Effects of Theo-Esberiven on the coronary circulation and myocardial metabolisms in dogs.

Sakai, Ken; Mizusawa, Hideo; Sakanashi, Matao; Sakamoto, Kiminori; S, Takeo; Takenaka, Fumio

doi:10.1254/fpj.74.37

Cited by 3 publications

(3 citation statements)

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“…Metoprolol, an antagonist of the β1 receptor, is also used to antagonize the tachycardia induced by catecholamines, by decreasing the heart rate, contractility and mean blood pressure [33]. Dobutamine on the other hand, is an inotropic positive drug that increases the frequency and the strength of the contractions by acting on the β1-adrenergic receptors while at the same time causing a vasodilatation of the peripheral blood vessels via the β2 receptors [34]. In this study, we chose to administer low doses of beta-blocker (0.2 mg/kg i.v.)…”

Section: Discussionmentioning

confidence: 99%

“…In this study, we chose to administer low doses of beta-blocker (0.2 mg/kg i.v.) and dobutamine (infused at a slower rate of 20 μg/kg/min), unlike other experimental protocols which used up to 0.5 mg/kg [35] and 40 μg/kg/min [34], respectively, in human studies. Although beyond the scope of the present work, it would be of interest to repeat these experiments at higher doses to extend the range of myocardial workload at which the perfusion and oxygen consumption can be measured with [ 11 C]acetate.…”

Section: Discussionmentioning

confidence: 99%

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[11C]Acetate rest–stress protocol to assess myocardial perfusion and oxygen consumption reserve in a model of congestive heart failure in rats

Croteau¹,

Gascon²,

Bentourkia³

et al. 2012

Nuclear Medicine and Biology

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This study describes an [ 11 C]acetate rest/stress method to obtain an indirect estimate of myocardial blood flow (MBF) and myocardial oxygen consumption (MVO 2 ) in rats. Doxorubicin cardiotoxicity was used to test the usefulness of this approach for the assessment of congestive heart failure. Methods-[11 C]acetate rest-stress have been used in clinical research to assess the capacity of the coronary arteries to respond to stress. In this article we used this approach to assess the cardiotoxicity of doxorubicin in a rat model. The method was first validated in a group of healthy rats and then used to follow the effect of doxorubicin chemotherapy on cardiac function. The effect of doxorubicin on myocardial perfusion and oxygen consumption reserve was measured at rest and under dobutamine stimulation.Results-Validation of the protocol showed a good correlation between the MBF and MVO 2 (r 2 = 0.68). The doxorubicin treated group showed a significant (p=0.04) decrease in cardiovascular perfusion reserve at 1.3 ± 0.2 compared to the control animals at 1.6 ± 0.2. Similar results were obtained for the myocardial oxygen consumption reserve (treated 1.8 ± 0.4 vs controls 2.3 ± 0.3; p=0.02).Conclusions-We describe an [ 11 C]acetate PET rest/stress protocol for the assessment of cardiotoxicity in rat and its application to the follow-up of doxorubicin chemotherapy. This is a CIHR Author ManuscriptCIHR Author Manuscript CIHR Author Manuscript rapid and reliable approach to the measurement of cardiac perfusion and oxygen consumption reserve that could be applied to the development of new strategies to reduce the cardiotoxicity of anthracycline.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

[11C]Acetate rest–stress protocol to assess myocardial perfusion and oxygen consumption reserve in a model of congestive heart failure in rats

Croteau¹,

Gascon²,

Bentourkia³

et al. 2012

Nuclear Medicine and Biology

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“…Theophylline and proxyphylline have been shown to inhibit tracheal PDE activity with a similar potency, whereas dyphylline was about 5 times less effective (Kukovetz et al 1983). In isolated dog heart, proxyphylline increased coronary blood flow, heart rate and myocardial contractile force (Sakai et al 1978).…”

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confidence: 84%

Synthesis, pharmacological activity and nitric oxide generation by nitrate derivatives of theophylline

Korzycka

Górska

2008

Journal of Pharmacy and Pharmacology

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Nitrates of theophylline derivatives - potential nitric oxide (NO) donors - were synthesized by esterification of 7-hydroxyalkyl theophylline derivatives with fuming nitric acid. The nitrates obtained were tested in-vitro in reactions with sulfydryl compounds at appropriately adjusted pH and temperature. Under the applied conditions, the synthesized compounds underwent decomposition to release NO, quantified using a polarographic method using a selective isolated (ISO-NO) sensor. The effects of dyphylline and proxyphylline and their new synthesized nitrates on arterial blood pressure (BP) were measured in spontaneously hypertensive (SH) rats. BP was measured in conscious SH rats using the tail-cuff method. Both short- and long-term administration of the xanthines tested significantly decreased systolic, diastolic and mean BP. The hypotensive effect of a single dose of nitrate dyphylline on mean BP was greater than that of the parent compound (P = 0.000012; P=0.000472 at 30 and 60 min post-dose, respectively), whereas proxyphylline and its nitrate derivative had similar activity. In rats treated with the tested compounds for 9 days twice daily, the decrease in BP persisted for at least 16 h after the last dose. Proxyphylline produced the most marked decrease in diastolic and mean BP. Among the xanthines examined, proxyphylline nitrate had the strongest hypotensive effect when administered in a single dose to animals pretreated with the same compound for 9 days. These results indicate that insertion of a nitrate group weakly modifies the hypotensive action of the studied xanthines in SH rats.

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M

Blaschek¹,

Hänsel²,

Keller³

et al. 1998

Hagers Handbuch Der Pharmazeutischen Praxis

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Effects of Theo-Esberiven on the coronary circulation and myocardial metabolisms in dogs.

Cited by 3 publications

References 0 publications

[11C]Acetate rest–stress protocol to assess myocardial perfusion and oxygen consumption reserve in a model of congestive heart failure in rats

[11C]Acetate rest–stress protocol to assess myocardial perfusion and oxygen consumption reserve in a model of congestive heart failure in rats

Synthesis, pharmacological activity and nitric oxide generation by nitrate derivatives of theophylline

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