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Dr masoudnia

Cardiovascular pharmacology. Dr masoudnia. degree of myocardial depression: difficult to establish alterations in: systemic hemodynamics pulmonary hemodynamics ANS

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Dr masoudnia

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  1. Cardiovascular • pharmacology Dr masoudnia

  2. degree of myocardial depression: difficult to establish • alterations in: • systemic hemodynamics • pulmonary hemodynamics • ANS complicate LVSfunction • The difference myocardial depression by VA :independent of ANS Activity

  3. Isovolumic and ejection phase measurement indices of ventricular contractility

  4. Ha=en > iso=des=sevo

  5. ↓myocardial contractility actility . negative inotropic actions exacerbated : ca↓, calcium (Ca2+) C.B., ß1-Chanel blocker reversed : Ca2+, cardiac PDE ifraction III , ß1-agonists, Ca2+ c. agonists, myofilament Ca2+ sensitizers. Myocardial Contractility

  6. Unique cardiovascular stimulation: • rapid increase in inspired DES. transient ↑ in myocardial contractility (augmentation of sympathetic nervous system tone.)

  7. contractility by ISO>HAL at identical MAC.(20%) • The differential on myocardial contractility : • maintained during ↑ or ↓inotropic state by vasoactivedrugs.

  8. DES=ISO • in systemic &coronary hemodynamic effects • Iso= des= sevo ↓contractile in normal ventricular myocardium.

  9. The effects of VA on myocardial contractility in animal models or patients with LVdysfunction have been less extensively studied

  10. Halothane:myocardial depression in ischemic heart > normal V.A: contractile dysfunction(HOCM) : sensitive to the negative inotropic effects ( in vivo=?) 2. not more negative inotropicin myocardium of DM.

  11. VA–induced declines in contractile function were well tolerated and did not precipitate frank systolic dysfunction in myocardial ischemia or infarction. important beneficial effects on mechanical function during myocardialischemia and reperfusioninjury.

  12. ↓ experimental myocardial infarctsize 2. preservedmetabolic &structural integrity in regional ischemia & reperfusion. functional recovery of stunned myocardium 4. ↑indicesLVDF in coronary artery occlusion. Effect on ischemia

  13. ISO : decreasepreload and afterload in IHD • offset the direct negative inotropic effects • maintenanceof COby optimizing the Starling operating range of the heart or by improving LV diastolic function.

  14. Cellular Mechanisms of Myocardial Depression

  15. ↓in intracellular Ca2+ homeostasisin cardiac myocyte. dose-related inhibition of the transsarcolemmal Ca2+ transient by L-andT-type Ca2+ channels. ↓avaibilityCa2+ for contractile activation, ↓release of Ca2+ from the sarcoplasmicreticulum ↓ca2+ stored in the SR

  16. 2. inhibiting Na+-Ca2+ exchange ↓ intracellular Ca2+ independent of the voltage-dependent Ca2+ channel in vitro. ( important in neonatal ) • 3.↓myofilament Ca2+ sensitivity.(minore role) • 4. ↓tension in skinned cardiac myofibrils. • 5.↓myofibrillar ATPaseactivity(ISO,SEVO,DES)

  17. ISO< HA.: ↓ in the intracellular Ca2+ transientR. • In contrast to ISO • HAL: stimulate release of Ca2+ from the SR directly activate ryanodine-sensitive SR Ca2+ release channels, thereby reducing SR Ca2+ storage. Different between hal & iso

  18. 2. Halothane: nonspecific leakage of Ca2+ from the SR, →↓ca accumulation.

  19. 1,2 important mechanisms : ↓the intracellular Ca2+ transient &myocardial contractility hal>iso, des, or sevo. (in identical mac)

  20. ISO & SEVO: inhibit Ca2+ transport from the cell through sarcolemmalCa2+ (ATPase), offsets in SR ↓ca2+ stores. • ↓ peak intracellular Ca2+ • exaggerated ↓in myofilament Ca2+ sensitivity in hypertrophied heart.

  21. abnormalities in Ca2+ homeostasis characteristic failing myocardium and VA will decrease↓ in contractile function by additive or synergistic effects on Ca2+ metabolism under these conditions.

  22. The timing, rate, and extent of LV filling include: • rate and degree of myocardial relaxation, • the intrinsic mechanical properties LV • external constraints • structure and function LA • pulmonary venous circulation • mitral valve Diastolic Function

  23. HF: may result from primary diastolic dysF in the absence of or before alterations in LVSF, including IHD, pressure- or volume-overload hypertrophy, HOCM & restrictive disease processes.

  24. 1.↑LV isovolumic relaxation in vivo. decrease in early LV filling but not affect LV chamber stiffness. 2.CBF is highest during isovolumicrelaxation delays in relaxation:↓coronary flow in early diastole. Effect of VA on diastolic dys

  25. Prolongation of LV relaxation as a result of depression of myocardial contractility, not due to direct negativelusitropic effect.

  26. Lusitropy is myocardialrelaxation. The increase in cytosoliccalcium of cardiomyocytes via increased uptake leads to increased myocardial contractility (positive inotropic effect), but the myocardial relaxation, or lusitropy, decreases. with catecholamine-induced calcium uptake into the sarcoplasmic reticulum, which increases lusitropy.

  27. 3.↓ rate & extent of early LV filling + 4. negative inotropic effects 5. ↓ LV filling associated with atrial systole.

  28. not exacerbate the preexisting diastolicdysfunction • Due to: ↓LV preload • not due to direct positive lusitropic effects. VA.

  29. iso-induced improvement LV isovolumicrelaxation & maintenance of CO in the presence of LVdys despite ↓contractility. • patients with severe IHD or CHF tolerate ISO or HAL without acute hemodynamic decompensation

  30. In failing myocardium: ↑dependence of LV relaxation on afterload ↓afterload : LV systolic performance ,↓impedance to LV ejection,& rate of LV relaxation ↑in LV diastolic filling &compliance. LV isovolumic relaxation in failing myocardium dependent of negative inotropiceffect.

  31. Left Ventricular–Arterial Coupling and Mechanical Efficiency

  32. The elastances of the contracting lv (Ees) • the elastances arterial vasculature (Ea) • The ratio of Ees to Ea : • coupling between the LV & the arterial circulation • useful technique for assessment of the actions of drugs(V.A) on LV-arterial matching .IN VIVO

  33. LV-arterial coupling maintained in anesthesia because: • declines in LV afterload may balance reductions in myocardial contractility.

  34. iso at 2 MAC ↓Ees/Ea Because vasodilating unable to compensate for the greater declinesin contractility.

  35. Des sev, and iso: maintained optimum LV-arterial coupling and mechanical efficiency as evaluated by Ees/Ea at low anesthetic concentrations (<0.9 MAC) by declines in myocardial contractility and LVafterload

  36. Halothane (<1.0 MAC) but not isoflurane also reduced the ratio of oscillatory to mean hydraulic power , which indicates that ↓ LV mechanical efficiency as well.

  37. LV afterload= the mechanical properties of the arterial vasculature opposing LVejection SVR=the ratio of MAP to CO, used of LV afterload. Left ventricle afterload

  38. SVR inadequately describes LV afterload ignores the mechanical characteristics of the blood and arterial walls, fails to account for the frequency-dependent, phasicnature of arterial blood pressure and blood flow not consider the potential effects of arterial wave reflection.

  39. SVR cannot be used reliably to quantify changes in LV afterload produced by drugs, V.A. or cardiovascular disease

  40. electrical three-element Windkessel model of the arterial circulation that describes characteristic aortic impedance (Zc), total arterial compliance (C), and total arterial resistance (R).

  41. Zcaortic resistance to LV ejection, C compliance of the aorta R combined resistance of the remaining arterial vasculature. iso :decreases in R consistent with effects on SVR

  42. ISO ,HAL: ↑in C and Zc↓MAP. the major difference between ISO,HAL on LV afterload : R,( arteriolar resistance vessels), not to C or Zc, mechanical characteristics of the aorta. sevo,des: ↓R in (more potent peripheralvasodilator.) the inverse relationship between C and MAP remains unchanged by VA, unlike arterial vasodilator sNP or propofol. VA do not fundamentally affect aortic mechanical characteristics.

  43. VA ↓arterial pressure but did not affect C and Zc in the presence of LV dysfunction. Iso not reduce R in the presence of DCM in contrast of normal LV performance. VA not beneficial actions on LV afterload in the presence of heart failure.

  44. The crescent-shaped RV is composed of embryologically distinct inflow and outflow tracts that differ in their structure and response to ANS. True isovolumic relaxation does not occur in the RV. Right Ventricular Function

  45. The effects of V.A. on the function & contraction sequence of the RV inflow and outflow tracts have been incompletely studied V.A. may alter RV contraction dynamics by adversely affecting cardiac ANS activity. Cont,

  46. ISO: different effects on RV and LV afterload and hydraulic power generation that mediated by ANS. HAL:↓contractile function ISO: different actions on RV and LV contraction dynamics in vivo.

  47. 3major roles : on LV filling& cardiovascular performance Left Atrial Function

  48. 1. a contractile chamber : empties immediately before the onset of LV systole and establishes the final LV end-diastolic volume.

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