of Arterioles, and Severe Systolic Dysfunction

Abstract

Background-Although thyroid dysfunction has been linked to heart failure, it is not clear whether hypothyroidism alone can cause heart failure. Methods and Results-Hypothyroidism was induced in adult rats by treatment with 0.025% propylthiouracil (PTU) for 6 weeks (PTU-S) and 1 year (PTU-L). Echocardiographic measurements, left ventricular (LV) hemodynamics, isolated myocyte length (KOH method), myocardial blood flow (fluorescent microspheres), arteriolar morphometry, and gene expression (Western blot) were determined. Heart weight, heart rate, LV systolic blood pressure, LV ejection fraction, LV fractional shortening, and systolic wall thickness were reduced in PTU-S and PTU-L rats. LV internal diameter in systole increased by 40% in PTU-S and 86% in PTU-L. LV internal dimension in diastole was increased in PTU-S and PTU-L rats, but only PTU-L rats showed a significant increase in myocyte length due to series sarcomere addition.Resting and maximum (adenosine) myocardial blood flow were reduced in both PTU-S and PTU-L rats. Impaired blood flow was due to a large reduction in arteriolar length density and small arterioles in PTU-S and PTU-L (PϽ0.05 or greater for all of the above comparisons). Expression of sarcoplasmic/endoplasmic reticulum Ca 2ϩ -ATPase (SERCA)-2a and ␣-myosin heavy chain were reduced in hypothyroidism, whereas phospholamban and ␤-myosin heavy chain were increased. Conclusions-Hypothyroidism led to severe, progressive systolic dysfunction and increased chamber diameter/wall thickness ratio despite a reduction in cardiac mass. Chamber dilatation in PTU-L rats was due to series sarcomere addition, typical of heart failure. Hypothyroidism resulted in impaired myocardial blood flow due to a dramatic loss of arterioles. Thus, we have identified 2 important new mechanisms by which low thyroid function may lead to heart failure. (Circulation. 2005;112:3122-3130.)

MECHANISMS IN ENDOCRINOLOGY: Heart failure and thyroid dysfunction

“…The relationship between thyroid hormone and the cardiovascular system has been extensively demonstrated in numerous experimental and clinical studies (14,15,16,17,18,19). This association has been recently confirmed by significant changes in cardiac structure and function in patients with persistent subclinical thyroid dysfunction (11,12,13,14,15,16).…”

“…The availability of T 3 , which is the active form of thyroid hormone in the heart, is controlled by the deiodinases, which regulate cardiac levels of T 3 (19,20). The heart is particularly vulnerable to the reduction in local T 3 levels because T 3 is essential to preserve both cardiac morphology and performance in adult life (16,17,18,19). In fact, thyroid hormone influences cardiac performance by genomic and non-genomic effects and increases cardiac output by affecting stroke volume and heart rate (14,15).…”

“…Moreover, normal thyroid hormone levels are required in adult life to maintain normal cardiovascular function (7,17,18,19). T 3 controls the inotropic and lusitropic properties of the myocardium, cardiac growth, myocardial contractility and vascular function (14,15).…”

“…Chronic hypothyroidism in adult rats leads to the loss of coronary arterioles and impaired blood flow; it induces maladaptive changes in the shape of myocytes and the development of HF (19). Important changes in cardiac structure and function have been reported in patients with overt and subclinical hypothyroidism (SHypo) with a severity depending on the degree and the duration of thyroid hormone deficiency (14,15,16,77,78,79).…”

Influência do exercício físico nas alterações cardiovasculares induzidas pelo hipotireoidismo

“…Para além do prejuízo na contratilidade miocárdica, o hipotireoidismo subclínico induz alterações no sistema cardiovascular em repouso, incluindo diminuição do fluxo sanguíneo e aumento da resistência periférica total. (18)(19) Tang et al (38) avaliaram a insuficiência cardíaca em ratos com hipotireoidismo subclínico induzido por meio da administração de 0,025% de propiltiouracil ao F=gênero feminino; M= gênero masculino; ↑ = aumento; ↓ = diminuição; ↔ = sem mudança; HSC= hipotireoidismo subclínico; HC= hipotireoidismo clínico; FCM= frequência cardíaca máxima; DMF= dilatação mediada pelo fluxo; CT= colesterol total; HDL= lipoproteínas de alta densidade; LDL= lipoproteínas de baixa densidade; TG= triglicerídeos; PCR= proteína C-reativa; TME= tempo máximo de exercício; Glic. Musc.= glicogênio muscular; Lept.= leptina; Cortic.= corticosterona; FVES= função ventricular esquerda sistólica; FVED= função ventricular esquerda diastólica; PASpico= pressão arterial sistólica no pico do exercício; PADpico= pressão arterial diastólica no pico do exercício; PASRec.1= pressão arterial sistólica após 1 minutos de recuperação; PASRec.3= pressão arterial sistólica após 3 minutos de recuperação; FERep.= fração de ejeção no repouso; FEExerc.= fração de ejeção no exercício; FS= fluxo sanguíneo; m/min= metros/minuto.…”