Controlled Calcium Ion Cardioplegic Solution for Heart Reperfusion
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Solution Overview
Problem
Current methods for preserving and reperfusing donor hearts for transplantation face challenges such as ischemic damage, limited heart availability due to donor shortages, and inefficiencies in maintaining cardiac function post-harvest, particularly in brainstem-dead and non-heart-beating donors, leading to suboptimal transplantation outcomes.
Innovation Solution
A novel cardioplegic solution with specific ion concentrations and pH levels is used for reperfusion, including adenosine, lidocaine, magnesium, and antioxidants, to maintain calcium ion homeostasis and reduce ischemic damage, allowing for improved cardiac function and extended preservation times at normothermic temperatures.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional reperfusion methods are used, then cardiac function is restored, but ischemic damage and reperfusion injury occur
Solution Approach 1:
The patent applies preliminary action by administering a controlled calcium ion solution to the donor heart before transplantation. This pre-treatment establishes calcium homeostasis and prevents calcium overload before the heart is implanted, thereby reducing reperfusion injury while maintaining cardiac function restoration.
Solution Approach 2:
The patent changes the calcium ion concentration parameter in the reperfusion solution from conventional high levels to a controlled, lower range (0.18-0.26 mmol/L). This parameter modification prevents calcium overload and associated reperfusion injury while still allowing adequate cardiac function restoration.
2Quantity of substance
If donor hearts are preserved for extended periods, then transplantation availability increases, but myocardial injury and dysfunction increase
Solution Approach 1:
The controlled calcium ion solution is administered to donor hearts during preservation to maintain calcium homeostasis throughout the storage period. This preliminary and continuous protection reduces myocardial injury accumulation during extended preservation, enabling longer storage times without proportionally increasing damage.
Solution Approach 2:
By maintaining calcium ion concentration within the specific range of 0.18-0.26 mmol/L during preservation, the patent modifies the ionic environment to prevent calcium-mediated myocardial injury. This parameter control allows extended preservation periods while limiting the accumulation of ischemic damage.
3Power
If calcium ion concentration is increased to maintain cardiac function, then contractility is improved, but reperfusion injury and cell damage increase
Solution Approach 1:
The patent optimizes the calcium ion concentration parameter to a specific range (0.18-0.26 mmol/L) that provides sufficient cardiac contractility while preventing calcium overload. This precise parameter control achieves the therapeutic benefit without triggering the harmful effects of excessive calcium.
Solution Approach 2:
The patent employs feedback control by monitoring and adjusting calcium ion concentration to maintain homeostasis. This feedback mechanism ensures that calcium levels remain within the optimal range for cardiac function while preventing the development of calcium overload and associated reperfusion injury.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The solution effectively minimizes myocardial injury, maintains cardiac function, and extends the viability of donor hearts for transplantation by reducing reperfusion injuries and ischemic damage, thereby increasing the availability of suitable hearts for transplantation.
Implementation Method 1
a buffer for maintaining a pH of the solution
Implementation Method 2
maintain calcium ion homeostasis
Implementation Method 3
The solution effectively minimizes myocardial injury, maintains cardiac function, and extends the viability of donor hearts for transplantation by reducing reperfusion injuries and ischemic damage
Data Source
AI summary
A solution comprises a preservation mixture comprising a calcium ion source; and a buffer for maintaining a pH of the solution. The molar concentration of calcium ion (Ca2+) in the solution is from 0.18 to 0.26 mmol/L, and the pH is lower than 7.4 and higher than 6.6. A composition for preparing the solution may comprise adenosine, lidocaine, and a calcium source, wherein the molar ratio of adenosine:calcium is from 0.3:0.26 to 0.45:0.18, and the molar ratio of lidocaine:calcium is from 0.04:0.26 to 0.09:0.18. A donor heart may be reperfused with the solution. The solution may be used for reperfusion of a donor heart, such as at a temperature from about 25 to about 37° C. The donor may be a donor after circulatory death.