SHAPE Society

1. Plaque pH Heterogeneity in
Physiological Media
Tania Khan
Morteza Naghavi, MD

2. Overview
• Eagle’s Medium - pH 7.2 - 7.5; essential amino acids, glucose (5.6
mM), sodium bicarb (26.2 mM) equilabrated with 75% O2 / 5% CO2
gas mixture (balance N2) warmed to ~37ºC and placed in incubator;
media pCO2 20-35 pO2 300-440 mmHg
• Sensor wire ~3 cm long sensing elements in the middle ~1-2 cm from
tip; sensor values validated with media values before placing in plaque
tissue; typically takes 30 min to equilibrate with tissue
• Distance between pH, pCO2, and pO2 sensors (in that order from tip)
may allow the pH reading to be in thinner tissue and pO2 in thicker
tissue
• Tissue pH and pCO2 stable for ~ 4 hours in the media
• Conclusion: perform readings in thicker (>0.7 mm) tissue areas first

3. 9/7 plaque
• Plaque thickness 0.35 - 0.8 mm; ~3
cm x 2 cm area
• plaque in media for one hour
before sensor put in
• 4.5 hrs in media; tissue values
– pH : 7.03 - 7.06
– pCO2 : 60 - 95 mmHg
– pO2 : 170 - 290 mmHg
– Correlations: pCO2 & T
strongest,R2
=0.74; pH-pCO2
R2
=0.38
• 2 hrs in humidified 37ºC air
– pH sl. increase as pCO2, pO2
temperature dropped
tip
Sensor wire
oxygenated liquid media

4. 9-07-01
30
31
32
33
34
35
36
37
10:30:00
10:45:00
11:00:00
11:15:00
11:30:00
11:45:00
12:00:00
12:15:00
12:30:00
12:45:00
13:00:00
13:15:00
13:30:00
13:45:00
14:00:00
14:15:00
14:30:00
14:45:00
15:00:00
15:15:00
15:30:00
15:45:00
16:00:00
16:15:00
Temp
6.80
6.90
7.00
7.10
7.20
7.30
7.40
7.50
7.60
7.70
7.80
pH
Temp pH
sensor in plaque out
of media

5. 9-07-01
0
10
20
30
40
50
60
70
80
90
100 10:30:00
10:45:00
11:00:00
11:15:00
11:30:00
11:45:00
12:00:00
12:15:00
12:30:00
12:45:00
13:00:00
13:15:00
13:30:00
13:45:00
14:00:00
14:15:00
14:30:00
14:45:00
15:00:00
15:15:00
15:30:00
15:45:00
16:00:00
16:15:00
pCO2(mmHg)
6.80
6.90
7.00
7.10
7.20
7.30
7.40
7.50
7.60
7.70
7.80
pH
pCO2 m pCO2 pH m pH
sensor in
plaque out of media
m = media values from blood-gas machine

6. 9-7-01
0
100
200
300
400
500
600
10:30:00
10:45:00
11:00:00
11:15:00
11:30:00
11:45:00
12:00:00
12:15:00
12:30:00
12:45:00
13:00:00
13:15:00
13:30:00
13:45:00
14:00:00
14:15:00
14:30:00
14:45:00
15:00:00
15:15:00
15:30:00
15:45:00
16:00:00
16:15:00
pO2(mmHg)
6.80
6.90
7.00
7.10
7.20
7.30
7.40
7.50
7.60
7.70
7.80
pH
p02 m p02 pH m pH
sensor in
plaque out of media
m = media values from blood-gas machine

7. 9/12 plaque
• Plaque thickness 0.7 - 1.6 mm;
ICA thickly stenosed; whitish;
branch lumen preserved
• ~4.5 hrs in media; tissue values
– pH : 6.89 - 7.06 (after 30 min
stabilization)
– pCO2 : 65 - 90 mmHg
– pO2 : 20 - 225 mmHg
• Correlations: pH-pCO2 strongest,
R2
=0.96; pH-temp R2
=0.69
Post-experiment picture

8. 9-12-01
32
33
34
35
36
37
38 10:00:00
10:15:00
10:30:00
10:45:00
11:00:00
11:15:00
11:30:00
11:45:00
12:00:00
12:15:00
12:30:00
12:45:00
13:00:00
13:15:00
13:30:00
13:45:00
14:00:00
14:15:00
14:30:00
14:45:00
15:00:00
15:15:00
15:30:00
Temp
6.80
6.90
7.00
7.10
7.20
7.30
7.40
7.50
7.60
7.70
7.80
pH
Temp pH
sensor in plaque
sensor out

9. 9-12-01
0
10
20
30
40
50
60
70
80
90
100
10:00:00
10:15:00
10:30:00
10:45:00
11:00:00
11:15:00
11:30:00
11:45:00
12:00:00
12:15:00
12:30:00
12:45:00
13:00:00
13:15:00
13:30:00
13:45:00
14:00:00
14:15:00
14:30:00
14:45:00
15:00:00
15:15:00
15:30:00
pCO2(mmHg)
6.80
6.90
7.00
7.10
7.20
7.30
7.40
7.50
7.60
7.70
7.80
pH
pCO2 m pCO2 pH m pH
sensor in

10. 9-12-01
0
50
100
150
200
250
300
350
400
450
500
10:00:00
10:15:00
10:30:00
10:45:00
11:00:00
11:15:00
11:30:00
11:45:00
12:00:00
12:15:00
12:30:00
12:45:00
13:00:00
13:15:00
13:30:00
13:45:00
14:00:00
14:15:00
14:30:00
14:45:00
15:00:00
15:15:00
15:30:00
pO2(mmHg)
6.80
6.90
7.00
7.10
7.20
7.30
7.40
7.50
7.60
7.70
7.80
pH
pO2 m pO2 pH m pH
sensor in
sensor out

11. 9/13 plaque
• Plaque thickness 1 - 2.2 mm; heavily
calcified
• ~3.5 hrs in media; tissue values
– pH : 6.93 - 7.08 (after 30 min
stabilization)
– pCO2 : 60 - 87 mmHg
– pO2 : 0 - 30 mmHg
• Correlations: pH-pCO2 strongest,
R2
=0.75; pCO2-pO2 R2
=0.66
• pO2 sensor element in thickest
calcified part of plaque
Post-experiment picture
Sensor tip

12. 9-13-01
32
33
34
35
36
37
38
39
8:50:00
9:05:00
9:20:00
9:35:00
9:50:00
10:05:00
10:20:00
10:35:00
10:50:00
11:05:00
11:20:00
11:35:00
11:50:00
12:05:00
12:20:00
12:35:00
12:50:00
13:05:00
13:20:00
13:35:00
13:50:00
14:05:00
Temp
6.80
6.90
7.00
7.10
7.20
7.30
7.40
7.50
7.60
7.70
7.80
pH
Temp pH
sensor in
moved sensor

13. 9-13-01
0
10
20
30
40
50
60
70
80
90
100 8:50:00
9:05:00
9:20:00
9:35:00
9:50:00
10:05:00
10:20:00
10:35:00
10:50:00
11:05:00
11:20:00
11:35:00
11:50:00
12:05:00
12:20:00
12:35:00
12:50:00
13:05:00
13:20:00
13:35:00
13:50:00
14:05:00
pCO2(mmHg)
6.80
6.90
7.00
7.10
7.20
7.30
7.40
7.50
7.60
7.70
7.80
pH
pCO2 m pCO2 pH m pH
sensor in
attempt to move
sensor into thinner part

14. 9-13-01
0
50
100
150
200
250
300
350
400
450
500
8:50:00
9:05:00
9:20:00
9:35:00
9:50:00
10:05:00
10:20:00
10:35:00
10:50:00
11:05:00
11:20:00
11:35:00
11:50:00
12:05:00
12:20:00
12:35:00
12:50:00
13:05:00
13:20:00
13:35:00
13:50:00
14:05:00
pO2(mmHg)
6.80
6.90
7.00
7.10
7.20
7.30
7.40
7.50
7.60
7.70
7.80
pH
p02 m pO2 pH m pH
sensor in
moved sensor

15. Purpose
• To demonstrate hypothesized pH heterogeneity in a plaque
is not equilibrating with oxygenated media
• To assess living state of plaque in physiologic conditions
over expected time course

16. Methods
• Sensor A:
– placed about half way into plaque thickness
– in semi-calcified/necrotic spot thickness along sensor ~1-2.6 mm
(pO2 near thinner end)
• Sensor B:
– placed closer to exterior portion of vessel wall ~0.75 mm in wall
– in/under thrombus 1.2-1.6 mm thickness (pO2 near thinner piece,
closest to media)
• After 1.5 hrs, tank w/ 75% O2, 5% CO2 was empty; switched
to 21% O2, 5% CO2 to keep same pH-pCO2buffering
capacity
• Monitored for additional 2.5 hrs at 21% Oxygen

17. Sensor A tip
Sensor B tip

18. m = media values

21. Results
Sensor A
R
2
= 0.9027
0
10
20
30
40
50
60
70
80
6.90 7.00 7.10 7.20 7.30 7.40
pH
pCO2
• Strong pH-pCO2 correlation suggest sensors are firmly placed in tissue
• Sensor A in thicker tissue exhibited lower pH than Sensor B over the 4
hr. time course
• Physiologic pH, CO2 readings and trend with different levels of
oxygenation suggest plaque is in living state closest to in vivo situation
Sensor B R
2
= 0.9464
0
10
20
30
40
50
60
7.20 7.30 7.40 7.50 7.60 7.70
pH
pCO2