Measurement of interstitial lactate during hypoxia-induced dilatation in isolated pressurised porcine coronary arteries.
Lactate is formed in the coronary arterial wall and in the myocardium as a consequence of ischaemia and infarction. We combined direct measurement of coronary artery diameter and interstitial arterial wall lactate concentration ex vivo in order to ascertain the possible role of lactate in hypoxia-induced vasodilatation. The wall of porcine coronary arteries, precontracted during an intraluminal pressure of 40 mmHg by addition of prostaglandin F2alpha, was cannulated using a microdialysis catheter, and exposed to hypoxia for 60 min, followed by 45 min of reoxygenation. The exchange fraction of [14C]lactate over the microdialysis membrane increased from 0.38 +/- 0.04 to 0.52 +/- 0.05 (P < 0.001) during the study period. Coronary artery diameter increased by 15.5 +/- 2.0 % (n = 20) during hypoxia (P < 0.001, compared to normoxic controls) and interstitial lactate concentration rose from 1.07 +/- 0.21 to 2.50 +/- 0.40 mmol x l(-1) during hypoxia (P < 0.01) and was unchanged in controls. The increase in coronary artery diameter correlated with the increase in interstitial lactate concentration in the period between 30 and 60 min of hypoxia (r = 0.62; P = 0.02). Dichloroacetate (10(-5) M), an agent that reduces lactate generation by activating pyruvate dehydrogenase, abolished hypoxia-induced lactate production, but caused a further increase in coronary arterial diameter (30.2 +/- 4.4 %, n = 9; P < 0.001 vs. hypoxia and no dichloroacetate). Under control conditions, the addition of L-lactate (10(-3)-10(-2) M) increased dose-dependently coronary arterial diameter by 22.0 +/- 4.2 % (n = 5) and interstitial lactate concentration from 0.52 +/- 0.04 to 5.70 +/- 0.66 mmol x l(-1) (P < 0.001). There was a correlation between the increase in coronary artery diameter and interstitial lactate concentration (r = 0.60; P = 0.02). The present observations represent the first direct measurements of metabolites by microdialysis in a blood vessel wall. The lactate concentration may affect, but is not essential for, hypoxia-induced vasodilatation in porcine coronary arteries.
Frøbert
Ole
O
Department of Cardiology B, Skejby Sygehus, University Hospital Aarhus, Denmark. frobert@dadlnet.dk
Mikkelsen
Erich O
EO
Bagger
Jens P
JP
Gravholt
Claus H
CH
D000818:Animals; D003331:Coronary Vessels / Q000503:physiopathology*; D003999:Dichloroacetic Acid / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D019344:Lactic Acid / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D011312:Pressure; D013552:Swine; D014664:Vasodilation
D019344:Lactic Acid; D003999:Dichloroacetic Acid; D005947:Glucose