Nicotine modifies cardiac growth during adolescence

Institution:	Veterans Medical Research Foundation
Investigator(s):	Wilbur Lew, M.D.
Award Cycle:	2007 (Cycle 16)	Grant #: 16IT-0007	Award: $128,358
Subject Area:	Cardiovascular Disease
Award Type:	Inno Dev & Exp Awards (IDEAS)

Abstracts

Initial Award Abstract

This study examines how nicotine modifies the growth of the heart during adolescence. During this period, heart size increases by 25-100% until it reaches a stable size as an adult. An abnormally large heart is associated with a higher incidence of deaths from heart and other diseases. In adolescent rats, nicotine was infused in doses to reach levels comparable to those with smoking or nicotine patches. After 4 weeks, there was no change in baseline heart function, but there was an increase in heart size that was directly related to circulating blood levels of nicotine or continine, a major breakdown product of nicotine. This proposal examines if these changes in heart size are associated with a depression in the maximal pumping capacity of the heart and function of the heart muscle cells. There may also be an abnormal vulnerability of the heart cells to be injured when stimulated, that cause the heart cells to die. After 4 weeks of nicotine exposure, rats will be treated with 4 more weeks of nicotine or salt water to determine if nicotine has cumulative effects, or if nicotine is stopped the effects on heart size are reversible. The mechanisms for mediating nicotine effects will be examined. This includes activation of recently discovered nicotine receptors on the heart muscle cell. These studies are clinically relevant as this may identify a new risk of smoking during adolescence. Nicotine may alter the normal growth and development of the heart during adolescence so that it reaches an abnormal size that will remain permanent as an adult, and make the heart more susceptible to injury.

Publications

Diastolic release of calcium from the sarcoplasmic reticulum: a potential target for treating triggered arrhythmias and heart failure.
Periodical: Journal of American College Cardiology			Index Medicus:
Authors: Shannon TR, Lew WYW				ART
Yr: 2009	Vol: 53	Nbr:	Abs:	Pg:

Cardiovascular effects of chronic subclinical exposure to lipopolysaccaride
Periodical: Journal of Heart Disease			Index Medicus:
Authors: Lew WYW				ABS
Yr: 2008	Vol: 6	Nbr: 3	Abs:	Pg:

Protein quality control in heart disease-using setablished durgs to target novel mechanisms.
Periodical: Journal American Coll Cardiol			Index Medicus:
Authors: Villarreal, F; Lew, WYW				ART
Yr: 2010	Vol:	Nbr:	Abs:	Pg:

Diastolic release of calcium from the sarcoplasmic reticulum: a potential target for treating triggered arrhythmias and heart failure.
Periodical: Journal of American College Cardiology			Index Medicus:
Authors: Shannon TR, Lew WYW				ART
Yr: 2009	Vol: 53	Nbr:	Abs:	Pg:

Cardiovascular effects of chronic subclinical exposure to lipopolysaccaride
Periodical: Journal of Heart Disease			Index Medicus:
Authors: Lew WYW				ABS
Yr: 2008	Vol: 6	Nbr: 3	Abs:	Pg:

Protein quality control in heart disease-using setablished durgs to target novel mechanisms.
Periodical: Journal American Coll Cardiol			Index Medicus:
Authors: Villarreal, F; Lew, WYW				ART
Yr: 2010	Vol:	Nbr:	Abs:	Pg: