1 / 47

ED Master 1 Analyse pharmacologique d ’un effet (un son) sur la pression artérielle

ED Master 1 Analyse pharmacologique d ’un effet (un son) sur la pression artérielle. Pr. Jean - Luc ELGHOZI INSERM U 652 Hôpital Necker. MAJ 02/05/06. PROBLEMATIQUE 1. Etablir qu ’un son fait varier la pression artérielle

sybil
Download Presentation

ED Master 1 Analyse pharmacologique d ’un effet (un son) sur la pression artérielle

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. ED Master 1Analyse pharmacologiqued ’un effet (un son) surla pression artérielle Pr. Jean - Luc ELGHOZI INSERM U 652 Hôpital Necker MAJ 02/05/06

  2. PROBLEMATIQUE 1. Etablir qu ’un son fait varier la pression artérielle 2. Pourquoi la pression artérielle varie-t-elle? Dissection pharmacologique 3. Un traitement prévient-il cette réponse? 4. Ces variations de pression artérielle ont-elles des répercussions médicales? EN PREAMBULE QUELQUES RAPPELS

  3. Les déterminants dela pression artérielle • Le débit de la pompe cardiaque (fréquence, volume éjecté) • La résistance du ‘ tuyau ’ (elle varie) • Le contenu = volume du sang dans le ‘ tuyau ’ (position, respiration)

  4. + parasympathique + sympathique - NA Le baroréflexe ‘normal’ PA  décharges 

  5. - parasympathique - sympathique + NA Le baroréflexe ‘normal’ PA  décharges 

  6. Mémento • nerfs vagues = frein du coeur, médiateur acétylcholine, antagoniste = atropine • nerfs sympathiques cardiaques = accélérateur, médiateur noradrénaline, antagonistes = bêtabloquants (aténolol...) • nerfs sympathiques vasculaires = vasoconstricteurs, médiateur noradrénaline, antagoniste = alphabloquants (prazosine)

  7. AUTONOMIC COMPONENTS OF THE CARDIOVASCULAR RESPONSES TO AN ACOUSTIC STARTLE STIMULUS IN RATS Véronique BAUDRIE, Joke H.M. TULEN, Jocelyne BLANC and Jean-Luc ELGHOZI

  8. Six rats, implanted with a BP telemetric system, were enrolled in a randomized crossover saline-controlled (saline vs autonomic blocker) study with a washout period of 7 days between each active session. A first acoustic stimulus (110 dB, 0.7 sec) was administered. An autonomic blocker i.e. atropine methylnitrate (15 mg/kg), atenolol (15 mg/kg) or prazosin (1 mg/kg), or physiological saline was administered i.p. 40 min prior to a second identical acoustic stimulus.

  9. Logiciel d'acquisition des données Plaque réceptrice Convertisseur Pressionambiante UA10 CHART Logiciel de conversion du signal

  10. Heavy metal

  11. SPECTRUM OF THE ACOUSTIC STIMULUS 125 115 105 95 dB 85 75 20000 65 2000 200 55 Hz 1.05 0.6 20 0.4 0.3 0.18 0.1 0.08 0.06 0.04 0.03 sec

  12. SALINE 180 40 160 SBP 30 140 mm Hg mm Hg 20 120 10 100 80 0 0 10 20 30 40 50 60 360 40 340 HR 30 320 bpm bpm 300 20 280 10 260 240 0 0 10 20 30 40 50 60 Time (sec) Average responses

  13. SYSTOLIC BLOOD PRESSURE 160 1 2 3 4 5 140 mm Hg 120 100 80 0 30 60 90 120 150 180 210 240 270 300 TIME (sec)

  14. Atropa Belladona Baies Fleur

  15. ATROPINE 15 mg/kg i.p. 180 40 SBP 160 30 mm Hg 140 mm Hg 20 120 10 100 0 80 control atropine 0 10 20 30 40 50 60 500 50 HR 480 40 460 30 bpm bpm 20 440 10 420 0 400 control atropine 0 10 20 30 40 50 60 Time (sec) Average responses

  16. ATENOLOL 15 mg/kg i.p. 180 30 SBP 160 20 140 mm Hg mm Hg 120 10 100 0 80 0 10 20 30 40 50 60 control atenolol 60 340 HR 40 310 20 bpm bpm 280 0 250 -20 -40 ** 220 control atenolol 0 10 20 30 40 50 60 Time (sec) Average responses

  17. PRAZOSIN 1mg/kg i.p. 160 40 SBP 140 30 20 120 mm Hg mm Hg 10 100 0 80 -10 60 -20 *** 0 10 20 30 40 50 60 control prazosin 440 100 HR 400 80 60 360 bpm bpm 320 40 280 20 240 0 control prazosin 0 10 20 30 40 50 60 Time (sec) Average responses

  18. These results indicate the BP rise resulting from an acute loud noise depends on a vascular sympathetic activation (prevented with prazosin) which is partly blunted by vasodilation (revealed with prazosin). The evoked HR changes combine a sympathetic activation (fully expressed following atropine) and a vagal activation (unmasked with atenolol). Further experiments are necessary to document the vasodilatory component unmasked with prazosin.

  19. Les réponses diffèrent selon les souches

  20. F344 WKY 50 50 40 40 30 30 SBP (mmHg) 20 20 10 10 0 0 -10 -10 50 50 25 25 HR (bpm) 0 0 -25 -25 -50 -50 -5 0 5 10 15 -5 0 5 10 15 Time (s)

  21. Acoustic startle stimulus in rat 45 40 35 mmHg 30 25 20 SHR F344 Wistar Lewis WF WKY Startle stimulus 40 160 20 bpm SBP (mmHg) 120 0 80 -20 0 10 20 30 40 50 60 -40 340 HR (bpm) -60 300 -80 260 SHR F344 Wistar Lewis WKY WF Baudrie et al., Clin Exp Pharmacol Physiol, 2001 0 10 20 30 40 50 60 Time (sec)

  22. EFFECTS OF AN AUDITORY STARTLE STIMULUS ON BLOOD PRESSURE AND HEART RATE IN NORMAL MAN S. Holand, A. Girard, C. Meyer-Bisch, J.L. Elghozi Centre de Pharmacologie Clinique, Hôpital Necker - Paris

  23. Arlette et l’équipement

  24. ECG EMG PC . ( ( ) ) ( ) I ( ( DATEX ) ) Eye blink 0 0 0 0 0 0 500 505 510 515 seconds MP100 WSW BIOPAC Systems Respiratory movement Soft ACQKNOWLEDGE Soft ALERT Soft BEATSCOPE Headphone FINAPRES Arterial Blood Pressure

  25. STARTLE STIMULUS : 110 dB - 0.150 s 150 125 dB 100 75 50 0 0.2 0.4 0.6 0.8 1 seconds

  26. Stimulation STARTLE STIMULUS AND BACKGROUND NOISE dB 150 Background noise 100 50 0 kHz 0.1 0.5 2.5 12.5

  27. 110 dB BP mmHg Respi. a.u. ECG Volt EOG a.u. Event a.u. 20 40 60 80 100 120 Sec

  28. 160 SBP 140 mmHg 120 100 0 10 20 30-0 10 20 30 110 HR 90 bpm 70 0 10 20 30-0 10 20 30 4.0 3.5 RESPI au 3.0 2.5 0 10 20 30-0 10 20 30 Time (sec)

  29. EARLY RESPONSE SBP DBP 20 20 15 15 mmHg mmHg 10 10 5 5 0 0 dB dB Sham Sham 95 110 120 95 110 120 HR 20 15 bpm 10 5 0 dB Sham 95 110 120

  30. RESPONDERS IN % DBP SBP % % 100 100 80 80 60 60 40 40 20 20 0 0 dB dB 95 110 120 95 110 120 HR % 100 80 60 40 20 0 dB 95 110 120

  31. POPULATION • 25 SUBJECTS : 18 WOMEN, 7 MEN • AGE : 45.6  2.2 years old • WEIGHT : 67.4  2.7 kg • HEIGHT : 166.5  2.0 cm • B.M.I. : 24.2  0.8 kg.m-2 • S.B.P. RANGE : 89.4 to 175.3mmHg • D.B.P. RANGE : 55.9 to 94.0mmHg • H.R. RANGE : 58.5 to 85.2bpm

  32. † † † * * MAXIMAL CHANGES IN THE EARLY PHASE * mmHg 20 mmHg 20 * * * DBP SBP 10 10 0 0 Placebo Stim 1 Stim 2 Stim 1 Stim 2 Placebo bpm 15 10 HR 5 0 Placebo Stim 1 Stim 2 * P<0.01, vs Placebo, protected t-test for multiple comparaisons † P<0.01, Stim 1 vs Stim 2, protected t-test for multiple comparaisons

  33. RESTING BLOOD PRESSURE MEASURED WITH FINAPRES 25 SUBJECTS IN SUPINE POSITION mmHg 200 180 160 140 120 100 80 60 40 20 0

  34. SBP DBP mmHg 50 50 0 0 60 80 100 120 100 150 200 r=0.22 r=0.045 -50 -50 HR bpm 20 0 50 60 70 80 90 100 r=0.02 -20 REGRESSION BETWEEN CHANGES IN SBP, DBP or HR AND CORRESPONDING RESTING LEVELS mmHg

  35. mmHg 20 SBP 15 10 5 0 DBP -5 -10 -15 -20 bpm 15 10 5 HR 0 -5 -10 -15 0 10 20 30 seconds La question: l ’accélération cardiaque élève-t-elle la pression? PA = DC X RP

  36. c ur

  37. DC = FC * VESFC et VES peuvent se ‘ contrarier ’ Exemple de la stimulation sonore

  38. Pompe Tuyau PA = DC X RP

  39. Wesseling et al. Computation of aortic flow from pressure in humans using a nonlinear, three-element model. J Appl Physiol 1993;74:2566-73. Finger Blood Pressure Aortic Flow

  40. Variations hémodynamiques résultant d’une stimulation sonore PAM FC % Placebo Stimulation 1 Stimulation 2 VES DC * 20 * * * * RP * 10 0 * -10 * -20 DC = FC * VES PA = DC * RP

  41. Antihypertensive monotherapy and cardiovascular responses to an acoustic startle stimulus Girard et al. J. Cardiovasc. Pharmacol. 2001; 37:101-107 • 10 sujets hypertendus sans traitement • 10 sujets traités par le losartan (50 mg/jour) • 10 sujets traités par l’aténolol (100 mg/jour) • 5 sujets traités par la prazosine (10 mg/jour)

  42. 110 dB, 150 ms 180 120 160 SBP (mmHg) 110 140 100 120 CONTROL HR (bpm) 90 100 80 80 60 70 0 10 20 30 10 20 30 180 100 90 SBP (mmHg) 160 80 140 70 120 HR (bpm) 60 BETABLOCKER 100 50 80 40 60 30 0 10 20 30 10 20 30 Time (sec)

  43. 110 dB, 150 ms 180 120 160 SBP (mmHg) 110 140 100 120 CONTROL HR (bpm) 90 100 80 80 60 70 0 10 20 30 10 20 30 120 180 SBP (mmHg) 160 110 140 100 ALPHABLOCKER 120 90 HR (bpm) 100 80 80 70 60 0 10 20 30 10 20 30 Time (sec)

  44. PAS mmHg PAD mmHg FC battements/min 40 20 ** 0 40 Non traités Losartan 20 Atenolol ** Prazosine 0 15 10 5 0

  45. % 40 ** Non traités 30 Losartan Atenolol 20 Prazosine 10 * 0 -10 -20 VES DC RP

  46. Travaux de l’équipe sur le ‘son’ • Baudrie V., Tulen J.H.M., Blanc J., Elghozi J.L.: Autonomic components of the cardiovascular responses to an acoustic startle stimulus in rats. J. Auton. Pharmacol. 17: 303-309, 1997. • Blanc J., Baudrie V., Tulen J., Ponchon P., Gaudet E., Elghozi J.L.: Social isolation affects the pattern of cardiovascular responses to repetitive acoustic startle stimuli. Clin. Exp. Pharmacol. Physiol. 24: 40-45, 1997. • Holand S., Girard A., Meyer-Bisch C., Elghozi J.L.: Réponses cardio-vasculaires à une alerte sonore chez l’homme Arch. Mal. Cœur 1999; 92 :1127-1131. • Holand S., Girard A., Laude D., Meyer-Bisch C., Elghozi J.L.: Effects of an auditory startle stimulus on blood pressure and heart rate in man J. Hypertension 1999, 17:1893-1897. • Baudrie V., Laude D., Chaouloff F ., Elghozi J.L. : Genetic influences on cardiovascular responses to an acoustic startle stimulus in rats Clin Exp Pharmacol Physiol 2001, 28 :1096-1099. • Girard A., Holand S., Laude D., Elghozi J.L.: Antihypertensive monotherapy and cardiovascular responses to an acoustic startle stimulus J Cardiovasc Pharmacol 2001;37: 101-107. • Blanc J., Lacolley P., Laurent S., Elghozi J.L.: Comparison of angiotensin II-, and acoustic startle stimulus-induced blood pressure changes in Fischer 344 and Wistar Kyoto rats. Clin Exp Pharmacol Physiol 2004, 31 :466-473.

  47. The end

More Related