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Method and kit for regulation of microvascular tone

a microvascular tone and kit technology, applied in the direction of biocide, cardiovascular disorder, drug composition, etc., can solve the problems of reduced oxygen delivery and exchange within the capillaries, insufficient tissue perfusion, and often fatal shock

Inactive Publication Date: 2006-10-26
MOORE BOB M II
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Shock is a progressive, widespread reduction in tissue perfusion that results from a decrease in effective circulating blood volume causing a decrease in oxygen delivery and exchange within capillaries.
If untreated, shock is often fatal.
Shock has also been classified as being vasogenic, that is due to a maldistribution of blood to the tissues, such as due to acute vasodilation without a concomitant increase in intravascular volume, resulting in inadequate tissue perfusion.
Regardless of the cause of shock, however, if untreated shock can lead to severe complications including myocardial depression, acute respiratory distress, renal failure, disseminated intravascular coagulation, and death.
However even with such treatment, severe shock, due to any or a combination of causes, may progress and result in permanent complications or death.
Short-term trials suggested that COX-2 inhibitors have no effect on blood pressure on normotensive patients, although these studies may have been flawed because the study subjects were restricted to a low-sodium diet.
In another study in which patients were administered either rofecoxib or celecoxib for six weeks, rofecoxib was found to elevate blood pressure and the results on celecoxib were inconclusive.
Johnson also reported that some limited data suggests that blood pressure may increase following initiation of therapy with COX-2 inhibitors.

Method used

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  • Method and kit for regulation of microvascular tone
  • Method and kit for regulation of microvascular tone
  • Method and kit for regulation of microvascular tone

Examples

Experimental program
Comparison scheme
Effect test

example 1

Cremaster Muscle Protocol

[0045] Male C57-BL mice age 7-8 weeks and weighing approximately 20 grams are anesthetized with an intramuscular injection of 100 to 150 microliters of a mixture of ketamine and xylazine (87 mg ketamine and 13 mg xylazine per ml) based on the weight of the individual animal. The body temperature was maintained at about 37° C. by convective heating. The animal is supinated, a midline incision is made in the ventrocervical region, and the underlying tissues are bisected laterally to expose the trachea. A tracheotomy is performed and the animal is intubated directly with PE50 tubing to facilitate ventilation. The wound is then closed.

[0046] The left rear limb is incised to expose the femoral neurovascular bundle and the femoral vein is isolated and catheterized with PE10 tubing attached to a syringe containing normal saline. The animal is then placed on a specially designed surgery board and the right testicle within the scrotum is oriented over a translumina...

example 2

Mesentery Protocol

[0047] Animals as described in Example 1 are prepared for surgery as described in Example 1. The animal is supinated on the surgery board so that the ventral portion of the animal faces the observation window. Upon irrigation with warmed physiological saline, a midline incision is made through the linea alba. A loop of small intestine from the lower duodenal segment is extracted and pinned around the observation window, with the pins passing through the proximal mesentery and not through the intestine proper.

example 3

Intravital Microscopy

[0048] All experiments are carried out using an industrial grade microscope (Nikon MM-11) with two light sources, bright field (OptiQuip 75 W xenon) and fluorescent (Nikon 150 W mercury). The primary camera assembly has a chilled charged coupled device (CCD) and controller (Hamamastu C5985). The secondary camera assembly has a CCD camera (MTI CCD72) in conjunction with an intensifier (MTI GENIISYS). Experiments are viewed on a video monitor and recorded on a digital video recorder for off-line processing.

[0049] The prepared animal, as described above in Examples 1 and 2, is placed on the stage of the microscope on the surgery board with the translumination window. Exposed tissues are irrigated with warmed physiological saline through which a N2 / CO2 (95% / 5%) mixture is bubbled. The tissue is allowed to equilibrate until normal blood flow is observed or perfusate flow stabilizes, during which time the tissue is scanned at 1-× for A1-A4 arterioles. The arterioles...

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Abstract

Methods and kits for regulating arterial microvascular tone in which a COX-2 inhibitor and a cannabinoid receptor agonist are co-administered to a subject.

Description

[0001] This application is a continuation-in-part of pending U.S. patent application Ser. No. 10 / 436,028, filed on May 12, 2003, incorporated herein by reference.FIELD OF THE INVENTION [0002] The invention pertains to the field of administration of pharmacologic chemical compounds to regulate the tone of small blood vessels. BACKGROUND OF THE INVENTION [0003] The circulatory system in humans and other vertebrate animals includes a heart, which pumps blood throughout the body, and a vascular system, which is a series of tubes supplying blood to all regions of the body. The blood leaves the heart through arteries, which transport the blood under high pressure to the tissues of the body. Blood returns to the heart from the tissues through veins. The arteries repeatedly subdivide into progressively thinner tubes and eventually give rise to arterioles. The arterioles feed into capillaries, which are thin walled structures through which oxygen exchange occurs within tissues. Blood from th...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/415A61K31/353A61K31/192A61K31/16A61K31/18A61K31/25A61K31/341A61K31/352A61K31/365A61K31/405A61K31/42A61K31/444A61K31/5415A61K31/542A61K31/60A61K45/06
CPCA61K31/42A61K31/415A61K31/5415A61K31/542A61K45/06A61K31/444A61K31/405A61K31/353A61K31/352A61K31/341A61K31/25A61K31/192A61K31/18A61K31/16A61K2300/00A61P17/02A61P43/00A61P9/00A61P9/02A61P9/10
Inventor MOORE, BOB M. II
Owner MOORE BOB M II
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