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Biomedical subjects

K Wildenthal

Publications and source records attributed to K Wildenthal.

At least 91 records · Page 5Linked to original sources
PubMed1973

Maturation of responsiveness to cardioactive drugs. Differential effects of acetylcholine, norepinephrine, theophylline, tyramine, glucagon, and dibutyryl cyclic AMP on atrial rate in hearts of fetal mice.

Freshly isolated hearts of fetal mice of gestational ages ranging between 12 and 22 days (term) were exposed to several concentrations of a variety of chronotropic agents. Acetylcholine (10(-4)-10(-2) M) caused marked bradycardia in all hearts, even after only 12-14 days' gestation (i.e., even before cardiac innervation had occurred), and the intensity of the response increased steadily with advancing age throughout gestation. Responsiveness to norepinephrine was present but minimal at 12-14 days, so that mean atrial rate rose by < 10% with a maximal concentration of the drug (10(-5) M); responsiveness became more marked by 15-16 days (just after the time atrial innervation is thought to begin) and still greater effects appeared just before term. Glucagon had no effect in hearts of < 17 days' gestational age, but caused tachycardia thereafter, indicating that cardiac responsiveness to glucagon differentiates later than does responsiveness to norepinephrine. Responses to theophyl-line in 12-14 day hearts exceeded those to norepinephrine, indicating that the drug can affect heart rate independently of its ability to cause release of endogenous catecholamines. In contrast, tyramine caused no response until 21-22 days, well after the time the beta-receptor has differentiated and after innervation is fairly well developed, suggesting that the drug's primary sympathomimetic effect is indirect rather than direct. Dibutyryl cyclic AMP did not cause tachycardia at any fetal age. It is concluded that maturation of responsiveness of the mouse heart to cardioactive drugs develops in specific patterns for different agents. The identification of differential patterns of maturation for various drugs may provide valuable means for characterizing the differentiation of specific receptors and for investigating possible mechanisms of action of the drugs.

Acetylcholine↗
PubMed1972

Studies of isolated fetal mouse hearts in organ culture. Evidence for a direct effect of triiodothyronine in enhancing cardiac responsiveness to norepinephrine.

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 x 10(-7) to 5 x 10(-6)m 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(-8)m norepinephrine increased the atrial rate by 20+/-6.1 (sem) beats/min in hearts exposed to 5 x 10(-6)m triiodothyronine and by 1+/-3.0 in control hearts (P < 0.02); 10(-7)m norepinephrine raised the rate by 79+/-22.3 in treated hearts vs. 17+/-9.8 in controls (P < 0.05). At maximal doses (10(-6)m norepinephrine), increases were identical. In addition, norepinephrine (10(-8)-10(-6)m) 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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