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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% FiO2 (hypoxic group) or in ambient air (normoxic group). These hearts were subjected to 30 min of normothermic global ischemia followed by 30 min of reperfusion using the Langendorff technique. Left ventricular functional recovery in hearts administered ANP (0.1 µM) 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.

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.

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.

This study sought to show the heterogeneity of myocardial blood flow in the chronically hypoxic infantile myocardium and its response to reoxygenation using a novel type of digital radiography. Newborn rats were housed in a hypoxic chamber or in a normal chamber (controls). After 4 or 8 weeks, the control rats were ventilated with normoxic conditions, and the rats housed under hypoxia were ventilated with either hypoxic (cyanotic group) or normoxic conditions (reoxygenation group). Desmethylimipramine labeled with tritium (HDMI) was injected into the left ventricle, and both ventricular free walls were sectioned and sliced from the subepicardium to the subendocardium at 10 mm thickness. The within-layer distribution of HDMI density was measured by digital radiography, and its spatial heterogeneity (i.e., flow heterogeneity) was quantified by the coefficient of variation (CV) of flows. There were no differences in the CV between the groups in either ventricle at 4 weeks of age and no differences in the right ventricle at 8 weeks of age. There was a trend toward a higher left ventricular CV in the cyanotic group than in the control group at 8 weeks of age (0.637 ± 0.099 vs. 0.510 ± 0.060, P = 0.06). At 8 weeks of age, the CV was lower in both ventricles in the reoxygenation group than in those of the control and cyanotic groups. 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.

Whether chronic hypoxia attenuates myocardial ischemia-reperfusion injury remains controversial because conflicting data have been reported probably due to the existence of many factors influencing the functional recovery of hearts. These factors include the differences of species, the time at which hypoxia begins, the degree of hypoxia, and so on. Regarding chronic hypoxia from birth, so far the only available data are based on findings in rabbit hearts. The purpose of this study was to describe the effect of chronic hypoxia from birth on myocardial reperfusion injury in the rat heart. Normoxic hearts were obtained from rats housed in ambient air for 6 weeks (normoxic group); hypoxic hearts were obtained from rats housed in a hypoxic chamber (13%–14% oxygen) from birth for 6 weeks (hypoxic group). Isolated, crystalloid perfused working hearts were subjected to 30 min of global normothermic ischemia followed by 15 min of reperfusion; functional recovery was then measured in the two groups. The excretion of cyclic guanosine monophosphate (cGMP) in the coronary drainage was measured at the end of the preischemia and reperfusion periods. The percent recovery of the left ventricular developed pressure and the first derivative of left ventricular pressure were significantly better in the hypoxic group than in the normoxic group. cGMP excretion in the coronary drainage was significantly increased during both the preischemia and reperfusion periods. Chronic hypoxia from birth increased myocardial tolerance to ischemia-reperfusion injury with increased cGMP synthesis in the isolated heart model in rats.