Files and links (1)
Sutliff_Roy_19964.73 MB
PDF Access upon request, Email title, URL, or DOI to archives@drexel.edu
Dissertation
Cardiovascular effects of cocaine administration in the nonpregnant and pregnant rabbit
Doctor of Philosophy (Ph.D.), Medical College of Pennsylvania and Hahnemann University
May 1996
DOI:
https://doi.org/10.17918/00007201
Abstract
Cocaine use in the United States is a major public health concern. An estimated 5-6 million people, a large proportion of which are women of childbearing age, regularly use the drug. Cocaine use is associated with numerous complications that have been attributed to its cardiovascular actions. The present studies attempted to determine the cardiovascular effects of cocaine administration and how the responses elicited by cocaine are affected by prior exposure to cocaine and pregnancy. Many of the sequelae associated with cocaine are attributable to the development of cardiovascular hypertrophy. Repeated cocaine administration increased the contractile response of the aorta to both receptor-dependent and depolarizing agents, however, this effect was eliminated when the contraction was corrected for tissue weight. These results support the contention that cocaine administration actually causes vascular hypertrophy. Consistent with previous studies the present investigation demonstrates pregnancy- enhanced cocaine-induced reductions in organ blood flow as well as increased dose-response relationships. The underlying mechanism of these reductions in organ blood flow appears to be due to cocaine's vasoconstrictor effects and not due to cardiac effects. Vasoconstrictors which act through the activation of L-type calcium channels appear to mediate these cocaine-induced reductions. Cocaine administration was also associated with an increase in nitrotyrosine immunoreactivity in the fetal brain, a marker for hypoxia/reactive oxygen species production. Nifedipine pretreatment inhibited the effects of cocaine on blood flow and nitrotyrosine immunoreactivity in the fetal brain. This suggests that cocaine-induced reductions in blood flow may cause fetal hypoxia resulting in the generation of reactive oxygen species. Studies in the pregnant rabbit also define the distinctive effects of repeated cocaine administration on the elicited cardiovascular responses. Increased basal organ blood flows were found in rabbits that received repeated administrations of cocaine during gestation. These rabbits also had more prolonged reductions in organ blood flows in response to an acute challenge of cocaine. In contrast to peripheral blood flows, repeated cocaine administration led to tolerance of cocaine-induced reductions in cerebral blood flow. In summary, these studies show that cocaine has marked cardiovascular effects and that pregnancy and repeated prior administrations of cocaine can enhance these effects.
Metrics
19 Record Views
Details
- Title
- Cardiovascular effects of cocaine administration in the nonpregnant and pregnant rabbit
- Creators
- Roy L. Sutliff
- Contributors
- Mark D. Johnson (Advisor) - Drexel University, Medical College of Pennsylvania and Hahnemann University (1993-1996, 1998-2002)
- Awarding Institution
- Medical College of Pennsylvania and Hahnemann University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Medical College of Pennsylvania and Hahnemann University; Philadelphia, Pennsylvania
- Number of pages
- xi, 108 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- School of Medicine (1993-1996, 1998-2002); Medical College of Pennsylvania and Hahnemann University (1993-1996, 1998-2002)
- Other Identifier
- 991021888545704721