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CHRONIC COCAINE EFFECTS ON NORMAL AND DISEASED HEARTS

Award Number: R01DA010480
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: HEALTH SERVICES
PERIOD OF PERFORMANCE START DATE: 09/01/1996
PERIOD OF PERFORMANCE END DATE: 05/31/2007

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CHRONIC COCAINE EFFECTS ON NORMAL AND DISEASED HEARTS - Chronic cocaine abuse remains a considerable public health problem among the nation's adolescent and young adult populations. In addition to the recognized psychosocial burdens associated with cocaine abuse, there are serious physiological consequences that remain poorly understood. Most prominent among the pathophysiological consequences are the cardiovascular toxicities attributed to chronic cocaine use. Myocardial ischemia and infarction and cardiomyopathy remain the most serious cardiovascular consequences of cocaine use in humans and a prominent cause of premature morbidity and mortality among the nation's youth. The fact that many more individuals abuse cocaine than ever develop these cardiovascular complications has suggested that there may be an underlying predisposition to the cardiovascular toxicity of cocaine. Furthermore, whether and to what extent these predisposing factors are genetically or environmentally determined remains a compelling clinical as well as biological question. During the last four years, our laboratory has made several fundamental observations with respect to the cardiovascular responses to cocaine in conscious dogs and non-human primates. Prominent among them is the importance of an intact autonomic nervous system in mediating the cardiovascular responses to cocaine. In addition, we have shown that altered myocardial substrates occur following ventricular denervation or the development of asymptomatic LV dysfunction, enhance the cardiovascular responses to acute cocaine administration. This has lead us to speculate that cardiac dysautonomia may represent an important acquired risk factor for enhanced cardiovascular toxicity following cocaine administration. In this renewal, we will determine the extent to which and the mechanisms whereby chronic cocaine exposure causes LV dysfunction in a conscious pig model. We will demonstrate that chronic cocaine exposure leads to increased myocardial stunning and larger infarct size as well as progressive ventricular dilitation in dilated cardiomyopathy. Finally, we will determine the role of altered SNS activity, altered nitric oxide activity, and increased cytokine expression, in the mechanisms of chronic cocaine toxicity.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2006 ( Subtotal = $256,332 )
2006	2006	ALLEGHENY SINGER RESEARCH CORP	2 ALLEGHENY CTR, 11TH FLOOR	PITTSBURGH	PA	15212	ALLEGHENY	USA	Drug Use and Addiction Research Programs	000	8	5/31/2006	NON-COMPETING CONTINUATION	$256,332
														Subtotal = $256,332

Issue Date FY: 2005 ( Subtotal = $262,500 )
2005	2005	ALLEGHENY SINGER RESEARCH CORP	503 MARTINDALE STREET	PITTSBURGH	PA	15212	ALLEGHENY	USA	Drug Use and Addiction Research Programs	000	7	5/27/2005	NON-COMPETING CONTINUATION	$262,500
														Subtotal = $262,500

Issue Date FY: 2004 ( Subtotal = $262,500 )
2004	2004	ALLEGHENY SINGER RESEARCH CORP	503 MARTINDALE STREET	PITTSBURGH	PA	15212	ALLEGHENY	USA	Drug Use and Addiction Research Programs	000	6	5/18/2004	NON-COMPETING CONTINUATION	$262,500
														Subtotal = $262,500

Issue Date FY: 2003 ( Subtotal = $262,500 )
2003	2003	ALLEGHENY SINGER RESEARCH CORP	503 MARTINDALE STREET	PITTSBURGH	PA	15212	ALLEGHENY	USA	Drug Use and Addiction Research Programs	000	5	9/22/2003	COMPETING CONTINUATION	$262,500
														Subtotal = $262,500

Issue Date FY: 1999 ( Subtotal = $253,431 )
1999	1999	ALLEGHENY UNIV OF THE HLTH SCIENCES	503 MARTINDALE STREET	PITTSBURGH	PA	15212	ALLEGHENY	USA	Drug Use and Addiction Research Programs	000	4	7/27/1999	NON-COMPETING CONTINUATION	$253,431
														Subtotal = $253,431

Issue Date FY: 1998 ( Subtotal = $243,685 )
1998	1998	ALLEGHENY UNIV OF THE HLTH SCIENCES	503 MARTINDALE STREET	PITTSBURGH	PA	15212	ALLEGHENY	USA	Drug Use and Addiction Research Programs	000	3	7/27/1998	NON-COMPETING CONTINUATION	$243,685
														Subtotal = $243,685

Grand Total All Awards = $1,540,948

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CHRONIC COCAINE EFFECTS ON NORMAL AND DISEASED HEARTS

Award Number: R01DA010480

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: HEALTH SERVICES

PERIOD OF PERFORMANCE START DATE: 09/01/1996

PERIOD OF PERFORMANCE END DATE: 05/31/2007

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