Advanced

Intravenous allopurinol decreases myocardial oxygen consumption and increases mechanical efficiency in dogs with pacing-induced heart failure

Ekelund, Ulf LU ; Harrison, R W; Shokek, O; Thakkar, R N; Tunin, R S; Senzaki, H; Kass, D A; Marban, E and Hare, J M (1999) In Circulation Research 85(5). p.437-445
Abstract
Allopurinol, an inhibitor of xanthine oxidase, increases myofilament calcium responsiveness and blunts calcium cycling in isolated cardiac muscle. We sought to extend these observations to conscious dogs with and without pacing-induced heart failure and tested the prediction that allopurinol would have a positive inotropic effect without increasing energy expenditure, thereby increasing mechanical efficiency. In control dogs (n=10), allopurinol (200 mg IV) caused a small positive inotropic effect; (dP/dt)(max) increased from 3103+/-162 to 3373+/-225 mm Hg/s (+8.3+/-3.2%; P=0.01), but preload-recruitable stroke work and ventricular elastance did not change. In heart failure (n=5), this effect was larger; (dP/dt)(max) rose from 1602+/-190 to... (More)
Allopurinol, an inhibitor of xanthine oxidase, increases myofilament calcium responsiveness and blunts calcium cycling in isolated cardiac muscle. We sought to extend these observations to conscious dogs with and without pacing-induced heart failure and tested the prediction that allopurinol would have a positive inotropic effect without increasing energy expenditure, thereby increasing mechanical efficiency. In control dogs (n=10), allopurinol (200 mg IV) caused a small positive inotropic effect; (dP/dt)(max) increased from 3103+/-162 to 3373+/-225 mm Hg/s (+8.3+/-3.2%; P=0.01), but preload-recruitable stroke work and ventricular elastance did not change. In heart failure (n=5), this effect was larger; (dP/dt)(max) rose from 1602+/-190 to 1988+/-251 mm Hg/s (+24.4+/-8.7%; P=0.03), preload-recruitable stroke work increased from 55.8+/-9.1 to 84. 9+/-12.2 mm Hg (+28.1+/-5.3%; P=0.02), and ventricular elastance rose from 6.0+/-1.6 to 10.5+/-2.2 mm Hg/mm (P=0.03). Allopurinol did not affect myocardial lusitropic properties either in control or heart failure dogs. In heart failure dogs, but not controls, allopurinol decreased myocardial oxygen consumption (-49+/-4.6%; P=0. 002) and substantially increased mechanical efficiency (stroke work/myocardial oxygen consumption; +122+/-42%; P=0.04). Moreover, xanthine oxidase activity was approximately 4-fold increased in failing versus control dog hearts (387+/-125 versus 78+/-72 pmol/min. mg(-1); P=0.04) but was not detectable in plasma. These data indicate that allopurinol possesses unique inotropic properties, increasing myocardial contractility while simultaneously reducing cardiac energy requirements. The resultant boost in myocardial contractile efficiency may prove beneficial in the treatment of congestive heart failure. (Less)
Please use this url to cite or link to this publication:
author
publishing date
type
Contribution to journal
publication status
published
subject
keywords
myocardial contractility, oxidant stress, xanthine oxidase, heart failure
in
Circulation Research
volume
85
issue
5
pages
437 - 445
publisher
American Heart Association
external identifiers
  • pmid:10473673
  • scopus:0033520357
ISSN
0009-7330
language
English
LU publication?
no
id
5d18e7c2-2836-4c2f-8c7a-43bd568fa3fe (old id 1114779)
alternative location
http://circres.ahajournals.org/cgi/content/full/85/5/437
date added to LUP
2008-07-04 16:28:41
date last changed
2017-10-08 04:22:31
@article{5d18e7c2-2836-4c2f-8c7a-43bd568fa3fe,
  abstract     = {Allopurinol, an inhibitor of xanthine oxidase, increases myofilament calcium responsiveness and blunts calcium cycling in isolated cardiac muscle. We sought to extend these observations to conscious dogs with and without pacing-induced heart failure and tested the prediction that allopurinol would have a positive inotropic effect without increasing energy expenditure, thereby increasing mechanical efficiency. In control dogs (n=10), allopurinol (200 mg IV) caused a small positive inotropic effect; (dP/dt)(max) increased from 3103+/-162 to 3373+/-225 mm Hg/s (+8.3+/-3.2%; P=0.01), but preload-recruitable stroke work and ventricular elastance did not change. In heart failure (n=5), this effect was larger; (dP/dt)(max) rose from 1602+/-190 to 1988+/-251 mm Hg/s (+24.4+/-8.7%; P=0.03), preload-recruitable stroke work increased from 55.8+/-9.1 to 84. 9+/-12.2 mm Hg (+28.1+/-5.3%; P=0.02), and ventricular elastance rose from 6.0+/-1.6 to 10.5+/-2.2 mm Hg/mm (P=0.03). Allopurinol did not affect myocardial lusitropic properties either in control or heart failure dogs. In heart failure dogs, but not controls, allopurinol decreased myocardial oxygen consumption (-49+/-4.6%; P=0. 002) and substantially increased mechanical efficiency (stroke work/myocardial oxygen consumption; +122+/-42%; P=0.04). Moreover, xanthine oxidase activity was approximately 4-fold increased in failing versus control dog hearts (387+/-125 versus 78+/-72 pmol/min. mg(-1); P=0.04) but was not detectable in plasma. These data indicate that allopurinol possesses unique inotropic properties, increasing myocardial contractility while simultaneously reducing cardiac energy requirements. The resultant boost in myocardial contractile efficiency may prove beneficial in the treatment of congestive heart failure.},
  author       = {Ekelund, Ulf and Harrison, R W and Shokek, O and Thakkar, R N and Tunin, R S and Senzaki, H and Kass, D A and Marban, E and Hare, J M},
  issn         = {0009-7330},
  keyword      = {myocardial contractility,oxidant stress,xanthine oxidase,heart failure},
  language     = {eng},
  number       = {5},
  pages        = {437--445},
  publisher    = {American Heart Association},
  series       = {Circulation Research},
  title        = {Intravenous allopurinol decreases myocardial oxygen consumption and increases mechanical efficiency in dogs with pacing-induced heart failure},
  volume       = {85},
  year         = {1999},
}