Hypoxic preconditioning attenuates ischemia-reperfusion injury in young healthy adults

2021 ◽  
Author(s):  
Caitlin P. Jarrard ◽  
Mercedes J. Nagel ◽  
Sten Stray-Gundersen ◽  
Hirofumi Tanaka ◽  
Sophie Lalande
Keyword(s):  
Blood Flow ◽  
Reperfusion Injury ◽  
Intermittent Hypoxia ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Arterial Oxygen ◽  
Flow Mediated Dilation ◽  
Healthy Individuals ◽  
Blood Flow Occlusion ◽  
Flow Occlusion

Ischemic preconditioning attenuates the reduction in brachial artery endothelial function following an ischemia-reperfusion injury. Brief bouts of systemic hypoxemia could similarly mitigate the blunted vasodilatory response induced by an ischemia-reperfusion injury. AIM: To determine whether an acute bout of intermittent hypoxia protects against an ischemia-reperfusion injury in young healthy individuals. METHODS: Brachial artery endothelial function was assessed by flow-mediated dilation in 16 young healthy individuals before and after a 20-minute blood flow occlusion to induce ischemia-reperfusion injury. Blood flow occlusion was preceded by either intermittent hypoxia or intermittent normoxia. Intermittent hypoxia consisted of three 4-minute hypoxic cycles at a targeted arterial oxygen saturation of 90% separated by 4-minute normoxic cycles. RESULTS: Intermittent hypoxia resulted in a lower arterial oxygen saturation (Hypoxia: 87±3 vs. Normoxia: 99±1%, p<0.01), which was equivalent to a lower fraction of inspired oxygen (Hypoxia: 0.123±0.013, Normoxia: 0.210±0.003, p<0.01). When preceded by intermittent normoxia, blood flow occlusion resulted in a blunted flow-mediated dilation. In contrast, the reduction in flow-mediated dilation following blood flow occlusion was attenuated by prior exposure to intermittent hypoxia (Hypoxia: 6.4±1.9 to 4.4±2.3, Normoxia: 7.1±2.5 to 4.0±2.4%, time x condition interaction p=0.048). Exposure to intermittent hypoxia did not affect mean arterial pressure (Hypoxia: 92±9, Normoxia: 89±8 mmHg, p=0.19) or cardiac output (Hypoxia: 5.8±1.1, Normoxia: 5.3±1.1 L·min-1, p=0.29). CONCLUSIONS: Hypoxic preconditioning attenuates the reduction in flow-mediated dilation induced by blood flow occlusion in young healthy individuals. Intermittent hypoxia represents a potential strategy to mitigate the effect of ischemia-reperfusion injury associated with ischemic events.

scholarly journals The use of pulse pressure variation for predicting impairment of microcirculatory blood flow

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Christoph R. Behem ◽  
Michael F. Graessler ◽  
Till Friedheim ◽  
Rahel Kluttig ◽  
Hans O. Pinnschmidt ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cardiac Output ◽  
Reperfusion Injury ◽  
Pulse Pressure ◽  
Pulse Pressure Variation ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Pressure Variation ◽  
Volume Loading ◽  
Microcirculatory Blood Flow

AbstractDynamic parameters of preload have been widely recommended to guide fluid therapy based on the principle of fluid responsiveness and with regard to cardiac output. An equally important aspect is however to also avoid volume-overload. This accounts particularly when capillary leakage is present and volume-overload will promote impairment of microcirculatory blood flow. The aim of this study was to evaluate, whether an impairment of intestinal microcirculation caused by volume-load potentially can be predicted using pulse pressure variation in an experimental model of ischemia/reperfusion injury. The study was designed as a prospective explorative large animal pilot study. The study was performed in 8 anesthetized domestic pigs (German landrace). Ischemia/reperfusion was induced during aortic surgery. 6 h after ischemia/reperfusion-injury measurements were performed during 4 consecutive volume-loading-steps, each consisting of 6 ml kg−1 bodyweight−1. Mean microcirculatory blood flow (mean Flux) of the ileum was measured using direct laser-speckle-contrast-imaging. Receiver operating characteristic analysis was performed to determine the ability of pulse pressure variation to predict a decrease in microcirculation. A reduction of ≥ 10% mean Flux was considered a relevant decrease. After ischemia–reperfusion, volume-loading-steps led to a significant increase of cardiac output as well as mean arterial pressure, while pulse pressure variation and mean Flux were significantly reduced (Pairwise comparison ischemia/reperfusion-injury vs. volume loading step no. 4): cardiac output (l min−1) 1.68 (1.02–2.35) versus 2.84 (2.15–3.53), p = 0.002, mean arterial pressure (mmHg) 29.89 (21.65–38.12) versus 52.34 (43.55–61.14), p < 0.001, pulse pressure variation (%) 24.84 (17.45–32.22) versus 9.59 (1.68–17.49), p = 0.004, mean Flux (p.u.) 414.95 (295.18–534.72) versus 327.21 (206.95–447.48), p = 0.006. Receiver operating characteristic analysis revealed an area under the curve of 0.88 (CI 95% 0.73–1.00; p value < 0.001) for pulse pressure variation for predicting a decrease of microcirculatory blood flow. The results of our study show that pulse pressure variation does have the potential to predict decreases of intestinal microcirculatory blood flow due to volume-load after ischemia/reperfusion-injury. This should encourage further translational research and might help to prevent microcirculatory impairment due to excessive fluid resuscitation and to guide fluid therapy in the future.

Mucosal arachidonate metabolism and intestinal ischemia-reperfusion injury

1989 ◽  
Vol 257 (2) ◽  
pp. G299-G307 ◽  
Author(s):  
M. J. Mangino ◽  
C. B. Anderson ◽  
M. K. Murphy ◽  
E. Brunt ◽  
J. Turk
Keyword(s):  
Blood Flow ◽  
Reperfusion Injury ◽  
Intestinal Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Leukotriene B4 ◽  
Time Dependent ◽  
Ischemia And Reperfusion ◽  
Synthesis Inhibitor ◽  
Intestinal Ischemia Reperfusion

Mucosal arachidonic acid metabolism was examined after 3 h of ischemia and 1 h of reperfusion in isolated ileal segments in the dog. The cyclooxygenase products thromboxane B2, 6-ketoprostaglandin F1 alpha, and prostaglandin E2 increased by 365%, 97%, and 158%, respectively, after ischemia and reperfusion but were not altered after 3 h of ischemia alone. The potent chemotactic lipoxygenase product leukotriene B4 (LTB4) increased by 687% after ischemia and reperfusion and was not affected by ischemia without reperfusion. In addition, tissue production of the thiol ether leukotrienes (LTC4, LTD4, and LTE4) increased threefold after ischemia and reperfusion. Quantitation of regionally isomeric hydroxy acids produced from arachidonate revealed a 300% increase in 12-hydroxyeicosatetraenoate (12-HETE) after intestinal ischemia and reperfusion without a change in other isomers (15-HETE and 5-HETE). Stereochemical analysis of 12-HETE demonstrated exclusive synthesis of the S-enantiomer. A significant and time-dependent decrease in intestinal blood flow also occurred during reperfusion. Administration of the dual cyclooxygenase-lipoxygenase synthesis inhibitor BW755C (1 mg/kg ia) did not alter time-dependent decreases in blood flow and failed to inhibit eicosanoid synthesis. Histologic examinations of intestinal samples revealed significant mucosal damage associated with ischemia alone and ischemia after reperfusion. This study indicates that intestinal ischemia-reperfusion injury is associated with dramatic alterations in mucosal production of vasoactive eicosanoids and with changes in blood flow that occur during reperfusion but not during ischemia alone. These events may be involved in the pathology characteristic of this injury.

scholarly journals Downstream effects of splanchnic ischemia-reperfusion injury on renal function and eicosanoid release

1997 ◽  
Vol 83 (2) ◽  
pp. 530-536 ◽  
Author(s):  
Patricia Rothenbach ◽  
Richard H. Turnage ◽  
Jose Iglesias ◽  
Angela Riva ◽  
Lori Bartula ◽  
...  
Keyword(s):  
Blood Flow ◽  
Renal Function ◽  
Reperfusion Injury ◽  
Renal Blood Flow ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Inulin Clearance ◽  
Downstream Effects ◽  
Splanchnic Ischemia ◽  
Eicosanoid Release

Rothenbach, Patricia, Richard H. Turnage, Jose Iglesias, Angela Riva, Lori Bartula, and Stuart I. Myers. Downstream effects of splanchnic ischemia-reperfusion injury on renal function and eicosanoid release. J. Appl. Physiol.82(2): 530–536, 1997.—This study examines the hypothesis that intestinal ischemia-reperfusion (I/R) injury contributes to renal dysfunction by altered renal eicosanoid release. Anesthetized Sprague-Dawley rats underwent 60 min of sham or superior mesenteric artery (SMA) occlusion with 60 min of reperfusion. The I/R groups received either allopurinol, pentoxifylline, 1-benzylimidazole, or carrier before SMA occlusion. In vivo renal artery blood flow was measured by Transonic flow probes, the kidneys were then perfused in vitro for 30 min, and the effluent was analyzed for eicosanoid release and renal function. Intestinal I/R caused a twofold increase in the ratio of renal release of thromboxane B2to prostaglandin E2and to 6-ketoprostaglandin F1αcompared with the sham level, with a corresponding 25% decrease in renal sodium and inulin clearance and renal blood flow. Pentoxifylline or allopurinol pretreatment restored renal eicosanoid release and renal sodium and inulin clearance to the sham level but did not alter renal blood flow. Pretreatment with 1-benzylimidazole restored renal function, eicosanoid release, and renal blood flow to sham levels. These data suggest that severe intestinal I/R contributes to the downregulation of renal function. The decrease in renal function is due in part to toxic oxygen metabolites, which occur in the milieu of altered renal eicosanoid release, reflecting a decrease in vasodilator and an increase in vasoconstrictor eicosanoids.

Effect of ischemia reperfusion or hypoxia reoxygenation on lung vascular permeability and resistance

1990 ◽  
Vol 69 (2) ◽  
pp. 597-603 ◽  
Author(s):  
R. C. Allison ◽  
J. Kyle ◽  
W. K. Adkins ◽  
V. R. Prasad ◽  
J. M. McCord ◽  
...  
Keyword(s):  
Blood Flow ◽  
Reperfusion Injury ◽  
Vascular Permeability ◽  
Vascular Resistance ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Pulmonary Vascular Permeability ◽  
Permeability Changes ◽  
Lung Vascular Permeability ◽  
Hypoxia Reoxygenation

The effect of ischemia reperfusion or hypoxia reoxygenation on pulmonary vascular permeability and resistance was studied in 25 isolated blood-perfused dog lungs. Vascular permeability, assessed by determining filtration coefficient (Kf), and vascular resistances were measured at the beginning and end of the experiment. Ischemia reperfusion was produced by occluding blood flow to the lung for 3 h and reperfusing for 1 h, whereas hypoxia reoxygenation was obtained by ventilating the lung with 95% N2-5% CO2 for 3 h and then ventilating with 95% O2-5% CO2 for 1 h with no interruption of perfusion. There was a significant increase in Kf in both ischemia reperfusion and hypoxia reoxygenation groups (51 and 85%, respectively), and total vascular resistance increased greatly in both groups (386 and 532%, respectively). Two additional groups were also studied in which the ischemia reperfusion or hypoxia reoxygenation lungs were pretreated with allopurinol (20 micrograms/ml). The Kf did not significantly increase in either the allopurinol ischemia reperfusion or the allopurinol hypoxia reoxygenation groups (22 and 6%, respectively). However, total vascular resistance significantly increased in both groups (239 and 224%, respectively). Although vascular permeability is modestly increased by both ischemia reperfusion and hypoxia reoxygenation, the predominant change in these conditions is the increased vascular resistance, which predominantly affects the postcapillary resistance and would result in a greater tendency for edema to develop in these slightly damaged lungs. Allopurinol, which inhibits xanthine oxidase, attenuated the permeability changes in both groups and may be useful in preventing ischemia reperfusion injury in certain conditions.

The Effect of Gradually Increased Blood Flow on Ischemia-Reperfusion Injury

2001 ◽  
Vol 47 (4) ◽  
pp. 412-416 ◽  
Author(s):  
??akir ??nal ◽  
Selahattin ??zmen ◽  
Yavuz Dem??r ◽  
Reha Yavuzer ◽  
Osman Lat??fo??lu ◽  
...  
Keyword(s):  
Blood Flow ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Increased Blood Flow

scholarly journals Beyond Preconditioning: Postconditioning as an Alternative Technique in the Prevention of Liver Ischemia-Reperfusion Injury

2016 ◽  
Vol 2016 ◽  
pp. 1-21 ◽  
Author(s):  
Kassiani Theodoraki ◽  
Iosifina Karmaniolou ◽  
Aliki Tympa ◽  
Marios-Konstantinos Tasoulis ◽  
Constantinos Nastos ◽  
...  
Keyword(s):  
Blood Flow ◽  
Reperfusion Injury ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Liver Ischemia ◽  
Neutrophil Accumulation ◽  
Postoperative Function ◽  
Early Reperfusion ◽  
And Function

Liver ischemia/reperfusion injury may significantly compromise hepatic postoperative function. Various hepatoprotective methods have been improvised, aiming at attenuating IR injury. With ischemic preconditioning (IPC), the liver is conditioned with a brief ischemic period followed by reperfusion, prior to sustained ischemia. Ischemic postconditioning (IPostC), consisting of intermittent sequential interruptions of blood flow in the early phase of reperfusion, seems to be a more feasible alternative than IPC, since the onset of reperfusion is more predictable. Regarding the potential mechanisms involved, it has been postulated that the slow intermittent oxygenation through controlled reperfusion decreases the burst production of oxygen free radicals, increases antioxidant activity, suppresses neutrophil accumulation, and modulates the apoptotic cascade. Additionally, favorable effects on mitochondrial ultrastructure and function, and upregulation of the cytoprotective properties of nitric oxide, leading to preservation of sinusoidal structure and maintenance of blood flow through the hepatic circulation could also underlie the protection afforded by postconditioning. Clinical studies are required to show whether biochemical and histological improvements afforded by the reperfusion/reocclusion cycles of postconditioning during early reperfusion can be translated to a substantial clinical benefit in liver resection and transplantation settings or to highlight more aspects of its molecular mechanisms.

scholarly journals Postconditioning ameliorates lipid peroxidation in liver ischemia-reperfusion injury in rats

2009 ◽  
Vol 24 (1) ◽  
pp. 52-56 ◽  
Author(s):  
Antonio Roberto Franchi Teixeira ◽  
Nilza T. Molan ◽  
Márcia Saldanha Kubrusly ◽  
Marta Bellodi-Privato ◽  
Ana Maria Coelho ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Blood Flow ◽  
Protective Effect ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Control Group ◽  
Liver Ischemia ◽  
Glutathione S Transferase ◽  
Ischemic Event

PURPOSE: Liver ischemia-reperfusion injury is a phenomenon presents in events like liver resections and transplantation. The restoration of blood flow may leads to local and systemic injury. Several techniques have been developed in order to avoid or ameliorate ischemia-reperfusion injury in clinical situations. The application of a sttuter reperfusion after the ischemic event (postconditioning) could alters the hydrodynamics and stimulates endogenous mechanisms that attenuate the reperfusion injury. The present study was designed to evaluate the potential protective effect of postconditioning in a model of ischemia-reperfusion in rats. METHODS: Hepatic anterior pedicle of median and left anterolateral segments were exposed and clamped for 1 hour. Two hours later, clamp was released in two different ways: Control Group (n=7): clamp was release straightforward; Postconditioning Group (n=7): clamp was released intermittently. Lipid peroxidation (malondialdehyde) and expression of the glutathione-s-transferase-α-3 gene were studied. RESULTS: Lipid peroxidation was significantly decreased in ischemic and non-ischemic liver by postconditioning. GST- α3 gene was overexpressed in postconditioned group, but not significantly. CONCLUSION: Postconditioning induced hepatoprotection by reducing lipid peroxidation in the ischemic and non-ischemic liver.

L-Arginine protects from ischemia-reperfusion-induced endothelial dysfunction in humans in vivo

2003 ◽  
Vol 95 (6) ◽  
pp. 2218-2222 ◽  
Author(s):  
John Pernow ◽  
Felix Böhm ◽  
Emma Beltran ◽  
Adrian Gonon
Keyword(s):  
Blood Flow ◽  
Endothelial Dysfunction ◽  
Reperfusion Injury ◽  
Forearm Blood Flow ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Venous Occlusion ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

It has been shown that nitric oxide (NO) protects from myocardial ischemia-reperfusion injury in animal models. The present study investigated whether administration of the NO substrate l-arginine protects against ischemia-reperfusion-induced endothelial dysfunction in humans. Forearm blood flow was measured with venous occlusion plethysmography in 16 healthy male subjects who were investigated on two occasions. Forearm ischemia was induced for 20 min followed by 60-min reperfusion. With the use of a crossover protocol, the subject received a 15-min intrabrachial artery infusion of l-arginine (20 mg/min) and vehicle (saline, n = 12 or d-arginine, n = 4) starting at 15 min of ischemia on two separate occasions. Compared with preischemia, endothelium-dependent increase in forearm blood flow induced by intra-arterial acetylcholine (3–30 μg/min) was significantly impaired at 15 and 30 min of reperfusion when the subjects received saline ( P < 0.001). When the subjects received l-arginine, the acetylcholine-induced increase in forearm blood flow was not significantly affected by ischemia-reperfusion. The recovery of endothelium-dependent vasodilatation at 15- and 30-min reperfusion was significantly greater after administration of l-arginine than after saline ( P < 0.05). d-Arginine did not affect the response to acetylcholine. Endothelium-independent vasodilatation to nitroprusside was not affected during reperfusion. These results demonstrate that the NO substrate l-arginine significantly attenuates ischemia-reperfusion-induced endothelial dysfunction in humans in vivo. This suggests that l-arginine may be useful as a therapeutic agent in the treatment of ischemia-reperfusion injury in humans.

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