title: Myocardial tissue perfusion determined by particulate and diffusible tracers during ischaemia: what is measured?
abstract: OBJECTIVE
  Myocardial perfusion can be determined by many techniques which can be broadly divided into those employing particulate tracers and those employing diffusible tracers. The most commonly used particulate tracer is radioactive microspheres. However, as with other particulate tracers, they only determine convective transport from pre-capillary arterioles. If convective transport is the limiting factor in solute exchange, then particulate tracers will give comparable measurements to diffusible tracer techniques. However, if solute transport becomes diffusion-limited or alternative pathways of convective transport become more important, which may occur during regional ischaemia, perfusion visualised with clearance techniques using diffusible tracers may be greater than that determined with particulate tracers. This study set out to investigate this possibility in the rabbit myocardium under normal and ischaemic conditions.
  
  
  METHODS
  A pentobarbitone-anaesthetised rabbit model of regional ischaemia was used. Ischaemia of the apical region was induced by ligation of the large left ventricular branch of the circumflex artery. Tissue perfusion was determined by radioactive microspheres (n = 5) and the clearance of hydrogen, which was detected voltammetrically by platinum microelectrodes (n = 5). Measurements were made prior to and following coronary ligation and the ischaemic region was demarcated using the particulate tracer monastral blue. The exchange of diffusible solutes was visualised using digital fluorescence microscopy on histological sections of tissue following systemic administration of the fluorophore Evans blue labelled albumin (n = 4).
  
  
  RESULTS
  Coronary ligation produced an ischaemic zone occupying 50 +/- 13% of the left ventricle. In ischaemic tissue, flow determined by microspheres fell to 3.9 +/- 4.1% of its pre-ligation value, but solute exchange fell only to 22 +/- 10% (adjusted for changes in the partition coefficient of H2 during ischaemia, P < 0.05). Perfusion measured by microspheres and hydrogen clearance was unchanged in the non-ischaemic area during coronary ligation. There was preferential uptake of Evans blue albumin towards the endocardial surface in the ischaemic region and areas of local uptake through the ventricular wall, which were possibly associated with vessels.
  
  
  CONCLUSIONS
  This work demonstrates that under normal physiological conditions nutrient supply is determined by pre-capillary delivery. However, during ischaemia diffusive transport plays an increasingly important role. The alternative pathways for solute exchange are likely to have an important influence on the rate and extent of myocardial necrosis during coronary occlusion.
authors.affiliation: Academic Cardiology Unit, Imperial College School of Medicine, St. Mary's Hospital, London, UK.
authors.forename: D S
authors.initials: DS
authors.lastname: Fluck
authors.forename: P J
authors.initials: PJ
authors.lastname: Etherington
authors.forename: D
authors.initials: D
authors.lastname: O'Hare
authors.forename: C P
authors.initials: CP
authors.lastname: Winlove
authors.forename: D J
authors.initials: DJ
authors.lastname: Sheridan
mesh_terms: D000818:Animals; D001692:Biological Transport; D006321:Heart / Q000503:physiopathology*; D006859:Hydrogen / Q000493:pharmacokinetics; D008297:Male; D008856:Microscopy, Fluorescence; D008863:Microspheres; D017202:Myocardial Ischemia / Q000378:metabolism / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism; D010477:Perfusion; D011817:Rabbits; D011868:Radioisotopes; D012039:Regional Blood Flow
chemical_list: D011868:Radioisotopes; D006859:Hydrogen