3-DIMENSIONAL CARDIOGENIC SHOCK SIMULATOR PHASE I: SUCCESSFUL DEVELOPMENT OF A LARGE ANIMAL CARDIOGENIC SHOCK MODEL

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): The Danish Heart Foundation Unrestricted research grant from Abiomed Background No strong evidence exists regarding the treatment of cardiogenic shock (CS) caused by acute right ventricular (RV) failure which has mainly consisted of vasoactive drugs. There is expert agreement that treatment with the recently developed Impella RP is feasible, but no previous studies have compared vasoactive treatment strategies with the Impella RP in terms of cardiac unloading and end-organ perfusion. Hypothesis Treatment with the Impella RP device will be associated with lower RV myocardial workload (pressure-volume area) compared to vasoactive treatment strategies and can furthermore be achieved without compromising organ perfusion. Methods CS was induced by a stepwise injection of polyvinyl alcohol microspheres into the right coronary artery in twenty adult female Danish landrace pigs weighing 75-80 kg. After induction of CS, the pigs were allocated to one of the two interventions for 180 minutes: 1) vasoactive therapy comprised a continuous infusion of norepinephrine (0.1 µg/kg/min) for the first 30 minutes, supplemented by an infusion of milrinone (0.4 µg/kg/min) for the remaining 150 minutes or 2) immediate insertion of and treatment with the Impella RP. The results are presented as median [Q1;Q3]. Results Treatment with the Impella RP was associated with a lower RV workload compared to the vasoactive group, while no difference was observed with regards to left ventricular workload among intervention groups, Figure 1. Renal venous oxygen saturation increased to a similar degree following both interventions compared to the state of CS. A trend towards a higher cerebral venous oxygen saturation was observed with norepinephrine compared to Impella RP (Impella RP 51 [47;61] % vs Norepinephrine 62 [57;71] % ; p = 0.07), which became significantly higher with the addition of milrinone (Impella RP 45 [32;63] % vs Norepinephrine +Milrinone 73 [66;81] %; p = 0.002). Conclusion In this large animal model of profound CS caused by predominantly RV failure the Impella RP unloaded the failing RV. The vasoactive treatment, however, caused a higher cerebral venous oxygen saturation, while both interventions increased renal venous oxygen saturation to a similar degree. Abstract Figure 1

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Gefitinib (ZD-1839) with concurrent docetaxel and conformal three-dimensional thoracic radiation followed by consolidative docetaxel/gefitinib for patients with stage III NSCLC: A phase I study

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.18165 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 18165-18165

Author(s):

A. Blackstock ◽

J. Petty ◽

T. Oaks ◽

M. Porosnicu ◽

H. Clark ◽

...

Keyword(s):

Phase I ◽

Dose Level ◽

Three Dimensional ◽

Maximum Tolerated Dose ◽

Stage Iii ◽

3 Dimensional ◽

Thoracic Radiation ◽

Stage Iii Nsclc ◽

Experienced Grade ◽

Grade Iii

18165 Background: The safety of 3-dimensional (3D) conformal thoracic radiation delivered with concurrent gefitinib/docetaxel chemotherapy in patients with inoperable stage III NSCLC has not been evaluated. Methods: Patients with inoperable stage III NSCLC received weekly intravenous (i.v.) docetaxel starting at a dose of 15 mg/m2 escalating to 30 mg/m2 in 5 mg/m2 increments and daily gefitinib (250 mg given orally). Patients recieved concurrent thoracic radiation to a dose of 70 Gy utilizing 3-D techniques. The chemoradiation therapy was followed by 2 cycles of consolidative docetaxel (75 mg/m2) given q 21 days and gefitinib 250 mg p.o. for 1 year or until disease progression. Results: Beginning December 2003, 15 patients have been entered to date to this IRB approved phase I trial to determine the maximum tolerated dose of weekly docetaxel when given concurrent with gefitinib and thoracic radiation. The dose-limiting toxicities (DLT) observed were primarily non-hematologic and occured at dose level 3 (25 mg/m2). One patient experienced grade III esophagitis that resulted in a grade III dehydration, a second patient experienced grade III diarrhea while a third patient suffered a grade V interstitial pneumonitis, believed to be related to the gefinitib. While 14 of 15 patients completed the chemoradiation portion of the study and 2 patients completed all planned therapy, 4 patients progressed during therapy, 3 patients discontinued treatment due to toxicity, and 2 patients refused to continue treatment. The median and 1-year survival thus far is 21 months and 56%, respectively. Conclusions: 70 Gy conformal thoracic radiation and concurrent gefitinib/docetaxel thus far appears feasible but with modest toxicity. The study is currently enrolling patients at the weekly 20 mg/m2 docetaxel dose level concurrent with 250 mg of daily gefitinib. This study was supported in-part by Sanofi-Aventis and Astra Zeneca. No significant financial relationships to disclose.

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Plasma Levels of Liver-Specific miR-122 Is Massively Increased in a Porcine Cardiogenic Shock Model and Attenuated by Hypothermia

Shock ◽

10.1097/shk.0b013e31823f1811 ◽

2012 ◽

Vol 37 (2) ◽

pp. 234-238 ◽

Cited By ~ 38

Author(s):

Patrik Andersson ◽

Olof Gidlöf ◽

Oscar Ö. Braun ◽

Matthias Götberg ◽

Jesper van der Pals ◽

...

Keyword(s):

Cardiogenic Shock ◽

Plasma Levels ◽

Shock Model

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Transaortic or Pulmonary Artery Drainage for Left Ventricular Unloading in Venoarterial Extracorporeal Life Support: A Porcine Cardiogenic Shock Model

Seminars in Thoracic and Cardiovascular Surgery ◽

10.1053/j.semtcvs.2020.11.001 ◽

2020 ◽

Author(s):

Paolo Meani ◽

Mikulas Mlcek ◽

Mariusz Kowalewski ◽

Giuseppe Maria Raffa ◽

Michaela Popkova ◽

...

Keyword(s):

Pulmonary Artery ◽

Cardiogenic Shock ◽

Life Support ◽

Extracorporeal Life Support ◽

Left Ventricular ◽

Shock Model

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Thickness of the Stifle Joint Articular Cartilage in Different Large Animal Models of Cartilage Repair and Regeneration

Cartilage ◽

10.1177/1947603520976763 ◽

2020 ◽

pp. 194760352097676 ◽

Cited By ~ 1

Author(s):

Tina Ruediger ◽

Victoria Horbert ◽

Anne Reuther ◽

Pavan Kumar Kalla ◽

Rainer H. Burgkart ◽

...

Keyword(s):

Articular Cartilage ◽

Animal Models ◽

Cartilage Repair ◽

Femoral Condyle ◽

Cartilage Thickness ◽

Large Animal ◽

3 Dimensional ◽

Large Animal Models ◽

Stifle Joint ◽

Regulatory Guidelines

Objective Regulatory guidelines for preclinical cartilage repair studies suggest large animal models (e.g., sheep, goat, [mini]-pig, or horse) to obtain results representative for humans. However, information about the 3-dimensional thickness of articular cartilage at different implantation sites in these models is limited. Design To identify the most suitable site for experimental surgery, cartilage thickness at the medial femoral condyle (MFC), lateral femoral condyle (LFC), and trochlea in ovine, caprine, and porcine cadaver stifle joints was systematically measured using hematoxylin-eosin staining of 6 µm paraffin sections and software-based image analysis. Results Regarding all ventral-dorsal regions of the MFC, goat showed the thickest articular cartilage (maximal mean thickness: 1299 µm), followed by sheep (1096 µm) and mini-pig (604 µm), with the highest values in the most ventral and dorsal regions. Also for the LFC, the most ventral regions showed the thickest cartilage in goat (maximal mean thickness: 1118 µm), followed by sheep (678 µm) and mini-pig (607 µm). Except for the mini-pig, however, the cartilage thickness on the LFC was consistently lower than that on the MFC. The 3 species also differed along the transversal measuring points on the MFC and LFC. In contrast, there were no consistent differences for the regional cartilage thickness of the trochlea among goat and sheep (≥780 µm) and mini-pig (≤500 µm). Conclusions Based on their cartilage thickness, experimental defects on goat and sheep MFC may be viable options for preclinical cartilage repair studies, in addition to well-established horse models.

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