Cardium's Innercool Therapies Unit Announces Publication of Positive Effects of Early and Rapid Hypothermia Following Heart Attack

   The study, conducted by a team of interventional cardiologists at the Lund University Hospital, Sweden, evaluated the effect of early and rapid cooling induced by a combination of cold saline infusion along with InnerCool's endovascular Celsius Control(TM) System, before or immediately after reperfusion when coronary blood flow was restored in the heart in a porcine heart attack model. Results from this study demonstrated that rapid cooling (to <35 degrees Celsius) prior to reperfusion significantly reduced overall myocardial infarct size (a measure of tissue damage in the heart) and protected the heart from other injury.

   "We believe that InnerCool's low-profile, high-performance endovascular cooling system has the capacity to achieve rapid cooling within the short time available before coronary reperfusion must occur in order to potentially limit the amount of damage due to reperfusion injury following heart attack," stated Christopher J. Reinhard, Chairman and Chief Executive Officer of Cardium Therapeutics and InnerCool Therapies. "To achieve cooling rates that were shown in the study to be beneficial requires the ability to lower core body temperature to 35 degrees Celsius or less within a time window as short as about 15 minutes while patients are awake. InnerCool's Accutrol catheter not only provides rapid cooling but the unique integrated temperature sensor enables fast and precise feedback of core body temperature, compared to delayed temperature feedback using peripheral temperature probes. Speed and precision are performance features that can be especially critical in acute care settings such as those following a heart attack."

   Rapid & Early Cooling Heart Attack Preclinical Study Results

   This study was designed to further investigate the therapeutic potential of early and rapid hypothermia to preserve heart tissue following a heart attack. Using a closed-chest porcine heart attack model in which the coronary artery supplying the heart muscle was initially blocked and later reopened, as occurs in patients after a heart attack or acute myocardial infarction (MI), the investigators evaluated the effects of rapid cooling to a target temperature of 33 degrees Celsius to 35 degrees Celsius on myocardial infarct size as assessed by cardiac magnetic resonance imaging (MRI). Rapid hypothermia, induced by the infusion of one liter of cold saline in combination with InnerCool's endovascular catheter-based temperature modulation system, initiated either prior to or after restoration of blood flow (reperfusion), was compared to a normal core body temperature of 38 degrees Celsius throughout the procedure.

   The data showed that early rapid cooling substantially reduced the damage to heart muscle that typically follows a heart attack and reperfusion. In particular, cooling prior to reperfusion reduced overall myocardial infarct size by 43% compared to hypothermia after reperfusion (p<0.05), and by 39% compared to normothermia (p<0.05). In addition, hypothermia initiated either before or after reperfusion also significantly reduced impairment of blood flow in the coronary microvasculature (microvascular obstruction) that may be associated with reperfusion injury.

   The results from this study are consistent with clinical findings from the Intravascular Cooling Adjunctive to Percutaneous Coronary Intervention (ICE-IT) study, a 228 patient study sponsored by InnerCool, in which infarct size was reduced (43% in anterior MIs and 39% in inferior MIs) in patients who were cooled rapidly to <35 degrees Celsius prior to reperfusion with an endovascular temperature modulation system as an adjunct to angioplasty and stent procedures. The current study further confirms this correlation between rapid cooling to a body core temperature of less than 35 degrees Celsius prior to reperfusion and reduction in infarct size.

   "Preclinical and preliminary clinical data suggest that rapid patient cooling using intravenous cold saline in combination with endovascular hypothermia can be initiated without causing delay of reperfusion therapy and may have the potential to enable interventional cardiologists to dramatically reduce heart tissue damage following a heart attack," stated David Erlinge, M.D., Ph.D. of the Lund University Cardiology Center.

   New Clinical Heart Attack Study Underway

   Based on these findings, InnerCool is sponsoring a study on the use of early and rapid cooling of patients with myocardial infarction (MI or heart attack), which is being co-sponsored and conducted by the interventional cardiology center at Lund University Hospital, Sweden. The ongoing clinical study, called RAPID MI-ICE (Rapid Intravascular Cooling in Myocardial Infarction as Adjunctive to Percutaneous Coronary Intervention), is expected to enroll approximately 20 patients who present within six hours of their heart attack and require angioplasty and stent procedures in order to restore blood flow to the heart. Eligible patients will be randomized to one of two treatment protocols, and the effects on heart tissue damage will be compared. Patients randomized to the cooling arm (hypothermia) will be infused with 1 liter of iced saline in addition to endovascular cooling with the InnerCool Accutrol(TM) catheter, which contains an integrated temperature sensor that accurately measures the patient's core body temperature. Patients assigned to the normothermia arm will receive routine standard of care without induced hypothermia. The trial will employ cardiac MRI to provide an assessment of the damage to the heart, as measured by infarct size, within days of the heart attack. Additional details of the study can be found at http://www.clinicaltrials.gov/.

   Myocardial Reperfusion Injury

   The American Heart Association estimates that the annual incidence of myocardial infarction (MI) is 600,000 new attacks and 320,000 recurrent attacks. After an acute myocardial infarction, early and successful myocardial reperfusion with the use of thrombolytic therapy such as tissue plasminogen activator (tPA) or primary percutaneous coronary intervention (PCI) is the most effective strategy for reducing the size of a myocardial infarct and other complications to lead to improved clinical outcome. Reperfusion, the process of restoring blood flow to the ischemic myocardium, can itself lead to additional injury beyond that caused by ischemia due to coronary blockage. This phenomenon, termed myocardial reperfusion injury, can reduce the beneficial effects of myocardial reperfusion. Preclinical studies in models of acute myocardial infarction suggest that reperfusion injury accounts for up to 50% of the final infarct size.

   Reperfusion injury refers to damage to tissue caused when blood supply returns to the tissue after a period of ischemia such as during blockage of the coronary arteries. The temporary absence of oxygen and nutrients from blood creates a condition in which the restoration of blood flow results in inflammation and damage through the induction of oxidative stress, caused by the production of reactive oxygen species. Reperfusion injury is due in part to the inflammatory response of damaged tissues. White blood cells carried to the area by the newly returning blood release a variety of inflammatory factors in response to tissue damage. The restored blood flow reintroduces oxygen within cells that damages cellular proteins, DNA, and the cell's plasma membrane. Damage to the cell's membrane may in turn cause the release of more inflammatory substances that may turn on apoptosis, or programmed cell death, involving a series of biochemical events that lead to a variety of cellular changes, including cell shrinkage, chromatin condensation, and chromosomal DNA fragmentation. White blood cells may also build up in small capillaries, obstructing them and leading to more ischemia. In its most extreme, myocardial reperfusion injury can result in the death of cardiac tissue that was viable immediately before the restoration of blood flow and, as a consequence, increased myocardial infarct size. Reperfusion injury is associated with adverse clinical outcomes after a heart attack and may contribute to patient mortality despite successful reperfusion.

   Keywords: Angiology, Angioplasty, BioMed Central Ltd., Biotechnology Business, Biotechnology Company, Blood Transfusion, Cardiology, Cardiovascular, Clinical Trial Research, Clinical Trials, Coronary Artery, Heart Attack, Hypothermia, Intravascular, Ischemia-Reperfusion Injury, Magnetic Resonance, Medical Device, Myocardial Infarction, Perfusion, Pre-Trials Research, Reperfusion, Therapy, Transfusion Medicine, Treatment, Cardium Therapeutics Inc.

   This article was prepared by Biotech Business Week editors from staff and other reports. Copyright 2008, Biotech Business Week via NewsRx.com.

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