Method and apparatus for direct mechanical ventricular actuation with favorable conditioning and minimal heart stress

Abstract

A process for assisting the function of a heart disposed within a body, comprising the steps of supporting the heart in providing circulation of blood for perfusion of an organ in the body, remodeling the heart to render the heart in an improved state, and stabilizing the heart in the improved state. The process is preferably performed with an apparatus comprising a cup-shaped shell having an exterior surface and an interior surface; a liner having an outer surface, an upper edge joined to said interior surface of said cup-shaped shell, and a lower edge joined of said interior surface of said cup-shaped shell, thereby forming a cavity between said outer surface thereof and said interior surface of said shell; a drive fluid cyclically interposed within said cavity; and at least one sensor measuring at least one macroscopic parameter indicative of said function of said heart. Further embodiments of the process and apparatus include means and use thereof for delivering a therapeutic agent to the heart.

1 - 29 . (canceled)  
   
   
       30 . A process for assisting in a body the function of a heart, comprising the step of inducing in said heart a change in the extracellular matrix of said heart, wherein said extracellular matrix is changed from an ordered state to a relaxed state.  
   
   
       31 . The process as recited in  claim 30 , wherein said step of inducing said change in said extracellular matrix from said ordered state to said relaxed state further comprises the step of administering at least one therapeutic agent to said heart.  
   
   
       32 . The process as recited in  claim 31 , wherein said at least one therapeutic agent is a matrix metallo-proteinase system promoter.  
   
   
       33 . The process as recited in  claim 30 , further comprising the step of supporting said heart in providing circulation of blood for perfusion of an organ in said body.  
   
   
       34 . A process for assisting in a body the function of a heart, comprising the steps of inducing in said heart a change in the extracellular matrix of said heart, wherein said extracellular matrix is changed from an ordered state to a relaxed state; and causing reverse remodeling of said heart to render said heart in an improved state.  
   
   
       35 . The process as recited in  claim 34 , wherein said step of causing reverse remodeling of said heart to render said heart in an improved state further comprises the step of administering at least one therapeutic agent to said heart.  
   
   
       36 . The process as recited in  claim 35 , wherein said at least one therapeutic agent is selected from the group consisting of genetic material, select DNA fragments, pre- and post-transcription regulation factors, pharmacologic agents, cytokines, pro-inflammatory agents, anti-inflammatory agents, beta-blockade, and membrane stabilizing agents.  
   
   
       37 . The process as recited in  claim 34 , further comprising the step of measuring at least one cellular level parameter.  
   
   
       38 . The process as recited in  claim 37 , wherein said at least one cellular level parameter is selected from the group of metabolic indicators consisting of biochemical markers of stress, biochemical markers of matrix metalloproteinases, and apoptotic cell signaling proteins.  
   
   
       39 . The process as recited in  claim 37 , wherein said at least one cellular level parameter is selected from the group of metabolic indicators consisting of heat shock proteins, cytokines, caspases, reactive oxygen species, nitric oxide, Janus kinase, protein kinase C and Src.  
   
   
       40 . The process as recited in  claim 37 , wherein said at least one cellular level parameter is an extracellular metabolic indicator.  
   
   
       41 . The process as recited in  claim 40 , wherein said extracellular metabolic indicator is a tissue inhibitor of metalloproteinases.  
   
   
       42 . The process as recited in  claim 37 , wherein said at least one cellular level parameter is an intracellular metabolic indicator.  
   
   
       43 . The process as recited in  claim 42 , wherein said intracellular metabolic indicator is selected from the group consisting of focal adhesion tyrosine kinase, Src, Fyn, p130Cas, and GTPase regulator.  
   
   
       44 . The process as recited in  claim 34 , further comprising the step of measuring at least one macroscopic level parameter.  
   
   
       45 . The process as recited in  claim 44 , wherein said at least one macroscopic level parameter is the first derivative of blood pressure.  
   
   
       46 . The process as recited in  claim 44 , wherein said at least one macroscopic level parameter is the thickness of at least a portion of the heart wall.  
   
   
       47 . The process as recited in  claim 44 , wherein said at least one macroscopic level parameter is the position of at least a portion of the heart wall.  
   
   
       48 . The process as recited in  claim 44 , wherein said at least one macroscopic level parameter is blood flow velocity.  
   
   
       49 . The process as recited in  claim 48 , wherein said blood flow velocity is measured proximate to a heart valve.  
   
   
       50 . The process as recited in  claim 34 , wherein said process is performed using a direct mechanical ventricular assistance apparatus comprising: 
 a. a cup-shaped shell having an exterior wall, an interior wall, an apex, and an upper edge;    b. a liner having an outer surface and an inner surface, an upper edge joined to said interior wall of said cup-shaped shell, and a lower edge joined of said interior wall of said cup-shaped shell, thereby forming a cavity between said outer surface thereof and said interior wall of said shell; and    c. a drive fluid cyclically interposed within said cavity, said drive fluid applying a force on a portion of an outer wall of said heart.    
   
   
       51 . The process as recited in  claim 50 , wherein said force on said portion of said outer wall of said heart is variable with respect to time.  
   
   
       52 . The process as recited in  claim 51 , wherein said force on said portion of said outer wall of said heart is periodically variable with respect to time.  
   
   
       53 . The process as recited in  claim 52 , wherein said force on said portion of said outer wall of said heart is varied synchronously with the cardiac cycle of said heart.  
   
   
       54 . The process as recited in  claim 53 , further comprising the step of causing said apparatus to change the timing of said force applied to said portion of said wall of said heart with respect to the timing of said cardiac cycle of said heart.  
   
   
       55 . The process as recited in  claim 52 , further comprising the step of causing said apparatus to change the frequency of said periodically variable force applied to said portion of said wall of said heart.  
   
   
       56 . The process as recited in  claim 50 , wherein said apparatus further comprises means for administering a therapeutic agent.  
   
   
       57 . The process as recited in  claim 34 , further comprising the step of supporting said heart in providing circulation of blood for perfusion of an organ in said body.  
   
   
       58 . A process for assisting in a body the function of a heart, comprising the steps of inducing in said heart a change in the extracellular matrix of said heart, wherein said extracellular matrix is changed from an ordered state to a relaxed state; and inducing in said heart a reversal of said change in said extracellular matrix of said heart, wherein said extracellular matrix is changed from said relaxed state to said ordered state.  
   
   
       59 . The process as recited in  claim 58 , further comprising the step of administering at least one therapeutic agent to said heart.  
   
   
       60 . The process as recited in  claim 58 , further comprising the step of supporting said heart in providing circulation of blood for perfusion of an organ in said body.  
   
   
       61 . A process for assisting in a body the function of a heart, comprising the steps of inducing in said heart a change in the extracellular matrix of said heart, wherein said extracellular matrix is changed from an ordered state to a relaxed state; causing reverse remodeling of said heart to render said heart in an improved state; and inducing in said heart a reversal of said change in said extracellular matrix of said heart, wherein said extracellular matrix is changed from said relaxed state to said ordered state.  
   
   
       62 . The process as recited in  claim 61 , wherein said step of inducing said change in said extracellular matrix from said relaxed state to said ordered state further comprises the step of administering at least one therapeutic agent to said heart.  
   
   
       63 . The process as recited in  claim 62 , wherein said at least one therapeutic agent is a tissue inhibitor of metalloproteinases.  
   
   
       64 . The process as recited in  claim 61 , further comprising the step of supporting said heart in providing circulation of blood for perfusion of an organ in said body.  
   
   
       65 - 113 . (canceled)