In vivo determination of left ventricular wall stress-shortening relationship in normal mice.
Although targeted alterations of the mouse genome are used increasingly to identify the mechanisms underlying cardiac function, the methods used to study the phenotypic expression of these alterations in vivo are limited. To derive a relatively noninvasive, load-independent measure of left ventricular (LV) contractility in mice, we cannulated the femoral artery and performed two-dimensional directed M-mode echo studies in 28 anesthetized FVB/N mice, using a 9-MHz transducer. Loading conditions were altered by intraarterial methoxamine (3-12 microg/g), and LV shortening fraction was determined at several steady states, both before and after myocardial contractility was altered by either 4 microg/g intraperitoneal dobutamine (n = 16) or 1-2 microg/g verapamil (n = 12). The relation between LV systolic meridional stress and fractional shortening derived from pooled baseline data was inverse and linear [r = 0.80, slope = -0.19, intercept = 48%, standard error of estimate (SEE) = 5.5%, P < 0.001]. Dobutamine produced a parallel upward shift of the relation (r = 0.87, slope = -0.21, intercept = 61%, SEE = 4.5%, P < 0.001), and verapamil produced a downward shift of the relation (r = 0.48, slope = -0.05, intercept = 24%, SEE = 3.7%, P < 0.05). At matched levels of end-systolic stress, dobutamine increased and verapamil decreased the LV shortening fraction. We conclude that 1) inverse stress-shortening relations can be assessed noninvasively in mice; and 2) these relations are sensitive to alterations in inotropic state, independent of loading conditions.
Hoit
B D
BD
Division of Cardiology, University of Cincinnati, Ohio 45267-0542, USA.
Khan
Z U
ZU
Pawloski-Dahm
C M
CM
Walsh
R A
RA
D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology; D004280:Dobutamine / Q000494:pharmacology; D004452:Echocardiography; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D009200:Myocardial Contraction / Q000187:drug effects; D012016:Reference Values; D013314:Stress, Mechanical; D013599:Systole; D016277:Ventricular Function, Left / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology
D002316:Cardiotonic Agents; D004280:Dobutamine; D014700:Verapamil; D008729:Methoxamine