|Year : 2012 | Volume
| Issue : 2 | Page : 27-34
Ischemia, reperfusion, and myocardial protection ( readdressed)
Department of Anesthesia and Critical Care, Ain Shams University, Cairo, Egypt
|Date of Submission||08-Sep-2012|
|Date of Acceptance||17-Sep-2012|
|Date of Web Publication||30-Jun-2014|
MD, AFSA, Department of Anesthesia and Critical Care, Ain Shams University, 11566 Cairo
Source of Support: None, Conflict of Interest: None
Measures to minimize myocardial damage have been an important target of research; therefore, a better understanding of the role of anesthetics in the prevention of myocardial injury may provide anesthesiologists with strategies to improve outcome. Myocardial ischemia initiates a range of cellular events, which are initially mild and become progressively damaging with increasing duration of ischemia. Perioperative myocardial ischemia is a serious adverse event that can increase morbidity and mortality after cardiac and noncardiac surgery. Several treatment approaches that prevent or lessen myocardial ischemia during and after surgery have been proposed. The use of particular anesthetics for the induction and maintenance of general anesthesia is one approach to protect against the adverse effects of ischemia. Experimental data indicate that some anesthetics, such as volatile general anesthetics, exert protective effects against ischemia–reperfusion injury that are independent of their hemodynamic effects. To approach this subject, several points should be well understood, such as myocardial metabolism, the pathophysiology of myocardial ischemia, myocardial stunning and hibernation, the effects of ischemia on myocardial metabolism, reperfusion injury, preconditioning, myocardial protection, temperature control, cardioplegia, ischemic and anesthetic preconditioning, and pharmacotherapy.
Keywords: anesthesia, myocardial protection, preconditioning, reperfusion injury
|How to cite this article:|
Eladawy M. Ischemia, reperfusion, and myocardial protection ( readdressed). Egypt J Cardiothorac Anesth 2012;6:27-34
| Introduction|| |
Because anesthesiologists frequently witness the occurrence of perioperative myocardial ischemia, measures to minimize myocardial damage have been an important target of research. Therefore, a better understanding of the role of anesthetics in the prevention of myocardial injury may provide anesthesiologists with strategies to improve outcome 1.
Myocardial protection refers to all strategies that increase the heart’s ability to withstand ischemic insult, which, together with reperfusion injury, are principally responsible for cardiac morbidity and mortality after a high-risk surgery.
Methods of myocardial protection include, among others, temperature and hemodynamic modulation, cardioplegic techniques, ischemic preconditioning, anesthetic preconditioning, and pharmacotherapy with β-blocker, α2-agonists, and the statin family of drugs 2.
The use of particular anesthetics for the induction and maintenance of general anesthesia is one such approach proposed to protect against the adverse effects of ischemia. Experimental data indicate that some anesthetics, such as volatile general anesthetics, exert protective effects against ischemia–reperfusion injury that are independent of their hemodynamic effects 3–5.
| Myocardial metabolism|| |
The heart requires ATP for the function of membrane transport systems (e.g. Na+/K+-ATPase) as well as for sarcomere contraction and relaxation, which involve myosin ATPase-dependent and ATP-dependent transport of calcium by the sarcoplasmic reticulum. Therefore, increasing the mechanical activity of the heart by increasing the heart rate and contractility increases myocardial metabolism 6.
The heart has an absolute requirement for aerobic production of ATP to maintain adequate ATP concentrations because anaerobic capacity is limited in the heart. Cellular ATP levels will decrease if there is insufficient O2 available to produce ATP aerobically or if there is an increase in ATP utilization that is not matched by a parallel increase in ATP synthesis 6.
The heart can use a variety of substrates to oxidatively regenerate ATP depending on availability; it can utilize amino acids and ketones instead of fatty acids. During ischemia and hypoxia, the coronary circulation is unable to deliver metabolic substrates to the heart to support aerobic metabolism. Under these conditions, the heart is able to utilize glycogen as a substrate for the anaerobic production of ATP and the formation of lactic acid. However, the amount of ATP that the heart is able to produce by this pathway is very small compared with the amount of ATP that can be produced through aerobic metabolism. Furthermore, the heart has a limited supply of glycogen, which is rapidly depleted under severely hypoxic conditions 6.
Under nonischemic conditions, almost about 95% of ATP formation in the heart arises from oxidative phosphorylation in the mitochondria, with the remainder derived from glycolysis and GTP formation. The heart has a relatively low ATP content and a high rate of ATP hydrolysis; thus, there is complete turnover of the myocardial ATP pool approximately every 10 s under normal conditions 2.
Approximately 60–70% of ATP hydrolysis fuels contractile shortening, and the remaining 30–40% is primarily used for the sarcoplasmic reticulum ion pumps. Mitochondrial oxidative phosphorylation is fueled with energy from electrons that are transferred from carbon fuels by dehydrogenation reactions that generate NADH and NADH2 produced primarily in the fatty acid-oxidation pathway. Thus, an increase in contractile power results in a concomitant increase in all of the components in the system. The regulation of myocardial metabolism is linked to arterial carbon substrate concentration, hormone concentrations, coronary flow, inotropic state, and the nutritional status of the tissue. The reducing equivalents (NADH and NADH2) that are generated by either the dehydrogenases of glycolysis or the oxidation of lactate and pyruvate and fatty acid oxidation deliver electrons to the electron transport chain, resulting in ATP formation by oxidative phosphorylation. These mechanisms allow for the rapid adaptation to acute stresses such as exercise, ischemia, or fasting 6.
| Pathophysiology of myocardial ischemia|| |
Hypoxia is the condition in which oxygen supply is reduced despite adequate perfusion. These conditions should be distinguished from ischemia, in which oxygen deprivation is accompanied by inadequate removal of metabolites. In the presence of coronary obstruction, an increase in myocardial oxygen requirements by tachycardia leads to transitory imbalance; this condition is termed demand ischemia. In other situations, the imbalance is caused by a reduction in oxygen supply secondary to increased coronary vascular tone or by platelet aggregation; this condition is termed supply ischemia 7.
Consequences of myocardial ischemia
Myocardial stunning and hibernation
After a brief episode of severe ischemia, prolonged myocardial dysfunction with a gradual return of contractile activity occurs, a condition termed myocardial stunning 8–10; this may occur following coronary spasm, and it affects both systolic and diastolic function. In patients with myocardial infarction, reversibly injured, functionally stunned myocardium lies adjacent to infarcted myocardium 11,12.
It was also discovered that chronic hypoperfusion of the myocardium (hibernation) is a reversible cause of left ventricular dysfunction.
The mechanism of pathogenesis of myocardial stunning and hibernation may be one of two theories: the oxyradical hypothesis, which relates the myocardial stunning and hibernation to the generation of reactive oxygen species (ROS), and the calcium hypothesis, which postulates that stunning and hibernation are the result of a disturbance of cellular calcium homeostasis 13.
Hemodynamic consequences of ischemia
Within seconds of coronary occlusion, the relatively high rate of energy expenditure results in a sudden decrease in myocardial oxygen tension and loss of contractility. If sufficiently widespread, regional impairment in myocardial contractile activity depresses global left ventricular function.
Myocardial ischemia and infarction not only alter the contractile properties of the heart but also its diastolic properties 14. Thus, ischemia causes impairment in cardiac contraction and incomplete ventricular emptying (systolic failure) and impairment in ventricular relaxation (diastolic failure); this combination leads to elevated ventricular filling pressures, causing pulmonary congestion.
Effects of ischemia on myocardial metabolism
During the first few minutes of ischemia, the production of high-energy phosphates (ATP and creatine phosphate) decreases and is exceeded by their utilization. Creatine phosphate is depleted by the transfer of high-energy phosphate to ADP; as oxidative synthesis of ATP decreases, ADP is converted into AMP, which is in turn broken down into adenosine 15.
The early electrophysiological hallmarks of ischemia include a marked decrease in resting membrane potential, the action potential amplitude, and duration, with a subsequent decrease in excitability and conduction block 16.
The ATP-dependent ion exchangers and transporters can no longer function, with the result that potassium ions start to leak into the extracellular space, and calcium ions leak into the cell. This leads to electrical instability and the failure of the cells to relax. Ischemia proceeds till the myocytes are swollen, acidotic, and show signs of structural disorganization 17.
Laboratory findings of myocardial infarction
The diagnosis of laboratory infarction is made on the basis of the detection of elevated serum activities of total creatine kinase (CK), creatine kinase isoenzyme MB fraction (CKMB), and troponin 18.
As myocytes become necrotic, the integrity of the sarcolemmal membrane is compromised and intracellular macromolecules (serum cardiac markers) begin to diffuse into the cardiac interstitium and ultimately into the microvasculature in the region of the infarct 19–21.
Serum CK activity exceeds the normal range within 4–8 h following the onset of acute myocardial infraction (AMI) and decreases to normal within 2–3 days 19, 20, 22.
Three isoenzymes of CK (MM, BB, and MB) have been identified; elevated serum activity of CKMB may be considered to be the result of AMI 23,24.
The troponin complex consists of three subunits that regulate the calcium-mediated contractile process of striated muscle 25. These are troponin C, which binds Ca, troponin I, (TnI) which binds to actin, and troponin T (TnT), which binds to tropomyosin 26.
Several studies have confirmed the reliability of quantitative assays of cardiac troponins for detecting myocardial injury 27–29. Cardiac troponins first begin to increase by 3 h and may persist for 7–10 days 28. It seems reasonable to measure either cardiac troponin T (cTnT) or cardiac troponin I (cTnI) in patients with suspected AMI by obtaining measurements every 8–12 h 30.
cTnT in the serum appears to be a more sensitive indicator of myocardial cell injury than CKMB activity, and it has been shown to be highly sensitive for cardiac injury and not elevated in any other trauma 31.
Techniques of myocardial ischemia detection, such as the presence of v-waves in the PCWP tracing or decreases in regional wall motion detected with TEE, are not useful after surgery because they are discontinuous, expensive, and relatively invasive 32.
In adult patients undergoing cardiac surgery, increased cTnI was associated with major postoperative complications and a high peak postoperative cTnI (>13 ng/ml) was a strong and independent predictor of in-hospital mortality after cardiac surgery. Moreover, nonfatal cardiac events (especially atrial fibrillation) were also more frequent in the hospital and within a 2-year period after coronary artery bypass grafting (CABG) in patients with a high postoperative cTnI. Thus, irrespective of the mechanism of myocardial tissue insult, the overall amount of cardiac cells injured during cardiac surgery, indicated by postoperative cTnI release, is correlated with the short-term and long-term cardiac clinical outcomes 33.
| Reperfusion injury|| |
Myocardial ischemia initiates a range of cellular events, which are initially mild and become progressively damaging with increasing duration of ischemia. The damage caused during ischemia is called ‘ischemic injury’. Although reperfusion means a termination of ischemia and is essential for the cell to survive and to restore normal function, it paradoxically causes damage to the cell; this injury is called ‘reperfusion injury’ 34.
The term ‘ischemia–reperfusion injury’ is also used to represent both types of damage together as (a) it is not always easy to distinguish one from the other and (b) ischemia is often accompanied by reperfusion and reperfusion cannot occur without previous ischemia 1.
Reperfusion injury can be defined alternatively as ‘those metabolic, functional, and structural consequences of restoring coronary arterial flow that can be avoided or reversed by modification of the conditions of reperfusion’. After ischemia, there is a certain population of cells that will be damaged irreversibly and will necrose. There is also a population that will be damaged, but it can be salvaged with the use of the correct reperfusion therapy, or sent down the path to necrosis with the incorrect reperfusion therapy. Unlike the injury because of the ischemic insult, which takes hours to become apparent, reperfusion injury occurs within minutes of reperfusion and is additive to the ischemic injury 35.
Despite the unequivocal utility of reperfusion in limiting cell death in the presence of severe ischemia, reperfusion can induce a number of adverse reactions that may limit its beneficial actions 36,37.
After reperfusion, ischemic cells often suddenly develop changes indicative of cell death, including ‘explosive swelling’ and widespread architectural disruption. Nevertheless, it is likely that most of the myocytes in which necrosis is accelerated by reperfusion were already irreversibly injured by the time reperfusion occurred and that reperfusion merely hastened the death of these cells 38.
Ischemia precludes adequate oxygen supply; the production of free radicals is also enhanced after the onset of ischemia and they are known to be derived mainly from neutrophils and mitochondria 17,39–41.
Neutrophils play a central role in the propagation of damage. They are attracted toward endothelial cells and subsequently migrate across the endothelium. They also release oxygen free radicals, cytokines, and other proinflammatory substances. These substances harm the endothelium, vascular smooth muscle, and myocardium 42.
On reperfusion, [H+] outside the cell is abruptly reduced to normal levels because it is washed out. This results in an increase in [Ca2+]i because of enhanced Na+–H+ and Na+–Ca2+ exchange 39–41.
Reperfusion also results in a burst of free radical generation because oxygen is abundantly supplied. Ca2+ and free radicals injure the heart further at reperfusion 17,39–41. The inflammatory response plays an important role in the pathophysiology of ischemia–reperfusion injury; a period of ischemia, followed by reperfusion is associated with acute inflammation and the release of proinflammatory cytokines. Tumor necrosis factor α and interleukin (IL)-6 are closely associated with myocardial ischemia–reperfusion injury. IL-6 has been implicated in the upregulation of intercellular adhesion molecule after myocardial ischemia–reperfusion 43.
Four types of reperfusion injury have been observed in experimental animals 44:
- Lethal reperfusion injury, a term referring to reperfusion-induced death of cells that were still viable at the time of restoration of coronary blood flow.
- Vascular reperfusion injury, which involves progressive damage to the microvasulature 45 with a possible reperfusion-induced hemorrhage in which reperfused infarcts contain hemorrhagic areas.
- Stunned myocardium: salvaged myocytes show a prolonged period of contractile dysfunction following restoration of blood flow 46.
- Reperfusion arrhythmias: bursts of ventricular tachycardia and sometimes ventricular fibrillation 47–52.
| Methods of myocardial protection|| |
Different methods of myocardial protection are temperature and hemodynamic modulation, cardioplegic techniques, ischemic preconditioning, anesthetic preconditioning, pharmacotherapy, and other strategies.
Temperature and hemodynamic modulation
In addition to being the primary mode of cerebral protection, hypothermia also offers myocardial protection. It achieves this by promoting electromechanical inactivity, impeding the process that results in apoptosis, and perhaps most importantly by reducing oxygen consumption. The lowest oxygen demands occur when the heart is arrested and decompressed. At 22°C, myocardial oxygen consumption is reduced from 80 to 0.3 ml/100 g/min. Increases in wall tension, contractility, and heart rate all serve to increase myocardial oxygen demand. There is a direct relationship between radius and wall tension that provides the rationale behind reducing ventricular wall tension as venting of the left side of the heart 2.
Cardioplegic diastolic arrest and hypothermia currently form the foundation of protective practice for on-pump cardiac surgery. Cardioplegia was introduced as a concept in 1958; it may be blood or crystalloid, warm or cold, and continuous or intermittent. The main component of cardioplegic solutions responsible for inducing diastolic cardiac arrest is potassium, and concentrations in the order of 20 mmol/liter are usually required. Blood is superior in preserving myocytes and endothelial function resulting in reduced incidence of mortality, myocardial infarction, and left ventricular failure in high-risk patients. In addition to the potential oxygen-carrying ability, blood delivers other nutrients, and also has an inherent buffering ability and scavenging of oxygen free radicals.
Optimal components for cardioplegia is a subject of continued research. It should be slightly hyperosmolar to limit edema, alkalotic to attenuate subsequent pH changes, and should have a low calcium concentration. The basic recipe can be complemented by a variety of substances aiming to supply metabolic substrates and enhanced cellular protection 2.
Ischemic preconditioning represents an adaptive endogenous response to brief sublethal episodes of ischemia, which results in protection against subsequent lethal ischemia 53 [Figure 1].
|Figure 1: Cellular mechanism of ischemic preconditioning. Adenosine A1 and A3 (A1/A3), bradykinin2 (B2), δ1-opioid (δ1), α1-adrenergic (α1), β-adrenergic (β) receptors, phospholipase C (PLC), guanine nucleotide-binding proteins (Gi protein), diacylglycerol (DAG), inositol trisphosphate (IP3), protein kinase C (PKC), ATP-sensitive K+ channels (KATP channels), mitogen-activated protein kinases (MAPK). NO, nitric oxide, NOS, nitric oxide synthase, PIP2, phosphatidylinositol bisphosphate, ROS, reactive oxygen species, SR, sarcoplasmic reticulum 53.|
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Ischemic preconditioning elicited by periods of aortic cross-clamping before cardiopulmonary bypass reduces myocardial enzyme leakage and free radical formation, increases ATP preservation 54, enhances contractility after weaning from cardiopulmonary bypass 55, decreases the need for inotropic support 56, and decreases TnT in blood 57,58.
However, one trial with patients undergoing CABG surgery using aortic cross-clamping before the onset of cardioplegic arrest failed to show beneficial effects 59. It is assumed that the protective effects of preconditioning during CABG surgery may only become demonstrable if cardioplegic protection is inadequate 12 or ischemic durations are long 60,61.
In off-pump, beating-heart CABG surgery, favorable effects of ischemic preconditioning were found such as improved regional wall motion abnormalities assessed by transesophageal echocardiography 62, and decreased myocardial enzyme release and increased myocardial function were observed in preconditioned patients 63.
Ischemic stimuli cause the release of stress mediators from the heart, including adenosine, bradykinin, opioids, noradrenaline, and free radicals. They contribute as initiators, which pass signals to intracellular components, such as inhibitory guanine nucleotide-binding proteins (Gi proteins) and protein kinase C (PKC). Eventually, ATP-sensitive K+ channels (KATP channels) on the sarcolemma and mitochondria are activated 13,64.
The activation of phospholipases C leads to the formation of inositol trisphosphate (IP3) for the release of Ca2+ from the sarcoplasmic reticulum through the IP3 receptor, and the production of diacylglycerol, which, in turn, activates PKC. PKC is activated by a large number of phosphorylating enzymes, including G-proteins, phospholipids, diacylglycerol, increased intracellular Ca2+, and nitric oxide; PKC can be activated by ROS arising from mitochondria either during the short ischemic or the subsequent repetitive reperfusion episodes. Activation of this key enzyme leads to phosphorylation and thus activation of the sarcolemmal and mitochondrial KATP channels, the putative end-effectors of early and delayed preconditioning 65.
ROS are important intracellular signaling molecules and are increased during sublethal oxidative stress (preconditioning stimulus). They play a pivotal role in triggering early and delayed cardioprotection 66. The administration of radical scavengers blocks the beneficial effects of early ischemic preconditioning 67, and evidence was found for an essential role of ROS in the establishment of late preconditioning 68. Thus, the generation of ROS during the initiation of preconditioning represents an essential trigger for early and delayed cardioprotection.
Infarct size reduction is mediated largely by mitochondrial KATP channels, but functional recovery is mediated by sarcolemmal KATP channels 69. Mitochondrial KATP channels also play an important role in the prevention of cardiomyocyte apoptosis 70 and in delayed preconditioning protection 71,72 [Figure 1].
Inhalational anesthetics and reperfusion injury
Volatile anesthetics may exert cardioprotective effects when administered during reperfusion 3–5,73. They may also protect the myocardium from cellular damage as a result of proposed anti-inflammatory properties that have been described in experimental studies 35.
Patients receiving a volatile anesthetic during and after coronary artery surgery have preserved cardiac performance and their need for inotropic support in the early postoperative period is significantly less; in addition, postoperative plasma concentrations of cTnI in those patients are less than those after the total intravenous anesthetic regimen 74. Sevoflurane preserves myocardial function after cardiopulmonary bypass (CPB) with less evidence for myocardial damage and better postoperative myocardial function compared with the intravenous anesthetic regimen 75.
The addition of sevoflurane 2% to a cardioplegia solution during aortic cross-clamping effectively reduces the generation of IL-6, inhibits neutrophil activation, and improves myocardial systolic function after CPB. The incidence of new RWMA detected after CPB was also reduced by the administration of sevoflurane, which also decreases the incidence of ventricular arrhythmia after an ischemic event 43.
The depression of myocardial contractility associated with the administration of sevoflurane is advantageous during coronary revascularization procedures if the decrease in myocardial oxygen consumption is greater than the regional decrease in myocardial perfusion caused by anesthetic-induced hemodynamic changes 43 [Figure 2].
|Figure 2: Signaling for cardiac preconditioning. Early (left of dashed line) and delayed (right of dashed line) cardiac preconditioning. AlRed, aldose reductase; Bcl-2, anti-apoptotic protein; Ca, sarcolemmal voltage-dependent Ca2+ channels; COX-2, cyclooxygenase type 2; DAG, diacylglycerol; eNOS, endothelial NO synthase; G-proteins, heterotrimeric G-proteins; HSP27 and HSP70, heat shock proteins; iNOS, inducible NO synthase; IP3, inositol trisphosphate; IP3R, inositol trisphosphate receptor; K, sarcolemmal and mitochondrial KATP channels; m, inner mitochondrial membrane potential; MnSOD, manganese superoxide dismutase; NF-B, nuclear factor-B; NO, nitric oxide; PIP2, phosphatidylinositol bisphosphate; PKC, protein kinase C; PLC/PLD, phospholipases C and D; ROS, reactive oxygen species; RYR, ryanodine Ca2+-release channel; SERCA2, Ca pump of the SR; SR, sarcoplasmic reticulum 76.|
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The administration of some anesthetics exerts a preconditioning-like effect, protecting the myocardium from the effects of myocardial infarction and dysfunction 77,78. A better recovery of myocardial function after coronary artery occlusion was achieved when a volatile anesthetic was administered before the occlusion 79. Several studies have shown that anesthetic preconditioning resulted in a similar degree of cardioprotection as observed after ischemic preconditioning, both for functional recovery and for protection from ischemic damage to the heart 80 and lungs 81. Beneficial effects on myocardial stunning have been described for all commercially available volatile anesthetics 77, 82, 83. In addition to attenuating the effects of ischemia on contractility, anesthetic preconditioning also decreases the area of the myocardium that was affected during ischemia 77.
Sevoflurane 4% administered during the first 10 min of CPB just before aortic cross-clamping significantly reduces the postoperative release of brain natriuretic peptide, a sensitive biochemical marker of myocardial contractile dysfunction 84. However, no differences were found for perioperative ST segment changes, arrhythmias, CKMB, and cTnT release 85.
Myocardial protection persists even though anesthetics were allowed to wash out. Because evidence indicated that halogenated anesthetics dilated the coronary arteries through KATP channels, known to be a key constituent of the ischemic preconditioning pathway, halogenated anesthetics induced an ischemic preconditioning-like effect and the protection by halogenated anesthetics has been reversed by a selective adenosine A1 receptor antagonist 86, a Gi protein inhibitor 87, 88, PKC inhibitors 58, 89, and KATP channel blockers 4, 79, 86–88,90–93.
Mitochondrial KATP channel activity was increased when exposed to sevoflurane 94. The concept of channel priming by volatile anesthetics was described by Sato et al. 95, who proposed a resting, primed, and open state of the mitochondrial KATP channel. Volatile anesthetics mediate their protection by selectively enhancing mitochondrial KATP channels through the triggering of multiple PKC-coupled signaling pathways 78. It is not surprising, therefore, that nitric oxide and cGMP may be major players in volatile anesthetic-induced protection 96.
Many studies have compared volatile anesthetic agents with propofol on the basis of the release of biochemical markers of myocardial damage, and concluded that inhalation agents were superior to propofol. However, not all studies have found differences between the two modalities 97, and some even showed a significant postoperative increase in the concentrations of cTnT, total CK, and CKMB activity in patients who were on sevoflurane 84 [Figure 3].
|Figure 3: Cellular mechanism of volatile anesthetic preconditioning. ATP-sensitive K+ channels (KATP channels), phospholipase C (PLC), adenosine A1 and A3 (A1/A3), nitric oxide synthase (NOS). B2, bradykinin2 receptors; DAG, diacylglycerol; Gi protein, inhibitory guanine nucleotide-binding proteins; IP3, inositol 1,4,5-triphosphate; MAPK, mitogen-activated protein kinases; NO, nitric oxide; PIP2, phosphatidylinositol bisphosphate; PKC, protein kinase C; ROS, reactive oxygen species; SR, sarcoplasmic reticulum; α1, α1-adrenergic receptor; β, β-adrenergic receptor; δ1, δ1-opioid receptor 53.|
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Postoperative myocardial infarction occurs within a few hours of completion of surgery and is associated with tachycardia and hypertension, which are factors contributing toward increased myocardial oxygen demand. β-Blocker reduces mortality after myocardial infarction in proportion to the reduction in heart rate 2.
The α2-agonist clonidine has shown perioperative myocardial protective properties 2.
The statin family of drugs offers both lipid lowering and a complex collection of unrelated benefits, including increased plaque stability, decreased platelet activity, decreased inflammatory markers, and improved arterial blood flow. The reduced mortality has been shown to extend up to 5 years after the operation 2.
Meta-analysis has indicated that despite the sound theoretical reasoning of improved analgesia and reduced stress response to surgery, thoracic epidural analgesia and intrathecal analgesia do not reduce the incidence of mortality or myocardial infarction.
It has been shown recently that a glucose–insulin–potassium infusion in nondiabetics reduces myocardial damage and inotrope requirements. Xenon, adenosine, nicorandil, and norepinephrine, among others, also have preconditioning properties. Aging, diabetes, and hypercholesterolemia all attenuate APC 2.
| Conclusion|| |
Several questions still remain unanswered about the role of ischemic and anesthetic preconditioning. The currently available clinical data on the cardioprotective effects of anesthetics are confined to cardiac surgical patients, mostly with an ejection fraction of more than 55. However, noncardiac surgery is also associated with a risk of perioperative cardiac morbid events.
Another important area of clinical research is the determination of whether the organ protective effects observed in the myocardium also apply to other tissues. Experimental evidence is emerging that volatile anesthetics may also confer a degree of protection against the effects of ischemia and reperfusion in the brain, liver, and kidney.
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[Figure 1], [Figure 2], [Figure 3]