1 Aarhus University Hospital, Skejby, Denmark; 2 Hospital for Sick Children and 4 University Health Network, Toronto, Ontario, Canada; and 3 Papworth Hospital and 5 University of Cambridge, ...Cambridge, United Kingdom
Submitted 11 June 2006
; accepted in final form 10 December 2006
Remote ischemic preconditioning reduces myocardial infarction (MI) in animal models. We tested the hypothesis that the systemic protection thus induced is effective when ischemic preconditioning is administered during ischemia (PerC) and before reperfusion and examined the role of the K + -dependent ATP (K ATP ) channel. Twenty 20-kg pigs were randomized (10 in each group) to 40 min of left anterior descending coronary artery occlusion with 120 min of reperfusion. PerC consisted of four 5-min cycles of lower limb ischemia by tourniquet during left anterior descending coronary artery occlusion. Left ventricular (LV) function was assessed by a conductance catheter and extent of infarction by tetrazolium staining. The extent of MI was significantly reduced by PerC (60.4 ± 14.3 vs. 38.3 ± 15.4%, P = 0.004) and associated with improved functional indexes. The increase in the time constant of diastolic relaxation was significantly attenuated by PerC compared with control in ischemia and reperfusion ( P = 0.01 and 0.04, respectively). At 120 min of reperfusion, preload-recruitable stroke work declined 38 ± 6% and 3 ± 5% in control and PerC, respectively ( P = 0.001). The force-frequency relation was significantly depressed at 120 min of reperfusion in both groups, but optimal heart rate was significantly lower in the control group ( P = 0.04). There were fewer malignant arrhythmias with PerC during reperfusion ( P = 0.02). These protective effects of PerC were abolished by glibenclamide. Intermittent limb ischemia during myocardial ischemia reduces MI, preserves global systolic and diastolic function, and protects against arrhythmia during the reperfusion phase through a K ATP channel-dependent mechanism. Understanding this process may have important therapeutic implications for a range of ischemia-reperfusion syndromes.
remote preconditioning; cardioprotection
Address for reprint requests and other correspondence: A. N. Redington, Hospital for Sick Children, 555 Univ. Ave., Toronto, ON, M5G 1X8 Canada (e-mail: andrew.redington{at}sickkids.ca )
Aims The SHould we emergently revascularize Occluded Coronaries in cardiogenic shocK (SHOCK) Trial showed no benefit of early revascularization in patients aged ≥75 years with acute myocardial ...infarction and cardiogenic shock. We examined the effect of age on treatment and outcomes of patients with cardiogenic shock in the SHOCK Trial Registry. Methods and results We compared clinical and treatment factors in patients in the SHOCK Trial Registry with shock due to pump failure aged <75 years \batchmode \documentclassfleqn,10pt,legalpaper{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \((n=588)\) \end{document} and ≥75 years \batchmode \documentclassfleqn,10pt,legalpaper{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \((n=277)\) \end{document}, and 30-day mortality of patients treated with early revascularization <18 hours since onset of shock and those undergoing a later or no revascularization procedure. After excluding early deaths covariate-adjusted relative risk and 95% confidence intervals were calculated to compare the revascularization strategies within the two age groups. Older patients more often had prior myocardial infarction, congestive heart failure, renal insufficiency, other comorbidities, and severe coronary anatomy. In-hospital mortality in the early vs. late or no revascularization groups was 45 vs. 61% for patients aged <75 years \batchmode \documentclassfleqn,10pt,legalpaper{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \((p=0.002)\) \end{document} and 48 vs. 81% for those aged ≥75 years \batchmode \documentclassfleqn,10pt,legalpaper{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \((p=0.0003)\) \end{document}. After exclusion of 65 early deaths and covariate adjustment, the relative risk was 0.76 (0.59, 0.99; \batchmode \documentclassfleqn,10pt,legalpaper{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(p=0.045\) \end{document}) in patients aged <75 years and 0.46 (0.28, 0.75; \batchmode \documentclassfleqn,10pt,legalpaper{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(p=0.002\) \end{document}) in patients aged ≥75 years. Conclusions Elderly patients with myocardial infarction complicated by cardiogenic shock are less likely to be treated with invasive therapies than younger patients with shock. Covariate-adjusted modeling reveals that elderly patients selected for early revascularization have a lower mortality rate than those receiving a revascularization procedure later or never.
CONTEXT Cardiogenic shock (CS) is the leading cause of death for patients hospitalized
with acute myocardial infarction (AMI). OBJECTIVE To assess the effect of early revascularization (ERV) on ...1-year survival
for patients with AMI complicated by CS. DESIGN The SHOCK (Should We Emergently Revascularize Occluded Coronaries for
Cardiogenic Shock) Trial, an unblinded, randomized controlled trial from April
1993 through November 1998. SETTING Thirty-six referral centers with angioplasty and cardiac surgery facilities. PATIENTS Three hundred two patients with AMI and CS due to predominant left ventricular
failure who met specified clinical and hemodynamic criteria. INTERVENTIONS Patients were randomly assigned to an initial medical stabilization
(IMS; n = 150) group , which included thrombolysis (63% of patients), intra-aortic
balloon counterpulsation (86%), and subsequent revascularization (25%), or
to an ERV group (n = 152), which mandated revascularization within 6 hours
of randomization and included angioplasty (55%) and coronary artery bypass
graft surgery (38%). MAIN OUTCOME MEASURES All-cause mortality and functional status at 1 year, compared between
the ERV and IMS groups. RESULTS One-year survival was 46.7% for patients in the ERV group compared with
33.6% in the IMS group (absolute difference in survival, 13.2%; 95% confidence
interval CI, 2.2%-24.1%; P<.03; relative risk
for death, 0.72; 95% CI, 0.54-0.95). Of the 10 prespecified subgroup analyses,
only age (<75 vs ≥ 75 years) interacted significantly (P<.03) with treatment in that treatment benefit was apparent only
for patients younger than 75 years (51.6% survival in ERV group vs 33.3% in
IMS group). Eighty-three percent of 1-year survivors (85% of ERV group and
80% of IMS group) were in New York Heart Association class I or II. CONCLUSIONS For patients with AMI complicated by CS, ERV resulted
in improved 1-year survival. We recommend rapid transfer of patients
with AMI complicated by CS, particularly those younger than 75 years,
to medical centers capable of providing early angiography and
revascularization procedures.
In this placebo-controlled trial, 7119 patients were randomly assigned at 3 months after PCI to either receive ticagrelor alone or continue dual therapy with ticagrelor plus aspirin. The trial ...evaluated bleeding and ischemic end points at 1 year.
Aims We analysed time trends in patient characteristics, management, and outcomes of cardiogenic shock complicating acute myocardial infarction in the international, prospective SHOCK Trial Registry ...and pre-study Registry. Background Despite therapeutic advances in its management, the incidence and high mortality of this complication has remained unchanged for decades. However, in recent years mortality was reported to decrease in one community concomitant with increasing use of revascularization. Methods Thirty-six centres registered 1380 patients with suspected cardiogenic shock complicating acute myocardial infarction from January 1992 to August 1997. Patient and myocardial infarction characteristics, haemodynamics, medications, procedure use, and vital status at discharge were recorded. Results In all, 79% of patients had shock due to predominant pump failure (non-mechanical aetiology). The aetiology, patient profile, and clinical characteristics of cardiogenic shock did not differ over time, except for increases in the incidence of prior bypass surgery (P=0·054) and transfers to tertiary centres (P=0·008). In all, 44% underwent revascularization (n=485), with angioplasty performed more often than bypass surgery (69% vs 31%). The revascularization rate increased over time (P=0·006) with a significant decrease in the time to revascularization (P=0·033). The use of Swan–Ganz catheterization decreased over time (P=0·018), as did the mean length of hospitalization (P=0·034). Overall in-hospital mortality was high (63%) but decreased over time in all patients (P=0·004) and those with pump failure (P=0·018). Mortality was lower for patients who underwent revascularization compared to those who were not revascularized (41% vs 79%,P <0·001). Conclusions Cardiogenic shock complicating acute myocardial infarction is associated with a high mortality rate, but mortality decreased significantly from 1992 to 1997. This partly reflects the greater use of revascularization, which was associated with better outcomes. The reported international trend towards shorter admissions for myocardial infarction was also observed in this cohort.
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