Adenosine, lidocaine and Mg2+improves cardiac and pulmonary function, induces reversible hypotension and exerts anti-inflammatory effects in an endotoxemic porcine model

Granfeldt, Asger; Letson, Hayley L.; Dobson, Geoffrey P.; Shi, Wei; Vinten‐Johansen, Jakob; Tønnesen, Else

doi:10.1186/s13054-014-0682-y

Cited by 37 publications

(38 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…115,116 Specifically, the combination of these three agents seems to confer cardiovascular protection, improvement of coagulation (presumably by inducing a shift in thrombin substrate specificity from the pro-fibrinolytic protein C pathway to the anti-fibrinolytic TAFI [thrombin-activatable-fibrinolysis-inhibitor] pathway at the endothelial thrombomodulin-thrombin complex level), reduction of proinflammatory factors (e.g., TNF-a) and increase of anti-inflammatory cytokines (e.g., IL-10). However, the mechanisms through which ALM ™ exerts the abovementioned beneficial effects remain elusive.…”

Section: Interventionsmentioning

confidence: 99%

Postinjury Inflammation and Organ Dysfunction

Sauaia

Moore

2017

Critical Care Clinics

146

106

View full text Add to dashboard Cite

Synopsis The development of organ dysfunction (OD) is related to the intensity and balance between trauma-induced simultaneous, opposite inflammatory responses. Early proinflammation via innate immune system activation may cause early OD, while anti-inflammation, via inhibition of the adaptive immune system and apoptosis, may induce immunoparalysis, impaired healing, infections, and late OD. Patients discharged with low level OD may develop the persistent inflammation-immunosuppression catabolism syndrome (PICS). Although the incidence of multiple organ failure (MOF) has decreased over time, it remains morbid, lethal and resource-intensive. Single OD, especially acute lung injury, however, remains frequent. At this time, treatment is limited, and prevention remains the mainstay strategy.

show abstract

Section: Interventionsmentioning

confidence: 99%

Postinjury Inflammation and Organ Dysfunction

Sauaia

Moore

2017

Critical Care Clinics

146

106

View full text Add to dashboard Cite

show abstract

“…We proposed that small-volume ALM assisted the heart and the body to recover with the blood left in the circulation after severe loss without large volume fluid therapy. In addition, ALM has potent anti-inflammatory properties by reducing the priming and activation of neutrophils ( 307 ), reduces TnF-alpha ( 308 ) and reduces endothelial damage ( 306 ). We have also shown similar protection in the rat model of 8 min asphyxial hypoxia where a small bolus of 0.9% NaCl ALM improved return of spontaneous circulation (ROSC), hemodynamics, coagulation status and survival ( 108 , 309 ).…”

Section: Search For New Therapies From a Systems-based Approachmentioning

confidence: 99%

Addressing the Global Burden of Trauma in Major Surgery

Dobson

2015

Front. Surg.

View full text Add to dashboard Cite

Despite a technically perfect procedure, surgical stress can determine the success or failure of an operation. Surgical trauma is often referred to as the “neglected step-child” of global health in terms of patient numbers, mortality, morbidity, and costs. A staggering 234 million major surgeries are performed every year, and depending upon country and institution, up to 4% of patients will die before leaving hospital, up to 15% will have serious post-operative morbidity, and 5–15% will be readmitted within 30 days. These percentages equate to around 1000 deaths and 4000 major complications every hour, and it has been estimated that 50% may be preventable. New frontline drugs are urgently required to make major surgery safer for the patient and more predictable for the surgeon. We review the basic physiology of the stress response from neuroendocrine to genomic systems, and discuss the paucity of clinical data supporting the use of statins, beta-adrenergic blockers and calcium-channel blockers. Since cardiac-related complications are the most common, particularly in the elderly, a key strategy would be to improve ventricular-arterial coupling to safeguard the endothelium and maintain tissue oxygenation. Reduced O2 supply is associated with glycocalyx shedding, decreased endothelial barrier function, fluid leakage, inflammation, and coagulopathy. A healthy endothelium may prevent these “secondary hit” complications, including possibly immunosuppression. Thus, the four pillars of whole body resynchronization during surgical trauma, and targets for new therapies, are: (1) the CNS, (2) the heart, (3) arterial supply and venous return functions, and (4) the endothelium. This is termed the Central-Cardio-Vascular-Endothelium (CCVE) coupling hypothesis. Since similar sterile injury cascades exist in critical illness, accidental trauma, hemorrhage, cardiac arrest, infection and burns, new drugs that improve CCVE coupling may find wide utility in civilian and military medicine.

show abstract

“…7 The ALM bolus and/or infusion treatments have been shown in rat and pig models to protect against regional myocardial ischemia, lethal arrhythmias, cardiac arrest, hemorrhagic shock, coagulopathy, inflammation, endotoxemia, infection and sepsis. [7][8][9][10][11][12] Adenosine, lidocaine and Mg 2+ alone do not confer these benefits. 7 In the present study, we hypothesized that the low-volume ALM drip/infusion may improve physiologic status in the first few hours following a single laparotomy.…”

Section: Introductionmentioning

confidence: 99%

Immune-inflammatory activation after a single laparotomy in a rat model: effect of adenosine, lidocaine and Mg²⁺ infusion to dampen the stress response

2017

Self Cite

View full text Add to dashboard Cite

Our aim was to examine the effect of low-volume 0.9% NaCl adenosine, lidocaine and Mg 2+ (ALM) 'drip' on early immune-inflammatory activation after a single laparotomy with no further manipulation. Male Sprague-Dawley rats were anesthetized and randomly assigned to one of the groups, baseline, 1 h infusion 0.9% NaCl AE ALM and metrics, 1 h infusion and 6-h metrics, and 6 h continuous infusion and metrics. Complete blood count, acid-base balance, systemic levels of IL-6 and IL-10, and coagulation status were measured. After 1 h, there was a disproportionate increase in circulating neutrophils between saline and ALM groups despite an identical 45% fall in lymphocytes. Disproportionate increases also occurred in platelet counts 1 h after surgery, and saline controls had increased respiratory alkalosis at 6 h with higher lactate. Systemic inflammation was also evident after 1 h in both groups (plasma IL-6 increase) and was amplified in saline-controls after 6 h. The ALM group increased anti-inflammatory cytokine IL-10. Surgery was not associated with acute coagulopathy; however, there were significant reductions in fibrinolysis. Following a single laparotomy, ALM infusion appeared to reduce stress-induced release of neutrophils and platelets into the circulation, and reduced acid-base disturbance. After 1 h, both groups had similar IL-6 levels, but ALM animals had increased IL-10, indicating improved inflammatory balance. The uncoupling of inflammation and coagulation activation but not fibrinolysis may offer a unique opportunity to investigate differential activation of innate immunity in response to sterile injury in this model.

show abstract

Adenosine, lidocaine and Mg2+improves cardiac and pulmonary function, induces reversible hypotension and exerts anti-inflammatory effects in an endotoxemic porcine model

Cited by 37 publications

References 60 publications

Postinjury Inflammation and Organ Dysfunction

Postinjury Inflammation and Organ Dysfunction

Addressing the Global Burden of Trauma in Major Surgery

Immune-inflammatory activation after a single laparotomy in a rat model: effect of adenosine, lidocaine and Mg²⁺ infusion to dampen the stress response

Contact Info

Product

Resources

About

Adenosine, lidocaine and Mg2+improves cardiac and pulmonary function, induces reversible hypotension and exerts anti-inflammatory effects in an endotoxemic porcine model

Cited by 37 publications

References 60 publications

Postinjury Inflammation and Organ Dysfunction

Postinjury Inflammation and Organ Dysfunction

Addressing the Global Burden of Trauma in Major Surgery

Immune-inflammatory activation after a single laparotomy in a rat model: effect of adenosine, lidocaine and Mg2+ infusion to dampen the stress response

Contact Info

Product

Resources

About

Immune-inflammatory activation after a single laparotomy in a rat model: effect of adenosine, lidocaine and Mg²⁺ infusion to dampen the stress response