| Mechanisms whereby rapid RV pacing causes LV dysfunction: perfusion-contraction matching and NO. | |
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MedLine Citation:
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PMID: 11709392 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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L A Nikolaidis; T Hentosz; A Doverspike; R Huerbin; C Stolarski; Y T Shen; R P Shannon |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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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:
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Created Date: 2001-11-15 Completed Date: 2002-01-07 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: United States |
Other Details:
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Languages: eng Pagination: H2270-81 Citation Subset: IM |
Affiliation:
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Department of Medicine, Allegheny General Hospital, MCP-Hahnemann University School of Medicine, Pittsburgh, Pennsylvania 15212, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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DA-10480/DA/NIDA NIH HHS; HL-59070/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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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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