Deep hypothermia during ischemia improves functional recovery and reduces free-radical generation in isolated reperfused rat heart

Gambert, Ségolène; Bès-Houtmann, Sandrine; Vandroux, David; Tissier, Cindy; Vergely, Catherine; Rochette, Luc; Athias, Pierre

doi:10.1016/s1053-2498(03)00211-0

Cited by 14 publications

(10 citation statements)

References 17 publications

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“…This mild uncoupling of oxidative phosphorylation during cold ischemia leads to attenuated mitochondrial dysfunction during warm reperfusion (4,44). Preservation of antioxidant capacity and reduction of free radicals during I/R may account for the protection afforded by hypothermia (21,23,29).…”

Section: Discussionmentioning

confidence: 99%

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ROS scavenging before 27°C ischemia protects hearts and reduces mitochondrial ROS, Ca²⁺ overload, and changes in redox state

Camara¹,

Aldakkak²,

Heisner³

et al. 2007

American Journal of Physiology-Cell Physiology

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In this study, we determined 1) whether ROS scavenging only during cold perfusion before global ischemia improves mitochondrial and myocardial function, and 2) which ROS leads to compromised cardiac function during ischemia and reperfusion (I/R) injury. Using fluorescence spectrophotometry, we monitored redox balance (NADH and FAD), O 2•Ϫ levels and mitochondrial Ca 2ϩ (m[Ca 2ϩ ]) at the left ventricular wall in 120 guinea pig isolated hearts divided into control (Con), MnTBAP (a superoxide dismutase 2 mimetic), MnTBAP (M) ϩ catalase (C) ϩ glutathione (G) (MCG), CϩG (CG), and N G -nitro-L-arginine methyl ester (L-NAME; a nitric oxide synthase inhibitor) groups. After an initial period of warm perfusion, hearts were treated with drugs before and after at 27°C. Drugs were washed out before 2 h at 27°C ischemia and 2 h at 37°C reperfusion. We found that on reperfusion the MnTBAP group had the worst functional recovery and largest infarction with the highest m [Ca 2ϩ ], most oxidized redox state and increased ROS levels. The MCG group had the best recovery, the smallest infarction, the lowest ROS level, the lowest m [Ca 2ϩ ], and the most reduced redox state. CG and L-NAME groups gave results intermediate to those of the MnTBAP and MCG groups. Our results indicate that the scavenging of cold-induced O 2•Ϫ species to less toxic downstream products additionally protects during and after cold I/R by preserving mitochondrial function. Because MnTBAP treatment showed the worst functional return along with poor preservation of mitochondrial bioenergetics, accumulation of H 2 O 2 and/or hydroxyl radicals during cold perfusion may be involved in compromised function during subsequent cold I/R injury. hypothermic ischemia; mitochondrial Ca 2ϩ ; reactive oxygen species HYPOTHERMIA of the arrested, ischemic heart improves its function on reperfusion compared with the normothermic arrested ischemic heart. The strategy behind hypothermic protection against ischemia, i.e., better tissue perfusion, and improved metabolic and mechanical function on reperfusion, is the reduced mitochondrial respiration and oxidative phosphorylation during ischemia that results in better mitochondrial respiration and regeneration of ATP on reperfusion. For example, we demonstrated that NADH, m [Ca 2ϩ ], and reactive O 2 species (ROS) levels were less altered during and after 30 min of ischemia at 17°C vs. 37°C (39). We reported that the more severe the hypothermia, the later is the onset of deleterious changes in mitochondrial function (1,2,16,22,31).Although hypothermia is very protective against ischemia, hypothermic perfusion, e.g., before subsequent cardiac ischemia, may cause injury due to altered cellular ion homeostasis resulting from impaired membrane ion pumps and exchangers and/or to reduced activity of enzymes responsible for mitochondrial respiration, scavenging of ROS, and contractile activity. A well-known effect of hypothermia is hypercontracture with elevated cytosolic [Ca 2ϩ ] (42). Another is a decreasing temperature-depende...

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Section: Discussionmentioning

confidence: 99%

“…Portions of this work were presented in abstract form at the 48th Annual Meeting of the Biophysical Society, Baltimore, MD, February 14 -18, 2004, and at the Experimental Biology Conference, Washington, DC, April [17][18][19][20][21] 2004.…”

Section: Acknowledgmentsmentioning

confidence: 99%

ROS scavenging before 27°C ischemia protects hearts and reduces mitochondrial ROS, Ca²⁺ overload, and changes in redox state

Camara¹,

Aldakkak²,

Heisner³

et al. 2007

American Journal of Physiology-Cell Physiology

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“…With deep hypothermia, an increase in 14 ROS formation occured during normoxia while it was conversely decreased after ischemia 15 and reperfusion 18 . In the same way, the use of electron spin resonance spectroscopy in 16 isolated rat heart allowed to evidence a reduced free-radical generation at reperfusion 17 following ischemia at 4°C 19 . The present study on mitochondria isolated at the end of an 18 ischemic episode without any reperfusion strongly suggested that the benefit offered by mild 19 hypothermia was directly related to the modulation of per-ischemic sensitivity to ischemia 20 rather than alterations occurring during reperfusion.…”

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confidence: 96%

Mild hypothermia reduces per-ischemic reactive oxygen species production and preserves mitochondrial respiratory complexes

et al. 2013

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“…39,40 Several experimental studies showed an attenuation in ischemia and reperfusion injury, in different organs (liver, lung, neuron), with hypothermia in different degrees. [17][18][19][20][21] Hypothermia was also used as a stimulating factor for the production of heat shock proteins, that showed a prophylactic protection of organ lesions including ischemia and reperfusion injury and acute pancreatitis. [41][42][43] Nevertheless, in clinical practice, some authors have found hyperamylasemia in hypothermic patients.…”

Section: Discussionmentioning

confidence: 99%

“…15,16 The ischemia and reperfusion injury has been also treated with hypothermia, and many authors have found an amelioration of the lesions in experimental studies. [17][18][19][20][21] Several studies have suggested that oxygen radicals play a role in a very early phase of AP, [22][23][24][25][26][27][28] and that the elevation of the pancreas oxidative status is related to the severity of the disease. 26,27 Exacerbated production of free oxygen radicals is related to the alteration of blood flow and to the ischemia/reperfusion phenomena.…”

Section: Introductionmentioning

confidence: 99%

Oxidative Stress Is Enhanced by Hypothermia Imposed on Cerulein-Induced Pancreatitis in Rats

Andraus

Jukemura

Dutra

et al. 2007

Clinics

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MC. Oxidative stress is enhanced by hypothermia imposed on cerulein-induced pancreatitis in rats. Clinics. 2007;62(4): 483-90. BACKGROUND:Hypothermia is a frequent event in severe acute pancreatitis (AP) and its real effects on the normal pancreas have not been well demonstrated. Moreover, neither have its effects on the outcome of acute pancreatitis been fully investigated. One hypothesis is that oxidative stress may be implicated in lesions caused or treated by hypothermia. Aim of the study: To investigate the effect of hypothermia in cerulein-induced acute pancreatitis (CIAP) in rats and the role played by oxidative stress in this process. METHODS: Male Wistar rats were divided into hypothermic and normothermic groups. Hypothermia was induced with a cold mattress and rectal temperature was kept at 30 o C for one hour. Acute pancreatitis was induced with 2 doses of cerulein (20 ìg/kg) administered at a one-hour interval. Serum amylase, pancreas vascular permeability by Evan's blue method, pancreas wet-to-dry weight ratio and histopathology were analyzed in each group. RESULTS: When compared with normothermic rats, hypothermic animals, with cerulein-induced acute pancreatitis, showed higher levels of pancreatic vascular permeability (P < 0.05), pancreas wet-to-dry weight ratio (P = 0.03), and histologically verified edema (P < 0.05), but similar serum amylase levels. The hypothermic group showed a higher oxidized-reduced glutathione ratio than the normothermic group. CONCLUSION: Moderate hypothermia produced a greater inflammatory response in established acute pancreatitis induced by cerulein in rats. Moreover, this study suggests that oxidative stress may be one of the mechanisms responsible for the worse outcome in hypothermic rats with cerulein-induced acute pancreatitis.

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Deep hypothermia during ischemia improves functional recovery and reduces free-radical generation in isolated reperfused rat heart

Cited by 14 publications

References 17 publications

ROS scavenging before 27°C ischemia protects hearts and reduces mitochondrial ROS, Ca²⁺ overload, and changes in redox state

ROS scavenging before 27°C ischemia protects hearts and reduces mitochondrial ROS, Ca²⁺ overload, and changes in redox state

Mild hypothermia reduces per-ischemic reactive oxygen species production and preserves mitochondrial respiratory complexes

Oxidative Stress Is Enhanced by Hypothermia Imposed on Cerulein-Induced Pancreatitis in Rats

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Deep hypothermia during ischemia improves functional recovery and reduces free-radical generation in isolated reperfused rat heart

Cited by 14 publications

References 17 publications

ROS scavenging before 27°C ischemia protects hearts and reduces mitochondrial ROS, Ca2+ overload, and changes in redox state

ROS scavenging before 27°C ischemia protects hearts and reduces mitochondrial ROS, Ca2+ overload, and changes in redox state

Mild hypothermia reduces per-ischemic reactive oxygen species production and preserves mitochondrial respiratory complexes

Oxidative Stress Is Enhanced by Hypothermia Imposed on Cerulein-Induced Pancreatitis in Rats

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ROS scavenging before 27°C ischemia protects hearts and reduces mitochondrial ROS, Ca²⁺ overload, and changes in redox state

ROS scavenging before 27°C ischemia protects hearts and reduces mitochondrial ROS, Ca²⁺ overload, and changes in redox state