A phosphorescent probe is used to determine oxygen tension at various points after an ischemic attack. Using this probe allows direct measurement of tissue oxygenation, while avoiding off-target scatter from blood in the ventricles.
Injection of S. elongatus is done in the dark and in light. For light tests, injection syringes loaded with the strain is prepared and placed in an incubator under plant lights. For dark tests, the strain is placed in black bags (opaque) to prevent exposure to light. After injection with the light-exposed strain, the subject is exposed directly to the light.
For the dark groups, injection is done in rooms with dim-lights; after which the lights are turned off and layers of aluminum foil are placed over the field operated to prevent exposure to light.
Reassessment of oxygen tension is done between 10 and 20 minutes after the injection. A 25-fold increase in oxygenation is expected in the light-exposed subjects from the nadir of ischemia at both 10 and 20 minutes after injection with the bacterial strain.
For the heart treated in the dark, not much increase in oxygen tension would be expected. Determining the elevated tissue oxygenation is essential because it serves as the basis for enhanced myocardial bioenergetics.
This model is of importance because it highlights the utilization of a photosynthetic model to treat heart disease, specifically tissue ischemia.
The S elongatus strain uses CO2 and H2O released by cells with low oxygen tension, and converts it to oxygen and glucose using light as the energy source. The S. elongatus retains the glucose produced – hence it is obvious that the ischemic cardiomyocytes does not benefit from this (the glucose). However, the levels of oxygen will be increased significantly. By balancing a pathologically unbalanced equation, there is the protection of the cardiomyocytes, resulting in an improved heart function. The implication is that the strain S. elongatus can be used efficiently to deliver oxygen directly to the ischemic myocardium. This treatment results in direct delivery of oxygen to the ischemic myocardium, increasing surface temperature of the myocardium probably secondary to metabolic activity, and also enhancing function of the left ventricle in an ischemic condition. Such would result in profound clinical implications in heart-diseased patients.
The effect of this on the immune system has been studied by Cohen et al (2017). According to the report by the researchers, there is no obvious inflammatory response to the therapy. A report by the researchers showed that “after intravenous delivery of 5 x 108 S. elongatus cells, blood cultures remained negative and did not show any signs of infection for the duration of 1-week observation period.” It is likely that the S. elongatus strain does not persist for long in the tissues, as most of the injected cells get cleared within 24 hours.
As such, this proposed therapy may prove very effective in situations where only a temporary supply of oxygen is needed, for instance, in the case of acute myocardial infarction prior to revascularization.
Increased oxygenation of the tissues forms the basis for good myocardial bioenergetics. By enhancing aerobic respiration, the production of ATP is boosted, while release of lactic acid is mitigated with a reduction in anaerobic glycolysis. This principle is applied in the clinical setting as healthcare providers strive to quickly revascularize the ischemic myocardium in the event of an ischemic myocardial infarction.
A range of possibilities can be linked to the use of S. elongatus to mitigate acute ischemia of the myocardium, and this includes using it as an adjunctive cardioplegia during cardiopulmonary bypass surgery, or as a perfusate in organ transplant to provide tissues with oxygen in the absence of blood flow during transport.
Alongside restoring oxygenation during ischemia, the S. elongatus – based therapy also bestows positive benefits after blood flow restoration. Studies have shown that there is a great chance of residual microvascular perfusion deficit even after revascularization with percutaneous coronary intervention or a coronary artery bypass grafting. This results in a remodeling of the ventricle, ischemic cardiomyopathy, failure of the heart, and ultimately, death. Many patients that survive acute myocardial infarction do succumb to this.
Stem cell-based therapies and angiogenic cytokine therapies have attempted to address this; unfortunately, these therapies do take weeks to cause a substantial therapeutic response, thus limiting the amount of heart muscle that can be salvaged. Using S. elongatus on its own or as an adjunct to cytokine or cell therapies could effectively address microvascular disease and mitigate the development of ischemic cardiomyopathy.
Based on the prevailing cost of heart disease to the global economy, and the “not-so-effective” treatment model, it is estimated that this model (the S. elongatus – based therapy) may have a god market value. Studies have shown that within 2 decades, the number of Americans with cardiovascular diseases will rise to about 131.2 million, making up 45 percent of the total population of the US. The cost is expected to reach $1.1 trillion.
By 2035, the cost of cardiovascular treatment (based on prevailing treatment model) will increase significantly, reaching over $1.1 trillion. The aging population and prevalence of cardiovascular disease contributes greatly to this.
Currently, cardiovascular disease costs about $555 billion in the US and $863 billion globally. It is expected to rise to $1.044 trillion globally, and so does the cost of this model.