Mechanisms whereby rapid RV pacing causes LV dysfunction: perfusion-contraction matching and NO
1 Department of Medicine, Allegheny General Hospital, MCP-Hahnemann University School of Medicine, Pittsburgh 15212; and 2 Merck Research Laboratories, West Point, Pennsylvania 19486 Incessant tachycardia induces dilated cardiomyopathy in humans and experimental models; mechanisms are incompletely...
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Published in | American journal of physiology. Heart and circulatory physiology Vol. 281; no. 6; pp. H2270 - H2281 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
01.12.2001
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Subjects | |
Online Access | Get full text |
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Summary: | 1 Department of Medicine, Allegheny General Hospital,
MCP-Hahnemann University School of Medicine, Pittsburgh 15212; and
2 Merck Research Laboratories, West Point, Pennsylvania
19486
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
(M O 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),
M O 2 (CBF/beat: 0.33 ± 0.02 to
0.19 ± 0.01 ml, P < 0.001, M O 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/d t )/LV end-diastolic diameter (EDD): 65 ± 4 to
44 ± 3 mmHg · s 1 · 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, M O 2 /beat:
0.013 ± 0.001 ml O 2 , P < 0.001).
Thereafter, CBF per beat and M O 2 per
beat increased (CBF/beat: 0.25 ± 0.01 ml,
M O 2 /beat: 0.021 ± 0.001 ml
O 2 at 28 days, P < 0.01 vs. 72 h).
Contractility declined [(LV dP/d t )/LVEDD: 19 ± 2 mmHg · s 1 · 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.
nitric oxide; cardiomyopathy; stunning; hibernation; myocardial
metabolism |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0363-6135 1522-1539 |
DOI: | 10.1152/ajpheart.2001.281.6.h2270 |