Knockout of adenylyl cyclase isoform 5 or 6 differentially modifies the β-adrenoceptor-mediated inotropic response.

Although only β-adrenergic receptors (βAR) dually couple with stimulatory G protein (G) and inhibitory G protein (G), inactivation of G enhances both βAR and βAR responsiveness. We hypothesize that G restrains spontaneous adenylyl cyclase (AC) activity independent of receptor activation. Subcellular localization of the AC5/6 subtypes varies contributing to the compartmentation of βAR signaling.

Hypothermia elongates the contraction-relaxation cycle in explanted human failing heart decreasing the time for ventricular filling during diastole.

Targeted temperature management is part of the standardized treatment for patients in cardiac arrest. Hypothermia decreases cerebral oxygen consumption and induces bradycardia; thus, increasing the heart rate may be considered to maintain cardiac output. We hypothesized that increasing heart rate during hypothermia would impair diastolic function.