Anesthetic preconditioning and perioperative myocardial protection

Reviewers: David Deyhimy, MD, Hong Liu, MD
University of California Davis Health System
Sacramento, CA

Myocardial ischemia during the perioperative period is a serious risk factor for patients undergoing both cardiac and noncardiac surgeries. Up to 74% of patients with coronary artery disease experience perioperative myocardial ischemia during noncardiac surgery.¹ Prevention of ischemia has traditionally focused on maintaining the balance between myocardial oxygen supply and demand using β-adrenergic antagonists, α-agonists, and/or calcium channel blockers. New evidence suggests that volatile anesthetics at clinical concentrations (1 MAC) may also be useful in pre-venting perioperative myocardial ischemia.

Ever since Murry first reported that multiple brief episodes of ischemia and reperfusion reduced subsequent myocardial ischemia/reperfusion (I/R) injury² (termed ischemic preconditioning), researchers have endeavored to understand the underlying mechanisms responsible. Current research is focused on determining how interactions at the cellular, sub-cellular, and molecular levels impart protection against myocardial ischemia and infarction. Several key intracellular signaling pathways resulting in the opening of sarcolemmal and mitochondrial K-ATP channels have now been identified.⁴ These K-ATP channels are thought to be one of the primary end effectors of preconditioning ultimately enabling the cell to withstand I/R injury. After sub-lethal ischemia, two distinct periods of protection have been identified. The first protective period occurs immediately and lasts about two hours. This is followed by a second period of protection appearing after 24 hours and lasting up to 72 hours.³ These are commonly referred to as the early and delayed "windows" of preconditioning. Investigators have also discovered that the administration of volatile anesthetics produces a preconditioned state with features similar to that seen with ischemic preconditioning (IPC). As with IPC, anesthetic preconditioning (APC) mediates protective effects via intracellular messaging pathways ultimately resulting in the opening of sarcolemmal and mitochondrial K-ATP channels.⁵ In 1997, Kersten reported that isoflurane imparted protection against I/R injury in dog myocardium.⁵ Subsequent studies have shown that all currently used inhalational anesthetic agents are capable of producing myocardial protection against I/R injury with an efficacy comparable to IPC.⁶

Currently, a great deal of effort is aimed at trying to determine how ischemic and anesthetic preconditioning can be used to benefit patients in clinical settings. Ottani (1995) reported that the presence of pre-infarction angina was associated with a decreased infarction size and better post-operative ventricular function. Similarly, Kloner reported that pre-infarction angina decreased the 30-day post-operative cardiac event rate.^7,8 It has also been reported that patients undergoing balloon angioplasty who had short repeated periods of ischemia (inflation and deflation of the angioplasty balloon prior to definitive prolonged balloon inflation) had fewer symptoms, less ST elevation, less frequent in-hospital cardiac events, and a decreased one-year mortality compared with patients who did not receive the ischemic preconditioning prior to balloon angioplasty.^9,10 Intermittent occlusion of coronary artery during coronary artery bypass graft (CABG) surgery has also been shown to be beneficial. These protective effects are not seen in diabetic patients for reasons not clearly understood. In addition, certain drugs such as glybenclamide, a selective ATP-sensitive K+ channel blocker, have been shown to prevent preconditioning.

Despite the protective effects of IPC, routine use has not becomew idely accepted. Conversely, the use of volatile anesthetics prior to ischemia is easy to apply and is gaining greater acceptance for this application. Although earlier studies were controversial, recent studies consistantly demonstrate that volatile anesthetics decreased release of CK-MB, troponin, TNF-a, and BNP. In addition, there is evidence that APC results in better preservation of cardiac function following ischemia, and often less inotropic support is required.12

In summary, laboratory studies have demonstrated that exposing the myocardium to a volatile anesthetic before a period of ischemia provides significant protection against subsequent I/R injury. Despite encouraging results in the small numbers of published clinical studies, more clinical data are needed to further our understanding. A large, multi-center clinical study is warranted to determine whether the cardioprotective effects seen with APC translate into decreased morbidity and mortality in patients undergoing cardiac and noncardiac surgery.

References:

1. Mongano DT. Perioperative cardiac morbidity. Anesthesiology 1990; 72:153-84
2. Murry CE, Jennings RB, Reimer KA. Preconditioning with ischemia: a delay in lethal cell injury in ischemic myocardium. Circulation 74(5):1124-36, 1986
3. Kuzuya T, Hoshida S, Yamashita N et al. Delayed effects of sublethal ischemia on the acquisition of tolerance to ischemia. Cic Res 1993; 72:1293-9
4. Fryer RM, Eells JT, Hsu AK et al. Ischemic preconditioning in rats: roleofmitochondrialK(ATP)channelinpreservationofmitochondrial function. Am J Physiol Heart Circ Physiol. 2000; 278(1):305
5. Kersten JR. et al. Isoflurane mimics ischemic preconditioning via activation of K(ATP) channels: reduction of myocardial infarct size with an acute memory phase. Anesthesiology 1997; 87: 360-70
6. Piriou V et al. Pharmacological preconditioning: comparison of des-flurane, sevoflurane, isoflurane and halothane in abbit myocardium. Br J Anaesth 2002; 89:486-91
7. Ottani F et al. Prodromal angina limits infart size: a role for ischemic preconditioning. Circulation 1995; 91:291-7
8. Kloner RA et al. Previous angina alters in-hospital outcome in IMI 4: a clinical correlate to preconditioning? Circulation 1995; 91:37-45
9. Laskey WK et al. Frequency and clinical significance of ischemic preconditioning during percutaneous coronary intervention. J Am Coll Cardiol 2003;42:998-1003
10. Tomai F et al. Ischemic preconditioning during coronary angioplasty is prevented by glybenclamide, a selective ATP-sensitive K+ channel blocker. Circulation 1994;90:700-5
11. Lambiase PD. et al. Exercise-induced ischemia initiates the second window of protection in humans independent of collateral recruitment. J Am Coll Cardiol 2003;41:1174-82
12. De Hert SG et al. Cardioprotection with volatile anesthetics: mecha-nisms and clinical implication. Anesth Analg 2005; 100: 1584-93

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Table of Contents:

• President's Message
• Call for Nominations


• Literature Reviews
  • Role of hemodilutional anemia and transfusion during cardiopulmonary bypass in renal injury after coronary revascularization: Implications on operative outcome.
  • Increased prothrombotic state lasting as long as one month after on-pump and off-pump coronary surgery.
  • Characterization of beta3-adrenoceptors in human internal mammary artery and putative involvement in coronary artery bypass management.
  • Aprotinin reduces bleeding and blood product use in patients treated with clopidogrel before coronary artery bypass grafting.
  • Secondary tricuspid regurgitation or dilatation: Which should be the criteria for surgical repair?
  • Stem cells in the dog heart are self-renewing, clonogenic, and multipotent and regenerate infarcted myocardium, improving cardiac function.
  • Overexpression of mitochondrial transcription factor A ameliorates mito­chondrial deficiencies and cardiac failure after myocardial infarction.
  • An essential role for mitochondrial aldehyde dehydrogenase in nitroglyc­erin bioactivation.


• Drug and Innovation Updates
  • Child-Pugh and MELD classifications and the mortality following cardiac surgery.
  • Anesthetic preconditioning and perioperative myocardial protection


• PRO/CON: Conscious Neuraxial Anesthesia is a Viable Alternative to General Anesthesia in Cardiac Surgery.
• Pro - Paul Kessler, MD
• Con - Peggy T. Y. Li, MBChB & Anthony M. H. Ho, MD, FRCPC, FCCP

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