Protection of ischemic myocardium by whole-body hypothermia after coronary artery occlusion in dogs

Abendschein, Dana R.; Tacker, Willis A.; Babbs, Charles F.

doi:10.1016/0002-8703(78)90010-8

Cited by 35 publications

(10 citation statements)

References 20 publications

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“…15, 16 Many animal models have shown that hypothermia is protective, including a study in dogs in which whole-body hypothermia protected the ischaemic myocardium. 17 Also, hypothermia localised to the myocardial risk zone early after the onset of coronary occlusion salvaged 18% of the risk region and significantly decreased the area of infarct in rabbit studies. 15 Since then, myocardial hypothermia by endovascular cooling has been shown to decrease infarct size in pigs if administered during ischaemia, but not to be beneficial if administered at reperfusion.…”

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confidence: 89%

Mitochondrial ROS production and subsequent ERK phosphorylation are necessary for temperature preconditioning of isolated ventricular myocytes

2012

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Hypothermia and hypothermic preconditioning are known to be profoundly cardioprotective, but the molecular mechanisms of this protection have not been fully explained. In this study, temperature preconditioning (16 °C) was found to be cardioprotective in isolated adult rat ventricular myocytes, enhancing contractile recovery and preventing calcium dysregulation after oxidative stress. Hypothermic preconditioning preserved mitochondrial function by delaying the pathological opening of the mitochondrial permeability transition pore (mPTP), whereas transient mPTP flickering remained unaltered. For the first time, reactive oxygen species (ROS) from the mitochondria are shown to be released exclusively during the hypothermic episodes of the temperature-preconditioning protocol. Using a mitochondrially targeted ROS biosensor, ROS release was shown during the brief bursts to 16 °C of temperature preconditioning. The ROS scavenger N-(2-mercaptopropionyl) glycine attenuated ROS accumulation during temperature preconditioning, abolishing the protective delay in mPTP opening. Temperature preconditioning induces ROS-dependant phosphorylation of the prosurvival kinase extracellular signal-regulated kinase (ERK)1/2. ERK1/2 activation was shown to be downstream of ROS release, as the presence of a ROS scavenger during temperature preconditioning completely blocked ERK1/2 activation. The cardioprotective effects of temperature preconditioning on mPTP opening were completely lost by inhibiting ERK1/2 activation. Thus, mitochondrial ROS release and ERK1/2 activation are both necessary to signal the cardioprotective effects of temperature preconditioning in cardiac myocytes.

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confidence: 89%

Mitochondrial ROS production and subsequent ERK phosphorylation are necessary for temperature preconditioning of isolated ventricular myocytes

2012

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“…Also, administration of melatonin in animal models and humans has been associated with lowering of body temperature (5)(6)(7)(8)(9). Hypothermia in several studies has been shown to be protective in reducing myocardial damage resulting from ischemia (10)(11)(12)(13)(14)(15)(16)(17). Thus, the potential for melatonin to have favorable effects during myocardial ischemia and reperfusion may exist; however, there have been no studies to assess the role of melatonin in reducing experimental myocardial infarct size in an in vivo animal model.…”

mentioning

confidence: 99%

The Effect of Melatonin on Hemodynamics, Blood Flow, and Myocardial Infarct Size in a Rabbit Model of Ischemia-Reperfusion

Dave

Hale

Kloner

1998

J Cardiovasc Pharmacol Ther

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BACKGROUND: Melatonin, a hormone, has gained popularity and is being used by millions for a variety of indications. There are few data on its safety or its effects on hemodynamics and coronary blood flow. Also, studies have confirmed that melatonin is a potent antioxidant. Therefore, it may be capable of scavenging free radicals during the reperfusion phase after a heart attack. This study evaluates the safety of melatonin with regard to its cardiovascular effects and tests the hypothesis that melatonin might be protective in the setting of ischemia-reperfusion and reduce myocardial infarct size. METHODS AND RESULTS: Anesthetized rabbits were treated with melatonin (n = 8, 10 mg/kg, intravenously) 10 minutes before coronary artery occlusion (CAO) and again 15 minutes before reperfusion. Control rabbits received vehicle (n = 8). All rabbits underwent 30 minutes of occlusion and 3 hour reperfusion. Both before and during CAO, melatonin did not alter heart rate compared with control (185 +/- 7 beats/min v 181 +/- 7 before; and 179 +/- 5 v 181 +/- 9 during, respectively, P = NS) or blood pressure (70 +/- 4 mmHg v 66 +/- 6 before and 59 +/- 4 v 58 +/- 5 during, respectively, P = NS). Regional myocardial blood flow (RMBF) was similar before CAO in the melatonin group (1.18 +/- 0.17 mL/min/g) versus the control group (1.15 +/- 0.10 mL/min/g). Infarct size, expressed as a fraction of ischemic risk zone, was similar in the melatonin (0.29 +/- 0.03) and control groups (0.29 +/- 0.06, P = NS). At a higher dose of 50 mg/kg in treated (n = 7) versus control (n = 7) rabbits, melatonin treatment did not alter heart rate (204 +/- 14 in melatonin group v 181 +/- 5 in controls, P = NS) or blood pressure (80 +/- 11 in melatonin v 66 +/- 7 in controls, P = NS) when compared with control. Melatonin at this dose also did not affect infarct size, 0.38 +/- 0.06, when compared with control, 0.34 +/- 0.07, P = NS. CONCLUSION: Melatonin's effects on hemodynamics and coronary blood flow were neutral, and it did not exacerbate myocardial ischemia or necrosis in this model. Melatonin appears to be a safe drug with no apparent effects on the cardiovascular system in this model.

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“…It has been known for over 30 years that deep hypothermia (< 30°C) reduces the extent of a myocardial infarct (Abendschein et al, 1978); however, the detrimental physiological effects on the heart (spontaneous ventricular fibrillation and reduced ventricular function) makes it less suitable for treating conscious patients. The first study to demonstrate cardioprotective effects of mild hypothermia in myocardial ischemia was published in 1994 by Chien and coworkers (Chien et al, 1994).…”

Section: Early Animal Experiments Using Mild Hypothermia For Amimentioning

confidence: 99%

A Review of Mild Hypothermia as an Adjunctive Treatment for ST-Elevation Myocardial Infarction

Erlinge

2011

Therapeutic Hypothermia and Temperature Management

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Hypothermia is an established form of treatment employed following cardiac arrest to limit cerebral injury. The question addressed in this review is whether it is possible to use hypothermia to protect the heart during ischemia resulting from ST-elevation myocardial infarction (STEMI). Mild hypothermia (32°C-35°C) may be of benefit as an adjunctive treatment for STEMI by reducing the extent of the infarct and the effects of the four components of ischemia reperfusion injury: myocardial stunning, microvascular obstruction, reperfusion arrhythmia, and lethal reperfusion injury. To reduce cerebral injury after cardiac arrest, hypothermia can be initiated after reperfusion, and should be maintained for 24-48 hours. However, evidence suggests that to protect the heart in cases of STEMI, hypothermia should be initiated as early as possible after the onset of ischemia, at least before reperfusion. Clinical and experimental results indicate that it is of paramount importance to achieve a body temperature below 35°C before reperfusion to reduce the size of the infarct in the treatment of STEMI patients, and that treatment need only be continued for a relatively short period after reperfusion. Hypothermia has wide-ranging effects on most of the mechanisms involved in ischemia and reperfusion injury, which may explain the potent, highly reproducible cardioprotective effects seen in a large number of studies in different species. Subjecting conscious patients with STEMI to hypothermia is safe, feasible, and well tolerated, but antishivering strategies must be employed. Clinical studies are ongoing to evaluate hypothermia as an adjunctive treatment for myocardial infarction. This review discusses the experimental basis for using mild hypothermia to provide cardioprotection, methods of inducing hypothermia, the timing and duration of treatment, and ways in which the knowledge gained can be translated into clinical treatment.

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Protection of ischemic myocardium by whole-body hypothermia after coronary artery occlusion in dogs

Cited by 35 publications

References 20 publications

Mitochondrial ROS production and subsequent ERK phosphorylation are necessary for temperature preconditioning of isolated ventricular myocytes

Mitochondrial ROS production and subsequent ERK phosphorylation are necessary for temperature preconditioning of isolated ventricular myocytes

The Effect of Melatonin on Hemodynamics, Blood Flow, and Myocardial Infarct Size in a Rabbit Model of Ischemia-Reperfusion

A Review of Mild Hypothermia as an Adjunctive Treatment for ST-Elevation Myocardial Infarction

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