Effect on ischemia - reperfusion injury in a D1 locus impairment mouse model
The prevalence of heart failure in the western world is estimated to be 1-2% and is expected to rise as a consequence of improved survival of other cardiac diseases and the aging population. The morbidity and mortality of patients with heart failure are high and the costs of treatment and follow-up of this group of patients are substantial.
Although many conditions can cause HF (coronary artery disease, hypertension, cardiomyopathies, valvular and congenital heart disease, arrhythmias, pericardial disease, myocarditis, pulmonary hypertension, and cardiotoxic substances - including alcohol), the predominant cause of HF in the western world is ischaemic heart disease (IHD)
After an ischaemic insult, the surgical procedure commonly used to restore proper blood flow to the heart triggers a phenomenon called reperfusion after ischemia (IR). However, paradoxically, reperfusion is usually associated with increase of the injured region, mainly due to mitochondrial dysfunction, increases in oxygen free radical production, intracellular calcium overload, hypercontracture, pH alterations, and myocardial inability to readjust to aerobic metabolism and oxidative phosphorylation, culminating in the loss of viable myocardium at the end of reperfusion.
After performing several lines of experiments using a model of hypoxia -reoxygenation in human cardiac cells we have strong indications on the regulation of a specific protein that potentially may be beneficial in the outcome of the heart following ischemic injury. We believe that this protein that protein is protecting the heart. To determine the effect on the heart we need to verify the effect of regulation of this protein in the ischemic -reperfusion situation. To verify this we will use a specific D1 locus impairment mouse model. The working hypothesis is that reduced levels of this protein (D1) that is verified in this model will cause significantly increased ischemic injury following reperfusion.
The established mouse model will be received from collaborators at John Hopkins Hospital, Baltimore, US.
All experiments are acute and the mice will not experience any pain. We will collect the heart during anaesthesia and thereafter transfer the hearts immediately to a langendorff perfusion system for retrograde perfusion. The hearts will thereafter undertake an ischema-reperfusion protocol. Finally, there will be conducted molecular analysis on isolated cardiac tissue.
In order to study the molecular effects in the intact heart it is necessary to use an animal model. The animal model that will be used in this study is well-known. The number of animals included in the study is set to a minimum of what is needed based on statistical analysis.
Although many conditions can cause HF (coronary artery disease, hypertension, cardiomyopathies, valvular and congenital heart disease, arrhythmias, pericardial disease, myocarditis, pulmonary hypertension, and cardiotoxic substances - including alcohol), the predominant cause of HF in the western world is ischaemic heart disease (IHD)
After an ischaemic insult, the surgical procedure commonly used to restore proper blood flow to the heart triggers a phenomenon called reperfusion after ischemia (IR). However, paradoxically, reperfusion is usually associated with increase of the injured region, mainly due to mitochondrial dysfunction, increases in oxygen free radical production, intracellular calcium overload, hypercontracture, pH alterations, and myocardial inability to readjust to aerobic metabolism and oxidative phosphorylation, culminating in the loss of viable myocardium at the end of reperfusion.
After performing several lines of experiments using a model of hypoxia -reoxygenation in human cardiac cells we have strong indications on the regulation of a specific protein that potentially may be beneficial in the outcome of the heart following ischemic injury. We believe that this protein that protein is protecting the heart. To determine the effect on the heart we need to verify the effect of regulation of this protein in the ischemic -reperfusion situation. To verify this we will use a specific D1 locus impairment mouse model. The working hypothesis is that reduced levels of this protein (D1) that is verified in this model will cause significantly increased ischemic injury following reperfusion.
The established mouse model will be received from collaborators at John Hopkins Hospital, Baltimore, US.
All experiments are acute and the mice will not experience any pain. We will collect the heart during anaesthesia and thereafter transfer the hearts immediately to a langendorff perfusion system for retrograde perfusion. The hearts will thereafter undertake an ischema-reperfusion protocol. Finally, there will be conducted molecular analysis on isolated cardiac tissue.
In order to study the molecular effects in the intact heart it is necessary to use an animal model. The animal model that will be used in this study is well-known. The number of animals included in the study is set to a minimum of what is needed based on statistical analysis.