Treatment of congestive heart failure

Abstract

A method of treating congestive heart failure (CHF) in a human patient comprises treating an aliquot of the patient's blood ex vivo with at least one stressor selected from the group consisting of a temperature above or below body temperature, an electromagnetic emission and an oxidative environment, followed by administering the aliquot of treated blood to the patient. The treatment can be used on its own or as an adjunctive therapy in combination with conventional CHF treatments.

Description

BACKGROUND OF THE INVENTION [0001] 1. Field of the Invention [0002] This invention relates to methods for treating congestive heart failure, in particular by the administration to a human subject of an aliquot of modified blood, optionally in combination with one or more other treatments for alleviating the symptoms of congestive heart failure. [0003] 2. Description of the Prior Art [0004] Congestive heart failure (CHF) is a relatively common disorder affecting approximately five million Americans, with a mortality rate of over 80,000 per year. It is believed that CHF is not a distinct disease process in itself, but rather represents the effect of multiple anatomic, functional and biologic abnormalities which interact together to ultimately produce progressive loss of the ability of the heart to fulfill its function as a circulatory pump. [0005] CHF may be caused by the occurrence of an index event such as a myocardial infarction (heart attack) or be secondary to other causes such a...

AI Technical Summary

Benefits of technology

[0015] With respect to immune activation, the treatment of the present invention has been found to modulate levels of inflammatory cytokines in several Th1 / TNF-α-dependent experimental inflammatory models in different species. For example, the treatment has been shown to reduce allergic contact hypersensitivity in Balb / c mice, a Th1-driven immune reaction mediated by TNF-α (Shivji et al., Journal of Cutaneous Medicine and Surgery 4: 132-137, 2000); to down-regulate expression of IL6 mRNA in adjuvant-induced arthritis in the Lewis rat model of inflammatory disease; and to decrease the proportion of Th1 to Th2 cells in patients with scleroderma, a Th1-driven autoimmune disease (Rabinovich et al., Poster presented at the XII Pan-American Congress of Rheumatology, Montreal, Canada, Jun. 21-25, 1998). It is believed that the treatment down-regulates the pro-inflammatory Th1-type immune response, for example by increasing anti-inflammatory TH2-type cytokines, including IL-10.

[0016] The treatment of the invention has been found to improve endothelial function in a number of studies conducted in humans and in animals. For example, the treatment has been found to improve endothelial-dependent vasodilator function in an open study on patients with severe primary Raynaud's disease (Cooke et al., International Journal of Angiology 16: 250-254, 1997), to improve the rate of recovery of skin blood flow following temporary occlusion in a double-blind, placebo-controlled study in patients with advanced peripheral vascular disease secondary to atheroscierosis (Courtman et al., Circulation Vol 102, #18, suppl II, 2000), to reduce progression of atherosclerosis in the cholesterol-fed LDD receptor deficient mouse (Babaei et al., Journal of the American College of Cardiology 35 (Suppl. A): 243, 1999), and to markedly improve endothelial-dependent vasodilator function to acetylcholine in severely atherosclerotic, hypercholesterolemic Watanabe rabbits as evidenced by an increased vasodilatory response to the nitric oxide agonist (acetylcholine) (Courtman et al., above). It is believed that the improvement in endothelial function is due to an anti-inflammatory effect and to increased availability of NO which may result in an improvement in vasodilatory capacity, known to be severely impaired in CHF patients.

[0017] With regard to myocyte loss, the method of the invention is believed to decrease levels of apoptosis and necrosis. It has been shown that the treatment can protect the kidney from ischemia / reperfusion (I / R) damage known to be associated with increased apoptotic cell death (Tremblay et al., Pathophysiology 5:26; Chen et al., Médecline Sciences 15 (Suppl. 1): 16), and can reduce apoptosis in the kidney following I / R as determined by DNA laddering and density of apoptotic nuclei stained by Tdt.

Problems solved by technology

The index event or other causes result in an initial decline in the pumping capacity of the heart, for example by damaging the heart muscle.

Therefore, the damaging changes caused by the disease are present and ongoing even while the patient remains asymptomatic.

In fact, the compensatory mechanisms which maintain normal cardiovascular function during the early phases of CHF may actually contribute to progression of the disease, for example by exerting deleterious effects on the heart and circulation.

In addition, levels of IL-10, a key anti-inflammatory cytokine, are inappropriately low in relation to TNF-α levels.

Although presently used treatments can alleviate symptoms of CHF and correct certain pathophysiologic abnormalities caused by the disease process, CHF remains a relentlessly progressive condition with a relatively high rate of mortality.

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