Presence Of Preinfarction Angina Research Articles

Ticagrelor Loading on ST-Elevation Myocardial Infarction: Interaction With Prodromal Angina on Infarct Size and Clinical Events.

Ticagrelor might reduce infarct size by exerting a more potent antiplatelet effect or by promoting a potential conditioning stimulus in ST-elevation myocardial infarction (STEMI) patients. Pre-infarction angina (PIA) is an effective preconditioning stimulus that reduces ischemia-reperfusion injury. Because little is known on the interaction of PIA in STEMI-patients loaded with ticagrelor, we sought to determine if patients loaded with ticagrelor had improved clinical outcomes as compared to clopidogrel and to study if it is modulated by the presence of PIA. From 1272 STEMI patients submitted to primary percutaneous coronary intervention and treated with clopidogrel or ticagrelor from January 2008 to December 2018, 826 were analyzed after propensity score matching. Infarct size was estimated using peak creatine kinase (CK) and troponin T (TnT), and clinical impact was evaluated through cumulative major cardiac and cerebrovascular events (MACCE) at 1-year follow-up. Matched patients and their interaction with PIA were analyzed. Patients loaded with ticagrelor had lower peak CK [1405.50 U/L (730.25-2491.00), P < .001] and TnT [3.58 ng/mL (1.73-6.59), P < .001)], regardless of PIA. The presence of PIA was associated with lower CK (P = .030), but not TnT (P = .097). There was no interaction between ticagrelor loading and PIA (P = .788 for TnT and P = .555 for CK). There was no difference in MACCE incidence between clopidogrel or ticagrelor loading (P = .129). Cumulative survival was also similar between clopidogrel or ticagrelor, regardless of PIA (P = .103). Ticagrelor reduced infarct sizes independently and without a synergic effect with PIA. Despite reducing infarct size, clinical outcomes were similar across both groups.

Relation between Preinfarction Angina and Coronary Collateral Circulation in Patients with Acute Myocardial Infarction

Background : Coronary collateral circulation conduits an alternative blood flow to the ischemic myocardium in the setting of coronary artery occlusion which can prevent the infarction area to extend more widely. Well-developed coronary collaterals are closely related with the presence of preinfarction angina. However, the duration of preinfarction angina which can induce well-developed coronary collateralization is in controversy. The aim of this study was to evaluate the relation between duration of preinfarction angina and coronary collaterals circulation in patients with acute myocardial infarction. Methods : This cross-sectional study was conducted from May to November 2013 in Dr. Hasan Sadikin General Hospital, Bandung, Indonesia. Seventy three acute myocardial infarction (AMI) patients were included in the study. The patients were divided into Group 1 (<7 days) and Group 2 (≥7 days) based on their preinfarction angina history. The coronary collaterals were assesed and graded as good (Rentrop score 2−3) and poor (Rentrop score 0−1).Statistical analysis was performed using the chi-square test. Result : The presence of a well-developed coronary collateral was not significantly different in <7days than ≥7 days duration of preinfarction angina [50.8% v 75.0%, p=0.124]. Conclusions : There is no relation between the duration of preinfarction angina and coronary collaterals circulation in patients with acute myocardial infarction. [ AMJ .2016;3(1):28–33] DOI: 10.15850/amj.v3n1.709

Pre-Infarction Angina and Outcomes in Non-ST-Segment Elevation Myocardial Infarction: Data from the RICO Survey

BackgroundThe presence of pre-infarction angina (PIA) has been shown to confer cardioprotection after ST-segment elevation myocardial infarction (STEMI). However, the clinical impact of PIA in non-ST-segment elevation myocardial infarction (NSTEMI) remains to be determined.Methods and ResultsFrom the obseRvatoire des Infarctus de Côte d'Or (RICO) survey, 1541 consecutive patients admitted in intensive care unit with a first NSTEMI were included. Patients who experienced chest pain <7 days before the episode leading to admission were defined as having PIA and were compared with patients without PIA. Incidence of in-hospital ventricular arrhythmias (VAs), heart failure and 30-day mortality were collected. Among the 1541 patients included in the study, 693 (45%) patients presented PIA. PIA was associated with a lower creatine kinase peak, as a reflection of infarct size (231(109–520) vs. 322(148–844) IU/L, p<0.001) when compared with the group without PIA. Patients with PIA developed fewer VAs, by 3 fold (1.6% vs. 4.0%, p = 0.008) and heart failure (18.0% vs. 22.4%, p = 0.040) during the hospital stay. Overall, there was a decrease in early CV events by 26% in patients with PIA (19.2% vs. 25.9%, p = 0.002). By multivariate analysis, PIA remained independently associated with less VAs.ConclusionFrom this large contemporary prospective study, our work showed that PIA is very frequent in patients admitted for a first NSTEMI, and is associated with a better prognosis, including reduced infarct size and in hospital VAs. Accordingly, protecting the myocardium by ischemic or pharmacological conditioning not only in STEMI, but in all type of MI merits further attention.

Association between preinfarction angina and coronary artery ectasia in the acute myocardial infarction

Objective The objective of this study was to investigate the predictors of preinfarction angina (PA) and to show the association between PA and coronary ectasia (CE).Methods A total of 222 patients with acute myocardial infarction were included. All patients were treated with primary coronary intervention and interviewed by the staff physicians within 24 h of presentation after reperfusion had succeeded. The patients were classified according to the presence of PA and CE. All groups were compared statistically according to their clinicodemographic characteristics and angiographic results. Regression analysis was performed to show the predictors of PA.Results Half of the patients were defined as preinfarction angina (48.2 %) and the success rate of primary coronary intervention did not differ statistically in the PA present group. More than half of the patients had multivessel disease and coronary ectasia was found in the 11.7%. The right coronary artery (RCA) was the most common localization for ectasia and 61.5% of the ectatic vessels were also infarct-related. Diabetes mellitus, hypertension and previous coronary heart disease were slightly more common in the PA present group. In the regression analysis, coronary ectasia, multivessel disease and previously diagnosed coronary artery disease were independent predictors of PA (P= 0.001, P= 0.01 and P= 0.03, respectively)Conclusions CE is more common in patients with PA and more than half of the patients showed CE in the infarct-related vessel. CE and multivessel disease are independent predictors of PA. The success rate of primary coronary intervention in ectatic infarct-related vessels did not diff er in the PA group.

Factors associated with use of emergency medical service for acute myocardial infarction in Beijing

To examine the current ambulance transport rates and ascertain factors associated with use of emergency medical service (EMS) in patients with acute myocardial infarction (AMI) in Beijing. Between January 1 and December 31, 2006, a cross-sectional and multicenter survey was conducted in 19 hospitals in Beijing and included patients with ST-elevation myocardial infarction (STEMI) admitted within 24 hours of onset of symptoms. Data were collected by structured interviews and medical records review within 1 week after admission. Patients were categorized into the EMS group and the self-transport group according to their modes of transport to the initial hospital. Data were analyzed by descriptive statistics, univariate and multivariate logistic analysis. Of the 789 patients with STEMI, only 260 (33.0%) arrived at the initial hospital by EMS, while the remaining 529 (77.0%) relied on self-transport. Multivariate logistic analysis showed that age >/= 65 years (OR: 1.530, 95%CI: 1.050 - 2.230, P = 0.027), higher education level (OR: 2.032, 95%CI: 1.257 - 3.284, P = 0.004), history of coronary artery disease (OR: 0.474, 95%CI: 1.049 - 2.458, P = 0.029), unbearable symptoms (OR: 0.592, 95%CI: 1.090 - 2.520, P = 0.008), anxiety (OR: 0.760, 95%CI: 1.238 - 3.695, P = 0.006) and attribution of symptoms to cardiac origin (OR: 0.402, 95%CI: 1.020 - 2.171, P = 0.041) were independent predictors of EMS use. However, presence of pre-infarction angina significantly decreased the likelihood of using EMS (OR: 0.626, 95%CI: 0.431 - 0.907, P = 0.013). Only one-third of patients with STEMI arrived at the hospital by EMS in Beijing. Demographics, history of coronary artery disease, symptoms characteristics and cognitive factors of patients were associated with the EMS use.

013 Pre-infarction angina and cardiovascular complications in non ST segment elevation myocardial infarction: Data from the RICO survey

The presence of preinfarction angina (PIA) has been shown to confer cardioprotection after ST segment elevation myocardial infarction (MI). However, the impact of PIA in non ST segment elevation (NSTEMI) remains to be determined. From the obseRvatoire des Infarctus de Côte d’Or (RICO) survey, 1541 consecutive patients admitted in intensive care unit with a first NSTEMI were included in the study. Patients who experienced chest pain <7 days before the episode leading to admission were defined as having PIA. Patients presenting with PIA were compared with patients without PIA. Prehospital resuscitated cardiac arrest (RCA), incidence of in-hospital ventricular arrhythmias (VA), heart failure (Killip class>1) and 30-day mortality were collected. Among the 1541 patients included in the study, 693 patients presented PIA. Baseline clinical characteristics were similar for the 2 groups. There was no significant difference for the GRACE risk score (p=0.942). However, PIA was associated with a lower creatine kinase peak, as a reflect of infarct size (231(109-520) vs. 322(148-844) IU/L, p<0.001) and a lower rate of patients with a troponin peak >100 ULN (31% vs. 39%, p<0.001) when compared with the group without PIA. Patients with PIA were admitted with markedly less pre-hospital RCA (0.6% vs. 3.4%, p<0.001) and developed fewer VA (1.6% vs. 4.0%, p=0.008) and heart failure (18.2% vs. 22.6%, p=0.037) during the hospital stay. There was a trend toward a decrease in 30-day death in patients with PIA (4.3% vs 6.1%, p=0.146). From this large contemporary observational study, PIA is observed in almost 50% of patients admitted for a first NSTEMI. In such patients, PIA is associated with less pre-hospital RCA, and decreased in-hospital VA and heart failure. These findings suggest that identifying lack of PIA in patients admitted for a NSTEMI could help for early risk stratification, in particular for ventricular arrhythmias.

Factors influencing ambulance use in patients with ST-elevation myocardial infarction in Beijing, China

Background Emergency medical service plays a key role in the early recognition and treatment of ST-elevation myocardial infarction (STEMI), but studies indicate that the patients experiencing STEMI symptoms often fail to call an ambulance as recommended. This study aimed to examine the current ambulance transport frequency and ascertain predictors and reasons for not choosing ambulance transportation by the patients with STEMI in Beijing. Methods A prospective, cross-sectional survey was conducted from January 1, 2006 through until June 30, 2007 in two tertiary hospitals in Beijing and included consecutive patients with STEMI admitted within 24 hours of onset of symptoms. Data were collected by structured interviews and medical records review. Results Of the 572 patients, only 172 (30.1%) used an ambulance, and the remaining 400 (69.9%) presented by self-transport. Multivariate analysis showed that age &lt;65 years (OR: 1.220; 95% CI: 1.001–2.043), lower education level (OR: 1.582; 95% CI: 1.003–2.512), presence of pre-infarction angina (OR: 1.595; 95% CI: 1.086–2.347), and attribution of symptoms to non-cardiac origin (OR: 1.519; 95% CI: 1.011–2.284) were independent predictors for not using an ambulance. However, history of coronary artery disease (CAD), dyspnea, perceiving symptoms to be serious, and knowing the meaning of cardiopulmonary resuscitation appeared to be independent predictors of ambulance use. The main reasons for not using an ambulance were convenience and quickness of self-transport and the decreased severity of symptoms. Conclusions A large proportion of patients in Beijing do not call for an ambulance after onset of STEMI symptoms. Several factors including demographics, previous CAD, symptoms and cognitive factors of patients are associated with the ambulance use. The public should be educated that an ambulance is not merely a transportation modality and that it also provides rapid diagnosis and treatment.

Angina pré-infarto na evolução intra-hospitalar de pacientes idosos com infarto agudo do miocárdio

Preinfarction angina (PIA) may be a marker of ischemic preconditioning. A decrease in infarct size, ventricular remodeling, congestive heart failure, cardiogenic shock or death was demonstrated in the presence of preinfarction angina. These findings were more evident in adults, but not in the elderly. To assess the relationship between PIA and the clinical course of elderly patients with acute myocardial infarction (AMI). This was a case-series study with a comparison group. A total of 36 patients with ST-segment elevation AMI were included in the study and divided into two groups: group A (21 patients with PIA) and group B (15 patients without PIA). Mean age of the study population was 70.5 years, and there was a predominance of males (73%). Mean body mass index was 25.3 Kg/m2. Hypertension was present in 77.8%, diabetes in 27.8% and dyslipidemia in 32.4%. Type-A chest pain was reported by 71.4% of patients, and the majority of them (72.2%) were in Killip class I. Clinical endpoints for groups A and B were as follows: postinfarction angina 9.5% versus 20%, p = 0.630; heart failure 23.8% versus 13.3%, p = 0.674; urgent revascularization 4.8% versus 6.7%, p = 1; and cardiac arrhythmia 0% versus 6.7%, p = 0.417. There was no case of reinfarction, cardiogenic shock or death within 30 days of follow up in either group. In this case series, preinfarction angina was not associated with better clinical course in elderly patients with AMI.

In-Hospital Mortality and Early Preinfarction Angina: a Meta-Analysis of Published Studies

The occurrence of preinfarction angina (PA) reduces the extent of myocardial necrosis, increases the volume of viable myocardium, and improves left ventricular function. However, there is no agreement about the effect of PA on mortality. The objective of this study was to determine whether PA is associated with in-hospital mortality. A meta-analysis (fixed effects model) of all published reports evaluating in-hospital mortality in patients with acute myocardial infarction according to the presence or absence of PA was performed. PA was defined as the occurrence of angina in the 24 hours before onset of the infarction. We searched the Medline and Embase databases in June 2004 using <<preinfarction angina or prodromal angina and mortality>> as search terms. Six studies involving a total of 3497 patients were finally identified. Only one study reported that PA had a statistically significant beneficial effect on in-hospital mortality. However, combining the data showed that the presence of PA was associated with a significant decrease in the probability of in-hospital death (odds ratio=0.61; 95% CI: 0.48-0.78; P<.0001. We did not detect any significant heterogeneity between the studies (chi2=5.92; P=.31). The occurrence of preinfarction angina in the 24 hours before the onset of myocardial infarction was associated with a significant reduction in in-hospital mortality of 39%.

Effect of pre-infarction angina on ventricular late potentials in patients with acute myocardial infarction and successful thrombolysis

Objective — Pre-infarction angina is considered as a good clinical model of ischaemic preconditioning which facilitates myocardial protection. Late potentials (LP) have prognostic significance following acute myocardial infarction (AMI). It is also well established that thrombolytic therapy reduces the incidence of LP. Our aim was to evaluate the relationship between pre-infarction angina and LP in patients receiving successful thrombolytic therapy.Methods and results — We prospectively studied 55 patients presenting with AMI (< 6 hours). All patients received thrombolytic therapy and were evaluated with coronary angiography at predischarge. Signal-averaged recordings (SAECG) were obtained serially prior to thrombolysis, 48 hours after and 10 days later. Pre-infarction angina was present in 14 (25%) patients.There were no significant differences between the clinical characteristics and angiographic findings of the groups. Baseline SAECG parameters of the groups were also similar. After thrombolysis, the 48th hour values of LAS (the duration of the terminal low amplitude signals), and both the 10th day values of LAS and RMS (root mean square voltage of the last 40 ms of the QRS) were significantly better in the pre-infarction angina group. The mean filtered QRS duration and RMS 40 values changed significantly at the 10th day recordings of patients with pre-infarction angina [QRS duration, 110±34 ms before to 91±11 ms after (p = 0.039); RMS 40, 40±17μV before to 50±14μV after (p = 0.02)].The incidence of LP significantly decreased after thrombolytic therapy in the pre-infarction angina group, however, this change was not observed in patients without angina.Conclusion — Presence of pre-infarction angina reduces the incidence of LP following thrombolysis in AMI. This might be explained by the possible beneficial effect of ischaemic preconditioning on the arrhythmogenic substrate.

Reduced microvascular and myocardial damage in patients with acute myocardial infarction and preinfarction angina.

After acute myocardial infarction, the presence of ischemic preconditioning as a result of preinfarction angina has a protective role, limiting necrosis extent and guaranteeing greater myocardial functional recovery. The relationship between preinfarction angina, microvascular reflow, and myocardial function is poorly known. We hypothesized that after acute myocardial infarction patients with preinfarction angina have both microvascular integrity and myocardial function preservation. In 51 patients with a first acute myocardial infarction, we noninvasively assessed microvascular perfusion and coronary flow reserve with intravenous myocardial contrast echocardiography and investigated myocardial contractile recovery with low-dose dobutamine and 90-day follow-up echocardiography. Typical angina was present in 25 patients and absent in 26 patients during the 7 days preceding the myocardial infarction. Compared with those patients without preinfarction angina, patients with preinfarction angina showed a greater microvascular reflow extent and coronary flow reserve (respectively, 25.2% +/- 22.8% vs 48.3% +/- 23.3%, P <.05, and 3.44 +/- 0.75 vs 1.95 +/- 0.67, P <.0001), a better regional myocardial function, as expressed with wall motion score index in the risk area at dobutamine (1.67 +/- 0.61 vs 2.10 +/- 0.43, P <.005) and at follow-up (1.72 +/- 0.56 vs 2.22 +/- 0.40, P <.0001) echocardiogram, despite being similar in the first echocardiogram (2.60 +/- 0.28 vs 2.63 +/- 0.28, P = not significant), and significantly less pronounced left ventricular dilation at follow-up. Presence of preinfarction angina, because of the preconditioning effect, reduces myocardial damage and favors myocardial viability, limiting left ventricular remodeling. This beneficial effect seems to be at least partly mediated by the more preserved microvascular integrity and functional vasodilation after acute myocardial infarction.

Effect of preinfarction angina pectoris on ST-segment resolution after primary coronary angioplasty for acute myocardial infarction

The presence of preinfarction angina has been shown to exert a favorable effect on left ventricular function after acute myocardial infarction (AMI). Whether or not preinfarction angina is beneficial for myocardial tissue reperfusion, however, remains to be determined. We sought to evaluate the influence of preinfarction angina on resolution of ST-segment elevation, which could be affected by microcirculatory damage after recanalization therapy. We studied 96 patients with a first AMI in whom Thrombolysis In Myocardial Infarction (TIMI)-3 flow in the infarct-related artery was established by primary angioplasty. Percent reduction in the sum of ST elevation from baseline to 1 hour after angioplasty (percent Δ∑ST) was examined. Poor ST resolution, defined as percent Δ∑ST <50%, was observed in 25 patients, who had a worse clinical outcome, larger infarct size, and poorer left ventricular function. On multivariate analysis, the absence of preinfarction angina, as well as anterior wall infarction, were major independent predictors of poor ST resolution, whereas age, sex, coronary risk factors, ischemic time, Killip class on admission, multivessel disease, initial TIMI flow grade, and extent of collaterals were not significant. Patients with preinfarction angina had a greater degree of ST-segment resolution than those without angina (71 ± 21% vs 49 ± 43%, p = 0.02). Additional ST elevation after reperfusion was noted exclusively in patients without preinfarction angina (p = 0.02). Preinfarction angina is associated with a greater degree of ST-segment resolution in patients with TIMI-3 flow after primary angioplasty, suggesting a protective effect of preinfarction angina against microcirculatory damage after reperfusion.

Influencia de la angina en la semana previa al primer infarto agudo de miocardio sobre su pronóstico intrahospitalario y a medio plazo

The implications of early angina on the prognosis of myocardial infarction are controversial. The aim of this study was to assess the effect of angina one week before the first myocardial infarction on short and medium-term prognosis. A total of 290 consecutive patients (107 with previous angina and 183 without it) with the first myocardial infarction were studied to determine the effect of preceding angina on short and medium-term prognosis. Further criteria for inclusion were no previous history of angina > 1 week before the first myocardial infarction, and no evidence of prior structural cardiopathy. The end points studied were death and congestive heart failure in the acute phase of myocardial infarction and during the follow-up. Patients with a history of prodromal angina were less likely to experience in-hospital death, heart failure or combined end-point (3.7 vs 11.5%; 4.6 vs 15.8%; 7.5 vs 21.3%) (p = 0.002). There was also a difference between groups in the follow-up (4.1 vs 13.2%; p = 0.03). Multivariate analysis confirmed that the presence of preinfarction angina was an independent predictor of death and heart failure in the acute phase of myocardial infarction as well as in the follow-up. The occurrence of angina one week before the first myocardial infarction protects against death and heart failure in the acute phase of myocardial infarction as well as in the medium follow-up.

Does angina the week before protect against first myocardial infarction in elderly patients?

Mortality rates for coronary artery disease are greater in elderly patients. Although prodromal angina occurring shortly before an acute myocardial infarction (MI) has protective effects against ischemia, this effect has not been well documented in older patients. This study investigated whether angina 1 week before a first MI provides protection in this group of patients. A total of 290 consecutive elderly (>64 years old, n = 143) and adult patients (<65 years old, n = 147) with a first MI were examined to assess the effect of preceding angina on the short- and long-term prognosis. Elderly patients with a history of prodromal angina were less likely than those without angina to experience in-hospital death, heart failure, or the combined end point of in-hospital death and heart failure (6% vs 20.4%, p = 0.02; 10% vs 23.7%, p = 0.07; 14% vs 32.3%, p = 0.01, respectively). Left ventricular function was more frequently depressed (ejection fraction <40%) in elderly patients without (44.8%) than with (26%, p = 0.04) preinfarction angina, and the incidence of arrhythmias (complete heart block and ventricular fibrillation) was greater in the former group (16.1% vs 4%, p = 0.03). Multivariate analysis confirmed that the presence of preinfarction angina was an independent predictor of in-hospital death and heart failure in older patients (odds ratio 0.28, p = 0.009). The occurrence of angina 1 week before a first MI may confer protection against in-hospital adverse outcomes, and may preserve left ventricular function in older patients.

Influencia de la angina preinfarto en la mortalidad a medio plazo tras infarto agudo de miocardio

Pre-infarction angina may reduce the extent of myocardial cell necrosis and improves the prognosis after myocardial infarction. The aim of this study was to analyze the total mortality six-month after acute myocardial infarction according to the presence or absence of pre-infarction angina. One hundred seventy-five consecutive patients with acute myocardial infarction were prospectively included, 72 (41.4%) with pre-infarction angina. They were followed for 6 months. There were 16 deaths (15.5%) in the group of patients without pre-infarction angina and 7 (9.7%) in the group with pre-infarction angina (log-rank = 1.03; p = 0.311). The hazard-risk function curves showed a higher risk of death during the entire follow-up in the group without pre-infarction angina. In the multivariate logistic regression model, the presence of pre-infarction angina does not significantly reduce the risk of death (OR = 0.43; CI 95% = 0.09-2. 22; p = 0.303). We detected a significant interaction between treatment with sulfonylureas before the infarction and the presence of pre-infarction angina (p = 0.017). In this study no significant differences were observed in total mortality six months after acute myocardial infarction according to the presence of pre-infarction angina. However, the risk of death seemed to be higher in the group of patients without pre-infarction angina during the entire follow-up. A significant interaction was found between the treatment with sulfonylurea drugs before infarction and the presence of pre-infarction angina.

Preinfarction angina as a major predictor of left ventricular function and long-term prognosis after a first Q wave myocardial infarction

Objectives. The purpose of this study was to assess the prognostic significance of preinfarction angina after a first Q wave myocardial infarction. Patients with anterior or inferior myocardial infarction were compared.Background. The effect of preinfarction angina on prognosis after anterior and inferior myocardial infarction remains unclear.Methods. A total of 291 patients with a first Q wave anterior (n = 171) or inferior (n = 120) myocardial infarction were examined to assess the effect of preinfarction angina on short- and long-term prognosis. The relation between predischarge left ventriculographic findings and preinfarction angina was also examined.Results. The presence of preinfarction angina was associated with lower peak creatine kinase activity, a lower in-hospital incidence of sustained ventricular tachycardia and fibrillation and a lower incidence of pump failure and cardiac mortality in patients with either anterior or inferior infarction. Among patients with anterior infarction, preinfarction angina was associated with a lower incidence of cardiac rupture and less need for readmission for heart failure within 1 year after the onset of infarction. In this subgroup it was also associated with a higher ejection fraction, a smaller end-diastolic volume and a lower incidence of aneurysm formation noted on ventriculography during convalescence. In patients with inferior infarction, these variables did not differ significantly in the presence or absence of preinfarction angina. Multivariate analysis confirmed that the presence of preinfarction angina was an independent predictor of development of ventricular aneurysm, late phase heart failure and 1-year cardiac mortality.Conclusions. The presence of preinfarction angina has a favorable effect on infarct expansion and late phase left ventricular function, especially in patients with anterior myocardial infarction. The mechanisms responsible for this phenomenon are not known but may be secondary to limitations of infarct size through unidentified mechanisms other than collateralization (e.g., ischemic preconditioning).