Abstract
Abstract 13670: Role of Transient Receptor Potential Ankyrin-1 in Isoflurane-Induced Myocardial Depression in Mice
Circulation (New York, N.Y.), Vol.140(Suppl_1 Suppl 1), pp.A13670-A13670
11/19/2019
DOI: 10.1161/circ.140.suppl_1.13670
Abstract
IntroductionPerioperative hypotension is a major risk factor for adverse cardiovascular (CV) outcomes after surgery. 7% of patients are susceptible to volatile anesthetics such as isoflurane (ISO) and present with low blood pressure and low EEG activity despite receiving a low anesthetic concentration - a constellation called “triple low.” ISO can activate calcium conducting transient receptor potential ankyrin-1 (TRPA1) channels distributed throughout the CV system and in sensory C-fibers to induce hypotension.HypothesisISO-induced hypotension may be a function of TRPA1 mediated cardiac depression.MethodsCardiac TRPA1 protein presence was confirmed by PCR, genome sequencing, Western blotting and immunohistochemistry. Myocardial function was assessed in female and male C57BL/6 wild type mice (WTs) and TRPA1-null mice using echocardiography (Vevo 770) and left ventricular pressure (LVP) dynamics (pressure-volume catheter, 1.2-Fr) under increasing levels of ISO (2-5 Vol. %) in a blinded manner. In a pharmacological test, male WTs were treated with either vehicle or a TRPA1 inhibitor (HC-030031, 200 mg/kg, ip) 30 min prior to ISO exposure and echocardiography. All values represent mean±SEM. StatisticsTwo-way repeated measures ANOVA with post-hoc tests vs. ISO (2 Vol.%).ResultsTRPA1 was immuno-localized in both coronary vessels and in intercalated discs (with Connexin 43). In WTs, ISO decreased level-dependent heart rate (HR), stroke volume (SV), and cardiac output (CO). Ejection fraction (EF) was suppressed slightly more at 5 Vol. % in male vs female WTs (p=0.02). ISO had similar effects in TRPA1-null mice; however, EF and CO were greater maintained compared to WTs. Administration of HC-030031 in male WTs, recapitulated TRPA1-null maintenance of SV and EF. LV hemodynamics confirmed ISO level-dependent reductions in HR, LVP, LV end-diastolic pressure in both WTs and TRPA1-null male mice.ConclusionsThese data indicate ISO-induced hypotension is likely a function of cardiac depression, and, in part, due to activation of cardiac TRPA1 - making TRPA1 a potential target for pharmacological intervention in the serious ‘triple low’ clinical condition. SupportNIH grantsGM127607; HL122676; and a University of Louisville SOM grant.
Details
- Title: Subtitle
- Abstract 13670: Role of Transient Receptor Potential Ankyrin-1 in Isoflurane-Induced Myocardial Depression in Mice
- Creators
- Detlef Obal - Stanford UniversityKartik Katragadda - University of LouisvilleGanapathy Jagatheesan - University of LouisvilleSujith Dassanayaka - University of LouisvilleKenneth Brittian - University of LouisvilleDaniel Riggs - University of LouisvilleDaniel Conklin - University of Louisville
- Resource Type
- Abstract
- Publication Details
- Circulation (New York, N.Y.), Vol.140(Suppl_1 Suppl 1), pp.A13670-A13670
- Publisher
- by the American College of Cardiology Foundation and the American Heart Association, Inc
- DOI
- 10.1161/circ.140.suppl_1.13670
- ISSN
- 0009-7322
- eISSN
- 1524-4539
- Language
- English
- Date published
- 11/19/2019
- Academic Unit
- Anesthesia
- Record Identifier
- 9984696679002771
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