No assignee for this patent application has been made.
Reporters obtained the following quote from the background information supplied by the inventors: "Anatomy of the Heart
"The heart is surrounded by the pericardium, which is a sac consisting of two layers of tissue (fibrous pericardium and parietal layer of the serous pericardium). The pericardial space (between the pericardium and the heart) contains some pericardial fluid that bathes the outer tissue heart in a stable osmotic and electrolytic environment.
"The heart tissue itself consists of four layers; the visceral layer of the serous pericardium, an adipose layer containing embedded arteries and veins, the myocardium, which is the major, muscular layer of the heart, and the inner epithelial layer, called the endocardium.
"The coronary arteries are the first vessels to branch off the aorta. Through these arteries, the heart receives (at rest) about 5% of the cardiac output. Coronary blood flow is governed by a pressure gradient and by resistance of the vessels.
"Ischemic Disease of the Heart
"Myocardial infarction is a common presentation of ischemic heart disease/coronary artery disease. The
"Rates of death from ischemic heart disease have slowed or declined in most high income countries, although cardiovascular disease still accounted for 1 in 3 of all deaths in the
"In contrast, ischemic heart disease is becoming a more common cause of death in the developing world. For example in
"Globally, it is predicted that disability adjusted life years (DALYs) lost to ischemic heart disease will account for 5.5% of total DALYs in 2030, making it the second most important cause of disability (after unipolar depressive disorder), as well as the leading cause of death by this date.
"A myocardial infarction (a common presentation of ischemic heart disease) often occurs when a coronary artery becomes occluded and can no longer supply blood to the myocardial tissue. The consequences of a myocardial infarction are often severe and disabling. When a myocardial infarction occurs, the myocardial tissue that is no longer receiving adequate blood flow dies and is replaced with scar tissue. The infarct (or infracted) tissue cannot contract during systole and can actually undergo lengthening in systole, resulting in immediate depression in ventricular function. The abnormal motion of the infarct tissue can cause delayed or abnormal conduction of electrical activity to the still surviving peri-infarct tissue (tissue at the junction between the normal tissue and the infarcted tissue) and also places extra structural stress on the peri-infarct tissue.
"Thus, in addition to immediate hemodynamic effects, the infarct tissue and the myocardium tissue undergo three major processes: infarct expansion, infarct extension, and chamber remodeling. These factors, individually and in combination, contribute to the eventual dysfunction observed in the cardiovascular tissue remote from the site of the infarction.
"Infarct expansion is a fixed, permanent, disproportionate regional thinning and dilatation of tissue within the infarct zone. Infarct expansion occurs early after a myocardial infarction. The mechanism of infarct expansion is slippage of the tissue layers.
"Infarct extension is additional myocardial necrosis following myocardial infarction. Infarct extension results in an increase in total mass of infarct tissue. The additional infarct tissue can also undergo infarct expansion.
"Infarct extension occurs days after a myocardial infarction. The mechanism for infarct extension is believed to be an imbalance in the blood supply to the peri-infarct tissue versus the increased oxygen demands on the tissue.
"Remodeling is usually the progressive enlargement of the ventricle accompanied by a depression of ventricular function. Myocyte function in the cardiac tissue remote from the initial myocardial infarction becomes depressed. Remodeling occurs weeks to years after myocardial infarction.
"Such remodeling usually occurs on the left side of the heart. Where remodeling does occur on the right side of the heart, it can generally be linked to remodeling (or some other negative event) on the left side of the heart. Remodeling can occur independently in the right heart, albeit less often than the left.
"There are many potential mechanisms for remodeling, but it is generally believed that the high stress on peri-infarct tissue plays an important role. Due to a variety of factors, such as altered geometry, wall stresses are much higher than normal in the cardiovascular tissue surrounding the infarction.
"The processes associated with infarct expansion and remodeling are believed to be the result of high stresses exerted at the junction between the infarct tissue and the normal cardiovascular tissue (i.e., the peri-infarct region). In the absence of intervention, these high stresses will eventually kill or severely depress cell function in adjacent cells. As a result, the peri-infarct region will therefore grow outwardly from the original infarct site over time. This resulting wave of dysfunctional tissue spreading out from the original myocardial infarct region greatly exacerbates the nature of the disease and can often progress into advanced stages of heart failure.
"Various methods for treating a myocardial infarction are often employed. Such methods include stabilizing the hemodynamics associated with a myocardial infarction via systemic delivery of various pharmacological agents and restoring the patency of occluded vessels via thrombolytic therapy or angioplasty and stents.
"Several additional methods for treating a myocardial infarction are directed to re-establishing blood flow to the ischemic area through stimulation of angiogenesis. Re-establishing blood flow at the ischemic area can, and in many instances will, reduce symptoms associated with a myocardial infarction and/or improve cardiac function.
"Some methods for re-establishing blood flow and rehabilitating the heart involve invasive surgery, such as bypass surgery or angioplasty. Other methods employ lasers to bore holes through the infarctions and ischemic area(s) to promote blood flow. As one can readily appreciate, there are numerous incumbent risks associated with the noted methods.
"A further method for treating a myocardial infarction is the 'direct' or selective delivery of pharmacological agents to the infarction and/or ischemic area (i.e. effected or damaged cardiovascular tissue).
"Various surgical approaches have also been employed to treat a myocardial infarction, including approaches to exclude, isolate, or remove the infarct region, and surround the heart, or a significant portion thereof, with a jacket or mesh type prosthesis to prevent remodeling.
"The conventional methods and systems for treating damaged or diseased cardiovascular structures and tissue, including infarct tissue, are discussed in detail below.
"Direct Delivery of Pharmacological Agents to Cardiovascular Tissue
"As indicated above, one commonly employed method of treating a myocardial infarction is the direct or selective delivery of pharmacological agents to the infarction and/or ischemic area. Direct delivery of a pharmacological agent to the effected cardiovascular tissue is often preferred over the systemic delivery for several reasons. A primary reason is that a substantially greater concentration of such agents that can be delivered directly into the effected cardiovascular tissue, compared with the dilute concentrations possible through systemic delivery. Another reason is the risk of systemic toxicity which can, and in many instances will, occur with doses of pharmacological agents that are typically required to achieve desired drug concentrations in the effected cardiovascular tissue.
"One common method of delivering pharmacological agents directly to effected or damaged myocardial tissue, e.g., infarct region, comprises advancing a catheter through the vasculature and into the heart to inject the agents directly into the effected cardiovascular tissue from within the heart.
"Another method of delivering pharmacological agents directly to effected cardiovascular tissue comprises epicardial injection into the tissue during an open chest procedure. The agents that can be, and have been, administered to the effected cardiovascular tissue include various pharmacological agents, such as antithrombotic agents, e.g., heparin, hirudin, and ticlopidine.
"Various controlled release agent delivery methods and systems have also been disclosed. Folkman, et al. in Drug Pacemakers in the Treatment of Heart Block, New York Acad. Sci., p. 857 (
"Labhasetwar, et al. in
"U.S. Pat. No. 5,154,182 also describes an implantable patch electrode that is surgically attached to the epicardium and capable of delivering a pharmacological agent.
"Various other methods and devices have been developed for delivering pharmacological agents directly to cardiovascular tissue. Illustrative are the myocardial implants disclosed in U.S. Pat. Nos. 6,258,119 and 6,053,924.
"In U.S. Pat. No. 6,258,119 a myocardial implant for insertion into a heart wall for trans myocardial revascularization (TMR) of the heart wall is disclosed. The implant provides a means to promote angiogenesis, and has a flexible, elongated body that contains a cavity and openings through the flexible, elongated body from the cavity. The TMR implant includes a coaxial anchoring element integrally formed at one end for securing the TMR implant in the heart wall.
"U.S. Pat. No. 6,053,924 also describes a medical device for performing TMR in a human heart. The device consists of a myocardial implant and a directable intracardiac catheter for delivery into a heart wall.
"Various mechanical means have also been employed to delivery one or more pharmacological agents directly to cardiovascular tissue. In U.S. Pat. No. 5,551,427 an implantable helical injection needle, which can be screwed into the heart wall and connected to an implanted drug reservoir outside the heart, is disclosed. The implantable system facilitates the delivery of pharmacological agents directly into the wall of the heart acutely by injection from the proximal end, or on an ongoing basis by a proximally located implantable subcutaneous port reservoir, or pumping mechanism.
"The agent delivery can be performed by a number of techniques, among them infusion through a fluid pathway, and delivery from controlled release matrices at a depth within the heart. Controlled release matrices are described as drug polymer composites in which a pharmacological agent is dispersed throughout a pharmacologically inert polymer substrate.
"U.S. Pat. No. 8,027,740 similarly discloses an implantable helical injection needle, which can be screwed into the heart wall and connected to an implanted drug reservoir outside the heart.
"U.S. Pat. No. 6,971,998 discloses an implantable drug-carrying coil or dart, which can be inserted into the center of the myocardium and isolated from the internal chambers of the heart and pericardial space outside the heart. The coil or dart is positioned in the myocardium via a catheter that is navigated through the patient's arteries.
"As also indicated above, various surgical approaches have been employed to treat a myocardial infarction. The surgical approaches include various means to exclude, isolate, or remove the infarct region.
"One surgical approach that has been employed is to apply heat to the infarct region to shrink the infarcted tissue, followed by suturing a patch onto the infarct region.
"Another surgical approach is to surround the heart, or a significant portion thereof, with a jacket or mesh type prosthesis to prevent remodeling. Illustrative are the prostheses disclosed in U.S. Pat. Nos. 6,508,756 and 5,800,528.
"A further surgical approach is to form a reinforcement region proximate infarct tissue. Illustrative is the method disclosed in
"There are various drawbacks and disadvantages associated with the noted methods for treating damaged or diseased cardiovascular structures and tissue; particularly, infarct tissue. A major drawback associated with many, if not all, of the agent delivery systems and methods is that they are devoid of effective means for assuring that a precise dose of a pharmacological agent is delivered to the treatment site.
"A further drawback is that most of the implantable delivery devices include lumens or other components that are constructed from various polymeric materials, such as poly(ethylene terephthalate) (PET). Such components can, and often will, cause irritation and undesirable biologic responses from surrounding biological tissue(s).
"A major drawback associated with surgical approaches for treating damaged or diseased cardiovascular structures and tissue is that the surgical techniques typically require a highly-invasive open chest procedure to access the heart. Such a procedure often poses the risk of infection and carries additional complications, such as instability of the sternum, post-operative bleeding, and mediastinal infection. The thoracic muscle and ribs are also severely traumatized, and the healing process results in an unattractive scar. Post-operatively, most patients endure significant pain and must forego work or strenuous activity for a long recovery period.
"It would thus be desirable to provide effective and accurate means for delivering pharmacological agents directly to cardiovascular tissue to treat a cardiovascular disorder and/or damaged or diseased cardiovascular tissue; particularly, infarct tissue, that substantially reduces or eliminates the noted drawbacks and disadvantages associated with existing means for delivering pharmacological agents to cardiovascular tissue.
"It would also be desirable to provide effecting means for reinforcing the myocardium or a refract region thereof that does not require a highly-invasive open chest procedure.
"It is therefore an object of the present invention to provide intra-myocardial agent delivery systems and methods that provide effective and accurate means for delivering pharmacological agents directly to cardiovascular tissue and/or regions proximate thereto to treat damaged or diseased cardiovascular tissue, such as infarct tissue, that substantially reduce or eliminate the drawbacks and disadvantages associated with existing means for delivering pharmacological agents to cardiovascular tissue.
"It is another object of the present invention to provide intra-myocardial agent delivery systems and methods that can be employed to reinforce the myocardium or a refract region thereof and do not require an open chest procedure for placement proximate the myocardium.
"It is another object of the present invention to provide extracellular matrix (ECM) compositions, which, when delivered to damaged biological tissue; particularly, cardiovascular tissue, induce neovascularization, host tissue proliferation, bioremodeling, and regeneration of cardiovascular tissue and associated structures with site-specific structural and functional properties.
"These and other objects, advantages, and features of the invention will become apparent to those persons skilled in the art upon reading the details of the invention as more fully described below."
In addition to obtaining background information on this patent application, NewsRx editors also obtained the inventor's summary information for this patent application: "The present invention is directed to intra-myocardial agent delivery devices, systems and methods for site specific delivery of pharmacological agents and compositions to damaged and diseased cardiovascular tissue; particularly, myocardial tissue, and means for implanting and using the delivery devices and systems to enable delivery of pharmacological agents and compositions to cardiovascular tissue.
"In some embodiments of the invention, the intra-myocardial agent delivery devices also comprise myocardium reinforcing members.
"Cardiovascular conditions that are amenable to treatment according to the invention include any pathological condition that is amenable to treatment by increasing the number of functional coronary blood vessels, including, without limitation, ischemic heart disease; particularly, myocardial infarction, arrhythmia, cardio-myopathy, coronary angioplasty restenosis, atherosclerosis of a coronary artery, thrombosis, a cardiac condition related to hypertension, cardiac tamponade, and pericardial effusion.
"In a preferred embodiment of the invention, the intra-myocardial agent delivery devices include a central tube and at least one, more preferably, a plurality of agent delivery tubes that are in fluid communication with the central tube.
"According to the invention, the intra-myocardial agent delivery devices of the invention can include any number of agent delivery tubes to, for example, deliver pharmacological agents to the desired number of delivery sites and/or provide the desired degree of reinforcement for the myocardium.
"In a preferred embodiment of the invention, the central tube includes a central lumen that extends through the central tube and is configured to receive and transfer a pharmacological agent or composition therethrough. Each agent delivery tube also includes a central lumen that is similarly configured to facilitate the transfer of a pharmacological agent or composition therethrough.
"In a preferred embodiment of the invention, at least one, more preferably, each agent delivery tube has at least one, more preferably, a plurality of laterally positioned perforations or lumens that facilitate delivery of pharmacological agents and compositions from the delivery tubes to adjacent biological tissue.
"In a preferred embodiment, the agent delivery devices are adapted to delivery at least one pharmacological agent or composition to a biological tissue site, e.g. infarct region, which can comprise, without limitation, antibiotics or antifungal agents, anti-viral agents, anti-pain agents, anesthetics, analgesics, steroidal anti-inflammatories, non-steroidal anti-inflammatories, anti-neoplastics, anti-spasmodics, modulators of cell-extracellular matrix interactions, proteins, hormones, growth factors, matrix metalloproteinases (MMPS), enzymes and enzyme inhibitors, anticoagulants and/or antithrombic agents, DNA, RNA, modified DNA and RNA, NSAIDs, inhibitors of DNA, RNA or protein synthesis, polypeptides, oligonucleotides, polynucleotides, nucleoproteins, compounds modulating cell migration, compounds modulating proliferation and growth of tissue, and vasodilating agents.
"In some embodiments of the invention, the pharmacological agent comprises an angiogenic factor, growth factor, antihypertensive agent, inotropic agent, antiatherogenic agent, beta-blocker, sympathomimetic agent, phosphodiesterase inhibitor, diuretic, vasodilator, thrombolytic agent, cardiac glycoside, and/or antineoplastic agent.
"In some embodiments of the invention, the pharmacological agent comprises at least one Class I, II, III or IV anti-arrhythmic agent.
"In some embodiments of the invention, the pharmacological agent comprises a statin. According to the invention, suitable statins include, without limitation, atorvastatin, cerivastatin, fluvastatin, lovastatin, mevastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin.
"In some embodiments of the invention, the pharmacological agent comprises an antibiotic. According to the invention, suitable antibiotics include, without limitation, aminoglycosides, cephalosporins, chloramphenicol, clindamycin, erythromycins, fluoroquinolones, macrolides, azolides, metronidazole, penicillins, tetracyclines, trimethoprim-sulfamethoxazole and vancomycin.
"In some embodiments of the invention, the pharmacological agent comprises a growth factor. According to the invention, suitable growth factors include, without limitation, platelet derived growth factor (PDGF), epidermal growth factor (EGF), transforming growth factor alpha (TGF-.alpha.), transforming growth factor beta (TGF-.beta.), fibroblast growth factor-2 (FGF-2), basic fibroblast growth factor (bFGF), vascular epithelial growth factor (VEGF), hepatocyte growth factor (HGF), insulin-like growth factor (IGF), nerve growth factor (NGF), platlet derived growth factor (PDGF), tumor necrosis factor alpha (TNA-.alpha.), and placental growth factor (PLGF).
"In some embodiments of the invention, the pharmacological agent comprises a steroid. According to the invention, suitable steroids include, without limitation, andranes (e.g., testosterone), cholestanes, cholic acids, corticosteroids (e.g., dexamethasone), estraenes (e.g., estradiol) and pregnanes (e.g., progesterone).
"In some embodiments of the invention, the pharmacological agent comprises an anti-inflammatory.
"In some embodiments of the invention, the pharmacological compositions comprise extracellular matrix (ECM) compositions that include at least one ECM material.
"According to the invention, the ECM material can be derived from various mammalian tissue sources, including, without limitation, stomach tissue (e.g., stomach submucosa (SS)), small intestinal tissue (e.g., small intestinal submucosa (SIS)), large intestinal tissue, bladder tissue (e.g., urinary bladder submucosa (UBS)), liver tissue (e.g., liver basement membrane (LBM)), heart tissue (e.g., pericardium), lung tissue, kidney tissue, pancreatic tissue, prostate tissue, mesothelial tissue, fetal tissue, a placenta, a ureter, veins, arteries, tissue surrounding the roots of developing teeth, and tissue surrounding growing bone.
"In some embodiments of the invention, the ECM compositions include at least one of the aforementioned pharmacological agents.
"Thus, in some embodiments of the invention, the ECM compositions include a cell.
"In some embodiments of the invention, the ECM compositions include a protein.
"In some embodiments of the invention, the ECM compositions include a statin.
"In some embodiments of the invention, the ECM compositions include chitosan.
"In some embodiments of the invention there is also provided methods for improving cardiovascular function in a subject. In one embodiment, the method comprises (i) implanting an intra-myocardial device (or system) in the subject's myocardium, transmitting a first dose of a pharmacological agent to the intra-myocardial device, and administering the first dose of the pharmacological agent to the subject for a first period of time, the first dose of pharmacological agent being sufficient to cause a measurable improvement in cardiovascular function.
"As set forth in detail herein, the present invention provides superior results and numerous advantages over prior art systems and methods for treating damaged or diseased cardiovascular tissue. One significant advantage of the present invention is that relatively small quantities of a pharmacological agent can be administered over an extended period of time to biological tissue; particularly, cardiovascular tissue. The methods of the present invention thus avoid the pitfalls associated with systemic delivery of a pharmacological agent.
"A further advantage of the present invention is that it avoids problems associated with bolus injection of a pharmacological agent, such as delivery of an amount of agent to cardiovascular tissue that is too high and, which therefore, can have deleterious effects on the cardiovascular tissue.
"Another advantage is that the intra-myocardial agent delivery systems and methods of the invention provide long-term delivery of pharmacological agents and compositions to cardiovascular tissue; particularly, myocardial tissue, with an even delivery rate, approximating to zero-order kinetics over a substantial period of delivery.
"Another important advantage is that extended delivery of pharmacological agents and compositions to cardiovascular tissue can be achieved without the need for repeated invasive surgery, thereby reducing trauma to the patient.
"Another advantage is that the intra-myocardial agent delivery devices and systems of the invention enhance the structural integrity of the cardiovascular structure; particularly, the myocardium when disposed therein.
BRIEF DESCRIPTION OF THE DRAWINGS
"Further features and advantages will become apparent from the following and more particular description of the preferred embodiments of the invention, as illustrated in the accompanying drawings, and in which like referenced characters generally refer to the same parts or elements throughout the views, and in which:
"FIG. 1 is a depiction of a normal heart;
"FIG. 2 is an illustration of a heart having an ischemic infracted region;
"FIG. 3 is a top plan view of one embodiment of an intra-myocardial agent delivery device, in accordance with the invention;
"FIG. 4 is a side plan view of the intra-myocardial agent delivery device shown in FIG. 3, in accordance with the invention;
"FIG. 5 is a partial side plan view of an agent delivery tube having a plurality of perforations, in accordance with the invention;
"FIG. 6 is an illustration of the placement of an intra-myocardial agent delivery device in a myocardium, in accordance with one embodiment of the invention; and
"FIG. 7 is a further illustration of the placement of an intra-myocardial agent delivery device in a myocardium, in accordance with one embodiment of the invention."
For more information, see this patent application: Matheny, Robert G. Intra-Myocardial Agent Delivery Device, System and Method. Filed
Keywords for this news article include: Patents, Surgery, Arteries, Angiology, Cardiology, Myocardium, Angioplasty, Pericardial, Pericardium, Heart Attack, Thrombolytic, Blood Vessels, Cardio Device, Heart Disease, Catheterization, Medical Devices, Extracellular Space, Myocardial Ischemia, Extracellular Matrix, Myocardial Infarction, Cardiovascular Diseases.
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