Gliflozins and a method for their delivery during resuscitation from cardiac arrest to improve survival outcomes
Inventors
Gazmuri, Raúl J. • Radhakrishnan, Jeejabai • Aiello, Salvatore
Assignees
United States Represented By Department Of Veterans Affairs Washington DC AS • Rosalind Franklin University of Medicine and Science • US Department of Veterans Affairs
Publication Number
US-11786540-B2
Publication Date
2023-10-17
Expiration Date
2041-07-09
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Abstract
A method of performing cardiopulmonary resuscitation on a mammalian subject including the step of delivering an effective amount of a gliflozin solution during cardiac resuscitation through an intravenous or intraosseous route.
Core Innovation
The invention describes a method of performing cardiopulmonary resuscitation (CPR) in a mammalian subject by administering an effective amount of a gliflozin solution during cardiac resuscitation, specifically via intravenous or intraosseous injection. The method aims to deliver gliflozin, such as empagliflozin (EMPA), concurrent with cardiac resuscitation efforts, whether mechanical, electrical, chemical, or a combination thereof. The innovation includes both bolus administration and, if needed, continuous infusion of gliflozin during CPR.
The problem addressed is the limited improvement in survival outcomes from cardiac arrest using conventional resuscitation techniques. Current therapies provide insufficient protection against myocardial injury resulting from cardiac arrest and subsequent reperfusion injury during resuscitation. Prior studies showed gliflozins, primarily used for diabetes mellitus due to their SGLT2 inhibitory action, also reduce cardiovascular events and improve myocardial outcomes in various models, but their use during active cardiac resuscitation had not been investigated for myocardial protection akin to NHE-1 inhibitors.
The core innovation is based on the finding that administering gliflozin solutions during cardiac resuscitation ameliorates myocardial abnormalities caused by both cardiac arrest and resuscitation efforts, improving post-resuscitation cardiac function and hemodynamic parameters. Experimental studies in animal models demonstrated that gliflozin administration during resuscitation led to improved cardiac index, left ventricular function, and coronary blood flow, without significant adverse effects, indicating the invention’s potential for improving resuscitation outcomes in both preclinical and clinical settings.
Claims Coverage
There is one independent claim providing the core inventive feature of the method for resuscitation using gliflozin.
Administration of gliflozin solution during cardiopulmonary resuscitation
A method of cardiopulmonary resuscitation on a mammalian subject comprising: - Administering an effective amount of a gliflozin solution to the subject concurrent with cardiac resuscitation. Additional dependent claims specify: - The gliflozin can be empagliflozin. - Applicable to human and other mammalian subjects. - Cardiac resuscitation can include mechanical, electrical, chemical, or combinations. - Cardiopulmonary resuscitation can be closed-chest or open-chest. - Administration routes include intravenous or intraosseous delivery. - Administration can be as a bolus, followed by continuous parenteral infusion if desired. - The method is applicable regardless of cardiac arrest type, including ventricular fibrillation, pulseless ventricular tachycardia, pulseless electrical activity, or asystole.
The inventive feature covered by the claims is the concurrent administration of a gliflozin solution during cardiac resuscitation to improve outcomes, regardless of the clinical or procedural specifics of the resuscitation method, targeted arrhythmia, or gliflozin compound chosen.
Stated Advantages
Administration of gliflozins during cardiac resuscitation attenuates myocardial abnormalities caused by cardiac arrest and resuscitation efforts, leading to improved resuscitation and post-resuscitation hemodynamic outcomes.
Gliflozin administration results in amelioration of post-resuscitation myocardial dysfunction and improved hemodynamic function, such as higher cardiac index, stroke volume index, and coronary blood flow.
Treatment with gliflozins during resuscitation can achieve these effects using lower doses of vasopressors like norepinephrine, suggesting enhanced myocardial protection.
The method offers potential for translation to clinical resuscitation, providing an improved therapeutic approach to address currently disappointing survival outcomes after cardiac arrest.
Documented Applications
Method for treating mammalian subjects, including human patients, in cardiac arrest by administering an effective amount of a gliflozin solution concurrent with cardiac resuscitation.
Kit for administering gliflozin solution to human patients in cardiac arrest during cardiopulmonary resuscitation, including pre-filled syringes or IV bags for intravenous or intraosseous injection.
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