A new method for combined isometric and isobaric pharmacodynamic studies on porcine coronary arteries.
1. The principal aim of the present study was to explore the isometric and isobaric capacity of a new intravascular technique, impedance planimetry, in basic pharmacodynamic investigations on porcine isolated epicardial coronary arteries. 2. The balloon-based catheter technique provides simultaneous measurements of luminal cross-sectional area and pressure. Sources of errors that may influence the accuracy of measurements were evaluated in detail. 3. Under isometric conditions, the stretch ratio-tension diagram showed typical developments of resting and active tensions of the smooth muscle when exposed to alternating maximal K+ depolarization and mechanical stretching. The mean (+/- SEM) maximum active tension was 28.43 +/- 1.72 mN/mm, which was reached at a stretch ratio of 1.26 +/- 0.02, corresponding to a resting tension of 10.50 +/- 0.53 mN/mm (n = 7). The concentration-response relationship to K+ at optimal basal tension was characterized by a mean (+/- SEM) pD2 value of 1.67 +/- 0.01 (n = 7). 4. Under isobaric conditions in the pressure range 40-140 mmHg, the method allowed the investigation of active vascular responses to partial K+ depolarization. The maximal active response to 25 mmol/L K+ was found at the transmural pressure of 60 mmHg (n = 7). To obtain full K+ concentration-response curves, a basal tension corresponding to a transmural pressure of 120 mmHg was required. The mean (+/- SEM) pD2 value for the concentration-response relationship to K+ was 1.53 +/- 0.01 (n = 10). 5. The vascular sensitivities to cumulatively added K+ and various agonists, such as acetylcholine, 5-hydroxytryptamine and noradrenaline, obtained from the same vessel segment at the same initial conditions corresponding to 120 mmHg were significantly higher with the isometric than with the isobaric approach. 6. The results of the present study suggest that impedance planimetry could be a useful tool in pharmacological and physiological investigations of medium-sized arteries, both under isometric and isobaric conditions.
Tankó
L B
LB
Institute of Pharmacology, Aarhus University, Denmark. tanko@farm.aau.dk
Mikkelsen
E O
EO
Frøbert
O
O
Bagger
J P
JP
Gregersen
H
H
D000109:Acetylcholine / Q000494:pharmacology; D000368:Aged; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology*; D017097:Electric Impedance; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D007537:Isometric Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011312:Pressure; D012680:Sensitivity and Specificity; D012701:Serotonin / Q000494:pharmacology; D013552:Swine; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D016166:Free Radical Scavengers; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D012701:Serotonin; D000109:Acetylcholine; D011188:Potassium; D009638:Norepinephrine