Pulmonary CT perfusion robustly measures cardiac output in the context of multilevel pulmonary occlusion: a porcine study.

BACKGROUND: To validate pulmonary computed tomography (CT) perfusion in a porcine model by invasive monitoring of cardiac output (CO) using thermodilution method. METHODS: Animals were studied at a single center, using a Swan-Ganz catheter for invasive CO monitoring as a reference. Fifteen pigs were included. Contrast-enhanced CT perfusion of the descending aorta and right and left pulmonary artery was performed. For variation purposes, a balloon catheter was inserted to block the contralateral pulmonary vascular bed; additionally, two increased CO settings were created by intravenous administration of catecholamines. Finally, stepwise capillary occlusion was performed by intrapulmonary arterial injection of 75-µm microspheres in four stages. A semiautomatic selection of AFs and a recirculation-aware tracer-kinetics model to extract the first-pass of AFs, estimating blood flow with the Stewart-Hamilton method, was implemented. Linear mixed models (LMM) were developed to calibrate blood flow calculations accounting with individual- and cohort-level effects. RESULTS: Nine of 15 pigs had complete datasets. Strong correlations were observed between calibrated pulmonary (0.73, 95% confidence interval [CI] 0.6-0.82) and aortic blood flow measurements (0.82, 95% CI, 0.73-0.88) and the reference as well as agreements (± 2.24 L/min and ± 1.86 L/min, respectively) comparable to the state of the art, on a relatively wide range of right ventricle-CO measurements. CONCLUSIONS: CT perfusion validly measures CO using LMMs at both individual and cohort levels, as demonstrated by referencing the invasive CO. RELEVANCE STATEMENT: Possible clinical applications of CT perfusion for measuring CO could be in acute pulmonary thromboembolism or to assess right ventricular function to show impairment or mismatch to the left ventricle. KEY POINTS: • CT perfusion measures flow in vessels. • CT perfusion measures cumulative cardiac output in the aorta and pulmonary vessels. • CT perfusion validly measures CO using LMMs at both individual and cohort levels, as demonstrated by using the invasive CO as a reference standard.

Measurement of Electrical Impedance Tomography-Based Regional Ventilation Delay for Individualized Titration of End-Expiratory Pressure.

RATIONALE: Individualized positive end-expiratory pressure (PEEP) titration might be beneficial in preventing tidal recruitment. To detect tidal recruitment by electrical impedance tomography (EIT), the time disparity between the regional ventilation curves (regional ventilation delay inhomogeneity [RVDI]) can be measured during controlled mechanical ventilation when applying a slow inflation of 12 mL/kg of body weight (BW). However, repeated large slow inflations may result in high end-inspiratory pressure (PEI), which might limit the clinical applicability of this method. We hypothesized that PEEP levels that minimize tidal recruitment can also be derived from EIT-based RVDI through the use of reduced slow inflation volumes. METHODS: Decremental PEEP trials were performed in 15 lung-injured pigs. The PEEP level that minimized tidal recruitment was estimated from EIT-based RVDI measurement during slow inflations of 12, 9, 7.5, or 6 mL/kg BW. We compared RVDI and PEI values resulting from different slow inflation volumes and estimated individualized PEEP levels. RESULTS: RVDI values from slow inflations of 12 and 9 mL/kg BW showed excellent linear correlation (R2 = 0.87, p < 0.001). Correlations decreased for RVDI values from inflations of 7.5 (R2 = 0.68, p < 0.001) and 6 (R2 = 0.42, p < 0.001) mL/kg BW. Individualized PEEP levels estimated from 12 and 9 mL/kg BW were comparable (bias -0.3 cm H2O ± 1.2 cm H2O). Bias and scatter increased with further reduction in slow inflation volumes (for 7.5 mL/kg BW, bias 0 ± 3.2 cm H2O; for 6 mL/kg BW, bias 1.2 ± 4.0 cm H2O). PEI resulting from 9 mL/kg BW inflations were comparable with PEI during regular tidal volumes. CONCLUSIONS: PEEP titration to minimize tidal recruitment can be individualized according to EIT-based measurement of the time disparity of regional ventilation courses during slow inflations with low inflation volumes. This sufficiently decreases PEI and may reduce potential clinical risks.

Assessing volume responsiveness using right ventricular dynamic indicators of preload.

PURPOSE: Dynamic indicators of preload currently only do reflect preload requirements of the left ventricle. To date, no dynamic indicators of right ventricular preload have been established. The aim of this study was to calculate dynamic indicators of right ventricular preload and assess their ability to predict ventricular volume responsiveness. MATERIALS AND METHODS: The study was designed as experimental trial in 20 anaesthetized pigs. Micro-tip catheters and ultrasonic flow probes were used as experimental reference to enable measurement of right ventricular stroke volume and pulse pressure. Hypovolemia was induced (withdrawal of blood 20 ml/kg) and thereafter three volume-loading steps were performed. ROC analysis was performed to assess the ability of dynamic right ventricular parameters to predict volume response. RESULTS: ROC analysis revealed an area under the curve (AUC) of 0.82 (CI 95% 0.73-0.89; p < 0.001) for right ventricular stroke volume variation (SVVRV), an AUC of 0.72 (CI 95% 0.53-0.85; p = 0.02) for pulmonary artery pulse pressure variation (PPVPA) and an AUC of 0.66 (CI 95% 0.51-0.79; p = 0.04) for pulmonary artery systolic pressure variation (SPVPA). CONCLUSIONS: In our experimental animal setting, calculating dynamic indicators of right ventricular preload is possible and appears promising in predicting volume responsiveness.

Cholecystokinin-8 treatment reduces acinar necrosis and edema of pigs with induced pancreatitis.

BACKGROUND: Acute pancreatitis is an inflammatory process of the pancreas and a leading cause of hospitalization amongst gastrointestinal disorders. Previously, cholecystokinin (CCK) has been described to play a role in regeneration of pancreas. The aim of this study was to analyse the function of cholecystokinin octapeptide (CCK-8) during induced pancreatitis in an animal model. METHODS: Overall acute pancreatitis was induced in 38 pigs. After the induction of acute pancreatitis, half of the animals were treated with CCK-8. Intraoperative clinical data, postoperative blood parameters, 'Porcine Well-being' (PWB) and fitness score and post-mortal histopathological data were analysed. RESULTS: At baseline, physiologically parameters of the pigs of both groups were comparable. No differences were observed regarding the overall survival of animals (p = 0.97). Postoperative PWB score were significantly enhanced in animals treated with CCK-8 as compared to the control group (p = 0.029). Moreover, histopathological analysis of the pancreatic tissue revealed that acinar necrosis and edema were significant reduced in the CCK-8 group in comparison to the control group (p = 0.016 and p = 0.019). CONCLUSIONS: In conclusion, we found that CCK-8 treatment reduces acinar necrosis and edema of pancreatic tissue after induction of an acute pancreatitis in pigs.

Melatonin treatment of pigs with acute pancreatitis reduces inflammatory reaction of pancreatic tissue and enhances fitness score of pigs: experimental research.

Background: Severe acute pancreatitis is associated with high morbidity and mortality. Melatonin is known as the activator of antioxidant enzymes. The main purpose of this study was to evaluate the clinical effect of melatonin treatment in a pig model with induced acute pancreatitis. Methods: In this study, acute pancreatitis was induced in 38 German domestic pigs (German Hybrid). After induction of acute pancreatitis, 18 animals were treated with melatonin. Intraoperative clinical data, postoperative blood parameters, fitness, and Porcine Well-being (PWB) score, and post-mortal histopathological data were analyzed in both study groups. Results: The matching procedure created two groups (melatonin group and control group) which were very similar. The fitness and PWB score were postoperative significantly enhanced in the melatonin group as compared to the control group (p = 0.005 and p = 0.003). Additionally, histological analysis revealed that acinar necrosis, fat tissue necrosis, and edema were significantly reduced in the melatonin group as compared to the non-melatonin group (p = 0.025, p = 0.003, and p = 0.028). Conclusions: Pigs, which were treated with melatonin, were characterized by higher fitness and PWB scores than those of the control group. Moreover, melatonin treatment reduces the acinar necrosis, fat tissue necrosis, and edema of pancreatic tissue. Thus, melatonin might be a useful therapeutic option in severe acute pancreatitis.

Robotic cholecystectomy: first experience with the new Senhance robotic system.

This retrospective study was performed to evaluate the safety and feasibility of the new Senhance robotic system (Transenterix) for robotic cholecystectomy. Our series is the first experience with cholecystectomies utilizing this new platform. From May 2017 to August 2017, 20 robotic cholecystectomies were performed using the Senhance robotic system. Patients were between 23 years and 78 years of age, eligible for a laparoscopic procedure with general anesthesia, with no life-threatening co-morbidities that limited the subjects' life-expectancy to fewer than 12 months. A retrospective chart review was performed for a variety of pre-, peri- and postoperative data including, but not limited to patient demographics, intraoperative complications and postoperative complications. 9 male and 11 female patients were included in this study. Median age was 39.5 years (range 23-78); median BMI was 27.35 kg/m2 (range 22.8-48.3). Median docking time was 10 min (range 2-26), and median operative time was 71.5 min (range 34-197). Conversion to standard laparoscopy occurred in one case for lysis of extensive adhesions. There were no conversions to open technique. There were no intra- or post-operative complications noted. We report the first series of robotic cholecystectomies using the new Senhance system. Docking time and total operative time decreased significantly over the course of this series and did not plateau; console time did not change significantly. This study demonstrates the feasibility of utilizing this platform in performing minimally invasive cholecystectomies.

Assessment of central hemodynamic effects of phenylephrine: an animal experiment.

Phenylephrine is an α1-adrenergic receptor agonist widely used to treat perioperative hypotension. Its other hemodynamic effects, in particular on preload and contractility, remain controversial. We, therefore, investigated the effect of continuously applied phenylephrine on central hemodynamics in eight mechanically ventilated domestic pigs. Mean arterial pressure (MAP) was increased in steps by 50%, and 100% using phenylephrine. Besides stroke volume (SV), cardiac output (CO), and MAP, mean systemic vascular resistance (SVR) and dynamic arterial elastance (Eadyn) were assessed for characterization of afterload. Changes in preload were assessed by central venous pressure (CVP), global end-diastolic volume (GEDV), mean systemic filling pressure analog (Pmsfa), pulse pressure variation (PPV), and stroke volume variation (SVV). Further, cardiac function index (CFI), global ejection fraction and dPmax were measured as markers of preload dependent contractility. MAP, SV, and CO significantly increased following both interventions, as did SVR. In contrast, Eadyn did not show significant changes. Although the volumetric preload variable GEDV increased after the first step of phenylephrine, this was not reflected by significant changes in CVP or Pmsfa. CFI and dPmax significantly increased after both steps. Phenylephrine does not only affect cardiac afterload, but also increases effective preload. In contrast to CVP and Pmsfa, this effect can be monitored by GEDV. Further, phenylephrine affects contractility.

Individualized early goal-directed therapy in systemic inflammation: is full utilization of preload reserve the optimal strategy?

OBJECTIVES: In severe acute pancreatitis, the administration of fluids in the presence of positive fluid responsiveness is associated with better outcome when compared to guiding therapy on central venous pressure. We compared the effects of such consequent maximization of stroke volume index with a regime using individual values of stroke volume index assessed prior to severe acute pancreatitis induction as therapeutic hemodynamic goals. DESIGN: Prospective, randomized animal study. SETTING: University animal research laboratory. SUBJECTS: Thirty domestic pigs. INTERVENTIONS: After randomization, fluid resuscitation was started 2 hours after severe acute pancreatitis induction and continued for 6 hours according to the respective treatment algorithms. In the control group, fluid therapy was directed by maximizing stroke volume index, and in the study group, stroke volume index assessed prior to severe acute pancreatitis served as primary hemodynamic goal. MEASUREMENTS AND MAIN RESULTS: Within the first 6 hours of severe acute pancreatitis, the study group received a total of 1,935.8 ± 540.7 mL of fluids compared with 3,462.8 ± 828.2 mL in the control group (p < 0.001). Pancreatic tissue oxygenation did not differ significantly between both groups. Vascular endothelial function, measured by flow-mediated vasodilation before and 6 hours after severe acute pancreatitis induction, revealed less impairment in the study group after treatment interval (-90.76% [study group] vs -130.89% [control group]; p = 0.046). Further, lower levels of heparan sulfate (3.41 ± 5.6 pg/mL [study group] vs 43.67 ± 46.61 pg/mL [control group]; p = 0.032) and interleukin 6 (32.18 ± 8.81 pg/mL [study group] vs 77.76 ± 56.86 pg/mL [control group]; p = 0.021) were found in the study group compared with control group. Histopathological examination of the pancreatic head and corpus at day 7 revealed less edema for the study group compared with the control group (1.82 ± 0.87 [study group] vs 2.89 ± 0.33 [control group, pancreatic head]; p = 0.03; 2.2 ± 0.92 [study group] vs 2.91 ± 0.3 [control group, pancreatic corpus]; p = 0.025). CONCLUSIONS: Individualized optimization of intravascular fluid status during the early course of severe acute pancreatitis, compared with a treatment strategy of maximizing stroke volume by fluid loading, leads to less vascular endothelial damage, pancreatic edema, and inflammatory response.

Darbepoetin improves endothelial function and increases circulating endothelial progenitor cell number in patients with coronary artery disease.

BACKGROUND: Atherosclerosis is a progressive disease characterised in part by an imbalance of endothelial decline and endothelial repair. Erythropoietin has been connected to vasculoprotective effects such as enhanced nitric oxide production in endothelial cells and mobilisation of endothelial progenitor cells (EPC). OBJECTIVE: To determine the effect of erythropoietin on endothelial function and EPC mobilisation in humans with atherosclerosis. DESIGN: A prospective single-blind monocentric study of 20 patients randomly assigned to the test drug or placebo treatment over 4 weeks. METHODS: 20 Patients with stable coronary artery disease receiving optimal medical treatment with either weekly subcutaneous injections of saline (placebo) or the recombinant erythropoietin darbepoetin (60 µg/injection) over 3 consecutive weeks. At the initial and final visits, flow mediated dilatation (FMD) was determined by ultrasound. The number of EPC was determined as the number of CD34/CD133 positive mononuclear cells in peripheral blood. RESULTS: Treatment with darbepoetin resulted in a significantly improved FMD in each patient, whereas no difference was seen in placebo-treated patients. The FMD of darbepoetin-treated patients increased by 7.5±1.64%. Additionally, an increase in peripheral blood EPC of 50±24% was seen. CONCLUSION: Darbepoetin given in addition to optimal medical treatment resulted in a significantly improved endothelial function in patients with coronary artery disease, indicating a promising new atheroprotective treatment option.