Cardioprotection with Volatile Anesthetics: Mechanisms and Clinical Implications

1
Cardioprotection with Volatile Anesthetics
Mechanisms and Clinical Implications

• Anesthesia and Analgesia
• 20051001584 93
• Reported by R3 ???

2

• Patients with CAD undergo non-cardiac surgery
  experience peri-operative myocardial ischemia
  18 74
• For preventing or lessening myocardial ischemia
  during and after surgery modulation of the
  myocardial oxygen supply-demand ratio

3

• Some anesthetics have protective effects against
  ischemia-reperfusion injury, like volatile
  anesthetics
• This review summarizes the recent data on the
  effects of volatile anesthetics on altering
  ischemia reperfusion injury as reported in
  various experimental and clinical studies

4

• Experimental Data
• Ischemic preconditioning
• Anesthetic preconditioning
• Clinic studies
• Ischemic preconditioning
• Anesthetic preconditioning
• Anesthetic, cardioprotective effects
• Future directions
• Conclusion

5
Experimental Data
6

• Ischemic preconditioning
• During ischemia, cardiac myocytes reduce their
  contractile effort within a few seconds and stop
  contracting within the first few minutes
• If ischemia continues gt 15 minutes
• ? cellular necrosis, apoptosis, or cell
  programmed death
• ? decrease of contractile function, even
  several hours
• Short periods of transient myocardial ischemia
  appear to protect the heart from extensive damage
  during subsequent longer periods of ischemia

7

• Murry et al.
• Dogs subjected to 4 5-min episodes of cardiac
  ischemia before a 40-min occlusion
• Result the infarct size became smaller, about
  25

8

• A single, brief period of ischemia appears
  sufficient to induce ischemic preconditioning
• If the time between preconditioning and prolonged
  ischemia was longer than 2 h, the effect of
  preconditioning decreased

9

• The intracellular signaling pathway and the
  primary target
• adenosine triphosphate - sensitive K channels
  (KATP channels)
• channels that open in response to ATP
• located on the sarcolemmal and mitochondrial
  membranes within cardiac myocytes
• found in smooth muscle, skeletal muscle, brain,
  and pancreatic cells

10

• Anesthetic Preconditioning
• The administration of some anesthetics produces a
  preconditioning-like effect

11

• Warltier et al.
• Dogs, 15-min coronary artery occlusion
• Isoflurane or halothane was administered before
  the occlusion
• Result myocardial function returned to baseline
  levels within 5 h after reperfusion

12

• Anesthetic preconditioning v.s Ischemic
  preconditioning similar degree in functional
  recovery of the heart and protection from
  ischemic damage to the heart and lungs
• In addition to attenuating the effects of
  ischemia on contractility, anesthetic
  preconditioning also decreased the area of the
  myocardium that was affected during ischemia

13

• In barbiturate-anesthetized dogs, occlusion of
  the LAD
• 1 MAC sevoflurane
• Result the infarct size decreased over 40
• If the anesthetic was stopped more than 30 min
  before the coronary artery was occluded, the
  preconditioning effect was lost

14

• The intracellular pathways involved in ischemic
  and anesthetic preconditioning have not been
  completely identified
• Anesthetic preconditioning appears to be
  initiated by an increase in reactive oxygen
  species (ROS)
• activation or translocation of protein kinase C
  (PKC), other downstream kinases
• The pathways seemed to act on KATP channel

15

• Ischemic and anesthetic preconditioning effects
  also in the vasculature
• Protect coronary endothelial cells against
  ischemia and reperfusion
• The protective effect against ischemia-reperfusion
  -induced coronary constriction was greater than
  on contractility

16

• Reperfusion injury
• Volatile anesthetics may also exhibit
  cardioprotective effects during reperfusion
• Volatile anesthetics may also protect the
  myocardium from cellular damage as
  antiinflammatory properties
• possible pathways
• attenuation of nuclear factor kB activation
• reduced expression of TNF-1, IL-1, intracellular
  adhesion molecules
• inducible nitric oxide synthase

17

• Varadarajan et al.
• Sevoflurane
• Mechanical and metabolic function improved
• either immediately before global myocardial
  ischemia or on reperfusion immediately after
  ischemia
• no additive protective effect both before and
  after ischemia
• Maximal effect ? before ischemia

18
Clinical Studies
19

• Ischemic Preconditioning
• The presence of pre-infarction angina
• decreased infarction size
• better postoperative ventricular function
• decreased 30-day cardiac event rate
• Interestingly, this protective effect of
  prodromal angina seemed to be absent in the
  presence of diabetes

20

• Another human model of ischemic preconditioning
  is coronary balloon angioplasty
• Repeated balloon angioplasty, fewer symptoms
• less ST segment elevation
• less frequent in-hospital cardiac event rate
• less frequent 1-yr mortality

21

• Warm-up angina
• correlated with ischemic preconditioning
• the severity of the symptoms of myocardial
  ischemia associated with angina during exercise
  or coronary angioplasty are reduced when they
  follow a previous period of exercise

22

• Coronary artery bypass surgery is yet another
  area where the application of ischemic
  preconditioning may have a potential therapeutic
  role
• increased myocardial ATP content
• decreased troponin T release
• reduced incidence of ventricular
  tachy-arrhythmias
• BUT the induction of an ischemic episode in a
  coronary patient may greatly exacerbate symptoms
  and reduce cardiac reserve

23

• A distinct difference in the effects of ischemic
  and anesthetic preconditioning on gene
  expression, different cardioprotective mechanisms
  
• Pharmacologically precondition the myocardium
• adenosine receptor agonists, KATP channel
  openers, activators of protein kinases, free
  radical scavengers, and other moieties
• No clinic use because of side effects and no
  clinical benefit

24

• Anesthetic Preconditioning
• In contrast to the experimental studies, results
  from clinical studies show highly variable
  results
• How to differentiate the preconditioning effects
  ?
• Anesthetic v.s Ischemic

25

• Belhomme et al. in 1999
• Isoflurane at 2.5 MAC was administered for 5
  minutes via the oxygenator in the CPB circuit and
  followed by a 10-min washout period before aortic
  cross-clamping
• Result increase in cytosolic activity of 5'
  nucleotidase (a surrogate marker for activation
  of PKC) no difference in postoperative CK-MB and
  troponin I

26

• Sevoflurane at 2.5 MAC given during the first 10
  minutes of CPB in 20 patients
• Result Tyrosine kinase increased
• Overlapping of the effect of anesthetic
  preconditioning and the ischemic preconditioning

27

• 22 patients, 1.3 enflurane, 5 min immediately
  before CPB
• Result postoperative left ventricular function
  was enhanced
• postoperative creatine kinase-MB and troponin I
  release were not different

28

• Tomai et al.
• 40 patients, isoflurane, 1.5, for 15 min,
  followed by a washout period of 10 min before the
  start of CPB
• Result no differences
• In a group of patients with LVEF 50,
• troponin I levels 24 h postoperatively were
  slightly lower

29

• Haroun-Bizri et al.
• 49 patients, isoflurane 0.52, until the start
  of CPB
• Result higher postoperative cardiac index

30

• Julier et al.
• 72 patients, sevoflurane 4, during the first 10
  min of CPB just before aortic crossclamping
• Result lower reduced postoperative release of
  brain natriuretic peptide
• a sensitive biochemical marker of myocardial
  contractile dysfunction
• no differences in perioperative ST segment
  changes, arrhythmias, creatine kinase MB, and
  cardiac troponin T release.

31

• Due to the above studies, clinical benefit for
  the patients couldnt be demonstrated
• ?small sample size
• inadequate power

32

• Anesthetic, Cardioprotective Effects
• Whether the choice of anesthetic regimen during
  the entire surgical procedure influence the
  myocardial outcome ?

33

• De Hert et al.
• compared sevoflurane and propofol on myocardial
  function during and after coronary artery surgery
• Result sevoflurane preserved cardiac
  performance
• preserved stroke volume
• length-dependent regulation of myocardial
  function
• less inotropic support
• less postoperative plasma concentrations of
  cardiac troponin I
• Cardioprotective effect provided by volatile
  anesthestics

34

• Elderly, high-risk patients with impaired
  myocardial function
• Sevoflurane and desflurane v.s IV anesthestics
• Result preserved myocardial function after CPB,
  less myocardial damage, better postoperative
  myocardial function

35

• The addition of sevoflurane to an IV anesthesia
  regimen for cardiac surgery
• Result decreased troponin T levels, less need
  for inotropic support for weaning from CPB and a
  reduced incidence of low cardiac output

36

• El Azab et al.
• 20 patients undergoing coronary surgery
• sevoflurane anesthesia compared with IV
  anesthesia with midazolam
• Result decreased plasma TNF-a
• ? protection against ischemia-reperfusion
  injury

37

• Conzen et al.
• Sevoflurane compared propofol
• Result better cardiac function, less serum
  troponin I levels, no significant effect on cK-MB

38

• Future Directions
• Any possible differences among the available
  volatile anesthetics in cardioprotective effects

39

• the contractile function of human atrial
  trabeculae dissected from atrial appendages
• Isoflurane ? greater recovery of force
• Halothane ? no cardioprotective effect and
  inhibit the cardioprotection provided by hypoxic
  preconditioning

40

• The risks associated with noncardiac surgical
  procedures were evaluated in the American College
  of Cardiology/American Heart Association practice
  guidelines on perioperative cardiovascular
  evaluation for noncardiac surgery

41

• The guidelines identified a number of procedures
  with a more than 5 risk of perioperative cardiac
  morbidity
• major emergency operations, particularly in the
  elderly
• aortic and other major vascular surgery
• peripheral vascular surgery
• anticipated prolonged surgical procedures
  associated with large fluid shifts or blood loss

42

• Remaining the implications of volatile anesthetic
  for outcome
• The length of stay in the intensive care unit
  seemed to be related to the choice of anesthetic
  regimen
• Decreased incidence of prolonged stay (48 h)
• atrial fibrillation, increase in postoperative
  troponin I levels (4 ng/mL), and the need for
  prolonged inotropic support
• Also, volatile anesthetics offer a degree of
  protection against the effects of ischemia and
  reperfusion in the brain, the liver, and the
  kidney

43
Conclusion
44

• Exposure of the myocardium to a volatile
  anesthetic before a period of ischemia
  significantly protects the myocardium against
  subsequent ischemia-reperfusion injury
• The cardioprotective effects anesthetic
  preconditioning is better in contractile function
  and reduced infarct size in animal models than
  ischemic preconditioning

45

• Further investigation is needed to determine
  whether the cardioprotective effects of volatile
  anesthetics indeed translate into decreased
  morbidity and mortality in patients undergoing
  cardiac and noncardiac surgery

46

• The end !