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A Vital Process for Oxygenation and Health


Different chemical processes occur in living beings which result in chemical reactions in the body referred to as biochemical events. When they occur in the lungs, these events are associated with ischemia reperfusion injury in the lungs caused by trauma, arthrosclerosis or surgical procedures such as cardiopulmonary bypass. The lungs are one of the most important organs from the human body and for the human life. Ischemia reperfusion(IR) injury is a disorder in blood flow in blood vessel or part of body, this vessel or part of a body did not get enough blood, oxygen and other necessary blood components and this can be happen in all the body. IR injury in the lungs induces oxidative stress as a result of a combination of reactive oxygen and reactive nitrogen to form nitric oxide. Nowadays, there are several treatment approaches for ischemia reperfusion injury. Pharmacological treatment and vitamin therapy have been widely used to inhibit Ischemia reperfusion injury. This review focuses on biochemical events that cause Ischemia reperfusion injury in the lungs. It also addresses the therapeutic strategies that have attempted to overwhelm IR injury. New evolving emergency care techniques in medical research have also been analyzed. However this review also analyses other conditions such as systemic reduction and resuscitation that share pathophysiological mechanisms in medical care.


The lungs are a pair of organs in the body, and specifically in the chest cavity. The lungs have pink-gray spongy tissue. They function by processing gas exchange from incoming air. The process of breath in O2 and breathe out CO2is called gas exchange. As a result, the lungs are responsible and required to live because they ensure that the O2gets to the body and get rid of the CO2 from the body (Curry, 2003). After this procedure, the oxygen moves from the blood everywhere in the body (arteries, veins, and blood vessels). Frequently, some of these blood vessels do not bleed; this means they do not get enough oxygen for any reason. Then the body has a problem known as ischemia, ischemia can cause different problems like angina, cramping pain in the legs or abdominal pain (Yasmine et al, 2020).


Ischemia reperfusion injury is caused by different diseases and there is a possibility of occurrences in every transplantation or any surgery (Soars et al., 2020). The primary reason of ischemia is atherosclerosis. The atherosclerotic plaque prevents proper blood flow and lessens the oxygen in this part of the body. Ischemia can cause several problems like strokes or heart attack. Also, another cause of ischemia is the blood clot (COVID-19) et al., 2020). The ischemia-reperfusion injury can occur in a variety of organs including the kidneys, gut, lungs, skeletal muscles, brain, and heart (Fitridge and Thompson, 2012). It is necessary to report that different organ systems present divergent vulnerability to ischemia. Moreover, small periods of ischemia can remain alive in any organ cells, with a changeable analogy of those cells allowing withstanding longer ischemic periods than other cells. The name of this is termed reversible injury (Krenz, Baines, Kalogeria and Korthuis, 2016).

Pathophysiology of Ischemia Reperfusion Injury

IR injury state induces anaerobic metabolism which leads to reduced production of ATP and low iron exchange levels. Cells in these organisms swell and impair in functioning in the cytoplasm (Kalogeris, Bao and Korthuis, 2014). Ischemia means that one organ or one part of the body does not receive blood and oxygen and as a result this organ or part of body does not work properly. If the ischemia injuries are not treated immediately the ischemic organ will start dying, resulting in a condition known as infarction (Yasmine S. Ali, MD, MSCI, 2020). The overall percentage of lung transplant is lower due to their sensitivity in injury which may lead to IR injury during transplant. (Laubach and Sharma, 2020).

The ischemia reperfusion injury causes oxidative stress and that congests reactive oxygen (ROS) and the reactive nitrogen species (RNS). Moreover, the high levels of Nitric oxide (NO) and nitric oxide synthesis (iNOS) are likely to cause ischemia reperfusion injury. Reaction with ROS and NO produces platelet – endothelial may play a significant role in post - ischemia alveolar hyper fusion (Ovechkin et al., 2007). In ischemia, human body fails to break down glucose and other substances. In this phase, of ischemia glucose breaks down by mitochondrial anaerobic glycolysis producing two molecules of ATP, and the lactic acid, which result to the reduction pH of tissue. Then the ATP breaks down to ADP and AMP and these two, break down to inosine, hypoxanthine, adenosine, and xanthine. Furthermore, some major and minor reactive oxygen species are involved in ischemia reperfusion injury. The major species are superoxide anion(O2-), hydrogen peroxide (H2O2), hydroxyl radical (OH.), nitric oxide (NO) and peroxynitrite (ONOO-), and the minor species are lipid hydroperoxide, lipid peroxyl radical, thiol radical and lipid alkoxyl radical. These types of oxygen have a catastrophic role in tissue injury in ischemic reperfusion injury (Fitridge and Thompson, 2012).

Lung Transplantation

Ischemia reperfusion injury is an inevitable side effect of organ transplantation (Orlando, Remuzzi and Williams, 2017). Human lung transplantation is further restricted; nevertheless, only about 20% of lungs donors are appropriate for transplantation due to facts like trauma, edema, and aspiration (Fischer et al., 2020). 30% of patients after lung transplantation appear ischemia reperfusion injury which is life – threatening for the human body (Fischer et al., 2020). Research shows that ischemia reperfusion injury rises the danger BOS (bronchiolitis obliterans syndrome) after lung transplantation (Fiser et al., 2002).Also, the ischemic time is not a danger for premature cell death after human lung transplantation (Novick, 2020).

The lung transplantation can treat the pulmonary hypertension, the chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis, and the cystic fibrosis. There are 3 type of lung transplant. The first type is a single lung transplant, the second is a double lung transplant, and the last type is a heart – lung transplant. The first type is recommended to people with pulmonary fibrosis, the second is for people with cystic fibrosis or COPD, and the last one is suitable for people with pulmonary hypertension. A lung transplant is a common type of surgery with high risk of complications (Lung transplant, 2020). The larger risk of transplant is organ rejection. Another risk of lung transplant is the bleeding and blood clot, the diabetes, stomach problem, cancer, kidney damage, and osteoporosis (Lung Transplant: Purpose, Procedure, and Risks, 2020).

Ischemia Reperfusion injury in different diseases

1. Ischemia heart diseases

This condition occurs by narrowing of heart arteries which later inhibits blood supply to the heart muscles. In most cases, it is referred to as coronary artery a disease which may lead to heart attacks in the long run(Coronary Heart Disease | NHLBI, NIH, 2020). This condition is common in US with painless episodes and no prior warnings. In some people, the condition may have angina pectoris with undiagnosed episodes of silent ischemia. Individuals with a history of heart attacks or those that are diabetic are at risk of developing silent ischemia. The symptoms of this disorder may develop slowly as the arteries gradually narrow (Cardiovascular disability, 2010). Lifestyle changes, medication and surgical procedures have been successful in the treatment of this condition. Low fat and sodium content in foods reduces the risk of ischemic heart diseases. If left untreated, this disorder may lead to severe heart damage and hence increased mortality. (Coronary Heart Disease | NHLBI, NIH, 2020).

2. Transient Ischemic attack

Transient ischemic attach (TIA) is a condition presented by temporary periods of symptoms that are similar to those of stroke. Stroke is the number-one reason of disability and the second main reason of death universally (Transient ischemic attack (TIA), 2020). The effect of this condition is not permanent and only lasts for a few minutes. A small percentage of individuals with this disorder usually suffer from stroke. It serves as a warning for possibility of future occurrence of stroke.

It is described as the most common type of stroke which has similar causes as those of stokes. TIA occurs when clots block blood supply to the brain; this blockage is temporary and causes no major damage (Transient ischemic attack (TIA), 2020). The underlying causes of this disorder are cholesterol build up in arteries. Most of the risk factors for this illness cannot be controlled, such as family history, age, sex and sickle cell diseases. Controlled risk factors include history of high blood pressure, high cholesterol, and heart failure and carotid artery diseases.

The signs and symptoms of this condition only prevail for a shorter time. These symptoms resemble those of a ministroke, such as general weakness of the body, slurred speech, blindness or loss of balance (Paul and Candelario-Jalil, 2020). Depending on which area of the brain the affected, one may have more than one TIA with recurrent signs and symptoms. Patients are advised to seek immediate medical attention as soon as these symptoms present themselves.

Avoiding smoking, limiting the cholesterol intake, regular exercise and maintaining a healthy weight prevents the risk of contacting the illness. In diagnosing the causes of TIA, it is vital to evaluate the symptoms before devising the best treatment method. Physical examination and neurological exams is the mostly used assessment method for this illness. Carotid ultrasounds are also used in situations where the physician suspects that carotid artery may be the main cause of this disorder. CT scanning may be used in assessment of brain composite for the 3D views (Stroke - Causes, 2020). Radiologists also use arteriography procedures to assess the arteries in the brain through X-ray imaging. Anti-platelet drugs are used for treatment of severe cases. It reduces the likelihood of stroke after these attacks. Severe or moderate carotid arteries require surgical treatment procedures. It clears narrowed neck arteries before another stroke occurs.

Biochemistry in Ischemia Reperfusion Injury

When the blood flow decreases in a part of a body, cells initializes the anaerobic metabolism, which results to the decrease of pH in the cells and the ATP production. When the oxygen reduces, it is required from the cells to produce anaerobically ATP. This situation leads to the calcium cell overload. The injury to endothelial capillary cells in the ischemic point that happens on a slower time scale presents lower requirement for energy. The immediate treatment of blood flow in vessels removes hydrogen anions (H+)which were collect in ischemia phase transplantation (Krenz, Baines, Kalogeris and Korthuis, 2016).

It is a fact, that a big number of pathologic processes have reperfusion injury. The molecular oxygen getting into the tissue via arterial blood, flows in the formerly ischemic tissue (Krenz, Baines, Kalogeris and Korthuis, 2016).

Some pathologic processes play an important role to preset of reperfusion injury. These processes are the endothelial dysfunction, growth of capillary, opening of the mPTP (mitochondrial permeability transition pores), development of a prothrombogenic phenotype and pronounces inflammatory responses. These pathologic processes target at treatment for ischemic reperfusion injury. Additionally, this kind of treatment is possible to extend the ischemic time before the injury in tissue be irrevocable, and the time margin is extended for surgeries like cardiopulmonary bypass and organ transplantation (Krenz, Baines, Kalogeris and Korthuis, 2016).

Treatment of Ischemia Reperfusion injury

There are several strategies for ischemia reperfusion injury treatment. Some of the contingent therapies are the ischemic preconditioning, vitamin therapy, pharmacological therapy, and the using of medical gases. These contingent therapies may aid to evolution of new strategies to suspend IR (Naito et al., 2020). There are more strategies regarding protection against ischemia reperfusion injury through the use of drugs. These strategies are evading oxidative injury, enhancing call energetics, modulating cells – surviving trail, and physically protecting cell membrane probity (Soares et al., 2020).

Also, the Resuscitative endovascular balloon occlusion of the aorta (REBOA), the utility of the REBOA restrict the damage by ischemia reperfusion injury after kidney or pulmonary diseases (Naito et al., 2020).

Moreover, there are more therapeutical ischemia reperfusion injury strategies such as therapeutic hypothermia, pharmaceutical intervention (edaravone, melatonin, bile pigments, anesthesia) and maintenance of blood flow (Naito et al., 2020).

According to the article, there is a different treatment of chronic myocardial ischemia injury if these treatment methods are effective this means that more treatment for ischemia reperfusion injury will be develop for other organs like lungs. This treatment comprises the choice of treatment and its effectiveness depends on the underlying reason of ischemia injury. Also, it involves the anti – angina medications which are the mainstay of anti – ischemic management, and finally the surgery which is the most common technique for patients with certain medical conditions. But this strategy is not recommended to patients with main artery diseases (Cohn PF. 1998.).

Apoptosis in Ischemia Reperfusion Injury

When a cell suffers by a damage there are two different types of cell death, apoptosis, and necrosis (Fischer et al., 2020). Apoptosis is a genetically regulated form of death in cells. Apoptosis is a part of a biological process, including ageing, embryogenesis, homeostasis, and other diseases. In these days, several treatments act through apoptosis like anticancer treatment or non – steroidal anti – inflammatory (Renehan, 2001).Nevertheless, overmuch or inadequate apoptosis becomes the reason for a variety of different infectious diseases, neurological diseases and others. Also, apoptosis plays a serious role and in the ischemic heart disease and contributes to the development of heart failure (Teringova and Tousek, 2017).Furthermore, apoptosis plays crucial role is several diseases like autoimmune diseases, cancer and other diseases (Fischer et al., 2020).

Cells types involved in Ischemia Reperfusion Injury in the Lungs

Ischemia formally has as a consequence the cellular dysfunction, without cell death in some cells types. Several cell types are more delicate to ischemic injury and end up to the cell death (King, 2007). Multiple types of cells involved in the pathophysiology of ischemia reperfusion injury such as vascular cells, neurons, mast cells, neutrophils, endothelial cells, monocytes, lymphocytes, parenchymal cells, platelets, and immune cells (Kalogeris, Bao and Korthuis, 2014).

The reperfusion injury mechanisms are several, such as the development of reactive oxygen (ROS), calcium overload, MPT pore opening, dysfunction of endothelial, appearance of a prothrombogenic phenotype, and profound inflammatory responses (Kalogeris, Bao and Korthuis, 2014).

Macrophages and monocytes will infiltrate the tissue at later time points during ischemia reperfusion injury (Zuidema, 2010).

During reperfusion, platelets have a necessary role in post – ischemic hypo-perfusion. The platelets undertake the lungs injury, by promoting hemostasis and growing of micro-thrombi (Ovechkin et al., 2007).

Platelets agglomeration after ischemia reperfusion with post – capillary venules depended upon leukocytes and P – selectin. Platelets and leukocytes can cause several ischemic injuries (Zuidema, 2010).

An increase of leukocytes presented in ischemia. In an ischemic organ the number of adherent leukocytes increases very fast (Krenz, Baines, Kalogeris and Korthuis, 2016).

Leukocyte and endothelial cell activation are connected with ischemia reperfusion in different tissue (Ovechkin et al., 2007). Endothelial cells are the 45% of total cells in human body. This percentage of endothelial cells presents that endothelial cells have an important role in ischemic injury. The ischemia reperfusion injury presents the function of endothelial barrier. Furthermore, ischemia reperfusion disrupts the audit of endothelial hemostatic mechanisms and the endothelium – dependent vasodilation (Krenz, Baines, Kalogeris and Korthuis, 2016).

Neutrophils play a necessary role in post - ischemic injury. Ischemia reperfusion causes release of cytokines, oxygen free radicals and some other activate mediators of neutrophils (Jordan, 2020).

Monocytes, T cells, mast cells, platelets and endothelial cells play a serious role in ischemia reperfusion injury in myocardial. Both T cells and mast cells are pro – fibrotic mediators and inflammatory. This kind of cells are responsible for the rapid response to mechanical stimuli, like vasodilation in reperfusion and vasoconstriction in ischemia (Zuidema, 2010).

Stem cells are this kind of cells that produce all the other cells with generated operations (Frequently asked questions about stem cell research, 2020). Stem cells can be classified in 5 groups of fetal, adult, embryonic, IPS, and perinatal (Barzegar et al., 2020).

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1. Fetal stem cells

Kind of cells that created from the fetal tissue and differentiate in the body.

2. Perinatal stem cells

There are in umbilical cords (UC), placenta membranes and amniotic fluid (AF).

3. Adult stem cells

They are divided into 4 categories.

a. Hematopoietic stem cells (HSC)

b. Neuronal stem cells (NSC)

c. Mesenchymal stem cells (MSC)

d. Epidermal stem cells (ECS)

4. Induced pluripotent stem cells.

This kind of cells are differentiated in somatic and germ cells.

5. Embryonic stem cells

Come from inner cell mass of embryo (Barzegar et al., 2020).


Biochemical events contribute to ischemia reperfusion injury in the lungs. Pulmonary IR injury has greatly contributed to mortality rates associated with other illnesses. This literature review has highlighted the better understanding of complex interactions that are involved with this disorder. It also highlights how these biochemical events relate to other pathophysiological consequences. The use of medication, therapy and surgical procedures has been widely applied in the treatment of ischemic injuries in different parts of the body affected.


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