Differences in the altered energy metabolism of hemorrhagic shock and hypoxemia

1976 ◽  
Vol 54 (5) ◽  
pp. 750-756 ◽  
Author(s):  
Irshad H. Chaudry ◽  
Mohammed M. Sayeed ◽  
Arthur E. Baue

The effect of hemorrhagic shock, hypoxemia, and anoxia on the levels of adenine and pyridine nucleotides of liver and kidney was assessed. ATP levels in liver and kidney of animals in shock or animals subjected to 7 min of anoxia decreased by 85 and 73%, respectively. Under hypoxic conditions (arterial [Formula: see text] at 18 mmHg), the decrease was only 62 and 48% in liver and kidney, respectively. Tissue NAD levels decreased and NADH levels increased during shock but were found to be essentially unaltered during experimental hypoxemia. Thus, shock produced greater alterations in adenine and pyridine nucleotides than did hypoxemia alone, indicating that stagnant hypoxemia due to shock is more deleterious to energy metabolism than is severe hypoxemia with an otherwise normal circulation. The results also suggest that if an arterial [Formula: see text] of 18 mmHg represents the initial stages of tissue hypoxia, then tissue ATP levels are a more sensitive indicator of this than NAD levels.

1977 ◽  
Vol 233 (3) ◽  
pp. R83-R88 ◽  
Author(s):  
I. H. Chaudry ◽  
M. M. Sayeed ◽  
A. E. Baue

It has been shown that infusion of ATP-MgCl2 proved beneficial in the treatment of shock; however, it is not known whether this effect is due to improvement in the microcirculation or direct provision of energy or a combination of the above or other effects. To elucidate the mechanism of the salutary effect of ATP-MgCl2, we have now examined the in vitro uptake of ATP by liver and kidney of animals in shock. Rats were bled to a mean arterial pressure of 40 Torr and so maintained for 2 hrs. After the rats were killed, liver and kidney were removed and slices of tissue (0.3-0.5 mm thick) were incubated for 1 h in 1.0 ml of Krebs-HCO3 buffer containing 10 mM glucose, 5 mM MgCl2, and 5 mM [8-14C]ATP or 5 mM [8-14C]ADP, or 5 mM [8-14C]AMP, or 5 mM [8-14C]adenosine in 95% O2-5% CO2 and then homogenized. Tissue and medium samples were subjected to electrophoresis to separate and measure the various nucleotides. The uptake of [14C]ATP but not that of [14C]ADP or [14C]adenosine by liver and kidney slices from animals in shock was 2.5 times greater than the corresponding uptake by control slices. Thus, the beneficial effect of ATP-MgCl2 in shock could be due to provision of energy directly to tissue in which ATP levels were lowered.


1984 ◽  
Vol 14 (1) ◽  
pp. 52-60 ◽  
Author(s):  
Masayuki Yamamoto ◽  
Yasuyuki Shimahara ◽  
Kazue Ozawa ◽  
Takayoshi Tobe ◽  
Wolf Isselhard

1997 ◽  
Vol 272 (6) ◽  
pp. F809-F815 ◽  
Author(s):  
A. Sahai ◽  
C. Mei ◽  
A. Zavosh ◽  
R. L. Tannen

The effect of chronic hypoxia on the proliferation and dedifferentiation of LLC-PK1 cells was examined. Cultures were exposed either to hypoxia (3% O2) or normoxia (18% O2), and [3H]thymidine incorporation, cell number, and sodium-dependent glucose (Na/Glc) uptakes were assessed. Cultures exposed to hypoxia for 16 h significantly increased [3H]thymidine incorporation followed by a significant increase in cell number both at 24 and 48 h in comparison with respective normoxic controls. Cultures exposed to 24 and 72 h of hypoxia exhibited significant inhibition of Na/Glc uptake when compared with their respective normoxic counterparts. Significant inhibition of cell ATP levels were observed under hypoxic conditions. Acute reoxygenation of hypoxic cells normalized cell ATP levels without any effect on the Na/Glc uptake. Hypoxia also activated protein kinase C (PKC) at 1 and 4 h followed by a subsequent return to baseline with reactivation at 24 h, which remained sustained up to 72 h, suggesting both acute and sustained activation of PKC. Furthermore, the hypoxia-induced alterations in [3H]thymidine incorporation as well as Na/Glc uptake were mitigated by inhibitors of PKC. These results indicate that chronic hypoxia induces both proliferation and dedifferentiation of LLC-PK1 cells mediated, in part, by the activation of PKC.


2021 ◽  
Vol 66 (1-2) ◽  
pp. 65-74
Author(s):  
Yu. Р. Orlov ◽  
V. V. Afanasyev ◽  
I. A. Khilenko

The aim of the work was the search for materials from experimental and clinical studies reflecting the pathogenetic role of the possible use of succinates for the correction of hypoxia in COVID-19. Materials and methods. 79 foreign and domestic literature sources were analyzed concerning the pathogenesis of COVID-19 and the pathogenetic role of succinates in hypoxia under conditions of COVID-19, oxidative stress, and diaphragmatic dysfunction were analyzed. The literature search was carried out using Pubmed and ELIBRARY.ru databases. Results. As the analysis of the literature has shown, tissue hypoxia is the basis of COVID-19 pathogenesis, triggering the entire cascade of  pathomorphological events leading to the development of multiple organ failure. A number of experimental and clinical studies (on a fairly large number of patients) reflect the positive effect of tissue hypoxia correction using succinates, both in adult patients and in children with a different spectrum of pathology associated with acute respiratory failure syndrome. Conclusion. Analysis of literature data allows to substantiate the prospect of using preparations containing succinate (reamberin, cytoflavin) in the complex therapy of severe cases of COVID-19. 


PLoS ONE ◽  
2015 ◽  
Vol 10 (5) ◽  
pp. e0127850 ◽  
Author(s):  
Puntita Siengdee ◽  
Nares Trakooljul ◽  
Eduard Murani ◽  
Manfred Schwerin ◽  
Klaus Wimmers ◽  
...  

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Masamichi Yamamoto ◽  
Yuichirou Kitai ◽  
Shigenori Yamamoto ◽  
Michael P Pieper ◽  
Yutaro Kotobuki ◽  
...  

Chronic pathological conditions, such as type 2 diabetes mellitus, involve various mechanisms in promoting heart failure by remodelling energy metabolic pathways and impairing cardiac contractility. The major source of myocardial energetics has been reported to shifts from OXPHOS in normal conditions to glycolysis in heart failure. Therefore, we decided to focus on the effect of empagliflozin on energy metabolic status in the heart.Recently, we generated two types of transgenic mice to monitor energy metabolism, intracellular ATP levels (iATP Tg) and mitochondrial ATP levels (mATP Tg) using FRET biosensor “ATeam” in the whole body, organ, and cellular levels as well as in beating heart. We intercrossed these mice with db/db, a mouse model of type 2 diabetes, and examined the energy metabolism of the heart in the empagliflozin -treated or non-treated groups.db/db;iATP Tg mice were fed EMPA-containing diets (30 mg/kg b.w., day) from 7 weeks of age for 10 weeks, and the ATP levels in the heart were measured by imaging with a fluorescence microscope. The results showed that, unlike the lowered ATP levels in the placebo group, the intracellular ATP level in the heart was significantly increased in the empagliflozin-treated group. Also, the ATP level was recovered in this empagliflozin-treated group to the same level as the wild type.Next, 8 weeks-old db/db;mATP Tg mice received a single dose of empagliflozin (30 mg/kg b.w.) via oral gavage after 4 hr of fasting. After another 3 hr of fasting, monitor the mitochondrial ATP level of the heart in vivo under the fluorescent microscope. The results showed that, unlike the placebo group, the ATP level in the mitochondria of the heart was significantly increased in the empagliflozin-treated group.These results suggest that empagliflozin may restore normal remodelling of energy metabolism in type 2 diabetic hearts.


1991 ◽  
Vol 261 (2) ◽  
pp. R351-R357 ◽  
Author(s):  
D. R. Meldrum ◽  
A. Ayala ◽  
P. Wang ◽  
W. Ertel ◽  
I. H. Chaudry

Although it is known that decreased ATP levels in liver and kidney contribute to organ dysfunction after shock, it remains unknown whether there is any association between decreased splenocyte ATP levels and splenic immune functions. Moreover, although studies have shown that ATP-MgCl2 treatment after shock improves hepatic and renal ATP levels and organ function, it remains unknown whether splenocyte ATP levels and immune functions are similarly affected by this agent. To study this, C3H/HeN mice were bled to a mean blood pressure of 35 mmHg, maintained at that pressure for 60 min, resuscitated with shed blood and Ringer lactate, and treated with ATP-MgCl2 (80 mumol/kg) or vehicle (saline). Splenocytes (SPL) were harvested at various intervals after hemorrhage, ATP levels were assessed by 31P nuclear magnetic resonance spectrometry, and functions were determined by measuring proliferative capacity and interleukin (IL)-2, and IL-3 synthesis. Hemorrhage depleted SPL ATP levels to 1.7 +/- 0.8% of control levels. However, there was a significant increase in ATP levels of ATP-MgCl2-treated mice (77 +/- 11%, P less than 0.05) compared with vehicle-treated animals (13 +/- 4.1%) at 1 h after resuscitation. SPL ATP levels returned to control by 2 h after resuscitation in the ATP-MgCl2 group, whereas ATP levels of the vehicle-treated mice remained significantly depressed (P less than 0.05) for up to 12 h after resuscitation. At 1 h after resuscitation, SPL proliferative capacity and IL-2 and IL-3 synthesis were all profoundly depressed in the vehicle-treated group (P less than 0.05 vs. control).(ABSTRACT TRUNCATED AT 250 WORDS)


2010 ◽  
Vol 16 (7-8) ◽  
pp. 254-261 ◽  
Author(s):  
Andrey V. Kozlov ◽  
J. Catharina Duvigneau ◽  
Tanya C. Hyatt ◽  
Raghavan Raju ◽  
Tricia Behling ◽  
...  

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