MECHANISMS FOR HYPOTHERMIA-INDUCED INCREASE IN CONTRACTILE-FORCE STUDIED BY MECHANICAL RESTITUTION AND POSTREST CONTRACTIONS IN GUINEA-PIG PAPILLARY-MUSCLE

Lowering myocardial temperature increases contractile force, presumabl y by increasing intracellular calcium content. To study the mechanisms behind this, we compared the effects of some known inotropic interven tions with hypothermia on mechanical restitution and post-rest contrac tile force in isolated guinea-pig papillary muscles. In four groups (n = 6 per group), the effects of: (1) reducing the ability for Na/Ca ex change to extrude Ca2+ (a) by increasing [Na+]i with ouabain or (b) by increasing [Ca2+]o; and (2) activation of calcium channels with Bay-K 8644, were compared with lowering temperature from 37 to 27-degrees-C . Normally (at 37-degrees-C and 2 mm CaCl2), mechanical restitution co uld be described by a rapid recovery phase with a time constant betwee n 180 and 220 ms, followed by a slowly decaying phase with a time cons tant between 5000 and 8000 ms and post-rest contractions (1-10 min res t) were markedly depressed compared to steady-state contractions. Stea dy-state developed force was markedly increased at 27-degrees-C, after 1 muM ouabain, 6 mm CaCl2 or 0.1 muM Bay-K 8644. At 27-degrees-C the rapid recovery phase of restitution was delayed while the slowly decay ing phase was not affected. Ouabain and increased [Ca2+]o caused eleva tion of the slowly decaying phase of restitution and markedly attenuat ed the post-rest depression of developed force, which may be attribute d to a reduced diastolic extrusion of Ca2+ via the Na/Ca exchanger. Hy pothermia and Bay-K 8644 on the other hand, augmented this post-rest d epression. Hence, this study suggests that increased Ca2+ influx due t o delayed inactivation of calcium channels may account for the increas ed developed force during hypothermia rather than reduced diastolic ex trusion of Ca2+ via the Na/Ca exchanger.