Protective effects of salvianolate on microvascular flow in a porcine model of myocardial ischaemia and reperfusion

Arch Cardiovasc Dis. 2011 May;104(5):313-24. doi: 10.1016/j.acvd.2011.02.004. Epub 2011 Jun 8.

Abstract

Background: Microvascular reflow is crucial for myocyte survival during ischaemia/reperfusion injury.

Aims: We aimed to assess if salvianolate, a highly purified aqueous extract from Radix salviae miltiorrhizae, could improve impaired microvascular reflow induced by ischaemia/reperfusion injury, using a porcine closed-chest model.

Methods: Left anterior descending coronary artery ligation was created by balloon occlusion for 2 h followed by reperfusion for 14 days. Salvianolate was administrated intravenously for 7 days at low dose (5 mg/kg/day), high dose (10 mg/kg/day) or high dose combined with one 20 mg intracoronary bolus injection just at the beginning of reperfusion. Control-group animals were only given the same volume of saline.

Results: After 14 days of reperfusion, animals treated with high-dose salvianolate showed improved myocardial perfusion assessed by real-time myocardial contrast echocardiography and coloured microspheres. The beneficial effect was further supported by increased capillary density and decreased infarct size. All these effects eventually resulted in well-preserved cardiac function detected by echocardiography. Moreover, we also demonstrated that salvianolate administration was associated with elevated superoxide dismutase activity, thioredoxin activity and glutathione concentration, and reduced malondialdehyde concentration, which, in turn, resulted in a significant decrease in terminal deoxynucleotide transferase-mediated dUTP nick end labelling-positive cells and an increased ratio of Bcl-2 to Bax expression.

Conclusion: Intravenous salvianolate at a dose of 10 mg/kg/day for 7 days had significant beneficial effects on myocardial microvascular reflow, which were associated with decreased oxidative stress and apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Apoptosis / drug effects
  • Cardiovascular Agents / administration & dosage
  • Cardiovascular Agents / pharmacology*
  • Contrast Media
  • Coronary Circulation / drug effects*
  • Disease Models, Animal
  • Glutathione / metabolism
  • Hemodynamics / drug effects
  • In Situ Nick-End Labeling
  • Injections, Intravenous
  • Malondialdehyde / metabolism
  • Microcirculation / drug effects*
  • Myocardial Infarction / diagnostic imaging
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / physiopathology
  • Myocardial Infarction / prevention & control*
  • Myocardial Perfusion Imaging
  • Myocardial Reperfusion Injury / diagnostic imaging
  • Myocardial Reperfusion Injury / metabolism
  • Myocardial Reperfusion Injury / physiopathology
  • Myocardial Reperfusion Injury / prevention & control*
  • Myocardium / metabolism
  • Myocardium / pathology
  • Oxidative Stress / drug effects
  • Plant Extracts / administration & dosage
  • Plant Extracts / pharmacology*
  • Plant Roots
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Salvia miltiorrhiza*
  • Superoxide Dismutase / metabolism
  • Swine
  • Thioredoxins / metabolism
  • Time Factors
  • Ultrasonography
  • Ventricular Function, Left / drug effects
  • bcl-2-Associated X Protein / metabolism

Substances

  • Cardiovascular Agents
  • Contrast Media
  • Plant Extracts
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • salvianolate
  • Malondialdehyde
  • Thioredoxins
  • Superoxide Dismutase
  • Glutathione