Adverse perinatal environment contributes to altered cardiac development and function.

Area of Science:

• Cardiovascular Physiology
• Developmental Biology
• Neonatal Medicine

Background:

• Intrauterine growth restriction (IUGR) is linked to cardiovascular diseases.
• Maternal inflammation during pregnancy is a common cause of IUGR.
• Perinatal inflammation and hyperoxia may induce early cardiac dysfunction.

Purpose of the Study:

• To investigate the effects of perinatal inflammation and hyperoxia on cardiomyocyte contractility and calcium signaling.
• To determine if these exposures lead to early cardiac dysfunction in a mouse model.
• To explore alterations in calcium handling proteins during neonatal development.

Main Methods:

• Mice were exposed to lipopolysaccharide (LPS) or saline during gestation, followed by neonatal hyperoxia (85% O2) or room air (RA).
• Cardiac function was assessed using echocardiography in vivo and isolated cardiomyocyte contractility assays ex vivo.
• Expression and phosphorylation of key calcium handling proteins (SERCA2a, phospholamban, Sorcin) were analyzed.

Main Results:

• LPS/O2 mice exhibited reduced birth weight and compromised left ventricular (LV) function by postnatal day 3.
• Isolated cardiomyocytes from LPS/O2 mice showed decreased shortening but increased calcium transient amplitude.
• Altered expression and phosphorylation of SERCA2a, phospholamban, and Sorcin were observed, resembling fetal developmental patterns.

Conclusions:

• Combined perinatal inflammation and hyperoxia exposure induce IUGR and early cardiac dysfunction in mice.
• These exposures alter cardiomyocyte contractility and calcium handling, potentially predisposing to long-term cardiovascular issues.
• Neonatal cardiac calcium handling protein expression patterns reflect fetal development, suggesting developmental programming.