Atrionatriuretic peptide (ANP) is reported to be useful for attenuating myocardial ischemia-reperfusion injury and improving left ventricular function after reperfusion. However, ANP may be either ineffectual or harmful in cases where the myocardium has been chronically hypoxic since birth. This can be a result of the concomitant high levels of cyclic guanosine monophosphate (cGMP) produced within the myocardium. This study aimed to verify the validity of using ANP to improve left ventricular function after myocardial ischemia-reperfusion injury. For this purpose, a cyanotic congenital disease model that was developed using isolated rat hearts was used. Hearts were obtained from Sprague-Dawley rats that were housed from birth until 6 weeks of age either in a hypoxic environment with 13-14% FiO(2) (hypoxic group) or in ambient air (normoxic group). These hearts were subjected to 30min of normothermic global ischemia followed by 30min of reperfusion using the Langendorff technique. Left ventricular functional recovery in hearts administered ANP (0.1µM) into the reperfusion solution was compared with those hearts that were not administered ANP in both hypoxic (without ANP: n=6, with ANP: n=6, with ANP and HS-142-1[an antagonist of ANP]: n=6) and normoxic hearts (without ANP: n =6, with ANP: n=6). In the hypoxic hearts, ANP administration improved the percent recovery of the left ventricular developed pressure (76.3±9.2% without ANP vs. 86.9±6.7% with ANP), maximum first derivative of the left ventricular pressure (82.4±1.1% without ANP vs. 95.8±6.5% with ANP), and heart rate (85.6±4.7% without ANP vs. 96.1±5.2% with ANP) after reperfusion. The improvement and recovery of these cardiac functions were closely related to significantly increased levels of postischemic cGMP release after ANP administration. The effect of ANP was blocked by HS-142-1. The improvements observed in the hypoxic group were similar to those found in the normoxic group. ANP administration during reperfusion improved left ventricular function after myocardial acute global ischemia-reperfusion equally in both the chronically hypoxic and age-matched normoxic groups.

Little is known about hypoxia-induced modification of the canal network in the cortical bone despite its involvement in intracortical vascularity and bone blood supply. In this study, we examined the effect of chronic hypoxia on the canal network in postnatal bone. Tibiae were harvested from 4- and 8-week-old rats (hyp-4 and -8, n = 8 each), whose growth was retarded owing to postnatal exposure to hypoxia (12-14% O₂), and from 3- and 4-week-old normoxic rats (cnt-4 and -5, n = 8 each), which were similar in tibial length and cortical cross-sectional area to hyp-4 and -8, respectively. The diaphyseal canals were detected by monochromatic synchrotron radiation CT with a 3.1-μm voxel resolution. The anatomical properties of the canal network were compared between age- or size-matched hypoxic and normoxic groups. The canals were larger in diameter, were more densely distributed and connected, and opened into the marrow cavity with a higher density in hyp-4 than in cnt-4. The canal density and connectivity were also higher in hyp-4 than in cnt-3. The canal diameter, density, and connectivity were smaller in hyp-8 than in cnt-4; however, the densities of endocortical and periosteal canal openings did not differ between hyp-8 and cnt-4. We concluded that chronic hypoxia enhanced the formation of cortical canal networks at the postnatal developmental stage, probably facilitating intra- and transcortical vascularization and bone perfusion accordingly.

Chronic hypoxia from birth increased myocardial tolerance to ischemia-reperfusion injury with increased cGMP synthesis in the isolated heart model in rats.

A recent study has shown that cryptogenic stroke can occur even in patients with small or insignificant atrial septal defects (ASD). However, clinical experience in this field is still limited in Japan, also the efficacy and safety of catheter closure of such defects have not been identified. To evaluate the efficacy and safety of catheter closure of interatrial communication in patients with cryptogenic stroke, 13 patients who were diagnosed with cerebrovascular events due to cryptogenic embolism were included in this study. Mean age at procedure was 43 ± 15 (range 17-68) years. In all patients, the presence of spontaneous or provoked interatrial right-to-left shunts was demonstrated by transesophageal contrast echocardiography. Mean defect size evaluated by the balloon sizing technique was 9.2 ± 2.8 mm, and mean size of the Amplatzer Septal Occluder deployed was 9.5 ± 2.8 mm. Devices were successfully deployed in all patients, though one device migrated into the descending aorta was retrieved by a snare catheter. Complete closure was detected by transesophageal contrast echocardiography at 12 months after the procedure was in 11 (85%) of the 13 patients. During the follow-up period (30.1 ± 9.4 months), no recurrent thromboembolic event was observed. Catheter closure of interatrial right-to-left communications can be safely performed. This procedure may contribute to reduction or prevention of recurrent neurological events in this patient population.

The chronically hypoxic infantile myocardium exhibits regional flow heterogeneity similar to that observed in the normal myocardium in both ventricles and exhibits reduced flow heterogeneity in response to reoxygenation.