Constructs, Agents, and Methods for Facilitated Ablation of Cardiac Tissue

• US 20190328877A1
• Filed: 05/04/2017
• Published: 10/31/2019
• Est. Priority Date: 05/04/2016
• Status: Active Grant

• Current Assignee: Duy Nguyen, William Sauer
• Original Assignee: The Board of Regents of the University of Colorado (University of Colorado System)
• Inventors: Sauer, William, Nguyen, Duy
• Granted Patent: US 11,458,200 B2
• Time in Patent Office: Days
• CPC Class Codes: A61B 18/02 by cooling, e.g. cryogenic techniques devices for cooling specific reflex points of the body within cell-life limits A61H39/06
• CPC Class Codes: A61B 18/1492 having a flexible, catheter-like structure, e.g. for heart ablation A61B18/1477 takes precedence
• CPC Class Codes: A61B 2018/00351 Heart
• CPC Class Codes: A61B 2018/00577 Ablation
• CPC Class Codes: A61B 2018/1472 for use with liquid electrolyte, e.g. virtual electrodes
• CPC Class Codes: A61B 34/73 Manipulators for magnetic surgery
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/352 condensed with carbocyclic rings, e.g. methantheline cannabinoids A61K31/658
• CPC Class Codes: A61K 31/366 having six-membered rings, e.g. delta-lactones
• CPC Class Codes: A61K 33/244 Lanthanides; Compounds thereof medicinal preparations containing radioactive lanthanides for use in therapy or testing in vivo A61K51/00
• CPC Class Codes: A61K 33/26 Iron; Compounds thereof
• CPC Class Codes: A61K 41/00 Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
• CPC Class Codes: A61K 41/0028 Disruption, e.g. by heat or ultrasounds, sonophysical or sonochemical activation, e.g. thermosensitive or heat-sensitive liposomes, disruption of calculi with a medicinal preparation and ultrasounds
• CPC Class Codes: A61K 41/0038 Radiosensitizing, i.e. administration of pharmaceutical agents that enhance the effect of radiotherapy radiotherapy per se A61N5/10
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 49/1818 particles, e.g. uncoated or non-functionalised microparticles or nanoparticles
• CPC Class Codes: A61K 9/127 Liposomes
• CPC Class Codes: A61K 9/5115 Inorganic compounds
• CPC Class Codes: A61N 2/002 in combination with another treatment
• CPC Class Codes: A61N 7/00 Ultrasound therapy lithotripsy A61B17/22, A61B17/225; massage using supersonic vibration A61H23/00 ; using ultrasound for introducing media into the body A61M37/0092
• CPC Class Codes: A61P 41/00 : Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution

Abstract

The presently disclosed subject matter provides agents, compositions, and methods for augmenting ablation of a target tissue in a subject in need thereof, for example, using agents that modulate protective and/or reparative cellular processes induced in target tissue by application of ablative energy to the target tissue to sensitize the target tissue to the ablative energy. The presently disclosed subject matter further provides methods for augmenting radiofrequency ablation of cardiac tissue, for example, by applying radiofrequency energy to ablate cardiac tissue in the presence of metallic nanoparticles magnetically guided to the cardiac tissue.

Claims

1. A method for augmenting ablation of a target tissue in a subject in need thereof, the method comprising:

(a) administering to a subject in need thereof an effective amount of an agent that modulates a protective and/or reparative cellular process induced in a target tissue by application of an ablative energy to the target tissue; and

(b) applying an ablative energy to the target tissue in the subject, wherein the agent modulates the protective and/or reparative cellular process induced in the target tissue by application of the ablative energy to the target tissue, and augmenting ablation of the target tissue in the subject.

2. The method of claim 1, wherein the protective and/or reparative cellular process induced in the target tissue comprises a cold shock response process modulated by a cold shock protein, the agent decreases the expression level and/or activity of a cold shock protein in the target tissue, and the ablative energy is a cryothermal energy.

3. The method of claim 1, wherein the protective and/or reparative cellular process induced in the target tissue comprises a heat shock response process modulated by a heat shock protein, the agent decreases the expression level and/or activity of a heat shock protein in the target tissue, and the ablative energy is a thermal energy, wherein the thermal energy is optionally selected from the group consisting of radiofrequency energy, microwave energy, ultrasound, and electromagnetic energy.

11. The method of claim 3, wherein the heat shock protein is selected from the group consisting of heat shock protein 60 (Hsp60), heat shock protein 70 (Hsp70), and heat shock protein 90 (Hsp90).

12. The method of claim 3, wherein the agent that decreases the expression level and/or activity of a heat shock protein is a heat shock protein inhibitor.

13. The method of claim 12, wherein the heat shock protein inhibitor is selected from the group consisting of quercetin, 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) and celestrol.

22. The method of claim 1, wherein the subject:

(i) has a pacemaker; and

/or

(ii) has an implantable cardiac defibrillator; and

/or

(iii) is selected for treatment of a cardiac arrhythmia selected from the group consisting of atrial fibrillation, premature atrial contractions, wandering atrial pacemaker, multifocal atrial tachycardia, atrial flutter, supraventricular tachycardia, atrial tachycardia, atrioventricular nodal reentrant tachycardia, atrioventricular reciprocating tachycardia, junctional rhythm, junctional tachycardia, premature junctional contraction, premature ventricular contractions, accelerated idioventricular rhythm, monomorphic ventricular tachycardia, polymorphic ventricular tachycardia, ventricular fibrillation, heart blocks, long QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, arrhythmogenic right ventricular dysplasia, dilated cardiomyopathy, cardiomyopathy due to prior myocardial infarction, and abnormal Purkinje potentials leading to ventricular arrhythmias including electrical storms; and

combinations thereof.

25. A method for treating a cardiac arrhythmia in a subject in need thereof, the method comprising performing a method according to claim 1.

28. The method of claim 25, further comprising administering to the subject an effective amount of at least one antiarrhythmic agents, at least one calcium channel blocker, at least one beta-blocker, at least one anticoagulant, at least one anti-inflammatory agent, at least one anti-fibrotic agent, and combinations thereof.

4. A method for augmenting radiofrequency ablation of a target cardiac tissue in a subject in need thereof, the method comprising:

(a) administering an effective amount of a composition comprising metallic nanoparticles to a subject;

(b) using a magnetic field to guide the metallic nanoparticles to a target cardiac tissue to be ablated in the subject; and

(c) applying a radiofrequency energy to the target cardiac tissue in the presence of the metallic nanoparticles guided to the target cardiac tissue, thereby augmenting radiofrequency ablation of the target cardiac tissue in the subject.

5. The method of claim 4, wherein the metallic nanoparticles are selected from the group consisting of copper nanoparticles, gadolinium nanoparticles, gold nanoparticles, iron nanoparticles, titanium nanoparticles, and combinations thereof.

8. The method of claim 4, wherein the metallic nanoparticles are encapsulated by liposomes.

10. The method of claim 4, wherein the composition further comprises an agent that decreases the expression level and/or activity of a heat shock protein.

14. The method of claim 4, wherein the magnetic field is generated by a magnet that exhibits a pull force of between 0.001 and 1000 pounds.

15. The method of claim 14, wherein the magnet is placed adjacent to the target cardiac tissue to be ablated.

18. The method of claim 4, wherein the radiofrequency energy is applied using an ablation catheter.

19. The method of claim 18, wherein the ablation catheter comprises a magnetic tip.

20. The method of claim 19, wherein the magnetic tip of the ablation catheter comprises an electromagnet that is used to guide the metallic nanoparticles to the target cardiac tissue to be ablated.

23. The method of claim 4, further comprising imaging the metallic nanoparticles in the subject.

24. The method of claim 4, further comprising administering an effective amount of at least one prophylactic agent to the subject to reduce the risk and/or severity of an adverse reaction to the composition administered to the subject.

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