Neuroprotective natural antibodies to assemblies of amyloidogenic peptides decrease with normal aging and advancing Alzheimer's disease.

A number of distinct beta-amyloid (Abeta) variants or multimers have been implicated in Alzheimer's disease (AD), and antibodies recognizing such peptides are in clinical trials. Humans have natural Abeta-specific antibodies, but their diversity, abundance, and function in the general population remain largely unknown. Here, we demonstrate with peptide microarrays the presence of natural antibodies against known toxic Abeta and amyloidogenic non-Abeta species in plasma samples and cerebrospinal fluid of AD patients and healthy controls aged 21-89 years. Antibody reactivity was most prominent against oligomeric assemblies of Abeta and pyroglutamate or oxidized residues, and IgGs specific for oligomeric preparations of Abeta1-42 in particular declined with age and advancing AD. Most individuals showed unexpected antibody reactivities against peptides unique to autosomal dominant forms of dementia (mutant Abeta, ABri, ADan) and IgGs isolated from plasma of AD patients or healthy controls protected primary neurons from Abeta toxicity. Aged vervets showed similar patterns of plasma IgG antibodies against amyloid peptides, and after immunization with Abeta the monkeys developed high titers not only against Abeta peptides but also against ABri and ADan peptides. Our findings support the concept of conformation-specific, cross-reactive antibodies that may protect against amyloidogenic toxic peptides. If a therapeutic benefit of Abeta antibodies can be confirmed in AD patients, stimulating the production of such neuroprotective antibodies or passively administering them to the elderly population may provide a preventive measure toward AD.

Myocardial and non-myocardial release of myoglobin and creatine-kinase MB following cardiac operations with hypothermic potassium cardioplegia.

Serum time-activity curves for myoglobin, creatine-kinase (CK) and its isoenzyme MB were determined during and after coronary bypass surgery and aortic valve replacement. Hypothermic potassium cardioplegia was the method employed to initiate cardiac arrest. Cardiac myoglobin and CK-MB release rates were maximal 0.5 to 1.0 h post aortic cross-clamp release (PACR) with maximal concentrations at 1 and 4 h PACR respectively. The cardiac release ceased within 5 h PACR but was followed by a noncardiac release with maximal concentrations from 10 to 35 h PACR. The cardiac myoglobin release was significantly lower in the coronary bypass group, whereas no significant intergroup difference was observed for CK-MB. The cumulative CK-MB release corresponded roughly to about 5 g of myocardium.

Right atrial-right ventricular anastomosis for correction of tricuspid atresia.

Previously reported methods for the correction of tricuspid atresia involve the use of conduits and/or valves. Since many of the younger patients will outgrow their conduits and the long-term durability of the valve prostheses is open to question, we have devised an operation in which the right atrial (RA) appendage is anastomosed to the right ventricle (RV) with the aid of a pericardial patch. The RV, if not too hypoplastic, is used as a pumping chamber and the pulmonary valve is in its normal position. Three patients, 8, 9, and 12 years of age, were operated on with good clinical and hemodynamic results. Postoperatively, all three were acyanotic and had improved physical capacity compared with their preoperative status. The RA pressure in the first two patients 1 year after operation was 12 mm. Hg and at angiocardiography the RA-RV anastomosis was widely patent. In one of the patients, the RV was too hypoplastic to function. It should be possible to perform this operation even in younger patients and it may eliminate the need for palliative procedures and reoperations.

Detachment of the septal tricuspid leaflet during transatrial closure of isolated ventricular septal defect.

In 27 (18%) of the 151 patients who underwent transatrial closure of isolated ventricular septal defect (VSD) between 1966 and 1979, the tricuspid valve was partially detached in order to achieve better exposure. All 27 patients had defects of the membranous or paramembranous type situated behind the tricuspid septal cases, tight chordae tendineae crossed over the defect and inserted in the edge of the VSD. A 15 to 20 mm incision in the septal leaflet was usually needed to expose the defect sufficiently. There were two operative deaths among the 27 patients, both unrelated to the tricuspid incision. The remaining patients had uncomplicated postoperative courses. There were no long-term complications or instances of significant tricuspid valve incompetence, major residual shunt, or heart block at follow-up. Three patients, operated upon at the ages of 3, 3, and 6 years, respectively, had residual pulmonary hypertension. In one patient, who died 4 years postoperatively in a traffic accident, the tricuspid valve was intact and the previous incision could hardly be seen. It is concluded that detachment of the septal tricuspid leaflet is a safe procedure during transatrial closure of a VSD.

Late outcome and quality of life after complicated heart operations.

BACKGROUND: Patients with severe postoperative complications consume a great deal of the economic resources for intensive care. Our knowledge of the late outcome and quality of life of these patients is scarce. METHODS: One thousand five hundred twenty-two patients undergoing cardiac operations during 1991 and 1992 were studied, and the 100 patients who needed the most expensive treatment were identified. The patients were retrospectively risk scored (Higgins score), and the clinical outcome was studied. The surviving patients were followed up for 2 years after the operation. Their quality of life and remaining symptoms were assessed. RESULTS: No significant age difference between groups was observed. There were significantly more women, emergency cases, high-risk patients, and postoperative complications in the studied group. Mortality rate during the first postoperative year was significantly higher in the studied group. Later the difference in mortality rate between the groups decreased. At the 2-year follow-up all the 72 surviving patients in the study group had returned home with less physical and psychological symptoms related to their heart disease. CONCLUSIONS: The cost of treating severe complications in the intensive care unit is high. However, the results of the present study indicate that even a very complicated postoperative course is not incompatible with a successful outcome in the long run.

Optimal insertion technique for the Björk-Shiley valve in the narrow aortic ostium.

The Björk-Shiley tilting disc valve was used for aortic valve replacement (AVR) in 250 consecutive patients between 1977 and 1982. One hundred and ninety-six patients had isolated AVR, and 54 had combined procedures (double- or triple-valve replacement in 31, associated coronary artery bypass grafting in 20, and miscellaneous procedures in 3). A special technique for inserting large Björk-Shiley valves without using outflow patches or annuloplastic procedures was developed. This method included allowing the right portion of the aortic incision to end about 0.5 cm above the noncoronary sinus; the use of simple interrupted sutures; placement of the prosthetic sewing ring on top of the annulus of the noncoronary sinus, thereby tilting the valve slightly in the outflow tract; and routine orientation of the major opening of the valve toward the annulus of the noncoronary sinus. This orientation resulted in the largest effective orifice area at postoperative catheterization. None of the male patients received a valve smaller than 23 mm, and none of the female patients were given a valve smaller than 21 mm. The convexoconcave model of the Björk-Shiley valve was used in 71% of the patients. An outflow patch was required only in 1 patient with concomitant supravalvular stenosis of the aorta. The combination of adequate myocardial protection, comparatively short aortic cross-clamping times, and the use of large, properly oriented Björk-Shiley valves resulted in satisfactory postoperative hemodynamics in all patients. In fact, none of the 196 patients undergoing isolated AVR and only 5 (9%) of the 54 patients undergoing combined procedures required postoperative inotropic stimulation. There were no operative deaths, and all patients left the hospital in good condition. The Björk-Shiley tilting disc valve is a reliable and well-functioning aortic valve substitute that is particularly suited for patients with narrow aortic ostia. With attention to certain details in the insertion technique, encouraging clinical results can be obtained with this prosthesis.

Heart valve replacement with the Björk-Shiley Monostrut valve: early results of a multicenter clinical investigation.

To evaluate the clinical performance of the Björk-Shiley Monostrut prosthesis, five centers combined their early experience. Between May, 1982, and June, 1985, 537 prostheses were implanted in 486 patients at these centers: 246 patients had aortic valve replacement (AVR), 163 underwent mitral valve replacement (MVR), and 47 had double-valve replacement (DVR). Thirty patients underwent other, more complex procedures. Concomitant cardiac procedures were performed in altogether 25%. Overall hospital (30 days) mortality was 5.1% (3.6% for AVR, 4.3% for MVR, 8.3% for DVR, and 16.6% for other procedures). The patients were followed up at 6- to 9-month intervals from 6 to 48 months (mean follow-up, 33 months). Follow-up was 99.6% complete. Late mortality was 7.2%. The three-year survival rate was 91.0% for AVR, 92.3% for MVR, and 76.2% for DVR. There was no structural failure of the prosthesis. No instances of valve thrombosis and fatal thromboembolism occurred in anticoagulated patients. The three-year incidence of freedom from thromboembolic events (including TIA) was 89.8% for AVR, 94.9% for MVR, and 90.2% for DVR. Preoperative and postoperative data for the assessment of mechanical hemolysis was available in 60% of the patients. The degree of mechanical hemolysis was low and did not change with time. Although the follow-up is still short, the Björk-Shiley Monostrut prosthesis appears to represent an improvement over previous Björk-Shiley models, particularly with regard to durability.

An in vivo method for testing hemocompatibility of materials used in prosthetic heart valves.

BACKGROUND AND AIMS OF THE STUDY: An in vivo method for testing hemocompatibility of materials used in mechanical heart valves was developed. METHODS: Discs of test materials were glued to specially designed plastic (Delrin) buttons and implanted into the superior and inferior venae cavae of sheep through a right thoracotomy. The button and disc had such configuration that the blood flow was minimally disturbed. Up to four different materials could be tested simultaneously in each animal: two in superior vena cava and two in inferior vena cava. The materials and their respective implantation sites were changed between different animals according to the Latin square principle. Ten animals were used. Three materials currently used in mechanical heart valve prostheses-titanium, cobalt-chromium alloy (Haynes 25) and pyrolytic carbon (Pyrolite)--together with a surface modified (methylated) titanium were evaluated. No heparin was given during the experiment. After two hours of testing the discs were explanted and evaluated for hemocompatibility. The thrombus area on each disc was measured with photography and planimetry. Platelet and leukocyte adhesion on the surfaces were quantitatively assessed by scanning electron microscopy (SEM). The results showed that there were significant differences in thrombus formation (p = 0.001) and leukocyte adhesion (p = 0.002) between the materials tested. There was no difference between implantation sites but significant differences between individual animals (p < 0.05). CONCLUSION: The results indicate that the method can be used to evaluate early hemocompatibility of biomaterials.

In vivo comparison of hemocompatibility of materials used in mechanical heart valves.

BACKGROUND AND AIMS OF THE STUDY: Most studies of mechanical heart valve prostheses in recent years have focused on the hydrodynamic and clinical performance of different valve designs. Little attention has been paid to the hemocompatibility (thrombogenicity) of materials used in the prostheses. METHODS: In the present study, three materials currently used in mechanical heart valves, titanium, cobalt-chromium alloy (Haynes 25) and pyrolytic carbon (Pyrolite), together with a surface-modified (methylated) titanium, were evaluated and compared for their hemocompatibility in a sheep model. The test materials in the form of discs were glued to plastic buttons and implanted into the intrathoracic venae cavae of anesthetized sheep. Four different materials were tested simultaneously in each animal: two in the superior and two in the inferior vena cava. Eight animals were used. After two hours of exposure to flowing blood, the discs were explanted and evaluated for their hemocompatibility using close-up photography and scanning electron microscopy (SEM). Thrombus formation and blood cell adhesion were studied quantitatively. RESULTS: The results showed that there was significantly more thrombus on pyrolytic carbon and methylated titanium than on titanium and cobalt-chromium (p < 0.05). More leukocytes adhered on pyrolytic carbon and cobalt-chromium than on titanium and methylated titanium (p < 0.05). CONCLUSION: The results indicate that titanium and cobalt-chromium under the present condition were more hemocompatible than pyrolytic carbon. The clinical significance of the finding remains to be investigated.

An initial investigation into the wear and damage within the pivots of three types of bileaflet mechanical heart valves.

Two 29 mm St. Jude Medical valves, two 29 mm CarboMedics valves and two 29 mm Sorin Bicarbon valves were tested in a real time fatigue test rig. The test rig was run at 72 beats/min with a stroke volume of 70 ml for approximately one million cycles. Optical microscopy was used to investigate the valve surfaces. Possible deterioration of the surface finish was observed on the stops of the hinge recesses in the St. Jude Medical and CarboMedics valves. In the Sorin valves areas of the pyrolytic carbon coating was worn away adjacent to and on the valve stops.

Periprosthetic leaks and valve dehiscence: alternative methods of repair.

BACKGROUND AND AIMS OF THE STUDY: Reoperations for periprosthetic leaks (PL) and valve dehiscence (VD) are associated with high mortality and substantial recurrence rate. Standard methods of repair are often not feasible due to friability of the annulus tissue or lack of space to locate the sutures. We have therefore used a variety of unconventional methods to close the leaks securely. CLINICAL MATERIAL AND METHODS: The clinical records of 25 patients reoperated for PL and VD between 1989 and 1995 were reviewed. Eighteen patients had aortic and seven mitral PL. Patients with mechanical heart valves were more frequently reoperated than those with bioprostheses (2.1% versus 0.7%). The PL was repaired in 16 cases, and the prosthesis was exchanged in nine cases with VD or large leaks. Six of the latter nine patients had active prosthetic endocarditis. A variety of surgical techniques was used to repair the leaks, including placing sutures from outside the aortic wall, through the atrial and ventricular septum, through the free left atrial wall and closure by single or double patch technique. RESULTS: Hospital mortality was 4% (1/25 patients) and one-year mortality 12.5%. None of the patients except one with active prosthetic endocarditis needed a second reoperation. CONCLUSIONS: If PLs are difficult to close with standard surgical technique, the alternative methods described might be useful. These methods can also be used during primary valve replacements where leaks remain.

Aortic valve replacement for aortic stenosis in patients with small aortic root.

BACKGROUND AND AIMS OF THE STUDY: Patients with aortic stenosis and small aortic ostia are getting more and more common in our practice. They now constitute a third of our aortic valve replacement (AVR) material. The patients are usually elderly women with small heart and body dimensions, sometimes making it difficult to implant sufficiently large valve prostheses. MATERIALS AND METHODS: We describe a non-selected series of 254 patients from a geographically defined area who underwent AVR during a six year period (1989-1995) and who were considered to have small aortic annulus, defined as patients receiving 19 and 21 mm prostheses. Mean age was 71 years, 42% were over the age of 75, 88% were women and 32% underwent concomitant coronary artery bypass grafting (CABG). Fifty-nine (23%) required pericardial patch enlargement of the aortic root to accommodate sufficiently large prostheses. Prostheses used included Björk-Shiley Monostrut (n = 54), CarboMedics (n = 58), St. Jude (n = 74), Sorin Bicarbon (n = 2), Mitroflow pericardial (n = 26) and Carpentier-Edwards pericardial valve (n = 40). Pericardial valves were usually employed in patients 75 years and older. RESULTS: Operative mortality was 3.1%. There was no mortality in patients undergoing isolated AVR. Late mortality, after a mean observation period of two years, was 4.9%. At Doppler echocardiography one week postoperatively, 95% had a gradient across the prosthesis that was considered to be within acceptable limits (resting mean gradient < 30 mmHg). In the remaining patients higher gradients indicated some degree of prosthesis-patient mismatch. CONCLUSIONS: To avoid this mismatch the surgical considerations include choosing a prosthesis with a large effective orifice area, using an optimal valve implantation technique (partly or completely supra-annular placement of the prosthesis) and, if this is not enough, enlarging the annulus with an outflow patch.

Primary idiopathic chylopericardium--a case report and review of the literature.

Primary idiopathic chylopericardium is a rare entity with obscure etiology. In recent years, a few reports have been published where the lymphatic leak and fistula were identified by combined lymphangiography and computed tomography or intraoperative thoracic ductogram. Here we report a case occurring in a previously healthy 51 year old woman, to our knowledge the first case described in Scandinavia. She presented with cough and dyspnea of about 1 year duration. Chest X-ray demonstrated enlargement of the cardiac silhouette. Echocardiography revealed pericardial effusion and at puncture pericardiocentecis 760 ml of chylous fluid was evacuated. There was no history of trauma, infection or neoplasm. She underwent extensive investigations but no apparent cause of the chylous effusion could be determined. Conservative treatment with pericardial drainage and low fat (medium chain triglyceride) diet failed. The patient was cured by surgical ligature of the thoracic duct and partial pericardectomy through a left anterolateral thoracotomy. At 12 months post operation she was doing well and echocardiography did not reveal any signs of recurrence. A brief review of the literature is presented.

Minimal access aortic valve surgery.

OBJECTIVE: We report our experience with minimal access aortic valve surgery and discuss the three approaches used. METHODS: From June 1996 to October 1997, 18 patients underwent minimally invasive aortic valve surgery through three different incisions: right parasternal minithoracotomy (three cases), upper ministernotomy (11 cases), and transverse sternotomy (four cases). No special surgical instrumentation was used. Aortic valve replacement was carried out in 17 patients and aortic valve repair in one patient. The patients ranged in age from 42 to 86 years (mean 64 years). Concomitant procedures involving the aortic root and the ascending aorta were performed in five patients. RESULTS: There was no mortality and no complications related to the procedure or the access. There was no instability or paradoxical movement of the chest wall. One patient was reoperated for postoperative bleeding. All patients were discharged from hospital within the usual time. No attempts were made to discharge them earlier, even if they recovered quickly. CONCLUSIONS: Of the three incisions used, the upper ministernotomy seemed to be the safest and easiest to perform. Through this incision, both the aorta and the right atrium could be cannulated, the right ventricle was accessible, and concomitant procedures on the ascending aorta could be carried out. The drawback of minimal access aortic valve surgery in general is that it is difficult to de-air the heart and more difficult to master intra- and postoperative complications should they occur.

Are electrocardiographic Q-wave criteria reliable for diagnosis of perioperative myocardial infarction after coronary surgery?

OBJECTIVE: A major assumption in cardiovascular medicine is that Q-waves on the electrocardiogram indicate major myocardial tissue damage. The appearance of a new Q-wave has therefore been considered the most reliable criterion for diagnosis of perioperative myocardial infarction (PMI) in cardiac surgery. In a study, originally intended to evaluate troponin-T as a marker of PMI, analysis of our data aroused the need to address the reliability of Q-wave criteria for diagnosis of PMI. METHODS: In 302 consecutive patients undergoing coronary surgery, Q-wave and other electrocardiogram (ECG) criteria were compared with biochemical markers of myocardial injury and the postoperative course. All ECGs were analysed by a cardiologist blinded to the biochemical analyses and the clinical course. RESULTS: The incidence of positive Q-wave criteria was 8.1%. Combined biochemical (CK-MB > or = 70 microg/l) and Q-wave criteria were found in 1.0%. Patients with new Q-waves did not have CK-MB or troponin-T levels significantly different from those without Q-waves. More than 25% of the Q-waves were associated with plasma troponin-T below the reference level (< 0.2 microg/l) on the fourth postoperative day. Q-wave criteria alone did not influence the postoperative course. In contrast, biochemical markers correlated with clinical outcome. CONCLUSIONS: The majority of Q-waves appearing after coronary surgery were not associated with major myocardial tissue damage, and according to troponin-T one-fourth of the Q-waves were not associated with myocardial necrosis. Furthermore, the appearance of Q-waves had little influence on short term clinical outcome. Therefore, the use of Q-wave criteria as the gold standard for diagnosis of PMI may have to be questioned.

Myocardial injury and CK-MB release during aortic valve surgery with selective coronary perfusion.

The postoperative serum activity of creatine kinase MB isoenzyme (CK-MB) was studied in 25 patients undergoing isolated aortic valve replacement (Björk-Shiley prosthesis). Hypothermia at 30 degrees C and selective coronary perfusion (CP) were used for myocardial protection. Repeated electrocardiograms revealed no signs of perioperative myocardial infarction. In all patients, CK-MB was detected in the serum. The CK-MB as a percentage of total CK at peak CK-MB [12 +/- 1 (mean +/- SEM)] was of the same magnitude as that found in acute myocardial infarction (AMI). Peak CK-MB occurred 2 +/- 0 h after the end of surgery. Peak total CK occurred after 17 +/- 3 h, and the plasma half-life for total CK was three times that of CK-MB. Thus, the kinetics of serum CK differed from those in AMI, but were similar to those reported after coronary bypass operations. The release of CK-MB, as well as of asparatate aminotransferase and thermostable lactate dehydrogenase, was related to the duration of aortic cross-clamping (AC), with a marked increase after 90 min. In two subgroups with similar AC time, postoperative CK-MB activity was higher in the subgroup with longer CP, indicating that CP as a method of myocardial protection may be entirely beneficial.