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. 1972 Oct;51(10):2702–2709. doi: 10.1172/JCI107089

Studies of Isolated Fetal Mouse Hearts in Organ Culture

EVIDENCE FOR A DIRECT EFFECT OF TRIIODOTHYRONINE IN ENHANCING CARDIAC RESPONSIVENESS TO NOREPINEPHRINE

Kern Wildenthal 1,2, Jacquline R Wakeland 1,2
PMCID: PMC332970  PMID: 5056662

Abstract

Definitive confirmation or denial of the hypothesis that thyrotoxic hearts are supersensitive to catecholamines has been difficult to obtain, largely because secondary alterations in neural and humoral factors that occur after thyroid administration in vivo may obscure the primary changes induced by the hormone on the myocardium itself. To study the direct action of thyroid hormone apart from secondary factors, thyrotoxicosis should be induced in isolated hearts in vitro, but the slow onset of thyroid action plus the rapid deterioration of conventional in vitro preparations have precluded such experiments.

Recen'ly a method was developed for maintaining intact, spontaneously-beating hearts from late-fetal mice in organ culture for several weeks. When 5 × 10−7 to 5 × 10−6m l-triiodothyronine is added to the culture medium arrhythmias and or tachycardia gradually appear, just as in thyrotoxicosis in vivo. Accordingly, these “thyrotoxic” hearts were used in the present experiments to test for altered responsiveness to norepinephrine. Dose-response curves to norepinephrine were identical for hearts maintained for 3 hr in triiodothyro-nine-treated or control medium. After 2 days, however, the curve was shifted to the left in triiodothyronine-treated hearts. Thus, 10−8m norepinephrine increased the atrial rate by 20±6.1 (sem) beats/min in hearts exposed to 5 × 10−6m triiodothyronine and by 1±3.0 in control hearts (P < 0.02); 10−7m norepinephrine raised the rate by 79±22.3 in treated hearts vs. 17±9.8 in controls (P < 0.05). At maximal doses (10−6m norepinephrine), increases were identical. In addition, norepinephrine (10−8-10−6m) induced arrhythmias in 56% of treated hearts vs. 14% of controls (P < 0.01). Thus, in a precisely controlled environment free of differences in neural and humoral factors, triiodothyronine can act directly on the fetal mouse heart to enhance sensitivity to norepinephrine.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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