title: Metabolic vasodilatation with glucose-insulin-potassium does not change the heterogeneous distribution of coronary blood flow in the dog.
abstract: OBJECTIVE
  The heterogeneous distribution of coronary blood flow could represent regional differences in demand, or mismatching of regional O2 supply to demand, caused by regionally exhausted vasodilatation (anatomical/mechanical factors) or by regional arteriovenous diffusional O2 shunting. Regional coronary blood flow and global myocardial oxygenation and metabolism were measured during metabolic vasodilatation with glucose-insulin-potassium (GIK).
  
  
  METHODS
  Variables were studied before and 30 and 60 min after start of a 30 min infusion of GIK (50% glucose, 4 ml.kg-1, 8 mM KCl, and 3 U insulin.kg-1). Regional blood flows were measured by radioactive microsphere technique and cardiac output by thermodilution. Experimental subjects were six anaesthetised mongrel dogs, weighing 20-27 kg.
  
  
  RESULTS
  GIK increased plasma osmolarity and lactate, decreased haemoglobin, and increased cardiac output by 67(29)% and systemic O2 supply by 32(13)%, at unchanged arterial and central venous pressures and heart rate. Coronary blood flow rose by 97(50)% and left ventricular O2 supply by 56(41)%. Although regional blood flows in small tissue samples of about 1 g in the left ventricle ranged from a factor 0.31 to 1.73 of mean flow, GIK did not change flow heterogeneity and regional flows significantly correlated in time. Left ventricular O2 uptake rose by 42(40)%, while venous PO2 increased and O2 extraction decreased. Global lactate uptake increased at unchanged extraction. Changes were reversed after GIK.
  
  
  CONCLUSIONS
  GIK transiently increases myocardial O2 uptake following a raised cardiac output, caused by a hyperosmolarity induced rise in cardiac contractility rather than by haemodilution. Although myocardial O2 supply is distributed heterogeneously, the fractional rise with GIK is almost equal among regions. At constant lactate extraction, increased venous PO2 and decreased O2 extraction do not indicate overperfusion in some regions at the cost of underperfusion in others, are probably caused by a small, direct vasodilating effect of hyperosmolarity, and argue against diffusional O2 shunting. As for global O2 supply to demand, the increase in regional O2 supply is probably well adapted to regionally increased demand during GIK, so that the heterogeneous distribution of O2 supply can be explained by regional differences in demand and not by regionally exhausted vasodilatation or O2 shunting.
authors.affiliation: Academic Hospital Free University, Amsterdam, The Netherlands.
authors.forename: A B
authors.initials: AB
authors.lastname: Groeneveld
authors.forename: A A
authors.initials: AA
authors.lastname: van Lambalgen
authors.forename: G C
authors.initials: GC
authors.lastname: van den Bos
authors.forename: J J
authors.initials: JJ
authors.lastname: Nauta
authors.forename: L G
authors.initials: LG
authors.lastname: Thijs
mesh_terms: D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D002314:Cardioplegic Solutions / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects*; D004285:Dogs; D005947:Glucose / Q000494:pharmacology; D006454:Hemoglobins / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D007773:Lactates / Q000097:blood; D009206:Myocardium / Q000378:metabolism; D009994:Osmolar Concentration; D010100:Oxygen / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000502:physiology*
chemical_list: D002314:Cardioplegic Solutions; D006454:Hemoglobins; D007328:Insulin; D007773:Lactates; C030396:glucose-insulin-potassium cardioplegic solution; D005947:Glucose; D011188:Potassium; D010100:Oxygen