Document Detail


Mechanisms whereby rapid RV pacing causes LV dysfunction: perfusion-contraction matching and NO.
MedLine Citation:
PMID:  11709392     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Incessant tachycardia induces dilated cardiomyopathy in humans and experimental models; mechanisms are incompletely understood. We hypothesized that excessive chronotropic demands require compensatory contractility reductions to balance metabolic requirements. We studied 24 conscious dogs during rapid right ventricular (RV) pacing over 4 wk. We measured hemodynamic, coronary blood flow (CBF), myocardial O(2) consumption (MVO(2)) responses, myocardial nitric oxide (NO) production, and substrate utilization. Early pacing (6 h) resulted in decreased heart rate (HR)-adjusted coronary blood flow (CBF), MVO(2) (CBF/beat: 0.33 +/- 0.02 to 0.19 +/- 0.01 ml, P < 0.001, MVO(2)/beat: 0.031 +/- 0.002 to 0.016 +/- 0.001 ml O(2), P < 0.001), and contractility [left ventricular (LV) first derivative pressure (dP/dt)/LV end-diastolic diameter (EDD): 65 +/- 4 to 44 +/- 3 mmHg x s(-1) x mm(-1), P < 0.01], consistent with flow-metabolism-function coupling, which persisted over the first 72 h of pacing (CBF/beat: 0.15 +/- 0.01 ml, MVO(2)/beat: 0.013 +/- 0.001 ml O(2), P < 0.001). Thereafter, CBF per beat and MVO(2) per beat increased (CBF/beat: 0.25 +/- 0.01 ml, MVO(2)/beat: 0.021 +/- 0.001 ml O(2) at 28 days, P < 0.01 vs. 72 h). Contractility declined [(LV dP/dt)/LVEDD: 19 +/- 2 mmHg x s(-1) x mm(-1), P < 0.0001], signifying flow-function mismatch. Cardiac NO production, endothelial NO synthase expression, and fatty acid utilization decreased in late phase, whereas glycogen content and lactate uptake increased. Incessant tachycardia induces contractile, metabolic, and flow abnormalities reflecting flow-function matching early, but progresses to LV dysfunction late, despite restoration of flow and metabolism. The shift to flow-function mismatch is associated with impaired myocardial NO production.
Authors:
L A Nikolaidis; T Hentosz; A Doverspike; R Huerbin; C Stolarski; Y T Shen; R P Shannon
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  281     ISSN:  0363-6135     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2001 Dec 
Date Detail:
Created Date:  2001-11-15     Completed Date:  2002-01-07     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H2270-81     Citation Subset:  IM    
Affiliation:
Department of Medicine, Allegheny General Hospital, MCP-Hahnemann University School of Medicine, Pittsburgh, Pennsylvania 15212, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Respiration / physiology
Consciousness
Coronary Circulation / physiology
Dogs
Enzyme Inhibitors / pharmacology
Female
Glycogen / metabolism
Lactic Acid / metabolism
Male
Myocardial Contraction / physiology*
Myocardial Stunning / metabolism,  physiopathology
Myocardium / metabolism*
Nitric Oxide / biosynthesis,  metabolism*
Nitric Oxide Synthase / antagonists & inhibitors,  metabolism
Nitric Oxide Synthase Type III
Nitroarginine / pharmacology
Pacemaker, Artificial
Tachycardia / metabolism,  physiopathology
Ventricular Dysfunction, Left / metabolism*,  physiopathology*
Grant Support
ID/Acronym/Agency:
DA-10480/DA/NIDA NIH HHS; HL-59070/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 10102-43-9/Nitric Oxide; 2149-70-4/Nitroarginine; 50-21-5/Lactic Acid; 9005-79-2/Glycogen; EC 1.14.13.39/Nitric Oxide Synthase; EC 1.14.13.39/Nitric Oxide Synthase Type III

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