Dataset Information

Maintenance of pig brain function under extracorporeal pulsatile circulatory control (EPCC).

ABSTRACT: Selective vascular access to the brain is desirable in metabolic tracer, pharmacological and other studies aimed to characterize neural properties in isolation from somatic influences from chest, abdomen or limbs. However, current methods for artificial control of cerebral circulation can abolish pulsatility-dependent vascular signaling or neural network phenomena such as the electrocorticogram even while preserving individual neuronal activity. Thus, we set out to mechanically render cerebral hemodynamics fully regulable to replicate or modify native pig brain perfusion. To this end, blood flow to the head was surgically separated from the systemic circulation and full extracorporeal pulsatile circulatory control (EPCC) was delivered via a modified aorta or brachiocephalic artery. This control relied on a computerized algorithm that maintained, for several hours, blood pressure, flow and pulsatility at near-native values individually measured before EPCC. Continuous electrocorticography and brain depth electrode recordings were used to evaluate brain activity relative to the standard offered by awake human electrocorticography. Under EPCC, this activity remained unaltered or minimally perturbed compared to the native circulation state, as did cerebral oxygenation, pressure, temperature and microscopic structure. Thus, our approach enables the study of neural activity and its circulatory manipulation in independence of most of the rest of the organism.

SUBMITTER: Shariff M

PROVIDER: S-EPMC10457326 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Maintenance of pig brain function under extracorporeal pulsatile circulatory control (EPCC).

Shariff Muhammed M Dobariya Aksharkumar A Albaghdadi Obada O Awkal Jacob J Moussa Hadi H Reyes Gabriel G Syed Mansur M Hart Robert R Longfellow Cameron C Douglass Debra D El Ahmadieh Tarek Y TY Good Levi B LB Jakkamsetti Vikram V Kathote Gauri G Angulo Gus G Ma Qian Q Brown Ronnie R Dunbar Misha M Shelton John M JM Evers Bret M BM Patnaik Sourav S Hoffmann Ulrike U Hackmann Amy E AE Mickey Bruce B Peltz Matthias M Jessen Michael E ME Pascual Juan M JM

Scientific reports 20230825 1

Selective vascular access to the brain is desirable in metabolic tracer, pharmacological and other studies aimed to characterize neural properties in isolation from somatic influences from chest, abdomen or limbs. However, current methods for artificial control of cerebral circulation can abolish pulsatility-dependent vascular signaling or neural network phenomena such as the electrocorticogram even while preserving individual neuronal activity. Thus, we set out to mechanically render cerebral h ...[more]

PMID: 37626089

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Project description:Despite progress with adult ventricular assist devices, limited options exist to support pediatric patients with life-threatening heart disease. Extracorporeal membrane oxygenation remains the clinical standard. To characterize (patho)physiologic responses to different modes of mechanical unloading of the failing pediatric heart, extracorporeal membrane oxygenation was compared to intra-aortic balloon pump, pulsatile-flow ventricular assist device, or continuous-flow ventricular assist device support in a pediatric heart failure model.Experimental.Large animal laboratory operating room.Yorkshire piglets (n = 47; 11.7 ± 2.6 kg).In piglets with coronary ligation-induced cardiac dysfunction, mechanical circulatory support devices were implanted and studied during maximum support.Left ventricular, right ventricular, coronary, carotid, systemic arterial, and pulmonary arterial hemodynamics were measured with pressure and flow transducers. Myocardial oxygen consumption and total-body oxygen consumption were calculated from arterial, venous, and coronary sinus blood sampling. Blood flow was measured in 17 organs with microspheres. Paired Student t tests compared baseline and heart failure conditions. One-way repeated-measures analysis of variance compared heart failure, device support mode(s), and extracorporeal membrane oxygenation. Statistically significant (p < 0.05) findings included 1) an improved left ventricular blood supply/demand ratio during pulsatile-flow ventricular assist device, continuous-flow ventricular assist device, and extracorporeal membrane oxygenation but not intra-aortic balloon pump support, 2) an improved global myocardial blood supply/demand ratio during pulsatile-flow ventricular assist device and continuous-flow ventricular assist device but not intra-aortic balloon pump or extracorporeal membrane oxygenation support, and 3) diminished pulsatility during extracorporeal membrane oxygenation and continuous-flow ventricular assist device but not intra-aortic balloon pump and pulsatile-flow ventricular assist device support. A profile of systems-based responses was established for each type of support.Each type of pediatric ventricular assist device provided hemodynamic support by unloading the heart with a different mechanism that created a unique profile of physiological changes. These data contribute novel, clinically relevant insight into pediatric mechanical circulatory support and establish an important resource for pediatric device development and patient selection.

Project description:IntroductionVeno-arterial extracorporeal life support (ECLS) is increasingly being used to treat rapidly progressing or severe cardiogenic shock. However, it has been repeatedly shown that increased afterload associated with ECLS significantly diminishes left ventricular (LV) performance. The objective of the present study was to compare LV function and coronary flow during standard continuous-flow ECLS support and electrocardiogram (ECG)-synchronized pulsatile ECLS flow in a porcine model of cardiogenic shock.MethodsSixteen female swine (mean body weight 45 kg) underwent ECLS implantation under general anesthesia and artificial ventilation. Subsequently, acute cardiogenic shock, with documented signs of tissue hypoperfusion, was induced by initiating global myocardial hypoxia. Hemodynamic cardiac performance variables and coronary flow were then measured at different rates of continuous or pulsatile ECLS flow (ranging from 1 L/min to 4 L/min) using arterial and venous catheters, a pulmonary artery catheter, an LV pressure-volume loop catheter, and a Doppler coronary guide-wire.ResultsMyocardial hypoxia resulted in declines in mean cardiac output to 1.7±0.7 L/min, systolic blood pressure to 64±22 mmHg, and LV ejection fraction (LVEF) to 22±7%. Synchronized pulsatile flow was associated with a significant reduction in LV end-systolic volume by 6.2 mL (6.7%), an increase in LV stroke volume by 5.0 mL (17.4%), higher LVEF by 4.5% (18.8% relative), cardiac output by 0.37 L/min (17.1%), and mean arterial pressure by 3.0 mmHg (5.5%) when compared with continuous ECLS flow at all ECLS flow rates (P<0.05). At selected ECLS flow rates, pulsatile flow also reduced LV end-diastolic pressure, end-diastolic volume, and systolic pressure. ECG-synchronized pulsatile flow was also associated with significantly increased (7% to 22%) coronary flow at all ECLS flow rates.ConclusionECG-synchronized pulsatile ECLS flow preserved LV function and coronary flow compared with standard continuous-flow ECLS in a porcine model of cardiogenic shock.

Dataset Information

Maintenance of pig brain function under extracorporeal pulsatile circulatory control (EPCC).

Publications

Maintenance of pig brain function under extracorporeal pulsatile circulatory control (EPCC).

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