Activation-induced apoptosis in human macrophages: developmental regulation of a novel cell death pathway by macrophage colony-stimulating factor and interferon gamma.

Activated macrophages (M phi s) are important participants in host defense, but their uncontrolled activation leads rapidly to septic shock and death. One mechanism for regulating other dangerous cells in the immune system is programmed cell death, or apoptosis. Monocytes are known to undergo spontaneous apoptosis upon leaving the circulation unless provided with specific survival signals, but mature tissue M phi s are more robust cells, and it was not clear that they could be similarly regulated by apoptosis. We now show that during differentiation monocytes rapidly lose their sensitivity to apoptosis triggered by passive cytokine withdrawal, but they may retain a novel pathway which initiates apoptosis after activation with specific stimuli (zymosan and phorbol esters). Sensitivity to activation-induced apoptosis was developmentally determined, being downregulated by the maturation-promoting cytokine macrophage colony-stimulating factor but stably upregulated by even transient exposure to the proinflammatory cytokine interferon gamma (IFN-gamma). Apoptosis began within 2-4 h of activation, occurred in > 95% of susceptible cells, and in mixed cocultures selectively affected only those M phi s with a history of IFN-gamma priming. Consistent with a possible role for protein kinase C in the signaling pathway leading to cell death, the kinase inhibitor staurosporine was protective against both phorbol ester- and zymosan-induced apoptosis. Our studies describe a novel form of activation-induced M phi apoptosis which is developmentally regulated by two physiologically relevant cytokines. We speculate that apoptosis may serve to restrict the destructive potential of inflammatory M phi s.

Immediate operative treatment for massive hemoptysis.

A series of 15 patients with life threatening, massive hemoptysis is reported. Thirteen of these patients underwent immediate operative treatment with only three deaths. One died after bronchoscopic identification of the bleeding site while awaiting elective thoracotomy. The other patient left the hospital against medical advice. Immediate identification of the site of bleeding by bronchoscopy followed by thoracotomy with resection of the bleeding source, is the preferred method of managing such patients, except when there are specific contraindications to resection.

Platelet aggregation: effects of cardiopulmonary bypass.

This study was designed to determine whether reduction in platelet aggregate microembolization during the first 30 minutes of cardiopulmonary bypass is due to thrombocytopenia or to decreased ability of platelets to aggregate. The total volume of platelet aggregates induced in blood by adenosine diphosphate (ADP) was measured with a Coulter counter. The volume of platelets in blood was calculated by multiplying hemocytometry platelet counts by the mean platelet volume. Immediately before cardiopulmonary bypass, the total volume of aggregates induced in blood by ADP (2muM) was reduced when compared to normal donors because of (1) a slight fall in the volume of platelets, and (2) reduction in the percentage by volume of platelets which aggregated. After 30 minutes on bypass, the volume of both platelets and aggregates fell, but a greater percentage of platelets aggregated. This indicates that reduction of platelet aggregate formation during cardiopulmonary bypass is due to thrombocytopenia. It also suggests that anesthesia, surgical trauma and heparinization alter platelet reactivity more than cardiopulmonary bypass.

Systemic air embolism following penetrating trauma to the lung.

Systemic air embolism following penetrating injuries of the lung has not been widely recognized clinically. Experimental studies designed to reproduce the phenomenon in dogs have been at variance, although none has taken into consideration the often high intrabronchial pressures created during resuscitative efforts in such patients. Twelve patients with systemic air embolism following penetrating traumatic injuries to the lung have been seen at our hospital. Ventilatory pressures created during resuscitative thoracotomy in traumatized patients were monitored and found to be as high as 100 mm Hg. Penetrating injuries of the lung were created in mongrel dogs, and the animals were ventilated with pressures reaching 90 mm Hg. All dogs unequivocally developed systemic air embolism, with air visualized in the coronary arteries. It would appear that systemic air embolism following penetrating injury to the lung may result when increased intrabronchial pressure, such as found during manual ventilatory assistance, forces air through traumatic bronchovenous fistulae into the systemic circulation.

Traumatic coronary artery-right heart fistula. Report of a case and review of the literature.

Although the left coronary artery is the most frequently injured vessel of the heart, traumatic fistulas appear more often in the right coronary vessels, as the initial injury to the left coronary artery usually results in early death prior to hospitalization. Indications for surgical repair include cardiac decompensation and signs of shunt progression. In asymptomatic patients with no changes in cardiac function, consideration for repair includes the following: (1) enlargement of the fistula, causing a large runofff into the low-pressure chamber, and reduction of blood supply to the local myocardium distal to the fistula; (2) progressive dilatation of a pseudoaneurysm when it exists; and (3) the presence of bacterial endarteritis. Surgery usually has been indicated in reported cases of coronary artery fistula. Conservative management is applicable when the shunt is small and cardiac function is normal, as evidenced by the present case report and the first case cited in the literature. Oversewing of the area of the fistula and bypass grafting from the ascending aorta to the distal coronary tree might provide an additional mode of management in selected cases.

Surgical management of penetrating injuries to the coronary arteries.

Among 76 patients with heart wounds treated over a 4 year period, nine had penetrating injuries to the coronary arteries with clinical presentations of pericardial tamponade, electrocardiographic abnormalities of bundle branch block or ST and T wave changes, and hemothorax. The right coronary artery was injured in two patients, the left anterior descending coronary artery in six patients, and the left circumflex coronary artery in one patient. All but one of these injured coronary arteries were treated by ligation. One patient with a proximal left anterior descending coronary artery transection presented with cardiac arrest and was managed successfully by emergency cardiopulmonary support and saphenous vein bypass with ligation of the transected ends of the artery. The only death occurred six days postoperatively in a patient with a right coronary artery laceration and was not related to the heart injury. No late symptomatic or hemodynamic sequelae have been noted among any of these patients. Principles of elective cardiac surgery are readily adaptable to the patient with a coronary artery injury.

Injuries to the visceral arteries.

Injuries of the major visceral arteries are among the more difficult to manage and rarely occur without serious associated injuries. Sixty-six patients are presented with injuries to the celiac, superior, and inferior mesenteric arteries. Fifty-three injuries resulted from gunshot wounds, nine from stab wounds, and four from blunt trauma. Operative management included vessel ligation in 11 patients, arteriorrhaphy in 43, resection and end-to-end anastomosis in six, Dacron graft interposition in four, and aortic reimplantation in two. Twenty-three patients died, 16 from failure to control hemorrhage. In two patients failure to restore adequate visceral circulation resulted in bowel ischemia and infarction. The successful management of patients with visceral arterial injuries is dependent upon rapid and adequate exposure followed by primary repair or revascularization utilizing available surgical techniques.

Traumatic injuries of the inferior vena cava.

Three hundred and one patients with injury to the inferior vena cava have been treated over the past 30 years. Penetrating injuries predominated, with gunshot injury in 228 patients. The inferior vena cava was injured above the renal veins in 84 patients. One hundred and forty-eight patients had shock, 55 without palpable pulse or blood pressure. Vascular repair was accomplished in 234 patients. Ligation or packing was performed in 32 patients. Thirty-five patients died prior to vascular control or repair. Placement of intravascular shunts or occluding balloons was utilized in 25 patients. Mortality has decreased from a high of 100% in 1955 to 30% during the last six years of this experience. Reduction in mortality probably has resulted from shortened wounding to therapy intervals with more effective resuscitation and vascular control.

Management of 1,590 consecutive cases of liver trauma.

Between 1939 and 1974, more than 1,500 patients have been treated for penetrating or blunt liver trauma at our institution. Gunshot wounds and major blunt trauma have increased, stab wounds decreased, as percent of total. In most cases techniques other than partial hepatic resection were used, although this was performed in 49 instances. Choledochostomy was infrequently employed. Intracaval shunts were useful in 15 selected patients with massive hepatic, concomitant suprarenal vena caval, or hepatic vein injuries. The overall mortality of this group was 13.1%. The improvement in mortality from liver injuries is attributable to (1) early exploration for suspected intra-abdominal traumatic injury, (2) a conservative approach to the liver injury, and (3) the limitation of lobar resection, vascular cannulae, and afferent vascular compression to highly selected cases.

Resuscitation of the moribund patient using portable cardiopulmonary bypass.

The advancements in extracorporeal cardiopulmonary support through oxygenation and pumping units have permitted the explosive development of heart surgery. A battery-powered portable cardiopulmonary bypass machine has been used in 39 patients whose conditions precluded transport to the operating room. Nineteen patients with massive pulmonary emboli, 10 with extensive cardiopulmonary trauma, who had sustained massive drug overdose, and 2 with cardiogenic shock from acute myocardial infarction were successfully placed on cardiopulmonary bypass at the bedside within 15 minutes of cardiac arrest using femoral artery and femoral vein cannulation. Six patients who had cardiac arrest and suspected massive pulmonary emboli were found to have no mechanical cause for their arrest. Thirteen of the patients with massive pulmonary emboli were saved. Eight of the 10 patients who required portable cardiopulmonary bypass for massive traumatic thoracic injuries had control of hemorrhage and repair, allowing bypass to be discontinued. Two of these 8 patients had sustained transection of the proximal left anterior descending coronary artery. Sixteen patients survived for more than 30 days, and there are 15 long-term survivors.

Congenital intrapericardial aneurysmal dilatation of the left atrial appendage.

Congenital intrapericardial aneurysmal dilatation of the left atrial appendage is a rare but correctable lesion. One such patient who underwent aneurysmectomy is described, and the literature is reviewed.

Diagnosis and operation for anomalous circumflex coronary artery.

BACKGROUND: Origin of the left circumflex coronary artery from the right sinus of Valsalva is the most common anatomic variation of the coronary artery circulation. However, there are few reports about the operative approach to this anomalous vessel. METHODS: Forty patients having this anomaly were identified from 10,216 adult cardiac catheterization procedures. Forty percent of the anomalous circumflex coronary arteries (ACCAs) had critical atherosclerotic lesions. Eighty cases needed bypass grafting. RESULTS: For diagnosis of ACCA, the aortic root sign was positive in 94.9% of the diagnosed patients and the nonperfused myocardium sign was found in 92.5%. Eighty percent of ACCAs were larger than 2 mm in radiographic diameter before their passage into the atrioventricular groove. However, after emerging from the atrioventricular groove, 70% measured less than 1.5 mm. Consequently, a technique was developed to bypass the proximal ACCA and was used in 2 cases. Six other patients with more distal disease and larger vessels underwent conventional bypass grafting. CONCLUSIONS: The aortic root sign and nonperfused myocardium are useful in diagnosing ACCA. The ACCA is usually too small for use of the conventional graft technique. Therefore, a technique was developed to graft more proximally and was applied successfully in 2 cases.

Massive hemoptysis due to broncholithiasis.

Massive hemoptysis due to broncholithiasis is rare. Such a case is presented here, and the literature is reviewed. Surgical resection is the preferred definitive therapy, as a lack of bronchial artery collaterals limits the utility of bronchial artery embolization.

Clamp/repair: a safe technique for treatment of blunt injury to the descending thoracic aorta.

Debate exists with regard to the use of pump bypass, shunt bypass, or clamp/repair techniques in treating injuries to the descending thoracic aorta. The objective in using any of these techniques is to minimize the complications of paraplegia and renal failure, while achieving the lowest possible mortality. During an eighteen-year period, 45 patients were seen with acute blunt injury to the descending thoracic aorta. The shunt bypass method of repair was used in 1; pump bypass in 8; and clamp/repair in 23. There were desperate unsuccessful attempts to resuscitate and control hemorrhage in 13 patients, 1 of whom was placed on portable pump bypass. Thirty-two patients survived resuscitation and operation, and 26 were long-term survivors. Among surviving patients with permanent paraplegia, 2 underwent pump bypass and 1, the clamp/repair technique. Four other patients were seen with paraplegia or paresis and had reversal of the paralysis. The clamp/repair technique was used in these patients with clamp times ranging from 35 to 62 minutes (mean, 47.4 +/- 13.3 minutes). Renal failure did not occur in any patient, despite clamp times of up to 62 minutes (mean, 37.5 minutes). Excluding patients seen in a moribund condition, mortality most often was secondary to neurological or multisystem injury. Debate continues concerning intraoperative management of this highly lethal vascular injury. The data presented here support the historical composite experience that clamp/repair is a safe and efficacious technique that minimizes paraplegia and mortality.

Surgical considerations in bypassing coronary arteries with 100% proximal occlusion.

Objective data on the ability of cineangiography to predict the size of reconstituted totally occluded coronary arteries, as well as the clinical outcome of such revascularization, are sparse. Accordingly, we reviewed 200 consecutive cases of coronary revascularization to determine the answers to these questions. Group I patients (n = 57, with 86 totally occluded coronary arteries) had at least one coronary artery with a 100% proximal occlusion that reconstituted distally. Group II patients (n = 143, with 205 subtotally occluded coronary arteries) had 50% to 99% proximal stenosis of at least one coronary artery. Cineangiograms were blindly reviewed to measure the size of the coronary arteries, which were compared with the actual vessel size at operation. In group I, the totally occluded coronary arteries had a cineangiographic size of 1.9 +/- 0.7 mm and an actual size of 1.6 +/- 0.4 mm (p = 0.00004). In group II, the subtotally occluded coronary arteries had a cineangiographic size of 1.8 +/- 0.4 mm compared with an actual size of 1.8 +/- 0.3 mm (p = not significant). The site of bypass grafting was significantly smaller in group I (1.6 +/- 0.4 mm versus 1.8 +/- 0.3 mm; p = 0.00008). The two groups were similar with respect to preoperative and intraoperative parameters. Operative mortalities were similar (group I, 1.8%; group II, 3.5%; p = 0.68). Creatine kinase isoenzyme profiles and electrocardiographic changes were similar, except for a significant late rise of creatine kinase-MB in group I (56.1 +/- 14.7 versus 30.7 +/- 33.7 MIU/mL; p < 0.001). In conclusion, cineangiography significantly overestimates the size of totally occluded coronary arteries.(ABSTRACT TRUNCATED AT 250 WORDS)

Use of the activated coagulation time in intraoperative heparin reversal for cardiopulmonary operations.

Activated clotting time (ACT) was used in 300 consecutive patients undergoing cardiac operations to determine the adequacy of heparin reversal. Mean ACT prior to protamine sulfate administration was 9 minutes 40 seconds. A return to normal value (less than 2 min 10 sec) occurred in three-fourths of our patients following administration of 1.5 mg of protamine sulfate for each 100 units of heparin. Additional protamine sulfate was administered in 50 mg doses to those having abnormal ACT until normal clotting was obtained. Normal values for ACT usually coincided with clotting in the operative field. ACT proved to be a reliable guide to protamine sulfate administration.

Right ventricular aneurysm associated with postinfarction ventricular septal defect.

Isolated right ventricular aneurysms are rare. Postinfarction right ventricular aneurysm associated with a ventricular septal defect is a very unusual complication. We present such a case that was successfully treated surgically.

Benefit from combining blood conservation measures in cardiac operations.

Conventional blood conservation techniques have been insufficient to decrease transfusion needs in increasingly complex cardiac operations. To evaluate combinations of conservation techniques, 300 patients were divided into three equal groups. Group 1 had intraoperative autotransfusion and return of mediastinal drainage for 4 hours postoperatively. Group 2 had these measures plus intraoperative plasmapheresis. These two groups were given a transfusion for a hematocrit of less than 0.21 on cardiopulmonary bypass. Group 3 was treated with the same measures as group 2 but did not receive transfusions while on pump unless the hematocrit decreased to less than 0.15. The percentage of patients in each group given transfusions in the operating room was 34% in group 1, 28% in group 2, and 7% in group 3 (p less than 0.05). The percentage of all patients receiving transfusions during hospitalization was 68% in group 1, 36% in group 2 (p less than 0.05), and 18% in group 3 (p less than 0.05). Average total units transfused were 2.16 +/- 0.25 in group 1, 0.7 +/- 0.15 in group 2 (p less than 0.05), and 0.37 +/- 0.07 in group 3 (p less than 0.05). The perioperative morbidity rates including myocardial infarctions and strokes were similar. There were no deaths in group 3. Combining complementary conservation measures is effective in reducing homologous blood transfusions, and the need for transfusion can be safely reduced by allowing profound hemodilution during bypass.

Improved survival with multiple left-sided bilateral internal thoracic artery grafts.

BACKGROUND: Although conceptually sound, the use of multiple internal thoracic artery (ITA) bypass grafts to improve long-term clinical results remains controversial. This operation typically involves grafting the left ITA to the anterior descending artery and the right ITA to the right coronary artery. Past clinical studies of bilateral ITA operations have not examined comparative results associated with which coronary arteries received the ITA bypass grafts. Because grafting a superior conduit to an artery of lesser physiologic importance might reduce the clinical benefits, we compared the outcomes of patients receiving different configurations of bilateral ITA operations. METHODS: The study group was 498 consecutive bilateral ITA operations, constituting the 10-year experience of a single surgeon. Follow-up averaged 7.1 years (mode 7.3 years), and was 94.2% complete. These patients were divided into two groups, 311 patients (group I) who underwent the traditional operation (left ITA to the left anterior descending artery, right ITA to the right coronary artery), and 187 patients (group II) who received revascularization of branches of the left coronary artery (left ITA to the circumflex system and right ITA to the left anterior descending artery). RESULTS: The study groups were similar in age, severity of disease, number of bypassed arteries, ejection fraction, diabetes, hypertension, and duration of operation. There were more male patients in group II (91.4% versus 82.3%). A multivariate analysis showed that the location of ITA bypass grafts influenced survival independent of gender (p = 0.0288). Operative morbidity and mortality were similar between groups. Ninety-three patients had repeat angiography with equivalent patency rates of the ITA conduits (91.7% versus 89.6%; p = 0.67). The Kaplan-Meier actuarial survival estimate demonstrated a significant improvement in survival of patients in group II who received both ITA bypass grafts to left-sided arteries (p = 0.021), with the survival curves diverging at 6 years. More patients in group II were in New York Heart Association class I or II, but the difference was not statistically significant (94.6% versus 91.6%). Only 2 patients required reoperation. CONCLUSIONS: It appears that maximum long-term benefit from bilateral ITA operations is achieved by grafting the ITA conduits to coronary arteries that supply more left ventricular muscle.

Cardiopulmonary bypass in patients with previously completed stroke.

It has been assumed that patients with neurological residua after a completed stroke are at increased risk of neurological complications associated with cardiac operations requiring cardiopulmonary bypass. To evaluate these assumptions, we reviewed retrospectively 1,163 consecutive patients undergoing cardiac operations with cardiopulmonary bypass. Among these 1,163 patients were 43 patients having a previously completed stroke with neurological residua, but without clinically significant extracranial carotid artery disease. Forty-one underwent coronary artery bypass grafting; of these, 1 required concomitant aortic valve replacement, 1 had mitral valve replacement, and 1 had aortic valve replacement. There was one death in this group of 43 patients, due to massive pulmonary embolism. Only 1 of these 43 patients experienced new neurological symptoms after operation, which would appear to indicate that patients with a previous, completed stroke may not be at increased risk of neurological complications from cardiac operations requiring cardiopulmonary bypass.