Acute Microvascular Changes With LDL Apheresis

Conditions:High Cholesterol
Therapuetic Areas:Cardiology / Vascular Diseases
Age Range:19 - Any
Start Date:March 1, 2015
End Date:July 1, 2018

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Severe hypercholesterolemia produced by conditions such as heterozygous familial
hypercholesterolemia is associated with multiple complications including premature
atherosclerotic disease. There is evidence that microvascular perfusion, particularly flow
reserve, in critical organs is limited due to abnormalities in plasma viscosity, abnormal RBC
deformability, and an imbalance between vasodilators and vasoconstrictors. There is little is
currently known about acute changes in microvascular blood flow and microvascular rheology
that occur in response to plasmapharesis which is used in some patients to lower critically
elevated cholesterol levels. Our research group has pioneered CEU methods for assessing
myocardial and skeletal muscle perfusion, and has previously demonstrated in pre-clinical
models that acute hyperlipidemia produces a reduction in microvascular RBC transit rate. In
this study, the investigators will assess acute changes in microvascular perfusion in
patients undergoing clinically-indicated plasmapharesis.

Subjects who are scheduled to have planned apheresis treatment for severe
hypercholesterolemia will be recruited into the study. They will undergo a screening
evaluation, including a medical history, physical examination, ECG, and limited
echocardiogram to evaluate for exclusion criteria. Before the apheresis procedure, blood
samples will be obtained for plasma markers of inflammation, erythrocyte deformability, and
plasma viscosity. Contrast enhanced ultrasound perfusion imaging will be performed to
evaluate blood flow in the myocardium at rest, as well as in the forearm skeletal muscle
before and after mild isometric exercise (50% maximal grip, 0.2 Hz). Flow mediated
vasodilation will be performed. The subjects will then undergo their planned apheresis
procedure. Within 2 hours of completion of apheresis, blood collection and CEU will be
repeated. Plasma lipids will be available as part of the standard apharesis protocol.

Inclusion Criteria:

- hypercholesterolemia (LDL >200 mg/dL)

- clinically-indicated aphersis for hyperlipidemia

- age >18 y.o.

Exclusion Criteria:

- pregnant or lactating females

- hypersensitivity to ultrasound contrast agents

- evidence for right to left or bidirectional shunt

- on anticoagulants
We found this trial at
3181 Southwest Sam Jackson Park Road
Portland, Oregon 97239
503 494-8311
Phone: 503-494-8750
Oregon Health and Science University In 1887, the inaugural class of the University of Oregon...
Portland, OR
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