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Purpose: Myocardial tissue ischemia may be mitigated by a well-developed coronary collateral circulation. Only few detailed 3D data are available of the entire human coronary arterial tree. Here, high-resolution reconstructions of the coronary vasculature of two human hearts were quantitatively analyzed.Methods: Two hearts became available through autopsy: heart #1 (64 years, 595 g) with left ventricular hypertrophy and a scar on the inferior wall, indicating an old infarction and heart #2 (84 years, 330 g) without prior cardiovascular events. The coronary arteries were cannulated, flushed with saline solution and thereafter filled with fluorescent replica material at 100 mmHg. After cast polymerization, the hearts were frozen and then alternately cut and en-face imaged using an imaging cryomicrotome, resulting in a complete 3D reconstruction (voxel size 32 μm). From the reconstructions, arterial segment length, diameter, and collateral presence were determined.Results: In heart #1, about 1300 collaterals were detected and evenly distributed over the myocardium. The scar tissue showed a lower vascular density compared to the rest of the myocardium. Bridging collaterals were most prevalent between LCX and LAD and between LAD and RCA. Collateral vessels connecting through the border zone of the scar tissue ran in multiple parallel pathways. In heart #2, about 4300 collaterals were found throughout the entire myocardium, but predominantly in the subendocardium. Bridging collaterals were mainly present between LCX and LAD territories. Although the total number of collaterals in heart #1 was lower than in heart #2, the mean collateral diameter in heart #1 was significantly higher (90.6 μm, SEM 1.30 vs. 66.8 μm, SEM 0.53. P<0.05).Conclusions: In the aged, but healthy heart, abundant collaterals were distributed throughout the entire myocardium providing the substrate for outward remodeling. In the hypertrophied heart with an old infarction, fewer but larger collaterals were found than in the healthy heart. These findings suggest that collateral development between perfusion territories differs distinctly between healthy and hypertrophied human hearts. [ABSTRACT FROM PUBLISHER]

Background: Acardiac twinning complicates monochorionic twin pregnancies in ≈2.6%, in which arterioarterial (AA) and venovenous placental anastomoses cause a reverse circulation between prepump and preacardiac embryos and cessation of cardiac function in the preacardiac. Literature suggested four acardiac body morphologies in which select (groups of) organs fail to develop, deteriorate, or become abnormal: acephalus (≈64%, [almost] no head, part of body, legs), amorphus (≈22%, amorphous tissue lump), anceps (≈10%, cranial bones, well-developed), and acormus (≈4%, head only). We sought to develop hypotheses that could explain acardiac pathogenesis, its progression, and develop methods for clinical testing., Methods: We used qualitatively described pathophysiology during development, including twin-specific AA and Hyrtl's anastomoses, the short umbilical cord syndrome, high capillary permeability, properties of spontaneous aborted embryos, and Pump/Acardiac umbilical venous diameter (UVD) ratios., Results: We propose that each body morphology has a specific pathophysiologic pathway. An acephalus acardius may be larger than an anceps, verifiable from UVD ratio measurements. A single umbilical artery develops when one artery, unconnected to the AA, vanishes due to flow reduction by Hyrtl's anastomotic resistance. Acardiac edema may result from acardiac body hypoxemia combined with physiological high fetal capillary permeability, high interstitial compliance and low albumin synthesis. Morphological changes may occur after acardiac onset. Pump twin risk follows from UVD ratios., Conclusion: Our suggested outcomes agree reasonably well with reported onset, incidence, and progression of acardiac morphologies. Guidance for clinical prediction and testing requires ultrasound anatomy/circulation study, from the first trimester onward., (© 2021 The Authors. Birth Defects Research published by Wiley Periodicals LLC.)

Background: We previously explained why acardiac twinning occurs in the first trimester. We raised the question why a sudden demised monochorionic twin beyond the first trimester does not lead to acardiac twinning. We argued that exsanguinated blood from the live twin would strongly increase the demised twins' vascular resistance, preventing its perfusion and acardiac onset. However, our current hypothesis is that perfusion of the demised twin does occur but that it is insufficient for onset of acardiac twinning., Methods: We analyzed blood pressures and flows in a vascular resistance model of a monochorionic twin pregnancy where one of the fetuses demised. The resistance model consists of a demised twin with a (former) placenta, a live twin and its placenta, and arterioarterial (AA) and venovenous placental anastomoses. We assumed that only twins with a weight of at least 33% of normal survived the first trimester and that exsanguination of more than 50% of its blood volume is fatal for the live twin., Results: At 20 weeks, only AA anastomoses with radii ≲1 mm keep the exsanguinated blood volume below 50%. Then, perfusion of the deceased body with arterial blood from the live fetus is about 5-40 times smaller than when that body was alive. Beyond 20 weeks, this factor is even smaller. At 14 weeks, this factor is at most 2., Conclusion: We hypothesize that this small perfusion flow of arterial blood prevents further growth of the deceased body and hence precludes onset of acardiac twinning., (© 2021 The Authors. Birth Defects Research published by Wiley Periodicals LLC.)

Background: Clinical observation suggests that acardiac twinning occurs only in the first trimester. In part, this contradicts our previous analysis (part IV) of Benirschke's concept that unequal embryonic splitting causes unequal embryo/fetal blood volumes and pressures. Our aim is to explain why acardiac onset is restricted to the first trimester., Methods: We applied the vascular resistance scheme of two fetuses connected by arterio-arterial (AA) and veno-venous (VV) anastomoses, the small VV resistance approximated as zero. The smaller twin has volume fraction α < 1 of the assumed normal larger twin, and has only access to fraction X < 1 of its placenta; the larger twin's larger mean arterial pressure accesses the remaining fraction. Before 13 weeks, embryos have a much smaller vascular resistance than placentas. After 13 weeks, when maternal blood provides oxygen, smaller twins can increase their vascular volume by hypoxemia-mediated neovascularization. Estimated AA radii at 40 weeks, r AA (40), are 0.5-1.3 mm., Results: Embryos with α < 0.33 unlikely survive 13 weeks and acardiac twinning occurs under appropriate conditions (AA-VV, small placenta). Acardiac body perfusion occurs because of a much smaller vascular resistance than the placenta. When α > 0.33 and r AA (40)=1.3 mm, modeled survival is >32 weeks., Conclusion: Before 13 weeks, embryos with α < 0.33 cannot survive and may result in the onset of acardia. Beyond 13 weeks, fetuses with α ≥ 0.33 survive because r AA (40) is too small for acardiac onset. Following fetal demise, exsanguination from the live twin increases its blood volume and, we assumed also, its vascular resistance. Perfusion then occurs through the lower resistance placenta., (© 2021 The Authors. Birth Defects Research published by Wiley Periodicals LLC.)

Background: Acardiac twinning is a complication of monochorionic twin pregnancies. From literature reports, 30 of 41 relatively large acardiac twins with renal tissue produced polyhydramnios within their amniotic compartment. We aim to investigate the underlying mechanisms that cause excess amniotic fluid using an established model of fetal fluid dynamics., Methods: We assumed that acardiac onset is before 13 weeks, acardiacs with renal tissue have normal kidney function and produce urine flow from 11 weeks on, and acardiac urine production requires a pressure of half the pump twin's mean arterial pressure. We apply a resistance network with the pump twin's arterio-venous pressure as source, pump umbilical arteries, placenta, placental arterio-arterial (AA) anastomoses and acardiac resistances. Acardiac amniotic fluid dynamics excluded acardiac lung fluid secretion, swallowing and the relatively small intramembranous flow., Results: In small acardiacs with sufficient urine production, polyhydramnios will occur due to the lack of amniotic fluid resorption. Urine production is dependent upon having sufficient mean arterial pressure, which requires nearly a two-fold larger resistance within the acardiac as compared to the placental AA resistance. Subphysiologic arterial pressure may result in renal dysgenesis., Conclusion: Our findings suggest the potential for prediction of which clinical acardiac cases may or may not develop polyhydramnios based upon noninvasive assessments of renal tissue, blood flow and urine production. This information would be of great value in determining early obstetric interventions as opposed to conservative management. These findings may also contribute to an improved knowledge of the fascinating pathophysiology that surrounds acardiac twinning., (© 2021 The Authors. Birth Defects Research published by Wiley Periodicals LLC.)

Background: Many processes contributing to the functional and structural regulation of the coronary circulation have been identified. A proper understanding of the complex interplay of these processes requires a quantitative systems approach that includes the complexity of the coronary network. The purpose of this study was to provide a detailed quantification of the branching characteristics and local hemodynamics of the human coronary circulation., Methods: The coronary arteries of a human heart were filled post-mortem with fluorescent replica material. The frozen heart was alternately cut and block-face imaged using a high-resolution imaging cryomicrotome. From the resulting 3D reconstruction of the left coronary circulation, topological (node and loop characteristics), topographic (diameters and length of segments), and geometric (position) properties were analyzed, along with predictions of local hemodynamics (pressure and flow)., Results: The reconstructed left coronary tree consisted of 202,184 segments with diameters ranging from 30 μm to 4 mm. Most segments were between 100 μm and 1 mm long. The median segment length was similar for diameters ranging between 75 and 200 μm. 91% of the nodes were bifurcations. These bifurcations were more symmetric and less variable in smaller vessels. Most of the pressure drop occurred in vessels between 200 μm and 1 mm in diameter. Downstream conductance variability affected neither local pressure nor median local flow and added limited extra variation of local flow. The left coronary circulation perfused 358 cm 3 of myocardium. Median perfused volume at a truncation level of 100 to 200 μm was 20 mm 3 with a median perfusion of 5.6 ml/min/g and a high local heterogeneity., Conclusion: This study provides the branching characteristics and hemodynamic analysis of the left coronary arterial circulation of a human heart. The resulting model can be deployed for further hemodynamic studies at the whole organ and local level., (Copyright © 2020 Schwarz, van Lier, van den Wijngaard, Siebes and VanBavel.)

Acardiac twinning is a rare anomaly of monochorionic twin pregnancies. Acardiac fetuses lack a functional heart but are passively perfused by arterial blood from their pump co-twin causing the acardiac body to be hypoxemic. In this report, we present an acardius anceps, therapeutically laser separated from its pump twin at 16 weeks. The healthy pump twin and macerated acardiac body were born at 40 3/7 weeks. A three dimensional (3D) reconstruction was made by CT images, showing cranial bones, spinal column, pelvis and lower extremities but absent arms. A cyst in the neck of the acardiac twin was identified by postnatal sonography; this was also described in four literature cases, and was additionally observed by us in two other acardiac twins. Median cleft palate was identified by oral cavity inspection but undetectable in the reconstruction. In the literature, we found 21 other acardiac anceps twins with a cleft palate. From the two larger published series, with 12 clefts in 21 acardiac anceps twins, a cleft palate occurs in over 50% during acardiac twinning. Our first hypothesis is that acardiac fetuses develop an oral cleft palate when acardiac onset starts prior to 11 weeks, because 11 weeks includes the period of embryonic oral cavity formation, and no cleft occurs when onset starts later than 11 weeks. Our second hypothesis is that cysts and cleft palates are more common in acardiac twins than currently known, likely reflecting that acardiac bodies are hypoxemic and that hypoxia contributes to the development of both cysts and clefts., (© 2019 Wiley Periodicals, Inc.)

Background: Sacrococcygeal teratomas (SCT) are often highly vascularized and may result in high-output cardiac failure, polyhydramnios, fetal hydrops, and demise. Delivery is guided by the SCT to fetus volume ratio (SCTratio), SCT growth rate, and cardiac output indexed for weight (CCOi)., Methods: We compared measurements and outcome in 12 consecutive fetuses referred with SCT. Adverse outcomes were: fetal surgery, delivery < 32 gestational weeks or neonatal demise. Only SCTratio and CCOi were used to manage the cases. SCT vascularization index (VI%) was derived from the 3D virtual organ computer-aided analysis (VOCAL) software. The SCTModel (modified from acardiac twins) calculated a hypothetical SCT draining vein size and derived a risk line, using diameters of the superior and inferior vena cava, the azygous and umbilical veins. VI% and a model of systemic and umbilical venous volumes (SCTModel) were tested as indicators for outcome in SCT., Results: Fetuses were monitored from 20.1 to 36.4 gestational weeks and 5/12 had adverse outcomes: 1 had successful open fetal surgery at 23.8 weeks and delivered at term, 4 delivered at < 32 weeks with 3/4 having neonatal demise between 25 and 29 weeks. VI% was significantly higher in cases with adverse outcomes (mean 10.3 [8.9-11.6] vs. 4.4 [3.4-5.3], p < 0.0001). The additional fraction of the fetal cardiac output required to perfuse the SCT-draining vein (XSCO%) (p = 0.46), SCTratio (p = 0.08), and CCOi (p = 0.64) were not significant. All cases with adverse outcome had VI% > 8%. The SCTModel risk line predicted nonadverse outcomes well but lacked data in 2/5 cases with adverse outcomes., Conclusions: VI% is a significant indicator of SCT cases with adverse outcomes and combined with SCTratio may guide timing of delivery better than current measures., (© 2019 S. Karger AG, Basel.)