Dichloroacetate combined with inotrope for heart protection

A dichloroacetate, heart protection technology, applied in the field of dichloroacetate, can solve the problems of increasing myocardial oxygen consumption, not improving mechanical efficiency, and increasing cardiac muscle

Inactive Publication Date: 2007-03-07
艾伯塔大学校董
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although inotropes such as dobutamine have been reported to increase myocardial stroke volume and work, they have also been reported to increase myocardial oxygen consumption and thus may not improve mechanical efficiency (Reference 1)

Method used

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  • Dichloroacetate combined with inotrope for heart protection
  • Dichloroacetate combined with inotrope for heart protection
  • Dichloroacetate combined with inotrope for heart protection

Examples

Experimental program
Comparison scheme
Effect test

Embodiment

[0068] Methods used in the studies described in Examples A to C

[0069] The studies described in Examples A to C describe three different clinical studies of the effects of DCA when administered to patients during and / or after cardiac surgery.

[0070] The study described in Example A involved adult patients investigating the effects of DCA on cardiometabolism. DCA is administered to patients undergoing elective cardiac bypass grafting (CABG). The study was conducted in coronary artery bypass grafting in the presence of clinically recommended doses of hemodynamic drugs.

[0071] The study described in Example B involved the administration of a single bolus dose of DCA to pediatric patients undergoing cardiac surgery to correct congenital heart defects. This regimen was performed in the presence of clinically recommended hemodynamic agents, and it was determined that the dose and total amount of these agents would be reduced when combined with DCA.

[0072] The study de...

Embodiment A

[0074] Description of the research protocol

[0075] DCA or saline was administered to 18 patients undergoing elective cardiac bypass grafting (CABG), with DCA (50 mg / kg in 100 ml saline) injected into the aortic root in a double-blind randomized fashion just before removal of the aortic cruciform or placebo. Based on the pharmacokinetics of DCA, we would expect this to yield plasma concentrations of approximately 1 mM. The study consisted of 8 patients treated with DCA and 10 patients treated with placebo.

[0076] 1. Intervention

[0077] a. "Conventional" treatment

[0078] All procedures and medications for patients normally administered CABG are routinely applied. A list of medications provided to these patients is shown in Figure 1.

[0079] b. "Intervention" therapy

[0080] The intervention involved intra-aortic root injection of DCA (50 mg / kg) or placebo just prior to removal of the aortic cross clip. The coded solution was formulated such that a dose of 1 ml / k...

Embodiment B

[0092] Description of the research protocol

[0093] This study was a randomized, placebo-controlled, double-blind, one-surgeon study of the use of DCA in 40 high-risk pediatric patients requiring cardiac surgery to correct a complex congenital heart defect.

[0094] 1. Research groups

[0095] In this trial, 40 children were recruited to participate in a surgeon's study, of which 18 received DCA and 22 received placebo. The 1995 power calculation is based on the separation of the CPB-1 trial of n=40 patients.

[0096] 2. Criteria for included studies

[0097] a. The age is less than 1 year old.

[0098] b. Parental or guardian consent.

[0099] c. Need for open heart surgery to correct complex congenital heart defects (eg, Tetralogy of Fallot).

[0100] d. Surgeons, anaesthetists and cardiologists agree.

[0101] e. There are no serious cardiac complications that would prevent the implementation of the study protocol.

[0102] 3. Exclusion criteria

[0103] a. Lack of...

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PUM

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Abstract

The present invention provides composition and methods for maintaining cardiac function by administering dichloroacetate (DCA) in combination with an inotrope.

Description

Background technique [0001] Currently, there is a need to develop methods of protecting the heart from damage that may occur due to ischemic events and during ischemia-reperfusion, and thereafter maintaining the function of the heart at predetermined levels. [0002] Clinically, ischemia-reperfusion may occur in the context of cardiac surgery. In order to perform many surgical procedures, it is necessary to interrupt coronary blood flow resulting in cardiac ischemia. Not only does this ischemia limit the duration of the surgical procedure, but it can also lead to systolic dysfunction once coronary blood flow is restored. This is not only a problem in adult patients undergoing coronary artery bypass surgery (CABG) or other surgical procedures, it is also an important clinical problem during surgical cardiac procedures to correct neonatal congenital heart defects. [0003] Current treatments aimed at improving systolic function after cardiac surgery in adults, young children, ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/19A61K31/00A61P9/04
CPCA61K31/19A61P9/00A61P9/04Y02A50/30A61K2300/00
Inventor G·D·罗帕舒克R·科林斯-纳凯
Owner 艾伯塔大学校董
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