Volume loading improves low cardiac output in experimental right ventricular infarction.

To evaluate the effect of volume loading in the low output state associated with right ventricular infarction, isolated right ventricular infarction was produced in seven dogs with the pericardium intact. Volume loading and pericardiotomy were then sequentially performed. After the production of right ventricular infarction, right ventricular systolic pressure decreased by 25%, aortic pressure by 36% and cardiac output by 32%. Right ventricular ejection fraction decreased by 57%, but left ventricular ejection fraction did not change significantly. Left ventricular transmural pressure and diastolic size decreased, and right ventricular diastolic size increased. Intrapericardial pressure increased and equalization of diastolic pressures was noted. Volume loading resulted in increased right ventricular systolic pressure and stroke work, increased aortic pressure and cardiac output and increased transmural pressure and diastolic size in both ventricles. Pericardiotomy resulted in further increases in right and left ventricular filling, stroke work and cardiac output, as well as resolution of equalized diastolic pressures. These results indicate that cardiac output in experimental right ventricular infarction increases with volume loading, which enhances left ventricular preload by augmenting right ventricular output. Elevated intrapericardial pressure affects filling of both ventricles and may play a role in the pathophysiology of low cardiac output in right ventricular infarction.

Intestinal infarction complicating phenobarbital overdose.

Nonocclusive intestinal infarction developed in a 29-year-old man after phenobarbital overdose. He was found 72 hours after the overdose, at which time examination of the abdomen disclosed no abnormalities and he was not hypotensive. During the next ten hours, abdominal distention, ileus, and gas within the intestinal wall and portal venous system developed. Laparotomy disclosed ischemic intestinal infarction of the right colon and distal ileum with no evidence of thrombosis of the mesenteric vessels. The patient recovered fully after ileostomy with subsequent reanastomosis. To our knowledge, ischemic intestinal infarction after drug overdose has not been reported previously.

Role of the pericardium in the regulation of myocardial blood flow and its distribution in the normal and acutely failing left ventricle of the dog.

The effects of the pericardium on the amount and distribution of left ventricular myocardial blood flow were studied. In 10 normal dogs, transfusion of blood from a donor dog resulted in modest increases in coronary flow and ventricular diameter that were greater with an open than a closed pericardium. The ratio of subendocardial to subepicardial flow remained normal with or without the pericardium, at low and high diastolic ventricular pressure, and before and after pharmacological vasodilation with chromonar. In 18 dogs, cardiac failure was induced by constant infusion of the metabolic inhibitor, phenformin. Modest ventricular dilatation occurred if the pericardium was open. A progressive rise in myocardial blood flow developed in those with the pericardium open (1.06 rising to 3.02 ml . g-1 . min-1). A lesser increase (0.62 to 1.75 ml . g-1 . min-1) was seen in dogs with the pericardium closed; they selectively increased subendocardial flow, producing an average subendocardial to subepicardial flow ratio of 2.25. Pharmacological vasodilatation then resulted in uniform transmural flow. The pericardium can influence myocardial flow indirectly by influencing myocardial metabolic demand, when the heart is stressed. It may have a beneficial role in preventing the increased oxygen and coronary flow requirements produced by ventricular dilatation.

Endothelial loss and regeneration in a model of transplant arteriosclerosis.

Early endothelial injury may play a role in the development of transplant arteriosclerosis. The present study documents early endothelial changes using a rat aortic graft model. Abdominal aortic allografts from PVG rats were orthotopically transplanted to DA rats. Controls were DA to DA transplants. Endothelial cell (EC) injury, regeneration, and leukocyte infiltration in the intima were evaluated using scanning electron microscopy and histological and immunocytochemical techniques. Nontransplanted aortic segments showed partial loss of ECs after 1 or 2 hr of preservation. Control isografts demonstrated extensive EC denudation and neutrophil adherence to residual ECs at 1 day post-transplantation. After 3 days, isografts showed continued regeneration of ECs in the central area and ingrowth of endothelium from both clamped sites in the recipient aorta. Reendothelialization was complete by day 14. Allografts showed similar findings to isografts up to day 3. In contrast to isografts, however, there was a secondary EC loss beginning at day 7. Monocytes/macrophages and T cells were noted to be adherent to residual ECs in 7- and 14-day allografts. At 20 days, ECs were absent from the luminal surface in the center of allografts. Endothelium did extend from clamped sites toward the midgraft region as in isografts. By 60 days allografts were completely reendothelialized. These results demonstrate that in both isografts and allografts there is initial EC loss due to mechanical trauma and ischemia/reperfusion injury, followed by partial reendothelialization. This latter process continues unabated in isografts, whereas in allografts the secondary EC loss occurs due to an allogenic response. This is followed by complete reendothelialization that occurs during the concurrent development of significant intimal hyperplasia.

Individual variations in the fibrinolytic response during and after cardiopulmonary bypass.

The purpose of this study was to determine whether individual patients show different patterns of fibrinolytic response to cardiopulmonary bypass (CPB) and whether preoperative or intraoperative parameters were predictive of these different patterns. Active t-PA, active PAI-1 and total t-PA antigen were measured in plasma samples obtained from 38 subjects, age 32 to 85 (median 69 years), before, during and after CPB. Four patterns of fibrinolytic response were noted: 1) 40% of patients showed the "typical" response, a rapid rise in active and total t-PA during CPB followed postoperatively by elevated PAI-1 and reduced t-PA, 2) 10% showed no change in t-PA or PAI-1 during or after CPB, 3) 24% showed no change in t-PA with an increase in PAI-1 postoperatively, and 4) 26% showed an increase in t-PA during CPB with no change in PAI-1 postoperatively. When present, the t-PA response was rapid, occurring within the first 30 min of CPB and was more common in patients undergoing valve surgery than in coronary artery bypass grafting (p < 0.005). Increased levels of PAI-1 postoperatively were associated with ischemic times greater than 70 min (p = 0.003) but not with the total length of CPB. Age, sex, CPB temperature, total CPB time and preoperative levels of t-PA and PAI-1 were not associated in the intra- or postoperative fibrinolytic response pattern. We conclude that the fibrinolytic response to CPB is heterogeneous. Further studies will be needed to determine whether different response patterns are clinically significant.

Getting started in academic cardiothoracic surgery.

Preparing to begin a career in academic cardiothoracic surgery requires forethought and desire. Success mandates honesty, discipline, opportunity, and support. This article will attempt to review some fundamental concepts important in starting such an academic career. The thoughts are somewhat personal and not meant to be inclusive. The article will briefly discuss the following issues: choosing the first job, transitions, effective time management, developing clinical confidence, the continued need for mentorship, developing educational value, developing a philosophy of academic growth, intellectual and emotional honesty, myths, mental and physical health, and keys to success.

Becoming a division chief.

Leading a division or department of cardiothoracic surgery is both a tremendous honor and a significant responsibility. Key to such a position of leadership are committed, functional, and loyal teams focused on the end points of success, and the ability of the leader to develop a strategic vision and to implement a functional operating system.

Management of air embolism in blunt and penetrating thoracic trauma.

The charts of 61 patients treated from 1970 through 1981 were reviewed to determine the clinical outcome after treatment of air embolism from blunt (15 patients) and penetrating (21 gunshot and 25 stabbing) thoracic injuries. The diagnosis of air embolism was confirmed by the presence of air in the coronary arteries (57%), air aspirated from the heart (30%) or major artery (10%), or Doppler findings (3%). All patients were in shock or cardiac arrest, and in 36% of these patients there were early signs of hemoptysis or unexpected arrest after intubation and positive-pressure ventilation. Successful management included (1) early thoracotomy for diagnosis as well as for specific treatment, (2) hilar cross-clamping for control of bronchovenous communication, (3) maintenance of perfusion pressures with fluids, vasopressors, or aortic cross-clamping, and (4) prompt correction of the embolic source, usually a lung resection. The overall survival rate was 44%, which correlated with the mechanism of injury, with associated nonthoracic injuries, and with the occurrence of arrest in a controlled setting. We conclude that (1) air embolism can insidiously occur even in blunt trauma; (2) suspicion should be high with hemoptysis or unexpected arrest; and (3) successful treatment includes immediate thoracotomy for diagnosis, resuscitation, and prompt control of the bronchovenous communication.

Modified conduit preparation creates a pseudosinus in an aortic valve-sparing procedure for aneurysm of the ascending aorta.

Mechanical valved conduit replacement of the aortic root is a durable and appropriate procedure for many diseases of the ascending aorta, but may sacrifice an anatomically salvageable aortic valve. For young active patients and for patients with "systemic" arterial disease (atherosclerosis, Marfan's syndrome) who may require future operations, life-long anticoagulation with its attendant thromboembolic versus hemorrhagic risks is not ideal. Several techniques have been suggested as aortic valve-sparing options. Recently, a procedure was described that combines the freehand homograft techniques with the standard Bentall techniques (David procedure). This innovative technique replaces the ascending aorta with a Dacron cylinder, spares the aortic valve, and restores competence and thus offers an excellent alternative. The durability of this procedure that places the aortic valve inside a cylindrical conduit without sinuses of Valsalva is unknown. In selected patients, we have used this technique to spare the aortic valve. On the basis of experimental data and preliminary computer modeling, with the hope of improving the durability, we have modified the conduit to create a "pseudosinus" in our most recent nine patients. We have done the David procedure in 10 patients. The pseudosinus modification was done in the most recent nine patients. Patients' ages ranged from 37 to 71 years (mean 49.9 years). There were five female and five male patients. Five patients had Marfan's syndrome and five patients had annuloaortic ectasia. There has been no mortality and all patients have had both early and late follow-up echocardiography. Five patients have zero to trace aortic insufficiency, four patients have trace to mild aortic insufficiency, and one patient has mild or "1+" aortic insufficiency. Aortic insufficiency has not progressed in any patient during the 18 months of follow-up. The patient with 1+ aortic insufficiency has no activity limits, good ventricular function, and no evidence of congestive symptoms. One patient who had extensive thoracoabdominal aneurysmal disease has undergone subsequent replacement of the descending aorta to the level of the renal arteries and has done well. Aortic valve-sparing replacement of the aortic root is an excellent procedure for any patient with an ascending aortic aneurysm and an anatomically salvageable valve. We believe that by modifying the proximal conduit and creating a "pseudosinus" into which the leaflets can retract without contact of the cylindrical conduit we may increase the longevity of the native aortic valve in this procedure.

The safety and efficacy of ten percent pentastarch as a cardiopulmonary bypass priming solution. A randomized clinical trial.

Ten percent pentastarch is a low-molecular-weight hydroxyethyl starch with greater oncotic pressure and shorter intravascular persistence than 6% hetastarch. To evaluate its safety and efficacy as a component of cardiopulmonary bypass priming solution, we prospectively studied 90 patients undergoing coronary artery bypass grafting or valve replacement necessitating cardiopulmonary bypass (bubble oxygenator and moderate systemic hypothermia). Sixty patients were randomized to receive 75 gm of either 10% pentastarch (group P) or 25% albumin (group A), and 30 patients received lactated Ringer's solution alone (group C). Intravascular colloid osmotic pressure during cardiopulmonary bypass was highest with either of the colloid primes (15-minute measurement: group P, 15.7 +/- 2.2 mm Hg (mean +/- standard deviation); group A, 15.2 +/- 2.0 mm Hg; group C, 11.3 +/- 1.7 mm Hg; p less than 0.05, groups P and A compared with group C). This was associated with a lower volume requirement during cardiopulmonary bypass to maintain the venous reservoir (group P, 333 +/- 318 ml; group A, 483 +/- 472 ml; group C, 1332 +/- 1013 ml; p less than 0.05, groups P and A compared with group C). Urine output during cardiopulmonary bypass was similar in each group. Net intraoperative fluid balance was lowest in the colloid groups (groups P and A, 5.7 +/- 1.4 L; group C, 6.9 +/- 1.3 L; p less than 0.05, groups P and A compared with group C). Cardiac index shortly after weaning from cardiopulmonary bypass was greatest in group P (group P, 3.2 +/- 0.9; group A, 2.8 +/- 0.8; group C, 2.7 +/- 0.6 dyne.sec.cm-5; p less than 0.05, group P compared with group C). Changes in alveolar-arterial oxygen gradients, shunt fraction, and effective compliance were similar in all groups. During cardiopulmonary bypass, pentastarch appeared to cause the greatest degree of hemodilution, as suggested by the lowest hemoglobin, factor VII and IX levels and platelet count. The activated partial thromboplastin time was significantly prolonged during and immediately after cardiopulmonary bypass in group P relative to groups A and C (p less than 0.05), although there were no significant differences in the activated clotting time before cardiopulmonary bypass, during cardiopulmonary bypass, or after heparin neutralization. As well, clinical indices of hemostasis, including mediastinal drainage, red cell, platelet, and fresh frozen plasma requirements, and reoperation for excessive postoperative bleeding, were similar. We conclude that pentastarch, when used in cardiopulmonary bypass prime, is as safe as either albumin or Ringer's solution alone.(ABSTRACT TRUNCATED AT 400 WORDS)

The fate of the 12 mm porcine valved conduit from the right ventricle to the pulmonary artery. A ten-year experience.

The 12 mm Dacron conduit containing a porcine valve is the smallest valved conduit manufactured and is used in the youngest infants with the most diminutive pulmonary arterial system. The outcome of patients with such a conduit is unknown. Between 1975 and 1985 there were 49 hospital survivors after placement of a 12 mm extracardiac valved conduit from the right ventricle to the pulmonary artery. Follow-up is available in 42 patients, aged 1 to 16 months (mean 3.5) and weighing 2.5 to 8.7 kg (mean 3.8). Twenty-eight patients (67%) have undergone subsequent conduit replacement, and 11 (26%) are alive and asymptomatic with a mean follow-up of 56 months. There were three late deaths. The interval between implantation and conduit change was 4.5 to 101 months (mean 44), allowing a weight gain of 2.7 to 23 kg (mean 10.4) before reoperation at age 12 to 117 months (mean 49). Despite elevated right ventricular pressures equaling systemic values, 37% of these patients were clinically asymptomatic. The gradient across the 12 mm valved conduit before explantation ranged from 30 to 173 torr (mean 83) with an almost equal predilection for stenosis at the proximal anastomosis, valve, conduit, distal anastomosis, and main pulmonary artery. The intervening pulmonary artery growth determined the size of the replacement conduit, 14 to 25 mm (mean 16), and was the main factor influencing the results of reoperation. This study demonstrates that the 12 mm porcine valve-containing conduit affords palliation in this difficult subset of patients with the smallest pulmonary arterial tree.

The Mustard procedure in infants (less than 100 days of age). Ten-year follow-up.

Surgical treatment of transposition of the great arteries and intact ventricular septum has changed markedly in the past 10 years. However, long-term follow-up on new approaches is not available. In a unique group of patients, operated on in the first 100 days of life with the Mustard procedure, such follow-up is available, and the results of these true infant repairs represent a benchmark against which subsequent techniques applied to infants should be compared. During the period of 1975 to 1980, 36 infants, less than 100 days of age, who had transposition of the great arteries and intact ventricular septum, underwent Mustard repair at the University of California, San Francisco. Ages ranged from 4 to 98 days (mean 46 days) and weights from 2.3 to 6.6 kg (mean 3.5 kg). There were no early deaths, and late follow-up was available from 8 to 13 years (mean 10 years). The late survival rate was 97% (mean 10 years). There was a 62% rhythm disturbance-free survival rate, 89% reoperation-free survival rate, and 91% pacemaker-free survival rate. Echocardiographic evaluation revealed obstruction of the superior vena cava in eight patients, tricuspid insufficiency in four, right ventricular dysfunction in two, and left ventricular outflow tract obstruction in three. The Mustard procedure, performed in the first 100 days of life, results in a high rate of survival (early 100% and late 97%, at a mean of 10 years) and a low incidence of late complications against which other techniques of infant repair should be compared.

Descending necrotizing mediastinitis: An analysis of the effects of serial surgical debridement on patient mortality.

OBJECTIVES: Descending necrotizing mediastinitis is a polymicrobial infection originating in the oropharynx with previously reported mortality rates of 25% to 40%. This investigation reviews the effects of serial surgical drainage and debridement on the survival of patients with descending necrotizing mediastinitis. METHODS: A retrospective review of patients from 1980 through 1998 with a diagnosis of descending necrotizing mediastinitis was performed. Their records were abstracted for personal demographics, hospital course, morbidity, and mortality. Also abstracted were all reports of patients with descending necrotizing mediastinitis published in English between 1970 and 1999. RESULTS: We treated 10 patients in whom descending necrotizing mediastinitis was identified. The mean age of the patients was 38 years. They underwent a mean of 6 +/- 4 computed tomographic imaging studies, 4 +/- 1 transcervical drainage procedures, and 2 +/- 1 transthoracic drainage procedures. Three patients required abdominal exploration and 4 underwent tracheostomy. No deaths occurred. In contrast, 96 patients with descending necrotizing mediastinitis were identified from the literature with a mean age of 38 years. They underwent a mean of 2 +/- 1 computed tomographic imaging studies, 2 +/- 1 transcervical drainage procedures, and 0.7 + 0.3 transthoracic drainage procedures. Sixteen (17%) patients required abdominal exploration and 34 (35%) underwent tracheostomy. Twenty-eight (29%) patients from the literature cohort died during their treatment. CONCLUSION: Descending necrotizing mediastinitis remains a life-threatening infection. On the basis of experience accrued in treating these patients, an algorithm incorporating computed tomographic imaging for diagnosis and surveillance and serial transcervical and transthoracic operative drainage is outlined in the hope of reducing the excessive mortality of descending necrotizing mediastinitis.

Aortic root and valve relationships. Impact on surgical repair.

A surgical procedure has recently been described for patients with aortic incompetence caused by annular dilation, but with normal aortic leaflets. The dilated aortic root is replaced with a Dacron graft, and the native aortic valve is resuspended within the graft. Matching the size and shape of the graft to the size of the leaflets may have significant effects on valve closure and leaflet stress and thus on the longevity of the repair. To define the relationship of native aortic root structure to leaflet size, we morphologically examined normal human aortic roots (n = 10) and valve leaflets and applied mathematic analyses to the results. Our data show that the root has a consistent shape with varying size and that there is a definable mathematic relationship between root diameter and clinically measurable leaflet dimensions. We derived an equation that allows calculation of the appropriate diameter of the root at the sinus of Valsalva level from leaflet heights and perimeters. The diameter of the graft at the sinotubular junction and base should follow the relationship of the normalized root dimensions, either by tailoring of the graft or by new graft design. The current data imply that the graft should incorporate sinuses for proper valve closure and for sharing stress with the leaflets. Application of these results will allow prosthetic graft design to more closely resemble the native aorta. These new grafts should improve physiologic function of the valve, reduce leaflet stress, and increase the durability of the repair.

Infusion of autologous platelet rich plasma does not reduce blood loss and product use after coronary artery bypass. A prospective, randomized, blinded study.

Prior nonblinded studies have suggested dramatic hemostatic effects and decreased plasma after cardiopulmonary bypass. Platelet rich plasma (8 to 10 ml/kg total body weight) was obtained (Haemonetics Plasma Saver; Haemonetics Corp., Natick, Mass.) from 51 patients undergoing primary coronary artery bypass grafting before heparinization. After double-blinded randomization, the platelet rich plasma was reinfused immediately in the control group or after heparin reversal in the treatment group. Homologous blood product usage, blood loss, and the surgeon's intraoperative subjective assessment of coagulation were evaluated. Additionally, thromboelastography, prothrombin time, partial thromboplastin time, activated clotting time, fibrinogen, platelet counts, and hematocrit values were evaluated before the operation, after heparin reversal, after infusion of platelet rich plasma or control solution, and 2 hours after infusion. The surgeon's subjective assessment of coagulation was not different between control and treatment groups (p = 0.78). According to specific predetermined transfusion guidelines, no statistically significant differences were found in the use of whole blood (p = 0.07), packed red blood cells (p = 0.62), platelets (p = 0.11), total units of blood products (p = 0.45), or in the percentage of patients receiving transfusions (control group 70%, treatment group 71%, p = 0.97). Cumulative amount of blood shed through the chest tube was not significantly different between the groups at any interval but tended toward significance at 4, 6, and 12 hours (p = 0.09, 0.07, and 0.09). The prothrombin time immediately after reinfusion of platelet rich plasma was significantly lower in the treatment group (p = 0.03), but all other laboratory studies were similar at each time interval. Infusion of platelet rich plasma after cardiopulmonary bypass in patients having uncomplicated primary coronary artery bypass grafting has minimal effects on the surgeon's assessment of coagulation, total transfusion requirements, mediastinal drainage, and laboratory studies of coagulation.

Decreased lung ischemia-reperfusion injury in rats after preoperative administration of cyclosporine and tacrolimus.

OBJECTIVES: Calcineurin inhibitors reduce experimental reperfusion injury in the liver, brain, heart, kidney, and small bowel. These studies were undertaken to determine whether these agents are similarly protective against lung ischemia-reperfusion injury. METHODS: Left lungs of male rats were rendered ischemic for 90 minutes and reperfused for as long as 4 hours. Treated animals received cyclosporine A (INN: ciclosporin; 1 or 5 mg/kg) or tacrolimus (0.2 mg/kg) 6 hours before ischemia, at reperfusion, or 2 hours after reperfusion. Injury was quantitated in terms of tissue polymorphonuclear leukocyte accumulation (myeloperoxidase content), vascular permeability (iodine 125-labeled bovine serum albumin extravasation), and bronchoalveolar lavage leukocyte content. Separate tissue samples were processed for nuclear protein and cytokine messenger RNA. RESULTS: Treatment with cyclosporine (5 mg/kg) or tacrolimus (0.2 mg/kg) 6 hours before reperfusion reduced lung vascular permeability by 54% and 56% relative to control animals (P <.03). The protective effects of cyclosporine and tacrolimus treatment before reperfusion correlated with 42% and 43% reductions in tissue polymorphonuclear leukocyte (myeloperoxidase) content (P <.008) and marked reductions in bronchoalveolar lavage leukocyte accumulation (P <.01). Administration of cyclosporine or tacrolimus at the time of reperfusion or 2 hours into the reperfusion period offered little or no protection. Animals treated before reperfusion also demonstrated marked reductions in nuclear factor kappaB activation and expression of proinflammatory cytokine messenger RNA. CONCLUSION: Cyclosporine and tacrolimus treatment before reperfusion was protective against lung ischemia-reperfusion injury in rats. The mechanism of these protective effects may involve the inhibition of nuclear factor kappaB, a central transcription factor mediating inflammatory injury. The decreased expression of cytokine messenger RNA indicates that both cyclosporine and tacrolimus may exert their protective effects at the pretranscriptional level.

Aspirin anticoagulation in children with mechanical aortic valves.

The optimal method of anticoagulation in children with mechanical heart valves is controversial. Between 1975 and 1986, aspirin or aspirin with dipyridamole has been used for anticoagulation in children receiving a mechanical aortic valve at the University of California, San Francisco. Fifty-one patients (ages 1 to 23 years, mean 12.9 years) were treated with aspirin (n = 45) or aspirin with dipyridamole (n = 6) and observed a mean of 36.5 months (range 3 to 100 months). There were four late deaths: two from endocarditis and two from other medical problems, but none related to thrombosis or embolus. Follow-up was accomplished by direct contact with the patient, parent, or referring physician. Two patients (3.9%) were lost to late follow-up. One minor neurologic event occurred perioperatively and resolved spontaneously. There were no postoperative thromboembolic events. Eleven asymptomatic children were recently studied by magnetic resonance imaging or computed axial tomography of the brain and had no evidence of prior silent cerebral thromboembolic defects. There were four patients (5.9%) who had minor hemorrhagic complications: Three patients had nosebleeds and one patient had an upper gastrointestinal hemorrhage. Five patients were changed to warfarin anticoagulation: the patient with upper gastrointestinal hemorrhage and four older patients because of physician preference, all after uncomplicated aspirin therapy. There were no mechanical valve failures, although one patient required reoperation 9 months later for perivalvular leak. All children have remained in normal sinus or paced rhythm during follow-up. These results show that children with mechanical aortic valves in normal sinus rhythm can be safely treated with aspirin (or aspirin with dipyridamole) with little risk of thromboembolic events, valve thrombosis, or valve failure. Hemorrhagic complications resulting from aspirin are minor and easily treated.

Neonatal model of heterotopic heart transplantation in pigs.

To investigate the long-term success of heart transplantation in newborn infants who have complex congenital heart disease, we have developed a model of heterotopic heart transplantation in immature pigs. We chose the heterotopic technique because it is simple, does not require cardiopulmonary bypass or heparin, allows for significant size disparity between the recipient and donor hearts, and allows for experimental comparisons between the two hearts. Small newborn piglet hearts are harvested, prepared, and then transplanted into the left chest of larger weanling pigs to augment or substitute for the native left ventricle. Preliminary data from transplants into 49 pigs suggest that the technique is technically possible, the pigs can be immunosuppressed over the long term, and the donor heart can contribute hemodynamically. Experimentally, the model is well designed for the investigation of issues critical for the long-term success of heart transplantation in infants and children, including growth and development, optimal long-term immunosuppression, differences in immunotolerance, and the study of coronary obliterative disease. Clinically, the model has potential applicability in congenital heart anomalies if one native functioning atrium and ventricle are present.

Inhibition of interleukin-8 blocks myocardial ischemia-reperfusion injury.

INTRODUCTION: Interleukin-8 is thought to play a role in neutrophil activation and transcapillary migration into the interstitium. Because neutrophils are principal effector cells in acute myocardial ischemia-reperfusion injury, we postulated that the inhibition of interleukin-8 activity with a neutralizing monoclonal antibody directed against rabbit interleukin-8 (ARIL8.2) would attenuate the degree of myocardial injury encountered during reperfusion. METHODS: In New Zealand White rabbits, the large branch of the marginal coronary artery supplying most of the left ventricle was occluded for 45 minutes, followed by 2 hours of reperfusion. Fifteen minutes before reperfusion, animals were given an intravenous bolus of either 2 mg/kg of ARIL8.2 or 2 mg/kg anti-glycoprotein-120, an isotype control antibody that does not recognize interleukin-8. At the completion of the 120-minute reperfusion period, infarct size was determined. RESULTS: In the area at risk for infarction, 44.3% +/- 4% of the myocardium was infarcted in the anti-glycoprotein-120 group compared with 24.8% +/- 9% in the ARIL8.2 group (p < 0.005). In control animals, edema and diffuse infiltration of neutrophils were observed predominantly in the infarct zone and the surrounding area at risk. Tissue myeloperoxidase determinations did not differ significantly between groups, indicating that the cardioprotective effect of ARIL8.2 was independent of an effect on neutrophil infiltration. CONCLUSIONS: A specific monoclonal antibody that neutralizes interleukin-8 significantly reduces the degree of necrosis in a rabbit model of myocardial ischemia-reperfusion injury.

A randomized clinical trial of 10% pentastarch (low molecular weight hydroxyethyl starch) versus 5% albumin for plasma volume expansion after cardiac operations.

Pentastarch is a hydroxyethyl starch similar to hetastarch, but with a lower average molecular weight (264,000 versus 450,000) and fewer hydroxyethyl groups (molar substitution ratio = 0.45 versus 0.70). These characteristics result in enhanced enzymatic hydrolysis, faster renal elimination (initial intravascular half-life = 2.5 versus 25.5 hours), and less effect on coagulation. We report on a randomized clinical trial comparing the clinical efficacy and safety of 10% pentastarch (group P) for plasma volume expansion after cardiac operations with that of 5% serum albumin (group A). During the first 24 hours after arrival of the patient in the intensive care unit, colloid was infused to maintain a cardiac index of 2.0 L/m2 or more and a mean arterial pressure within 10% of the preinduction value. Group P (n = 50) received 1706 +/- 393 ml of colloid (mean +/- standard deviation) during this period, and group A (n = 44), 1794 +/- 341 ml (p = no significant difference). Hemodynamic responses to infusion were similar for both groups, although in group P a greater increase in both cardiac index (0.5 +/- 0.5 versus 0.3 +/- 0.5 L/min/m2 in group A, p less than 0.01) and left ventricular stroke work index (10.8 +/- 8.0 versus 5.8 +/- 6.0 gm-m/m2, p less than 0.01) was observed during infusion of the first 500 ml. There were no significant differences in any of the measured respiratory parameters (alveolar-arterial oxygen gradient, estimated shunt fraction, and effective pulmonary compliance). Hemodilution with colloid significantly reduced serum protein levels in group P by 24 hours postoperatively (4.0 +/- 0.6 versus 5.0 +/- 0.7 gm/dl in group A, p less than 0.05), although mean serum colloid osmotic pressure was similar (15.4 +/- 2.6 [P] versus 15.5 +/- 2.7 mmHg [A], p = no significant difference). There were no significant between-group differences in prothrombin time, activated partial thromboplastin time, platelet count, bleeding time, or coagulation factors (fibrinogen, V, VII, VIII, or IX) on postoperative days 1 and 7. Perioperative fluid balance, weight change, chest tube output, red blood, platelet, or fresh frozen plasma usage, reexploration for bleeding, and clinical outcome were also similar. These findings indicate that pentastarch is as safe and effective s 5% albumin for plasma volume expansion after cardiac operations with no apparent adverse effects on coagulation. If commercially available at a lower cost than albumin, it would appear to be a reasonable first choice for colloid therapy in this setting.