Coronary flow reserve in pregnant rats with increased left ventricular afterload

PLoS One. 2014 Jul 9;9(7):e102147. doi: 10.1371/journal.pone.0102147. eCollection 2014.

Abstract

Background: Coronary flow reserve (CFR) is used as a measure of coronary endothelial function. We investigated the effect of increased afterload on CFR of pregnant and non-pregnant rats.

Methods: Afterload increase in Wister rats (both pregnant and non-pregnant) was achieved by the infusion of angiotensin II (Ang II) for ∼10 days or by subjecting them to transverse aortic constriction (TAC) for ∼14 days. Control groups were infused with 0.9% NaCl or had sham surgery, respectively. In pregnant rats, the experiments were performed close to term gestation. Doppler velocity waveforms of the left main coronary artery were recorded using a high resolution ultrasound imaging system (Vevo 770, VisualSonics, Canada) at baseline while the animals were anesthetized with 1.5% inhaled isoflurane, and during maximal coronary dilatation obtained by the inhalation of 3.5% of isoflurane. CFR was calculated as the ratio between the peak coronary flow velocities (CFRpeak) and the velocity-time integrals (CFRVTI) recorded at hyperemia and at baseline.

Results: CFR could be calculated in 60 of 75 (80%) animals. There were no differences in CFR between intervention and control groups irrespective of whether afterload was increased by Ang II or TAC. In the TAC-study CFRpeak (1.54±0.07 vs 1.85±0.17; p = 0.03) was decreased in pregnant compared to non-pregnant shams. When sham animals from both studies were pooled together both CFRpeak (1.42±0.07 vs 1.86±0.16; p = 0.005) as well as CFRVTI (1.45±0.07 vs 1.78±0.12; p = 0.03) were significantly lower in pregnant rats compared to non-pregnant.

Conclusions: CFR can be measured non-invasively in rats using Doppler echocardiography and high concentrations of inhaled isoflurane as a coronary vasodilator. In pregnant rats, CFR is reduced close to term. CFR is not affected by increased left ventricular afterload caused by chronic Ang II infusion or TAC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / administration & dosage
  • Animals
  • Blood Flow Velocity / drug effects
  • Blood Flow Velocity / physiology*
  • Coronary Vessels / drug effects
  • Coronary Vessels / physiology*
  • Echocardiography, Doppler / methods*
  • Female
  • Pregnancy
  • Rats
  • Rats, Wistar
  • Vasoconstrictor Agents / administration & dosage
  • Ventricular Function, Left* / drug effects

Substances

  • Vasoconstrictor Agents
  • Angiotensin II

Grants and funding

This work was supported by research grants from the Northern Norway Regional Health Authority, grant numbers 1411, 1668 and 2038 (http://www.helse-nord.no/about-helse-nord/category5770.html). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.