title: Effects of injectable anesthetic combinations on left ventricular function and cardiac morphology in Sprague-Dawley rats.
abstract: Novel anesthetic agents or combinations may provide superior general anesthesia for echocardiography in rodents with the potential for reduced adverse effects. This study sought to characterize the effects of 3 injectable anesthetics on left ventricular (LV) systolic function and cardiac morphology in healthy male and female rats. Rats underwent echocardiographic assessment after general anesthesia via pentobarbital or combinations of ketamine and medetomidine (KME) and ketamine and midazolam (KMI) according to a crossover Latin-square design. Blood samples for serum estradiol measurements were obtained from all females after echocardiography with each anesthetic. Rats given KMI showed superior LV systolic function with the highest values for fractional shortening (FS), ejection fraction (EF) and stroke volume, whereas heart rate was greatest with pentobarbital, followed by KMI and then KME. KME produced the greatest effects on cardiac morphology, most notably during systole, including reduced septal and posterior wall thickness and increased LV chamber dimensions and volumes. In addition, KME had the greatest cardiac-depressing effects on LV systolic function, including reduced FS, EF, and heart rate values. Compared with male rats, female rats had superior LV function with greater EF and FS values, whereas male rats showed higher heart rate. Significant negative correlations were noted between serum estradiol levels and FS and EF values in female rats receiving KME. We conclude that the combination of KMI may be a superior anesthetic for use in male and female rats undergoing echocardiography.
authors.affiliation: Department of Biomedical Sciences, University of Guelph, Guelph, Ontario, Canada.
authors.forename: Carla F
authors.initials: CF
authors.lastname: Sabatini
authors.forename: M Lynne
authors.initials: ML
authors.lastname: O'Sullivan
authors.forename: James E
authors.initials: JE
authors.lastname: Valcour
authors.forename: William
authors.initials: W
authors.lastname: Sears
authors.forename: Ron J
authors.initials: RJ
authors.lastname: Johnson
mesh_terms: D000768:Anesthesia, General / Q000662:veterinary*; D000777:Anesthetics / Q000008:administration & dosage*; D000818:Animals; D004452:Echocardiography / Q000662:veterinary; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D007649:Ketamine / Q000008:administration & dosage; D008297:Male; D008874:Midazolam / Q000008:administration & dosage; D010424:Pentobarbital / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors; D013318:Stroke Volume / Q000187:drug effects; D013599:Systole / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects* / Q000502:physiology
chemical_list: D000777:Anesthetics; D007649:Ketamine; D010424:Pentobarbital; D008874:Midazolam
references.citation: Coron Artery Dis. 2007 Jun;18(4):283-91
references.pmid: 17496492
references.citation: Circ Res. 1991 Mar;68(3):827-35
references.pmid: 1683821
references.citation: Circ Res. 1976 Oct;39(4):512-7
references.pmid: 963835
references.citation: Lab Anim Sci. 1987 Dec;37(6):726-30
references.pmid: 3437748
references.citation: J Am Coll Cardiol. 1999 Jul;34(1):264-73
references.pmid: 10400020
references.citation: Am J Physiol Heart Circ Physiol. 2006 Dec;291(6):H2807-15
references.pmid: 16877563
references.citation: J Am Coll Cardiol. 1997 Dec;30(7):1872-7
references.pmid: 9385921
references.citation: Life Sci. 2001 Jun 1;69(2):213-22
references.pmid: 11441911
references.citation: J Am Soc Echocardiogr. 2003 Nov;16(11):1150-7
references.pmid: 14608286
references.citation: Biometrics. 1977 Mar;33(1):159-74
references.pmid: 843571
references.citation: J Am Coll Cardiol. 1998 Oct;32(4):1118-25
references.pmid: 9768741
references.citation: J Pharmacol Toxicol Methods. 1997 Nov;38(3):157-62
references.pmid: 9523769
references.citation: J Cardiovasc Pharmacol. 2003 Aug;42(2):182-90
references.pmid: 12883320
references.citation: J Am Soc Echocardiogr. 1989 Sep-Oct;2(5):358-67
references.pmid: 2698218
references.citation: Basic Res Cardiol. 2007 Jan;102(1):28-41
references.pmid: 17006633
references.citation: Lab Anim Sci. 1978 Apr;28(2):157-62
references.pmid: 642434
references.citation: J Am Assoc Lab Anim Sci. 2007 Mar;46(2):74-80
references.pmid: 17343357
references.citation: J Pharmacol Sci. 2005 Sep;99(1):95-104
references.pmid: 16177543
references.citation: J Am Soc Echocardiogr. 2006 Dec;19(12):1520-5
references.pmid: 17138038
references.citation: Am J Physiol Heart Circ Physiol. 2002 Jun;282(6):H2134-40
references.pmid: 12003821
references.citation: Echocardiography. 2005 Sep;22(8):665-70
references.pmid: 16174120
references.citation: J Clin Invest. 2003 Aug;112(3):302-7
references.pmid: 12897194
references.citation: Clin Exp Pharmacol Physiol. 2007 May-Jun;34(5-6):499-507
references.pmid: 17439422
references.citation: Vet Anaesth Analg. 2005 May;32(3):117-27
references.pmid: 15877658
references.citation: J Am Coll Cardiol. 2004 Feb 4;43(3):317-27
references.pmid: 15013109
references.citation: Cardiology. 1992;81(1):8-13
references.pmid: 1477859
references.citation: J Am Soc Echocardiogr. 2006 Oct;19(10):1272-9
references.pmid: 17000367
references.citation: Biometrics. 1989 Mar;45(1):255-68
references.pmid: 2720055
references.citation: Int J Cardiovasc Imaging. 2006 Jun-Aug;22(3-4):353-62
references.pmid: 16518668