Remote Ischemic Preconditioning in Non-cardiac Surgery: A Systematic Review and Meta-analysis.

BACKGROUND: Remote ischemic preconditioning (RIPC) may mitigate physiological stress related to surgery. There is no clear consensus on conduct of RIPC studies, or whether it is effective. The aim of this study was to (i) assess delivery of RIPC, (ii) identify reported outcomes, (iii) measure effect on key clinical outcomes. METHODS: This review was registered on PROSPERO (CRD:42020180725). EMBASE and Medline databases were searched, and results screened by two reviewers. Full-texts were assessed for eligibility by two reviewers. Data extracted were methods of RIPC and outcomes reported. Meta-analysis of key clinical events was performed using a Mantel-Haenszel random effects model. The TIDieR framework was used to assess intervention reporting, and Cochrane risk of bias tool was used for all studies included. RESULTS: Searches identified 25 studies; 25 were included in the narrative analysis and 18 in the meta-analysis. RIPC was frequently performed by occluding arm circulation (15/25), at 200 mmHg (9/25), with three cycles of 5 min ischemia and 5 min of reperfusion (16/25). No study fulfilled all 12 TIDieR items (mean score 7.68). Meta-analysis showed no benefit of RIPC on MI (OR 0.71 95% CI 0.48-1.04, I2 = 0%), mortality (OR 0.56, 95% CI 0.31-1.01, I2 = 0%), or acute kidney injury (OR 0.72 95% CI 0.48-1.08). CONCLUSIONS: RIPC could be standardized as 200 mmHg pressure in 3 × 5 min on and off cycles. The signal of benefit should be explored in a larger well-designed randomized trial.

Myocardial Infarct Size Reduction Provided by Local and Remote Ischaemic Preconditioning: References Values from the Hatter Cardiovascular Institute.

PURPOSE: To accurately estimate the effect size of both local or classic ischaemic preconditioning (IPC) and remote ischaemic preconditioning (RIPC) using a pooling data set of 91 animals. METHODS: We combined all the available mouse data collected from our Institute over the last 3 years regarding (i) local IPC (4 cycles of 5 min of global ischaemia/reperfusion injury, IRI, followed by 35-min ischaemia and 2-h reperfusion) in the Langendorff-isolated perfused mouse heart model and (ii) RIPC (3 cycles of 5 min of limb occlusion followed by 40-min ischaemia and 2-h reperfusion) in the in vivo mouse model. RESULTS: Five independent experiments containing 27 control and 29 IPC mice were used to estimate the overall (i) local IPC effect, which reduced infarct size in the ex-vivo setting by a mean difference of 24.1% (95% CI 19.5, 28.6%) when compared to untreated controls (P < 0.001) and for (ii) RIPC, three independent experiments including data for 16 control and 19 RIPC mice were used to estimate that RIPC diminished infarct size in the in-vivo setting by a mean difference of 20.8% (95% CI 14.7, 26.9%) when compared to controls (P < 0.001). CONCLUSIONS: Using a significant animal dataset, we found that local IPC reduces myocardial infarct size by 24.1% and RIPC by 20.8% in the ex vivo and in vivo mouse models of IRI, respectively. These differences may be used as reference values to either establish positive controls or to determine by how much myocardial infarct size can be reduced by novel cardioprotective interventions following an IRI insult.

Novel targets and future strategies for acute cardioprotection: Position Paper of the European Society of Cardiology Working Group on Cellular Biology of the Heart.

Ischaemic heart disease and the heart failure that often results, remain the leading causes of death and disability in Europe and worldwide. As such, in order to prevent heart failure and improve clinical outcomes in patients presenting with an acute ST-segment elevation myocardial infarction and patients undergoing coronary artery bypass graft surgery, novel therapies are required to protect the heart against the detrimental effects of acute ischaemia/reperfusion injury (IRI). During the last three decades, a wide variety of ischaemic conditioning strategies and pharmacological treatments have been tested in the clinic-however, their translation from experimental to clinical studies for improving patient outcomes has been both challenging and disappointing. Therefore, in this Position Paper of the European Society of Cardiology Working Group on Cellular Biology of the Heart, we critically analyse the current state of ischaemic conditioning in both the experimental and clinical settings, provide recommendations for improving its translation into the clinical setting, and highlight novel therapeutic targets and new treatment strategies for reducing acute myocardial IRI.

Ischemic preconditioning and spinal cord function monitoring in the descending thoracic aorta approach.

OBJECTIVES: To evaluate the effectiveness of acute ischemic preconditioning (IP), based on somatosensory evoked potentials (SSEP) monitoring, as a method of spinal cord protection and to asses SSEP importance in spinal cord neuromonitoring. METHODS: Twenty-eight dogs were submitted to spinal cord ischemic injury attained by descending thoracic aorta cross-clamping. In the C45 group, the aortic cross-clamping time was 45 min (n=7); in the IP45 group, the dogs were submitted to IP before the aortic cross-clamping for 45 min (n=7). In the C60 group, the dogs were submitted to 60 min of aortic cross-clamping (n=7), as in the IP60 group that was previously submitted to IP. The IP cycles were determined based on SSEP changes. RESULTS: Tarlov scores of the IP groups were significantly better than those of the controls (p = 0.005). Paraplegia was observed in 3 dogs from C45 and in 6 from C60 group, although all dogs from IP45 group were neurologically normal, as 4 dogs from IP60. There was a significant correlation between SSEP recovery time until one hour of aortic reperfusion and the neurological status (p = 0.011), showing sensitivity of 75% and specificity of 83%. CONCLUSION: Repetitive acute IP based on SSEP is a protection factor during spinal cord ischemia, decreasing paraplegia incidence. SSEP monitoring seems to be a good neurological injury assessment method during surgical procedures that involve spinal cord ischemia.

Pré-condicionamento isquêmico e monitorização da função medular na abordagem da aorta torácica descendente / Ischemic preconditioning and spinal cord function monitoring in the descending thoracic aorta approach

OBJETIVOS: Avaliar a eficácia do pré-condicionamento isquêmico (PI) agudo, guiado por potenciais evocados somatossensoriais (PESS), como método de proteção medular em cães e analisar o valor dos PESS na monitorização da função medular. MÉTODOS: Foram utilizados 28 cães submetidos à isquemia medular obtida pelo pinçamento da aorta torácica descendente. No grupo C45, o tempo de oclusão aórtica foi de 45 min (n = 7); no grupo PI45, os cães foram submetidos ao PI antes do pinçamento aórtico por 45 min (n = 7). No grupo C60, os cães foram submetidos a 60 min de oclusão aórtica (n = 7) e no grupo PI60, os cães foram submetidos ao PI, seguido pelo pinçamento aórtico por 60 min. Os ciclos de PI foram determinados pelas alterações dos PESS. RESULTADOS: Os índices de Tarlov dos grupos pré-condicionados foram significativamente melhores que os dos grupos de controle (p = 0,005). Observou-se paraplegia em três cães do C45 e em seis do C60, enquanto todos os cães do PI45 permaneceram neurologicamente normais, assim como quatro do grupo PI60. Houve correlação entre o tempo de recuperação dos PESS após a reperfusão aórtica e o estado neurológico pós-operatório (p = 0,011), com sensibilidade e especificidade de 0,75 e 0,83, respectivamente. CONCLUSÃO: O PI agudo repetitivo, baseado na monitorização do PESS, induziu proteção à isquemia medular causada pelo pinçamento aórtico prolongado. A monitorização do PESS parece ser um bom método de detecção precoce do comprometimento isquêmico medular.

OBJECTIVES: To evaluate the effectiveness of acute ischemic preconditioning (IP), based on somatosensory evoked potentials (SSEP) monitoring, as a method of spinal cord protection and to asses SSEP importance in spinal cord neuromonitoring. METHODS: Twenty-eight dogs were submitted to spinal cord ischemic injury attained by descending thoracic aorta cross-clamping. In the C45 group, the aortic cross-clamping time was 45 min (n=7); in the IP45 group, the dogs were submitted to IP before the aortic cross-clamping for 45 min (n=7). In the C60 group, the dogs were submitted to 60 min of aortic cross-clamping (n=7), as in the IP60 group that was previously submitted to IP. The IP cycles were determined based on SSEP changes. RESULTS: Tarlov scores of the IP groups were significantly better than those of the controls (p = 0.005). Paraplegia was observed in 3 dogs from C45 and in 6 from C60 group, although all dogs from IP45 group were neurologically normal, as 4 dogs from IP60. There was a significant correlation between SSEP recovery time until one hour of aortic reperfusion and the neurological status (p = 0.011), showing sensitivity of 75 percent and specificity of 83 percent. CONCLUSION: Repetitive acute IP based on SSEP is a protection factor during spinal cord ischemia, decreasing paraplegia incidence. SSEP monitoring seems to be a good neurological injury assessment method during surgical procedures that involve spinal cord ischemia.

Factors during donor care that may affect liver transplantation outcome.

Publications are reviewed that identify factors during donor care and characteristics of the donor liver that may be associated with outcome following liver transplantation. The procurement coordinator has the opportunity to influence cold ischemia time, blood pressure, the serum sodium concentration and, perhaps, liver glycogen reserves. These variables may significantly affect postimplantation graft performance and graft or recipient survival. Summaries of those publications comprising this database are presented, and several limitations in their interpretation are discussed.

Effect of ischaemic preconditioning on genomic response to cerebral ischaemia: similarity to neuroprotective strategies in hibernation and hypoxia-tolerant states.

BACKGROUND: Molecular mechanisms of neuroprotection that lead to ischaemic tolerance are incompletely understood. Identification of genes involved in the process would provide insight into cell survival and therapeutic approaches for stroke. We developed a mouse model of neuroprotection in stroke and did gene expression profiling to identify potential neuroprotective genes and their associated pathways. METHODS: Eight mice per condition were subjected to occlusion of the middle cerebral artery for 15 min (preconditioning), 60 min (injurious ischaemia), or preconditioning followed 72 h later by injurious ischaemia. RNA was extracted from the cortical regions of the ischaemic and non-ischaemic hemispheres. Three pools per condition were generated, and RNA was hybridised to oligonucleotide microarrays for comparison of ischaemic and non-ischaemic hemispheres. Real-time PCR and western blots were used to validate results. Follow-up experiments were done to address the biological relevance of findings. FINDINGS: Microarray analysis revealed changes in gene expression with little overlap among the conditions of injurious ischaemia, ischaemic preconditioning, or both. Injurious ischaemia induced upregulation of gene expression; 49 (86%) of 57 genes regulated showed increased expression in the ischaemic hemisphere. By contrast, preconditioning followed by injurious ischaemia resulted in pronounced downregulation; 47 (77%) of 61 regulated genes showed lower expression. Preconditioning resulted in transcriptional changes involved in suppression of metabolic pathways and immune responses, reduction of ion-channel activity, and decreased blood coagulation. INTERPRETATION: Preconditioning reprogrammes the response to ischaemic injury. Similar changes reported by others support an evolutionarily conserved endogenous response to decreased blood flow and oxygen limitation such as seen during hibernation.