While it is known that ADM is increased in failing human ventricles, the expression of ADM in human ventricular allografts remains unknown.
Monocyte chemotactic protein-1 (MCP-1) has been shown to be produced and released by the heart and to be increased in failing heart [ 38, 39].
On the other hand, the reduced myofilament Ca2+ sensitivity may help myocardial relaxation as Ca2+ concentrations are increased in failing hearts [ 3, 9].
Chronic heart failure is associated with an increase in circulating catecholamines [ 16], PKA phosphorylation of RyR2 is markedly increased in failing human hearts [ 17], and mice with constitutive activation of PKA show hyperphosphorylation of RyR2 and dilated cardiomyopathy [ 13].
While the mean systemic arterial pressure, the rate-pressure product, the mean pulmonary arterial pressure, and the pulmonary artery occlusion pressure increased in failing trials, these variables remained stable during nitroglycerin administration.
Studies in mice with cardiac-specific deletion [ 15] or overexpression [ 16] of PKD1 corroborate a key role for PKD1 in pathological cardiac remodelling, and PKD1 expression and activation have been shown to be increased in failing human myocardium [ 17].
In our study, RPP, a global index of myocardial workload and oxygen demand [ 21], increased during failing trials on Control day, whereas nitroglycerin infusion restored this change, thus suggesting a beneficial effect of nitroglycerin on reducing myocardial oxygen demand and weaning-induced myocardial ischemia.
A previous study reported that corin expression was upregulated, whereas corin activity did not increase in failing heart tissues.
The ratio of fasting proinsulin to insulin was used as an index of insulin secretion, since this ratio increases with failing β-cell function (27, 28).
However, several attempts resulted in the rate of change in exposure levels at Peakyear −45 increasing and failing to converge, as well as the rate at Peakyear −35 eventually taking up negative values.
