Inhibition of adenylyl cyclase 8 prevents the upregulation of Orai1 channel, which improves cardiac function after myocardial infarction.

The upregulation of Orai1 and subsequent store-operated Ca2+ entry (SOCE) has been associated with adverse cardiac remodeling and heart failure (HF). However, the mechanism underlying Orai1 upregulation and its role in myocardial infarction remains unclear. Our study investigated the role of Orai1 in activating adenylyl cyclase 8 (AC8) and cyclic AMP (cAMP) response element-binding protein (CREB), as well as its contribution to cardiac dysfunction induced by ischemia and reperfusion (I/R). We found that I/R evoked an increase in the expression of Orai1 and AC8 in rats' hearts, resulting in a substantial rise in diastolic Ca2+ concentration ([Ca2+]i), and reduced ventricular contractions. The expression of Orai1 and AC8 was also increased in ventricular biopsies of post-ischemic HF patients. Mechanistically, we demonstrate that I/R activation of Orai1 stimulated AC8, which produced cAMP and phosphorylated CREB. Subsequently, p-CREB activated the ORAI1 promoter, resulting in Orai1 upregulation and SOCE exacerbation. Intramyocardial administration of AAV9 carrying AC8 short hairpin RNA decreased the expression of AC8, Orai1 and CREB, which restored diastolic [Ca2+]i and improved cardiac contraction. Therefore, our data suggests that the axis composed by Orai1/AC8/CREB plays a critical role in I/R-induced cardiac dysfunction, representing a potential new therapeutic target to limit the progression of the disease toward HF.

Mechanical ventilation during cardiopulmonary bypass in neonates improves postoperative outcome.

OBJECTIVES: Cardiopulmonary bypass generates a systemic inflammatory response. This inflammatory response is reduced if patients are ventilated during bypass, as evidenced by lower levels of postoperative circulating inflammatory mediators. However, this does not appear to make much clinical difference in adults, at least not consistently, but, to our knowledge, has never been assessed in paediatric cardiac surgery, which is the objective of this study. METHODS: This is a prospective clinical study of 12 consecutive neonates operated for the correction of either transposition of the great arteries ± ventricular septal defect or aortic arch hypoplasia ± ventricular septal defect, who were ventilated during cardiopulmonary bypass. These were compared to 11 neonates with the same malformations, who had undergone the same operations but without being ventilated during bypass (historical control group). RESULTS: One patient from the control group died on the 15th postoperative day due to sepsis and multi-organ failure. Bypass times and cross-clamp times were similar in the 2 groups. Ventilation on bypass was associated with significantly lower postoperative serum concentrations of C-reactive protein, shorter mechanical ventilation and lower vasoactive-inotropic score. Duration of stay on intensive care unit (ICU) showed a tendency to be shorter in patients who were ventilated on bypass, but this did not reach statistical significance. There were no differences between the 2 groups with respect to postoperative mixed venous oxygen saturations and serum concentrations of lactate and troponin I. CONCLUSIONS: Mechanical ventilation during cardiopulmonary bypass in neonates improves postoperative outcome.

The morphologically right and left ventricles cannot be distinguished by their coronary arterial pattern.

OBJECTIVES: The morphologically right and left ventricles are distinguished from each other based on their internal anatomical features, because their external (epicardial) surfaces do not appear to have any distinguishing mark for such ventricular identification. Nevertheless, ventricular identification based on epicardial characteristics, if these were possible, would be interesting to surgeons, because this would enable them to identify each ventricle rapidly upon opening the chest. This made us curious as to whether or not the two ventricles may be distinguished based on their epicardial coronary arterial patterns, because this is the most obvious epicardial ventricular feature. METHODS: This idea led us to formulate the following 2 hypotheses: (i) The morphologically left ventricle is always the one that receives the higher number of the marginal arteries as compared to the morphologically right ventricle. (ii) Only the morphologically left ventricle receives the diagonal arteries from the anterior and posterior interventricular arteries. These hypotheses were tested in this anatomical observational study by examination of 98 normal and 398 congenitally malformed formaldehyde-preserved hearts encompassing most malformations, including rare ones and hearts in which 1 ventricle is hypoplastic. RESULTS: These examinations show that both hypotheses are false. CONCLUSIONS: The two ventricles cannot be distinguished from each other based on the number of marginal arteries that they receive or which one receives diagonal arteries; both ventricles may receive diagonal arteries from either or both interventricular arteries.

A simple surgical technique to prevent atrial reentrant tachycardia in surgery for congenital heart disease†.

OBJECTIVES: To present and test a simple surgical technique that may prevent atrial reentrant tachycardia following surgery for congenital heart disease. This arrhythmia is one of the commonest long-term complications of such a surgery. It may occur many years (even decades) after the operation. It is usually explained as a late consequence of right atriotomy, which is an inherent component of many operations for congenital heart disease. Right atriotomy results in a long scar on the right atrial myocardium. This scar, as any scar, is a barrier to electrical conduction, and macro-reentrant circuits may form around it, causing reentrant tachycardia. However, this mechanism may be counterchecked and neutralized by our proposed method, which prevents reentrant circuits around right atriotomy scars. METHODS: The proposed method is implemented after termination of cardiopulmonary bypass and tying the venous purse-strings. It consists of constructing a full-thickness suture line on the intact right atrial wall from the inferior vena cava (IVC) (a natural conduction barrier) to the atriotomy incision. This suture line is made to cross the venous cannulation sites if these are on the atrial myocardium (rather than being directly on the venae cavae). Thus, the IVC, atriotomy and cannulation sites are connected to each other in series by a full-thickness suture line on the atrial wall. If this suture line becomes a conduction barrier, it would prevent reentrant circuits around right atrial scars. This was tested in 13 adults by electroanatomical mapping. All 13 patients had previously undergone right atriotomy for atrial septal defect closure: 8 of them with the addition of the proposed preventive suture line (treatment group) and 5 without (control group). RESULTS: In all 13 cases, the atriotomy scar was identified as a barrier to electrical conduction with electrophysiological evidence of fibrosis (scarring). In the 8 patients with the proposed suture line, this had also become a scar and a complete conduction barrier. In the 5 patients without this suture line, there was free electrical conduction between the IVC and atriotomy scar. CONCLUSIONS: The proposed suture line becomes a scar and conduction barrier. Therefore, it would prevent reentrant circuits around atrial scars and their consequent arrhythmias.