Statins for post resuscitation syndrome
Introduction
Following successful cardiopulmonary resuscitation (CPR) after cardiac arrest a multi-faceted disorder currently known as the post resuscitation syndrome develops [1]. There is evidence that this syndrome carries similarities to the systemic inflammatory changes of sepsis with the presence of circulating endotoxins and leukocyte dysregulation, increase in plasma cytokines, and adrenal dysfunction [2], [3], [4]. The disorder includes systemic reperfusion deficits due to endothelial swelling, vasospasm, increased blood viscosity, disseminated intravascular coagulopathy (DIC) and leukocyte interactions with the endothelium [5], [6], [7], [8]. These changes are more pronounced in the cerebrum as the autoregulation of cerebral blood flow is lost for an imbalance of vasoactive substances such as nitrous oxide, adenosine, endothelin and cyclic guanosine monophosphate causing vasoconstriction [8], [9], [10].
In addition, reoxygenation after return of spontaneous circulation accelerates the production of reactive oxygen species that alongside continued glutamate mediated excitatory neurotoxicity and renewed calcium shifts further activate cytotoxic enzymes such as endonucleases, proteases, phospholipases and xanthine oxidase [11], [12]. This reperfusion cascade leads to disseminated cell death and apoptosis following fragmentation of the DNA and mitochondrial lesions, thereby exacerbating the primary intra-arrest injury [8]. The importance of these injury mechanisms especially in the cerebrum is reflected by the fact that two thirds of the patients who eventually die after successful resuscitation from prehospital cardiac arrest and ICU admission die due to neurological injury [13].
Optimal treatment of the resuscitated patient includes early coronary reperfusion and haemodynamic optimization if necessitated, control of ventilation, blood glucose control, temperature control and the treatment of seizures [1]. In this hypothesis, we propose an additional pharmacological approach to the post resuscitation syndrome with statins and their pleiotropic effects for suppression of the exacerbated inflammatory/coagulation disorder.
Section snippets
Hypothesis
In addition to the lipid profile adjusting function of the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors or statins, they also exert effects independent of lipid metabolism via inhibition of isoprenoid synthesis [14], [15]. These pleiotropic effects are numerous and some may have a beneficial role in the post resuscitation phase. We have postulated a hypothesis that administrating statins immediately after cardiac arrest and resuscitation, or more preferably, already during the
Discussion
We propose four intertwined injury cascades of post resuscitation syndrome with potential for treatment with HMG CoA reductase inhibitors more commonly known as statins. Although the present data to support our hypothesis are mainly derived from clinical and experimental studies on cardiovascular diseases and focal ischaemia, there is evidence that similar injury cascades potentially responsive to statins are present in human cardiac arrest victims also [2], [3], [11], [12]. This hypothesis
References (36)
- et al.
Post resuscitation care – time for a care bundle?
Resuscitation
(2008) - et al.
Coagulopathy after successful cardiopulmonary resuscitation following cardiac arrest: implication of the protein C anticoagulant pathway
J Am Coll Cardiol
(2005) - et al.
Cerebral resuscitation: state of the art, experimental approaches and clinical perspectives
Neurol Clin
(2006) - et al.
Statins do more than just lower cholesterol
Lancet
(1996) - et al.
Reduction of platelet activity markers in type II hypercholesterolemic patients by a HMG-CoA-reductase inhibitor
Thromb Res
(1999) - et al.
The evolving role of statins in the management of atherosclerosis
J Am Coll Cardiol
(2000) - et al.
Tissue factor and tissue factor pathway inhibitor levels during and after cardiopulmonary resuscitation
Thromb Res
(1999) - et al.
Lipophilic HMG-CoA reductase inhibitor has an anti-inflammatory effect: reduction of MRNA levels for interleukin-1beta, interleukin-6, cyclooxygenase-2, and p22phox by regulation of peroxisome proliferator-activated receptor alpha (PPARalpha) in primary endothelial cells
Life Sci
(2000) - et al.
HMG-CoA reductase inhibition by atorvastatin reduces neointimal inflammation in a rabbit model of atherosclerosis
J Am Coll Cardiol
(1998) - et al.
Anti-oxidative properties of fluvastatin, an HMG-CoA reductase inhibitor, contribute to prevention of atherosclerosis in cholesterol-fed rabbits
Atherosclerosis
(2001)
Successful cardiopulmonary resuscitation after cardiac arrest as a “sepsis-like” syndrome
Circulation
Cortisol levels and adrenal reserve after successful cardiac arrest resuscitation
Shock
Cerebral ischemia II. The no-reflow phenomenon
Am J Pathol
Cerebral ischemia III. Vascular changes
Am J Pathol
Cerebral resuscitation potentials for cardiac arrest
Crit Care Med
Cerebrovascular reactivity in comatose patients resuscitated from a cardiac arrest
Stroke
Cerebral vasoconstriction in comatose patients resuscitated from a cardiac arrest?
Intensive Care Med
Mechanisms of injury in hypoxic-ischemic encephalopathy: implications to therapy
Semin Neurol
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