Cardiovascular Toxicology

, Volume 11, Issue 2, pp 91–112

Merits of Non-Invasive Rat Models of Left Ventricular Heart Failure

  • Alex P. Carll
  • Monte S. Willis
  • Robert M. Lust
  • Daniel L. Costa
  • Aimen K. Farraj
Article

DOI: 10.1007/s12012-011-9103-5

Cite this article as:
Carll, A.P., Willis, M.S., Lust, R.M. et al. Cardiovasc Toxicol (2011) 11: 91. doi:10.1007/s12012-011-9103-5

Abstract

Heart failure (HF) is characterized as a limitation to cardiac output that prevents the heart from supplying tissues with adequate oxygen and predisposes individuals to pulmonary edema. Impaired cardiac function is secondary to either decreased contractility reducing ejection (systolic failure), diminished ventricular compliance preventing filling (diastolic failure), or both. To study HF etiology, many different techniques have been developed to elicit this condition in experimental animals, with varying degrees of success. Among rats, surgically induced HF models are the most prevalent, but they bear several shortcomings, including high mortality rates and limited recapitulation of the pathophysiology, etiology, and progression of human HF. Alternatively, a number of non-invasive HF induction methods avoid many of these pitfalls, and their merits in technical simplicity, reliability, survivability, and comparability to the pathophysiologic and pathogenic characteristics of HF are reviewed herein. In particular, this review focuses on the primary pathogenic mechanisms common to genetic strains (spontaneously hypertensive and spontaneously hypertensive heart failure), pharmacological models of toxic cardiomyopathy (doxorubicin and isoproterenol), and dietary salt models, all of which have been shown to induce left ventricular HF in the rat. Additional non-invasive techniques that may potentially enable the development of new HF models are also discussed.

Keywords

Heart failure Heart failure model Cardiomyopathy Echocardiography Rat Isoproterenol Doxorubicin Spontaneously hypertensive SHHF Salt diet 

Abbreviations

ACE

Angiotensin-converting enzyme

ANG II

Angiotensin II

βAR

Beta adrenergic receptor

CO

Cardiac output

DM

Diabetes mellitus

DOX

Doxorubicin

dP/dtmax

Peak rate of increase in LV pressure

dP/dtmin

Peak rate of decrease in LV pressure

DOCA

Deoxycorticosterone acetate

DS

Dahl salt sensitive

E/A

Ratio of early-to-late inflow velocities

EF

Ejection fraction

ESV

End-systolic volume

FS

Fractional shortening

HF

Heart failure

HR

Heart rate

i.v.

Intravenous

ISO

Isoproterenol

LAD

Left anterior descending coronary artery

LV

Left ventricular

LVP

LV pressure

LVEDP

LV end-diastolic pressure

LVESP

LV end-systolic pressure

LVOT

LV outflow tract

MAP

Mean arterial pressure

MHC

Myosin heavy chain

MI

Myocardial infarction

PO

Pressure overload

PTU

Propylthiouracil

s.c.

Subcutaneous

SD

Sprauge Dawley

SERCA

Sarcoplasmic reticulum Ca2+ ATPase pump

SERCA2a

SERCA type “2”, isoform ‘a’

SH

Spontaneously hypertensive

SHHF

Spontaneously hypertensive heart failure

SHR

Spontaneously hypertensive rat

SV

Stroke volume

T3

Triiodothyronine

T4

Thyroxine

TAC

Transverse aortic constriction

TNF-α

Tumor necrosis factor-α

UPS

Ubiquitin–proteasome system

VO

Volume overload

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Alex P. Carll
    • 1
  • Monte S. Willis
    • 2
  • Robert M. Lust
    • 3
  • Daniel L. Costa
    • 4
  • Aimen K. Farraj
    • 5
  1. 1.Department of Environmental Sciences and Engineering, Gillings School of Global Public HealthUniversity of North CarolinaChapel HillUSA
  2. 2.McAllister Heart Institute & Department of Pathology and Laboratory Medicine, School of MedicineUniversity of North CarolinaChapel HillUSA
  3. 3.Department of Physiology, Brody School of MedicineEast Carolina UniversityGreenvilleUSA
  4. 4.Office of Research and DevelopmentU. S. Environmental Protection AgencyResearch Triangle ParkUSA
  5. 5.Cardiopulmonary and Immunotoxicology Branch, Environmental Public Health Division, National Health and Environmental Effects Research Lab, Office of Research and DevelopmentU. S. Environmental Protection AgencyResearch Triangle ParkUSA