Physiologic Response to a Simplified Venovenous Perfusion-Induced Systemic Hyperthermia System

Ballard-Croft, Cherry; Wang, Dongfang; Jones, Cameron; Sumpter, L. Ryan; Zhou, Xuguo; Thomas, Joe; Topaz, Stephen R.; Zwischenberger, Joseph B.

doi:10.1097/mat.0b013e318271badb

Cited by 6 publications

(10 citation statements)

References 17 publications

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“…The heated blood is well mixed with unheated venous blood through the pulmonary circulation and is distributed to the systemic circulation by the heart, which results in homogenous delivery of systemic hyperthermia. 14–15 Fast heating can also be achieved with the vv-PISH system, which enhances cancer cell kill. 19 Thus, vv-PISH rapidly and homogeneously delivers a therapeutic dose, meeting the requirements needed for efficacious hyperthermic cancer therapy.…”

Section: Discussionmentioning

confidence: 99%

“…Despite these improvements in the vv-PISH circuit, significant pulmonary hypertension developed during the heating phase, resulting in circulatory instability. 15 …”

Section: Discussionmentioning

confidence: 99%

“…15 Our goal, in this study, was to develop a protocol to prevent pulmonary hypertension for safe application of our simplified vv-PISH system. We hypothesized that fast heating of the priming solution in the heat exchanger circuit from room temperature (20 °C) to 45 °C at the beginning of the heating phase would decrease priming solution air solubility, generating numerous micro air bubbles and causing global pulmonary air embolism with subsequent pulmonary hypertension.…”

Section: Discussionmentioning

confidence: 99%

“…Although this pulmonary hypertension was temporary, it was severe enough to cause the death of one swine from circulatory collapse. 15 In anticipation of long-term survival studies, we replaced the swine model with a sheep model for more practical post-procedure care. Pulmonary hypertension also developed during the heating phase in our sheep model.…”

Section: Introductionmentioning

confidence: 99%

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Resolution of Pulmonary Hypertension Complication During Venovenous Perfusion-Induced Systemic Hyperthermia Application

Ballard-Croft

Wang²,

Jones³

et al. 2013

ASAIO Journal

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We are developing a venovenous perfusion-induced systemic hyperthermia (vv-PISH) system for advanced cancer treatment. The vv-PISH system consistently delivered hyperthermia to adult healthy swine, but significant pulmonary hypertension developed during the heating phase. The goal of this study was to develop a method to prevent pulmonary hypertension. We hypothesized that pulmonary hypertension results from decreased priming solution air solubility which causes pulmonary gas embolism. Healthy adult sheep (n=3) were used to establish a standard vv-PISH sheep model without priming solution preheating. In subsequent sheep (n=7), the priming solution was preheated (42–46°C) and the hyperthermia circuit flushed with CO2. All sheep survived the experiment and achieved 2 hrs of 42 °C hyperthermia. In the group lacking priming solution preheating, significant pulmonary hypertension (35–44 mm Hg) developed. In the sheep with priming solution preheating, pulmonary artery pressure was very stable without pulmonary hypertension. Blood electrolytes were in physiological range, and complete blood counts were unaffected by hyperthermia. Blood chemistries revealed no significant liver or kidney damage. Our simple strategy of priming solution preheating completely resolved the problem of pulmonary hypertension as a milestone toward developing a safe and easy to use vv-PISH system for cancer treatment.

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Section: Discussionmentioning

confidence: 99%

“…Despite these improvements in the vv-PISH circuit, significant pulmonary hypertension developed during the heating phase, resulting in circulatory instability. 15 …”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Resolution of Pulmonary Hypertension Complication During Venovenous Perfusion-Induced Systemic Hyperthermia Application

Ballard-Croft

Wang²,

Jones³

et al. 2013

ASAIO Journal

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“…18 For practical clinical application of hyperthermia, we recently developed a simplified vv-PISH system and management protocol. 20-21 In this paper, we report the results of our preclinical Good Laboratory Practice (GLP) investigation which was designed to prove the safety and accuracy of the simplified vv-PISH system in a 5 day sheep survival study. Our results showed that an accurate dose of therapeutic hyperthermia was safely delivered to sheep with no hyperthermia-related complications.…”

Section: Introductionmentioning

confidence: 99%

Venovenous perfusion-induced systemic hyperthermia: Five-day sheep survival studies

Ballard-Croft

Wang

Rosenstein

et al. 2014

The Journal of Thoracic and Cardiovascular Surgery

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Objective Since hyperthermia selectively kills lung cancer cells, we developed a venovenous perfusion-induced systemic hyperthermia (vv-PISH) system for advanced lung cancer therapy. Our objective was to test the safety/accuracy of our vv-PISH system in five day sheep survival studies, following Good Laboratory Practice standards. Methods The vv-PISH system, which included a double lumen cannula (DLC, AvalonElite™); a centrifugal pump (Bio-Pump 560®); a heat exchanger (BIOtherm™); and a heater/cooler (modified Blanketrol III™), was tested in healthy adult sheep (n=5). The perfusion circuit was primed with pre-warmed Plasma-Lyte®A and de-aired. Calibrated temperature probes were placed in right/left nasopharynx, bladder, and blood in/out of animal. The DLC was inserted in jugular vein into the superior vena cava, with the tip in the inferior vena cava. Results Therapeutic core temperature (42-42.5°C), calculated from right/left nasopharnx and bladder temperatures, was achieved in all sheep. Heating time was 21±5 minutes. Therapeutic core temperature was maintained for 120 minutes followed by a cooling phase (35±6 min) to reach baseline temperature. All sheep recovered from anesthesia with spontaneous breathing within 4 hours. Arterial, pulmonary, and central venous pressures were stable. Transient increases in heart rate, cardiac output, and blood glucose occurred during hyperthermia but returned to normal range after vv-PISH termination. Electrolytes, complete blood counts, and metabolism enzymes were within normal to near normal range throughout the study. No significant vv-PISH-related hemolysis was observed. Neurological assessment showed normal brain function all 5 days. Conclusion Our vv-PISH system safely delivered the hyperthermia dose with no significant hyperthermia-related complications.

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The anti-hepatoma effect of nanosized Mn–Zn ferrite magnetic fluid hyperthermia associated with radiationin vitroandin vivo

et al. 2013

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Joint therapy is a promising area of study in cancer treatment. In this paper, we prepared Mn-Zn ferrite (Mn0.5Zn0.5Fe2O4) magnetofluid using PEI as a surfactant, and investigated the anticancer effect of Mn0.5Zn0.5Fe2O4 magnetic fluid hyperthermia (MFH) combined with radiotherapy on hepatocellular carcinoma. Both in vitro and in vivo results suggest that this combined treatment with MFH and radiation has a better therapeutic effect than either of them alone. The apoptotic rate and necrotic rate of the combined treatment group was 38.80 and 25.20%, respectively. In contrast, it was only 7.49 and 3.62% in the radiation-alone group, 15.23 and 7.90% in the MFH-alone group, only 3.52 and 2.16% in the blank control group, and 23.56 and 27.56% in the adriamycin group. The cell proliferation inhibition rate of the combined treatment group (88.5%) was significantly higher than that of the radiation-alone group (37.5%), MFH-alone group (60.6%) and adriamycin group (70.6%). The tumor volume inhibition and mass inhibition rate of the combined treatment group was 87.62 and 88.62%, respectively, obviously higher than the 41.04 and 34.20% of the radiation-alone group, 79.87 and 77.92% of the MFH-alone group and 71.76 and 66.87% of the adriamycin group. It is therefore concluded that this combined application of MFH and radiation can give good synergistic and complementary effects, which offers a viable approach for treatment of cancer.

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Physiologic Response to a Simplified Venovenous Perfusion-Induced Systemic Hyperthermia System

Cited by 6 publications

References 17 publications

Resolution of Pulmonary Hypertension Complication During Venovenous Perfusion-Induced Systemic Hyperthermia Application

Resolution of Pulmonary Hypertension Complication During Venovenous Perfusion-Induced Systemic Hyperthermia Application

Venovenous perfusion-induced systemic hyperthermia: Five-day sheep survival studies

The anti-hepatoma effect of nanosized Mn–Zn ferrite magnetic fluid hyperthermia associated with radiationin vitroandin vivo

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