Quantification of heterosubtypic immunity between avian influenza subtypes H3N8 and H4N6 in multiple avian host species.

Low-pathogenicity avian influenza virus (LPAIV) can lead to epizootics that cause economic losses in poultry or the emergence of human-infectious strains. LPAIVs experience a complex immunity landscape as they are endemic in numerous host species, and many antigenically distinct strains co-circulate. Prevention and control of emergence of detrimental strains requires an understanding of infection/transmission characteristics of the various subtypes in different hosts, including interactions between subtypes. In order to develop analytical frameworks for examining control efficacy, quantification of heterosubtypic immunity interactions is fundamental. However, these data are scarce, especially for wild avian subtypes in natural hosts. Consequently, in this study, three host species (mallards, quail and pheasants) were infected with two LPAIV subtypes isolated from wild birds: H3N8 and H4N6. The recovered hosts were also reinfected with the alternate subtype to measure the effects of heterosubtypic immunity. Oropharyngeal and cloacal swabs were collected and viral RNA load was quantified by real-time RT-PCR. For secondary infections in recovered hosts, peak viral load was up to four orders of magnitude lower and shedding length was up to 4 days shorter. However, both the magnitude and presence of heterosubtypic immunity varied across specific host species/subtype combinations. Using a mathematical model of virus replication, the variation in virus replication dynamics due to host individuals was quantified. It was found that accounting for individual heterogeneity is important for drawing accurate conclusions about treatment effects. These results are relevant for developing epidemiological models to inform control practices and for analysing virus replication data.

Coronary angioplasty, atherectomy and bypass surgery in cardiac transplant recipients.

OBJECTIVES: This study sought to analyze the outcomes of revascularization procedures in the treatment of allograft coronary disease. BACKGROUND: Allograft vasculopathy is the main factor limiting survival of heart transplant recipients. Because no medical therapy prevents allograft atherosclerosis, and retransplantation is associated with suboptimal allograft survival, palliative coronary revascularization has been attempted. METHODS: Thirteen medical centers retrospectively analyzed their complete experience with percutaneous transluminal coronary angioplasty, directional coronary atherectomy and coronary bypass graft surgery in allograft coronary disease. RESULTS: Sixty-six patients underwent coronary angioplasty. Angiographic success (< or = 50% residual stenosis) occurred in 153 (94%) of 162 lesions. Forty patients (61%) are alive without retransplantation at 19 +/- 14 (mean +/- SD) months after angioplasty. The consequences of failed revascularization were severe. Two patients sustained periprocedural myocardial infarction and died. Angiographic restenosis occurred in 42 (55%) of 76 lesions at 8 +/- 5 months after angioplasty. Angiographic distal arteriopathy adversely affected allograft survival. Eleven patients underwent directional coronary atherectomy. Angiographic success occurred in 9 (82%) of 11 lesions. Two periprocedural deaths occurred. Nine patients are alive without transplantation at 7 +/- 4 months after atherectomy. Bypass graft surgery was performed in 12 patients. Four patients died perioperatively. Seven patients are alive without retransplantation at 9 +/- 7 months after operation. CONCLUSIONS: Coronary revascularization may be an effective palliative therapy in suitable cardiac transplant recipients. Angioplasty has an acceptable survival in patients without angiographic distal arteriopathy. Because few patients underwent atherectomy and coronary bypass surgery, assessment of these procedures is limited. Angiographic distal arteriopathy is associated with decreased allograft survival in patients requiring revascularization.

Lung transplantation for advanced bronchioloalveolar carcinoma confined to the lungs.

BACKGROUND: Bronchioloalveolar carcinoma (BAC) is a well-differentiated lung adenocarcinoma that has a tendency to spread chiefly within the confines of the lung by aerogenous and lymphatic routes and may therefore be amenable to local therapy. However, a high rate of local recurrence after lung transplantation was recently reported. We describe two patients with unresectable and recurrent extensive BAC limited to the lung parenchyma who underwent lung transplantation with curative intent. METHODS: Patients were chosen to receive lung transplants for BAC if they met the following criteria: (1) recurrent or unresectable BAC limited to the lung parenchyma without nodal involvement and (2) suitable candidate for lung transplantation. RESULTS: The first patient relapsed in the lungs at 9 months after transplantation. The pattern of disease suggested contamination of the new lungs at the time of implantation. Repeat lung transplantation was performed, with cardiopulmonary bypass and irrigation of the remaining upper airway. This patient has had no evidence of local or systemic tumor recurrence at more than 4 years since the second transplantation. The second patient underwent transplantation using the modified technique and expired 16 months after transplantation of other causes. An autopsy showed no evidence of recurrent BAC in the lungs or of metastatic lesions at any site. CONCLUSIONS: Lung transplantation may be an option for unresectable or recurrent BAC confined to the lungs. Isolation of the diseased lungs and the use of cardiopulmonary bypass during surgery may be important in this disease and should be studied further.

Disc variance: a potentially lethal complication of the Beall valve prosthesis.

During 1975, 4 patients with erosion of the disc in Beall valve prostheses were seen. In one case the eroded disc was found loose in the distal aorta at postmortem examination. In 3 other cases, clinical diagnoses were made and successful reoperations performed. Because disc variance represents a potentially lethal complication, patients with disc prostheses should be examined at frequent intervals. When signs and symptoms of mechanical malfunction develop, the valve prosthesis should be replaced immediately to prevent death.

Experience with simultaneous myocardial revascularization and carotid endarterectomy.

Fifty-four patient had coexisting stenosis of the carotid artery (70% or greater) and coronary artery disease. Simultaneous carotid endarterectomy and myocardial revascularization were done in all cases. One permanent postoperative neurologic deficit occurred (1.9%). There were no deaths. Our experience with simultaneous correction of combined carotid and coronary disease leads us to conclude that simultaneous myocardial revascularization and carotid endarterectomy have low mortality and neurologic morbidity rates. The policy at Loyola University Medical Center at this time is to routinely perform simultaneous endarterectomy and myocardial revascularization in all patients with significant coexisting carotid and coronary disease.

Myocardial revascularization for the third time. Clinical characteristics and follow-up.

Twenty-five patients presenting for a third revascularization procedure were retrospectively reviewed at Loyola University Medical Center, Maywood, IL. This represents 0.5 percent of the total revascularization cases over a five-year period extending from 1985 through 1989. Perioperative mortality was none, and seven complications occurred in six patients. Internal mammary arteries were used for revascularization in 60 percent of this group. Follow-up reveals that only one patient has died secondary to an arrhythmia. All patients except one are symptomatically improved, and 18 patients remain angina free at a mean follow-up of 22.3 months. It is therefore concluded that patients are clinically improved with a third revascularization, and this procedure should be offered as an effective means of treatment.

Cardiac surgery for chronic renal dialysis patients.

Twenty-two open-heart operations have been performed on 21 patients receiving chronic renal dialysis. These cases include 16 aortocoronary bypasses and six valve replacements. The average time on dialysis prior to surgery was 26 months; 18 of 21 patients were in NYHA grade 3 or 4. Twenty-seven postoperative complications occurred, with six requiring further surgery and 21 treated nonsurgically. Two perioperative deaths occurred, both due to sepsis. Long-term follow-up was achieved on all hospital survivors. Ten patients remain alive with a mean follow-up of 21 months. At a mean of 16.5 months after surgery, nine deaths occurred, with only two due to known cardiac problems. In summary, indicated cardiac surgery can be performed on chronic renal dialysis patients with a reasonable morbidity and mortality; however, the long-term survival of our patients has not been assured by a successful cardiac operation.

Acute coronary artery occlusion secondary to blunt chest trauma.

Two patients suffered an acute transmural MI due to complete occlusion of the proximal LAD after blunt chest trauma. One developed a rupture of the ventricular septum with a ventricular aneurysm and the other an acute ventricular aneurysm, both accompanied by congestive heart failure. Neither had a history of ischemic heart disease; both had normal right and circumflex coronary arteries by arteriography. An intimal tear or subintimal hemorrhage with luminal thrombosis, or both, are the suggested mechanisms of coronary artery occlusion. Both patients were operated upon successfully. Patient 1 underwent closure of the VSD and resection of the ventricular aneurysm. The LAD had returned to normal and required no aortocoronary bypass graft. Patient 2 underwent arteriotomy of the LAD with Fogarty catheter embolectomy and aortocoronary bypass graft, combined with resection of the ventricular aneurysm. We recommend that patients who suffer blunt chest trauma and show ECG changes should undergo cardiac catheterization and coronary arteriography, followed by the pertinent treatment.

The advantages of open mitral commissurotomy for mitral stenosis.

Mitral commissurotomy is the treatment of choice for mitral stenosis. If this is not feasible, replacement of the valve becomes necessary. Open commissurotomy has been performed at Loyola University Medical Center, Maywood, Ill, in 105 patients since 1970. The mean age was 45 years. The indication for surgery was heart failure in 92 of the cases. Sixty of the patients were in class 3 of the New York Heart Association (NYHA) classification. Eighty-five underwent open mitral commissurotomy alone. This was not feasible in 42 patients scheduled for it who required valvular replacement. Twenty-five patients had a left atrial thrombus. Two patients died, one from aortic dissection and the other from acute infarction in the perioperative period. Ninety-eight patients are NYHA class 1 or 2 at present. Two patients required valvular replacement following the commissurotomy. The low mobidity and mortality with excellent long-term results support our contention that open mitral commissurotomy is the treatment of choice for mitral stenosis.

Management of postoperative heparin rebound following cardiopulmonary bypass.

Postoperative heparin rebound was investigated in 50 adult patients undergoing cardiopulmonary bypass with the use of the Hepcon heparin analyzer. Prior to bypass each patient received 2 mg/kg of heparin. During bypass, the activated clotting time (ACT) was utilized to assess the need for additional heparin to maintain the value between 300 and 400 seconds. The average amount of heparin given was 160 mg. Once cardiopulmonary bypass was terminated the Hepcon unit was employed to determine the actual amount of active circulating heparin and to calculate the dose of protamine sulfate. The average amount of protamine administered intraoperatively was 200 mg. The overall mean ratio of protamine-to-heparin was 1.25 : 1. Once hemostasis was achieved, no circulating heparin was measured with the Hepcon unit, and the ACT value had returned to its baseline, the incisions were closed and the patients were transferred to the intensive care unit. One hour later a blood sample was obtained and analyzed by the Hepcon unit for any heparin rebound. We found that 26 patients (52%) had circulating heparin and required an additional dose of protamine, averaging 70 mg. Drainage from the thoracotomy tubes averaged 400 cc in the first 24 hours, and a mean of 2 units of packed cells was infused. Three patients (6%) did not require any blood transfusions. The use of the Hepcon unit has produced a safe and expedient method of analyzing and neutralizing active circulating heparin in patients following cardiopulmonary bypass. It is a useful adjunct in blood conservation because it reduces excessive postoperative blood loss associated with heparin rebound.

Nonthoracotomy lead system for implantable defibrillator.

Over a 2-year period, 110 patients underwent attempted implantation of an automatic cardioverter-defibrillator using the nonthoracotomy lead system. Indications included sustained monomorphic ventricular (n = 62), nonsustained with poor ventricular function (n = 7), ventricular fibrillation (n = 21), ventricular tachycardia/fibrillation (n = 18), and familial long QT syndrome (n = 2). There were 90 male and 20 female patients. Mean age was 57 +/- 15 years. Sixty percent had previous coronary bypass or valve operations, or both. Mean left ventricular ejection fraction was 30% +/- 14%, cardiac index was 2.4 +/- 0.9 L/m2, and systolic pulmonary artery pressure was 41 +/- 14 mm Hg. Under general anesthesia, the nonthoracotomy lead was introduced through the left subclavian vein. The subcutaneous patch and generator were placed posteriorly on the serratus muscle and left upper quadrant, respectively. The length of the procedure was 116 +/- 44 minutes and the mean number of defibrillation shocks for a successful implant was 8 +/- 4. Eighty-five patients (77%) had successful implantations. Failures were due to high defibrillation threshold (n = 23) and inability to place a right ventricular lead (n = 2). Predictors of failure included preoperative antiarrhythmic drugs and cardiac index of 1.8 +/- 4 L/m2 or less (p = 0.004). Three patients (2.7%) died after the operation of heart failure (n = 2) and chronic heart transplant rejection (n = 1). Complications included lead migration or dislodgment (n = 8), infection (n = 1), and hematoma (n = 3). In summary, the nonthoracotomy lead system may provide an alternative in patients undergoing cardioverter-defibrillator implantation.

Multivariate discriminant analysis of risk factors for operative mortality following isolated coronary artery bypass graft. Loyola University Medical Center experience, 1970 to 1984.

The Loyola Open-Heart Registry is a fully operational database that contains detailed data on approximately 9,000 patients who have undergone coronary bypass or cardiac valve replacement from January 1970 to December 1984. We analyzed the registry data using multivariate discriminant analysis to identify and quantitate those factors that might predict operative mortality (OM) for patients undergoing coronary artery bypass grafts at Loyola University Medical Center: Operative mortality was defined as death within 30 days following surgery. A total of 50 clinical and angiographic variables were analyzed for possible univariate association with operative mortality. Twenty-two variables were found to have significant univariate association with OM, and these 22 variables were subjected to multivariate discriminant analysis. For patients undergoing isolated, elective coronary artery bypass, the factors found to be predictive of OM are age (greater than 70) (F = 11.57), severe (more than six stenoses) coronary artery disease (F = 5.81), diffuse disease (F = 5.54), positive family history (F = 5.17), and number of coronary arteries bypassed (F = 4.78).

Measurement of right ventricular volume in human explanted hearts using ultrafast cine computed tomography.

The quantitative measurement of right ventricular (RV) volume has been attempted by a number of methods, including nuclear magnetic resonance imaging, contrast angiography, echocardiography, and radionuclide angiography. All of these methods have limitations. Ultrafast cine computed tomographic (CT) scan is a new technology that may have an important role in on-line ventricular volume measurements. Twelve human explanted hearts, fixed in formalin, were subjected to ultrafast cine CT scans to estimate RV volume. The volumes derived from the CT scans were compared with actual fluid volumes needed to fill the RV volume measurements. All measurements were conducted independently by two observers. Actual RV volumes in the 12 hearts ranged from 29.8 ml to 174.6 ml. A strongly significant correlation between actual volume and CT volume was seen (r = 0.99). Agreement between observers was also seen to be highly significant (r = 0.992). Limitations to accurate in vivo assessment due to bolus injection of contrast medium might include alterations in ventricular pressure change. Similarly, differentiation of the endocardial border with contrast may not be as sharp as that with an air-tissue interface. This study demonstrates that RV volumes can be reliably determined by ultrafast cine CT scans in explanted hearts. On-line systolic and diastolic volumes and thus stroke volume, ejection fraction, etc, can be accurately defined independent of cardiac orientation. This technique offers opportunities to study ventricular function under various conditions.

Management of left ventricular rupture complicating myocardial infarction.

Rupture of the left ventricle secondary to myocardial infarction may occur more often than is suspected. More time than anticipated may be available between rupture and catastrophic deterioration. Hemodynamic stabilization, diagnostic studies, and surgical treatment can be successfully undertaken. Four patients have been successfully treated in our institution. Rupture occurred from 1 to 14 days after infarction. Persistent chest pain was present in all. All were hemodynamically unstable and all stabilized with counterpulsation. One patient was in cardiogenic shock, two had a cardiac arrest, and one presented with cardiac tamponade requiring two emergency pericardiocenteses. Coronary arteriography was done in all four patients. Surgical management consisted of infarctectomy and repair of the ventricular rupture. Additionally, a single aortacoronary bypass graft was needed in two patients and repair of a ventricular septal rupture was necessary in a third. There was no operative mortality. One patient drowned 1 year later. We conclude that successful surgical management requires (1) suspicion of ventricular rupture, (2) hemodynamic stabilization by counterpulsation, (3) coronary arteriography, and (4) combined infarctectomy and repair with revascularization.

Topography of cardiac ganglia in the adult human heart.

Published descriptions of the topography of cardiac ganglia in the human heart are limited and present conflicting results. This study was carried out to determine the distribution of cardiac ganglia in adult human hearts and to address these conflicts. Hearts obtained from autopsies and heart transplant procedures were sectioned, stained, and examined. Results indicate that the largest populations of cardiac ganglia are near the sinoatrial and atrioventricular nodes. Smaller collections of ganglia exist on the superior left atrial surface, the interatrial septum, and the atrial appendage-atrial junctions. Ganglia also exist at the base of the great vessels and the base of the ventricles. The right atrial free wall, atrial appendages, trunk of the great vessels, and most of the ventricular myocardium are devoid of cardiac ganglia. These findings suggest modifications to surgical procedures involving incisions through regions concentrated with ganglia to minimize arrhythmias and related complications. Repairs of septal defects, valvular procedures, and congenital reconstructions, such as the Senning and Fontan operations, involve incisions through areas densely populated with cardiac ganglia. The current standard procedure for orthotopic heart transplantation severs cardiac ganglia and their projections to nodal and muscular tissue. One modification of the current heart transplantation procedure, involving bicaval anastomosis, preserves atrial anatomy and the cardiac ganglia. Preservation of cardiac ganglia within the donor heart may provide additional neuronal substrate for intracardiac processing and targets for regenerating nerve fibers to the donor heart.

Oversizing of donor hearts: beneficial or detrimental?

To determine the effects of donor/recipient weight mismatch on allograft function and survival after orthotopic heart transplantation, we retrospectively compared the clinical and the hemodynamic characteristics of recipients weighing more than their donor ("undersized") with those of recipients weighing less than their donor ("oversized"). The median follow-up period was 24 months (range, 0 to 67 months). In 88 patients (59%) donor weight was 1% to 46% less than recipient weight (13.5 +/- 8.9 means +/- SD). In 61 patients (41%) donor weight exceeded recipient weight by 0% to 139% (20% +/- 23%). When recipient ideal body weight was used in the analysis, 75 patients (51%) were undersized by 1% to 59% (13% +/- 10%), and 72 patients (49%) were oversized by 0% to 67% (19% +/- 18%). Preoperative transpulmonary gradient, ventricular function, and exercise tolerance were similar in the two groups. The number and severity of episodes of rejection and infection after transplantation were also similar in the two groups 1, 6, and 12 months after transplantation. When recipient ideal weight was used in the analysis, right ventricular (RV) and left ventricular (LV) ejection fractions (EFs) were within normal limits (RVEF greater than 40%; LVEF greater than or equal to 45%) and similar in the two groups. When recipient actual weight was used in the analysis, the LVEF measured at 12 months after heart transplantation was higher in the oversized than in the undersized group (52 +/- 11 vs 46 +/- 10; p less than 0.05). Postoperative hemodynamic values and exercise tolerance were similar in the two groups regardless of whether recipient weight or ideal body weight were used in the analysis. Forty-six recipients died 0 to 46 months (median, 7 months) after orthotopic heart transplantation. In a Cox regression model, recipients with donor weight greater than recipient ideal weight had a significantly greater risk of death within the follow-up period than did recipients with donor weight less than recipient ideal weight (relative risk = 2.19; p less than 0.05). When percent donor weight/recipient ideal weight mismatch was used as a continuous variable, donor heart oversizing was negatively related to survival, independent of preoperative transpulmonary gradient values (p less than 0.05). In contrast to common belief, oversizing of donor hearts does not improve the outcome of orthotopic heart transplant recipients who have reversible preoperative pulmonary hypertension. Acceptance of undersized donor hearts is not detrimental to allograft function and recipient survival. Use of undersized donor hearts may maximize the use of critically scarce donor organs.

The use of the Jarvik-7 total artificial heart and the Symbion ventricular assist device as a bridge to transplantation.

The proliferation of transplantation programs has not been paralleled by a similar increase in the availability of organ donors. Between 1984 and 1987, 104 orthotopic heart transplantations were performed at Loyola University Medical Center. During the same period, 25 patients died while awaiting a donor organ. To reduce the mortality, we began using the total artificial heart (TAH) and a ventricular assist device (VAD) as a bridge to transplantation in 1988. Of 29 patients who underwent transplantation, 15 patients required a TAH and three patients required a VAD as a bridge. The underlying heart conditions were ischemic cardiomyopathy (11 patients), dilated cardiomyopathy (5 patients), giant cell myocarditis (1 patient), and allograft failure (1 patient). The average duration of mechanical support was 10 days (range, 1 to 35 days). Of the 17 patients who successfully underwent transplantation, 1 patient died at 17 days because of acute rejection of the transplanted heart, and another patient died at 14 days because of a cerebral vascular event. Fifteen patients (83%) were long-term survivors. Nine patients required reoperation for bleeding. While the mechanical device was in place, the activated clotting time was maintained between 170 and 200 seconds with heparin. Dipyridamole was given. We conclude that the TAH and VAD are excellent mechanical bridges to transplantation.

Coronary embolism: surgical management.

The successful use of Fogarty catheter embolectomy combined with aortocoronary vein bypass graft in 4 patients with an acute myocardial infarction is presented. Three patients sustained acute occlusion of the coronary artery secondary to an embolus during cardiac catheterization. In the fourth patient, the left anterior descending coronary artery was occluded with a fragment of calcium debris during aortic valve replacement. All patients survived the operation. Acute occlusion of the coronary artery secondary to an embolus is uncommon, but its early recognition and appropriate surgical management may be lifesaving.

Internal mammary artery revascularization in the patient on long-term renal dialysis.

Twenty-six patients on long-term renal dialysis underwent coronary artery bypass grafting. The patients were divided into two groups: group 1, (16 patients) saphenous vein bypass grafts, and group 2, (10 patients) internal mammary artery in combination with saphenous vein bypass grafts. Both groups were similar in terms of cardiac hemodynamics and previous number of myocardial infarctions, though more group 1 patients were in New York Heart Association class III or IV. Patients in group 1 received 2.9 bypass grafts per patient; patients in group 2 received 4.0 bypass grafts per patient (4 with bilateral mammary arteries). No wound healing problems occurred in either group. Blood replacement was similar for both groups (group 1, 5.5 units/patient; group 2, 5.3 units/patient). More platelets were given to group 1 patients (16.2 units/patient) than group 2 patients (3.1 units/patient). We conclude that use of the internal mammary artery in patients on long-term renal dialysis does not alter wound healing or increase blood loss in this subset of patients.

Chronic cardiac rejection masking as constrictive pericarditis.

The hemodynamic changes consistent with constrictive pericarditis are often encountered in patients who have undergone cardiac transplantation. We describe here 4 patients who underwent pericardiectomy after cardiac transplantation. All were found to have evidence of a thickened and constricting peel of pericardium at surgical exploration. Their postoperative clinical courses were variable. One patient with primarily effusive constriction experienced marked improvement. Three patients failed to show clinical improvement and had persistently elevated atrial and ventricular end-diastolic pressures. A coexisting restrictive cardiomyopathy secondary to chronic rejection, coronary arteriopathy, or long-standing constriction may have been the cause of this poor outcome. Many patients with transplanted hearts exhibit evidence of poor diastolic ventricular compliance without evidence of classic constriction; some manifest both the restrictive and constrictive components. The careful selection of patients with constrictive pericarditis can optimize the outcome.