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Stimulation for delivery of molecular therapy

a technology stimulatory device, which is applied in the field of stimulatory device for the controlled production of angiogenic growth factor, can solve the problems of ischemic heart area, occurrence of myocardial infarction, and starvation of oxygen and nutrients

Inactive Publication Date: 2005-05-05
MEDTRONIC INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0008] The present invention provides an electrical pulse generator for providing subthreshold pulses. The present device can be adapted to a range of subthreshold pulses by modulating the time, frequency, and delivery of a given stimulus. The present generator allows the use of a constant voltage, regardless of the distance between electrodes by allowing a variable field density. The present generator allows for control over the amplitude of the voltage and for charge balancing of the delivered and recovered charged pulse.

Problems solved by technology

Often the arteries of the heart can suddenly become so severely blocked that there is inadequate blood supply to areas of the heart, leading to the occurrence of a myocardial infarction.
The ischemic area of the heart, because it does not get adequate blood flow, is starved of oxygen and nutrients.
This blockage, if not treated quickly, can lead to severe tissue damage.
However, by-passing or reopening of the arteries is often not possible because of limitations of present methodologies and the risk to the patient from surgical intervention.
Damage from ischemia from insufficient blood circulation can also occur in blood vessels peripheral to the heart.
The direct injection of angiogenic growth factors has many problems associated with it, most notably problems with effective delivery of the factors into the cells.
Electroporation is a possible method of delivery of genetic materials encoding angiogenic factors; however, the transfection efficiency is still very low and the high-energy pulses directed to the tissue often kill many healthy cells.
Although extensive research continues in the areas of gene delivery, very little has been reported on methods to control and regulate gene expression in vivo.
The inability to effectively deliver the agent to the target tissue, therefore, is one of the major limitations of the use of such agents.
During delivery of the angiogenic factors the effectiveness is often destroyed or lost.

Method used

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  • Stimulation for delivery of molecular therapy
  • Stimulation for delivery of molecular therapy
  • Stimulation for delivery of molecular therapy

Examples

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Effect test

example 1

[0091] Sterile 6 well culture plates (Corning) were seeded with cells on six well culture inserts using SmGM growth media; C2C12 cells (mouse myoblasts) were seeded at 7.5×103 / cm2; Human Coronary Smooth Muscle Cells (HCASMC) were seeded at 2.5×103 / cm2. After two days' growth (confluent), the wells were washed twice with electrical stimulation medium (DMEM with 1% bovine serum albumin). 2.0 ml of serum free medium was added but without any fetal bovine serum in the medium. Wells contained approximately 4 ml of total growth medium, approximately 2.0 ml inside well insert and 2.0 ml outside well insert. The cells were electrically stimulated using a circular graphite electrode for 8 hours per stimulation condition. Cells were stimulated at one volt in the stimulation chamber for 1 msec stimulation pulse width with a 4 msec discharge pulse width. The escape period was adjusted to achieve the desired frequency. Samples were harvested after 22 hours post-stimulation. Cell culture supernat...

example 2

In Vivo Subthreshold Stimulation in Canine Model of Regional Ischemic Cardiomyopathy

[0093] Dogs were initially anesthetized with intramuscular morphine sulfate (4 mg / kg) / A bolus injection of pentothal (20 mg / kg) was given followed by continuous inhaling of isoflurane (0.5%-2% in oxygen) after endotracheal intubation. A left lateral thoracotomy was performed, and the pericardium opened. A micromanometer pressure transducer (MPC-500, Millar Instruments, Houston, Tex.) was inserted into the left ventricle through an apical incision. Pairs of 5 MHz ultrasonic crystals also was implanted in the area supplied by the distal left anterior descending (LAD) and left circumflex (LCX) arteries just distal to the first diagonal branch of measurement of coronary flow. Two heart wire electrodes were inserted in the LAD perfusion area. A catheter was inserted into the left atrium for injection of colored 15 um microspheres to measure regional myocardial blood flow. Ameriod constrictors were placed...

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Abstract

The present invention provides a novel stimulatory device for the controlled production of angiogenic growth factors. More specifically, the present invention provides a subthreshold pulse generator for the local production of vascular endothelial growth factor.

Description

FIELD OF THE INVENTION [0001] The present invention provides a novel stimulatory device for the controlled production of angiogenic growth factors. More specifically, the present invention provides a subthreshold pulse generator for the local production of vascular endothelial growth factor. BACKGROUND OF THE INVENTION [0002] Coronary artery disease (CAD) results from arteriosclerosis of blood vessels serving the heart. Arteriosclerosis is a hardening and narrowing of the arteries. Often the arteries of the heart can suddenly become so severely blocked that there is inadequate blood supply to areas of the heart, leading to the occurrence of a myocardial infarction. The area of damage where the reduced blood flow has occurred is called the ischemic area. The ischemic area of the heart, because it does not get adequate blood flow, is starved of oxygen and nutrients. This blockage, if not treated quickly, can lead to severe tissue damage. Often surgical procedures are used to graft new...

Claims

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Application Information

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IPC IPC(8): A61N1/32
CPCA61N1/326
Inventor DONOVAN, MAURA G.SOYKAN, ORHANDENO, D. CURTISMULLIGAN, LAWRENCE J.FERNANDES, BRIAN C.A.
Owner MEDTRONIC INC
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