sense, antisense, nonsense, and missense

1
Ann Thorac Surg 1993;56:39W2 CORRESPONDENCE 397 2. Sauvage LR. Healing basis and surgical techniques for com- plete revascularization of the left ventricle using only the internal mammary arteries. Ann Thorac Surg 1986;42:449-67. 3. Cosgrove DM. Techniques to maximixe mammary artery length. Ann Thorac Surg 1985;40:7&9. 4. Huddleston CB, Stoney WS, Alford WC Jr, et al. Internal mammary artery grafts: technical factors influencing patency. Ann Thorac Surg 1986;42:54>9. Sense, Antisense, Nonsense, and Missense To the Editor: 1 read with interest Wagner’s editorial entitled “Making some SENSE out of thoracoscopy” [l]. I must admit that I was initially enticed to read the article by the attractive title, especially the word “SENSE.” I thought it was about sense, antisense, non- sense, and missense, which were terms commonly seen in writings in molecular biology. Nowadays, techniques of cellular and molecular biology can be applied to the study of particular aspects of disease mechanisms already identified, in finer and finer details, in nearly every specialty. I, therefore, was anticipating Wagner to discuss thora- coscopy using a genetic approach, such as sense strand, an- tisense RNA, nonsense codon, and missense mutation. Al- though l was disappointed in one way, I was delighted in another way, because the content of Wagner’s article was quite amusing and enlightening in its own right. Tsung 0. Cheng, M D Division of Cardiology The George Washington University Department of Medicine 2150 Pennsylvania Ave N W Washington, DC 20037 Reference 1. Wagner RB. Making some SENSE out of thoracoscopy. Ann Thorac Surg 1993;55:332. Hypothermic Thoracoabdominal Aneurysm Operation To the Editor: We read with interest the article “Hypothermic thoracic and thoracoabdominal aneurysm operation: a central cannulation technique” by Stephen Westaby [I]. The idea of using cardiopul- monary bypass and hypothermia in these operations has been rightly highlighted. But we were surprised to read the technique of central venous cannulation using the two-stage venous can- nula through the right internal jugular vein for institution of cardiopulmonary bypass. Femoral venous cannulation is by far easier and safer than the jugular approach. As has been our experience, it is possible to achieve central cannulation with adequate venous drainage through the femoral approach by using a Bio-Medicus venous cannula. These cannulas are thin walled (0.3 mm) and are long enough to reach the right atrium. The gravity venous drainage thus obtained is enough to go on full cardiopulmonary bypass with a flow of 2.4 L . m-’. min-’. We have used this technique in 4 cases, which included redo coronary artery bypass grafting, operation for aortic cannulation blow-outs, and operation for aneurysm of the right ventricular outflow tract patch after cor- rection of tetralogy of Fallot. These cannulae are wire reinforced and have the added advan- tage of being kink resistant. They are also coated with the Carmeda surface, which reduces the susceptibility to clot forma- tion. Mahadev D. Dixit, M D Devi P. Shetty, M D K. V. Surendranath, BSc Department of Cardiothoracic Surgery and Extra Corporeal Technology B. M . Birla Heart Research Centre 1 11, National Library Ave Calcutta 700 027 India Reference 1. Westaby S. Hypothermic thoracic and thoracoabdominal an- eurysm operation: a central cannulation technique. Ann Tho- rac Surg 1992;54:25?-8. Release of Vasoactive Substances During Cardiopulmonary Bypass To the Editor: The recent review by Downing and Edmunds [l] provided an excellent and comprehensive list of vasoactive substances re- leased during cardiopulmonary bypass (CPB). We wish to high- light an important role of plasma hemoglobin that was only mentioned briefly. Plasma hemoglobin, both bound and in its free state, may have more important influence on the blood vasculature than has been thought. Red blood cells are traumatized during CPB by various means including shear stress and contact with synthetic surfaces of the perfusion circuit, bubbling oxygenators, and the cardiot- omy sucker. Once hemolysis occurs, hemoglobin is released into the plasma and is rapidly bound to haptoglobin to form the haptoglobin-hemoglobin complex to prevent iron loss and renal failure. This complex is then metabolized by the reticuloendothe- lial system. The disposal of free plasma hemoglobin during CPB is rapid but soon saturated due to the continual generation of more hemoglobin coupled with the depletion of haptoglobin. This results in an increase in plasma free hemoglobin during CPB that correlates well with the length of bypass. A study in our cardiac unit on 15 patients undergoing elective operations with CPB demonstrated this. Blood samples were collected before, during, and at regular intervals for 48 hours after CPB and quantified for plasma hemoglobin. Plasma hemoglobin level increased with time on CPB, reaching a peak of 5.09 5 0.75 pmol/L. This level was still significantly raised at 2 hours but returned to baseline level by 6 hours [2]. Similar results have been reported by Tanaka and associates [3]. The effect of plasma free hemoglobin and the haptoglobin- hemoglobin complex is to inactivate endothelium-derived relax- ing factor-nitric oxide, hence inhibiting endothelium-derived relaxation [4], which could result in an increase in vascular tone. The increased tone and reduced relaxation in turn increase vascular resistance, which may be reflected by an increase in systemic blood pressure and may account for the post-CPB hypertension seen in approximately 8% to 73% of patients after CPB [5]. The time scale of this transient hypertensive state correlates well with the raised levels of plasma hemoglobin. Plasma hemoglobin has also been implicated in the pathogenesis of other hypertensive conditions such as preeclampsia [6]. The effects of plasma hemoglobin on endothelium-derived relaxation have been reported in animal studies 171. Organ bath studies in our laboratory have confirmed this and demonstrated a marked reduction in endothelium-dependent relaxation in

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Page 1: Sense, antisense, nonsense, and missense

Ann Thorac Surg 1993;56:39W2

CORRESPONDENCE 397

2. Sauvage LR. Healing basis and surgical techniques for com- plete revascularization of the left ventricle using only the internal mammary arteries. Ann Thorac Surg 1986;42:449-67.

3. Cosgrove DM. Techniques to maximixe mammary artery length. Ann Thorac Surg 1985;40:7&9.

4. Huddleston CB, Stoney WS, Alford WC Jr, et al. Internal mammary artery grafts: technical factors influencing patency. Ann Thorac Surg 1986;42:54>9.

Sense, Antisense, Nonsense, and Missense To the Editor:

1 read with interest Wagner’s editorial entitled “Making some SENSE out of thoracoscopy” [l]. I must admit that I was initially enticed to read the article by the attractive title, especially the word “SENSE.” I thought it was about sense, antisense, non- sense, and missense, which were terms commonly seen in writings in molecular biology.

Nowadays, techniques of cellular and molecular biology can be applied to the study of particular aspects of disease mechanisms already identified, in finer and finer details, in nearly every specialty. I, therefore, was anticipating Wagner to discuss thora- coscopy using a genetic approach, such as sense strand, an- tisense RNA, nonsense codon, and missense mutation. Al- though l was disappointed in one way, I was delighted in another way, because the content of Wagner’s article was quite amusing and enlightening in its own right.

Tsung 0. Cheng, M D

Division of Cardiology The George Washington University Department of Medicine 2150 Pennsylvania Ave N W Washington, DC 20037

Reference 1. Wagner RB. Making some SENSE out of thoracoscopy. Ann

Thorac Surg 1993;55:332.

Hypothermic Thoracoabdominal Aneurysm Operation To the Editor:

We read with interest the article “Hypothermic thoracic and thoracoabdominal aneurysm operation: a central cannulation technique” by Stephen Westaby [I]. The idea of using cardiopul- monary bypass and hypothermia in these operations has been rightly highlighted. But we were surprised to read the technique of central venous cannulation using the two-stage venous can- nula through the right internal jugular vein for institution of cardiopulmonary bypass.

Femoral venous cannulation is by far easier and safer than the jugular approach. As has been our experience, it is possible to achieve central cannulation with adequate venous drainage through the femoral approach by using a Bio-Medicus venous cannula. These cannulas are thin walled (0.3 mm) and are long enough to reach the right atrium. The gravity venous drainage thus obtained is enough to go on full cardiopulmonary bypass with a flow of 2.4 L . m-’. min-’. We have used this technique in 4 cases, which included redo coronary artery bypass grafting, operation for aortic cannulation blow-outs, and operation for aneurysm of the right ventricular outflow tract patch after cor- rection of tetralogy of Fallot.

These cannulae are wire reinforced and have the added advan- tage of being kink resistant. They are also coated with the

Carmeda surface, which reduces the susceptibility to clot forma- tion.

Mahadev D. Dixit, M D Devi P. Shetty, M D K . V . Surendranath, BSc

Department of Cardiothoracic Surgery and Extra Corporeal Technology B. M . Birla Heart Research Centre 1 11, National Library Ave Calcutta 700 027 India

Reference 1. Westaby S. Hypothermic thoracic and thoracoabdominal an-

eurysm operation: a central cannulation technique. Ann Tho- rac Surg 1992;54:25?-8.

Release of Vasoactive Substances During Cardiopulmonary Bypass To the Editor:

The recent review by Downing and Edmunds [ l ] provided an excellent and comprehensive list of vasoactive substances re- leased during cardiopulmonary bypass (CPB). We wish to high- light an important role of plasma hemoglobin that was only mentioned briefly.

Plasma hemoglobin, both bound and in its free state, may have more important influence on the blood vasculature than has been thought. Red blood cells are traumatized during CPB by various means including shear stress and contact with synthetic surfaces of the perfusion circuit, bubbling oxygenators, and the cardiot- omy sucker. Once hemolysis occurs, hemoglobin is released into the plasma and is rapidly bound to haptoglobin to form the haptoglobin-hemoglobin complex to prevent iron loss and renal failure. This complex is then metabolized by the reticuloendothe- lial system. The disposal of free plasma hemoglobin during CPB is rapid but soon saturated due to the continual generation of more hemoglobin coupled with the depletion of haptoglobin. This results in an increase in plasma free hemoglobin during CPB that correlates well with the length of bypass. A study in our cardiac unit on 15 patients undergoing elective operations with CPB demonstrated this. Blood samples were collected before, during, and at regular intervals for 48 hours after CPB and quantified for plasma hemoglobin. Plasma hemoglobin level increased with time on CPB, reaching a peak of 5.09 5 0.75 pmol/L. This level was still significantly raised at 2 hours but returned to baseline level by 6 hours [2]. Similar results have been reported by Tanaka and associates [3].

The effect of plasma free hemoglobin and the haptoglobin- hemoglobin complex is to inactivate endothelium-derived relax- ing factor-nitric oxide, hence inhibiting endothelium-derived relaxation [4], which could result in an increase in vascular tone. The increased tone and reduced relaxation in turn increase vascular resistance, which may be reflected by an increase in systemic blood pressure and may account for the post-CPB hypertension seen in approximately 8% to 73% of patients after CPB [5]. The time scale of this transient hypertensive state correlates well with the raised levels of plasma hemoglobin. Plasma hemoglobin has also been implicated in the pathogenesis of other hypertensive conditions such as preeclampsia [6].

The effects of plasma hemoglobin on endothelium-derived relaxation have been reported in animal studies 171. Organ bath studies in our laboratory have confirmed this and demonstrated a marked reduction in endothelium-dependent relaxation in