Necrosis Case Studies

It is believed that, in the majority of patients who have involved prolonged ischemia, significantly reperfusion cause necrosis and increase infarct size, therefore therapeutic interventions is vital [101]. Adenosine A2 beta receptor agonists [102,103], sodium calcium exchanger blockers [104,105] and cyclosporine A [106, 107] at the ischemia reperfusion injury, two defined pathways cause necrosis. The first one is sarcolemma damage and hypercontraction at the time of reperfusion and the second one is mitochondrial dysfunction by the opening of the mitochondrial permeability transition pore (MPTP) that cause of irreversible damage. During reperfusion, oxygen and supplements are accessible for ischemic cardiomyocytes, so, intracellular acidosis washes out; however, calcium overload and dysfunction of contractile protein stimulation thanks to hypo contractility and sarcolemmal rupturing. MPTP is a nonspecific channel in the mitochondrial inner membrane and allows to the molecules smaller than 1.5 kDa to pass through [108, 109, 110]. In normal and physiological conditions, MPTP is closed; However, it is notable that during ischemia reperfusion and not ischemia alone, MTPT is open. After MPTP opening, mitochondrial membrane potential is lost just after 10 minutes of opening the pores. Also, mitochondria lost its normal dynamics and
The main proteins for MPTP function and regulation are ANT and Cyp D. Cyp D binds to the ANT and sensitized the MPTP to calcium and facilitates MPTP opening, suggested that Pi has the same function, also Pi control the matrix pH when generation polyphosphates groups or decreasing magnesium of matrix [113].
During ischemia reperfusion, surprisingly at the, MPTP is opened and Pi is elevated. There is calcium overloading thanks to ROS generation, thus necrosis and apoptosis happen