Samples From Human Subjects to Facilitate Basic, Translational and Clinical Research

We are evaluating the role of endothelial dysfunction and inflammation in cardiopulmonary and
vascular disease states, such as, but not limited to, pulmonary hypertension (PH) and other
pulmonary vascular diseases, arteriosclerosis, transplantation, inflammatory processes and
sepsis. The collection of human blood and urine from both research subjects and healthy
volunteers is necessary for the development of relevant laboratory assays and protocols, and
to further research studies requiring such evaluations. In research subjects undergoing renal
replacement therapy who produce limited urine we may also sample ultrafiltrate as a surrogate
for urine. This protocol defines in general terms the purposes for which blood, urine and
ultrafiltrate will be collected by members of the NIH s Clinical Center (CC), Critical Care
Medicine Department (CCMD) and collaborating institutions and establishes general conditions
under which sampling will be performed.

- INCLUSION CRITERIA FOR RESEARCH SUBJECTS WITH CARDIOPULMONARY AND VASCULAR DISEASES
RELATED TO BUT NOT LIMITED TO ARTERIOSCLEROSIS, TRANSPLANTATION, PULMONARY
HYPERTENSION, OTHER ADVANCED LUNG OR HEART DISEASE, AND OTHER DISEASES INVOLVING
INFLAMMATION OR ENDOTHELIAL DYSFUNCTION:

1. Males or females of age greater than or equal to18 years old.

2. Subjects unable to provide informed consent must have a surrogate decision maker
or another legally authorized representative (such as a legal guardian or holder
of the DPA)

EXCLUSION CRITERIA FOR RESEARCH SUBJECTS WITH CARDIOPULMONARY AND VASCULAR DISEASES RELATED
TO BUT NOT LIMITED TO ARTERIOSCLEROSIS, TRANSPLANTATION, PULMONARY HYPERTENSION, OTHER
ADVANCED LUNG OR HEART DISEASE, AND OTHER DISEASES INVOLVING INFLAMMATION OR ENDOTHELIAL
DYSFUNCTION:

1. Hemoglobin <7.0 g/dL

2. Currently receiving infusion of any dosage of norepinephrine, vasopressin, or
epinephrine; or dopamine at an infusion rate >2.5

micro g/kg/min

3. In the presence of known coronary artery disease (CAD) a systolic blood pressure (SBP)
<90 mmHg. In the absence of known CAD a SBP <80 mmHg or mean arterial pressure (MAP)
<60 mmHg.

Research subjects may be excluded if in the opinion of the study investigators they have a
condition that may adversely affect the outcome of the study or the safety of the
volunteer.

INCLUSION CRITERIA FOR SUBJECTS WHO ARE TO RECEIVE CRRT (IRRESPECTIVE OF DIAGNOSIS) IN WHOM
THE TOTAL AMOUNT OF PROTOCOL RELATED BLOOD WILL NOT EXCEE 8 ML.

1. Males or females of age (Bullet)18 years old.

2. Subjects unable to provide informed consent must have a surrogate decision maker or
another legally authorized representative (such as a legal guardian or holder of the
DPA)

EXCLUSION CRITERIA FOR SUBJECTS WHO ARE TO RECEIVE CRRT (IRRESPECTIVE OF DIAGNOSIS) IN WHOM
THE TOTAL AMOUNT OF PROTOCOL RELATED BLOOD WILL NOT EXCEED 8 ML)

1. Hemoglobin <7.0 g/dL

2. In the presence of known coronary artery disease (CAD) a systolic blood pressure (SBP)
<90 mmHg. In the absence of known CAD a SBP <80 mmHg or mean arterial pressure (MAP)
<60 mmHg.

INCLUSION CRITERIA FOR HEALTHY VOLUNTEERS:

1. Males or females of age greater than or equal to 18 years old

2. Must be able to provide informed, written consent.

EXCLUSION CRITERIA FOR HEATLHY VOLUNTEERS:

1. Blood or platelet donation within the last 6 weeks.

2. Hemoglobin below normal (e.g. below 11.2 g/dl for females and below 13.7 mg/dl for
males at the NIH CC); subjects may return for evaluation at a later date. (After
initial enrollment, hematocrit does not need to be done prior to subsequent blood
draws unless there is interval development of symptomatic anemia)

3. History of recreational drug use with the exception of marijuana (as long as marijuana
use was >3 months from the time of study screening).

4. Active acute illness (i.e viral syndrome). Subjects may return for evaluation at a
later date once the acute illness resolves.

5. Volunteers may be excluded if in the opinion of the study investigators they have a
condition that may adversely affect the outcome of the study or the safety of the
volunteer, such as, active tobacco use (> 6 months) in the past ten years, any tobacco
use within 3 months prior to the screening evaluation, a history of clinically
relevant and active cardiopulmonary disease (e.g. Including but not limited to any
cardiopulmonary diseases not well controlled by medications, EKG with evidence of
clinically relevant heart disease, COPD with hypoxemia and forced expiratory
volume/forced vital capacity (FEV1/FVC) > 2 standard deviations from normal, etc.).