Location
Philadelphia, PA
Start Date
30-4-2025 1:00 PM
End Date
30-4-2025 4:00 PM
Description
INTRODUCTION: Myocardial infarction, or death of heart tissue due to ischemia following obstruction of blood flow through one or more of the vessels supplying the myocardium, is a major cause of mortality in the United States and worldwide. Currently, treatment of ischemia centers around relieving the obstruction to blood flow, allowing for reperfusion of ischemic tissue. However, this inevitably causes ischemia-reperfusion injury (IRI), additional tissue damage following restoration of blood flow to an area previously deprived of blood and oxygen. Research on how to mitigate the effects of IRI is ongoing, and several different compounds have been shown to be somewhat effective in reducing the extent of injury following an ischemia-reperfusion event. Mitochondrial-targeted antioxidants are particularly attractive, as they work by suppressing the formation of reactive oxygen species (ROS) and neutralizing already-produced ROS. The formation and dissemination of ROS is known to be a major player in the tissue injury that ensues following reperfusion of ischemic tissue. SkQ1 (10-(6′-plastoquinone) decyl triphenylphosphonium) is a specific mitochondrial-targeted antioxidant that has a great deal of potential as a pharmaceutical agent. In the literature, SkQ1 has been shown to mitigate the extent of cardiac IRI through a variety of measures, including reduced size of infarcted tissue, reduced levels of molecular markers of myocardial damage, and more normal measures of myocardial mitochondria function following IRI. While this is very promising, experimenters used a variety of different routes of administration of SkQ1, including oral, intraperitoneal, and retrograde perfusion of the ex-vivo heart through cannulation of the aorta, known as the Langendorff method. Similarly, ideal dosages of SkQ1 are not yet universally accepted, and whether it is more beneficial to pre-condition, administer SkQ1 prior to ischemia, or post-condition, administer SkQ1 after ischemia, is unknown.
METHODS: We studied the effects of SkQ1 on cardiac IRI in male Sprague-Dawley rats. The purpose of our study was to determine the effectiveness of SkQ1 at reducing infarct size and improving measures of cardiac function in hearts exposed to IRI. The effects of various concentrations of SkQ1 (0.02 µM, 0.1 µM, 1 µM, 5 µM, and 10 µM) infused via the Langendorff retrograde perfusion method either immediately prior to induction of ischemia (pre-conditioning) or immediately after induction of ischemia (post-conditioning) were assessed on 19 isolated hearts of male Sprague-Dawley rats. 12 hearts were perfused in the same manner with control solution.
RESULTS: Ultimately, we were not able to demonstrate a significant reduction in infarct size or improvement of cardiac function parameters in isolated rat hearts perfused with a solution containing SkQ1 versus a control solution.
DISCUSSION: Limitations of our study include a low sample size, the inherent complexity of the Langendorff technique, and an inability to perform this experiment in vivo. Further research with a larger sample size and different routes of compound administration will be necessary to further explore the effects of SkQ1 on cardiac IRI, learn optimal dosages, and understand whether pre-conditioning or post-conditioning yields more favorable results.
Embargo Period
5-29-2025
Included in
The role of SkQ1 in mitigating myocardial ischemia-reperfusion injury in rats ex vivo
Philadelphia, PA
INTRODUCTION: Myocardial infarction, or death of heart tissue due to ischemia following obstruction of blood flow through one or more of the vessels supplying the myocardium, is a major cause of mortality in the United States and worldwide. Currently, treatment of ischemia centers around relieving the obstruction to blood flow, allowing for reperfusion of ischemic tissue. However, this inevitably causes ischemia-reperfusion injury (IRI), additional tissue damage following restoration of blood flow to an area previously deprived of blood and oxygen. Research on how to mitigate the effects of IRI is ongoing, and several different compounds have been shown to be somewhat effective in reducing the extent of injury following an ischemia-reperfusion event. Mitochondrial-targeted antioxidants are particularly attractive, as they work by suppressing the formation of reactive oxygen species (ROS) and neutralizing already-produced ROS. The formation and dissemination of ROS is known to be a major player in the tissue injury that ensues following reperfusion of ischemic tissue. SkQ1 (10-(6′-plastoquinone) decyl triphenylphosphonium) is a specific mitochondrial-targeted antioxidant that has a great deal of potential as a pharmaceutical agent. In the literature, SkQ1 has been shown to mitigate the extent of cardiac IRI through a variety of measures, including reduced size of infarcted tissue, reduced levels of molecular markers of myocardial damage, and more normal measures of myocardial mitochondria function following IRI. While this is very promising, experimenters used a variety of different routes of administration of SkQ1, including oral, intraperitoneal, and retrograde perfusion of the ex-vivo heart through cannulation of the aorta, known as the Langendorff method. Similarly, ideal dosages of SkQ1 are not yet universally accepted, and whether it is more beneficial to pre-condition, administer SkQ1 prior to ischemia, or post-condition, administer SkQ1 after ischemia, is unknown.
METHODS: We studied the effects of SkQ1 on cardiac IRI in male Sprague-Dawley rats. The purpose of our study was to determine the effectiveness of SkQ1 at reducing infarct size and improving measures of cardiac function in hearts exposed to IRI. The effects of various concentrations of SkQ1 (0.02 µM, 0.1 µM, 1 µM, 5 µM, and 10 µM) infused via the Langendorff retrograde perfusion method either immediately prior to induction of ischemia (pre-conditioning) or immediately after induction of ischemia (post-conditioning) were assessed on 19 isolated hearts of male Sprague-Dawley rats. 12 hearts were perfused in the same manner with control solution.
RESULTS: Ultimately, we were not able to demonstrate a significant reduction in infarct size or improvement of cardiac function parameters in isolated rat hearts perfused with a solution containing SkQ1 versus a control solution.
DISCUSSION: Limitations of our study include a low sample size, the inherent complexity of the Langendorff technique, and an inability to perform this experiment in vivo. Further research with a larger sample size and different routes of compound administration will be necessary to further explore the effects of SkQ1 on cardiac IRI, learn optimal dosages, and understand whether pre-conditioning or post-conditioning yields more favorable results.