Loading…
Pyruvate potentiates inotropic effects of isoproterenol and Ca 2+ in rabbit cardiac muscle preparations
Catecholamines and elevated extracellular Ca 2+ concentration ([Ca 2+ ] o ) augment contractile force by increased Ca 2+ influx and subsequent increased sarcoplasmic reticulum (SR) Ca 2+ release. We tested the hypothesis that pyruvate potentiates Ca 2+ release and inotropic response to isoproterenol...
Saved in:
| Published in: | American journal of physiology. Heart and circulatory physiology 2000-08, Vol.279 (2), p.H702-H708 |
|---|---|
| Main Authors: | , , , , |
| Format: | Article |
| Language: | English |
| Citations: | Items that this one cites Items that cite this one |
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | Catecholamines and elevated extracellular Ca
2+
concentration ([Ca
2+
]
o
) augment contractile force by increased Ca
2+
influx and subsequent increased sarcoplasmic reticulum (SR) Ca
2+
release. We tested the hypothesis that pyruvate potentiates Ca
2+
release and inotropic response to isoproterenol and elevated [Ca
2+
]
o
, since this might be of potential importance in a clinical setting to circumvent deleterious effects on energy demand during application of catecholamines. Therefore, we investigated isometrically contracting myocardial preparations from rabbit hearts at 37°C, pH 7.4, and a stimulation frequency of 1 Hz. At a [Ca
2+
]
o
of 1.25 mM, pyruvate (10 mM) alone increased developed force (F
dev
) from 1.89 ± 0.42 to 3.62 ± 0.62 (SE) mN/mm
2
( n = 8, P < 0.05) and isoproterenol (10
−6
M) alone increased F
dev
from 2.06 ± 0.55 to 25.11 ± 2.1 mN/mm
2
( P < 0.05), whereas the combination of isoproterenol and pyruvate increased F
dev
overproportionally from 1.89 ± 0.42 to 33.31 ± 3.18 mN/mm
2
( P < 0.05). In a separate series of experiments, we assessed SR Ca
2+
content by means of rapid cooling contractures and observed that, despite no further increase in F
dev
by increasing [Ca
2+
]
o
from 8 to 16 mM, 10 mM pyruvate could still increase F
dev
from 26.4 ± 6.8 to 29.7 ± 7.1 mN/mm
2
( P < 0.05, n = 9) as well as the Ca
2+
load of the SR. The results show that the positive inotropic effects of pyruvate potentiate the inotropic effects of isoproterenol or Ca
2+
, because in the presence of pyruvate, Ca
2+
and isoproterenol induced larger increases in inotropy than can be calculated by mere addition of the individual effects. |
|---|---|
| ISSN: | 0363-6135 1522-1539 |
| DOI: | 10.1152/ajpheart.2000.279.2.H702 |