The actions of corticotropin-releasing hormone (Crh), a mediator of endocrine and behavioural responses to stress, and the related hormone urocortin (Ucn) are coordinated by two receptors, Crhr1 (encoded by Crhr) and Crhr2. These receptors may exhibit distinct functions due to unique tissue distribution and pharmacology. Crhr-null mice have defined central functions for Crhr1 in anxiety and neuroendocrine stress responses. Here we generate Crhr2-/- mice and show that Crhr2 supplies regulatory features to the hypothalamic-pituitary-adrenal axis (HPA) stress response. Although initiation of the stress response appears to be normal, Crhr2-/- mice show early termination of adrenocorticotropic hormone (Acth) release, suggesting that Crhr2 is involved in maintaining HPA drive. Crhr2 also appears to modify the recovery phase of the HPA response, as corticosterone levels remain elevated 90 minutes after stress in Crhr2-/- mice. In addition, stress-coping behaviours associated with dearousal are reduced in Crhr2-/- mice. We also demonstrate that Crhr2 is essential for sustained feeding suppression (hypophagia) induced by Ucn. Feeding is initially suppressed in Crhr2-/- mice following Ucn, but Crhr2-/- mice recover more rapidly and completely than do wild-type mice. In addition to central nervous system effects, we found that, in contrast to wild-type mice, Crhr2-/- mice fail to show the enhanced cardiac performance or reduced blood pressure associated with systemic Ucn, suggesting that Crhr2 mediates these peripheral haemodynamic effects. Moreover, Crhr2-/- mice have elevated basal blood pressure, demonstrating that Crhr2 participates in cardiovascular homeostasis. Our results identify specific responses in the brain and periphery that involve Crhr2.

Background-Patients treated for transposition of the great arteries by atrial redirection surgery have a right ventricle (RV) that sustains systemic pressures long term. Late RV dysfunction occurs in these patients; the reasons for this are unclear, but myocardial fibrosis may be important. Myocardial fibrosis can be visualized by late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR). We hypothesized that LGE would be present in the systemic RV and relate to adverse clinical features. Methods and Results-We performed CMR on 36 consecutive adult patients (mean age, 27 years) after atrial redirection surgery for transposition of the great arteries. Late gadolinium RV enhancement was seen in 22 patients (61%) with various patterns. Patients with RV LGE were older (30 versus 22 years; PϽ0.001) and had increased RV end-systolic volume index (43 versus 35 mL/m 2 ; Pϭ0.03), decreased RV ejection fraction (57% versus 62%; Pϭ0.02), increased QRS duration (108 versus 97 ms; Pϭ0.01), and increased QT dispersion (93 versus 71 ms; Pϭ0.002). The extent of LGE correlated with age (rϭ0.59, PϽ0.001) and QRS duration (rϭ0.67, PϽ0.001) and inversely with RV ejection fraction (rϭϪ0.76, PϽ0.001). The incidence of documented arrhythmia and/or syncope (10 of 36) was significantly higher in the late gadolinium-positive group (9/22 versus 1/14; Pϭ0.03). Key Words: heart ventricles Ⅲ magnetic resonance imaging Ⅲ heart defects, congenital Ⅲ transposition of great vessels Ⅲ fibrosis B efore use of the arterial switch operation, patients with transposition of the great arteries were palliated by redirection of blood at the atrial level with the Senning 1 or Mustard operation. 2 There is a contemporary adult population in whom the right ventricle (RV) must sustain systemic pressure long term. Late RV dysfunction is common in these patients 3 and may be related to myocardial fibrosis. In patients with a systemic left ventricle (LV), cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE) can detect myocardial fibrosis in both ischemic and nonischemic cardiomyopathies. 4,5 We hypothesized that LGE would be present in the systemic RV and that it would be associated with markers of adverse clinical outcome. 4 Conclusions-LGE Methods Patient PopulationConsecutive patients with transposition of the great arteries who had undergone either the Mustard or Senning procedure were invited to participate. Patients with a permanent pacemaker in situ were excluded. The local research ethics committee approved the study, and all patients gave written informed consent. Cardiovascular Magnetic ResonanceA 1.5-T scanner was used (Siemens Sonata). After routine assessment of anatomy, the patency of atrial pathways and function of valves were assessed by steady-state free precession (SSFP) cine imaging in a sequence of specified oblique planes. They were aligned with each atrial pathway, the inflow valves in long-axis planes, and the outflow tracts. Peak velocity was measured at the narrowest point of each caval pathwa...

The coronary circulation of swine was studied to establish adequate baseline information for using swine in cardiovascular research. Of 65 hearts from domestic and miniature pigs, 45 were injected with a methacrylate plastic and prepared as coronary artery casts whose branches were described and measured, and 20 were injected with different coloured dyes in the right, left anterior descending, and circumflex coronary arteries so that horizontal sections of the heart showed the distribution of each artery and the source of blood supply to particular areas or structures of the heart. Like man, the swine had a left coronary artery that was larger in diameter and longer than the right coronary artery. The right coronary artery was almost always dominant (78%), supplying the posterior septum and atrioventricular node via the posterior descending coronary artery. Eight (17%) of the hearts possessed a balanced blood supply. Two (5%) hearts had a left dominant supply. The intracoronary artery dye injections showed that 72.4% of the right ventricular mass was supplied by the right coronary artery and 27.6% by the left anterior descending coronary artery. In the left ventricle 49% of the mass was supplied by the left anterior descending coronary artery, 25.5% by the right coronary artery, and 25.5% by the circumflex coronary artery. The left anterior descending coronary artery supplied 58% of the interventricular septal mass, while the posterior descending coronary artery supplied 42%. The distribution of the left anterior descending coronary artery branches to the ventricular wall varied inversely in number and size of its diagonal branches (2-9) with the obtuse marginal branches of the circumflex coronary artery which were occasionally more numerous or extended to the apex. The blood supply to the sinoatrial node was always by a branch of the right coronary artery. This analysis shows that not only the coronary anatomy but also the distribution of blood supply to particular areas or structures of the swine heart are very similar to that of humans.

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