Adrenergic Antagonists Reduce Lactic Acidosis in Response to Hemorrhagic Shock

Luchette, Fred A.; Robinson, B. R. H.; Friend, Lou Ann; McCarter, Freda D; Frame, Sharon; James, J. Howard

doi:10.1097/00005373-199905000-00017

Cited by 45 publications

(29 citation statements)

References 21 publications

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“…Lactate traditionally "lags" due to its dependence on hepatic clearance, making it less of an accurate, dynamic marker of status. Also, it has been well-documented that epinephrine, produced abundantly during physiologic stress, stimulates lactate production by well-oxygenated skeletal muscle [Luchette 1999] [Luchette 2002. Due to these limitations, an elevated lactate level may not translate to a DO 2 deficiency.…”

Section: Discussionmentioning

confidence: 99%

Use of Near-Infrared Spectroscopy in Early Determination of Irreversible Hemorrhagic Shock

Taylor

Mulier

Myers

et al. 2005

The Journal of Trauma: Injury, Infection, and Critical Care

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Section: Discussionmentioning

confidence: 99%

Use of Near-Infrared Spectroscopy in Early Determination of Irreversible Hemorrhagic Shock

Taylor

Mulier

Myers

et al. 2005

The Journal of Trauma: Injury, Infection, and Critical Care

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“…Many had already pointed out catecholamine 183 treatment carries risk in treating shock (30,34). In fact adrenergic blockers are already used long 184 time back in shock states in animals and in patients (10,11,30,35,36).We will see more about this 185 aspect in vascular dysfunction section. 186…”

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confidence: 99%

Fundamental role of Warburg effect in various pathophysiological processes

Natesan¹

2017

Preprint

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Even though high NO via iNOS was involved in most of the pathologies including sepsis, any 56 substance that inhibits or uncouples the mitochondrial respiration can initiate this Warburg effect 57 and irreversible dedifferentiation. A mild and reversible Warburg differentiation dedifferentiation 58 effect may be necessary for normal functioning and the same effect in exaggerated and irreversible 59 way leading to irreversible dedifferentiation states may be the underlying mechanism in most of the 60 diseases including septic shock. 61 62 Keywords: Septic shock, Warburg effect, dedifferentiation, differentiation therapy, ascorbic acid, 63 adrenergic blockers, glycolysis. 64Abbreviations : systemic hypertension(SHT), pulmonary arterial hypertension (PAH),congestive 65 heart failure (CHF), acute kidney injury(AKI),acute respiratory distress syndrome(ARDS),diabetes 66 mellitus(DM),inducible nitric oxide synthase (iNOS) . 67 68 69 70 INTRODUCTION: 71This review article tries to show the fundamental role played by Warburg effect in most of the 72 pathologies. Warburg common pathogenesis model is proposed to show the common underlying 73 mechanism in most of the pathologies and septic shock was used as the base model. 74Sepsis is the harmful systemic response of the host to the infection (1). According to Lewis Thomas 75 the host's response to pathogen is more detrimental than the pathogen itself (2). Septic shock and 76 severe sepsis associated multi-organ dysfunction carries high mortality rate ~ 40 -70% (3,4). 77Septic shock is refractory to the vasopressors in most of the cases; this includes norepinephrine, the 78 primary drug used in reviving blood pressure in septic shock. Vascular hypo reactivity to various 79 vasopressors in septic shock has been studied extensively, many reviews are available (5,86). 80Irrespective of advances in this field, exact underlying mechanism behind septic shock is still a 81 mystery. Post mortem studies couldn't find the underlying cause in most of the cases, surprisingly 82 most of the organs looked normal (6).Lot of treatment options which were successful in animal 83 models were failed to show benefit in human studies, ranging from Nitric oxide Synthase (NOS) 84Inhibitors, Cyclooxygenase (COX) Inhibitors, endotoxin neutralizing proteins, TNF alpha 85 antagonists etc.., (3). Some of the recent promising directions include, counterintuitive use of 86 antihypertensive in septic shock -alpha2 adrenergic receptor agonists -clonidine (7-9), beta 87 blockers reviewed in (10, 11) -aimed to reduce the sympathetic hyper activation and hyper 88 metabolism associated with sepsis. Alpha2 AR antagonist also has been shown to improve survival 89 in sepsis animal model (12). Vitamin C has been used in sepsis reviewed in (13), Glycolysis 90 inhibitor shikonin (14), cytochrome C (15) and Caffeine (16). 91 Warburg common pathogenesis model has been proposed in this review article to explain the role of 92Warburg effect in most of the pathologies using septic shock as the base model. The model was 9...

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“…Infact all the current antihypertensive drugs may be used 785 to treat septic shock, as mentioned earlier, hypertension can be seen as the chronic 786 phase result of septic shock (Please see figure 2). As mentioned earlier adrenergic 787 blockers were already used in septic shock long time back and now there is a revived 788 interest in using adrenergic blockers in septic shock (89,90,(9)(10)(11)13,(141)(142)(143).Also as 789 mentioned earlier treatment depends on which phase the patient is in, as some drugs 790 which are helpful in one phase may not work or detrimental in other phase, e.g. 791 methylene blue and β blockers should be given only in late phase.…”

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“…Many had already 273 pointed out catecholamine treatment carries risk in treating shock, catecholamine treatment 274 in septic shock may do harm rather than saving the patient (85,87,88). In fact adrenergic 275 blockers -α & β adrenergic blockers were already used long time back in shock states in 276 animals and in patients (85,89,90).It is interesting to see the use of prazosin for treating 277 scorpion sting in this context (91). 278…”

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Becoming Archaea: Septic Shock, Warburg effect and loss of endosymbiotic relation-Billion year war of two genomes

Natesan¹

2017

Preprint

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: 31Septic shock is a major problem in medicine and carries high mortality rate. 32Irrespective of the advances in this field the underlying mechanism behind septic shock still 33 remains a mystery. To understand septic shock we need to understand the evolution of 34 eukaryotic cell and the billion year war between archaeal/nuclear genome and the 35 bacterial/mitochondrial genome. The ancient infection of archaeal host by the bacteria 36 (α-proteobacteria) resulted in the formation of eukaryotes and mitochondrial endosymbiont 37 occurred >1.5 billion years ago and this extraordinary event is occurring from then on all the 38 time till now resulted in formation of complex life forms. In this article I propose 'Warburg 39 common pathogenesis evolutionary model', which has the potential to explain septic shock 40 and most of the pathophysiological processes. I hypothesize that the bacterial/mitochondrial 41 invasion of the eukaryote cell is supported by the mitochondrial system of the host 42 eukaryotic cell and resisted by the innate immune system which is the archaeal part of the 43 host eukaryotic cell, as archaea is the real host before it became eukaryote.Three major 44 outcomes may result because of the bacterial /mitochondrial invasion related event, 45 1) PAMP/DAMP via PRR eg.TLR4 over activates innate immune system which in turn 46 inhibits the mitochondrial respiration and decreases the mitochondrial genome. Nuclear 47 genome overpowers mitochondrial genome which results in the loss of the endosymbiotic 48 relation between them, produces Warburg effect and the bacterial /mitochondrial invasion is 49 successfully defeated. By Warburg effect, the eukaryotic host cell now returned to its original 50 billion year old primitive form i.e. it became archaea like. This dedifferentiated state switching 51 can be seen as the cells local survival strategy in response to injuries as the cells are now 52 archaea like which has the ability to live in harsh environments. But returning to their 53 primitive forms leads to disorder and ends in global collapse of the organ systems and 54 organism which requires order in terms of differentiation which is maintained by the 55 mitochondrial system in the eukaryotic cell and across the cells by intercellular mitochondrial 56 transfer. Death of the organism may be due to the immortality pathway chosen by the cells 57 locally. 2) Successful bacterial /mitochondrial invasion of the eukaryotic host will increase the 58 mitochondrial genome and overpower the nuclear genome which may trigger apoptosis by 59 degrading the nuclear genome and expelling it. 3) Partially successful invasion may result in 60 the formation of cellular memory by increase in both OXPHOS and glycolysis. 61 I propose that the treatment in septic shock should aim at activation of mitochondrial 62 respiration thereby decreasing the aerobic glycolysis and changing the cell to its normal 63 adult dynamic differentiation phenotype i.e all the drugs should be used as differentiation 64 therapy. Adrenergic b...

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Adrenergic Antagonists Reduce Lactic Acidosis in Response to Hemorrhagic Shock

Cited by 45 publications

References 21 publications

Use of Near-Infrared Spectroscopy in Early Determination of Irreversible Hemorrhagic Shock

Use of Near-Infrared Spectroscopy in Early Determination of Irreversible Hemorrhagic Shock

Fundamental role of Warburg effect in various pathophysiological processes

Becoming Archaea: Septic Shock, Warburg effect and loss of endosymbiotic relation-Billion year war of two genomes

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