Vagal nerve stimulation started just prior to reperfusion limits infarct size and no-reflow

Vagal nerve stimulation (VNS) started prior to, or during, ischemia has been shown to reduce infarct size. Here, we investigated the effect of VNS when started just prior to, and continued during early, reperfusion on infarct size and no-reflow and studied the underlying mechanisms. For this purpose, swine (13 VNS, 10 sham) underwent 45 min mid-LAD occlusion followed by 120 min of reperfusion. VNS was started 5 min prior to reperfusion and continued until 15 min of reperfusion. Area at risk, area of no-reflow (% of infarct area) and infarct size (% of area at risk), circulating cytokines, and regional myocardial leukocyte influx were assessed after 120 min of reperfusion. VNS significantly reduced infarct size from 67 ± 2 % in sham to 54 ± 5 % and area of no-reflow from 54 ± 6 % in sham to 32 ± 6 %. These effects were accompanied by reductions in neutrophil (~40 %) and macrophage (~60 %) infiltration in the infarct area (all p < 0.05), whereas systemic circulating plasma levels of TNFα and IL6 were not affected. The degree of cardioprotection could not be explained by the VNS-induced bradycardia or the VNS-induced decrease in the double product of heart rate and left ventricular systolic pressure. In the presence of NO-synthase inhibitor LNNA, VNS no longer attenuated infarct size and area of no-reflow, which was paralleled by similarly unaffected regional leukocyte infiltration. In conclusion, VNS is a promising novel adjunctive therapy that limits reperfusion injury in a large animal model of acute myocardial infarction

Remote Ischemic Conditioning in Percutaneous Coronary Intervention and Coronary Artery Bypass Grafting - Meta-Analysis of Randomized Trials -

Background: Although remote ischemic conditioning (RIC) by transient limb ischemia in percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) has shown favorable effects on myocardial (ischemiareperfusion) injury, recent trials provide inconsistent results. The aim of the present study was to assess the effect of RIC in PCI or CABG. Methods and Results: Medline/Embase/conference reports were searched for randomized RIC trials and were included if they reported on biomarkers of myocardial injury (CK-MB/troponin T/I), after which, standardized mean differences (SMDs) were calculated (Hedges g statistic). Meta-analysis of 4 studies on PCI, involving 557 patients, indicated reduced biomarkers for myocardial injury with RIC compared to control (random effects model: SMD,-0.21; 95% confidence interval [CI]:-0.66 to 0.24). Analysis of primary PCI studies, involving 314 patients, indicated a highly significant positive effect of RIC on myocardial injury (SMD,-0.55; 95% CI:-0.77 to-0.32). The 13 CABG studies taken together, involving 891 patients, indicated a significant effect of RIC on myocardial injury (SMD,-0.34; 95% CI:-0.59 to-0.08). The statistical tests indicated moderate to high heterogeneity across the studies (Q-statistic: PCI, P=0.0006, I2=83%; CABG, P<0.0001, I2=69%). Conclusions: In patients undergoing PCI or CABG, RIC with transient episodes of limb ischemia is associated with lower biomarkers of myocardial injury compared to control, but this effect failed to reach statistical significance in the overall PCI analysis

Impact of multiple balloon inflations during primary percutaneous coronary intervention on infarct size and long-term clinical outcomes in ST-segment elevation myocardial infarction: Real-world postconditioning

Interrupting myocardial reperfusion with intermittent episodes of ischemia (i.e., postconditioning) during primary percutaneous coronary intervention (PPCI) has been suggested to protect myocardium in ST-segment elevation myocardial infarction (STEMI). Nevertheless, trials provide inconsistent results and any advantage in long-term outcomes remains elusive. Using a retrospective study design, we evaluated the impact of balloon inflations during PPCI on enzymatic infarct size (IS) and long-term outcomes. We included 634 first-time STEMI patients undergoing PPCI with an occluded infarct-related artery and adequate reperfusion thereafter and divided these into: patients receiving 1-3 inflations in the infarct-related artery [considered minimum for patency/stent placement (controls); n = 398] versus ≥4 [average cycles in clinical protocols (postconditioning analogue); n = 236]. IS, assessed by peak creatine kinase, was lower in the postconditioning analogue group compared with controls [median (interquartile range) 1,287 (770-2,498) vs. 1,626 (811-3,057) UI/L; p = 0.02], corresponding to a 21 % IS reduction. This effect may be more pronounced in women, patients without diabetes/hypercholesterolemia, patients presenting within 3-6 h or with first balloon re-occlusion ≤1 min. No differences were observed in 4-year mortality or MACCE between groups. Four or more inflations during PPCI reduced enzymatic IS in STEMI patients under well-defined conditions, but did not translate into improved long-term outcomes in the present study. Large-scale randomized trials following strict postconditioning protocols are needed to clarify this effect

Bone regeneration during distraction osteogenesis

Bone has the capacity to regenerate in response to injury. During distraction osteogenesis, the renewal of bone is enhanced by gradual stretching of the soft connec- tive tissues in the gap area between two separated bone segments. This procedure has received much clinical atten- tion as a way to correct congenital growth retardation of bone tissue or to generate bone to fill skeletal defects. The process of bone regeneration involves a complex system of biological changes whereby mechanical stress is converted into a cascade of signals that activate cellular behavior resulting in (enhanced) formation of bone. Over the last decade, significant progress has been made in understand- ing the bone regeneration process during distraction osteo- genesis. The mechanical and biological factors that are important for the success of the distraction treatment have been partially characterized and are discussed in this review