Surgery – Miscellaneous – Methods
Reexamination Certificate
1998-07-15
2002-05-28
McDermott, Corrine (Department: 3738)
Surgery
Miscellaneous
Methods
C604S507000
Reexamination Certificate
active
06394096
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to a method and apparatus for reducing mineralization of a cardiovascular tissue in a subject, particularly to the use of an acid treatment solution for reducing mineralization of cardiovascular tissue such as a vessel or a valve.
BACKGROUND OF THE INVENTION
Atherosclerosis is commonly understood to be a deposition of cholesterol in the vessels of the cardiovascular system. An additional significant complication is pathologic calcification, which takes place both in blood vessels and in heart tissue. Cardiovascular bioprostheses also host calcific deposits that may severely limit longevity and performance of the device. Calcium deposits have been shown to be calcium phosphates that contain several inorganic components such as carbonate, acidic phosphate, sodium, magnesium, and fluoride (Tomazic, B. B., et al.,
Ann. Thorac. Surg
. 60(2 Suppl.):S322-S327, 1995). All deposits, regardless of the site of formation, are carbonated apatites that contain an appreciable fraction of carbonate (Tomazic, B. B., et al.,
Atherosclerosis
69:5-19, 1988). It has been suggested that octacalcium phosphate (Ca
4
H(PO
4
)
3
.2.5 H
2
O), could be a precursor mineral in the formation of cardiovascular calcium deposits, however the mechanism is in fact poorly understood (see Tomazic, B. B., In:
Hydroxyapatite and Related Materials
, pp. 93-115, P. W. Brown and B. Constantz, eds., CRC Press, Brown, Boca Ratan, Fla., 1994, herein incorporated by reference).
Surgical implantation of prosthetic devices (prosthesis) into humans and other mammals has been carried out with increasing frequency in the United States. Such protheses include heart valves, vascular grafts, urinary bladders, heart bladders, left ventricular-assist devices, hip prosthesis, breast implants, and tendon prosthesis, amongst others. At least forty models of substitute heart valves, including mechanical and bioprosthetic valves, have been used in the United States. Mechanical heart valve prostheses typically are composed of rigid materials such as polymers and metals, and use a poppet occluder which responds to changes in intracardiac pressure or flow. Bioprostheses have also been utilized for the replacement of heart valves. These are usually fabricated from porcine aortic valves or bovine epicardium, although only the porcine aortic valve or, occasionally, valves fashioned from human tissue, are used in the United States (see Hancock, E. W., in:
Scientific American Medicine
, Vol. 1, Section 1, Ch. IX, pp. 1-16, D. C. Dale and D. D. Friedman (eds)., Scientific American, N.Y., 1997).
Bioprostheses are typically pretreated with glutaraldehyde and then sewn onto a flexible metallic alloy or a flexible polymeric (plastic) stent which is then coved with a poly(ethylene terephthalate) cloth ring covering. Tissue valves are less likely than mechanical valves to produce thrombosis and systemic embolism. In addition, bioprostheses generally do not require routine anticoagulation. However, bioprostheses structurally deteriorate over time. This deterioration is usually related to mineralization (especially calcification) of the valve leaflets. Calcification is an important limitation on the useful life expectancy of bioprosthetic valves, and accounts for over sixty percent of the cardiac bioprostheses failures. Calcification of bioprosthetic valves develops more rapidly in children, which have an incidence of calcification of about 40% to 50% at four years. Adults have an incidence of calcification of between 5% to 20% at ten years (Carpentier, A., et al.,
Circulation
70 (suppl. I):I165-I168, 1984). Calcification causes thickening, retraction and reduced mobility of the leaflets and can lead to stenosis, insufficiency, or both. Currently, treatment of a functionally compromised bioprosthetic valve requires replacement with a new valve.
Several strategies to decrease or prevent mineralization of bioprosthetic heart valves have been described. Generally the methods involve treating the tissue with substances prior to implantation. Examples of pretreatment solutions to prevent calcification are a water-soluble phosphate ester (e.g., sodium dodecyl hydrogen phosphate, see U.S. Pat. No. 4,402,697), a water soluble quaternary ammonium salt (e.g., dodecyltrimethyammonium chloride, see U.S. Pat. No. 4,405,327), a sulfated higher aliphatic alcohol, (e.g., sodium dodecyl sulfate, see U.S. Pat. No. 4,323,358), or covalent coupling of an aliphatic carboxylic acid (see U.S. Pat. No. 4,976,733). Treatment of a bioprosthesis with a buffered solution having a pH in the range of 5.0 to 8.0, to generate an acellular graft prior to implantation (see U.S. Pat. No. 5,720,777) has also been described. However, none of these methods have proven successful in completely preventing mineralization. Thus, there remains a need for a postimplantation method useful in removing mineralized deposits on the tissue postimplantation.
Atherosclerotic calcification is an organized, regulated process similar to bone formation that occurs only when other aspects of atherosclerosis are also present. Calcium phosphate, in the crystalline form of carbonated apatite (dahllite), which contains 40% calcium by weight, precipitates in diseased coronary arteries by a mechanism similar to that found in active bone formation and remodeling (Bostom, K., et al.,
J. Clin. Invest
. 91:1800-9, 1993; Lowenstam, H. A., and Wiener, S.,
On Biomineralization
, Oxford University Press, N.Y). This was previously thought to be calcium phosphate (hydroxyapatite, Ca
3
[—PO
4
]
2
Ca[OH]
2
). Atherosclerotic calcification begins as early as the second decade of life, just after fatty streak formation (Stary, H. C.,
Eur. Heart J.
11l(Suppl. E):3-19, 1990). The lesions of younger adults have revealed small aggregates of crystalline calcium phosphate among the lipid particles of lipid cores (Stary, H. C., et al.,
Circulation
92:1355-74, 1995). Calcific deposits are found more frequently and in greater amounts in elderly individuals and more advanced lesions (Doherty, T. M, and Detrano, R. C.,
Calcif. Tissue Int
. 54:224-30, 1994). In most advanced lesions, when mineralization dominates the picture, components such as lipid deposits and increased fibrous tissue may also be present. The biochemical sequence of events leading to atherosclerotic calcification is not well understood.
Coronary artery calcification is potentially detectable in vivo by the following methods: plain film roentgenography; coronary arteriography; fluoroscopy, including digital subtraction fluoroscopy; cinefluorography; conventional, helical, and electron beam computed tomography (“EBCT”); intravascular ultrasound (“IVUS”); magnetic resonance imaging; and transthoracic and transesophageal echocardiography. In current practice, fluoroscopy and EBCT are most commonly used to detect coronary calcification noninvasively, while cinefluorography and IVUS are used by coronary interventionalists to evaluate calcification in specific lesions before angioplasty.
Histopathological investigation has shown that plaques with microscopic evidence of mineralization are generally larger and associated with larger arteries than are plaques or arteries without calcification. The relation of arterial calcification to the probability of plaque rupture is unknown. However, correlative studies indicate that patients with greater amounts of coronary calcification are more likely to suffer a clinical event compared with patients without calcification or lesser amounts (Detrano, R. C., et al.,
J. Am. Coll. Cardiol
. 24:354-8, 1994). There is evidence linking radiographically detectable coronary calcium to future coronary heart disease events of death and infarction, which suggests that this link is strongest in symptomatic and very high-risk subjects (Naito, S., et al.,
J. Cardiol
. 20:249-258, 1990).
SUMMARY OF THE INVENTION
This invention is based on the discovery that acid can be used to demineralize cardiovascular tissue in situ or in vitro, such as a calcified bioprosthetic heart v
Barrett Thomas
Bozicevic, Field & Francis
Corazon Technologies, Inc.
Field Bret E.
McDermott Corrine
LandOfFree
Method and apparatus for treatment of cardiovascular tissue... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Method and apparatus for treatment of cardiovascular tissue..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method and apparatus for treatment of cardiovascular tissue... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2845810