Coronary sinus (CS) rupture occurring during retrograde cardioplegia (RCP) is a rare complication. Patients with left ventricular hypertrophy are at higher risk for injury to the CS. The patient was a 66-year-old female with hypertension, ischemic cardiomyopathy and dysrhythmias, who had evidence of an anterior wall myocardial infarction, congestive heart failure and angina. During coronary artery bypass surgery, antegrade cardioplegia was initially administered, but aortic insufficiency prevented adequate myocardial cooling. RCP was then administered and the heart cooled appropriately. After approximately 300 ml of blood cardioplegic solution had been given, the CS pressure suddenly dropped from 30 mmHg to zero. RCP administration was stopped, and the surgeon palpated a hematoma over the area of the CS, which later ruptured upon rotation of the heart. A primary repair could not be performed, so a pericardial patch was placed over the area of disruption, which appeared to provide adequate hemostasis. The patient was weaned from cardiopulmonary bypass (CPB), but began to bleed freely from the CS distal to the pericardial patch. The patient was placed back on CPB to allow further repair of the CS, but the tissues were thin and friable and the ventricle disassociated from the ventricular septum. The situation was deemed not salvageable and further attempts at repair were stopped. The perfusionist should monitor infusion pressures and the CS waveform during RCP delivery. Changes in the waveform may indicate cannula malposition, loss of balloon seal, or, more rarely, CS rupture; such changes should prompt immediate cessation of RCP delivery.

BACKGROUND:Reperfusion injury remains a significant and sometimes fatal problem in clinical lung transplantation. Controlled reperfusion of the transplanted lung using white cell-filtered, nutrient-enriched blood has been shown recently to significantly ameliorate reperfusion damage in a porcine model. We modified this experimental technique and applied it to human lung transplantation.METHODS:Approximately 1,500 mL of arterial blood was slowly collected in a cardiotomy reservoir during the lung implant, and mixed to make a 4:1 solution of blood:modified Buckberg perfusate. This solution was passed through a leukocyte filter and into the transplant pulmonary artery for 10 minutes, at a controlled rate (200 mL/min) and pressure (less than 20 mm Hg), immediately before removal of the vascular clamp.RESULTS:Five patients underwent lung transplantation (1 bilateral, 4 single lung) using this technique. All patients were ventilated on a 40% fraction of inspired oxygen within a few hours and extubated on or before the first postoperative day.CONCLUSIONS:Controlled reperfusion of the transplanted lung with white cell-filtered, nutrient-enriched blood has given excellent functional results in our small initial clinical series.

I read with interest the paper by Lick and associates in which they cite using our technique of controlled pulmonary reperfusion to limit reperfusion damage in patients undergoing lung transplantation [1Lick S.D. Brown Jr, P.S. Kurusz M. Vertrees R.A. McQuitty C.K. Johnston W.E. Technique of controlled reperfusion of the transplanted lung in humans.Ann Thorac Surg. 2000; 69: 910-912Abstract Full Text Full Text PDF PubMed Scopus (41) Google Scholar, 2Halldorsson A. Kronon M.T. Allen B.S. et al.Controlled reperfusion after lung ischemia implications for improved function after lung transplantation.J Thorac Cardiovasc Surg. 1998; 115: 415-425Abstract Full Text Full Text PDF PubMed Scopus (64) Google Scholar, 3Halldorsson A. Kronon M.T. Allen B.S. et al.Controlled reperfusion prevents pulmonary injury after 24 hours of lung preservation.Ann Thorac Surg. 1998; 66: 877-885Abstract Full Text Full Text PDF PubMed Scopus (53) Google Scholar, 4Halldorsson A.O. Kronon M.T. Allen B.S. Rahman S. Wang T. Lowering the pressure of the initial reperfusate reduces the reperfusion injury after pulmonary ischemia.Ann Thorac Surg. 2000; 69: 198-204Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar]. The authors are to be commended for applying the principles of controlled reperfusion to the clinical setting. Their excellent results confirm the validity of the experimental studies, and demonstrate that controlled reperfusion prevents a reperfusion injury in transplant patients.My concern is that they have unnecessarily complicated the method of reperfusion by modifying our technique. Most problematic is that the authors leave the atrial clamp in place and the anastomosis open during the entire 10 minutes of controlled reperfusion. They collect the effluent (reperfusate) with a cell saver for reinfusion after it has been washed [1Lick S.D. Brown Jr, P.S. Kurusz M. Vertrees R.A. McQuitty C.K. Johnston W.E. Technique of controlled reperfusion of the transplanted lung in humans.Ann Thorac Surg. 2000; 69: 910-912Abstract Full Text Full Text PDF PubMed Scopus (41) Google Scholar]. This necessitates temporarily removing 1,500 cc’s of blood from the patient in order to make the modified reperfusate. The authors state they do this to prevent hypotension from substances in the reperfusate solution, and to limit wash-out of active metabolites. I understand their concerns, but believe that this modification is completely unnecessary, increases potential problems, and make the procedure unduly complex.In our laboratory studies, we took blood directly from the aorta, mixed it with a crystalloid solution using a cardioplegic mixer (BCD Blood Cardioplegia System, Sorin Biomedica, Arvada, CO), and then infused the modified blood solution into the transplanted lung (controlled reperfusion) for 10 minutes [2Halldorsson A. Kronon M.T. Allen B.S. et al.Controlled reperfusion after lung ischemia implications for improved function after lung transplantation.J Thorac Cardiovasc Surg. 1998; 115: 415-425Abstract Full Text Full Text PDF PubMed Scopus (64) Google Scholar, 3Halldorsson A. Kronon M.T. Allen B.S. et al.Controlled reperfusion prevents pulmonary injury after 24 hours of lung preservation.Ann Thorac Surg. 1998; 66: 877-885Abstract Full Text Full Text PDF PubMed Scopus (53) Google Scholar, 4Halldorsson A.O. Kronon M.T. Allen B.S. Rahman S. Wang T. Lowering the pressure of the initial reperfusate reduces the reperfusion injury after pulmonary ischemia.Ann Thorac Surg. 2000; 69: 198-204Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar]. The atrial clamp was only left in place for approximately the first 60 seconds, to wash out the lung preservation solution to avoid electrolyte problems. This also allowed for deairing. The atrial clamp was then removed, so that blood from the aorta (modified reperfusate) immediately returned to the systemic circulation; this prevented hypovolemia and the need for blood transfusions. We used a clinically relevant large animal transplant model, without bypass, and had no episodes of hypotension or need for transfusions. In contrast, with their modification of first withdrawing 1,500 ccs of blood, the authors experienced both hypotension and increased need for transfusion.Furthermore, we showed that the contralateral (nontransplanted) lung injury that occurs with uncontrolled reperfusion was completely prevented with controlled reperfusion. This indicates that wash-out of active inflammatory mediators is not a reason to modify our reperfusion protocol [2Halldorsson A. Kronon M.T. Allen B.S. et al.Controlled reperfusion after lung ischemia implications for improved function after lung transplantation.J Thorac Cardiovasc Surg. 1998; 115: 415-425Abstract Full Text Full Text PDF PubMed Scopus (64) Google Scholar]. During the experimental studies, we initially worried that the high concentration of citrate in the reperfusate solution might cause hyocalcemia and hypotension; however, no animal became hypotensive. Nevertheless, we recommend that calcium be available in the event hypotension occurs during reperfusion. We agree with Lick and associates that the modified reperfusate should be infused at a pressure of 20 mm Hg. In contrast to our early studies, we confirmed this in an article just published in this journal [4Halldorsson A.O. Kronon M.T. Allen B.S. Rahman S. Wang T. Lowering the pressure of the initial reperfusate reduces the reperfusion injury after pulmonary ischemia.Ann Thorac Surg. 2000; 69: 198-204Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar]. Lastly, based on our recent work in the heart, we believe that prostaglandins should probably replace nitroglycerine in the modified reperfusate solution [5Kronon M.T. Allen B.S. Halldorsson A.O. Rahman S. Wang T. Ilbawi M.N. L-Arginine, prostaglandin, and white cell filtration equally improve myocardial protection in stressed neonatal hearts.J Thorac Cardiovasc Surg. 1999; 118: 665-673Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar].I again congratulate the authors and their coworkers on their pioneering clinical study. Now that the experimental findings have been confirmed clinically, I hope that they, and others, will undertake the necessary larger randomized trial. I read with interest the paper by Lick and associates in which they cite using our technique of controlled pulmonary reperfusion to limit reperfusion damage in patients undergoing lung transplantation [1Lick S.D. Brown Jr, P.S. Kurusz M. Vertrees R.A. McQuitty C.K. Johnston W.E. Technique of controlled reperfusion of the transplanted lung in humans.Ann Thorac Surg. 2000; 69: 910-912Abstract Full Text Full Text PDF PubMed Scopus (41) Google Scholar, 2Halldorsson A. Kronon M.T. Allen B.S. et al.Controlled reperfusion after lung ischemia implications for improved function after lung transplantation.J Thorac Cardiovasc Surg. 1998; 115: 415-425Abstract Full Text Full Text PDF PubMed Scopus (64) Google Scholar, 3Halldorsson A. Kronon M.T. Allen B.S. et al.Controlled reperfusion prevents pulmonary injury after 24 hours of lung preservation.Ann Thorac Surg. 1998; 66: 877-885Abstract Full Text Full Text PDF PubMed Scopus (53) Google Scholar, 4Halldorsson A.O. Kronon M.T. Allen B.S. Rahman S. Wang T. Lowering the pressure of the initial reperfusate reduces the reperfusion injury after pulmonary ischemia.Ann Thorac Surg. 2000; 69: 198-204Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar]. The authors are to be commended for applying the principles of controlled reperfusion to the clinical setting. Their excellent results confirm the validity of the experimental studies, and demonstrate that controlled reperfusion prevents a reperfusion injury in transplant patients. My concern is that they have unnecessarily complicated the method of reperfusion by modifying our technique. Most problematic is that the authors leave the atrial clamp in place and the anastomosis open during the entire 10 minutes of controlled reperfusion. They collect the effluent (reperfusate) with a cell saver for reinfusion after it has been washed [1Lick S.D. Brown Jr, P.S. Kurusz M. Vertrees R.A. McQuitty C.K. Johnston W.E. Technique of controlled reperfusion of the transplanted lung in humans.Ann Thorac Surg. 2000; 69: 910-912Abstract Full Text Full Text PDF PubMed Scopus (41) Google Scholar]. This necessitates temporarily removing 1,500 cc’s of blood from the patient in order to make the modified reperfusate. The authors state they do this to prevent hypotension from substances in the reperfusate solution, and to limit wash-out of active metabolites. I understand their concerns, but believe that this modification is completely unnecessary, increases potential problems, and make the procedure unduly complex. In our laboratory studies, we took blood directly from the aorta, mixed it with a crystalloid solution using a cardioplegic mixer (BCD Blood Cardioplegia System, Sorin Biomedica, Arvada, CO), and then infused the modified blood solution into the transplanted lung (controlled reperfusion) for 10 minutes [2Halldorsson A. Kronon M.T. Allen B.S. et al.Controlled reperfusion after lung ischemia implications for improved function after lung transplantation.J Thorac Cardiovasc Surg. 1998; 115: 415-425Abstract Full Text Full Text PDF PubMed Scopus (64) Google Scholar, 3Halldorsson A. Kronon M.T. Allen B.S. et al.Controlled reperfusion prevents pulmonary injury after 24 hours of lung preservation.Ann Thorac Surg. 1998; 66: 877-885Abstract Full Text Full Text PDF PubMed Scopus (53) Google Scholar, 4Halldorsson A.O. Kronon M.T. Allen B.S. Rahman S. Wang T. Lowering the pressure of the initial reperfusate reduces the reperfusion injury after pulmonary ischemia.Ann Thorac Surg. 2000; 69: 198-204Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar]. The atrial clamp was only left in place for approximately the first 60 seconds, to wash out the lung preservation solution to avoid electrolyte problems. This also allowed for deairing. The atrial clamp was then removed, so that blood from the aorta (modified reperfusate) immediately returned to the systemic circulation; this prevented hypovolemia and the need for blood transfusions. We used a clinically relevant large animal transplant model, without bypass, and had no episodes of hypotension or need for transfusions. In contrast, with their modification of first withdrawing 1,500 ccs of blood, the authors experienced both hypotension and increased need for transfusion. Furthermore, we showed that the contralateral (nontransplanted) lung injury that occurs with uncontrolled reperfusion was completely prevented with controlled reperfusion. This indicates that wash-out of active inflammatory mediators is not a reason to modify our reperfusion protocol [2Halldorsson A. Kronon M.T. Allen B.S. et al.Controlled reperfusion after lung ischemia implications for improved function after lung transplantation.J Thorac Cardiovasc Surg. 1998; 115: 415-425Abstract Full Text Full Text PDF PubMed Scopus (64) Google Scholar]. During the experimental studies, we initially worried that the high concentration of citrate in the reperfusate solution might cause hyocalcemia and hypotension; however, no animal became hypotensive. Nevertheless, we recommend that calcium be available in the event hypotension occurs during reperfusion. We agree with Lick and associates that the modified reperfusate should be infused at a pressure of 20 mm Hg. In contrast to our early studies, we confirmed this in an article just published in this journal [4Halldorsson A.O. Kronon M.T. Allen B.S. Rahman S. Wang T. Lowering the pressure of the initial reperfusate reduces the reperfusion injury after pulmonary ischemia.Ann Thorac Surg. 2000; 69: 198-204Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar]. Lastly, based on our recent work in the heart, we believe that prostaglandins should probably replace nitroglycerine in the modified reperfusate solution [5Kronon M.T. Allen B.S. Halldorsson A.O. Rahman S. Wang T. Ilbawi M.N. L-Arginine, prostaglandin, and white cell filtration equally improve myocardial protection in stressed neonatal hearts.J Thorac Cardiovasc Surg. 1999; 118: 665-673Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar]. I again congratulate the authors and their coworkers on their pioneering clinical study. Now that the experimental findings have been confirmed clinically, I hope that they, and others, will undertake the necessary larger randomized trial. ReplyThe Annals of Thoracic SurgeryVol. 70Issue 4Preview Full-Text PDF

The purpose of this study was to determine what influence various combinations of mechanical and bioprosthetic valves in the aortic, mitral, and tricuspid positions had on late morbidity and mortality of 40 hospital survivors of triple-valve replacement. At operation the patients ranged in age from 27 to 69 years; 73% were women. The mean postoperative follow-up interval was 8.3 years, with a total follow-up of 331 years (100% complete). At 12 months after operation, functional class decreased from 3.3 to 1.6 (p < 0.05), cardiac index increased from 2.0 to 2.6 L.min-1 x m-2 (p < 0.05), and pulmonary artery pressures decreased from 59/27 to 40/17 mm Hg (p < 0.05). There were no differences in preoperative variables between groups. Actuarial survival for the 40 patients (exclusive of 30-day or in-hospital mortality, which was 31%) was 78% and 74% at 5 and 10 years. At the same milestones, freedom from reoperation was 96% and 54%, freedom from combined thromboembolism and anticoagulant-related hemorrhage was 68% and 56%, and freedom from all late valve-related morbidity and mortality was 64% and 25%. Comparison of the patients with two or more mechanical prostheses with the patients having two or more bioprostheses indicated no significant differences in actuarial freedom from late death, thromboembolic events, or anticoagulant-related hemorrhage. However the actuarial freedom from reoperation in the groups with two or more mechanical valves was lower than that of the groups with two or more bioprosthetic valves (0/10 versus 13/30; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

The purpose of this study was to determine if the combination of a mechanical and bioprosthetic valve in the aortic and mitral positions influences late morbidity and mortality when compared with patients who had dual mechanical or dual bioprosthetic valves inserted. We reviewed the course of 89 hospital survivors of combined aortic and mitral valve replacement. The mean postoperative follow-up interval was 6.6 years, with a total follow-up of 583 years (98% complete). At 12 months after operation, mean functional class decreased from 3.1 to 1.7 (p < 0.05) and mean cardiac index increased from 2.1 to 2.5 L.min-1.m-2 (p < 0.05). Actuarial survival for the 89 patients (exclusive of < 30-day or in-hospital mortality, 14%) was 70%, 51%, and 33% at 5, 10, and 15 years. Freedom from reoperation was 93%, 78%, and 68%, and freedom from combined thromboembolism and anticoagulant-related hemorrhage was 82%, 60%, and 50%. These results show that there was no difference in overall survival in patients with dual mechanical valves, dual bioprosthetic valves, or a combination of both types at 15 years. There was, however, a lower reoperation rate in the group with dual mechanical valves as compared with the group with dual bioprosthetic valves (p < 0.05 at 10 years) or with a combination of valves (p < 0.05 at 15 years). The higher the number of mechanical valves the higher the combined risk of thromboembolism and anticoagulant-related hemorrhage.(ABSTRACT TRUNCATED AT 250 WORDS)

The purpose of this study was to determine the effects of triiodothyronine (T3) on postischemic left ventricular performance and high-energy phosphate content in a severe injury model. Isolated working rat hearts (n = 63) received 20 mL of hyperkalemic NIH No. 1 cardioplegia and were subjected to 20 minutes of ischemia at 37 degrees C. Treated hearts were reperfused with T3-supplemented modified Krebs-Henseleit buffer. Control hearts did not receive T3 supplementation. All treated hearts (n = 44) performed work after ischemia, whereas 26% (5/19) of the control hearts were not able to perform any left ventricular work after ischemia. Comparisons with preischemic values demonstrated significant progressive hemodynamic recovery with increasing concentrations of T3 (0, 0.06, 0.15, and 0.60 ng/mL) with concomitant recovery of left ventricular stroke work index (63%, 72%, 89% [p less than 0.05], and 99% [p less than 0.05], respectively). There were corresponding increases in recovery of aortic flow, systolic pressure, cardiac index, and stroke volume index (p less than 0.05). There were no significant changes in coronary sinus flow or heart rate in any group compared with preischemic values. Comparisons of postischemic high-energy phosphate concentrations also demonstrated no change between treated and untreated groups (p greater than 0.05). We conclude that administration of T3 in a severe left ventricular injury model significantly augments rapid ventricular recovery with no change in postischemic high-energy phosphate concentrations.

Acylation of Ph2P(O)Me with a lactone gives a Horner-Wittig intermediate with a Z-double bond protected as a Diels-Alder adduct with furan and hence (Z)-penta-2,4-dien-1-ol. Substituted (E)-penta-2,4-dien-1-ols are available by a more general route involving addition of enals to phosphine oxides, a regiochemically controlled allylic alcohol transposition, and a Horner-Wittig reaction. The geometry of only one double bond can be controlled.

Calcium antagonists have a protective effect on postischemic myocardial function when included in normothermic cardioplegia solutions. This effect varies with the calcium antagonist, but is generally lost under hypothermic conditions. The hypothesis tested was that a calcium antagonist would increase postischemic myocardial performance if given before the onset of hypothermic arrest. Isolated working rat hearts were used with an oxygenated modified Krebs-Henseleit buffer solution as a perfusion media. Rats were pretreated with 1 of 9 doses of a nicardipine solution (0 to 100 micrograms/kg, intraperitoneally) 20 minutes before excision of the heart. Nicardipine is a light-stable, water-soluble calcium antagonist with minimal myocardial depressant effects. The hearts were arrested for 25 minutes at 37 degrees C or 93 minutes at 24 degrees C with 20 mL of cardioplegia solution containing 0.05 mmol/L CaCl2. Postischemic performance and adenosine triphosphate content were used as determinants of efficacy. Eighty-three percent of 101 treated hearts recovered in contrast to a mortality of 50% in the 24 nontreated hearts. Pretreatment with 25 micrograms/kg significantly increased (p less than 0.05) the percent recovery (compared with the nontreated group) of the following variables of cardiac function: systolic pressure, 74% to 96% (37 degrees C), 76% to 90% (24 degrees C); cardiac output, 61% to 90% (37 degrees C), 62% to 84% (24 degrees C); stroke work, 49% to 95% (37 degrees C), 50% to 92% (24 degrees C); and adenosine triphosphate, 76% to 87% (37 degrees C), 58% to 68% (24 degrees C). Progressive increases in postischemic function at 37 degrees and 24 degrees C were seen as the dose of nicardipine was increased from 0 to 25 micrograms/kg and decreased function was seen with a pretreatment dose greater than 25 micrograms/kg of nicardipine. Pretreatment with nicardipine significantly improved postischemic myocardial performance under hypothermic conditions and should be administered or at least not discontinued before cardiac operations.

The role of magnesium ion and its relation to the calcium concentration of cardioplegic solutions was reexamined in this study. Isolated rat hearts were used with an oxygenated modified Krebs-Henseleit bicarbonate buffer as perfusion medium. The hearts were arrested for 20 minutes at 37-degrees-C or 90 minutes at 24-degrees-C. Treatment groups received one dose of nine possible cardioplegic solutions containing magnesium (0, 1.2, or 15 mmol/L) and calcium (0.05, 1.5, or 4.5 mmol/L). Ninety-six percent of the 75 magnesium-treated hearts recovere, regardless of the calcium concentraion, in contrast to a 52% recovery rate in the 69 hearts that did not receive magnesium. The addition of 15 mmol/L Mg2+ to a cardioplegic solution containing no magnesium but 0.05 mmol/L Ca2+ significantly increased (p < 0.01) the percent recovery of the following parameters of cardiac function: systolic pressure, 74% to 93% (37-degrees-C), 64% to 98% (24-degrees-C); cardiac output, 76% to 101% (37-degrees-C), 71% to 102% (24-degrees-C); stroke work, 64% to 104% (37-degrees-C), 52% to 99% (24-degrees-C); and adenosine triphosphate level, 75% to 83% (37-degrees-C), 58% to 90% (24-degrees-C). There were significant reductions (p < 0.03) in percent recovery (37-degrees-C and 24-degrees-C) of cardiac output, stroke work, and adenosine triphosphate level in the groups that contained 0 or 15 mmol/L Mg2+ as the calcium concentration was increased from 0.05 to 4.5 mmol/L. Significant progressive augmentation of ventricular recovery and decreased overall mortality is produced at 37-degrees and 24-degrees-C with cardioplegia containing high levels of magnesium and low levels of calcium. These data demonstrate the importance of the Mg2+/Ca2+ relation in an oxygenated crystalloid solution with a pH of 7.45, carbon dioxide tension of 40 mm Hg, and oxygen tension of 750 mm Hg containing 142 mmol/L Na+.

This study compares results of a second left ventricular myotomy and myectomy (M + M) with those of mitral valve replacement (MVR) as reoperative procedures for persistent left ventricular outflow obstruction after M + M in hypertrophic cardiomyopathy. Comparison of the second M + M group (n = 12) with the MVR group (n = 11) disclosed significant difference (p less than 0.05) in mean age at the initial operation (29 +/- 11 years versus 40 +/- 8 years), interval between operations (46 +/- 57 months versus 18 +/- 13 months), and age at reoperation (33 +/- 10 years versus 42 +/- 8 years); and insignificant differences in mean preoperative functional class, cardiac index, left ventricular outflow gradients at rest or with provocation, and hospital mortality at reoperation (2/12 versus 1/11). At 6 months after reoperation, comparison of results of a second M + M with MVR showed that mean functional class, cardiac index, and left ventricular outflow gradient at rest were similarly improved, but the outflow gradient with provocation was significantly higher in the second M + M group (57 +/- 44 mm Hg versus 14 +/- 9 mm Hg, p less than 0.05). Total follow-up was 108 patient-years (100% complete) with an average of 5.9 years per patient in the second M + M group and 3.4 years per patient in the MVR group. Actuarial survival, including hospital mortality, at 3 and 5 years was 83% and 76%, respectively, after the second M + M, which was similar to 92% and 77% after MVR.(ABSTRACT TRUNCATED AT 250 WORDS)

High-affinity interleukin 2 receptors (IL-2Rs) are expressed by T cells activated in response to foreign histocompatibility antigens but not by normal resting T cells. To exploit this difference in IL-2R expression, anti-Tac-M, a murine monoclonal antibody specific for the IL-2R alpha chain, was used to inhibit organ allograft rejection. However, the use of murine anti-Tac as an immunosuppressive agent was limited by neutralization by human anti-murine antibodies and by weak recruitment of effector functions. To circumvent these difficulties, a humanized antibody to the IL-2R, anti-Tac-H, was prepared. This molecule is human with the exception of the hypervariable segments, which are retained from the mouse. In vivo survival of anti-Tac-H is 2.5-fold longer than simultaneously administered anti-Tac-M (terminal t1/2, 103 hr vs. 38 hr). In addition, anti-Tac-H is less immunogenic than anti-Tac-M when administered to cynomolgus monkeys undergoing heterotopic cardiac allografting. Specifically, all monkeys treated with anti-Tac-M developed measurable anti-anti-Tac-M levels by day 15 (mean onset, 11 days). In contrast, none of the animals receiving anti-Tac-H produced measurable antibodies to this monoclonal antibody before day 33. Finally, there was a prolongation of graft survival in the cynomolgus heterotopic cardiac allograft model in animals receiving anti-Tac. In animals that received anti-Tac-M, the allograft survival was prolonged compared to that of the control group (mean survival, 14 +/- 1.98 days compared to 9.2 +/- 0.48 days; P less than 0.025). Graft survival was further prolonged by anti-Tac-H with a mean survival of 20.0 +/- 0.55 days (compared to controls, P less than 0.001; compared to anti-Tac-M, P less than 0.02). There was no toxicity attributable to the administration of either form of anti-Tac. Thus, anti-Tac-H significantly prolonged allograft survival in primates, without toxic side effects, and may be of value as an adjunct to standard immunosuppressive therapy in humans.

The purpose of this prospective study was to define the effect of cardiopulmonary bypass on the concentrations of thyroid hormones and metabolites. Blood samples were obtained from 14 patients preoperatively, at specific times throughout cardiopulmonary bypass, and serially to 24 hours postoperatively. Thyroid-stimulating hormone, thyroid-binding globulin, total thyroxine, triiodothyronine (T3), and reverse T3, an inactive metabolite of thyroxine, were measured by radioimmunoassay. Free T3 was assayed by equilibrium dialysis. Values of total T3 and free T3, the active hormone, were significantly depressed (75% and 50%, respectively) up to 24 hours after bypass (p < 0.05). Reverse T3 demonstrated a greater than fourfold rise at 8 and 24 hours postoperatively (p < 0.05). Thyroid-binding globulin was decreased at all sampling times (p < 0.05). Thyroid-stimulating hormone, thyroxine, and free thyroxine levels remained within normal ranges at all sampling times. These results indicate that cardiopulmonary bypass simulates the "euthyroid sick syndrome" as seen in severely burned patients and critically ill patients, which is characterized by depression of T3 and free T3 concentrations with a concomitant increase in reverse T3 levels and normal concentrations of thyroid-stimulating hormone, thyroxine, and free thyroxine. The hemodynamic effects of primary hypothyroidism are well established. These data provide further support for investigational trials of intravenous administration of T3 in the prevention or treatment of low cardiac output syndrome after cardiopulmonary bypass.

Five hundred twenty-five patients with hypertrophic cardiomyopathy underwent left ventricular myotomy and myectomy (LVMM) from 1960 to 1990. Four hundred ninety-six had nonregurgitant trileaflet aortic valves before LVMM. In 19 (4%) of these patients, aortic regurgitation developed after LVMM. Age of the 19 patients ranged from 10 to 58 years (mean age, 35 +/- 3 [+/- standard error of the mean]]. Seven were male and 12, female. Five patients underwent LVMM followed immediately by aortic valve replacement or valvuloplasty. Aortic regurgitation developed in 14 patients at a later date. The average New York Heart Association functional class improved from 3.2 +/- 0.1 to 1.3 +/- 0.1 (p less than 0.05, Student's t test) after operation. The average peak systolic left ventricular outflow tract gradient at rest and with provocation decreased from 65 +/- 8 to 14 +/- 5 mm Hg (p less than 0.05) and 108 +/- 9 to 45 +/- 7 mm Hg (p less than 0.05), respectively, 6 to 8 months after operation. Aortic regurgitation occurred in 7 of the 14 patients at 6 months or less after operation, and 3 required operative repair. In the other 7 patients, aortic regurgitation developed 3 years or more after LVMM, and 3 of them also required operative repair. All 12 patients in whom aortic regurgitation developed at operation or within 6 months postoperatively had either a very small aortic annulus (less than or equal to 21 mm, 5 patients), a low mitral-septal contact lesion (greater than or equal to 35 mm below the aortic annulus, 3 patients), or both (4 patients).(ABSTRACT TRUNCATED AT 250 WORDS)

A case is presented of a 17-year-old man with combined myocardial contusion, traumatic ventricular septal defect, and disruption of the descending thoracic aorta after a rapid deceleration injury to the chest.

Hypertrophic cardiomyopathy (HC) is a congenital heart disease. Persons with 1 type of congenital heart disease are more prone to a second congenital heart condition than are persons without any congenital cardiac condition. The frequency of the congenitally bicuspid aortic valve in the general population is believed to be about 1%.1 Therefore, it might be expected to be present in an occasional patient with a more uncommon condition, such as HC. The present report describes findings in 4 patients with coexisting HC and a congenitally bicuspid aortic valve.

Nuclear weapons are the ultimate weapons. Hence, for many who would debate military research and development, research on nuclear weapons represents the ultimate point of contention. Those of us involved in nuclear weapons research are frequently asked why we do what we do, rather than participating in the supposedly more peaceful endeavors open to scientists and engineers. There are a variety of answers to this question.

"Round two of test ban flap: No I didn't/Yes you did." Bulletin of the Atomic Scientists, 44(10), pp. 5–6