Canadian Journal of Cardiology 29 (2013) 1084e1089

Clinical Research

Remote Ischemic Preconditioning Reduces Myocardial Injury in Patients Undergoing Coronary Stent Implantation
Sheng Jie Luo, MMed,a,b Yu Jie Zhou, MD,a Dong Mei Shi, MD,a Hai Long Ge, MD,a Jian Long Wang, MMed,a and Rui Fang Liu, MMeda
a b

Department of Cardiology, An Zhen Hospital, Capital Medical University, Beijing, China

Capital Medical University School of Rehabilitation Medicine (China Rehabilitation Research Centre), Beijing, China

ABSTRACT
Background: Myocardial necrosis occurs frequently in elective percutaneous coronary intervention (PCI) and is associated with subsequent major adverse cardiovascular events (MACEs). This study assessed the protective effect of remote ischemic preconditioning (RIPC) in patients undergoing successful drug-eluting stent implantation with normal baseline troponin values. Methods: We analyzed 205 participants with normal baseline troponin values undergoing successful coronary stent implantation. Subjects were randomized to 2 groups: The RIPC group (n 101), whose members received RIPC (created by three 5-minute inations of a pneumatic medical tourniquet cuff to 200 mm Hg around the upper arm, interspersed with 5-minute intervals of reperfusion) < 2 hours before the PCI procedure, and the control group (n 104). Results: The primary outcomes were high sensitive cardiac troponin I (hscTnI) levels and incidence of myocardial infarction (MI 4a, dened as hscTnI > 0.20 ng/mL) at 16 hours after the PCI procedure. The median hscTnI at 16 hours after PCI was lower in the RIPC group compared with the unpreconditioned, control group (0.11 vs 0.21 ng/mL; P < 0.01). The incidence of MI 4a was lower in the RIPC

  RESUM E
crose myocardique apparat fre quemment lors Introduction : La ne e (ICP) non urgente et est dintervention coronarienne percutane e des e ve nements cardiovasculaires inde sirables majeurs associe quents. Cette e tude a e value  leffet protecteur du (CIM) subse conditionnement ische mique distance (PCID) chez les patients pre ayant des valeurs initiales normales de troponine qui ont subi avec . succs limplantation dun tuteur medicamente thodes : Nous avons analyse  205 patients ayant des valeurs iniMe tiales normales de troponine qui ont subi avec succs limplantation te  re partis au hasard en 2 dun tuteur coronarien. Les sujets ont e groupes : le groupe PCID (n 101), o les membres ont reu le PCID e  par 3 compressions de 5 minutes 200 mm Hg au moyen dun (cre te  entrecoupe es dintergarrot pneumatique autour du bras qui ont e valles de reperfusion de 5 minutes) < 2 heures avant lICP, et le moin (n 104). groupe te sultats : Les principaux critres de jugement ont e  te  les concentraRe tions de troponine cardiaque I hypersensible (hscTnl) et lincidence de ni par une hscTnI > 0,20 ng/ml) 16 linfarctus du myocarde (IM 4a, de diane 16 heures aprs lICP a e te  plus heures aprs lICP. La hscTnI me

According to the latest guidelines from the European Society of Cardiology/American College of Cardiology/American Heart Association/World Health Federation, myocardial infarction (MI) related to percutaneous coronary intervention (PCI), designated MI 4a, is dened as cardiac troponin I (cTnI) > 0.20 ng/mL (5 times the upper reference limit).1 Recent studies have demonstrated that PCI-related troponin elevation is associated with subsequent major adverse cardiovascular events (MACEs).2,3 Elective PCI is frequently associated with elevation of cTnI, and drug-eluting stent

Received for publication October 12, 2012. Accepted November 17, 2012. Corresponding author: Dr Yu Jie Zhou, Department of Cardiology, An Zhen Hospital, Capital Medical University, Anzhenli Avenue, Chao Yang District, Beijing 100029, China. E-mail: azcardiom@163.com See page 1089 for disclosure information.

implantation is associated with a higher incidence of periprocedural elevation of cTnI compared with bare metal stent implantation.2-4 Since 1986, when Murry et al. rst described the phenomenon of ischemic preconditioning,5 a host of studies have shown that ischemic preconditioning could reliably offer myocardial protection.6 Although preconditioning is one of the most powerful and reproducible phenomena in cardioprotection, it has not been readily translated into routine clinical use because of methodological hurdles. The major breakthrough in clinical applicability of preconditioning protection came with the discovery from Kharbanda et al. that transient limb ischemia provided cardiovascular protection in humans and animals.7 The idea of obtaining good myocardial protection with transient limb ischemia is highly attractive to clinicians because it requires nothing other than a blood pressure cuff or a pneumatic medical tourniquet. This single-centre, randomized controlled trial aimed to investigate the ability of remote ischemic preconditioning (RIPC) to

0828-282X/$ - see front matter 2013 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.cjca.2012.11.022

Luo et al. Remote Preconditioning Reduces Injury group compared with the control group (39% vs 54%, P < 0.05). Index of renal function showed no difference between the 2 groups at 16 hours after PCI (P > 0.05). Conclusion: RIPC reduced post-PCI TnI release and incidence of MI 4a in patients undergoing elective coronary stent implantation.

1085 moin sans faible dans le groupe PCID comparativement au groupe te conditionnement (0,11 vs 0,21 ng/ml; P < 0,01). Lincidence de pre te  plus faible dans le groupe PCID comparativement au lIM 4a a e moin (39 % vs 54 %, P < 0,05). Lindice de fonctionnement groupe te nal na montre  aucune diffe rence entre les 2 groupes 16 heures re aprs lICP (P < 0,05). duit la libe ration de la TnI aprs lICP et Conclusion : Le PCID a re lincidence dIM 4a chez les patients ayant subi limplantation dun tuteur coronarien.

reduce high sensitive cTnI (hscTnI) level and MI 4a incidence after elective PCI. Methods Identication and recruitment of participants Participants were identied from the waiting list for elective PCI between March 2012 and August 2012 and invited to participate in the trial before their angiography. All patients aged  18 years who were undergoing elective angiography as well as PCI and able to give informed consent were eligible for the trial. Exclusion criteria were (1) emergency PCI, (2) baseline troponin value  0.04 ng/mL, (3) nicorandil or glibenclamide use (preconditioning-mimetic and preconditioning-blocking medication, respectively), (4) patients who had some inability to cooperate with the trial, (5) those who could not give informed consent, and (6) second procedure of staged elective PCI in this hospitalization. The subjects received written information about the trial and, after conrmation of eligibility, were randomized to either the control treatment or the RIPC group. No changes were made to the clinical care of the patients enrolled in this trial. The institutional review board of Beijing An Zhen Hospital approved the study protocol, and the study conformed to the principles outlined in the Declaration of Helsinki. RIPC and control interventions At their admission to Beijing An Zhen Hospital, participants were instructed to avoid any strenuous activity that could provoke angina before their procedure. Consent was conrmed on the day of the procedure. Those participants randomized to RIPC had a pneumatic medical tourniquet cuff (width, 5 cm; length, 40 cm) placed around their upper arm at < 2 hours before the PCI procedure. The pneumatic medical cuff was inated to a pressure of 200 mm Hg for 5 minutes, followed by 5 minutes of deation to allow reperfusion. This procedure was repeated 3 times. Control participants did not experience this procedure of transient upper-limb ischemia. Patients in both groups had a conventional single-use medical tourniquet around the wrist for closing the radial artery puncture site for 6 hours after PCI. The interventionists were blinded to the study allocation of the participants. PCI PCI was performed via a radial arterial (right, 198; left, 7) approach with 3.5F or 4F guiding catheters. All participants received statins before and after admission, and all participants received aspirin 300 mg and clopidogrel 300 mg, followed

with 100 to 300 mg aspirin and 75 to 150 mg clopidogrel daily, according to their platelet aggregation test after admission, and were anticoagulated with a heparin bolus (70-100 U/kg) after arterial sheath insertion. Glycoprotein IIb/IIIa antagonist (tiroban) was administered according to the judgement of the interventionists. Ultravist (iopromide; Bayer Schering Pharmaceuticals, Berlin, Germany) was used as the contrast in all cases. All other medication was given at the discretion of the attending physician, and the PCI strategy was at the discussion and discretion of the treating interventional cardiologists group according to conventional practice. All the participants received second-generation drug-eluting stents. Hydration procedure Patients were hydrated with intravenous saline infusion 1 mL/kg/hr 12 hours before and 12 hours post contrast and encouraged to drink lots of water after PCI (except those with left ventricular dysfunction). Outcome measurements Biochemistry. Venous blood samples were taken on the morning of admission to the hospital, when subjects had been in a fasting state for more than 10 hours (baseline), and again 16 hours after PCI for serum hscTnI and creatine. HscTnI was analyzed with an automated immunoassay (UniCel DxI 800 Access AccuTnI chemiluminescence method, Beckman Coulter, Fullerton, CA, USA). The 99th percentile of the hscTnI level in a reference population (upper reference limit) of healthy volunteers was below the lower limit of detection of 0.04 ng/mL. The variation coefcient, a measure of precision within the analytical range, is < 10%. The analytical range was 0.01 to 102 ng/mL, with an assay sensitivity of 0.006 ng/ mL. Serum creatine was analyzed with an Olympus AU5400 biochemistry analyzer (Pureauto S CRE-N method, Tokyo, Japan). An estimate of the glomerular ltration rate (expressed as millilitres per minute per 1.73 m2 of body surface area) was calculated with the modied glomerular ltration rate estimating equation for the Chinese population: 175 (serum creatinine in milligrams per deciliter)1.234 (age in years)0.179 ( 0.79 if patient is a woman).8 A serum creatinine increase of > 25% over the baseline value or by more than 44.2 mmol/L was prospectively considered as a clinically signicant decline in renal function at 16 hours. All biochemical measurements were made without knowledge of group allocation.

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Angiographic and PCI-related parameters. The target vessel characteristics and the nal result of PCI (predilation, diameter of stent, length of stent, and number of stents, postdilation) were noted. Preprocedural and postprocedural assessments of coronary blood ow (thrombolysis in myocardial infarction ow score) were performed as described by Gibson et al.9 Other angiographic complications (artery dissection, perforation, or jailed side branch with compromised ow) occurring during PCI were noted, as were the radiation exposure and total uoroscopic screening time and contrast dose. Arterial blood pressure was measured by monitoring intra-aortic pressure through guiding catheter without guide wire. Heart rate was measured by real-time electrocardiographic monitoring at the moment of balloon ination. Occurrences of angina (chest pain, tightness, and similar symptoms of myocardial ischemia) during PCI were assessed. Specic objectives The primary objectives were to assess whether RIPC < 2 hours before elective PCI procedure reduced hscTnI level and incidence of MI 4a at 16 hours after PCI. Secondary outcome was the index of renal function at 16 hours after PCI procedure. Randomization Participants were randomly allocated to the treatment group by a simple digital method of randomization. Statistical methods and analysis Statistical analysis was performed with SPSS version 17.0 software (SPSS Inc). The distribution of hscTnI observed was abnormal. Therefore, analysis was based on nonparametric analysis with the Mann-Whitney test. In addition, data were analyzed by categorizing the hscTnI data into those with a dened MI 4a and those with hscTnI below certain times of the upper reference limit. Continuous variables were summarized as mean standard deviation or as median (quartiles) and compared by the Student t test or a Mann-Whitney test, as appropriate. Categorical data were expressed as numbers (percentages) and compared by means of a c2 test. A value of P < 0.05 was considered signicant. Results Subjects A total of 205 patients were recruited and analyzed. RIPC was successfully administered to 101 participants without complication. Demographic and clinical details showed no difference between control and RIPC groups (Table 1). PCI procedure There were no major PCI-related complications in either group (death or urgent revascularization within the rst 24 hours). Angiographic and PCI-related parameters, clinical details during procedure, and complication rates were similar in both groups (Table 2).

Primary outcomes After PCI, the median hscTnI level at 16 hours was signicantly lower in the RIPC group than in the control group (0.11 vs 0.21 ng/mL, P < 0.01; Table 3). In addition, more participants who received RIPC had hscTnI levels < 0.08 ng/mL, < 0.12 ng/mL, < 0.16 ng /mL, < 0.20 ng/ mL, < 0.24 ng/mL, < 0.28 ng/mL, and < 0.32 ng/mL, respectively, when compared with the control group. Fewer participants in the RIPC group (39%) had an MI 4a than in the control group (54%; Table 3). Secondary outcomes

mmol/L. The number of participants with an increase in

No participant had a serum creatinine increase > 44.2

serum creatinine > 25% was not signicantly different between the control (1 case) and the RIPC (2 cases) group at 16 hours after PCI (P 0.544). The estimated glomerular ltration rate was similar in both groups after PCI (Table 3).

Discussion The present study demonstrated that RIPC, created by repeated transient upper-limb ischemia, which was rstly reported in human by Kharbanda et al.,7 signicantly reduced post-PCI hscTnI level and incidence of MI 4a in patients undergoing implantation of coronary drug-eluting stents. PCI-related myocardial necrosis is due to MI both downstream of the stented lesion and adjacent to the implanted stent.10,11 Microembolization of plaque debris and sidebranch occlusion during the PCI procedure have been proposed as the most likely causes of myocardial necrosis.12 Myocardial necrosis could also be associated with ischemia and reperfusion injury after stent implantation and sudden blood supply of ischemic myocardial tissues.13 PCI-related myocardial necrosis was associated with a worse prognosis, especially in individuals with the most markedly elevated cTnI level.2,3 An earlier study established that post-PCI elevation of cTnI level > 5 times the baseline value limit, which was specically identied as MI 4a in the latest guideline,1 was an independent predictor of a composite of death, MI, and revascularization at 1 year.14 In another study, post-PCI cTnI elevation was identied as a predictor of increased long-term mortality and MI.15 The initial study suggesting that one vascular ischemia could precondition another vascular bed came from Przyklenk et al. in 1993.16 This basic concept was followed by subsequent animal studies suggesting that ischemia of remote organs could confer protection to the ischemic myocardium. In 2002, Kharbanda et al. reported the study suggesting that transient limb ischemia could remotely prevent ischemia and reperfusion-induced endothelial dysfunction in humans and reduce the extent of myocardial infarction in experimental animals.7 In 2009, Hoole et al.17 extended the concept of RIPC to show that RIPC induced by three 5-minute blood pressure cuff inations to 200 mm Hg around the upper arm, interspersed with 5 minutes of reperfusion, before arrival in the catheterization laboratory for stenting signicantly reduced median troponin I concentrations at 24 hours (0.06 ng/mL) compared with control patients (0.16 ng/mL; P < 0.04). A recently published study showed that two

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Table 1. Demographic and clinical data of participants randomized to remote ischemic preconditioning and control groups before percutaneous coronary intervention Variables Demographics Age, years Men, n (%) Risk factors Hypertension, n (%) Diabetes mellitus, n (%) LDL, mmol/L, mean SD Active or ex-smoker, n (%) BMI, kg/m2 Clinical details LVEF, % Previous MI, n (%) Previous CABG, n (%) Previous stent implantation, n (%) Time since the latest angina before PCI <24 hours, n (%) 24 hours, <72hours, n (%) 72 hours, n (%) Angina CCS grade III/IV, n (%) GFR, mL/min/1.73 m2 hsCRP, mg/L Medications, n (%) b-Blockers ACEI/ARB Trimetazidine Tiroban Control (n 104) 59.3 9.5 78 (75) 67 (64) 31 (30) 2.56 1.00 70 (67) 26.3 3.2 64 9 20 (19) 2 (1.9) 25 (17) 23 (22) 16 (15) 65 (63) 59 (57) 100 20 2.60 4.46 84 58 39 54 (81) (56) (38) (52) RIPC (n 101) 59.2 10.3 78 (77) 68 (67) 26 (26) 2.45 1.00 64 (63) 26.6 3.2 64 7 24 (24) 4 (4.0) 22 (14) 21 (21) 16 (16) 64 (63) 54 (54) 101 20 2.42 3.78 85 61 39 51 (84) (60) (39) (51) P 0.97 0.71 0.66 0.52 0.42 0.55 0.52 0.84 0.43 0.39 0.70 0.82 0.93 0.90 0.64 0.49 0.76 0.52 0.50 0.87 0.84

ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker; BMI, body mass index; CABG, coronary artery bypass graft; CCS, Canadian Cardiology Society; GFR, glomerular ltration rate; hsCRP, high sensitive C-reactive protein; LDL, low density lipoprotein; LVEF, left ventricular ejection fraction; MI, myocardial infarction; PCI, percutaneous coronary intervention; RIPC, remote ischemic preconditioning.

5-minute lower limb ischemias before PCI reduced the absolute risk of postprocedure cardiomyocyte necrosis by 27.5%.18 The results of our study are consistent with the above research and suggest that RIPC is a safe, effective, and noninvasive strategy for providing cardioprotection when myocardial necrosis is expected. Although the present and above-mentioned studies demonstrated the cardioprotective effect of RIPC, Prasad et al. reached a different conclusion. In Prasad et al.s study,19 RIPC immediately prior to PCI did not offer cardioprotection. The potential reasons for Prasad et al.s nding include the following: First, their sample size was smaller than ours, raising the possibility of a false negative result (type II error). Second, Prasad et al. induced ischemia-reperfusion by using 3-minute cycles as opposed to 5-minute cycles, resulting in a shorter period of preconditioning. Third, they performed cuff inations immediately preceding PCI as opposed to less than 2 hours before PCI, which raises the possibility that there might be a delay in the onset of cardioprotection. In recent years, more and more individuals are undergoing coronary stent implantation in China. The clinical application of RIPC to attenuate myocardial injury in a therapeutic procedure is highly intriguing, particularly to clinicians in interventional centres. One might argue whether there is any real advantage of RIPC involving a limb compared with local preconditioning to condition the ischemic myocardium in the setting of PCI. Local preconditioning with repeated balloon ination and deation, although demonstrated to be effective, itself could potentially contribute to the risks of severe ischemic arrhythmia such as ventricular brillation, mechanic trauma to vascular intima, increased procedure time,

showering of the distal myocardium with microemboli of atherosclerotic and thrombotic debris, and provocation of angina. Furthermore, repeated mechanical stimuli to the underlying artery might worsen endothelial dysfunction and contribute to subsequent restenosis and in-stent thrombosis. Transient upper-limb ischemia was shown in our study to be well tolerated and to have no adverse effects. The approach of creating preconditioning by pneumatic medical tourniquet to cause transient ischemia of the upper limb is noninvasive and technically easy. Moreover, it requires no expensive medicine or equipmentda trained health care professional with a pneumatic medical tourniquet can perform it. The actual cardioprotective mechanism of RIPC is as yet not fully elucidated. Theories are multifactorial and may include regulation of neurogenic pathways; humoral substances such as adenosine and bradykinin; elaboration of endogenous myocardial mediators including erythropoietin, nitric oxide, delta 1-opioid, and free radicals; and reduction of myocardial inammatory cytokine production, including tumour necrosis factor-a, attenuation of ischemia/reperfusioninduced endothelial dysfunction, and activation of the adenosine triphosphate-sensitive potassium channel.20,21 Although this mechanism has been proven mainly in animal models, an increasing number of clinical studies are proposing possible analogous benets in humans. It is difcult to obtain funding support for studies involving this simple and commercialinterest-free approach if no new pharmacologic agent or device is required, and as yet no large, adequately powered study has been conducted to demonstrate the effect of RIPC in reducing long-term MACEs, although RIPC has already shown promise in a limited number of clinical trials. In our

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Table 2. Angiographic and periprocedural data of participants randomized to remote ischemic preconditioning and control groups Variables Control (n 104) RIPC (n 101) P

Angiographic parameters Target vessel, n (%) LM 3 (3) LAD 54 (52) LCx 21 (20) RCA 35 (34) Side branch 25 (24) Combined 28 (27) CTO, n (%) 12 (12) Subtotal occlusion, n (%) 8 (8) PCI-related parameters Predilation 95 (91) Postdilation 82 (79) Mean number of stents 1.63 0.95 per case Mean stent diameter 2.99 0.72 per case, mm Mean stent length 41 25 per case, mm Screen time, min 16 11 Radiation dose, cGy/cm2 29.4 39.6 Contrast, mL 145 41 Clinical state during angioplasty SBP, mm Hg 135 20 DBP, mm Hg 78 11 HR, beats per minute 70 14 Onset of angina, n (%) 54 (52) Complications, n (%) Dissection 10 (10) Jailed side branch 6 (6) (TIMI 0/1) After stent implantation, n (%) TIMI ow score 0-2 5 (5) 3 99 (95%)

6 51 20 40 20 29 19 9

(6) (51) (20) (40) (20) (29) (19) (9)

0.29 0.84 0.94 0.38 0.46 0.78 0.15 0.75 0.76 0.81 0.93 0.25 0.74 0.66 0.38 0.15 0.13 0.78 0.27 0.18 0.60 0.39

91 (90) 81 (80) 1.62 0.93 2.86 0.91 42 25 17 9 24.9 32.4 154 46 131 17 78 11 68 10 43 (43) 12 (12) 9 (9)

Contrast-induced nephropathy (CIN) is an important and common complication after PCI.22 The most recognized risk factor for development of CIN is baseline renal impairment.23 The recently published study from Er et al. showed that RIPC before contrast medium use prevented CIN in high-risk patients.24 In our study, the incidence of CIN showed no difference between the control and the RIPC group (1% vs 2%, P 0.544). The potential reasons for our ndings include the following: First, most of our participants had normal baseline renal function before PCI. Second, more CIN occurred at 48 hours than at 16 hours after PCI. An adequately powered trial is merited to establish the effect of RIPC on prevention of CIN. Clinical implications We have demonstrated that the simple, cheap, safe, and well-tolerated application of RIPC in a busy PCI centre is feasible and can provide urgent myocardial protection for patients undergoing elective PCI, which may offer prognostic benet. RIPC appears to be one of the few nonpharmacologic and noninvasive therapeutic methods that can effectively reduce the amount of ischemic myocardial necrosis. Study limitations Because it is difcult to continuously monitor troponin release after PCI, the above-mentioned studies obtained the measurement at 24 hours after PCI.17,18 It is generally accepted that the maximum concentration occurs between 12 and 24 hours after myonecrosis.25 Although the measurement was not obtained in an interval of every 2 to 4 hours, our choice of a single sample at 16 hours was in the middle of the time window of peak release and probably nearer to the true peak level than others samples at 24 hours. Patients with staged elective PCI for complex lesions were common in our centre. And patients undergoing a second elective PCI was excluded from this study because the rst myocardial injury from the last PCI might affect the second myocardial injury. Subsequent MACEs may result from the second PCI, so outcome of the follow-up was not analyzed. During PCI, predilation and postdilation stimulus from balloon ination was probably able to provide local preconditioning and postconditioning protection in the setting of balloon angioplasty. This means that the control group also received some additional protection by these mechanisms. We could not dene the area of myocardium at risk during PCI.

2 (2) 99 (98%)

0.27

CTO, chronic total occlusion; DBP, diastolic blood pressure; HR, heart rate; LAD, left anterior descending artery; LCx, left circumex artery; LM, left main artery; PCI, percutaneous coronary intervention; RCA, right coronary artery; RIPC, remote ischemic preconditioning; SBP, systolic blood pressure; TIMI, thrombolysis in myocardial infarction.

real-world study, incidence of MI 4a was reduced from 54% in the control group to 39% in the RIPC group; this means that 15 per 100 patients undergoing elective PCI were saved from MI 4a. Therefore, further large-scale, multicentre studies are called for in order to endorse the clinical usefulness of RIPC in the future. If rm evidence can be obtained that shows the effectiveness of this noninvasive approach, it would help many sick patients suffering from cardiovascular diseases.

Table 3. Serum high sensitive cardiac troponin I and eGFR at 16 hours after percutaneous coronary intervention Variables HscTnI, median (IQR), ng/mL HscTnI < 0.08 ng/mL, n (%) HscTnI < 0.12 ng/mL, n (%) HscTnI < 0.16 ng/mL, n (%) HscTnI < 0.20 ng/mL, n (%) HscTnI > 0.20 ng/mL, n (%) HscTnI < 0.24 ng/mL, n (%) HscTnI < 0.28 ng/mL, n (%) HscTnI < 0.32 ng/mL, n (%) eGFR, mL/min/1.73 m2 Serum creatinine > 25%: increase, n (%) Control (n 104) 0.21 (0.09, 0.63) 20 (19) 32 (31) 40 (39) 48 (46) 57 (54) 54 (52) 58 (56) 60 (58) 101 22 1 (1) RIPC (n 101) 0.11 (0.05,0.38) 35 (35) 54 (54) 58 (57) 62 (61) 39 (39) 71 (70) 73 (72) 74 (73) 102 21 2 (2) P 0.004 0.013 0.001 0.007 0.029 0.029 0.007 0.014 0.019 0.664 0.544

eGFR, estimated glomerular ltration rate; HscTnI, high sensitive cardiac troponin I; IQR, interquartile range; RIPC, remote ischemic preconditioning.

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However, the surrogate measures to ascertain the extent of myocardium subtended by the vessel undergoing intervention did not differ between the two groups. Although the RIPC was administered before PCI, the time from the rst cuff ination to the rst balloon dilation was unforeseen and frequently delayed. It is possible that if the cuff-to-balloon time had been shorter, the cardioprotection observed would have been better. Conclusions RIPC reduced post-PCI troponin release and incidence of MI 4a in patients undergoing elective coronary stent implantation. Further large and adequately powered studies are needed to endorse the clinical usefulness of RIPC in the future. Acknowledgements We thank the study participants and staff at Beijing An Zhen Hospital. Funding Sources This work was funded by the Capital Foundation of Medical Developments (TCM) (No. SF-2009-II-12) and Beijing Nova program (No. 2006B02). Disclosures The authors have no potential conicts of interest to report. References
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