Hypoxia as a Modulator of Cardiac Disease in Duchenne Muscular - - PowerPoint PPT Presentation

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Mar 14, 2024 476 likes •618 views

Hypoxia as a Modulator of Cardiac Disease in Duchenne Muscular Dystrophy Natural History of DMD Skeletal Muscle Weakness Wheelchair Bound Subclinical Ventilatory Hypoxia? Support Cardiac Best to Dysfunction Prevent Time Damage is

SLIDE 1

Hypoxia as a Modulator of Cardiac Disease in Duchenne Muscular Dystrophy

SLIDE 2

Natural History of DMD

Skeletal Muscle Weakness Wheelchair Bound Ventilatory Support Subclinical Hypoxia? Cardiac Dysfunction Damage is Done Best to Prevent Time

SLIDE 3

Preventing Cardiac Injury

Things that we know

damage dystrophic hearts

Time
Increases in work

load

Increased Heart

Rate

Increased Blood

Pressure

Disruption of Various

Pathways (mice)

Utrophin
Integrin Expression
Altered glycosylation

patterns (Cmah)

Calcium Handling

Proteins

Mitochondrial targeted

proteins

Regulators of fibrosis
Hypoxia

SLIDE 4

Hypoxia in Dystrophic Mice

With acute hypoxia- mdx mice develop a significant acidosis.
Likely caused by increased lactate production

SLIDE 5

Metabolic Inefficiency of the Dystrophic Heart

Dystrophic hearts need more
xygen to do the same amount of

work as healthy hearts.

Dystrophic hearts are not able to

fully use the oxygen available.

SLIDE 6

Hypoxia in the Dystrophic Heart

3 weeks of hypoxia is sufficient to cause significant damage in

young mdx mice.

SLIDE 7

Normal Breathing

SLIDE 8

Dystrophic Breathing

SLIDE 9

Hypoxia is Very Common in Duchenne Muscular Dystrophy Patients

Standard practice is that patients generally have

evidence of sleep disruption prior to initiation of ventilatory support.

Hypoxia creates periods of increased cardiac

activity, increased heart rate and strength of contraction.

Hypoxia is sufficient to damage the dystrophic

mouse heart.

SLIDE 10

Safe and Effective Methods Exist to Treat Hypoxia

In stark contrast to most novel pathways that

exacerbate dystrophic cardiomyopathies. Hypoxia can be prevented by clinically accepted methods.

No FDA approval necessary

SLIDE 11

Dystrophic Breathing with Extra Oxygen

SLIDE 12

Current Proposal

Examine how supplemental oxygen improves

cardiac function and structure with challenge.

Assess the effect of supplemental oxygen on

skeletal muscle function, both limb and diaphragm.

Oxygen will be increased by both increasing the

fraction of oxygen inhaled and the pressure of the air.

SLIDE 13