Sildenafil as “first line therapy” in pulmonary persistent hypertension of the newborn?

Despite the recent advances, the clinical approach to persistent pulmonary hypertension of the newborn (PPHN) still represents an important challenge for neonatologists. The care of newborns with PPHN requires meticulous therapeutic and ventilation strategies including, besides the stabilization of the newborn, the use of nitric oxide and high-frequency ventilation. However, not all the neonates with PPHH are responsive to this clinical approach. Recent studies have proposed the use of sildenafil, a phosphodiesterase 5 inhibitor, in refractory forms of PPHN. The aim of this study is to review the cases and the clinical approach of PPHN in the Neonatal Intensive Care Unit of Meyer Children Hospital in the year 2009 and to discuss the possible role of sildenafil in the management of PPHN.

Comparison between pulse oximetry and transthoracic impedance alarm traces during home monitoring.

OBJECTIVE: To compare transthoracic impedance (TTI/ECG) and pulse oximetry alarm traces detected during home monitoring in infants at risk of apnoea, bradycardia and hypoxaemia. STUDY DESIGN: A retrospective evaluation of the monitor downloads of 67 infants who had undergone either TTI/ECG or pulse oximetry home monitoring using a device which can detect both parameters. METHODS: The patients were categorised as: apparent life-threatening events (n = 39), preterm infants (n = 21) and miscellaneous (n = 7). TTI/ECG and pulse oximetry alarm traces were scored as either true or false alarms. Classification criteria were based on visual analysis of the impedance and plethysmographic waveforms captured by the memory monitor every time alarm thresholds were violated. RESULTS: 5242 alarms occurred over 3452 days of monitoring: 4562 (87%) were false and 680 (13%) true. The mean duration of monitoring was 51 days (range 5-220 days). There were 2982 TTI/ECG false alarms (65% of the total) and 1580 pulse oximetry false alarms (35%) (p = 0.0042). Of the 680 true alarms, 507 (74%) were desaturations not attributable to central apnoea and 173 (26%) were true TTI/ECG alarms (p = 0.0013). CONCLUSIONS: Comparison of pulse oximetry and TTI/ECG alarm traces shows that true events were mostly attributable to desaturations, while false alarms were mainly provoked by TTI/ECG. The total number of false alarms is lower than reported in other studies using TTI/ECG only, thus indicating that monitoring using both pulse oximetry and TTI/ECG is suitable for home use. When the combination of both techniques is not feasible or not required, we recommend the use of motion resistant pulse oximetry alone.

Protective effects of the PARP-1 inhibitor PJ34 in hypoxic-reoxygenated cardiomyoblasts.

To clarify the role of poly(ADP-ribose)polymerase-1 (PARP-1) in myocardial ischemia-reperfusion injury, we explored some effects of PJ34, a highly specific inhibitor of this enzyme, in hypoxic-reoxygenated (HR) H9c2 cardiomyoblasts. Compared to the control, HR cells showed signs of oxidative stress, marked PARP-1 activation, NAD(+) and ATP depletion and impaired mitochondrial activity. HR cardiomyoblasts were affected by both necrosis and apoptosis, the latter involving the nuclear translocation of apoptosis-inducing factor. In HR cardiomyoblasts treated with PJ34, oxidative stress and PARP-1 activity were decreased, and NAD(+) and ATP depletion, as well as mitochondrial impairment, were attenuated. Above all, PJ34 treatment improved the survival of HR cells; not only was necrosis significantly diminished, but apoptosis was also reduced and shifted from a caspase-independent to a caspase-dependent pathway. These results suggest that PARP-1 modulation by a selective inhibitor such as PJ34 may represent a promising approach to limit myocardial damage due to post-ischemic reperfusion.

Cardiac volume overload rapidly induces oxidative stress-mediated myocyte apoptosis and hypertrophy.

Oxidative stress stimulates both growth and apoptosis in cardiac myocytes in vitro. We investigated the role of oxidative stress in the initial phases of cardiac remodeling induced in an animal model by volume overload. As plausible candidates for a connection between oxidative stress and cardiomyocyte apoptosis or hypertrophy, we explored the behaviour of two MAPKs, specifically JNK and ERK. At 48 h of overload, the greatest increase in oxidative stress coincided with a peak of cardiomyocyte apoptosis. This was possibly induced through the mitochondrial metabolism, as evidenced by the release of cytochrome c and a significant increase in the active forms of caspase-9 and -3, but not caspase-8. Oxidative stress markers significantly decreased at 96 h of overload, combined with a marked attenuation of apoptosis and the appearance of hypertrophy. The highest levels of JNK and the lowest levels of ERK phosphorylation were observed at 48 h of overload. Conversely, a sharp increase in ERK phosphorylation was detected at 96 h of overload coinciding with the hypertrophic response. Together these results show that oxidative stress is an early and transient event in myocardial volume overload. They suggest that oxidative stress mediates amplitude dependent apoptotic and hypertrophic responses in cardiomyocytes through the selective activation of, respectively, JNK and ERK.