Myocardial Afterload Is a Key Biomechanical Regulator of Atrioventricular Myocyte Differentiation in Zebrafish

Heart valve development is governed by both genetic and biomechanical inputs. Prior work has demonstrated that oscillating shear stress associated with blood flow is required for normal atrioventricular (AV) valve development. Cardiac afterload is defined as the pressure the ventricle must overcome in order to pump blood throughout the circulatory system. In human patients, conditions of high afterload can cause valve pathology. Whether high afterload adversely affects embryonic valve development remains poorly understood. Here we describe a zebrafish model exhibiting increased myocardial afterload, caused by vasopressin, a vasoconstrictive drug. We show that the application of vasopressin reliably produces an increase in afterload without directly acting on cardiac tissue in zebrafish embryos. We have found that increased afterload alters the rate of growth of the cardiac chambers and causes remodeling of cardiomyocytes. Consistent with pathology seen in patients with clinically high afterload, we see defects in both the form and the function of the valve leaflets. Our results suggest that valve defects are due to changes in atrioventricular myocyte signaling, rather than pressure directly acting on the endothelial valve leaflet cells. Cardiac afterload should therefore be considered a biomechanical factor that particularly impacts embryonic valve development.

Identification of cardiac afterload dynamics from data

The prospect of ex vivo functional evaluation of donor hearts is considered. Particularly, the dynamics of a synthetic cardiac afterload model are compared to those of normal physiology. A method for identification of continuous-time transfer functions from sampled data is developed and verified against results from the literature. The method relies on exact gradients and Hessians obtained through automatic differentiation. This also enables straightforward sensitivity analyses. Such analyses reveal that the 4-element Windkessel model is not practically identifiable from representative data while the 3-element model underfits the data. Pressure–volume (PV) loops are therefore suggested as an alternative for comparing afterload dynamics.

Using velocity-pressure loops in the operating room: a new approach of arterial mechanics for cardiac afterload monitoring under general anesthesia

Cardiac afterload is usually assessed in the ascending aorta and can be defined by the association of peripheral vascular resistance (PVR), total arterial compliance (Ctot), and aortic wave reflection (WR). We recently proposed the global afterload angle (GALA) and β-angle derived from the aortic velocity-pressure (VP) loop as continuous cardiac afterload monitoring in the descending thoracic aorta. The aim of this study was to 1) describe the arterial mechanic properties by studying the velocity-pressure relations according to cardiovascular risk (low-risk and high-risk patients) in the ascending and descending thoracic aorta and 2) analyze the association between the VP loop (GALA and β-angle) and cardiac afterload parameters (PVR, Ctot, and WR). PVR, Ctot, WR, and VP loop parameters were measured in the ascending and descending thoracic aorta in 50 anesthetized patients. At each aortic level, the mean arterial pressure (MAP), cardiac output (CO), and PVR were similar between low-risk and high-risk patients. In contrast, Ctot, WR, GALA, and β-angle were strongly influenced by cardiovascular risk factors regardless of the site of measurement along the aorta. The GALA angle was inversely related to aortic compliance, and the β-angle reflected the magnitude of wave reflection in both the ascending and descending aortas ( P < 0.001). Under general anesthesia, the VP loop can provide new visual insights into arterial mechanical properties compared with the traditional MAP and CO for the assessment of cardiac afterload. Further studies are necessary to demonstrate the clinical utility of the VP loop in the operating room. NEW & NOTEWORTHY Our team recently proposed the global afterload angle (GALA) and β-angle derived from the aortic velocity-pressure (VP) loop as continuous cardiac afterload monitoring in the descending thoracic aorta under general anesthesia. However, the evaluation of cardiac afterload at this location is unusual. The present study shows that VP loop parameters can describe the components of cardiac afterload both in the ascending and descending thoracic aorta in the operating room. Aging and cardiovascular risk factors strongly influence VP loop parameters. The VP loop could provide continuous visual additional information on the arterial system than the traditional mean arterial pressure and cardiac output during the general anesthesia.

Resuscitative Endovascular Balloon Occlusion of the Aorta To Augment Afterload in Non-Traumatic Cardiac Arrest

We describe the first case report of using a REBOA catheter to augment cardiac afterload in a non-traumatic cardiac arrest patient.

Left ventricular strain rate is reduced during voluntary apnea in healthy humans

During an apneic event, sympathetic nerve activity increases resulting in subsequent increases in left ventricular (LV) afterload and myocardial work. It is unknown how cardiac mechanics are acutely impacted by the increased myocardial work during an apneic event. Ten healthy individuals (23 ± 3 yr) performed multiple voluntary end-expiratory apnea (VEEA) maneuvers exposed to room air, while a subset ( n = 7) completed multiple VEEA exposed to hyperoxic air (100% [Formula: see text]). Beat-by-beat blood pressure, heart rate, and stroke volume were measured continuously. Effective arterial elastance (EA) was calculated as an index of cardiac afterload, and myocardial work was calculated as the rate pressure product (RPP). Tissue Doppler echocardiography was used to measure LV tissue velocities, deformation via strain, and strain rate (SR). Systolic blood pressure (Δ18 ± 13 mmHg, P < 0.01), EA (Δ0.13 ± 0.10 mmHg/ml, P < 0.01), and RPP (Δ9 ± 10 beats/min × mmHg 10−2, P < 0.01) significantly increased with room air VEEA. This occurred in parallel with decreases in peak longitudinal systolic (Δ−0.62 ± 0.41 cm/s, P < 0.01) and early LV filling (Δ−2.81 ± 1.99 cm/s, P < 0.01) myocardial velocities. Longitudinal SR (Δ−0.30 ± 0.32 1/s, P = 0.01) was significantly decreased during room air VEEA. VEEA with hyperoxia did not alter ( P > 0.18) EA or RPP and attenuated the systolic blood pressure response compared with room air. Myocardial velocities and LV strain rate response to VEEA were unchanged ( P = 0.30) with hyperoxia. Consistent with our hypotheses, VEEA-induced increases in EA and myocardial work impact LV mechanics, which may depend, in part, on stimulation of peripheral chemoreceptors. NEW & NOTEWORTHY Transient increases in arterial blood pressure and systemic vascular resistance occur during sleep apnea events and may contribute to the associated daytime hypertension and risk of overt cardiovascular disease. To date, the link between this apnea pressor response and acute changes in left ventricular function remains poorly understood. We demonstrate that in parallel to increases in cardiac afterload a depressed left ventricular systolic function occurs at end apnea.