Treatment of myocardial ischaemia-reperfusion injury in patients with ST-segment elevation myocardial infarction: promise, disappointment, and hope.

Acute myocardial infarction (AMI) is a major cause of morbidity and mortality worldwide. Timely reperfusion with primary percutaneous coronary intervention (PPCI) remains the gold standard in patients presenting with ST-segment elevation myocardial infarction (STEMI), limiting infarct size, preserving left ventricular ejection fraction (LVEF), and improving clinical outcomes. Despite this, a significant proportion of STEMI patients develop post-infarct heart failure. We review the current understanding and up-to-date evidence base for therapeutic intervention of ischaemia-reperfusion injury (IRI), a combination of myocardial ischaemia secondary to acute coronary occlusion and reperfusion injury leading to further myocardial injury and cell death. Multiple treatment modalities have been shown to be cardioprotective and reduce IRI in experimental animal models. Recent phase II/III randomised controlled trials (RCT) have assessed multiple cardioprotective strategies ranging from ischaemic conditioning, therapeutic hypothermia and hyperoxaemia to pharmacological therapies. While several therapies have been shown to reduce infarct size in animal models or proof-of-concept studies, many larger scale trial results have proven inconsistent and disappointing. Hard clinical outcomes remain elusive. We discuss potential reasons for the difficulties in translation to clinical practice.

The protective effects of L-carnitine on myocardial ischaemia-reperfusion injury in patients with rheumatic valvular heart disease undergoing CPB surgery are associated with the suppression of NF-κB pathway and the activation of Nrf2 pathway.

Myocardial ischaemia-reperfusion injury (MIRI) is a main pathophysiologic change following CPB surgery. L-carnitine, a natural amino acid, is able to transport fatty acids for generating energy and has a protective effect on MIRI. We aim to investigate the protective effect of L-carnitine on MIRI in patients with rheumatic valvular heart disease (RVHD) performed CPB surgical operation and the underlying mechanism. In this study, patients were randomized to three groups. L-carnitine was added to the crystalloid cardioplegic solution for experimental group 1 (6 g/L) and experimental group 2 (12 g/L), whereas no L-carnitine was used in the control group. Our results showed that L-carnitine significantly attenuated myocardial injury after surgery in these patients. L-carnitine decreased serum markers of myocardial injury including CK-MB, cTnI, hs-cTnT and IMA. L-carnitine increased left ventricular ejection fraction (LVEF) but reduced wall motion score index (WMSI) after operation. L-carnitine also inhibited myeloperoxidase (MPO) activity and inflammatory cytokines in the myocardium of patients after unclamping the aorta. Additionally, L-carnitine increased levels of superoxide dismutase (SOD) and catalase (CAT) while decreased levels of malondialdehyde (MDA) and protein carbonyl content in the myocardium of patients after unclamping the aorta. Moreover, L-carnitine suppressed the activation of nuclear factor kappa B (NF-κB) and activated nuclear factor erythroid 2-related factor 2 (Nrf2). There was also no significant difference in these indices between two experimental groups after unclamping the aorta. Taken together, L-carnitine had a protective effect against CPB-induced MIRI in patients with RVHD, which might be related to its modulation of NF-κB and Nrf2 activities.

The Role of O-GlcNAcylation for Protection against Ischemia-Reperfusion Injury.

Ischemia reperfusion injury (IR injury) associated with ischemic heart disease contributes significantly to morbidity and mortality. O-linked ß-N-acetylglucosamine (O-GlcNAc) is a dynamic posttranslational modification that plays an important role in numerous biological processes, both in normal cell functions and disease. O-GlcNAc increases in response to stress. This increase mediates stress tolerance and cell survival, and is protective. Increasing O-GlcNAc is protective against IR injury. Experimental cellular and animal models, and also human studies, have demonstrated that protection against IR injury by ischemic preconditioning, and the more clinically applicable remote ischemic preconditioning, is associated with increases in O-GlcNAc levels. In this review we discuss how the principal mechanisms underlying tissue protection against IR injury and the associated immediate elevation of O-GlcNAc may involve attenuation of calcium overload, attenuation of mitochondrial permeability transition pore opening, reduction of endoplasmic reticulum stress, modification of inflammatory and heat shock responses, and interference with established cardioprotective pathways. O-GlcNAcylation seems to be an inherent adaptive cytoprotective response to IR injury that is activated by mechanical conditioning strategies.

DELAYED REPERFUSION FOR SAVING VITAL MYOCARDIUM IN THE ACUTE PERIOD OF MYOCARDIAL INFARCTION WITH ELEVATION OF ST SEGMENT.

Reperfusion therupy in case of acule inl , voc'ardial infiction is especialli desirble within 12 hr cfierfirs/ clinical manifestalions as show in stidies with the use of thrombolytic therapy (TLT). Its efficiency for saving ischemic myocardum decreqses as the time from the onset of pain syndrome increasrs. Nevertheless, patients admitted to the clinic in the period deemed infavourable for TLT still preserve large part of vital myocardium even if in the risk zone. Delayed saving myocardum impossible by TLT can be ensured by transdermal coronary interventions. The depence of myocardial necrois on the duration of occlution of coronary artery is as well recognized as the necessity of early interventions. Transdermal coronary interventions can be perforned within days 2 or 3 after onset of acute myocarial infraction if it was impracticable in an earlier period.

Dexmedetomidine Pretreatment Confers Myocardial Protection and Reduces Mechanical Ventilation Duration for Patients Undergoing Cardiac Valve Replacement under Cardiopulmonary Bypass.

PURPOSE: The study aims to assess the effects of dexmedetomidine (Dex) pretreatment on patients during cardiac valve replacement under cardiopulmonary bypass. METHODS: For patients in the Dex group (n = 52), 0.5 µg/kg Dex was given before anesthesia induction, followed by 0.5 µg/kg/h pumping injection before aortic occlusion. For patients in the control group (n = 52), 0.125 ml/kg normal saline was given instead of Dex. RESULTS: The patients in the Dex group had longer time to first dose of rescue propofol than the control group (P = 0.003). The Dex group required less total dosage of propofol than the control group (P = 0.0001). The levels of cardiac troponin I (cTnI), creatine kinase isoenzyme MB (CK-MB), malondialdehyde (MDA), and tumor necrosis factor-α (TNF-α) were lower in the Dex group than the control group at T4, 8 h after the operation (T5), and 24 h after the operation (T6) (P <0.01). The Dex group required less time for mechanical ventilation than the control group (P = 0.003). CONCLUSION: The study suggests that 0.50 µg/kg Dex pretreatment could reduce propofol use and the duration of mechanical ventilation, and confer myocardial protection without increased adverse events during cardiac valve replacement.

Metformin therapy in diabetes: the role of cardioprotection.

In patients with diabetes mellitus, the incidence of cardiovascular disease is increased, and the outcome following cardiovascular events is worse. The antihyperglycemic drug metformin appears to limit cardiovascular death in patients with type 2 diabetes. Indeed, preclinical studies have demonstrated that metformin limits (myocardial) ischemia and reperfusion injury, independent from its glucose-lowering effect. This cardioprotection is mediated by activation of the Reperfusion Injury Salvage Kinase (RISK) pathway, activation of AMPK and by an increased formation of adenosine. In addition, metformin can modulate several cardiovascular risk factors and reduces the development of heart failure in murine models. Consequently, treatment with metformin might potentially improve cardiovascular outcome in patients at risk for myocardial ischemia, even if these patients do not have diabetes. In the current paper, we focus on the direct cardioprotective actions of metformin and the mechanisms that underlie these effects.

Myocardial ischemia-reperfusion injury and the influence of inflammation.

Acute myocardial infarction is caused by a sudden coronary artery occlusion and leads to ischemia in the corresponding myocardial territory which generally results in myocardial necrosis. Without restoration of coronary perfusion, myocardial scar formation will cause adverse remodelling of the myocardium and heart failure. Successful introduction of percutaneous coronary intervention and surgical coronary artery bypass grafting made it possible to achieve early revascularisation/reperfusion, hence limiting the ischemic zone of myocardium. However, reperfusion by itself paradoxically triggers an exacerbated and accelerated injury in the myocardium, called ischemia-reperfusion (I/R) injury. This mechanism is partially driven by inflammation through multiple interacting pathways. In this review we summarize the current insights in mechanisms of I/R injury and the influence of altered inflammation. Multiple pharmacological and interventional therapeutic strategies (ischemic conditioning) have proven to be beneficial during I/R in preclinical models but were notoriously unsuccessful upon clinical translation. In this review we focus on common mechanisms of I/R injury, altered inflammation and potential therapeutic strategies. We hypothesize that a dual approach may be of value because I/R injury patients are predestined with multiple comorbidities and systemic low-grade inflammation, which requires targeted intervention before other strategies can be fully effective.

Local ischemic postconditioning during primary percutaneous coronary intervention: a meta-analysis.

OBJECTIVES: To investigate current evidence linking ischemic postconditioning (IPC) to cardioprotection in patients receiving primary percutaneous coronary intervention (PCI). METHODS: We performed searches of PubMed, Embase, MEDLINE and Cochrane databases from January 1998 to May 2011 for identifying relevant studies comparing IPC with usual care in patients undergoing primary PCI. A meta-analysis of eligible studies was assessed by Review Manager 5.0. RESULTS: Thirteen studies were eligible. Compared to the control, observed outcomes such as peak creatine kinase [weighted mean difference (WMD) -537.48, 95% confidence interval (CI) -779.32 to -295.65 IU/l], peak creatine kinase-myocardial band (WMD -61.11, 95% CI -76.56 to -45.66 U/l), complete ST-segment resolution (risk ratio 1.38, 95% CI 1.07 to 1.77), blush grade during reflow (WMD 0.64, 95% CI 0.49 to 0.78), corrected TIMI frame count, single-photon emission computed tomography determining infarct size, long-term left ventricular ejection fraction and short-term and long-term wall motion score indexes were improved in IPC group, with less occurrence of heart failure during the 3-month to 3.4-year follow-up. CONCLUSIONS: Though current evidence indicates that IPC provides potential cardioprotection to patients receiving primary PCI, larger adequately powered studies should be undertaken to confirm its advantages.

Nicorandil attenuates ventricular dysfunction and organ injury after cardiopulmonary bypass.

BACKGROUND: Nicorandil, an adenosine triphosphate-sensitive potassium channel agonist and nitric oxide donor, is a coronary vasodilator used to treat ischemia-induced chest pain, but it's potential cardioprotective benefits during open heart surgery have not been thoroughly investigated. The study objective was to assess the impact of nicorandil on postoperative ventricular dysfunction and end-organ injury in an established experimental model of open-heart surgery with cardiopulmonary bypass (CPB) and cardioplegic arrest. We hypothesized that nicorandil would attenuate myocardial ischemia-reperfusion (IR) injury, preserve ventricular function, and reduce end-organ injury. METHODS: Rabbits were cannulated for CPB, followed by 60 min of aortic cross-clamp (ACC) with cold cardioplegic arrest, and 120 min of recovery after ACC removal. Nicorandil (or normal saline vehicle) was given intravenously 5 min before ACC and continued throughout the recovery period. Left ventricular developed pressure (LVDP), systolic contractility (LV + dP/dt), and diastolic relaxation (LV -dP/dt) were continuously recorded, and blood and tissue samples were collected for measurement of oxidant stress (OS), inflammation, apoptosis, and organ injury. RESULTS: Nicorandil significantly attenuated IR-induced LV dysfunction compared to saline control (R-120: LV + dP/dt: 1596 ± 397 vs. 514 ± 269 mmHg/s, p = 0.010; LV -dP/dt: -1524 ± 432 vs. -432 ± 243 mmHg/s, p < 0.001; LVDP: 55 ± 11 vs. 22 ± 5 mmHg, p = 0.046). Furthermore, nicorandil inhibited IR-induced increases in OS, inflammation, apoptosis, and organ injury. CONCLUSIONS: Nicorandil exhibits myocardial protection by attenuation of IR-induced LV dysfunction associated with OS, inflammation, apoptosis, and organ injury. Nicorandil should be explored further as a potential therapeutic strategy for limiting global IR injury during open-heart surgery in humans.

The combination approach with Rhokinase inhibition and mechanical circulatory support in myocardial ischemia-reperfusion injury: Rho-kinase inhibition and ventricular unloading.

BACKGROUND: It remains unclear whether the Rho-kinase (ROCK) inhibition in combination with mechanical circulatory support (MCS) had a synergic protective effect on myocardial ischemia (MI)/reperfusion injury in therapeutic strategies for acute myocardial infarction (AMI). We report the results of an approach using a rat model consisting of a miniaturized cardiopulmonary bypass (CPB) and AMI. METHODS: A total of 25 male Wistar rats were randomized into 5 groups: (1) Sham: a suture was passed under the left anterior descending artery (LAD) creating no MI. A vehicle solution (0.9% saline) was injected intraperitoneally. (2) Myocardial ischemia (MI) + vehicle (MI + V): LAD was ligated for 30 min and reperfused for 120 min, followed by administration of vehicle solution. (3) MI + fasudil (MI + F): the work sequence of group 2, but the selective ROCK inhibitor fasudil (10 mg/kg) was administered instead. (4) MI + V + CPB: CPB was initiated 15 min after the ligation of the LAD to the end of the reperfusion, in addition to the work sequence in group 2. (5) In the MI + F + CPB group, the work sequence of group 4, but with fasudil administration (10 mg/kg). RESULTS: Measurements of cardiac function through conductance catheter indicated that the drop of + dP/dt after reperfusion was moderately limited in MI + F + CPB (vs. MI + V, dP/dt p = 0.22). The preload recruitable stroke work was moderately improved in the MI + F + CPB (p = 0.23) compared with the corresponding control animals (MI + V). Phosphorylated protein kinase B expression in the MI + V + CPB and MI + F + CPB was higher than that in MI + V (p = 0.33). CONCLUSION: Therefore, fasudil administration with MCS resulted in a moderately better left ventricular performance.

Ischemia-modified albumin reduction after coronary bypass surgery is associated with the cardioprotective efficacy of cold-blood cardioplegia enriched with N-acetylcysteine: a preliminary study.

BACKGROUND: The aims of this preliminary study were to determine the alteration of serum ischemia-modified albumin (IMA) levels and to investigate whether IMA may be used as an indicator of the cardioprotective efficacy of N-acetylcysteine (NAC) in patients undergoing coronary bypass grafting (CABG). PATIENTS AND METHODS: Forty-four patients were randomized into one of two groups on the basis of cardioplegic strategies, either cold-blood cardioplegia enriched with NAC (50 mg/kg) or cold-blood cardioplegia alone. Serum IMA, cardiac troponin T (cTnT) and malondialdehyde (MDA) levels determined in NAC-enriched patients before and after CABG were compared with those of the NAC-free group. The albumin cobalt binding assay was used for IMA determination. RESULTS: Serum IMA levels were significantly elevated after cross-clamping and peaked at 6 h after reperfusion in the two groups. In NAC-enriched patients, IMA levels determined 6, 12, 24 and 48 h after reperfusion were significantly lower than those of the NAC-free group (p < or = 0.001, p < 0.001, p < 0.001 and p < 0.001, respectively). IMA returned to baseline 24 h after reperfusion differently from cTnT and MDA in the NAC-enriched group. CONCLUSIONS: IMA may be used as not only an indicator of myocardial ischemia-reperfusion injury, but also as a useful indicator of the cardioprotective effect of NAC in CABG.

Cardioprotection and the mitochondrial permeability transition.

Although in developed countries, the rates of cardiovascular mortality show a decreasing trend, both the incidence and the prevalence of cardiovascular disease are on the rise in developing countries. It is likely that the currently unfolding epidemics of diabetes and obesity will erode recent gains in decreasing cardiovascular mortality in the Western countries as well. This article will focus on recent research which suggests that induction of mitochondrial permeability transition (MPT) during ischemia/ reperfusion (I/R) injury is a critical event that triggers both necrotic and apoptotic cell death. Additionally we will examine mechanisms that limit or prevent MPT which may be targeted to decrease ischemic cell death and to promote postischemic recovery of the heart. Nevertheless, the role of the mitochondria in myocardial I/R injury is complex and the signal transduction mechanisms that regulate MPT and its downstream consequences remain unclear and represent the current focus of several strategies of cardioprotection. Decades of exploration of the mitochondrial domains and the role of these organelles in regulating cell death and ischemic injury have brought us to a place where clinical interventions to limit infarct size seem to be realizable possibilities. The purpose of this review is to examine the possibility that inhibition of MPT may provide a clinically relevant target for decreasing I/R injury. Understanding MPT provide new insight into the role mitochondria play in decisions of cell survival and death.

The Dual Role of Inducible Nitric Oxide Synthase in Myocardial Ischemia/Reperfusion Injury: Friend or Foe?

Nitric oxide synthases (NOSs) are a family of enzymes that are responsible for the synthesis of nitric oxide (NO) from the amino acid L-arginine in the body. Among the three key NOSs, the expression of inducible NOS (iNOS) can only be induced by inflammatory stimuli and contribute to the large amount of NO production. iNOS-derived NO plays an important role in various physiological and pathophysiological conditions, including the ischemic heart disease. Nowadays, the development of specific iNOS inhibitors and the availability of iNOS knockout mice have provided substantial evidence to support the role of iNOS/NO signaling in the myocardium. Nevertheless, the role of iNOS/NO signaling in the myocardial ischemic reperfusion injury is very complex and highly perplexing; both detrimental and beneficial effects of iNOS have been described. Thus, this review will aim at providing basic insights into the current progress of the role of iNOS in myocardial ischemia reperfusion injury. A better understanding of the dual role of iNOS in details may help facilitate the development of more effective therapies for the management of ischemic heart diseases.

The Lectin Pathway of Complement in Myocardial Ischemia/Reperfusion Injury-Review of Its Significance and the Potential Impact of Therapeutic Interference by C1 Esterase Inhibitor.

Acute myocardial infarction (AMI) remains a leading cause of morbidity and mortality in modern medicine. Early reperfusion accomplished by primary percutaneous coronary intervention is pivotal for reducing myocardial damage in ST elevation AMI. However, restoration of coronary blood flow may paradoxically trigger cardiomyocyte death secondary to a reperfusion-induced inflammatory process, which may account for a significant proportion of the final infarct size. Unfortunately, recent human trials targeting myocardial ischemia/reperfusion (I/R) injury have yielded disappointing results. In experimental models of myocardial I/R injury, the complement system, and in particular the lectin pathway, have been identified as major contributors. In line with this, C1 esterase inhibitor (C1INH), the natural inhibitor of the lectin pathway, was shown to significantly ameliorate myocardial I/R injury. However, the hypothesis of a considerable augmentation of myocardial I/R injury by activation of the lectin pathway has not yet been confirmed in humans, which questions the efficacy of a therapeutic strategy solely aimed at the inhibition of the lectin pathway after human AMI. Thus, as C1INH is a multiple-action inhibitor targeting several pathways and mediators simultaneously in addition to the lectin pathway, such as the contact and coagulation system and tissue leukocyte infiltration, this may be considered as being advantageous over exclusive inhibition of the lectin pathway. In this review, we summarize current concepts and evidence addressing the role of the lectin pathway as a potent mediator/modulator of myocardial I/R injury in animal models and in patients. In addition, we focus on the evidence and the potential advantages of using the natural inhibitor of the lectin pathway, C1INH, as a future therapeutic approach in AMI given its ability to interfere with several plasmatic cascades. Ameliorating myocardial I/R injury by targeting the complement system and other plasmatic cascades remains a valid option for future therapeutic interventions.

Effects of N-acetyl cysteine and melatonin on early reperfusion injury in patients undergoing coronary artery bypass grafting: A randomized, open-labeled, placebo-controlled trial.

OBJECTIVES: This study assessed the efficacy of oral consumption of N-acetyl cysteine (NAC) and melatonin (ML) in reducing early reperfusion injury and acute oxidative stress in patients undergoing coronary artery bypass grafting (CABG) with respect to the measurements of cardiac troponin I, lactate, malondealdehyde (MDA), and tumor necrosis factor-α (TNF-α) levels in the blood. METHODS: This study was a randomized, open-label, placebo-controlled trial. Eighty eight patients, aged between 39 to 76 years and eligible for CABG, were recruited and randomly assigned into 3 intervention groups through a simple randomization method and underwent CABG surgery. Blood samples were withdrawn from arterial line, before the induction of anesthesia (before the start of surgery), after incision (before aortic cross-clamping), during global ischemia (during aortic cross-clamping), after aortic cross-clamping (on set of reperfusion), 15 minutes after reperfusion, and after recovery at the intense care unit. The blood samples were analyzed for troponin I, lactate, MDA and TNF-α levels. RESULTS: There was no significant difference in influencing variables among the groups at the baseline. Overall mean troponin I, lactate, and TNF- α levels were significantly different between the intervention groups (all P < .001) at the recovery phase. Post-hoc pairwise comparisons showed that the differences of mean serum levels between ML and control groups were statistically significant for MDA, TNF- α, lactate, and troponin I (P < .001, P = .001, and P = .001, respectively). The differences between NAC and control groups and between ML and NAC groups were only significant for mean lactate level (P < .001). CONCLUSION: The current study revealed that ML and NAC are potent antioxidants with similar efficacy in terms of reducing CABG related cardiac injury and oxidative stress with the dosage employed for the intervention.

Impact of cyclosporine A use in the prevention of reperfusion injury in acute myocardial infarction: A meta-analysis.

BACKGROUND: Reperfusion injury is an important limiting factor associated with revascularization in acute myocardial infarction (AMI). Various therapies have been tried in an attempt to prevent reperfusion injury, but the search has been elusive. The role of cyclosporine A (CsA) in the prevention of reperfusion injury in AMI is still not clear. The objective of this study was to find out whether CsA is beneficial in reducing reperfusion injury in acute ST elevation myocardial infarction. METHODS: We performed a systematic search of Pubmed, Scopus, clinicaltrial.gov, and Cochrane Database for randomized control trials (RCT) measuring the effect of CsA in AMI compared to a placebo. The Mantel-Haenszel method and random effect model were used to analyze the data. A total of 1,566 patients (776 in the CsA group and 790 in the placebo group), who participated in 5 RCTs were included in our meta-analysis. RESULTS: We did not find any significant differences between the CsA and placebo groups in terms of all-cause death (odds ratio [OR] 1.21, 95% confidence interval [CI] 0.78-1.87) and cardiovascular death (OR 1.05, 95% CI 0.66-2.49). Similarly, we did not find any significant differences in terms of cardiogenic shock, recurrent ischemia and myocardial infarction, heart failure and echocardiographic outcomes. CONCLUSIONS: Cyclosporine A is not helpful in preventing reperfusion injury in AMI.

Myocardial inflammation, injury and infarction during on-pump coronary artery bypass graft surgery.

BACKGROUND: Myocardial inflammation and injury occur during coronary artery bypass graft (CABG) surgery. We aimed to characterise these processes during routine CABG surgery to inform the diagnosis of type 5 myocardial infarction. METHODS: We assessed 87 patients with stable coronary artery disease who underwent elective CABG surgery. Myocardial inflammation, injury and infarction were assessed using plasma inflammatory biomarkers, high-sensitivity cardiac troponin I (hs-cTnI) and cardiac magnetic resonance imaging (CMR) using both late gadolinium enhancement (LGE) and ultrasmall superparamagnetic particles of iron oxide (USPIO). RESULTS: Systemic humoral inflammatory biomarkers (myeloperoxidase, interleukin-6, interleukin-8 and c-reactive protein) increased in the post-operative period with C-reactive protein concentrations plateauing by 48 h (median area under the curve (AUC) 7530 [interquartile range (IQR) 6088 to 9027] mg/L/48 h). USPIO-defined cellular myocardial inflammation ranged from normal to those associated with type 1 myocardial infarction (median 80.2 [IQR 67.4 to 104.8] /s). Plasma hs-cTnI concentrations rose by ≥50-fold from baseline and exceeded 10-fold the upper limit of normal in all patients. Two distinct patterns of peak cTnI release were observed at 6 and 24 h. After CABG surgery, new LGE was seen in 20% (n = 18) of patients although clinical peri-operative type 5 myocardial infarction was diagnosed in only 9% (n = 8). LGE was associated with the delayed 24-h peak in hs-cTnI and its magnitude correlated with AUC plasma hs-cTnI concentrations (r = 0.33, p < 0.01) but not systemic inflammation, myocardial inflammation or bypass time. CONCLUSION: Patients undergoing CABG surgery invariably have plasma hs-cTnI concentrations >10-fold the 99th centile upper limit of normal that is not attributable to inflammatory or ischemic injury alone. Peri-operative type 5 myocardial infarction is often unrecognised and is associated with a delayed 24-h peak in plasma hs-cTnI concentrations.

The effect of desflurane and propofol protocols on preconditioning.

BACKGROUND: Preconditioning is one of the most powerful mechanisms preventing the myocardial ischemic damage that occurs during coronary artery bypass grafting. OBJECTIVES: We aimed to investigate the effects of different propofol and/or desflurane administration protocols in terms of the prevention of ischaemia-reperfusion damage. MATERIAL AND METHODS: Ninety patients, aged > 18 years, American Society of Anesthesiologists (ASA) category III, scheduled to undergo primary elective coronary artery bypass grafting (CABG), were included in the study. During maintenance, the patients in group 1 (n = 30) received a propofol infusion (5-6 mg/kg/h) combined with a fentanyl infusion (3-5 mcg/kg/h); the patients in group 2 (n = 30) also received a propofol infusion (5-6 mg/kg/h) combined with a fentanyl infusion (3-5 mcg/kg/h), but they were also given 6% desflurane inhalation for 15 min both before cross-clamping of the aorta and after removal of the clamp; the patients in group 3 (n = 30) received a propofol infusion (2-3 mg/kg/h) combined with a fentanyl infusion (3-5 mcg/kg/h) and received the continuous 6% desflurane inhalation. Blood samples were drawn in the preoperative period (S1), during cardiopulmonary bypass, before cross-clamping the aorta (S2), after removal of the cross-clamp (S3) and 24 h after the operation (S4). RESULTS: All groups were similar in terms of age and BMI (p > 0.05). TNF-α levels were higher at S3 compared to S1, S2 and S4 (p > 0.001). The TNF-α levels at S4 were lower in group 3 than those in group 1 and group 2 (p < 0.05). In all groups, h-FABP levels showed an increase in S3 but were significantly lower at S4 (p < 0.05). In group 3, h-FABP levels at S2 and S3 were significantly lower than those in group 1 (p < 0.05). There was a moderate correlation between h-FABP and TNF-α levels (Spearman's rho = 0.472, p < 0.001). CONCLUSIONS: On the basis of the measurement of h-FABP and TNF-α, low-dose propofol and continuous desflurane inhalation provide more effective preconditioning than propofol alone or a short course of desflurane in patients undergoing CABG.

Mechanisms, management and future directions for reperfusion injury after acute myocardial infarction.

Animal models of sustained ischemia have shown exacerbation of myocardial injury during reperfusion, mediated largely by cytotoxic effects of free radical generation, complement activation, shifts in substrate use and inflammation. On the basis of current understanding of the pathogenesis of reperfusion injury, numerous therapies have shown a reduction in infarct size and improved ventricular function in animal models. Clinical trial experience has, however, so far been disappointing for the use of these therapies in patients with acute myocardial infarction (MI), being associated with no or inconsistent benefit to left-ventricular function, complications of MI or survival. The growing emphasis on early revascularization with primary coronary intervention and stenting in the management acute MI, with the potential for more complete drug delivery to injured myocardium, could provide greater opportunities for pharmacologic cardioprotection as adjunctive therapy in the future.