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Velocity profiles at coronary artery stenoses
94 CONDENSED PHASE RADIOLUMINESCENCE: A NEW TECHNIQUE FOR MEASURING THE KINETICS OF DRUG BINDING TO INTACT CARDIAC MYOCYTES. Vinzenz von Tscharner and Ian A. Bailey, Biozentrum der Universitaet Basel, Klingelbergstrasse 70, 4056 Basel, (Switzerland), and ICI Pharmaceuticals Division, Alderley Park, Macclesfield SKlD 4TG. (U.K.) Condensed Phase Radioluminescence (CPR) is a new technique which uses the Bdecay of a tritiated molecule to excite a fluorophore in a protein in a membrane. We have demonstrated that CPR may be used to measure bound drugreceptor complexes in myocyte cultures providing that the specific activity of the drug is in excess of 50 i1C$0m1ol. The kinetics of association and dissociation of 3H-nitrendipine and H-dihydroalprenolol have been measured non-invasively on single batches of beating cells. Binding was monoexponential, dihydroalprenolol withl:= 3.5 min and nitrendipine withr= 5 min. The rates of dissociation were almost identical (15< c:< 30 min)! The cells continued to beat after a medium change at the end of the experiment. Cells preincubated with 0.1 uM nifedipine (non-radioactive) for 20 min shgwed, a 33% lower amplitude and 70% slower rate of binding rhen added to 2.1 uM H-nitrendipine but neither parameter changed w$en z.1 uM H-dihydroalprenolol was used. 1 UM nlfediplne virtually abollshed H-nltrendipine binding. The technique appears to measure specific binding to intact cells. CPR has the potentiality to measure conformational changes in and aggregation of drug-receptor complexes in living cells. 95
VELOCITY ment of
PROFILES Medicine,
AT CORONARY University
of
D. Kilpatrick, Australia.
ARTERY STENOSES. Tasmania, Hobart,
S.
Webber.
Depart-
The reduction of blood flow through an arterial stenosis is accompanied by a loss of energy, the mechanism of which depends on whether there is turbulence within the vessel. Classical theory suggests that turbulence is only possible above Reynolds numbers of about 2000, but in the coronary arteries Reynolds numbers are much lower (200 maxI. To determine if turbulence exists in coronary arteries an in vitro study of intra-arterial velocity was performed. The technique of fibre optic laser Doppler anemometry (FOLDA) was used to measure velocity profiles in isolated arteries perfused at constant pressure by whole blood. Flow was measured by timing the collected volume. Variable stenoses were induced using a matrix band occtuder and the degree of stenosis measured by velocity measurement at very slow, constant flows (0.003 ml/set). If velocity measured from the peak of the profile velocity assuming lamiwr flow and measuring flow rate, less than the calculated and the gap increased as both degree of stenosis increased. This was due to flattening The deviation from predicted velocity started at flows (area) stenosis and 0.02 ml/set with a 91% stenosis. consistent with the development of turbulence as flow
demonstrated.
Ai P'tOST~~c.C:i'CJJ3 ‘VLLLGGVL: , d. ~;aclcely
G. I~ovac, s
ClIlX~IlJ
L.Szelceres, .School of
V.Udvary Szeged
The
purpose
of
isolated guinea was contracted by the coalpound. lzharmacological tory coolponents
and
the
l'kwmaceut 2epartment
Prostacyclin
,
ical of
;:I?‘;1
was
compared to the measured velocity rates increased of the velocity of 0.2 ml/set with A sudden decrease in was increased could the flow
vA:JoL)n,A’roI1Y
:;,:I,IxCT=V>,
I.:itadler, Saeredi, Ltd. Ijudapest rJort~, Pharmacology University
J.
analoeue
research
calculated was and the profile. a 607” velocity not be
is
J
to reach
.Ivanics, iiedical
a hichor
the bovine coronary artery pig trachea was relaxed, while the in vivo dog coronary resistance was reduced It is suggested that 5-nitro-PGIl could serve as tool in studying the vasodilatinc versus anti-a,-crewregarding; the actions of Prostacyclin.
a
VELOCITY ment of
PROFILES Medicine,
AT CORONARY University
of
D. Kilpatrick, Australia.
ARTERY STENOSES. Tasmania, Hobart,
S.
Webber.
Depart-
The reduction of blood flow through an arterial stenosis is accompanied by a loss of energy, the mechanism of which depends on whether there is turbulence within the vessel. Classical theory suggests that turbulence is only possible above Reynolds numbers of about 2000, but in the coronary arteries Reynolds numbers are much lower (200 maxI. To determine if turbulence exists in coronary arteries an in vitro study of intra-arterial velocity was performed. The technique of fibre optic laser Doppler anemometry (FOLDA) was used to measure velocity profiles in isolated arteries perfused at constant pressure by whole blood. Flow was measured by timing the collected volume. Variable stenoses were induced using a matrix band occtuder and the degree of stenosis measured by velocity measurement at very slow, constant flows (0.003 ml/set). If velocity measured from the peak of the profile velocity assuming lamiwr flow and measuring flow rate, less than the calculated and the gap increased as both degree of stenosis increased. This was due to flattening The deviation from predicted velocity started at flows (area) stenosis and 0.02 ml/set with a 91% stenosis. consistent with the development of turbulence as flow
demonstrated.
Ai P'tOST~~c.C:i'CJJ3 ‘VLLLGGVL: , d. ~;aclcely
G. I~ovac, s
ClIlX~IlJ
L.Szelceres, .School of
V.Udvary Szeged
The
purpose
of
isolated guinea was contracted by the coalpound. lzharmacological tory coolponents
and
the
l'kwmaceut 2epartment
Prostacyclin
,
ical of
;:I?‘;1
was
compared to the measured velocity rates increased of the velocity of 0.2 ml/set with A sudden decrease in was increased could the flow
vA:JoL)n,A’roI1Y
:;,:I,IxCT=V>,
I.:itadler, Saeredi, Ltd. Ijudapest rJort~, Pharmacology University
J.
analoeue
research
calculated was and the profile. a 607” velocity not be
is
J
to reach
.Ivanics, iiedical
a hichor
the bovine coronary artery pig trachea was relaxed, while the in vivo dog coronary resistance was reduced It is suggested that 5-nitro-PGIl could serve as tool in studying the vasodilatinc versus anti-a,-crewregarding; the actions of Prostacyclin.
a