Selepressin and Arginine Vasopressin Do Not Display Cardiovascular Risk in Atherosclerotic Rabbit

Autor: Marie Henriksson, Torsten M. Reinheimer, Regent Laporte, Gerard Haroutunian, Robert Blakytny, Olivier Boucheix, Stéphane Milano
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Male
Vasopressin
Peptide Hormones
Receptor agonist activity
lcsh:Medicine
Blood Pressure
030204 cardiovascular system & hematology
Pathology and Laboratory Medicine
Vascular Medicine
Biochemistry
0302 clinical medicine
Medicine and Health Sciences
lcsh:Science
Aorta
Mammals
Multidisciplinary
Pharmaceutics
Dosage Regimen Design Methods
Animal Models
Hematology
Stroke volume
Blood Circulation
Vertebrates
Rabbits
Anatomy
Research Article
medicine.drug
Risk
medicine.medical_specialty
Log Dose-Response Method
Research and Analysis Methods
Norepinephrine (medication)
03 medical and health sciences
Selepressin
Model Organisms
Signs and Symptoms
Diagnostic Medicine
Sepsis
Internal medicine
Heart rate
medicine
Animals
Arterial Pressure
Septic shock
business.industry
lcsh:R
Organisms
Hemodynamics
Biology and Life Sciences
030208 emergency & critical care medicine
Atherosclerosis
medicine.disease
Hormones
Arginine Vasopressin
Endocrinology
Blood pressure
Amniotes
Cardiovascular Anatomy
Blood Vessels
lcsh:Q
business
Biomarkers
Zdroj: PLoS ONE, Vol 11, Iss 10, p e0165422 (2016)
PLoS ONE
ISSN: 1932-6203
Popis: Background Septic shock remains associated with significant mortality rates. Arginine vasopressin (AVP) and analogs with V1A receptor agonist activity are increasingly used to treat fluid-resistant vasodilatory hypotension, including catecholamine-refractory septic shock. Clinical studies have been restricted to healthy volunteers and catecholamine-refractory septic shock patients excluding subjects with cardiac co-morbidities because of presumed safety issues. The novel selective V1A receptor agonist selepressin, with short half-life, has been designed to avoid V2 receptor-related complications and long-term V1A receptor activation. Cardiovascular safety of selepressin, AVP, and the septic shock standard of care norepinephrine was investigated in a rabbit model of early-stage atherosclerosis. Methods Atherosclerosis was established in New Zealand White rabbits using a 1% cholesterol-containing diet. Selepressin, AVP, or norepinephrine was administered as cumulative intravenous infusion rates to atherosclerotic and non-atherosclerotic animals. Results Selepressin and AVP induced a slight dose-dependent increase in arterial pressure (AP) associated with a moderate decrease in heart rate, no change in stroke volume, and a moderate decrease in aortic blood flow (ABF). In contrast, norepinephrine induced a marked dose-dependent increase in AP associated with a lesser decrease in the heart rate, an increase in stroke volume, and a moderate increase in ABF. For all three vasopressors, there was no difference in responses between atherosclerotic and non-atherosclerotic animals. Conclusion Further studies should be considered using more advanced atherosclerosis models, including with septic shock, before considering septic shock clinical trials of patients with comorbidities. Here, selepressin and AVP treatments did not display relevant cardiovascular risk in early-stage rabbit atherosclerosis.
Databáze: OpenAIRE