Detailed Instructions: Given a passage, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage.
Q: A major concern of using phosphodiesterase (PDE) inhibitors in heart failure is their potential to increase mortality by inducing arrhythmias. By diminishing cyclic adenosine monophosphate (cAMP) hydrolysis, they promote protein kinase A (PKA) activity under -adrenergic receptor (-AR) stimulation, hence enhancing Ca(2+) cycling and contraction. Yet, cAMP also activates CaMKII via PKA or the exchange protein Epac, but it remains unknown whether these pathways are involved in the pro-arrhythmic effect of PDE inhibitors.', 'Excitation-contraction coupling was investigated in isolated adult rat ventricular myocytes loaded with Fura-2 and paced at 1 Hz allowing coincident measurement of intracellular Ca(2+) and sarcomere shortening. The PDE4 inhibitor Ro 20-1724 (Ro) promoted the inotropic effects of the non-selective -AR agonist isoprenaline (Iso) and also spontaneous diastolic Ca(2+) waves (SCWs). PDE4 inhibition potentiated RyR2 and PLB phosphorylation at specific PKA and CaMKII sites increasing sarcoplasmic reticulum (SR) Ca(2+) load and SR Ca(2+) leak measured in a 0Na(+)/0Ca(2+) solution tetracaine. PKA inhibition suppressed all the effects of Iso Ro, whereas CaMKII inhibition prevented SR Ca(2+) leak and diminished SCW incidence without affecting the inotropic effects of Ro. Inhibition of Epac2 but not Epac1 diminished the occurrence of SCWs. PDE3 inhibition with cilostamide induced an SR Ca(2+) leak, which was also blocked by CaMKII inhibition.
A:
Does calmodulin kinase II inhibition limit the pro-arrhythmic Ca2+ waves induced by cAMP-phosphodiesterase inhibitors?