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<strong>Whole</strong> <strong>Body</strong> <strong>Hyperthermia</strong> <strong>using</strong> <strong>Extra</strong>-<strong>Corporeal</strong><br />

Membrane Oxygenation and Antegrade Carotid<br />

Cerebral <strong>Perfusion</strong>, an effective safe model.<br />

Ahmses Maat, BS, RRT, CCP,<br />

Ta Meri Inc., Lake Elsinore, CA, USA<br />

Ferdinand. Masau, MD,<br />

Tanzania Heart Institute, Dar es Salaam, TZ<br />

Disclosures: Ta Meri Inc,<br />

© 2010 Ahmses S. Maat All Rights Reserved www.TaMeriInc.<strong>com</strong>


Medline/ Pub Med Search<br />

ASAIO J. 1996 Jul-Aug;42(4):250-4.<br />

Induction of whole body hyperthemia with venovenous perfusion.<br />

Vertrees RA, Tao W, Pencil SD, Sites JP, Althoff DP, Zwischenberger JB.<br />

Department of Surgery, University of Texas Medical Branch, Galveston 77554-0528, USA.<br />

<strong>Whole</strong> body hyperthermia can be used for the treatment of metastatic cancer and human immunodeficiency<br />

virus infections. The therapeutic effects of hyperthermia are dependent upon the actual temperature of the<br />

target tissues. Therefore, homogeneous distribution of heat and precise control of temperature gradients is<br />

critical. To describe heat distribution during hyperthermia induced by venovenous perfusion, the authors used<br />

multiple channel temperature monitoring and a servo-regulated perfusion/heat exchange system. Young swine<br />

were randomly assigned to either a heated group (perfusion-induced hyperthermia, target core temperature at<br />

43 degrees C, n = 6), or a control group (perfusion alone, target core temperature at 38 degrees C, n = 6). Blood<br />

was drained from the external jugular vein, heated with a <strong>com</strong>puter assisted heat exchange system, and<br />

reinfused through the femoral vein at a flow of 10 ml/kg-1/min-1. Temperature probes in the esophagus, right<br />

and left tympanic canals, brain, pulmonary artery, arterial and venous blood, rectus spinae muscle, kidney,<br />

rectum, bone marrow, bladder, subcutaneous tissue, gluteus, and skin were simultaneously recorded. During<br />

the heat induction phase, the maximum water temperature was 54 degrees C, with a heating gradient of the<br />

blood (blood in-blood out) at 6 degrees C. The maximum temperature difference between tissues was 3.6<br />

degrees C (kidney and esophagus) during heat induction, but decreased to 1.75 degrees C during maintenance.<br />

Bone marrow temperature was consistently 1-2 degrees C below the average core temperature of 43 degrees C<br />

throughout the experiment. The authors conclude that venovenous perfusion can predictably induce<br />

hyperthermia, but is associated with heterogenous temperature distribution among organs. Further studies are<br />

necessary to evaluate different perfusion and heating patterns to achieve homogenous hyperthermia.<br />

PMID: 8828779 [PubMed - indexed for MEDLINE]<br />

© 2010 Ahmses S. Maat All Rights Reserved www.TaMeriInc.<strong>com</strong>


Medline/ Pub Med Search<br />

ASAIO J. 1997 Sep-Oct;43(5):M830-8.<br />

<strong>Extra</strong>corporeal whole body hyperthermia treatments for HIV infection and AIDS.<br />

Ash SR, Steinhart CR, Curfman MF, Gingrich CH, Sapir DA, Ash EL, Fausset JM, Yatvin MB.<br />

HemoCleanse Inc., West Lafayette, Indiana 47906, USA.<br />

<strong>Whole</strong> body hyperthermia therapy (WBHT) is the elevation of the core body temperature to 42<br />

degrees C. In vitro studies have confirmed that 42 degrees C is cytocidal for virally infected<br />

lymphocytes, and even more effective when heating is repeated 4 days later. The safety and efficacy<br />

of two successive sessions of WBHT (4 days apart) was evaluated in 30 patients with AIDS (not on<br />

protease inhibitors), randomized to: 1) untreated controls, 2) low temperature WBHT for 1 hour at 40<br />

degrees C and repeated 96 hours later, and 3) high temperature WBHT for 1 hour at 42 degrees C<br />

and repeated 96 hours later. The sorbent suspension in the ThermoChem System (HemoCleanse,<br />

West Lafayette, IN) system automatically controlled blood phosphate, calcium, and other electrolyte<br />

concentrations during WBHT. In 1 year of follow-up after WBHT, there were positive effects of the<br />

therapy on frequency of AIDS defining events, Karnofsky score, and weight maintenance. However,<br />

effects on plasma HIV RNA and CD4 counts were transient. Two successive WBHT treatments were<br />

performed in four patients who were on protease inhibitor/triple drug therapy, but had suboptimal<br />

response. In follow-up for 6 months, plasma HIV RNA and CD4 improved after WBHT, and the patients<br />

remained clinically well. This WBHT may have specific advantages in patients with suboptimal<br />

response to protease inhibitor therapy.<br />

PMID: 9360163 [PubMed - indexed for MEDLINE]<br />

© 2010 Ahmses S. Maat All Rights Reserved www.TaMeriInc.<strong>com</strong>


Medline/ Pub Med Search<br />

ASAIO Journal: July/August 2002 - Volume 48 - Issue 4 - pp 350-354<br />

<strong>Perfusion</strong> Induced <strong>Hyperthermia</strong> for Oncologic Therapy<br />

with Cardiac and Cerebral Protection<br />

Hemmila, Mark R.; Foley, David S.; Casetti, Alfredo V.; Soldes, Oliver S.; Hirschl, Ronald B.; Bartlett, Robert H.<br />

Abstract<br />

Cancer can be preferentially damaged and killed at<br />

temperatures above 41.0° C. However, the heart and<br />

brain malfunction at this temperature, limiting the<br />

application of systemic hyperthermia in the treatment of<br />

metastatic cancer. We created a hyperthermic perfusion<br />

system that maximizes the temperature differential<br />

produced and extends the safe hyperthermic time.<br />

© 2010 Ahmses S. Maat All Rights Reserved www.TaMeriInc.<strong>com</strong>


Medline/ Pub Med Search<br />

ASAIO Journal: July/August 2002 - Volume 48 - Issue 4 - pp 350-354<br />

<strong>Perfusion</strong> Induced <strong>Hyperthermia</strong> for Oncologic Therapy with Cardiac and Cerebral<br />

Protection<br />

Hemmila, Mark R.; Foley, David S.; Casetti, Alfredo V.; Soldes, Oliver S.; Hirschl, Ronald B.; Bartlett, Robert H.<br />

Abstract<br />

• Venoarterial perfusion was instituted and the<br />

perfusate was warmed to 44 to 45°C. The dogs'<br />

rectal temperature was elevated to ≥ 42° C for 4<br />

hours. A small amount of venous blood was cooled<br />

to 28 to 30° C and reperfused into the right atrium<br />

to maintain the pulmonary artery temperature ≤<br />

38° C.<br />

© 2010 Ahmses S. Maat All Rights Reserved www.TaMeriInc.<strong>com</strong>


Medline/ Pub Med Search<br />

ASAIO Journal: July/August 2002 - Volume 48 - Issue 4 - pp 350-354<br />

<strong>Perfusion</strong> Induced <strong>Hyperthermia</strong> for Oncologic Therapy with Cardiac and Cerebral<br />

Protection<br />

Hemmila, Mark R.; Foley, David S.; Casetti, Alfredo V.; Soldes, Oliver S.; Hirschl, Ronald B.; Bartlett, Robert H.<br />

Abstract<br />

• Ten of 11 dogs survived the operative procedure,<br />

and no neurologic deficits were observed. The<br />

rectal temperature was successfully elevated to ≥<br />

42° C for 4 hours while maintaining the heart and<br />

brain at ≤ 38° C. Moderate serum biochemical<br />

changes were observed postprocedure.<br />

© 2010 Ahmses S. Maat All Rights Reserved www.TaMeriInc.<strong>com</strong>


Medline/ Pub Med Search<br />

ASAIO Journal: July/August 2002 - Volume 48 - Issue 4 - pp 350-354<br />

<strong>Perfusion</strong> Induced <strong>Hyperthermia</strong> for Oncologic Therapy with Cardiac and Cerebral<br />

Protection<br />

Hemmila, Mark R.; Foley, David S.; Casetti, Alfredo V.; Soldes, Oliver S.; Hirschl, Ronald B.; Bartlett, Robert H.<br />

Abstract<br />

• Lower abdominal and pelvic hyperthermia at 42° C<br />

can be safely produced and maintained for 4 hours<br />

<strong>using</strong> an extracorporeal perfusion circuit, while<br />

protecting the heart and brain from temperature<br />

elevation.<br />

© 2010 Ahmses S. Maat All Rights Reserved www.TaMeriInc.<strong>com</strong>


Medline/ Pub Med Search<br />

Immunol Res. 2010 Mar;46(1-3):137-54.<br />

Diverse immune mechanisms may contribute to the survival benefit seen in<br />

cancer patients receiving hyperthermia.<br />

Peer AJ, Grimm MJ, Zynda ER, Repasky EA.<br />

Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY, 14263, USA.<br />

There is increasing documentation of significant survival benefits achieved in cancer patients<br />

treated with hyperthermia in <strong>com</strong>bination with radiation and/or chemotherapy. Most evidence<br />

collected regarding the mechanisms by which hyperthermia positively influences tumor control<br />

has centered on in vitro data showing the ability of heat shock temperatures (usually above 42<br />

degrees C) to result in radio- or chemosensitization. However, these high temperatures are<br />

difficult to achieve in vivo, and new thermometry data in patients reveal that much of the tumor<br />

and surrounding region is only heated to 40-41 degrees C or less as a result of vascular drainage<br />

from the target zone of the heated tumor. Thus, there is now a growing appreciation of a role for<br />

mild hyperthermia in the stimulation of various arms of the immune system in contributing to long<br />

term protection from tumor growth. Indeed, a review of recent literature suggests the existence<br />

of an array of thermally sensitive functions which may exist naturally to help the organism to<br />

establish a new "set point" of immune responsiveness during fever. This review summarizes recent<br />

literature identifying <strong>com</strong>plex effects of temperature on immune cells and potential cellular<br />

mechanisms by which increased temperature may enhance immune surveillance.<br />

PMID: 19756410 [PubMed - in process]<br />

© 2010 Ahmses S. Maat All Rights Reserved www.TaMeriInc.<strong>com</strong>


Hyperthermic Isolated Limb <strong>Perfusion</strong><br />

© 2010 Ahmses S. Maat All Rights Reserved www.TaMeriInc.<strong>com</strong>


Hyperthermic Intraperitoneal<br />

Chemotherapy (HIPEC)<br />

Cytoreduction<br />

(Debulking) Surgery<br />

© 2010 Ahmses S. Maat All Rights Reserved www.TaMeriInc.<strong>com</strong>


<strong>Whole</strong> <strong>Body</strong> <strong>Hyperthermia</strong> <strong>using</strong> <strong>Extra</strong>-<strong>Corporeal</strong> Membrane<br />

Oxygenation and Antegrade Carotid Cerebral <strong>Perfusion</strong>,<br />

an effective safe model.<br />

• Background: <strong>Whole</strong> <strong>Body</strong> <strong>Hyperthermia</strong> (WBH) Heat Shock (HS) level of<br />

44°C has a proven direct cytocidal effect on cancer and thermo-liable<br />

pathogens. With WBH, HS, critical Cerebral Hyperthermal Injury (CHI)<br />

may occur.<br />

• Purpose: To asses CHI prevention, cerebral hypothermia with<br />

simultaneous WBH, HS was performed. WBH gives a significant global<br />

therapeutic HS to all direct and adjoining tissues with vascular access.<br />

Target temperature for core body is T rectal @ 44°C, and cerebral is T-<br />

tympanic@ 35°C, respectively. To trial a rapid cerebral cooling the T<br />

tympanic@ 28°C was earmarked.<br />

© 2010 Ahmses S. Maat All Rights Reserved www.TaMeriInc.<strong>com</strong>


BIZ ≤ 30<br />

<strong>Whole</strong> <strong>Body</strong> <strong>Hyperthermia</strong> <strong>using</strong> <strong>Extra</strong>-<strong>Corporeal</strong> Membrane Oxygenation and Antergrade Carotid Cerebral <strong>Perfusion</strong>, an effective safe model.<br />

Tympanic Temp 35C<br />

Pulse Ox 96 ±2<br />

HYPERTHERMIC DIAGRAM<br />

*Confidential Ta Meri Inc*<br />

Art by:<br />

Ahmses Maat ,RRT, CCP, DMD<br />

Carotid<br />

Temp 44<br />

Foley<br />

Vent<br />

NG<br />

EKG 100<br />

±20<br />

MAP 80 ± 20<br />

I.V.<br />

Fem Art<br />

ABG<br />

Pump 2 Pump 1<br />

Fem Vein<br />

Sat %/ HCT<br />

Pedal<br />

Doppler<br />

Warming<br />

Blanket at 42C<br />

CVP<br />

15 ±3<br />

Art<br />

Line<br />

Heat<br />

Exchanger #2<br />

to 33C<br />

Oxygenator / Forane<br />

Heat Exchanger #1 to<br />

46C<br />

ABG, K, Na,<br />

Hct, Glucose<br />

ACT<br />

200s+<br />

© 2010 Ahmses S. Maat All Rights Reserved www.TaMeriInc.<strong>com</strong>


<strong>Whole</strong> <strong>Body</strong> <strong>Hyperthermia</strong> <strong>using</strong> <strong>Extra</strong>-<strong>Corporeal</strong> Membrane<br />

Oxygenation and Antegrade Carotid Cerebral <strong>Perfusion</strong>,<br />

an effective safe model.<br />

• Methods: Using the Aorta and Right Atria for vascular access on a 35kg<br />

goat, <strong>Extra</strong>-<strong>Corporeal</strong> Membrane Oxygenation (ECMO) was initiated.<br />

Using a cardioplegia delivery system, a proprietary cerebral protection<br />

solution was delivered.<br />

• Right antegrade carotid cerebral perfusion (ACCP) @ 300 ml/min ± 100<br />

ml/ min at 160 mmHg ± 30 mmHg was achieved and maintained. With<br />

systemic flows of 2.45 l/m ± 0.45 l/m, the mean BP was maintained at 80<br />

mmHg ± 20 mmHg. The HR was maintained at 100 ± 40 bpm. The digital<br />

Pulse Ox and Ear Ox was 96% ± 2%.<br />

• During systemic warming, the standard 1°C to 2°C gradient range was kept<br />

within the T-systemic water, arterial, venous, and rectal respectively. The<br />

pump time was 106 minutes. At 90 minutes, T –rectal @ 44°C and T-<br />

tympanic @ 35°C was achieved.<br />

• Then testing rapid cerebral hypothermia, T tympanic @ 28°C was achieved<br />

within 15 minutes while keeping T rectal@ 44°C.<br />

© 2010 Ahmses S. Maat All Rights Reserved www.TaMeriInc.<strong>com</strong>


<strong>Whole</strong> <strong>Body</strong> <strong>Hyperthermia</strong> <strong>using</strong> <strong>Extra</strong>-<strong>Corporeal</strong> Membrane<br />

Oxygenation and Antegrade Carotid Cerebral <strong>Perfusion</strong>,<br />

an effective safe model.<br />

• Summary: WBH with ECMO, HS therapy at T rectal 44°C, and ACCP,<br />

with cerebral hypothermia @ ≤ 35°C was achieved; thereby avoidance of<br />

CHI is implied.<br />

• Conclusion: While further study with additional indicators for validity is<br />

needed, this methodology, offers a potential solution to the threat of cancer<br />

metastasis and systemic thermo-liable pathogens that are sensitive to<br />

internal HS treatment while offering avoidance of CHI.<br />

© 2010 Ahmses S. Maat All Rights Reserved www.TaMeriInc.<strong>com</strong>


Tanzania Heart Institute<br />

Special Thanks for equipment donation to:<br />

Armando Rosales – Sales- Terumo Cardiovascular Medical<br />

Paul Johnson CP, Pomona Valley Hospital<br />

Bill Casey CCP and Monte McKrinstry CCP- Desert<br />

D`Salaam Regional hosts Hospital continental heart specialists seminar<br />

By The guardian reporter / www.ippmedia.<strong>com</strong><br />

7th November 2009<br />

Permanent Secretary in the Ministry of Health and Social Welfare Blandina Nyoni<br />

will today officiate at the sixth African Heart seminar to be held in Dar es Salaam.<br />

Briefing reporters in Dar es Salaam yesterday, Tanzania Heart Institute (TAHI)<br />

founder and president Dr. Ferdinand Masau said the four-day seminar would bring<br />

together more than 150 medical specialists from different countries across the<br />

world.<br />

www.TaMeriInc.<strong>com</strong><br />

HL-Machine, ECMO, VADs, ATS, Cancer<br />

<strong>Hyperthermia</strong><br />

© 2010 Ahmses S. Maat All Rights Reserved www.TaMeriInc.<strong>com</strong><br />

15


Thank<br />

You.<br />

© 2010 Ahmses S. Maat All Rights Reserved www.TaMeriInc.<strong>com</strong><br />

16

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