a-large-animal-model-for-pulmonary-hypertension-right-ventricular

A Large Animal Model for Pulmonary Hypertension and Right Ventricular Failure: Left Pulmonary Artery Ligation and Progressive Main Pulmonary Artery Banding in Sheep

Decompensated right ventricular failure (RVF) in pulmonary hypertension (PH) is fatal, with limited medical treatment options. Developing and testing ...

Vanderbilt University Medical Center

The American College of Surgeons (ACS) National Surgical Quality Improvement Program Surgical Risk Calculator (ACS Calculator) provides empirically derived, patient-specific risks for common adverse perioperative outcomes. The ACS Calculator is promoted as a tool to improve shared decision-making and informed consent for patients undergoing elective operations. However, to our knowledge, no data exist regarding the use of this tool in actual preoperative risk discussions with patients. Accordingly, we performed a survey to assess (1) whether patients find the tool easy to interpret, (2) how accurately patients can predict their surgical risks, and (3) the impact of risk disclosure on levels of anxiety and future motivations to decrease personal risk.

Use of the American College of Surgeons National Surgical Quality Improvement Program Surgical Risk Calculator During Preoperative Risk Discussion: The Patient Perspective.

POINT: Should Patients With Advanced Lung Disease Be Offered Extracorporeal Membrane Oxygenation as a Bridge to Transplant If They Have Not Yet Been Listed for Lung Transplant? Yes.

Rebuttal From Ms Gannon and Drs Stokes and Bacchetta.

Bleeding and thromboembolism are common during venovenous extracorporeal membrane oxygenation. The relative frequency of these complications and their impact on clinical outcomes have not been described, and no randomized trials exist to guide anticoagulation strategies in extracorporeal membrane oxygenation. Our objective was to examine the relative frequencies of bleeding and thromboembolic events and their associations with survival among a cohort of consecutive patients receiving venovenous extracorporeal membrane oxygenation.

Bleeding, Thromboembolism, and Clinical Outcomes in Venovenous Extracorporeal Membrane Oxygenation.

Extracorporeal life support (ECLS) is a resource-intensive technology. Disposable components are modifiable through device selection. Cost analysis tools are needed to inform cost-conscious device selection. We generated a disposable cost analysis to forecast estimated costs of device disposables that included an assumption table, net present value (NPV) analysis, and sensitivity analysis to examine device disposable costs over 5 years with different case volumes and device mixes. To demonstrate the function of the analysis, we included four device options using the following assumptions: 100 cases in year 1, 2.5% case growth rate, 10% discount rate, and $5,000 incremental cost (Device 4 only). Using estimated device costs of $3,000, $12,000, $13,000, and $20,000 and device mix percentages of 65%, 8%, 25%, and 2% for Device 1, 2, 3, and 4, respectively, the 5 year unadjusted and NPV of disposable device costs were $3,691,000 and $2,765,000, respectively. The sensitivity analysis incorporated six separate models with different device mix percentages. The highest and lowest estimated costs were found in Model F (75% Device 3 and 25% Device 4; NPV = $6,64,400) and Model B (100% Device 1; NPV = 1,246,000) respectively. Extracorporeal life support programs may apply this disposable cost analysis tool to reduce programmatic costs.

Disposable Component Selection in Extracorporeal Life Support: A Cost Analysis.

Pulmonary hypertension (PH) is a progressive disease that leads to cardiopulmonary dysfunction and right heart failure from pressure and volume overloading of the right ventricle (RV). Mechanical cardiopulmonary support has theoretical promise as a bridge to organ transplant or destination therapy for these patients. Solving the challenges of mechanical cardiopulmonary support for PH and RV failure requires its testing in a physiologically relevant animal model. Previous PH models in large animals have used pulmonary bead embolization, which elicits unpredictable inflammatory responses and has a high mortality rate. We describe a step-by-step guide for inducing pulmonary hypertension and right ventricular hypertrophy (PH-RVH) in sheep by left pulmonary artery (LPA) ligation combined with progressive main pulmonary artery (MPA) banding. This approach provides a controlled method to regulate RV afterload as tolerated by the animal to achieve PH-RVH, while reducing acute mortality. This animal model can facilitate evaluation of mechanical support devices for PH and RV failure.

Left Pulmonary Artery Ligation and Chronic Pulmonary Artery Banding Model for Inducing Right Ventricular-Pulmonary Hypertension in Sheep.

Pneumomediastinum in Acute Respiratory Distress Syndrome from COVID-19.

Extracorporeal Carbon Dioxide Removal or Extracorporeal Membrane Oxygenation: Why Should We Care?

 Despite the rapid integration of extracorporeal membrane oxygenation (ECMO) into intensive care units over the past decade, established programs for training critical care clinicians to provide ECMO are lacking.

Rapid Training in Extracorporeal Membrane Oxygenation for a Large Health System.

Decompensated right ventricular failure (RVF) in patients with pulmonary hypertension (PH) is fatal, with limited treatment options. Novel mechanical circulatory support systems have therapeutic potential for RVF, but the development of these devices requires a large animal disease model that replicates the pathophysiology observed in humans. We previously reported an effective disease model of PH in sheep through ligation of the left pulmonary artery (PA) and progressive occlusion of the main PA. Herein, we report a case of acute decompensation with this model of chronic RVF. Gradual PA banding raised the RV pressure (maximum RV systolic/mean pressure = 95 mmHg/56 mmHg). Clinical findings and laboratory serum parameters suggested appropriate physiologic compensation for 7 weeks. However, mixed venous saturation declined precipitously on week 7, and creatinine increased markedly on week 9. By the 10th week, the animal developed dependent, subcutaneous edema. Subsequently, the animal expired during the induction of general anesthesia. Post-mortem evaluation revealed several liters of pleural effusion and ascites, RV dilatation, eccentric RV hypertrophy, and myocardial fibrosis. The presented case supports this model's relevance to the human pathophysiology of RVF secondary to PH and its value in the development of novel devices, therapeutics, and interventions.

Progression Toward Decompensated Right Ventricular Failure in the Ovine Pulmonary Hypertension Model.

Extracorporeal membrane oxygenation (ECMO) is a cardiopulmonary technology capable of supporting cardiac and respiratory function in the presence of end-stage lung disease. Initial experiences using ECMO as a bridge to lung transplant (ECMO-BTLT) were characterized by high rates of ECMO-associated complications and poor posttransplant outcomes. More recently, ECMO-BTLT has garnered success in preserving patients' physiologic condition and candidacy prior to lung transplant due to technological advances and improved management. Despite recent growth, clinical practice surrounding use of ECMO-BTLT remains variable, with little data to inform optimal patient selection and management. Although many questions remain, the use of ECMO-BTLT has shown promising outcomes suggesting that ECMO-BTLT can be an effective strategy to ensure that complex and rapidly decompensating patients with end-stage lung disease can be safely transplanted with good outcomes. Further studies are needed to refine and inform practice patterns, management, and lung allocation in this high-risk and fragile patient population.

Extracorporeal Membrane Oxygenation as a Bridge to Lung Transplant.

Decannulation from venovenous extracorporeal membrane oxygenation (VV-ECMO) at the earliest and safest possible time may improve outcomes and reduce cost. Yet, there are no prospective studies comparing weaning strategies for liberation from ECMO.

Article	Year
Use of the American College of Surgeons National Surgical Quality Improvement Program Surgical Risk Calculator During Preoperative Risk Discussion: The Patient Perspective. Anesthesia and analgesia\| PubMed ID: 30169413	2019
POINT: Should Patients With Advanced Lung Disease Be Offered Extracorporeal Membrane Oxygenation as a Bridge to Transplant If They Have Not Yet Been Listed for Lung Transplant? Yes. Chest\| PubMed ID: 32654711	2020
Rebuttal From Ms Gannon and Drs Stokes and Bacchetta. Chest\| PubMed ID: 32654713	2020
Bleeding, Thromboembolism, and Clinical Outcomes in Venovenous Extracorporeal Membrane Oxygenation. Critical care explorations\| PubMed ID: 33196049	2020
Disposable Component Selection in Extracorporeal Life Support: A Cost Analysis. ASAIO journal (American Society for Artificial Internal Organs : 1992)\| PubMed ID: 33315654	2020
Left Pulmonary Artery Ligation and Chronic Pulmonary Artery Banding Model for Inducing Right Ventricular-Pulmonary Hypertension in Sheep. ASAIO journal (American Society for Artificial Internal Organs : 1992)\| PubMed ID: 33346995	2021
Pneumomediastinum in Acute Respiratory Distress Syndrome from COVID-19. American journal of respiratory and critical care medicine\| PubMed ID: 33448891	2021
Extracorporeal Carbon Dioxide Removal or Extracorporeal Membrane Oxygenation: Why Should We Care? Critical care medicine\| PubMed ID: 33854019	2021
Rapid Training in Extracorporeal Membrane Oxygenation for a Large Health System. ATS scholar\| PubMed ID: 33870310	2020
Progression Toward Decompensated Right Ventricular Failure in the Ovine Pulmonary Hypertension Model. ASAIO journal (American Society for Artificial Internal Organs : 1992)\| PubMed ID: 33883506	2021
Extracorporeal Membrane Oxygenation as a Bridge to Lung Transplant. Seminars in respiratory and critical care medicine\| PubMed ID: 34030201	2021
Safety and Feasibility of a Protocolized Daily Assessment of Readiness for Liberation from Venovenous Extracorporeal Membrane Oxygenation. Chest\| PubMed ID: 34166644	2021

John W. Stokes

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