Effects of intracoronary melatonin on ischemia-reperfusion injury in ST-elevation myocardial infarction.

Acute coronary occlusion is effectively treated by primary percutaneous coronary intervention. However, myocardial ischemia-reperfusion injury is at the moment an unavoidable consequence of the procedure. Oxidative stress is central in the development of ischemia-reperfusion injury. Melatonin, an endogenous hormone, acts through antioxidant mechanisms and could potentially minimize the myocardial injury. The aim of the experimental study was to examine the cardioprotective effects of melatonin in a porcine closed-chest reperfused infarction model. A total of 20 landrace pigs were randomized to a dosage of 200 mg (0.4 mg/mL) melatonin or placebo (saline). The intervention was administered intracoronary and intravenous. Infarct size, area at risk and microvascular obstruction were determined ex vivo by cardiovascular magnetic resonance imaging. Myocardial salvage index was calculated. The plasma levels of high-sensitive troponin T were assessed repeatedly. The experimenters were blinded with regard to treatment regimen. Melatonin did not significantly increase myocardial salvage index compared with placebo [melatonin 21.8% (16.1; 24.8) vs. placebo 20.2% (16.9; 27.0), p = 1.00]. The extent of microvascular obstruction was similar between the groups [melatonin 3.8% (2.7; 7.1) vs. placebo 3.7% (1.3; 7.7), p = 0.96]. The area under the curve for high-sensitive troponin T release was insignificantly reduced by 32% in the melatonin group [AUC melatonin 12,343.9 (6,889.2; 20,147.4) ng h/L vs. AUC placebo 18,285.3 (5,180.4; 23,716.8) ng h/L, p = 0.82]. Combined intracoronary and intravenous treatment with melatonin did not reduce myocardial reperfusion injury. The lack of a positive effect could be due to an ineffective dose of melatonin, a type II error or the timing of administration.

Reduced oxidative stress in STEMI patients treated by primary percutaneous coronary intervention and with antioxidant therapy: a systematic review.

PURPOSE: Coronary reperfusion by primary percutaneous coronary intervention (PCI) has been established as an essential therapy of ST-elevation myocardial infarction (STEMI). Although the coronary intervention is undoubtedly beneficial, reperfusion itself can induce processes resulting in additional myocardial damage-a phenomenon known as ischemia-reperfusion injury (IRI). Oxidative stress is one of the major factors contributing to IRI. This systematic review focuses on the effect of antioxidant therapy on reperfusion triggered oxidative stress and myocardial IRI in patients with STEMI. METHODS: We performed a systematic search in EMBASE and Pubmed and included eight randomised clinical trials evaluating edaravone, allopurinol, vitamin c, nicorandil, N-acetylcysteine, glucose-insulin-potassium, atorvastatin and deferoxamine. RESULTS: Administration of edaravone, allopurinol, atorvastatin and nicorandil as a supplement to primary PCI significantly reduced oxidative stress and myocardial damage as well as improved cardiac function and clinical outcomes. Treatment with deferoxamine and N-acetylcysteine reduced the oxidative stress but an effect on the clinical outcome parameters could not be shown. CONCLUSIONS: Preliminary studies of edaravone, allopurinol, atorvastatin and nicorandil seems promising though larger clinical trials with a wider range of clinical outcome parameters and trials of higher methodological quality should confirm the clinical benefits before a general recommendation can be given. Moreover, the included studies revealed a complex link between oxidative stress and cardiac function and/or cardiac adverse events and in order to further elucidate the detrimental role of oxidative stress in IRI in relation to primary PCI the assessment of oxidative stress and the clinical outcome parameters should be standardized.

Complications and Their Association with Mortality Following Emergency Gastrointestinal Surgery-an Observational Study.

PURPOSE: Emergency gastrointestinal surgery is followed by a high risk of major complications and death. This study aimed to investigate which complications showed the strongest association with death following emergency surgery for gastrointestinal obstruction or perforation. METHODS: We retrospectively included adults who had undergone emergency gastrointestinal surgery for radiologically verified obstruction or perforation at three Danish hospitals between 2014 and 2015. The exposure variables comprised 16 predefined Clavien-Dindo-graded complications. Cox regression with delayed entry was used to analyze the association of these complications with 90-day mortality. We adjusted for hospital, age, American Society of Anesthesiologists classification, pre-operative Sepsis-2 score, cardiac comorbidity, renal comorbidity, hypertension, active cancer, bowel obstruction or perforation, and the surgical procedure. Subgroup analyses were done for patients with gastrointestinal obstruction or perforation. RESULTS: Of the 349 included patients, 281 (80.5%) experienced at least one complication. The risk of death was 20.6% (14) for patients with no complications and varied between 21 and 57% for patients with complications. Renal impairment (hazard ratio (HR): 6.8 (95%CI: 3.7-12.4)), arterial thromboembolic events (HR 4.8 (2.3-9.9)), and atrial fibrillation (HR 4.4 (2.8-6.8)) showed the strongest association with 90-day mortality. Atrial fibrillation was the only complication significantly associated with death in patients with gastrointestinal obstruction as well as perforation. CONCLUSION: This study of patients undergoing emergency gastrointestinal surgery revealed that renal impairment, arterial thromboembolic events, and atrial fibrillation had the strongest association with death. Atrial fibrillation may serve as an in-situ marker of patients needing escalation of care.

Associations between malignancy and cardiovascular complications following emergency laparotomy - A retrospective cohort study.

BACKGROUND: Systemic inflammation in patients with malignant disease has been associated with increased risk of cardiovascular events. The pro-inflammatory perturbations following surgical trauma may further promote adverse perioperative cardiovascular events and increase the risk of patients with cancer undergoing major surgery. Our objective was to estimate the association between malignant disease and postoperative cardiovascular complications. Secondarily, we aimed to identify risk factors for postoperative cardiovascular complications. METHODS: We conducted a retrospective cohort study of all patients ≥18 years undergoing emergency laparotomy between 2010 and 2016 at Department of Surgery, Zealand University Hospital, Denmark. Complications were graded according to Clavien-Dindo classification of surgical complications. Multivariate logistic regression analysis was performed to estimate association between malignant disease and cardiovascular complications within 30 days of emergency laparotomy and to identify other risk factors for postoperative cardiovascular complications after emergency laparotomy. RESULTS: We identified 1188 patients ≥18 years undergoing emergency laparotomy between 2010 and 2016, in which 254 (21%) had malignant disease. Within 30 days of emergency laparotomy, 89 (9.5%) of patients without malignancy died, as compared with 45 (18%) of patients with malignancy (p < 0.001). Cardiovascular death occurred in 17 (1.8%) and 5 (2.0%) patients in the non-malignant and malignant group, respectively. Severe cardiovascular complication graded CD 3-5 occurred in 93 (8%) of all patients within 30 days of emergency laparotomy. We found no association between malignancy and postoperative cardiovascular complications in patients undergoing emergency surgery (OR 0.8, 95% CI; 0.4, 1.5). Increasing age and ASA physical status classification system (ASA) score ≥ III were the only independent risk factors of cardiovascular complications graded CD 3-5. CONCLUSIONS: Malignancy was not associated with postoperative cardiovascular complications after emergency laparotomy. Risk factors for major cardiovascular complications after emergency abdominal surgery were age and ASA score ≥ III.

[Intra-operative continuous non-invasive blood pressure monitoring].

Intra-operative hypotension is associated with increased risk of 30-day mortality and organ ischaemia. Thus, a reliable monitoring of blood pressure is desirable. New clinical studies indicate, that monitoring of middle arterial pressure with continuous non-invasive monitoring during stable haemodynamic conditioning provides accurate changes in blood pressure. The potential of continuous non-invasive monitoring is promising, but not fully developed.

[Sparse knowledge about patient-reported outcomes after major emergency abdominal surgery].

Little is known about patient-reported outcomes after major emergency abdominal surgery. Studies on patients undergoing major elective abdominal surgery and patients in the intensive care unit report significant challenges with chronic pain, functional impairment, quality of life, depression and post-traumatic stress disorder (PTSD). Approximately one out of three patients experience chronic pain and functional impairment after major emergency abdominal surgery. The magnitude of depression and PTSD after major emergency abdominal surgery have not been studied before.

[Administration of norepinephrine in peripheral venous catheter on surgical patients].

Hypotension is a common event during surgery and can cause serious post-operative complication, but vasoactive drugs can stabilize the cardiovascular system and reduce the risk of post-operative complications. Norepinephrine is an ideal vasopressor. Due to the risk of extravasation and ischaemic tissue damage norepinephrine is often administered via a central venous catheter. Administration of norepinephrine via a peripheral venous catheter may be a safe alternative during surgery, if the drug is administered correctly.

[Ischaemic preconditioning for protection against reperfusion injury in non-cardiac surgery]. / Iskæmisk prækonditionering til forebyggelse af reperfusionsskade ved ikkekardial kirurgi.

Remote ischaemic preconditioning is a non-invasive intervention that is done by transient occlusion of the blood flow to a limb with a blood pressure cuff. The intervention initiates a systemic endogenous protective response, which may confer multi-organ protection against acute ischaemia reperfusion injury. Originally discovered as a therapeutic strategy in cardiac surgery for protecting the myocardium against ischaemia reperfusion injury, it has been discovered that remote ischaemic preconditioning may confer protection against surgical stress and reperfusion injury in non-cardiac surgery.

[Myocardial injury and infarction is an overlooked complication after non-cardiac surgery]. / Myokardieskade er en overset komplikation efter ikkekardial kirurgi.

Annually, several million patients undergoing non-cardiac surgery develop myocardial injury or a myocardial infarction in the perioperative period. This frequent complication is associated with a high mortality. Despite an increasing focus on the issue the pathophysiology and the treatment of perioperative myocardial injury and infarction still remains partly unclear. Recently a new risk stratification tool was developed, which allows physicians to identify patients at risk. This review offers insight into the prevalence, pathophysiology, diagnostics, risk stratification and treatment of perioperative myocardial injury and infarction.

Pharmacological attenuation of myocardial reperfusion injury in a closed-chest porcine model: a systematic review.

Myocardial ischemia-reperfusion injury is a clinical challenge in interventional cardiology, and at the moment, no pharmacological agent is universally accepted in the prevention. In order to prevent inappropriate clinical trials, a potential pharmacological agent should be proved reproducibly effective in clinically relevant experimental studies before initiation of human studies. The closed-chest porcine model is a promising experimental model of ischemia-reperfusion injury. The purpose of this systematic review was to describe the pharmacological treatments evaluated in the closed-chest porcine model and discuss different aspects of the model for future use. The systematic review was performed according to the PRISMA guidelines.

Melatonin does not affect oxidative/inflammatory biomarkers in a closed-chest porcine model of acute myocardial infarction.

AIM: To test whether melatonin reduces oxidative and inflammatory biomarkers in a closed-chest porcine model of acute myocardial infarction. MATERIALS AND METHODS: Twenty pigs were randomized to receive a total dosage of 200 mg (0.4 mg/ml) of melatonin, or placebo immediately prior to reperfusion of a coronary artery balloon occlusion in a randomized, observer-blinded, placebo-controlled trial. We assessed high-sensitivity troponin T (hs-TnT), malondialdehyde and interleukin-1b, -6 and -10 at baseline, 30 min and 1, 2, 3 and 4 h after the start of reperfusion. RESULTS: Seventeen pigs completed the trial. There was an increase in hs-TnT, but no significant difference between the melatonin-treated and placebo-treated groups. There were no significant differences in development of any of the circulating plasma markers between the two groups. CONCLUSION: Melatonin treatment did not result in reduction of inflammatory or oxidative stress markers after experimental myocardial infarction compared to placebo.