Shear Stress Induced by Acute Heat Exposure Is Not Obligatory to Protect Against Endothelial Ischemia-reperfusion Injury in Humans

2021 ◽  
Author(s):  
Holden W. Hemingway ◽  
Rauchelle E. Richey ◽  
Amy M. Moore ◽  
Austin M. Shokraeifard ◽  
Gabriel C. Thomas ◽  
...  
Keyword(s):  
Shear Stress ◽  
Endothelial Function ◽  
Reperfusion Injury ◽  
Brachial Artery ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Heat Exposure ◽  
Body Core Temperature ◽  
Whole Body ◽  
Flow Mediated Dilatation

Acute heat exposure protects against endothelial ischemia-reperfusion (I/R) injury in humans. However, the mechanism/s mediating this protective effect remain unclear. We tested the hypothesis that inhibiting the increase in shear stress induced by acute heat exposure would attenuate the protection of endothelial function following I/R injury. Nine (3 women) young healthy participants were studied under 3 experimental conditions: 1) thermoneutral control; 2) whole-body heat exposure to increase body core temperature by 1.2 °C; 3) heat exposure + brachial artery compression to inhibit the temperature-dependent increase in shear stress. Endothelial function was assessed via brachial artery flow-mediated dilatation before (pre-I/R) and after (post-I/R) 20 min of arm ischemia followed by 20 min of reperfusion. Brachial artery shear rate was increased during heat exposure (681 ± 359 s-1), but not for thermoneutral control (140 ± 63 s-1; P < 0.01 vs. heat exposure) nor heat + brachial artery compression (139 ± 60 s-1; P < 0.01 vs. heat exposure). Ischemia-reperfusion injury reduced flow-mediated dilatation following thermoneutral control (pre-I/R, 5.5 ± 2.9 % vs. post-I/R, 3.8 ± 2.9 %; P = 0.06), but was protected following heat exposure (pre-I/R, 5.8 ± 2.9 % vs. post-I/R, 6.1 ± 2.9 %; P = 0.5) and heat + arterial compression (pre-I/R, 4.4 ± 2.8 % vs. post-I/R, 5.8 ± 2.8 %; P = 0.1). Contrary to our hypothesis, our findings demonstrate that shear stress induced by acute heat exposure is not obligatory to protect against endothelial I/R injury in humans.

Ticagrelor Does Not Protect Against Endothelial Ischemia-Reperfusion Injury in Patients With Coronary Artery Disease

2020 ◽  
pp. 107424842096869
Author(s):  
Dinos Verouhis ◽  
Mattias Ekström ◽  
Magnus Settergren ◽  
Peder Sörensson ◽  
John Pernow ◽  
...  
Keyword(s):  
Endothelial Function ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Experimental Studies ◽  
Platelet Inhibition ◽  
Ischaemia Reperfusion Injury ◽  
Coronary Syndrome ◽  
Flow Mediated Dilatation ◽  
Significant Impairment

Background: Ticagrelor is a recommended P2Y12 receptor inhibitor after acute coronary syndrome (ACS). Its superiority has been suggested to rely on pleiotropic effects beyond platelet inhibition. Experimental studies indicate that ticagrelor may protect from ischemia-reperfusion injury but no data are available from such studies on patients. This study aimed to determine if chronic ticagrelor treatment protects against endothelial ischemia-reperfusion injury in patients with a previous ACS. Methods: Patients with a previous ACS were studied with flow mediated dilatation of the left brachial artery to determine the degree of endothelial ischemia-reperfusion injury before and after discontinuation of ticagrelor treatment, which had been continuous since 1 year. Each patient underwent 3 identical examinations. The first examination (Visit A) was at the end of ticagrelor treatment and the following 2 (Visit B and C) were after cessation of this treatment with an interval of 2 to 4 weeks. Results: Ischemia and reperfusion induced significant impairment of endothelial function at all 3 occasions (absolute decline in flow mediated dilatation 3.0% ± 0.7 at Visit A (p < 0.001), 1.9% ± 0.9 at Visit B (p < 0.05) and 1.9% ± 0.4 at Visit C (p < 0.0001)). However, there was no difference in the degree of endothelial ischemia-reperfusion injury or baseline endothelial function between the visits. Conclusion: Chronic ticagrelor treatment in patients 1 year after an ACS does not protect against endothelial ischaemia-reperfusion injury. Nor is it associated with better basal endothelial function compared to after discontinuation of treatment.

scholarly journals Influence of long-term treatment with glyceryl trinitrate on remote ischemic conditioning

2018 ◽  
Vol 315 (1) ◽  
pp. H150-H158 ◽  
Author(s):  
Marie Hauerslev ◽  
Sivagowry Rasalingam Mørk ◽  
Kasper Pryds ◽  
Hussain Contractor ◽  
Jan Hansen ◽  
...  
Keyword(s):  
Endothelial Function ◽  
Glyceryl Trinitrate ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Rat Myocardium ◽  
Remote Ischemic Conditioning ◽  
Ischemic Conditioning ◽  
Human Endothelium

Remote ischemic conditioning (RIC) protects against sustained myocardial ischemia. Because of overlapping mechanisms, this protection may be altered by glyceryl trinitrate (GTN), which is commonly used in the treatment of patients with chronic ischemic heart disease. We investigated whether long-term GTN treatment modifies the protection by RIC in the rat myocardium and human endothelium. We studied infarct size (IS) in rat hearts subjected to global ischemia-reperfusion (I/R) in vitro and endothelial function in healthy volunteers subjected to I/R of the upper arm. In addition to allocated treatment, rats were coadministered with reactive oxygen species (ROS) or nitric oxide (NO) scavengers. Rats and humans were randomized to 1) control, 2) RIC, 3) GTN, and 4) GTN + RIC. In protocols 3 and 4, rats and humans underwent long-term GTN treatment for 7 consecutive days, applied subcutaneously or 2 h daily transdermally. In rats, RIC and long-term GTN treatment reduced mean IS (18 ± 12%, P = 0.007 and 15 ± 5%, P = 0.002) compared with control (35 ± 13%). RIC and long-term GTN treatment in combination did not reduce IS (29 ± 12%, P = 0.55 vs. control). ROS and NO scavengers both attenuated IS reduction by RIC and long-term GTN treatment. In humans, I/R reduced endothelial function ( P = 0.01 vs. baseline). Separately, RIC and long-term GTN prevented the reduction in endothelial function caused by I/R; given in combination, prevention was lost. RIC and long-term GTN treatment both protect against rat myocardial and human endothelial I/R injury through ROS and NO-dependent mechanisms. However, when given in combination, RIC and long-term GTN treatment fail to confer protection. NEW & NOTEWORTHY Remote ischemic conditioning (RIC) and long-term glyceryl trinitrate (GTN) treatment protect against ischemia-reperfusion injury in both human endothelium and rat myocardium. However, combined application of RIC and long-term GTN treatment abolishes the individual protective effects of RIC and GTN treatment on ischemia-reperfusion injury, suggesting an interaction of clinical importance.

Effect of 3-aminotriazole on hyperthermia-mediated cardioprotection in rabbits

1996 ◽  
Vol 270 (4) ◽  
pp. H1165-H1171 ◽  
Author(s):  
J. G. Kingma ◽  
D. Simard ◽  
J. R. Rouleau ◽  
R. M. Tanguay ◽  
R. W. Currie
Keyword(s):  
Reperfusion Injury ◽  
Catalase Activity ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Whole Body ◽  
Cellular Protection ◽  
Whole Body Hyperthermia ◽  
Tetrazolium Staining

Hyperthermia-induced cardioprotection during myocardial ischemia may involve increased activity of antioxidative enzymes. In this study we investigated the effects of 3-amino-1,2,4-triazole (3-AT), an irreversible catalase inhibitor, in heat-shocked (HS) rabbits subjected to ischemia-reperfusion injury. Rabbits underwent whole body hyperthermia at 42 degrees C for 15 min. Twenty-four hours later, rabbits were administered either saline vehicle or 3-AT (1 or 2 g/kg i.p.) 30 min before undergoing 30 min of regional coronary occlusion and 3 h reperfusion. Controls did not undergo whole body hyperthermia and were given either saline or 3-AT. Heart rate and left ventricular pressure were recorded continuously during these experiments. Infarct area (tetrazolium staining) was normalized to anatomic risk zone size (microsphere autoradiography). Expression of HSP 71 was verified using Western blot analysis; myocardial catalase activity was determined in tissue biopsies. Infarct size was significantly reduced in HS rabbits (25.1 +/- 2.8%, P = 0.2; means +/- SE) compared with controls (53.6 +/- 4.7%). Treatment with 1 g/kg 3-AT attenuated HS-mediated cardioprotection (36.9 +/- 4.9%, P = 0.063 vs. HS); protection was abolished with 2 g/kg 3-AT (48.9 +/- 6.6%). Myocardial catalase activities were higher in tissue biopsies from HS rabbits (47.0 +/- 4.5 U/mg protein, P < or = 0.02) compared with controls (33.4 +/- 1.9 U/mg protein); catalase activities were significantly reduced in rabbits treated with 3-AT. In conclusion, whole body hyperthermia increases expression levels of HSP 71; myocardial catalase activity is also significantly increased. Myocardial protection is HS rabbits subjected to ischemia-reperfusion injury was reversed with 3-AT. These data suggest that increased intracellular activities of catalase and possibly other antioxidant enzymes is an important mechanism for hyperthermia-mediated cellular protection.

scholarly journals Influence of Hypoxic and Hyperoxic Preconditioning on Endothelial Function in a Model of Myocardial Ischemia-Reperfusion Injury with Cardiopulmonary Bypass (Experimental Study)

2020 ◽  
Vol 21 (15) ◽  
pp. 5336
Author(s):  
Irina A. Mandel ◽  
Yuri K. Podoksenov ◽  
Irina V. Suhodolo ◽  
Darya A. An ◽  
Sergey L. Mikheev ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cardiopulmonary Bypass ◽  
Endothelial Function ◽  
Light Microscopy ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Control Group ◽  
Endothelin 1 ◽  
Nitric Oxide Metabolites

The aim of the experiment was to evaluate the effect of preconditioning based on changes in inspiratory oxygen fraction on endothelial function in the model of ischemia-reperfusion injury of the myocardium in the condition of cardiopulmonary bypass. The prospective randomized study included 32 rabbits divided into four groups: hypoxic preconditioning, hyperoxic preconditioning, hypoxic-hyperoxic preconditioning, and control group. All animals were anesthetized and mechanically ventilated. We provided preconditioning, then started cardiopulmonary bypass, followed by induced acute myocardial infarction (ischemia 45 min, reperfusion 120 min). We investigated endothelin-1, nitric oxide metabolites, asymmetric dimethylarginine during cardiopulmonary bypass: before ischemia, after ischemia, and after reperfusion. We performed light microscopy of myocardium, kidney, lungs, and gut mucosa. The endothelin-1 level was much higher in the control group than in all preconditioning groups after ischemia. The endothelin-1 even further increased after reperfusion. The total concentration of nitric oxide metabolites was significantly higher after all types of preconditioning compared with the control group. The light microscopy of the myocardium and other organs revealed a diminished damage extent in the hypoxic-hyperoxic preconditioning group as compared to the control group. Hypoxic-hyperoxic preconditioning helps to maintain the balance of nitric oxide metabolites, reduces endothelin-1 hyperproduction, and enforces organ protection.

Chronic activation of PPARα is detrimental to cardiac recovery after ischemia

2006 ◽  
Vol 290 (1) ◽  
pp. H87-H95 ◽  
Author(s):  
Nandakumar Sambandam ◽  
Dominique Morabito ◽  
Cory Wagg ◽  
Brian N. Finck ◽  
Daniel P. Kelly ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Glucose Oxidation ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
High Fatty Acid ◽  
Whole Body ◽  
Cardiac Recovery ◽  
Oxidation Rates ◽  
Cardiac Power ◽  
Chronic Activation

High fatty acid oxidation (FAO) rates contribute to ischemia-reperfusion injury of the myocardium. Because peroxisome proliferator-activated receptor (PPAR)α regulates transcription of several FAO enzymes in the heart, we examined the response of mice with cardiac-restricted overexpression of PPARα (MHC-PPARα) or whole body PPARα deletion including the heart (PPARα−/−) to myocardial ischemia-reperfusion injury. Isolated working hearts from MHC-PPARα and nontransgenic (NTG) littermates were subjected to no-flow global ischemia followed by reperfusion. MHC-PPARα hearts had significantly higher FAO rates during aerobic and postischemic reperfusion (aerobic 1,479 ± 171 vs. 699 ± 117, reperfusion 1,062 ± 214 vs. 601 ± 70 nmol·g dry wt−1·min−1; P < 0.05) and significantly lower glucose oxidation rates compared with NTG hearts (aerobic 225 ± 36 vs. 1,563 ± 165, reperfusion 402 ± 54 vs. 1,758 ± 165 nmol·g dry wt−1·min−1; P < 0.05). In hearts from PPARα−/− mice, FAO was significantly lower during aerobic and reperfusion (aerobic 235 ± 36 vs. 442 ± 75, reperfusion 205 ± 25 vs. 346 ± 38 nmol·g dry wt−1·min−1; P < 0.05) whereas glucose oxidation was significantly higher compared with wild-type (WT) hearts (aerobic 2,491 ± 631 vs. 901 ± 119, reperfusion 2,690 ± 562 vs. 1,315 ± 172 nmol·g dry wt−1·min−1; P < 0.05). Increased FAO rates in MHC-PPARα hearts were associated with a markedly lower recovery of cardiac power (45 ± 9% vs. 71 ± 6% of preischemic levels in NTG hearts; P < 0.05). In contrast, the percent recovery of cardiac power of PPARα−/− hearts was not significantly different from that of WT hearts (80 ± 8% vs. 75 ± 9%). This study demonstrates that chronic activation of PPARα is detrimental to the cardiac recovery during reperfusion after ischemia.

Periodic acceleration (pGz) prior to whole body Ischemia reperfusion injury provides early cardioprotective preconditioning

Life Sciences ◽  
2010 ◽  
Vol 86 (19-20) ◽  
pp. 707-715 ◽  
Author(s):  
Jose A. Adams ◽  
Heng Wu ◽  
Jorge A. Bassuk ◽  
Jaqueline Arias ◽  
Arkady Uryash ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Whole Body ◽  
Periodic Acceleration
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