Characterisation of vasodilatory responses in the presence of the CGRP receptor antibody erenumab in human isolated arteries.

BACKGROUND: Migraine is associated with activation of the trigeminovascular system, release of calcitonin gene-related peptide (CGRP) and dilation of dural arteries. Novel treatments target calcitonin gene-related peptide or its receptor, which are present in all vascular beds, raising cardiovascular concerns. Erenumab is a human CGRP-receptor antibody approved for the prophylactic treatment of migraine. METHODS: We characterised the relaxant responses to CGRP in the absence and presence of erenumab (1 µM) in isolated human middle meningeal, internal mammary and (proximal and distal) coronary arteries. Furthermore, in human internal mammary arteries from cardiovascularly-compromised patients, we assessed the pharmacological specificity of erenumab by investigating whether the vasodilatory responses to acetylcholine, sodium nitroprusside, pituitary adenylate cyclase activating polypeptide-38 (PACAP), vasoactive intestinal peptide and nicardipine, along with the vasoconstrictor responses to dihydroergotamine, were modified by erenumab. RESULTS: Calcitonin gene-related peptide induced concentration-dependent vasodilatory responses in all vessels studied that were significantly antagonised by erenumab. In human internal mammary arteries from cardiovascularly-compromised patients, the responses to acetylcholine, sodium nitroprusside, PACAP, vasoactive intestinal peptide, nicardipine and dihydroergotamine were unaffected by erenumab. CONCLUSION: Erenumab inhibits calcitonin gene-related peptide-induced vasodilatory responses in human middle meningeal arteries, human internal mammary arteries and human coronary arteries. Moreover, erenumab shows functional specificity as no interaction was observed with the relaxant responses to several vasodilators, nor the dihydroergotamine-dependent vasoconstrictor responses.

Virtual Reality Simulation Training for Cardiopulmonary Resuscitation After Cardiac Surgery: Face and Content Validity Study.

BACKGROUND: Cardiac arrest after cardiac surgery commonly has a reversible cause, where emergency resternotomy is often required for treatment, as recommended by international guidelines. We have developed a virtual reality (VR) simulation for training of cardiopulmonary resuscitation (CPR) and emergency resternotomy procedures after cardiac surgery, the Cardiopulmonary Resuscitation Virtual Reality Simulator (CPVR-sim). Two fictive clinical scenarios were used: one case of pulseless electrical activity (PEA) and a combined case of PEA and ventricular fibrillation. In this prospective study, we researched the face validity and content validity of the CPVR-sim. OBJECTIVE: We designed a prospective study to assess the feasibility and to establish the face and content validity of two clinical scenarios (shockable and nonshockable cardiac arrest) of the CPVR-sim partly divided into a group of novices and experts in performing CPR and emergency resternotomies in patients after cardiac surgery. METHODS: Clinicians (staff cardiothoracic surgeons, physicians, surgical residents, nurse practitioners, and medical students) participated in this study and performed two different scenarios, either PEA or combined PEA and ventricular fibrillation. All participants (N=41) performed a simulation and completed the questionnaire rating the simulator's usefulness, satisfaction, ease of use, effectiveness, and immersiveness to assess face validity and content validity. RESULTS: Responses toward face validity and content validity were predominantly positive in both groups. Most participants in the PEA scenario (n=26, 87%) felt actively involved in the simulation, and 23 (77%) participants felt in charge of the situation. The participants thought it was easy to learn how to interact with the software (n=24, 80%) and thought that the software responded adequately (n=21, 70%). All 15 (100%) expert participants preferred VR training as an addition to conventional training. Moreover, 13 (87%) of the expert participants would recommend VR training to other colleagues, and 14 (93%) of the expert participants thought the CPVR-sim was a useful method to train for infrequent post-cardiac surgery emergencies requiring CPR. Additionally, 10 (91%) of the participants thought it was easy to move in the VR environment, and that the CPVR-sim responded adequately in this scenario. CONCLUSIONS: We developed a proof-of-concept VR simulation for CPR training with two scenarios of a patient after cardiac surgery, which participants found was immersive and useful. By proving the face validity and content validity of the CPVR-sim, we present the first step toward a cardiothoracic surgery VR training platform.

CT angiography for depiction of complications after the Bentall procedure.

Following a Bentall procedure, which comprises a composite replacement of both the aortic valve and the ascending aorta, the imaging modality of choice to depict known or suspected complications is CT angiography. An update and extension of the literature regarding complications after the Bentall procedure is provided. The wider availability of ECG-gating has allowed for a clearer depiction of the aortic valve and ascending aorta. This resulted not only in the identification of previously undetectable complications, but also in a more precise assessment of the pathophysiology and morphology of known ones, reducing the need for additional imaging modalities. Moreover, the possibility to combine positron emission tomography images with CT angiography offers new insights in case of suspected infection. Due to the complexity of the operation itself and concomitant or subsequent additional procedures, as well as the wide spectrum of underlying pathology, new scenarios with multiple complications can be expected.

Anatomy of the aortic and pulmonary roots.

The use of the pulmonary autograft for aortic root replacement has renewed interest in the morphology of the arterial roots. In this article the basic construction of the roots, their anchorage, and their support from surrounding structures are reviewed. The arterial roots manifest a complex anatomy, with an intricate relation between the anulus and its adjacent structures, which span the transition from ventricle to the great vessel. The pulmonary root is anchored over its entire circumference to the thin myocardium of the free-standing pulmonary infundibulum. The anchorage of the aortic root is more extensive, being partly inserted into the thick left ventricular and septal myocardium and partly continuous with fibrous structures such as the membranous septum and the mitral valve. The pulmonary root is supported only by a slight collar of myocardium. The aortic root is better encased, supported by the more pronounced bulging of ventricular myocardium as well as the adjacent atrial myocardium and atrial septum. When the pulmonary autograft is used for aortic root replacement it will obtain maximum support from the surrounding tissues by implanting the autograft as proximal as possible. Copyright 1998 by W.B. Saunders Company

Assessment of right ventricular fibrosis in different forms of pulmonary atresia with ventricular septal defect.

BACKGROUND: In pulmonary atresia with ventricular septal defect (PA-VSD), the corrective surgical strategy aims to reduce the right ventricular (RV) overload and restore physiological pulmonary perfusion before the characteristic RV hypertrophy and fibrosis become irreversible. OBJECTIVE: To assess RV fibrosis in different forms of PA-VSD. METHODS: RV biopsies were obtained at corrective surgery from PA-VSD patients (n=14, mean age 2.5+/-1.2 years) with patent arterial duct (PAD group, n=6; mean age 1.7+/-0.5 years) or systemic-pulmonary collateral arteries (SPCA group, n=8; mean age 3.2+/-1.2 years) and from age-matched controls (control group, n=6; mean age 2.5+/-1.8 years). Myocardial expression patterns (messenger RNA [mRNA] and protein levels) of the extracellular matrix proteins (eg, fibronectin and collagens [subtype I alpha and III) were quantitatively analyzed in relation to myocardial cell hypertrophy. RESULTS: Comparing the age of PA-VSD patients at surgery, the SPCA group was older than the PAD group (P=0.01). Expression analysis by reverse transcriptase polymerase chain reaction showed significantly higher mRNA levels in patients with PA-VSD for collagen III (PA-VSD versus controls; 0.9+/-0.2 versus 0.6+/-0.1, P=0.03) than in controls, whereas collagen I alpha and fibronectin mRNA levels did not differ. No differences were found between the PAD and SPCA groups. The myocyte cross sectional surface area showed enhanced myocyte hypertrophy in patients with PA-VSD compared with the control group (P=0.015), with no significant difference between the PAD and SPCA groups. Video image analysis of immunohistochemical staining corrected for hypertrophy revealed unchanged interstitial collagens and fibronectin levels in all groups. However, perivascular staining corrected for the vessel lumen area showed significantly lower total collagen levels in patients with PA-VSD than in the control group (3.2+/-1.2 versus 7.2+/-2.8, respectively; P=0.004). CONCLUSIONS: The results indicate that the extracellular matrix support for the coronary blood vessels appears to be suboptimal in patients with PA-VSD. The staged surgical approach in the SPCA group (with a higher age at correction) did not result in an excessive accumulation of fibrosis markers in the RV myocardium.