Atrial chronotropic reactivity to catecholamines in neonatal rats: Contribution of β-adrenoceptor subtypes

Oliveira, Evelyn S.; Pereira, Ana Helena Macedo; Cardoso, Alisson C.; Franchini, Kleber G.; Bassani, José Wilson Magalhães; Bassani, Rosana A.

doi:10.1016/j.ejphar.2015.07.031

Cited by 5 publications

(4 citation statements)

References 52 publications

(55 reference statements)

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“…Possible underlying mechanism include immature coupling between β1-AR and Gs in the early postnatal period. 34 In our relatively small study group, we could not detect the role of the studied genetic polymorphisms in predisposition to haemodynamic instability and need for inotropic treatment during the transitional period. The allele incidences of all studied SNPs were comparable to the general population.…”

Section: Discussionmentioning

confidence: 73%

Pharmacogenetics may explain part of the interindividual variability of dobutamine pharmacodynamics in neonates

Hallik

Soeorg

Kahre

et al. 2022

Preprint

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Aim: To determine whether the known single nucleotide polymorphisms in adrenoreceptor associated genes affect the hemodynamic response to dobutamine in critically ill neonates. Methods: Alleles in the known genetic single nucleotide polymorphisms in β1 and β2 adrenoceptor (AR) genes and Gs protein α-subunit gene (GNAS) possibly affecting inotropic effect were identified in patients of neonatal dobutamine pharmacokinetic-pharmacodynamic study. Linear mixed-effect models were used to describe the effect of genetic polymorphisms to heart rate (HR), left ventricular output (LVO) and right ventricular output (RVO) during dobutamine treatment. Results: 26 neonates (5 term, 21 preterm) were studied. Dobutamine plasma concentration and exposure time respective HR (adjusted to gestational age) is dependent on β1-AR Arg389Gly polymorphism so that in G/G (Gly) homozygotes and G/C heterozygotes dobutamine increases HR more than in C/C (Arg) homozygotes, with parameter estimate (95% CI) of 38.3 (15.8 – 60.7) bpm per AUC of 100 mg·h, p=0.0005. LVO (adjusted to antenatal glucocorticoid administration and illness severity) and RVO (adjusted to gestational age and illness severity) is dependent on GNAS c.393C>T polymorphism so that in T/T homozygotes and C/T heterozygotes but not in C/C homozygotes LVO and RVO increase with dobutamine treatment, 24.5 (6.2 – 42.9) mL kg-1 min-1 per AUC of 100 mg·h, p=0.0116 and 33.2 (12.1 – 54.3) mL kg-1 min-1 per AUC of 100 mg·h, p=0.0025, respectively. Conclusion: In critically ill neonates, β1-AR Arg389Gly and GNAS c.393C>T polymorphisms may play a role in the haemodynamic response to dobutamine during the first hours and days of life.

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Section: Discussionmentioning

confidence: 73%

Pharmacogenetics may explain part of the interindividual variability of dobutamine pharmacodynamics in neonates

Hallik

Soeorg

Kahre

et al. 2022

Preprint

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“…In the control group, α2-AR activation induced biphasic change in CF: an increase by 9% (p<0.01) by minute 1 followed by gradual decrease by 13% (p<0.05). Despite the fact that final development of the adrenergic innervation of the heart occurs not earlier than 2-3 weeks after birth, cardiomyocytes in rodents respond to adrenergic receptors agonists even in the embryonic period [11]. In addition, prenatal effect of catecholamines is essential for the development of normal heart function [3].…”

Section: Resultsmentioning

confidence: 99%

Effect of Clonidine Hydrochloride on Isolated Newborn Rat Heart

et al. 2021

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The concentration dependenies of the chronotropic response and changes in blood supply to the isolated heart of 7-day-old newborn rats induced by application of α2-adrenergic receptor agonist clonidine hydrochloride in concentrations of 10 -9 -10 -6 M were revealed. The minimum concentration of α2-adrenergic receptor agonist caused tachycardia, while higher concentrations led to bradycardia. The maximum effect manifesting in a decrease in coronary flow was recorded at the minimum concentration of the agonist, while the highest concentration had no effect on the coronary flow. When comparing these results with those obtained in control adult rats, we found that the most pronounced differences in the chronotropic effects were observed after addition of the minimum concentration of the α2-adrenergic receptor agonist: bradycardia in adult rats and tachycardia in newborns. The maximum differences in coronary flow parameters were observed after addition of α2-adrenergic receptor agonist in the maximum concentration that induced a two-phase response in adult rats and had no effect on the blood supply in newborns.

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“…Enhanced role of β2‐AR and β3‐AR, as compared to β1‐AR, in chronotropic effects of β‐adrenergic agonists has been suggested in both immature rat and large mammal heart. Possible underlying mechanisms include immature coupling between β1‐AR and Gs in the early postnatal period 35 . There are only sparse data from animal studies about ontogeny and nondevelopmental regulation of the AC enzyme system, that may also play an important role describing the discordant effect of those polymorphisms in neonates and adults 36–38 …”

Section: Discussionmentioning

confidence: 99%

“…Possible underlying mechanisms include immature coupling between β1-AR and Gs in the early postnatal period. 35 There are only sparse data from animal studies about ontogeny and nondevelopmental regulation of the AC enzyme system, that may also play an important role describing the discordant effect of those polymorphisms in neonates and adults. [36][37][38] In our relatively small study group, we could not detect the role of the studied genetic polymorphisms in predisposition to haemodynamic instability and need for inotropic treatment during the transitional period.…”

Section: Discussionmentioning

confidence: 99%

Pharmacogenetics may explain part of the interindividual variability of dobutamine pharmacodynamics in neonates

Hallik

Soeorg

Kahre

et al. 2022

Brit J Clinical Pharma

View full text Add to dashboard Cite

To determine whether the known single nucleotide polymorphisms in adrenoreceptor associated genes affect the haemodynamic response to dobutamine in critically ill neonates. Methods: Alleles in the known genetic single nucleotide polymorphisms in β1and β2-adrenoceptor (AR) genes and Gs protein α-subunit gene (GNAS) possibly affecting inotropic effect were identified in patients of neonatal dobutamine pharmacokineticpharmacodynamic study. Linear mixed-effect models were used to describe the effect of genetic polymorphisms to heart rate (HR), left ventricular output (LVO) and right ventricular output (RVO) during dobutamine treatment. Results: Twenty-six neonates (5 term, 21 preterm) were studied. Dobutamine plasma concentration and exposure time respective HR (adjusted to gestational age) is dependent on β1-AR Arg389Gly polymorphism so that in G/G (Gly) homozygotes and G/C heterozygotes dobutamine increases HR more than in C/C (Arg) homozygotes, with parameter estimate (95% CI) of 38.3 (15.8-60.7) beats/min per AUC of 100 μg L À1 h, P = .0008. LVO (adjusted to antenatal glucocorticoid administration

show abstract

Atrial chronotropic reactivity to catecholamines in neonatal rats: Contribution of β-adrenoceptor subtypes

Cited by 5 publications

References 52 publications

Pharmacogenetics may explain part of the interindividual variability of dobutamine pharmacodynamics in neonates

Pharmacogenetics may explain part of the interindividual variability of dobutamine pharmacodynamics in neonates

Effect of Clonidine Hydrochloride on Isolated Newborn Rat Heart

Pharmacogenetics may explain part of the interindividual variability of dobutamine pharmacodynamics in neonates

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