July 14, 2006

We are pleased to present to you an interim summary of the activities of our Institute. It summarizes the activities and accomplishments of the three functional divisions of the Institute, namely Experimental Laboratories, Biomedical Engineering Laboratories, and Community Resuscitation Programs, since March 2005. We have tried to edit out some technical terminology, though admittedly not all, with consideration for the background of the majority of supporters.

I am very pleased by the accomplishments of our highly motivated and devoted group of co-workers who are in every respect fulfilling the mission of our Institute “Saving Lives Through Intensive Care Research and Education” and I know you will share in my pride as I plan to relinquish my executive role.

Max Harry Weil

  I  Experimental Laboratory  

Large Animal Laboratory

With the great effort of the research team, the large animal laboratory was on a full schedule one week after move-in. During the last 15 months, seven (7) research projects were completed. These studies focused on; (1) Optimal timing of defibrillation; (2) Microcirculation of the brain after vasopressor agents; (3) Optimal algorithm for defibrillation; (4) The potential adverse effects of interruption of chest compression imposed by Automated External Defibrillators (AEDs); (5) Algorithm for determining the likelihood that an electrical shock will reverse ventricular fibrillation; (6). The mechanisms by which a new cardiovascular drug, levosimendan, acts as a KATP channel opener and thereby mitigates myocardial (heart) ischemic injury and death; and (7) Comparisons of the miniature chest compressor designed by our engineering group with that of a commercially available mechanical compression devices and specifically the “Thumper®”. These studies yielded a total of 22 publications.

Small Animal Laboratory   

The small animal laboratory was returned to a full schedule within one week after move-in. During the last 15 months, the following studies have been completed: (1) Effects of pre-existing coronary artery disease on the outcomes of CPR; (2) Effects of β-blocking agents on post resuscitation myocardial dysfunction; (3) Distinguishing between the roles of ischemia (failure to provide blood flow) and reperfusion (restoring blood flow) on post resuscitation myocardial function in the isolated, perfused rat heart; (4) Comparison of local and systemic delivery of stem cells for the treatment of myocardial dysfunction. A total of 15  published reports have resulted from these studies.

Cell Laboratory  

With the support of Mr. and Mrs. Jerry Blue, the cell laboratory was established at the end of 2005. Dr. Tong Wang, who is an expert and has had an 8 year career in this field, was invited to join our team approximately six month ago. During these last six months, we have achieved the following:

(1) Established our own rat bone marrow derived mesenchymal stem cell line. The line was certified by both UC Riverside and UCLA;

(2) Successfully obtained heart muscle cells (myocytes) from the stem cells and this accomplishment was again certified by UC Riverside;

(3) Implemented a model in which myocytes are harvested from a rat heart for investigation of mechanisms of myocardial dysfunction;

(4) Demonstrated that systemic infusions of stem cells which are expected to serve as heart cells are as effective after local injection of stem cells directly into the heart.

During the last 15 months, the biomedical engineers of the research team have: (1) Refined the miniature chest compressor; (2) Developed the next generation of a miniature chest compressor; (3) Developed software to identify heart rhythm without interrupting chest compression as mandated by the American Heart Association (in part on the basis of earlier research by our group); and (4) Refined the “resuscitation box”, a more complete measuring and prompting capability incorporated into Automated External Defibrillators (AEDs). These were achieved in close collaboration with the physician scientists of the Institute.

Industry Contracts    

High quality of our research and scholarship allowed us to expand industry support during the last decade. We have had continuous research contract/consulting support from Philips Medical and Zoll Medical.

Publications

Since we occupied our new facilities, we have exceeded the number of scientific reports published by the Institute in any earlier like period. A total of 39 reports were published during the last 15 months. An additional 7 manuscripts have been accepted for publication. This represents a remarkable achievement for an Institution of our size.

Grant Applications   

During the last 15 months, 7 grant applications have been submitted to NIH , US army, and AHA. Three of these applications are still under review.

Patent Issued   

During the last 15 months, one US patent was issued, namely for the miniaturized chest compressor.

Literature Citations since March 2005

Pellis T, Weil MH, Tang W, Sun S, Csapozi P, Castillo, C. Increases in both buccal and sublingual partial pressure of carbon dioxide reflect decreases of tissue blood flows in a porcine model during hemorrhagic shock. J Trauma 2005; 58(4):817-824.

Huang L, Weil MH, Tang W, Sun S, Wang J. Comparison between dobutamine and levosimendan for management of postresuscitation myocardial dysfunction. Crit Care Med 2005;33(3):487-491.

Yannopoulos D, Tang W, Roussos C, Aufderheide TP, Idris A, Lurie KG. Reducing ventilation frequency during cardiopulmonary resuscitation in a porcine model of cardiac arrest. Respir Care 2005;50:628-635

Hazinski MF, Idris AH, Kerber RE, Epstein A, Atkins D, Tang W, Lurie K. Lay rescuer automated external defibrillator (“public access defibrillation”) programs: Lessons learned from an internal multicenter trial. Advisory statement from the American Heart Association emergency cardiovascular committee; the council on cardiopulmonary, perioperative, and critical care; and the council on clinical cardiology. Circulation 2005;111:3336-3340

Huang L, Weil MH, Sun SJ, Tang W, Fang X. Carvedilol mitigates adverse effects of epinephrine during cardiopulmonary resuscitation. J Cardiovasc Pharmacol The 2005;10:113-120

Weil MH, Sun S. Devices and drugs for cardiopulmonary resuscitation – opportunities and restraints. Crit Care 2005;9:287-290. Clinical review

Wang J, Weil MH, Tang W, Sun S, Huang L. Levosimendan improves postresuscitation myocardial dysfunction after beta-adrenergic blockade. J Lab Clin Med 2005;146(3):179-183.

Huang L, Weil MH, Sun S, Cammarata, G, Cao L, Tang W. Levosimendan improves postresuscitation outcomes in a rat model of CPR. J Lab Clin Med 2005;146(3):256-261.

Huang L, Sun S, Fang X, Tang W, Weil MH. Carvedilol combined with epinephrine improves post resuscitation outcomes of CPR in a rat model. Crit Care Med 2005; 32(Suppl 12):A8.

Fries M, Tang W, Chang Y-T, Castillo C, Weil MH. Assessment of microcirculatory blood flow in a porcine model of cardiac arrest. Crit Care Med 2005; 32(Suppl 12):A8.

Sun S, Tang W, Fang X, Huang L, Weil MH. Decreased sensitivity of 1-adrenergic receptors after prolonged cardiac arrest. Crit Care Med 2005; 32(Suppl 12):A8.

Cammarata GA, Castillo CJ, Chang Y-T, Fries M, Tang W, Sun S, Weil MH. Buccal PCO₂ for identifying immediate life threatening blood loss. Crit Care Med 2005; 32(Suppl 12):A32.

Chang Y-T, Tang W, Sun S, Wang J, Huang L, Fries M, Weil MH. The ST segment elevation reflects post-resuscitation myocardial dysfunction. Crit Care Med 2005; 32(Suppl 12):A54.

Wang J, Huang L, Chang Y-T, Tang W, Weil MH, Brewer J. Biphasic waveform defibrillation in a pediatric model. Crit Care Med 2005; 32(Suppl 12):A54.

Huang L, Sun S, Tang W, Wang J, Weil MH. Right ventricular volume during cardiac arrest. Crit Care Med 2005;32(Suppl 12):A54.

Fang X, Tang W, Weil MH. Characteristics of resuscitable and non-resuscitable postcountershock pulseless electrical activity. Crit Care Med 2005;32(Suppl 12):A54. 

Fries M, Tang W, Chang Y-T, Castillo C, Weil MH. Detrimental effects of epinephrine on microcirculatory blood flow in a porcine model of cardiac arrest. Crit Care Med 2005;32(Suppl 12):A56.

Chang YT, Tang W, Russell J, Huang L, Ristagno G, Sun S, Weil MH. Immediate resumption of CPR without delay for assessment after delivery of an electrical shock. Circulation 2005; 112:II-389. (Abstr)

Ristagno G, Tang W, Chang YT, Russell J, Huang L, Sun S, Weil MH. Prolonging the interval of CPR between defibrillation attempts improves post-resuscitation outcomes. Circulation 2005; 112:II-389. (Abstr)

Fang X, Tang W, Sun S, Huang L, Weil MH. Activation of δ–opioid receptors protects heart during CPR by opening KATP channels. Circulation 2005; 112:II-434. (Abstr)

Wang J, Tang W, Huang L, Sun S, Chang YT, Weil MH. Levosimendan: A new antiarrhythmic and inotropic agent acting through selective KATP channel opening. Circulation 2005; 112:II-488-II-489. (Abstr)

Huang L, Sun S, Fang X, Tang W, Weil MH. Mechanisms by which delta–opioid receptor activation protects the heart during cardiac resuscitation. Circulation 2005; 112:II-489.

Ristagno G, Sun S, Chang YT, Tang W, Weil MH. Gasping during cardiac arrest increases cerebral blood flow. Circulation 2005; 112:II-1099. (Abstr)

Chang YT, Tang W, Wang J, Brewer J,E, Freeman G, Sun S, Huang L, Weil MH. Simultaneous dual pathway shocks for electrical defibrillation. Circulation 2005; 112:II-1100. (Abstr)

Chang YT, Tang W, Wang J, Brewer J,E, Freeman G, Sun S, Huang L, Weil MH. Comparison of two biphasic waveforms for defibrillation. Circulation 2005; 112:II-1103. (Abstr)

Huang L, Sun S, Fang X, Tang W, Weil MH. Validation of volumetric conductance catheter for measurements of stroke volumes and ejection fractions in the rat during hemorrhagic shock. Circulation 2005; 112:II-1107-II-1108. (Abstr)

Yannopoulos D, Aufderheide TP, Gabrielli A, Beiser DG, McKnite S, Pirrallo RG, Wigginton J, Becker L, Venden Hoek T, Tang W, Nadkarni V, Idris A, Lurie KG. Clinical and hemodynamic comparison of 15:2 and 30:2 compression-to-ventilation ratios for cardiopulmonary resuscitation. Circulation 2005;112:II-1099.

Cammarata GA, Weil MH, Fries M, Tang W, Sun S, Castillo CJ. Buccal capnometry to guide management of massive blood loss. J Appl Physiol 2006;100:304-306

Yannopoulos D, Aufderheide TP, Gabrielli A, Beiser DG, McKnite SH, Pirrallo RG, Wigginton J, Becker L, Vanden Hoek T, Tang W, Nadkani VM, Klein JP, Idris AH, Lurie KG. Clinical and hemodynamic comparison of 15:2 and 30:2 compression-to-ventilation ratio for cardiopulmonary resuscitation. Crit Care Med 2006;34:1444-1449

Chang YT, Tang W, Wang J, Sun S, Huang L, Fang X, Weil MH. Sequential dual-path low energy biphasic waveform defibrillation. Crit Care Med 2006; 33(Suppl 12):A24. (Abstr)

Ristagno G, Sun S, Chang YT, Fang X, Castillo C, Tang W, Weil MH. Epinephrine reduces cerebral microcirculatory blood flow during CPR. Crit Care Med 2006; 33(Suppl 12):A24. (Abstr)

Ristagno G, Sun S, Chang YT, Fang X, Castillo C, Tang W, Weil MH. Effects of hypercarbia on cerebral microcirculatory blood flow. Crit Care Med 2006; 33(Suppl 12):A51. (Abstr)

Ristagno G. Sun S, Chang YT, Fang X, Castillo C, Tang W, Weil MH. Persistent cerebral microcirculatory blood flow after onset of cardiac arrest. Crit Care Med 2006; 33(Suppl 12):A100. (Abstr)

Fang X, Tang W, Sun S, Huang L, Chang YT, Weil MH. Microcirculation in buccal mucosa: A comparison between septic and hemorrhagic shock. Crit Care Med 2006; 33(Suppl 12):135. (Abstr)

Fries M, Weil MH, Sun S, Huang L, Fang X, Cammarata G, Castillo C, Tang W. Increases in tissue PCO₂ during circulatory shock reflect selective decreases in capillary blood flow. Crit Care Med 2006; 34:446-452.

Cammarata G, Weil MH, Csapoczi P, Sun S, Tang W. Challenging the rationale of three sequential shocks for defibrillation. Resuscitation 2006; 69(1):23-27.

Fang X, Tang W, Sun S, Wang J, Huang L, Weil MH. The characteristics of postcountershock pulseless electrical activity may indicate the outcome of CPR. Resuscitation 2006; 69:303-309.

Cammarata GA, Weil MH, Sun SJ, Huang L, Fang X, Tang W. Levosimendan improves cardiopulmonary resuscitation and survival by KATP channel activation. J Am Coll Cardiol 2006;47:1083-1085

Tang W, Snyder D, Wang J, Chang D, Huang L, Sun SJ, Weil MH. One-shock versus three-shock defibrillation protocol significantly improves outcome in a porcine model of prolonged cardiac arrest. Circulation 2006; 113:2683-2689

  II Biomedical Engineering Laboratories

Seven projects are active as follows:

The Resuscitation Blanket  (Patent - US 6,360,125)

       A commercially available electricity absorbing material has been identified and tested that meets the entire requirement for protecting the rescuer from electrical shock during defibrillation. The raw materials are manufactured in standard 36 inch wide rolls and can be sized as desired and readily available from the manufacturers listed below.

The Cardiac Arrest Detector (Patent - US 6,821,254).

Hardware design and fabrication for ECG and Impedance measurement with conventional AED defibrillation/ECG electrode pads are completed. Algorithm for parsing respiratory and cardiac impedance signal from composite thoracic impedance signal is completed. Algorithm for distinguishing normal breathing from gasping or choking is ongoing.  

The Chest Compressor (MCC) (Patent - US 7,060,041 B! 6/13/2006 )

       An engineering prototype has been fabricated and its performance has been compared to industry standard, Michigan Instrument’s “Thumper”® on animal experiments. Hemodynamic results of the MCC are equivalent to those of the Thumper®.

The most significant attribute of the MCC is its portability. The MCC (5 pounds) is lighter than the Thumper® (32 pounds) and lower in height (MCC = 9 cm and Thumper® = 68 cm). This is accomplished by using a telescoping piston to minimize the height without sacrificing the depth of compression. A torso restraint replaces a base board for support.

We are in the process of obtaining manufacturing quotations for fabricating sub-assemblies such as cylinders, pistons and manifolds for at least 5 units for clinical evaluation.

The Rhythm Identifier (Patent - US 7,039,457 B2 5/2/2006 )

An algorithm for discriminating between organized and disorganized rhythms during uninterrupted chest compression has been developed and evaluated on recorded patient data. Refinement of the algorithm will include capability for determining heart rate and when an organized rhythm is recognized during uninterrupted compression. Preliminary results indicate that outcome of CPR will be greatly improved when chest compression need not be interrupted for analysis of the electrocardiogram. It would enhance prompting of automated defibrillators (AEDs). for more effective intervention.

The Low Profile Chest Compressor (Provisional Patent applied for 3/23/2006 )

A low profile chest compressor implements the concept of an “inflatable balloon” for direct chest compression and has been fabricated. The “inflatable balloon” approach contrasts with the majority of existing devices that rely on “piston” driven method for chest compressor including The Institute’s MCC. Initial bench testing suggests that the “inflatable balloon” has a high probability that its performance may be equivalent to that of the Michigan “Thumper®”.  

The advantage of this method is that there would be further reduction in weight and height but much lower manufacturing cost of the “inflatable balloon” as compared to a cylinder/piston combination.

The Resuscitation Box

The resuscitation box integrates algorithms for rhythm identification (QRSID), AMSA for optimal timing of defibrillation during uninterrupted compression, thoracic impedance measurements (CAD) for more rapid diagnosis of the presence or absence of the heartbeat and breathing and for prompting a provider for prioritizing and sequencing of interventions. 

Hardware for ECG and thoracic impedance measurements including data acquisition has been fabricated. Data acquisition software including integration of the QRSID, AMSA and CAD algorithms has been implemented.  Real time evaluation of the Resuscitation Box is ongoing in the Experimental Laboratories. The prompting algorithm continues to evolve. Refinement of the system is ongoing.   

The Vascular Interface

A device for facilitating the administration of fluids and medication is presently in development especially for use during transport and in intensive care units. The system will be capable of multiple infusions of fluids or medication through a single vascular site. The system provides for a combination of up to four medications and/or fluids. Intelligence provides for automatic control of rate and volume of fluids or medication. The delivery system is based on The Institute’s patented Vascular Interface (Patent No. 4,638,811) and Closely Controllable Intravenous Injection System (Patent No. 4,345,594).

GRANTS

American Heart Association

1.         Cardiac Arrest Detector 1/1/2003 – 12/31/2005

Principal Investigator: Max  H. Weil MD. Ph.D.

PATENTS

Awarded: US 7,039,457 ( May 2, 2006 ) Rhythm identification in compression corrupted ECG signal

Notice of allowance: Chest Compressor ( Jan. 31, 2006 )

Pending:

1.    Light Weight Chest Compressor (Filing Date – Feb 8, 2005 )

2.    Low Profile Chest Compressor – (Provisional application – March 23, 2006 )

PUBLICATIONS

1.    AUTOMATED RHYTHM IDENTIFICATION TO GUIDE DEFIBRILLATION WITHOUT INTERRUPTING CPR:  Yongqin Li  et al

2.    AUTOMATED DETECTION OF BREATHING AND PULSE PRESSURE DURING CARDIAC ARREST:  Yongqin Li  et al

The following paper is in final editing preparation:

  III Community Resuscitation Programs

Cardiac arrest strikes without warning and knows no boundaries.  Every year more than 350,000 U. S. fall residents fall victim to sudden cardiac arrest outside of the hospital, including more than 5,000 teenagers.  Unfortunately, more than 95% of these cardiac arrest victims die before reaching the hospital. That equates to about 917 victims each day.  Working together there is something communities can do to increase  chances of survival of such a deadly attack. Las Vegas casinos boast save rates as high as 60%. Seattle reports survivability rates of 30%.  The common denominator of such is quick action by bystanders who witness the event.  Knowing how to recognize when cardiac arrest strikes, knowing how to access the Emergency Medical System, initiating early CPR and, when available, utilize the Automated External Defibrillator (AED).  Victims of cardiac arrest have only 4-6 minutes before the brain sustains irreversible damage.  For every minute a person is in untreated cardiac arrest the likelihood of survival is diminished by ten percent.  Average EMS response times (fire department and ambulance services) typically exceed the golden window of time.  The only hope is bystander intervention.  Training many thousands of citizens with the capability to perform CPR greatly increases the odds that lives will be saved. 

Our Community Resuscitation Program was initially funded by the Desert Healthcare District with additional grants from the City of Rancho Mirage , City of Indian Wells and Riverside County EMS Agency with the objective of enhancing the save rate for cardiac arrest victims  within the Coachella Valley by 25% over the next 3-4 years.  We are to recruit and train ten percent of the Coachella Valley ’s adult population in CPR. CPR training utilizes the American Heart Association’s NEW self instruction CPR, also named the Anytime® Family & Friends Training Kit.  The instruction kit expedites training. In contrast to the traditional 4 hours, training with comparable retention and such training is accomplished within 30 minutes. Many residents may therefore be more efficiently trained in life saving rescue. Training is provided in both English and Spanish.  When CPR training kits are given to a resident, we ask that they be shared with family members and friends. Thereby the impact of each kit is multiplied. Residents are therefore trained in CPR so that they may have both the mindset and the skills to intervene promptly during those first crucial minutes before emergency services arrive.

We have developed a partnership with school districts, Rotarians and its youth group. Interact, county government, municipalities and senior centers to help us serve as instructor/facilitators of the CPR training sessions.

Method of Training and Program Delivery:

The current training sessions have been streamlined to include an overview of the intent of CPR, acknowledgment of sponsorship, presentation of the kit to attendees, and training using the kit.

A video is included as part of the American Heart Association CPR Anytime® Kit. The instructor/facilitator guides the attendees to open their kits and inflate the manikins which are a major component of the kit. The instructor/facilitator then demonstrates how to perform the ABC’s (Airway, Breathing, Chest Compression) as mandated by the Heart Association Guidelines and in accord with the Heart Association’s “Chain of Survival” CPR techniques are then exercised by the students. Appropriate performance of the chest compressions and live saving breaths are cconfirmed by the instructors. The attendees then take the kits home with a serious request that they again practice the CPR techniques after they have viewed the VCR or DVD that is supplied to them as part of the take-home kit. A lively question and answer session invariably follows. Instruction requires approximately 30 minutes and the question and answer session between 10 and 15 minutes for a maximum of 45 minutes.

These training sessions are held on diverse sites including homeowner club houses, churches, synagogues, schools, recreation centers, senior centers, medical facilities, larger businesses, malls/shopping centers, chambers of commerce, and government facilities. In addition, a regularly scheduled session is held at the Institute’s Education Center every Tuesday at 11am .

We also support and coordinate placement of automated external defibrillators (AEDs) in public locations within the Coachella Valley .  The Institute serves as medical oversight for those locations with respect to resuscitation. We inspect and upgrade existing AEDs as requested and assist those who seek to purchase equipment including AEDs.

The Institute also organizes traditional CPR, AED and first aid training courses for a moderate fee for health workers at the Institute as a service to the community.  We will soon institute Advanced Life Support (ALS) and Pediatrics Advanced Life Support (PALS) training for health professionals. We have collaborated with the San Francisco Paramedics Association to facilitate more advanced programs for the Institute’s Training Center . We believe that the benefit of such a training facility in the Coachella Valley is persuasive and that such may be financially self-sustaining.

Funding

We acknowledge the sponsorship and financial support of the Desert Healthcare District, the City of Rancho Mirage , the City of Indian Wells , the County of Riverside , and private donations.