Submitted on January 15, 2007
Accepted on March 26, 2007
THE CARDIOPROTECTIVE EFFECTS OF STRETCH ARE MEDIATED BY ACTIVATION OF SARCOLEMMAL NOT BY MITOCHONDRIAL ATP-SENSITIVE POTASSIUM CHANNELS
Susana María Mosca1*
1 Facultad de Ciencias Médicas. Universidad Nacional de La Plata, Centro de Investigaciones Cardiovasculares, La Plata, Buenos Aires, Argentina
* To whom correspondence should be addressed. E-mail: smosca{at}atlas.med.unlp.edu.ar.
To determine whether sarcolemmal and/or mitochondrial KATP channels (sarc-KATP ; mito-KATP) are involved in the protection, isolated isovolumic rat hearts were assigned to the following protocols: non-stretched hearts (NS) = 20 min of global ischemia (Is) and 30 min of reperfusion and stretched hearts (S): before Is, hearts received 5 min of stretch + 10 min of no intervention. Stretch was induced by a transient increase in left ventricular end diastolic pressure (LVEDP) from 10 to 40 mmHg. Other hearts received 5-HD (100 µM), a selective inhibitor of mito-KATP or HMR 1098 (20 µM), a selective inhibitor of sarc-KATP, before stretch protocol. Systolic function was assessed through left ventricular developed pressure (LVDP) and +dP/dtmax and diastolic function through-dP/dtmax and LVEDP. Lactate dehydrogenase (LDH) release and ATP content were also measured. Stretch resulted in a significant increase of postischemic recovery and attenuation of diastolic stiffness. At 30 min of reperfusion LVDP and +dP/dtmaxwere 87 ± 4 % and 92 ± 6 %, -dP/dtmax and LVEDP were 95 ± 9 % and 10 ± 4 mmHg vs 57 ± 6 % , 53± 6 %, 57 ± 10 % and 28 ± 5 mmHg, respectively in NS hearts. Stretch increased ATP content and did not produce LDH release. 5-HD did not modify and HMR 1098 prevented the protection achieved by stretch.
Our results show that the beneficial effects of stretch on postischemic myocardial dysfunction, cellular damage and energetic state involve the participation of sarc-KATP but not mito-KATP .
