Cardiovascular effects of intravenous colforsin in normal and acute respiratory acidosis canine models: A dose-response study
- PMID: 31291253
- PMCID: PMC6619603
- DOI: 10.1371/journal.pone.0213414
Cardiovascular effects of intravenous colforsin in normal and acute respiratory acidosis canine models: A dose-response study
Abstract
In acidosis, catecholamines are attenuated, and higher doses are often required to improve cardiovascular function. Colforsin activates adenylate cyclase in cardiomyocytes without beta-adrenoceptor. Here, six beagles were administered colforsin or dobutamine four times during eucapnia (partial pressure of arterial carbon dioxide 35-40 mm Hg; normal) and hypercapnia (ibid 90-110 mm Hg; acidosis) conditions. The latter was induced by CO2 inhalation. Anesthesia was induced with propofol and maintained with isoflurane. Cardiovascular function was measured by thermodilution and a Swan-Ganz catheter at baseline and 60 min after 0.3 μg/kg/min (low), 0.6 μg/kg/min (middle), and 1.2 μg/kg/min (high) colforsin administration. The median pH was 7.38 [range 7.33-7.42] and 7.01 [range 6.96-7.08] at baseline in the Normal and Acidosis conditions, respectively. Endogenous adrenaline and noradrenaline levels at baseline were significantly (P < 0.05) higher in the Acidosis than in the Normal condition. Colforsin induced cardiovascular effects similar to those caused by dobutamine. Colforsin increased cardiac output in the Normal condition (baseline: 3.9 ± 0.2 L/kg/m2 [mean ± standard error], low: 5.2 ± 0.4 L/kg/min2, middle: 7.0 ± 0.4 L/kg/m2, high: 9.4 ± 0.2 L/kg/m2; P < 0.001) and Acidosis condition (baseline: 6.1 ± 0.3 L/kg/m2, low: 6.2 ± 0.2 L/kg/m2, middle: 7.2 ± 0.2 L/kg/m2, high: 8.3 ± 0.2 L/kg/m2; P < 0.001). Colforsin significantly increased heart rate and decreased systemic vascular resistance compared to values at baseline. Both drugs increased pulmonary artery pressure, but colforsin (high: 13.3 ± 0.6 mmHg in Normal and 20.1 ± 0.2 mmHg in Acidosis) may have lower clinical impact on the pulmonary artery than dobutamine (high: 19.7 ± 0.6 in Normal and 26.7 ± 0.5 in Acidosis). Interaction between both drugs and experimental conditions was observed in terms of cardiovascular function, which were similarly attenuated with colforsin and dobutamine under acute respiratory acidosis.
Conflict of interest statement
The authors have declared that no competing interests exist.
Figures
![Fig 1](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/6619603/bin/pone.0213414.g001.gif)
![Fig 2](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/6619603/bin/pone.0213414.g002.gif)
Similar articles
-
Cardiovascular effects of intravenous pimobendan in dogs with acute respiratory acidosis.J Vet Emerg Crit Care (San Antonio). 2022 May;32(3):341-349. doi: 10.1111/vec.13178. Epub 2022 Jan 25. J Vet Emerg Crit Care (San Antonio). 2022. PMID: 35080109
-
Cardiovascular responses to graded doses of three catecholamines during lactic and hydrochloric acidosis in dogs.Br J Anaesth. 1995 May;74(5):583-90. doi: 10.1093/bja/74.5.583. Br J Anaesth. 1995. PMID: 7772436
-
Hemodynamic effects of amrinone in dogs anesthetized with halothane: comparison with isoproterenol and dobutamine.Res Commun Chem Pathol Pharmacol. 1984 Jun;44(3):347-54. Res Commun Chem Pathol Pharmacol. 1984. PMID: 6463363
-
Acute respiratory acidosis decreases left ventricular contractility but increases cardiac output in dogs.Circ Res. 1990 Sep;67(3):628-35. doi: 10.1161/01.res.67.3.628. Circ Res. 1990. PMID: 2118837
-
Dobutamine increases heart rate more than epinephrine in patients recovering from aortocoronary bypass surgery.J Cardiothorac Vasc Anesth. 1992 Oct;6(5):535-41. doi: 10.1016/1053-0770(92)90095-o. J Cardiothorac Vasc Anesth. 1992. PMID: 1421064
Cited by
-
Adenylyl cyclase isoforms 5 and 6 in the cardiovascular system: complex regulation and divergent roles.Front Pharmacol. 2024 Apr 3;15:1370506. doi: 10.3389/fphar.2024.1370506. eCollection 2024. Front Pharmacol. 2024. PMID: 38633617 Free PMC article. Review.
-
Use of a gum elastic bougie in a cat with severe upper airway stenosis.Open Vet J. 2023 Jan;13(1):114-118. doi: 10.5455/OVJ.2023.v13.i1.12. Epub 2023 Jan 23. Open Vet J. 2023. PMID: 36777444 Free PMC article.
-
Evaluation of Renal Blood Flow in Dogs during Short-Term Human-Dose Epoprostenol Administration Using Pulsed Doppler and Contrast-Enhanced Ultrasonography.Animals (Basel). 2022 May 4;12(9):1175. doi: 10.3390/ani12091175. Animals (Basel). 2022. PMID: 35565601 Free PMC article.
References
-
- Lindner E, Metzger H. The action of forskolin on muscle cells is modified by hormones, calcium ions and calcium antagonists. Arzneimittelforschung. 1983;33(10):1436–41. - PubMed
-
- Metzger H, Lindner E. The positive inotropic-acting forskolin, a potent adenylate cyclase activator. Arzneimittelforschung. 1981;31(8):1248–50. - PubMed
-
- Hosono M. Cardiovascular effects of colforsin daropate hydrochloride, a novel drug for the treatment of acute heart failure. Nihon Yakurigaku Zasshi. 1999;114(2):83–8. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Miscellaneous