Method to modulate cellular regeneration post myocardial infarct

Abstract

A system delivers cardiac pacing therapy and chemical and/or biological therapy to modulate myocardial tissue growth in a heart after myocardial infarction (MI). The system includes an agent delivery device to release one or more agents to an MI region to modulate myocardial tissue growth in that region, and a cardiac rhythm management (CRM) device to deliver pacing pulses to enhance the effects of the one or more agents by altering myocardial wall stress and cardiac workload. In one embodiment, the system is an implantable system including an implantable agent delivery device and an implantable CRM device.

1 . A method for modulating tissue growth in a myocardial infarct region, the method comprising:
 delivering one or more agents to a cardiac region including at least portions of the myocardial infarct region in an amount effective to modulate myocardial tissue growth; and   delivering pacing pulses to the cardiac region to enhance the modulation of myocardial tissue growth by the one or more agents.   
     
     
         2 . The method of  claim 1 , wherein delivering the one or more agents alters one or more mechanical properties of tissue in the cardiac region. 
     
     
         3 . The method of  claim 1 , wherein delivering the one or more agents alters stress, strain or work in the cardiac region. 
     
     
         4 . The method of  claim 1 , wherein delivering the one or more agents promotes vascularization in the cardiac region. 
     
     
         5 . The method of  claim 1 , wherein delivering the one or more agents reduces adverse remodeling of tissue in the cardiac region. 
     
     
         6 . The method of  claim 1 , wherein the one or more agents modulate hypertrophic signaling in the cardiac region, modulates fibrosis signaling in the cardiac region, or enhances localization, implantation, or proliferation of stem cells in the cardiac region. 
     
     
         7 . The method of  claim 1 , wherein at least one agent is stem cell growth factor (SCF), granulocyte colony-stimulation factor (G-CSF), granulocyte macrophage colony-stimulating growth factor (GM-CSF), stem cell homing factor (SDF-1), bone morphogenetic protein 2 (BMP-2), or Wnt protein, a gene encoding SCF, G-CSF, GM-CSF, SDF-1, BMP-2 or a Wnt protein, hepatocyte growth factor (HGF), insulin-like growth factor (IGF), fibroblast growth factor (FGF), or transforming growth factor-beta (TGF-β), a gene encoding HGF, IGF, FGF, or TGF-β, or a cytokine. 
     
     
         8 . The method of  claim 1 , wherein delivering the pacing pulses comprises executing a cardiac resynchronization therapy (CRT) pacing algorithm or a remodeling control therapy (RCT) pacing algorithm. 
     
     
         9 . The method of  claim 1 , wherein the one or more agents are released from an implantable agent delivery device and wherein delivering the pacing pulses comprises delivering the pacing pulses from an implantable cardiac rhythm management (CRM) device. 
     
     
         10 . The method of  claim 9 , wherein delivering the pacing pulses comprises delivering the pacing pulses through a pacing lead having at least one electrode placed in or near the myocardial infarct region. 
     
     
         11 . The method of  claim 10 , wherein the one or more agents are released from an agent delivery device incorporated in the pacing lead near the at least one electrode and wherein delivering the one or more agents comprises releasing the one or more agents from an agent eluting stent or an agent eluting epicardial patch placed in or near the myocardial infarct region. 
     
     
         12 . The method of  claim 1 , wherein delivering the one or more agents comprises releasing the one or more agents in response to an agent delivery control signal. 
     
     
         13 . The method of  claim 12 , further comprising:
 sensing a physiological signal indicative of a need for releasing the one or more agents; and   producing the agent delivery control signal based on the physiological signal.   
     
     
         14 . The method of  claim 13 , wherein sensing the physiological signal comprises sensing a signal indicative of ischemia, sensing at least one electrogram indicative of arrhythmia, sensing a signal indicative of a strain of myocardial tissue, sensing a signal indicative of hypertrophic signaling, sensing a signal indicative of a metabolic need of a body, or sensing a signal indicative of a perfusion of thermal energy through myocardial tissue. 
     
     
         15 . The method of  claim 14 , wherein the signal indicative of hypertrophic signaling is the concentration of endothelin-1, BNP or p38MAPK. 
     
     
         16 . The method of  claim 13 , wherein sensing the physiological signal comprises sensing one or more of a blood pH, an oxygen pressure (PO 2 ), a carbon dioxide pressure (PCO 2 ), glucose level, creatine level a C-creative protein level, creatine kinase level, and a creatine kinase-MB level. 
     
     
         17 . The method of  claim 13 , further comprising controlling a rate of releasing the one or more agents by an amplitude of the agent delivery control signal. 
     
     
         18 . The method of  claim 13 , wherein the site of the delivery of the pacing pulses is controlled. 
     
     
         19 . The method of  claim 13 , further comprising receiving a user command, and wherein producing the agent delivery control signal comprises producing the agent delivery control signal in response to at least one of the detection of the condition and the user command. 
     
     
         20 . The method of  claim 19 , wherein receiving the user command comprises receiving the user command issued from a remote location through a communication network.