Gadolinium prevents stretch-mediated contractile dysfunction in isolated papillary muscles.
We tested the hypothesis that overstretching the myocardium could induce and/or exacerbate contractile dysfunction via stretch-activated (SA) ion channels. Maximum developed tension (T(max)), normalized to a control value, was compared in guinea pig papillary muscles held at one of three resting lengths (physiological stretch, overstretch, and unloaded) for 85 min. Overstretched muscles exhibited decreased contractile force (T(max) = 0.77 +/- 0.03) compared with physiological and unloaded muscles (T(max) = 0.93 +/- 0.05 and 1.03 +/- 0.07, respectively). Gd(3+), an SA channel antagonist, eliminated the adverse effect of overstretching (T(max) = 0.98 +/- 0.06), but nifedipine, a dihydropyridine (DHP) antagonist of L-type calcium channels, did not (T(max) = 0.82 +/- 0.04). Exposure to modified hypoxia-reoxygenation (MHR) during physiological stretch resulted in decreased contractility (T(max) = 0.63 +/- 0.07), an effect that was exacerbated by overstretching (T(max) = 0.44 +/- 0.04). Gd(3+) mitigated the effects of overstretch during MHR (T(max) = 0.64 +/- 0.05), but DHP did not (T(max) = 0.48 +/- 0.04). These data suggest that overstretching of the myocardium contributes to contractile abnormalities via SA channels that are distinct from L-type calcium channels.
Nicolosi
A C
AC
Department of Surgery, The Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA. nicolosi@mcw.edu
Kwok
C S
CS
Contney
S J
SJ
Olinger
G N
GN
Bosnjak
Z J
ZJ
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000502:physiology; D004095:Dihydropyridines / Q000494:pharmacology; D005682:Gadolinium / Q000494:pharmacology*; D006168:Guinea Pigs; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D010100:Oxygen / Q000494:pharmacology; D010210:Papillary Muscles / Q000502:physiology*
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D004095:Dihydropyridines; C038806:1,4-dihydropyridine; D005682:Gadolinium; D009543:Nifedipine; D010100:Oxygen