THORACIC SURGERY DIRECTORS ASSOCIATION AWARD
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The Thoracic Surgery Directors Association (TSDA) Resident Research Award, sponsored by Medtronic, lnc, was established in 1990 to encourage resident research in cardiothoracic surge y. Abstracts submitted to The Society of Thoracic Surgeons (STS) Program Committee representing research performed by residents were forwarded to the TSDA to be considered for this award. The abstracts were reviewed by the TSDA Executive Committee consisting of: William A . Gay, Ir, President; Martin F . McKneally, President-Elect; Gordon F . Murray, SecretarylTreasurer; Stanton P. Nolan, Councillor-at-Large; and Bruce A. Reitz, Councillor-at-
Large.
The first T S D A Resident Research Award was given to Dr Todd L. Demmy, resident in training at Allegheny General Hospital, Pittsburgh, Pennsylvania, who received a sum of $2,500 and had his expenses paid to the STS meeting. The TSDA, with support by Medtronic, Inc, will make this award annually, using the above selection procedure. The resident author of the selected study will be recognized at the STS meeting.
Resuscitation of Injured Myocardium With Adenosine and Biventricular Assist Todd L. Demmy, MD, James A. Magovern, MD, Race L. Kao, PhD, and George J. Magovern, MD Allegheny Campus of the Medical College of Pennsylvania, Allegheny General Hospital, and Allegheny-Singer Research Institute, Pittsburgh, Pennsylvania
Recovery of energy metabolism and contractility in stunned myocardium requires several days, even when mechanical circulatory support is employed. This double-blind study was undertaken to determine if myocardial recovery could be accelerated by intracoronary infusion of adenosine during reperfusion. Ten mongrel dogs were subjected to 45 minutes of global normothermic ischemia while on biventricular support with centrifugal pumps. During initial reperfusion, 20 minutes later, and at hourly intervals for 4 hours, dogs received 100 mL/min of unaltered blood or blood enriched with adenosine (0.2 mmollL) into the coronary arteries for 5 minutes. Circulatory support was discontinued after 4 hours or sooner if the first time derivative of left ventricular pressure exceeded 2,000 mm Hg/s. Animals that received adenosine were weaned sooner (72 f 27 versus 216 f 54 minutes) and had higher systolic pressure (110 f 21 versus 57 2
36 mm Hg), lower left ventricular end-diastolic pressure (23.8 & 4.8 versus 34.0 & 7.2 mm Hg), and higher first time derivative of left ventricular pressure (3,407 k 812 versus 1,510 f 1376 mm Hg/s) than controls at the completion of the experiment ( p < 0.05). Final myocar-
L
counterpulsation, or mechanical circulatory assist until hemodynamic function returns. Unfortunately, up to a week of support may be necessary during which time renal, pulmonary, neurologic, or infectious complications can develop that limit survival [l].Shortening the time for hemodynamic recovery of injured myocardium may prevent such complications and thereby improve the prognosis for this group of patients. Adenosine-enriched cardioplegic solutions have been
ow cardiac output can occur after a heart operation or other causes of reversible myocardial injury. Death in many instances can be avoided by supporting the stunned myocardium with inotropic drugs, intraaortic balloon Presented at the Twenty-seventh Annual Meeting of The Society of Thoracic Surgeons, San Francisco, CA, Feb l b 2 0 , 1991. Address reprint requests to Dr Magovern, Allegheny General Hospital, 320 E. North Ave, Pittsburgh, PA 15212.
0 1991 by The Society of Thoracic Surgeons
dium adenosine triphosphate levels were higher i n the adenosine group (20.0 f 3.6 versus 14.2 f 4.0 pmol/g protein; p < 0.05). Determination of infusion and coronary sinus blood concentrations demonstrated a 90% uptake of adenosine. All adenosine animals survived, but 2 of 5 control animals died within 1 hour of weaning. Reperfusion with adenosine-enriched blood accelerated recovery of ischemic myocardium and should be considered for patients requiring mechanical circulatory support after a heart operation.
(Ann Thorac Surg 1991;52:1044-51)
0003-4975/91/$3.50
TSDA AWARD DEMMY ET AL RESUSCITATION OF INJURED MYOCARDIUM
Ann Thorac Surg 1991;52:104451
1045
Fig 1 . Experimental model of biventricular cardiac assist. Heart is placed on biventricular assist by cannulation of femoral artery, left atrial appendage, jugular and femoral veins, and main pulmonary artery. ( A 0 = aorta; IVC = inferior vena cam; LA = left atrium; LV = left ventricle; PA = pulmonary artery; RA = right atrium; RIL = rapid infusion line; RV = right ventricle; SVC = superior uena cavu; IVC = inferior vena cava; heavy dashed lines = sites of cross-clamping; -+ = direction of flow.)
lcc'min
shown to provide excellent myocardial preservation [2-81. Preliminary studies from our laboratory have suggested that reperfusion solutions containing adenosine may also accelerate the recovery of stunned myocardium [9]. This study was undertaken to determine the effect of intracoronary adenosine administration after global normothermic ischemia in a canine model.
Material and Methods Male mongrel dogs weighing 25 to 30 kg were anesthetized with 1% inhaled enflurane after induction with intravenous sodium thiopental (25 mg/kg) and pancuronium bromide (0.1 mg/kg). The animals were positioned in a right lateral decubitus position. The right common femoral vein, left common femoral artery, and left internal jugular vein were exposed for later cannulation. An 18-gauge plastic catheter was inserted into the right femoral artery and a 7F pulmonary artery catheter was introduced through the left common femoral vein. A left anterolateral thoracotomy was performed through the fifth intercostal space. A Tru-Cut biopsy needle (Travenol Labs, Deerfield, IL) was used to obtain a baseline fullthickness left ventricular specimen for measurement of myocardial high-energy phosphates. A second catheter was inserted through the cardiac apex to measure left ventricular pressure. Hemodynamic variables including aortic pressures, pulmonary artery pressures, cardiac output, intraventricular developed pressure (peak systolic minus end-diastolic pressure), and its first derivative (maximal positive dP/dt) were measured using an HP 8890B system (Hewlett-Packard Company, Andover, MA). One thousand units of heparin were given intrave-
nously before initiation of left-sided assistance. Blood was drained from the left heart with a modified 26F two-stage cannula (inserted through the left atrial appendage) and returned to the left common femoral artery through a 16F arterial cannula. The two-stage cannula was modified by excising most of the distal stage and adding additional side holes. Positioning of the cannula across the mitral valve resulted in excellent drainage with consistent left ventricular decompression. Right-sided venous drainage was achieved using two 20F cannulas, one inserted from the left jugular and advanced into the superior vena cava and one inserted from the right femoral vein and advanced into the inferior vena cava. Blood was returned to the pulmonary artery through a 20F arterial cannula. Two Bio-Medicus (Eden Prairie, MN) Bio-pumps (BP-80, see Fig 1) were used for the biventricular assist (BVA). The assist circuits were modified by inserting a %-inch%-inch connector, which contained a Luer-lock port, into the tubing. On the right side this port was used for infusion of blood and crystalloid solutions. On the left side, the port supplied oxygenated blood from the circuit to serve as the carrier fluid for infusion of the adenosine or control solution after the ischemic period. Ischemia was caused by occluding the ascending aorta with a vascular clamp. To prevent any blood not captured by the left heart drainage from entering the coronary arteries, a second cross-clamp was passed through the transverse sinus and applied across both ventricular outflow tracts below the aortic valve. A rapid mechanical cardiac arrest consistently ensued in less than 5 minutes. After the heart was arrested, a 22G catheter was introduced into the coronary sinus through a coronary vein. Myocardial temperature was maintained between 36" and
1046
TSDA AWARD DEMMY ET AL RESUSCITATION OF INJURED MYOCARDIUM
37°C by irrigation of the pericardial cavity with warm saline solution. After 45 minutes of ischemia, the clamp across the ventricular outflow tract was removed, but the ascending aortic clamp remained in place. Left ventricular biopsy specimens were obtained. Arterial blood was drained from the left assist circuit and infused at a rate of 100 mL/min into the aortic root through a 12-gauge aortic root catheter. A Harvard infusion pump was used to infuse 1 mL/min of either the adenosine (20 mmol/L) or the control solution (0.9% saline solution) into the roller pump circuit. Infusing 1 mL/min of 20 mmol/L adenosine into 100 mL/min of blood resulted in a 0.2 mmoVL adenosine solution, which was infused directly into the coronary circulation for 5 minutes. During the infusion period, blood samples were obtained from the infusate and the coronary sinus to measure levels of adenosine and its metabolites. After the 5 minutes of reperfusion, the ascending aortic clamp was removed and the roller pump circuit was flushed and stopped. Hemodynamic readings were then made with the assist pumps at minimal flow (
~
'
The Thoracic Surgery Directors Association (TSDA) Resident Research Award, sponsored by Medtronic, lnc, was established in 1990 to encourage resident research in cardiothoracic surge y. Abstracts submitted to The Society of Thoracic Surgeons (STS) Program Committee representing research performed by residents were forwarded to the TSDA to be considered for this award. The abstracts were reviewed by the TSDA Executive Committee consisting of: William A . Gay, Ir, President; Martin F . McKneally, President-Elect; Gordon F . Murray, SecretarylTreasurer; Stanton P. Nolan, Councillor-at-Large; and Bruce A. Reitz, Councillor-at-
Large.
The first T S D A Resident Research Award was given to Dr Todd L. Demmy, resident in training at Allegheny General Hospital, Pittsburgh, Pennsylvania, who received a sum of $2,500 and had his expenses paid to the STS meeting. The TSDA, with support by Medtronic, Inc, will make this award annually, using the above selection procedure. The resident author of the selected study will be recognized at the STS meeting.
Resuscitation of Injured Myocardium With Adenosine and Biventricular Assist Todd L. Demmy, MD, James A. Magovern, MD, Race L. Kao, PhD, and George J. Magovern, MD Allegheny Campus of the Medical College of Pennsylvania, Allegheny General Hospital, and Allegheny-Singer Research Institute, Pittsburgh, Pennsylvania
Recovery of energy metabolism and contractility in stunned myocardium requires several days, even when mechanical circulatory support is employed. This double-blind study was undertaken to determine if myocardial recovery could be accelerated by intracoronary infusion of adenosine during reperfusion. Ten mongrel dogs were subjected to 45 minutes of global normothermic ischemia while on biventricular support with centrifugal pumps. During initial reperfusion, 20 minutes later, and at hourly intervals for 4 hours, dogs received 100 mL/min of unaltered blood or blood enriched with adenosine (0.2 mmollL) into the coronary arteries for 5 minutes. Circulatory support was discontinued after 4 hours or sooner if the first time derivative of left ventricular pressure exceeded 2,000 mm Hg/s. Animals that received adenosine were weaned sooner (72 f 27 versus 216 f 54 minutes) and had higher systolic pressure (110 f 21 versus 57 2
36 mm Hg), lower left ventricular end-diastolic pressure (23.8 & 4.8 versus 34.0 & 7.2 mm Hg), and higher first time derivative of left ventricular pressure (3,407 k 812 versus 1,510 f 1376 mm Hg/s) than controls at the completion of the experiment ( p < 0.05). Final myocar-
L
counterpulsation, or mechanical circulatory assist until hemodynamic function returns. Unfortunately, up to a week of support may be necessary during which time renal, pulmonary, neurologic, or infectious complications can develop that limit survival [l].Shortening the time for hemodynamic recovery of injured myocardium may prevent such complications and thereby improve the prognosis for this group of patients. Adenosine-enriched cardioplegic solutions have been
ow cardiac output can occur after a heart operation or other causes of reversible myocardial injury. Death in many instances can be avoided by supporting the stunned myocardium with inotropic drugs, intraaortic balloon Presented at the Twenty-seventh Annual Meeting of The Society of Thoracic Surgeons, San Francisco, CA, Feb l b 2 0 , 1991. Address reprint requests to Dr Magovern, Allegheny General Hospital, 320 E. North Ave, Pittsburgh, PA 15212.
0 1991 by The Society of Thoracic Surgeons
dium adenosine triphosphate levels were higher i n the adenosine group (20.0 f 3.6 versus 14.2 f 4.0 pmol/g protein; p < 0.05). Determination of infusion and coronary sinus blood concentrations demonstrated a 90% uptake of adenosine. All adenosine animals survived, but 2 of 5 control animals died within 1 hour of weaning. Reperfusion with adenosine-enriched blood accelerated recovery of ischemic myocardium and should be considered for patients requiring mechanical circulatory support after a heart operation.
(Ann Thorac Surg 1991;52:1044-51)
0003-4975/91/$3.50
TSDA AWARD DEMMY ET AL RESUSCITATION OF INJURED MYOCARDIUM
Ann Thorac Surg 1991;52:104451
1045
Fig 1 . Experimental model of biventricular cardiac assist. Heart is placed on biventricular assist by cannulation of femoral artery, left atrial appendage, jugular and femoral veins, and main pulmonary artery. ( A 0 = aorta; IVC = inferior vena cam; LA = left atrium; LV = left ventricle; PA = pulmonary artery; RA = right atrium; RIL = rapid infusion line; RV = right ventricle; SVC = superior uena cavu; IVC = inferior vena cava; heavy dashed lines = sites of cross-clamping; -+ = direction of flow.)
lcc'min
shown to provide excellent myocardial preservation [2-81. Preliminary studies from our laboratory have suggested that reperfusion solutions containing adenosine may also accelerate the recovery of stunned myocardium [9]. This study was undertaken to determine the effect of intracoronary adenosine administration after global normothermic ischemia in a canine model.
Material and Methods Male mongrel dogs weighing 25 to 30 kg were anesthetized with 1% inhaled enflurane after induction with intravenous sodium thiopental (25 mg/kg) and pancuronium bromide (0.1 mg/kg). The animals were positioned in a right lateral decubitus position. The right common femoral vein, left common femoral artery, and left internal jugular vein were exposed for later cannulation. An 18-gauge plastic catheter was inserted into the right femoral artery and a 7F pulmonary artery catheter was introduced through the left common femoral vein. A left anterolateral thoracotomy was performed through the fifth intercostal space. A Tru-Cut biopsy needle (Travenol Labs, Deerfield, IL) was used to obtain a baseline fullthickness left ventricular specimen for measurement of myocardial high-energy phosphates. A second catheter was inserted through the cardiac apex to measure left ventricular pressure. Hemodynamic variables including aortic pressures, pulmonary artery pressures, cardiac output, intraventricular developed pressure (peak systolic minus end-diastolic pressure), and its first derivative (maximal positive dP/dt) were measured using an HP 8890B system (Hewlett-Packard Company, Andover, MA). One thousand units of heparin were given intrave-
nously before initiation of left-sided assistance. Blood was drained from the left heart with a modified 26F two-stage cannula (inserted through the left atrial appendage) and returned to the left common femoral artery through a 16F arterial cannula. The two-stage cannula was modified by excising most of the distal stage and adding additional side holes. Positioning of the cannula across the mitral valve resulted in excellent drainage with consistent left ventricular decompression. Right-sided venous drainage was achieved using two 20F cannulas, one inserted from the left jugular and advanced into the superior vena cava and one inserted from the right femoral vein and advanced into the inferior vena cava. Blood was returned to the pulmonary artery through a 20F arterial cannula. Two Bio-Medicus (Eden Prairie, MN) Bio-pumps (BP-80, see Fig 1) were used for the biventricular assist (BVA). The assist circuits were modified by inserting a %-inch%-inch connector, which contained a Luer-lock port, into the tubing. On the right side this port was used for infusion of blood and crystalloid solutions. On the left side, the port supplied oxygenated blood from the circuit to serve as the carrier fluid for infusion of the adenosine or control solution after the ischemic period. Ischemia was caused by occluding the ascending aorta with a vascular clamp. To prevent any blood not captured by the left heart drainage from entering the coronary arteries, a second cross-clamp was passed through the transverse sinus and applied across both ventricular outflow tracts below the aortic valve. A rapid mechanical cardiac arrest consistently ensued in less than 5 minutes. After the heart was arrested, a 22G catheter was introduced into the coronary sinus through a coronary vein. Myocardial temperature was maintained between 36" and
1046
TSDA AWARD DEMMY ET AL RESUSCITATION OF INJURED MYOCARDIUM
37°C by irrigation of the pericardial cavity with warm saline solution. After 45 minutes of ischemia, the clamp across the ventricular outflow tract was removed, but the ascending aortic clamp remained in place. Left ventricular biopsy specimens were obtained. Arterial blood was drained from the left assist circuit and infused at a rate of 100 mL/min into the aortic root through a 12-gauge aortic root catheter. A Harvard infusion pump was used to infuse 1 mL/min of either the adenosine (20 mmol/L) or the control solution (0.9% saline solution) into the roller pump circuit. Infusing 1 mL/min of 20 mmol/L adenosine into 100 mL/min of blood resulted in a 0.2 mmoVL adenosine solution, which was infused directly into the coronary circulation for 5 minutes. During the infusion period, blood samples were obtained from the infusate and the coronary sinus to measure levels of adenosine and its metabolites. After the 5 minutes of reperfusion, the ascending aortic clamp was removed and the roller pump circuit was flushed and stopped. Hemodynamic readings were then made with the assist pumps at minimal flow (
