Introduction
Protecting the Heart with Remote Ischaemic Preconditioning
Clinical Applications
Study | Number of patients | RIPC stimulus: limb(s) used, duration of I-R (min), number of RIPC cycles, cuff inflation pressure | Outcome |
---|---|---|---|
Cheung et al. [18] | 37 | Lower limb 5′ I 5′ R (x4); 15 mmHg above systolic arterial BP | Reduced cTnT release, Reduced inotrope requirement after surgery, Reduced airway resistance |
Venugopal et al. [26] | 45 | Upper limb 5′ I 5′ R (x3); 200 mmHg | Reduced absolute cTnT release post surgery |
Hausenloy et al. [22] | 57 | Upper limb 5′ I 5′ R (x3); 200 mmHg | Reduced cTnT release postoperatively |
Thielmann et al. [25] | 53 | Upper limb 5′ I 5′ R (x3); 200 mmHg | Reduced cTnI release postoperatively |
Gunaydin et al. [21] | 8 | Lower limb 3′ I 2′ R (x2); 200 mmHg | No change in CK-MB |
Rahman et al. [24] | 162 | Upper limb 5′ I 5′ R (x3); 200 mmHg | Troponin-T release unaffected by RIPC |
Wagner et al. [27] | 101 | Upper limb 5′ I 5′ R (x3); 40 mm Hg above resting systolic BP- given 18 h prior to surgery | Reduced cTnI release post-operatively |
Kottenberg et al. [23] | 72 | Upper limb 5′ I 5′ R (x3); 200 mmHg | RIPC during isoflurane anaesthesia reduces post-op cTnI release, but not during Propofol anesthesia |
Candilio et al. [19] | 180 | One upper and one lower limb simultaneously 5′I 5′R (x2); 200 mm Hg or to 15 mmHg above systolic BP if systolic BP >185 mmHg | Reduced perioperative TnI release, reduced incidence of post-op AF/AKI and duration of ICU stay |
Gedik et al. [20] | 20 | Upper limb 5′ I 5′ R (x3) | Reduced TnI release post-operatively |
Hausenloy et al. [30] | 1,610 | Upper limb 5′ I 5′ R (x4); 200 mm Hg | No significant difference in 30 day MACCE or 1 year clinical outcomes |
Study | Number of patients | RIPC stimulus: Limb(s) used, duration of ischemic and reperfusion episodes in min (where specified), number of cycles, cuff inflation pressure, clinical setting | Timing of RIPC in relation to PCI | Outcome |
---|---|---|---|---|
RIPC in non-emergent PCI | ||||
Pei et al. (Metanalysis) [42] | 1,713 | Upper/Lower limb 3–5′ I 1–5′ R (x1-4); 200 mm Hg or 50 mm Hg> Systolic BP (Elective PCI) | Wide range | RIPC significantly reduced incidence of perioperative MI and CI AKI |
Zografos et al., Metanalysis [44] | 1,066 | Upper/Lower limb 3–5′ I 3–5′ R (x1-3); 200 mm Hg (Elective PCI) | Wide range | RIPC reduces incidence of peri-procedural MI |
D′Ascenzo et al. (Metanalysis) [41] | 731 | Upper/Lower limb 5′ I 5′ R (x3); 200 mm Hg (x2–3) (Elective PCI/PCI for unstable angina) | Wide range (Immediately before, up to 2 h before PCI) | Reduced incidence of perioperative MI (defined by increase of cTnT to >3x 99th percentile URL); more benefit when RIPC was delivered on lower extremity |
Lavi et al. [36] | 360 | Upper limb vs. Lower limb 5′ I 5′ R (x3); 200 mm Hg (PCI for stable/unstable angina) | Post PCI | RiPostC did not change the incidence of peri-procedural MI |
Carrasco-Chinchilla et al. [33] | 232 | Upper limb 5′ I 5′ R (x3); 200 mm Hg Post PCI (Elective PCI for stable/unstable angina) | Post PCI | RiPostC did not reduce troponin release, peri-operative MI and had no impact on clinical outcomes |
Xu et al. [39] | 200 | Upper limb 5′ I 5′ R (x3); 200 mm Hg (Elective PCI); Included patients with DM & >/=65 years of age) | <2 h prior to PCI | No significant difference in release of hs-cTnI or incidence of post-procedure MI 4a |
Liu et al. [37] | 200 | Upper limb 5′ I 5′ R (x3); 200 mm Hg (Elective PCI) | 18 h before PCI | Reduced release of cardiac enzyme post-PCI and reduced adverse events at 6 months |
CRISP stent trial Hoole et al. [31] Davies et al.[34] | 242 in initial trial (192 in 6 years follow-up) | Upper limb 5′ I 5′ R (x3); 200 mm Hg (Elective PCI) | Variable time before PCI | Reduced perioperative myocardial injury; Reduced MACCE rate at 6 months and 6 years (HR 0.58 p = 0.039). RIPC protection was seen early (within 1–2 h of RIPC); No difference in MACCE at 6 years in diabetics |
Ahmed et al. [32] | 149 | Upper limb 5′ I 5′ R (x3); 200 mm Hg (Elective PCI) | Variable time before PCI | Reduced procedure-related cTnT release |
Prasad et al.[38] | 95 | Upper limb 3′ I 3′ R (x3); 200 mm Hg (Non-emergent PCI for stable/unstable coronary disease) | Immediately before PCI | No difference in post procedure cTnT release |
Zografos et al. [40] | 94 | Upper limb 5′ I 5′ R (x1); 200 mm Hg (Elective PCI) | Immediately before PCI | Reduced peri-procedural cTnI release and lesser incidence of peri-operative MI |
MERIT trial Ghaemian et al.[35] | 80 | Lower Limb 5′ I 5′ R (x2) (Elective PCI) | 1 h before procedure | Reduced release of cTnT at 24 h |
Remote Ischemic Conditioning in Acute Myocardial Infarction | ||||
ERIC-LYSIS [16] Yellon et al. | 519 | Upper limb 5′ I 5′ R (x4); 200 mm Hg (Thrombolysis for STEMI) | RIPC before thrombolysis | RIPC reduced AUC for cTnI and CK-MB release post pPCI |
333 | Upper limb 5′ I 5′ R (x4); 200 mm Hg (pPPCI for STEMI) | Before PCI (in-ambulance) | Significant reduction in HR for MACCE extending beyond 3 years | |
RIPOST-MI Prunier et al. [13] | 151 | Upper limb 5′ I 5′ R (x3); 200 mm Hg (STEMI patients undergoing pPCI) | Perconditioning (Before PCI) | RIPerconditioning significantly reduced Peak CK-MB, CK-MB AUC to area at risk (AAR) ratio, and peak CK-MB level to AAR ratio |
Crimi et al. [11] | 100 | Lower limb 5′ I 5′ R (x3); 200 mm Hg (Anterior STEMI patient undergoing pPCI) | post PCI | RiPostC reduced peri-operative myocardial infarction measured by AUC for CK-MB release, reduced T2-weighted edema on MRI |
Yamanaka et al. [15] | 94 | Upper limb 5′ I 5′ R (x3); 200 mm Hg (STEMI patients undergoing pPCI) | With pPCI | Reduced incidence of contrast induced AKI |
Metanalyses combining studies of Remote Ischemic Conditioning in both emergent and non-emergent setting | ||||
Zuo et al. (Metanalysis) [45] | 1542 | Various protocols including RIPostC (various indications for PCI) | Variable (before/after PCI) | RIPC/RIPostC reduces the incidence of PCI related AKI; Also RIPC reduces in hospital mortality and MACEs |
Yetgin et al. (Metanalysis) [43] | 557 (PCI) 314 (pPCI) 891 (CABG) | Various protocols in the setting of PCI (pPCI for STEMI and CABG) | Variable | RIPC reduced perioperative myocardial necrosis, measured by increase in cardiac enzymes (overall analysis showed a trend but were not significant for PCI studies) |
Mechanisms Underlying RIPC Mediated Protection of the Heart
Innate Protective Pathways within the Myocardium Activated by RIPC
Mechanisms Involved in Transmission of RIPC Signal to the Heart
Improving Exercise Performance with Limb IPC
Study | Exercise Setting/Fitness level of subjects | No. of subjects | Limb IPC stimulus: limb(s) used, duration of I-R (min), number of cycles, cuff inflation pressure | Timing of Limb IPC/RIPC | Time between exercise session/Sham inflation pressure | Results |
---|---|---|---|---|---|---|
Tocco et al. [108] | 5000 m self-paced running /Skilled runners (10–12 h/week of training) | 11 | Both lower limbs 5′ I 5′ R (x3); 50 mmHg above resting systolic | 5 min before exercise (no warm-up) | 7–14 days, 10 mm below diastolic pressure | No change in average running speed, oxygen uptake, aerobic energy cost during exercise and post-race blood lactate |
Patterson et al. [109] | Repeated sprint test during cycling ergometry/ Mean 6.7 +/− 2.3 h per week of training | 14 | Both lower limbs 5′ I 5′ R (x4); 220 mmHg | 30 min before warm up for exercise | 5–7 days, 20 mmHg | Limb IPC improved peak and mean power output during the early stages of repeated sprint cycling |
Gibson et al. [107] | Maximal sprinting performance over 30 m/ Well trained individuals | 25 | One lower limb 5′ I 5′ R (x3); 220 mmHg | 5 min before warm up | <7 days, 50 mmHg | No improvement in sprint speed with limb IPC |
Bailey et al. [99] | Graded maximal treadmill running test, followed by a 5-km time trial /Moderately trained individuals <10 h/week | 12 | Both lower limbs 5′ I 5′ R (x4); 50 mmHg above resting systolic | 20 min before running test and 100 min before 5-km time trial | 5–7 days, 20 mmHg | Lower Limb IPC preserved post exercise brachial artery endothelium-dependent function (remote effect) |
Bailey et al. [103] | 5 km time trial/Moderately trained individuals | 13 | Both lower limbs 5′ I 5′ R (x4); 220 mmHg | 90 min before 5 km time trial | Not available, 20 mmHg | IPC improved 5-km time trial performance; IPC was associated with lesser rise in blood lactate concentration at submaximal level during incremental running test. |
Crisafulli et al. [102] | Incremental, maximal exercise tests on a cycle ergometer/Healthy individuals | 17 | Both lower limbs 5′ I 5′ R (x3); 50 mmHg above resting systolic | 5 min before exercise | >7 days, No sham group | Limb IPC improved maximal exercise performance but not maximal oxygen uptake |
Jean-St-Michel [104] | Swimming/Competitive swimmers (with previous times meeting Canadian national championship qualification standards) | 16–18 | Upper limb 5′ I 5′ R (x4); 15 mmHg above resting systolic blood pressure | Immediately before warm-up | >7 days, 10 mmHg | Improved maximum swim time. Dialysed blood taken from subjects after RIPC reduced myocardial infarct in mouse Langendorff heart preparations |
de Groot et al. [95] | Incremental maximal exercise tests on a bicycle ergometer (Well trained cyclists) | 15 | Both lower limbs 5′ I 5′ R (x3); 220 mmHg | 5 min before exercise | >7 days apart, No sham group | IPC had no effect on ventilation, respiratory quotient, maximal heart rate, blood pressure or blood lactate. Limb IPC improved maximal oxygen consumption |