Monitoring of cardiovascular physiology augmented by a patient-specific biomechanical model during general anesthesia. A proof of concept study.
ABSTRACT: During general anesthesia (GA), direct analysis of arterial pressure or aortic flow waveforms may be inconclusive in complex situations. Patient-specific biomechanical models, based on data obtained during GA and capable to perform fast simulations of cardiac cycles, have the potential to augment hemodynamic monitoring. Such models allow to simulate Pressure-Volume (PV) loops and estimate functional indicators of cardiovascular (CV) system, e.g. ventricular-arterial coupling (Vva), cardiac efficiency (CE) or myocardial contractility, evolving throughout GA. In this prospective observational study, we created patient-specific biomechanical models of heart and vasculature of a reduced geometric complexity for n = 45 patients undergoing GA, while using transthoracic echocardiography and aortic pressure and flow signals acquired in the beginning of GA (baseline condition). If intraoperative hypotension (IOH) appeared, diluted norepinephrine (NOR) was administered and the model readjusted according to the measured aortic pressure and flow signals. Such patients were a posteriori assigned into a so-called hypotensive group. The accuracy of simulated mean aortic pressure (MAP) and stroke volume (SV) at baseline were in accordance with the guidelines for the validation of new devices or reference measurement methods in all patients. After NOR administration in the hypotensive group, the percentage of concordance with 10% exclusion zone between measurement and simulation was >95% for both MAP and SV. The modeling results showed a decreased Vva (0.64±0.37 vs 0.88±0.43; p = 0.039) and an increased CE (0.8±0.1 vs 0.73±0.11; p = 0.042) in hypotensive vs normotensive patients. Furthermore, Vva increased by 92±101%, CE decreased by 13±11% (p < 0.001 for both) and contractility increased by 14±11% (p = 0.002) in the hypotensive group post-NOR administration. In this work we demonstrated the application of fast-running patient-specific biophysical models to estimate PV loops and functional indicators of CV system using clinical data available during GA. The work paves the way for model-augmented hemodynamic monitoring at operating theatres or intensive care units to enhance the information on patient-specific physiology.
Project description:We evaluated the impact of increasing tidal volume (V (t)), decreased chest wall compliance, and left ventricular (LV) contractility during intermittent positive-pressure ventilation (IPPV) on the relation between pulse pressure (PP) and LV stroke volume (SV(LV)) variation (PPV and SVV, respectively), and intrathoracic blood volume (ITBV) changes.Sixteen pentobarbital-anesthetized thoracotomized mongrel dogs were studied both before and after propranolol-induced acute ventricular failure (AVF) (n = 4), with and without chest and abdominal pneumatic binders to decrease chest wall compliance (n = 6), and during V (t) of 5, 10, 15, and 25 ml/kg (n = 6). SV(LV) and right ventricular stroke volume (SV(RV)) were derived from electromagnetic flow probes around aortic and pulmonary artery roots. Arterial pressure was measured in the aorta using a fluid-filled catheter. Arterial PPV and SVV were calculated over three breaths as (max - min)/[(max + min)/2]. ITBV changes during ventilation were inferred from the beat-to-beat volume differences between SV(RV) and SV(LV).Arterial PP and SV(LV) were tightly correlated during IPPV under all conditions (r (2) = 0.85). Both PPV and SVV increased progressively as V (t) increased and with thoraco-abdominal binding, and tended to decrease during AVF. SV(RV) phasically decreased during inspiration, whereas SV(LV) phasically decreased 2-3 beats later, such that ITBV decreased during inspiration and returned to apneic values during expiration. ITBV decrements increased with increasing V (t) or with thoraco-abdominal binding, and decreased during AVF owing to variations in SV(RV), such that both PPV and SVV tightly correlated with inspiration-associated changes in SV(RV) and ITBV.Arterial PP and SV(LV) are tightly correlated during IPPV and their relation is not altered by selective changes in LV contractility, intrathoracic pressure, or V (t). However, contractility, intrathoracic pressure, and V (t) directly alter the magnitude of PPV and SVV primarily by altering the inspiration-associated decreases in SV(RV) and ITBV.
Project description:Transforming growth factor-beta is a pleiotropic cytokine having diverse roles in vascular morphogenesis, homeostasis, and pathogenesis. Altered activity of and signaling through transforming growth factor-beta has been implicated in thoracic aortic aneurysms and dissections, conditions characterized by a reduced structural integrity of the wall that associates with altered biomechanics and mechanobiology. We quantify and contrast the passive and active biaxial biomechanical properties of the ascending and proximal descending thoracic aorta in a mouse model of altered transforming growth factor-beta signaling, with and without treatment with rapamycin.Postnatal disruption of the gene (Tgfbr2) that codes the type II transforming growth factor-beta receptor compromises vessel-level contractility and elasticity. Daily treatment with rapamycin, a mechanistic target of rapamycin inhibitor that protects against aortic dissection in these mice, largely preserves or restores the contractile function while the passive properties remain compromised. Importantly, this increased smooth muscle contractility protects an otherwise vulnerable aortic wall from pressure-induced intramural delaminations in vitro.Notwithstanding the protection afforded by rapamycin in vivo and in vitro, the residual mechanical dysfunctionality suggests a need for caution if rapamycin is to b