The Impact of Sevoflurane on Coupling of the Left Ventricular-to-Systemic Vasculature in Rats With Chronic Pulmonary Hypertension

J Cardiothorac Vasc Anesth. 2017 Dec;31(6):2027-2034. doi: 10.1053/j.jvca.2017.02.049. Epub 2017 Feb 13.

Abstract

Objectives: The relationship between left ventricular function and afterload has not been investigated as much as the right ventricular function under chronic pulmonary hypertension (PH) during anesthesia. This study was designed to investigate effects of sevoflurane on the intrinsic coupling relationship between the left ventricle and systemic vasculature in the presence of PH.

Design: A randomized, controlled study.

Setting: University hospital.

Participants: Sprague-Dawley rats.

Interventions: Monocrotaline (MCT) was injected intraperitoneally to induce a PH model.

Measurements and main results: Four weeks later, rats with MCT injection demonstrated significantly increased pulmonary arterial pressure and right/left ventricular systolic ratio of ventricular pressure (p < 0.001). Rats were treated with 1.5% sevoflurane inhalation. The PV catheters were inserted and left ventricular pressure-volume loops were measured at baseline, 30, 60, and 90 minutes during sevoflurane treatment. Preload recruitable stroke work and end-systolic elastance were decreased markedly in rats with MCT injection (p < 0.05). However, arterial elastance decreased similarly in both groups. Sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) level was decreased and the expression of phospholamban (PLB) was increased in the PH group and after sevoflurane treatment. PH rats suffered further SERCA2/PLB ratio decrease from their already low baseline. The left ventricular contractility and ventricular-vascular coupling were decreased in rats with PH after sevoflurane inhalation.

Conclusions: Sevoflurane reduced SERCA2a expression and increased PLB expression in PH rats. This partially could explain why the LV contractility and ventricular-to-vasculature coupling of PH rats were attenuated after sevoflurane treatment.

Keywords: SERCA2a; cardiac contractility; hypertension; left ventricle; pulmonary.

MeSH terms

  • Anesthetics, Inhalation / administration & dosage*
  • Animals
  • Chronic Disease
  • Heart Ventricles / drug effects
  • Hypertension, Pulmonary / drug therapy*
  • Hypertension, Pulmonary / physiopathology
  • Male
  • Methyl Ethers / administration & dosage*
  • Myocardial Contraction / drug effects*
  • Myocardial Contraction / physiology
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Sevoflurane
  • Ventricular Function, Left / drug effects*
  • Ventricular Function, Left / physiology

Substances

  • Anesthetics, Inhalation
  • Methyl Ethers
  • Sevoflurane