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167 plaque p h heterogeneity in physiological media

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167 plaque p h heterogeneity in physiological media

  1. 1. Plaque pH Heterogeneity in Physiological Media Tania Khan Morteza Naghavi, MD
  2. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 17. Sensor A tip Sensor B tip
  18. 18. m = media values
  19. 19. 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

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