Facilitation of resuscitation from cardiac arrest by erythropoietin
Inventors
Assignees
Rosalind Franklin University of Medicine and Science • US Department of Veterans Affairs
Publication Number
US-8067366-B2
Publication Date
2011-11-29
Expiration Date
2026-07-20
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Abstract
The present invention relates generally to the use of erythropoietin (EPO) to facilitate resuscitation from cardiac arrest. For a mammalian subject suffering from cardiac arrest, concurrent administration of EPO with resuscitation after the onset of ventricular fibrillation facilitates the resuscitation. Administration of EPO serves to attenuate myocardial abnormalities caused by cardiac arrest and the resuscitation efforts and favor improved resuscitation outcomes. The main effect of EPO that facilitates resuscitation is the preservation of left ventricular myocardial distensibility leading to improve left ventricular preload and the amount of blood ejected by chest compression. This effect enables higher coronary perfusion pressures to be generated resulting in a higher rate of return of spontaneous circulation and higher survival rates. The very same effect enables the return of spontaneous circulation to occur faster reducing the time a human subject is in cardiac arrest. These effects lead to a higher number of cardiac arrest victims to survive and to do so with intact neurological function in most of the survivors.
Core Innovation
The invention relates to the use of erythropoietin (EPO) to facilitate resuscitation from cardiac arrest in a mammalian subject. Administration of EPO concurrent with resuscitation but after the onset of cardiac arrest preserves left ventricular myocardial distensibility, enabling more hemodynamically effective chest compression. This leads to increased coronary perfusion pressure and higher myocardial blood flow, resulting in higher rates and faster return of spontaneous circulation, thus shortening the duration of resuscitation.
The problem addressed is the low survival rate of cardiac arrest victims despite emergency medical services' initial success in restoring cardiac activity. Severe tissue injury due to global myocardial ischemia and reperfusion injury compromises the capability to reestablish cardiac activity. Post-cardiac arrest myocardial abnormalities such as loss of left ventricular distensibility reduce the efficacy of chest compression, further hindering resuscitation and increasing mortality. Existing interventions have not sufficiently prevented these myocardial dysfunctions or improved neurologically intact survival.
The invention demonstrates that administering EPO during resuscitation attenuates these myocardial abnormalities, preserves left ventricular compliance, enhances hemodynamic efficacy of chest compression, and improves post-resuscitation myocardial function. These effects increase the rate and speed of return of spontaneous circulation and improve survival rates, including neurologically intact survival. The invention also notes that EPO’s beneficial effects increase with the severity of ischemic injury from cardiac arrest.
Claims Coverage
The patent includes two independent claims describing methods for facilitating cardiac resuscitation and improving hemodynamic efficacy during cardiopulmonary resuscitation using erythropoietin.
Administration of EPO concurrent with resuscitation after cardiac arrest onset to improve resuscitation outcomes
A method for facilitating cardiac resuscitation in a mammalian subject suffering from cardiac arrest by administering an effective amount of erythropoietin (wildtype or recombinant) concurrent with resuscitation and after cardiac arrest onset. This administration increases the rate of return of spontaneous circulation and shortens the duration of resuscitation compared with resuscitation without EPO.
Improving hemodynamic efficacy of chest compression by preserving left ventricular myocardial distensibility with EPO
A method to improve the hemodynamic efficacy of chest compression during cardiopulmonary resuscitation by administering an effective amount of erythropoietin (wildtype or recombinant) concurrent with cardiac resuscitation. This preserves left ventricular myocardial distensibility, leading to increased blood flow generated per chest compression as evidenced by increased coronary perfusion pressure to compression depth ratio compared to subjects resuscitated without EPO.
The claims cover methods to facilitate cardiac resuscitation and improve mechanical efficacy of chest compressions using erythropoietin administered concurrent with resuscitation after cardiac arrest onset, enhancing rates and speed of return of spontaneous circulation and survival outcomes.
Stated Advantages
Administration of erythropoietin during cardiac resuscitation preserves left ventricular myocardial distensibility, leading to more hemodynamically effective chest compression.
EPO treatment increases coronary perfusion pressure, resulting in higher rates and faster return of spontaneous circulation.
EPO administration shortens the duration of resuscitation and reduces the time a subject remains in cardiac arrest.
Improved survival rates with mostly intact neurological function in survivors receiving EPO treatment during resuscitation.
Documented Applications
Use of erythropoietin to facilitate resuscitation in mammalian subjects, including humans, suffering from cardiac arrest precipitated by ventricular fibrillation, pulseless electrical activity, or asystole.
Administration of EPO concurrent with various forms of cardiac resuscitation methods including manual, mechanical, electrical, chemical, or combinations, with either closed-chest or open-chest procedures.
Use of EPO administered by routes including intravenous, intraarterial, intraperitoneal, intracardiac, and intraosseous, in bolus or continuous dosing to improve resuscitation effectiveness and survival outcomes in cardiac arrest.
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