Perfusion circuit and use therein in targeted delivery of macromolecules

Abstract

A perfusion circuit and a use thereof for delivering a substance to a subject's heart in situ during cardiopulmonary bypass surgery are provided. The perfusion circuit defines a path for re-circulating a solution containing a macromolecular complex through a coronary circulation circuit ( 50 ) through a subject's heart during a surgical procedure in which the substance is prevented from being delivered to the subject's other organs.

1 . A perfusion circuit for use during cardiopulmonary bypass surgery, comprising a circuit ( 50 ) for re-circulating a solution through a coronary circulation path of a subject's heart in situ that has been isolated from a subject's systemic circulation, wherein a part ( 52 ) of the circuit ( 50 ) that extends exterior of the heart includes a pump ( 54 ), a vacuum-assist volume regulator ( 56 ), an air-bubble removing filter ( 60 ), and an apparatus ( 62 ) for controlling the concentration of a macromolecular complex in the solution, whereby the circuit ( 50 ) enables safe and efficient delivery, circulation and re-circulation of substances to an isolated heart during cardiopulmonary bypass surgery. 
   
   
       2 . The perfusion circuit according to  claim 1 , wherein the circuit ( 50 ) includes a perfusion catheter ( 64 ) for retrograde delivery of the solution to the coronary sinus. 
   
   
       3 . The perfusion circuit according to  claim 2 , wherein said pump ( 54 ) is a roller pump. 
   
   
       4 . The perfusion circuit according to  claim 3 , wherein the circuit ( 50 ) includes a waste cardiotomy ( 58 ) to remove particulate debris from the solution. 
   
   
       5 . The perfusion circuit according to  claim 4 , wherein the circuit ( 50 ) includes a heat exchanger to control the temperature of the solution. 
   
   
       6 . The perfusion circuit according to  claim 5 , wherein the circuit ( 50 ) includes an oxygenator to control the oxygen content of the solution. 
   
   
       7 . The perfusion circuit according to  claim 2 , wherein the retrograde perfusion catheter ( 64 ) includes asymmetric dumbbell-shaped balloons, or balloon sections ( 66 ,  68 ), that are expanded on opposite sides of the subject's coronary sinus ostium to anchor the catheter ( 64 ) to the ostium and provide an occlusive seal at the ostium. 
   
   
       8 . The perfusion circuit according to  claim 7 , wherein the asymmetric dumbbell-shaped balloons, or balloon sections ( 66 ,  68 ), include a first balloon ( 66 ) that is expanded within the right atrium of the subject's heart for engagement with a wall of the right atrium surrounding the ostium and a second balloon ( 68 ) that is expanded within the coronary sinus into engagement with walls of the coronary sinus. 
   
   
       9 . The perfusion circuit according to  claim 2 , wherein the circuit ( 50 ) includes a cannula ( 70 ) for receiving the solution from the aorta. 
   
   
       10 . The perfusion circuit according to  claim 9 , wherein the circuit ( 50 ) includes cannulae ( 72 ,  74 ) placed within the right and left ventricles of the subject's heart for decompressing the right and left ventricles during circulation of the solution. 
   
   
       11 . A method of delivering a macromolecular complex to a subject's heart, said method comprising the steps of:
 (a) forming a cardiac circuit ( 50 ) that isolates a subject's cardiac circulation from the subject's systemic circulation; and   (b) perfusing a first macromolecular complex solution into the cardiac circuit ( 50 ) in a retrograde manner.   
   
   
       12 . The method according to  claim 11 , wherein the macromolecular complex solution is recirculated in the cardiac circuit ( 50 ) for up to 30 minutes. 
   
   
       13 . The method according to  claim 11 , wherein the subject's cardiac circulation is stopped for up to 10 minutes, thereby allowing the macromolecular complex solution to dwell. 
   
   
       14 . The method according to  claim 13 , wherein the subject's cardiac circulation is restarted and a second macromolecular complex solution is infused in the circuit for up to 20 minutes. 
   
   
       15 . The method according to  claim 13 , wherein the second macromolecular complex is different from the first macromolecular complex solution. 
   
   
       16 . The method according to  claim 11 , wherein the macromolecular complex solution is infused in a retrograde direction and an antegrade direction simultaneously. 
   
   
       17 . The method according to  claim 11 , wherein retrograde infusion is through the coronary sinus. 
   
   
       18 . The method according to  claim 16 , wherein the antegrade infusion is through the ascending aorta. 
   
   
       19 . The method according to  claim 18 , wherein the first macromolecular complex solution is infused retrograde and a third macromolecular complex solution is infused antegrade. 
   
   
       20 . The method according to  claim 19 , wherein the first macromolecular complex and the third macromolecular complex solution are different. 
   
   
       21 . The method according to  claim 19 , wherein the first macromolecular complex and the third macromolecular complex solution are the same. 
   
   
       22 . (canceled) 
   
   
       23 . A method of delivering a macromolecular complex to a subject's heart such that the delivery of the substance to other organs in the subject's body is minimized, comprising the steps of:
 forming and isolating separate systemic and cardiac circuits ( 38 ,  50 ) during cardiopulmonary bypass surgery;   pumping a solution through the cardiac circuit ( 50 );   controlling the volume of the solution flowing within the cardiac circuit ( 50 );   removing air-bubbles and particulate debris from the solution flowing in the cardiac circuit ( 50 ); and   controlling the concentration of a macromolecular complex in the solution.   
   
   
       24 . The method according to  claim 23 , wherein the solution and substance is re-circulated multiple times through the cardiac circuit ( 50 ). 
   
   
       25 . The method according to  claim 23 , wherein an occlusive plug ( 66 ,  68 ) is formed at the ostium of the coronary sinus of the subject's heart into which the solution is circulated retrograde through a coronary circulation path through the heart. 
   
   
       26 . The method according to  claim 24 , wherein the heart is isolated by blocking flow to and from the heart via the superior vena cava, inferior vena cava, pulmonary artery, aorta and pulmonary veins. 
   
   
       27 . The method according to  claim 26 , wherein the solution exits the heart via cannula ( 70 ) positioned in the aorta. 
   
   
       28 . The method according to  claim 27 , wherein the left ventricle and right ventricles are decompressed during circulation of the solution. 
   
   
       29 . The method according to  claim 28 , wherein a roller pump ( 54 ) is utilized to pump the solution through the cardiac circuit ( 50 ) and a vacuum-assist volume regulator ( 56 ) controls the volume of the circulating solution. 
   
   
       30 . The method according to  claim 23 , further comprising the step of controlling the temperature and oxygen content of the solution.