Where does all the oxygen go?

Computational Modeling to
Support Heart Therapies
Diviyashree Kasiviswanathan 1
Kevin J. Haworth, PhD 1,2

1: Medical Sciences Baccalaureate Program

2: Department of Internal Medicine

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Background – Myocardial Infarction
• Myocardial Infarction (MI) = Heart Attack

Facts
Someone has a heart attack
every 40 seconds

805,000 people have a heart

attack every year

CDC.org/heartdisease/facts.htm https://my.clevelandclinic.org/health/diseases/16818-heart-attack-myocardial-infarction
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Reasons for Cardiomyocyte Death
• In a MI event, cardiac muscle cells die due to lack of oxygen

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Kelman Oxygen Dissociation Curve
PO2 vs SO2

• PO2 refers to the oxygen in the plasma

• SO2 refers to the oxygen bound to
hemoglobin

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Current Practice: Angioplasty

Balloon
inserted into Balloon Artery
a narrowed becomes widens
area of plaque inflated

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Significance of this Research Project

The problem with these methods is that it quickly re-introduces oxygen into the
heart, which can cause further damage

According to Fischesser et al. (2021), lowering the magnitude of oxygen

significantly improves recovery

BUCL’s research with microbubbles helps to develop new therapies that will
alleviate the damage

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Scavenging Oxygen with ADV

O2 = oxygen = perfluorocarbon droplet ADV = Acoustic Droplet Vaporization

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Scavenging Oxygen with ADV

O2 = oxygen = perfluorocarbon droplet

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Scavenging Oxygen with ADV

O2 = oxygen = perfluorocarbon droplet

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Scavenging Oxygen with ADV
Acoustic Droplet Vaporization (ADV) can produce
microbubbles that scavenge oxygen

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Radhakrishnan Oxygen Scavenging Curve

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Current Model
 Accurately predicts the amount of
oxygen that can be scavenged from
water
 Project Goal: We need to modify the
model to account for the variables
present in the whole blood

pCO2 Temperature Factors influencing the number

of oxygen molecules bound to a
single hemoglobin molecule.

pH
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Project Aims

Modify the existing model to

account for the variables present in
the whole blood (ex. oxygen bound
to hemoglobin)

Combine Kelman equations and

Radhakrishnan equations to
predict changes in oxygen
saturation

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Method: Kelman Model – Equation 1
This equation creates
the hemoglobin-oxygen
dissociation curve.

2 3 4
𝑎 1 𝑥 +𝑎 2 𝑥 +𝑎 3 𝑥 + 𝑥
𝑆𝑂 2 =100 × 2 3 4
, 𝑥= 𝑃𝑂2
𝑎 4 +𝑎 5 𝑥 +𝑎 6 𝑥 + 𝑎7 𝑥 + 𝑥
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Method: Kelman Model – Equation 2

This equation determines

how much the saturation
curve shifts to the right/left
depending on the values for
pH, temperature, and pCO2.

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Method: Combining Kelman Equations

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Dissolved Oxygen Curve –
Conservation of Mass

Radhakrishnan Model

Revised equation with Hemoglobin

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Dissolved Oxygen Curve –
Partial Pressures

Radhakrishnan Model

Revised equation with Hemoglobin

=

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Final Derivation Steps

Determine whether replaces PO2 or PO2,vir

Rearrange PO2 equation as a function of PO2,vir

Insert the revised SO2 equation into the revised Conservation of Mass
equation

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 Results: Determine whether replaces PO2 or
PO2,vir

S replaces PO2
 Increased/decreased temperature
 Increased/decreased pH
 Increased/decreased PCO2 value

The graph shifted as expected for each

of these cases

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 Results: Determine whether replaces PO2 or
PO2,vir

Scenario 2: replaces PO2,vir

The graph shifted in the opposite

direction than expected

Logically, it made sense that should

replace PO2 and not PO2,vir

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Results: Insert the revised SO2 equation into
the revised Conservation of Mass equation

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Results: Derive nd and nb as a function of nl
Deriving nb
Deriving nd

𝑅𝑇 𝑛𝑏 𝑘 𝑛𝑙
=
𝑣𝑏 𝑣𝑙

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 Results: Insert the revised SO2 equation into
revised Conservation of Mass equation

( )( )( )( )( ) ( ) ( ) ) ( )
𝟑 𝟑 𝟑 𝟑 𝟑 𝟑 𝟐 𝟐 𝟑
𝒂𝟒𝒌 𝟒 𝒂 𝒂 𝒌 +𝒂 𝒂 +𝒂 𝒂 𝒌 𝒗 +𝒂 𝒂 𝒌 𝒗 𝒂 𝒂 𝒌 +𝒂 𝒗 +𝒂 𝒂 𝒌 𝒗 +𝒂 𝒂 𝒌 𝒗 𝒂 𝒗 +𝒂 𝒂 𝒗 +𝒂 𝒂 𝒂 𝒗 +𝒂 𝒂 𝒗 𝒂 𝒗 𝒂 𝒂 𝟏
𝟑 𝟒 𝟓 𝟑 𝟔 𝟑 𝟓 𝒍 𝟐 𝟒 𝒍 𝟐 𝟑 𝟔 𝟕 𝒍 𝟐 𝟓 𝒍 𝟏 𝟒 𝒍 𝟑 𝒍 𝟐 𝟕 𝒍 𝟏 𝟔 −𝟏 𝟐 𝒍 𝟏 𝟕 𝒍 −𝟐 𝟏 𝒍 −𝟑 𝟔𝟐 𝑺𝑽𝒅 𝑽 𝒃 𝑷 𝒂𝒕𝒎 𝒌
𝟒𝟎 𝒉 𝟒 𝒏𝒍 + 𝒏 +
𝟑 𝒍 𝟑 𝒍
𝒏+ 𝒍 𝒏 + 𝒏 + 𝒏 + 𝒏 +𝒂 𝒂 +𝒂 𝒂 + + (𝑽 𝑷 −𝟒.𝟕 𝟑 𝒌𝒏𝒍)+𝒏𝒍 𝟏+ (𝑽𝒍𝑷𝒂𝒕𝒎−𝟒.𝟕 𝟑 𝒌𝒏𝒍)+𝒏𝒍( )
𝒍 𝟐 𝒍 𝟑 𝒍 𝟑 𝟕 𝟏 𝟓 𝟑 𝒍 𝒂𝒕𝒎
𝒐

𝒗𝒍 𝒗 𝒌𝒗 𝒍 𝒍
𝟐𝟐
𝒍 𝒌𝒗 𝒌 𝒌 𝒌 𝒗𝒌 𝒍 𝑽𝒍 𝑹𝑻
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Conclusion

This combined model that includes the effect of

hemoglobin in whole blood will help us provide new
therapies that will help treat myocardial infarctions
without causing further damage to the heart.

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Future Work

Compare mathematical model to experimental data

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What the UPRISE Program meant to me

First Full-Time Exceptional Mentors

Research Experience & Lab environment

Increased Interest in
Research Pursue an MD/PhD

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Acknowledgements
 UPRISE Program: Tiffany Grant, PhD and Heather Norton, PhD
 Kateryna Stone, BS
 Nour Al Rifai, PhD
 Bin Bo, MD, PhD
 Mona Mirheydari, PhD
 Rachel Benton, BS
 Weston Gaskins
 Bissem Gill , BS
 John Dumancic
NIH Grant R01HL148451

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?
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Thank You!

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