Moderate but not severe hypothermia increases intracellular cyclic AMP through preserved production and reduced elimination

Abstract

Rewarming from accidental hypothermia could be complicated by acute cardiac dysfunction but providing supportive pharmacotherapy at low core temperatures is challenging. Several pharmacological strategies aim to improve cardiovascular function by increasing cAMP in cardiomyocytes as well as cAMP and cGMP levels in vascular smooth muscle, but it is not clear what effects temperature has on cellular elimination of cAMP and cGMP. We therefore studied the effects of differential temperatures from normothermia to deep hypothermia (37 ◦C–20 ◦C) on cAMP levels in embryonic H9c2 cardiac cells and elimination of cAMP and cGMP by PDEenzymes and ABC-transporter proteins. Our experiments showed significant elevation of intracellular cAMP in H9c2-cells at 30 ◦C but not 20 ◦C. Elimination of both cAMP and cGMP through ABC transport-proteins and PDEenzymes showed a temperature dependent reduction. Accordingly, the increased cardiomyocyte cAMP-levels during moderate hypothermia appears an effect of preserved production and reduced elimination at 30 ◦C. This correlates with earlier in vivo findings of a positive inotropic effect of moderate hypothermia.