Naltrindole Pretreatment Elicits Potent Dose Dependent Effects on Reducing Infarct Size During Ischemia Reperfusion In-Vivo

Autor: Annam Humayun, Sunit Singh, Arianna Gray, Devani Johnson, Tameka Dean, Qian Chen, Robert Barsotti, Lindon Young, Wangde Dai, Robert Kloner
Rok vydání: 2023
Předmět:
Zdroj: Physiology. 38
ISSN: 1548-9221
1548-9213
DOI: 10.1152/physiol.2023.38.s1.5733986
Popis: Over one million individuals experience a myocardial infarction (MI) every year. Currently, no therapeutic is available to salvage necrotic cardiac tissue following an MI. The use of a prophylactic agent to reduce infarct size in patients at high risk for an MI would attenuate the development of heart failure. Interventional cardiologists state that a 25% reduction in infarct size is clinically meaningful to reduce heart failure. Previously, a 5 min pretreatment with high dose (HD) naltrindole (NTI) (7.5 mg/kg x 5 min = 37.5 mg/kg, n=3) resulted in a robust 74% (15±6%) reduction in infarct size compared to control in an in-vivo model of ischemia reperfusion injury (IRI). This effect was accompanied by a reduction in irreversible hypercontracture known as rigor. However, it caused a transient reduction in cardiac function during the infusion period. In this study, we aim to determine the effect of intermediate (ID; 3.75 mg/kg x 5 min = 18.75 mg/kg) and low dose (LD; 0.2-1.0 mg/kg x 5 min = 1.0-5.0 mg/kg) NTI pretreatment on infarct size and cardiac function in a rat in vivo model of IRI.Female Sprague-Dawley rats (~250g) were divided into four cohorts: non-treated control (n=15), LD (n=18), ID (n=5), and HD (n=5) NTI groups. All cohorts were anesthetized with Ketamine-xylazine (90 mg/kg, 9 mg/kg). Control rats received normal saline (0.9% NaCl), while treatment groups received either HD, ID, or LD NTI infused through the jugular vein (0.4mL/min) over 5 mins before inducing regional ischemia by occluding the left descending coronary artery for 30 min followed by 3 hr reperfusion. Cardiac function was measured through a pressure transducer catheter placed into the left ventricle (LV) in NTI treated groups. Planimetered photographs of heart slices were used to determine infarct size. Data were analyzed via ANOVA, Bonferroni-Dunn, and post-hoc analysis. Probability values Funding was supported by Young Therapeutics LLC and internal grants from Philadelphia College Of Osteopathic Medicine This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Databáze: OpenAIRE
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