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The Future is Here

#pericardium #pericardialspace #epicardium #drug_therapy


Self driving cars, robots serving our food, and personal 3-D printers. These are all technologies you may think of when considering what our future will look like. There are also some lesser known innovations that will greatly shape our future and in particular, our health. One of these is a new device for accessing the pericardium. This will allow for safer and more effective drug delivery to treat a variety of heart conditions.


Current methods of drug delivery can have dangerous and sometimes deadly side effects

Drug therapies for cardiovascular diseases have unintended side effects on nearby organs and parts of the heart that are not meant to be affected. Additionally, high doses must be delivered because of short-term pharmacokinetics (1). One example is the drugs used to treat or prevent arrhythmias in open-heart cases which, when delivered intravenously, can produce drops in blood pressure and renal dysfunction. This is very dangerous in already compromised cardiac patients and can create problems in anesthesia management (2). fortunately, when drugs are delivered through the pericardial space, many of these complications are not in effect.


Accessing the pericardium is currently a dangerous process

The current technology uses a needle pointed directly towards the heart, posing a risk of puncturing and damaging the heart (mostly the Right Ventricle), lungs, Liver and Diaphragma. CardioVia is developing a safer alternative, one that does not point a needle towards the heart. With safer, easier, and more efficient pericardial access, the pericardial space can be used for treating a wide variety of heart conditions and one of these ways of treatment within the space can be drug delivery based.


Potential for safe and effective drug delivery through the pericardial space

Multiple studies have demonstrated the benefits of delivering drugs intrapericardialy:

One study from the Journal of Controlled Release sought to explore the kinetics of myocardial penetration and retention after pericardial nanoparticle drug delivery. They wanted to understand the idea that this could be a strategy to concentrate therapeutics for sustained drug penetration into the myocardium.

In rabbits, tagged nanoparticles were loaded with a fluorophore called BODIPY and percutaneously administered into the pericardium. The hearts were examined at certain time points for the presence of the BODIPY. The nanoparticles displayed a half-life of around 2.5 days in the heart.

According to the authors Our findings demonstrate the potential of utilizing the pericardial space as a sustained drug-eluting reservoir through the application of nanoparticle-based drug delivery, opening several exciting avenues for selective and prolonged cardiac therapeutics.” (3)

Another study, from the American Journal of Physiology-Heart and Circulatory Physiology, investigated if pericardial delivery of omega-3 (n-3) polyunsaturated fatty acids (PUFAs) would protect the myocardium from ischemic damages and arrhythmias. In most studies n-3 PUFAs are delivered through dietary supplements but this is not always effective because in blood, albumins bind to n-3 PUFAs which greatly reduces their concentrations.

In this study, they tested the delivery of n-3 PUFAs through the pericardial space as a more effective way to build up a high concentration surrounding the heart. N-3 PUFAs are known to risk acute myocardial infarction and studies have shown that fish oil as a dietary supplement attenuates myocardial infarct size, cardiac dysfunction, and lethal ventricular arrhythmias in animal models.

A porcine model was used for this study. “These data demonstrate that pericardial infusion of n-3 PUFA DHA can significantly reduce both malignant arrhythmias and infarct sizes in a porcine infarct model. Pericardial administration of n-3 PUFAs could represent a novel approach to treating or preventing myocardial infractions.” (4)





A study from the journal of cardiovascular pharmacology examined whether IPC delivery of sotalol and atenolol in rats offers advantages over intravenous (IV) application.

The researchers proposed this study based on the idea that local drug delivery means more of the drug can be taken up by cardiac tissue meaning a lower dose can have a higher effect and peripheral side effects can be minimized. “Therefore the present study addressed the question whether pharmacokinetic advantages are observed after sustained IPC infusion of the small positively charged β-blocking agents d,l- sotalol and d,l- atenolol and whether IPC infusion of the agents results in a more effective cardiac β-blocking action than intravenous (IV) infusion.”

They found that “The approach of sustained application of drugs via the pericardium improves the efficacy of sotalol and atenolol since cardiac β-receptor blockade is obtained at low systemic drug levels.” They believe this is a promising new technique to minimize side effects (5).

The future is here

We may not have flying cars or teletransportation machines for many years, but we will have new lifesaving methods of drug delivery in the very near future.





Sources:

1.https://www.sciencedirect.com/science/article/pii/S0168365917307216?via%3Dihub

2.https://www.jove.com/video/52600/testing-efficacy-pharmacological-agents-pericardial-target-delivery

3.https://www.sciencedirect.com/science/article/pii/S0168365917307216?via%3Dihub

4.https://www.physiology.org/doi/full/10.1152/ajpheart.91502.2007

5.https://journals.lww.com/cardiovascularpharm/Fulltext/2004/07000/Intrapericardial_Delivery_Enhances_Cardiac_Effects.7.aspx

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