Vascular Reaction to Medications
Conditions
Keywords
Hand vein sensitivity, phenylephrine, nitroglycerin
Brief summary
The goal of this project is to determine the genetic factors contributing to interindividual differences in response to physiological and pharmacological vasoconstrictors and vasodilators.
Detailed description
The dorsal hand vein model is a relatively non-invasive and robust experimental model to examine the local in vivo effect of vasoactive drugs without elucidating systemic counterregulatory reflexes. Infusion of incremental low doses of phenylephrine into a dorsal hand vein results in increasing local venoconstriction, without systemic effects. Similarly, infusion of incremental low doses of nitroglycerin into a preconstricted dorsal hand vein results in increasing local venodilation, without systemic effects. Systemic vascular responses can be measured by the cold pressor test (CPT),that leads to increase in blood pressure and heart rate , or mental stress that is also known to stimulate cardiovascular responses. Individuals vary in their local and systemic vascular responses but the genetic determinants of these are not clear.
Interventions
DRUGPhenylephrine
Intravenous phenylephrine at low doses (approximately 10 doses ranging from 0-5000 ng/min) Intravenous nitroglycerin at low doses (approximately 10 doses ranging from 0.05-100 ng/min)
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
National Center for Research Resources (NCRR)
Vanderbilt University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* Age between 18 and 40 years, inclusive. * Subject must be willing to give written informed consent and be able to adhere to diet and study schedules. * Subjects must be free of any clinically significant disease that requires a physician's care and/or would interfere with the study evaluations. * Subjects must have a normal or clinically acceptable physical examination and ECG. * Clinical laboratory tests (CBC, blood chemistries, and urinalysis) must be within normal limits or clinically acceptable to the investigator.
Exclusion criteria
* Any subject who has taken any prescription or over-the-counter drugs, other than oral contraception if female, within two weeks prior to study drug administration. * Subjects who are presently, or were formerly, narcotic addicts or alcoholics. * Subjects who have a clinically significant allergy/intolerance to phenylephrine. * Females with a positive serum/urine pregnancy test at screening. * Females who are nursing. * Subject using sildenafil or other phosphodiesterase inhibitors.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ED50 After Phenylephrine | 70 minutes | ED50 is a measurement of vein constriction and indicates 50% of maximal constriction after being given medication phenylephrine, representing sensitivity to the drug. Phenylephrine was infused at increasing dose rates, ranging from 12-9600 ng/min. The infusion at each dose rate lasted 7 minutes, with the vein diameter measured during the last 2 minutes of the infusion. The number represents the ng/ml of phenylephrine needed to reach 50% of maximal vein constriction. ED50 values were not normally distributed and were log-transformed for analysis and expressed as geometric means. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Blood Pressure | baseline to 2 minutes | change in systolic and diastolic blood pressure, comparing before and after cold pressor test. A subset of 57 participants (of the 106) who were in the primary outcome measure also participated in the cold pressor test. |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited by advertisement within the Vanderbilt University campus and through the Vanderbilt University Clinical Research Center study volunteer database,
Participants by arm
| Arm | Count |
|---|---|
| African Americans Subjects' hand veins will be measured for maximum constriction while being infused with phenylephrine, and then mental stress and cold pressor testing
Phenylephrine: Intravenous phenylephrine at low doses (approximately 10 doses ranging from 0-5000 ng/min) Intravenous nitroglycerin at low doses (approximately 10 doses ranging from 0.05-100 ng/min) | 42 |
| Caucasians Subjects' hand veins will be measured for maximum constriction while being infused with phenylephrine, and then mental stress and cold pressor testing
Phenylephrine: Intravenous phenylephrine at low doses (approximately 10 doses ranging from 0-5000 ng/min) Intravenous nitroglycerin at low doses (approximately 10 doses ranging from 0.05-100 ng/min) | 64 |
| Total | 106 |
Baseline characteristics
| Characteristic | African Americans | Caucasians | Total |
|---|---|---|---|
| Age, Continuous | 28.1 years STANDARD_DEVIATION 8 | 26.9 years STANDARD_DEVIATION 6.8 | 27 years STANDARD_DEVIATION 7 |
| plasma epinephrine | 21.0 pg/ml STANDARD_DEVIATION 15.6 | 18.5 pg/ml STANDARD_DEVIATION 12.5 | 19.4 pg/ml STANDARD_DEVIATION 13.7 |
| plasma norepinephrine | 179.5 pg/ml STANDARD_DEVIATION 70.8 | 162.3 pg/ml STANDARD_DEVIATION 58 | 168.9 pg/ml STANDARD_DEVIATION 63.2 |
| Region of Enrollment United States | 42 Participants | 64 Participants | 106 Participants |
| Sex: Female, Male Female | 18 Participants | 31 Participants | 49 Participants |
| Sex: Female, Male Male | 24 Participants | 33 Participants | 57 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 42 | 0 / 64 |
| other Total, other adverse events | 0 / 42 | 0 / 64 |
| serious Total, serious adverse events | 0 / 42 | 0 / 64 |
Outcome results
Primary
ED50 After Phenylephrine
ED50 is a measurement of vein constriction and indicates 50% of maximal constriction after being given medication phenylephrine, representing sensitivity to the drug. Phenylephrine was infused at increasing dose rates, ranging from 12-9600 ng/min. The infusion at each dose rate lasted 7 minutes, with the vein diameter measured during the last 2 minutes of the infusion. The number represents the ng/ml of phenylephrine needed to reach 50% of maximal vein constriction. ED50 values were not normally distributed and were log-transformed for analysis and expressed as geometric means.
Time frame: 70 minutes
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| African Americans | ED50 After Phenylephrine | 172 ng/min |
| Caucasians | ED50 After Phenylephrine | 310 ng/min |
Secondary
Change in Blood Pressure
change in systolic and diastolic blood pressure, comparing before and after cold pressor test. A subset of 57 participants (of the 106) who were in the primary outcome measure also participated in the cold pressor test.
Time frame: baseline to 2 minutes
Population: A subset of participants (57 of the 106) in the primary outcome measure also participated in the cold pressor test.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| African Americans | Change in Blood Pressure | Change in Systolic Blood Pressure | 23.0 mmHg | Standard Deviation 12.3 |
| African Americans | Change in Blood Pressure | Change in Diastolic Blood pressure | 16.9 mmHg | Standard Deviation 9.3 |
| Caucasians | Change in Blood Pressure | Change in Systolic Blood Pressure | 18.9 mmHg | Standard Deviation 11.7 |
| Caucasians | Change in Blood Pressure | Change in Diastolic Blood pressure | 16.4 mmHg | Standard Deviation 8.8 |