Mitochondrial role in ischemia–reperfusion of rat hearts exposed to high-K + cardioplegia and clonazepam: energetic and contractile consequences

• Autores: Consolini, Alicia Elvira; Ragone, María Inés; Conforti, Paula Andrea; Volonté, Maria Guillermina
• Año de publicación: 2007
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: CALORIMETRY; ISCHEMIA-REPERFUSION; HEART; MITOCHONDRIA; CARDIOPLEGIA
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

The role of the mitochondrial Na/Ca-exchanger (mNCX) in hearts exposed to ischemia–reperfusion (I/R) and pretreated with cardioplegia (CPG) was studied from a mechano-calorimetric approach. No-flow ischemia (ISCH) and reperfusion (REP) were developed in isolated rat hearts pretreated with 10 µmol/L clonazepam (CLZP), an inhibitor of the mNCX, and (or) a high K+ – low Ca2+ solution (CPG). Left ventricular end diastolic pressure (LVEDP), pressure development during beats (P), and the steady heat release (Ht) were continuously measured and muscle contents of ATP and PCr were analyzed at the end of REP. During REP, Ht increased more than P, reducing muscle economy (P/Ht) and the ATP content. CPG induced an increase in P recovery during REP (to 90% ± 10% of preISCH) with respect to nonpretreated hearts (control, C, to 64% ± 10%, p < 0.05). In contrast, CLZP reduced P recovery of CPG-hearts (50% ± 6.4%, p < 0.05) and increased LVEDP in C hearts. To evaluate effects on sarcoplasmic reticulum (SR) function, ischemic hearts were reperfused with 10 mmol/L caffeine –36 mmol/L Na (C – caff – low Na). It increased LVEDP, which afterwards slowly relaxed, whereas Ht increased (by about 6.5 mW/g). CLZP sped up the relaxation with higher ΔHt, C – caff – low Na produced higher contracture and lower Ht in perfused than in ischemic hearts. Values of ΔHt were compared with reported fluxes of Ca2+-transporters, suggesting that mitochondria may be in part responsible for the ΔHt during C – caff – low Na REP. Results suggest that ISCH–REP reduced the SR store for the recovery of contractility, but induced Ca2+ movement from the mitochondria to the SR stores. Also, mitochondria and SR are able to remove cytosolic Ca2+ during overloads (as under caffeine), through the mNCX and the uniporter. CPG increases Ca2+ cycling from mitochondria to the SR, which contributes to the higher recovery of P. In contrast, CLZP produces a deleterious effect on ISCH–REP associated with higher heat release and reduced resynthesis of high energy phosphates, which suggests the induction of mitochondrial Ca cycling and uncoupling.
Fil: Consolini, Alicia Elvira. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Cátedra de Farmacología; Argentina
Fil: Ragone, María Inés. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Cátedra de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Conforti, Paula Andrea. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Centro de Investigación y Desarrollo en Criotecnología de Alimentos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Criotecnología de Alimentos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Criotecnología de Alimentos; Argentina
Fil: Volonté, Maria Guillermina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Cátedra de Control de Calidad de Medicamentos; Argentina