Left atrial isomerism associated with asplenia: prenatal echocardiographic detection of complex congenital cardiac malformations.

Complex congenital heart disease with suspected isomerism of the atria was diagnosed in two fetuses of 20 and 29 weeks' gestation using two-dimensional and M-mode scanning techniques. The first pregnancy was terminated at 21 weeks' gestation and stillbirth occurred at 31 weeks' gestation in the second pregnancy. At postmortem examination, a thoracoabdominal discordancy was found; the spleen was absent and the arrangement of the abdominal vessels was as anticipated for asplenia, but the thoracic situs revealed a bilateral right-sided arrangement with left isomerism of the atria. The heart, otherwise, showed complex abnormalities as anticipated for asplenia.

Vaporization of atherosclerotic plaques by spark erosion.

An alternative to the laser irradiation of atherosclerotic lesions has been developed. A pulsed electrocardiogram R wave-triggered electrical spark erosion technique is described. Controlled vaporization of fibrous and lipid plaques with minimal thermal side effects was achieved and documented histologically in vitro from 30 atherosclerotic segments of six human aortic autopsy specimens. Craters with a constant area and a depth that varied according to the duration of application were produced. The method was confirmed to be electrically safe during preliminary in vivo trials in the coronary arteries of seven anesthetized pigs. The main advantages of this technique are that it is simpler to execute than laser irradiation and potentially more controllable.

Right to left shunt, with severe hypoxemia, at the atrial level in a patient with hemodynamically important right ventricular infarction.

This report describes a patient with a massive right ventricular infarction, complicated by severe hypoxemia. Contrast echocardiography demonstrated a right to left shunt through a previously asymptomatic atrial septal defect. This phenomenon should be considered as a possible cause of hypoxemia in the presence of right ventricular infarction.

Arterial wall characteristics determined by intravascular ultrasound imaging: an in vitro study.

The feasibility of assessing arterial wall configuration with an intravascular 40 MHz ultrasound imaging device was investigated in an in vitro study of 11 autopsy specimens of human arteries. The system consists of a single element transducer, rotated with a motor mounted on an 8F catheter tip. Cross sections obtained with ultrasound were matched with the corresponding histologic sections. The arterial specimens were histologically classified as of the muscular or elastic type. Muscular arteries interrogated with ultrasound presented with a hypoechoic media, coinciding with the smooth muscle cells. In contrast, the media of an elastic artery densely packed with elastin fibers was as echogenic as the intima and the adventitia. On the basis of the cross-sectional image, it was possible to determine the nature of the atherosclerotic plaque. The location and thickness of the lesion measured from the histologic sections correlated well with the data derived from the corresponding ultrasound images. This study indicates that characterization of the type of artery and detection of arterial wall disease are possible with use of an intravascular ultrasound imaging technique.

In vitro cyclic AMP induced phosphorylation of phospholamban: an early marker of long-term recovery of function following reperfusion of ischaemic myocardium?

Changes in myocardial membrane biochemistry and ultrastructure, determined shortly (2 h) after reperfusion of ischaemic myocardium, were compared with the long term (4 wk) recovery of regional myocardial function. Anaesthetised pigs were subjected to 30 min (n = 14, group I) or 60 min (n = 14, group II) of left circumflex coronary artery occlusion. Seven animals of each group were studied 2 h and the others 4 weeks after flow was reinstated. After 2 h of reperfusion, regional myocardial function was absent in both groups. At 4 weeks regional function had returned to normal in group I, but was still significantly depressed in group II. Biochemical studies after 2 h of reperfusion showed that a functional index of the cardiac membrane, the in vitro cyclic AMP dependent 32P incorporation into phospholamban, was 71 (SEM 9)% compared to non-ischaemic myocardium in group I and 31 (6)% in group II (p less than 0.05). After 4 weeks this index had completely recovered in group I, 114 (13)%, but a significant decrease to 79 (2)% could still be observed in group II (p less than 0.05). After 2 h of reperfusion as well as after 4 weeks of recovery the myocytes in group II were more severely damaged than in group I. This study suggests that determination of in vitro phosphorylation of phospholamban shortly after reperfusion of ischaemic myocardium may be of value in the prediction of long term recovery of regional myocardial function.

Does platelet aggregation play a role in the reduction in localized intimal proliferation in normolipidemic pigs with fixed coronary artery stenosis fed dietary fish oil?

In order to investigate the effect of fish oil on intimal proliferation of coronary arteries with a fixed stenosis normolipidemic piglets received a basic diet to which either 9% (w/w) lard (L, n = 8) or 4.5% (w/w) lard and 4.5% (w/w) mackerel oil (ML, n = 8) was added for 4 months. Stenosis was applied by implanting a 4.0 X 2.0 mm (i.d.) Teflon constrictor around the left anterior descending coronary artery (LADCA) (o.d. 2.7 +/- 0.1 mm). During the dietary period ADP-induced platelet aggregation in whole blood was higher in L than in ML. Partial replacement of 20:4 n - 6 by 20:5 n - 3 fatty acids in the platelet membranes of ML may have altered platelet aggregation by changes in eicosanoid synthesis. The plasma cholesterol and triglyceride levels did not change in L, but decreased in ML. At the end of the 4-month dietary period the animals were again anesthetized and regional myocardial perfusion (radioactive labelled microspheres) and systolic segment length shortening (SLS) were measured while the hearts were paced at 160 pulses/min. Perfusion and SLS of non-LADCA nourished segment were similar for L and ML. However, transmural flow to the LADCA perfused myocardium was impaired in both groups, but the deficiency in endocardial perfusion was considerably larger in L than in ML, resulting in a larger loss of SLS in the former. Remote (2-3 cm from the site of the constrictor) luminal encroachment was minimal (less than 2%) in both groups, but at the site of the constrictor there was significant encroachment in both groups which was higher in L (62 +/- 7%) than in ML (11 +/- 4%). It is thought that in these normolipidemic pigs the reduction in platelet aggregation may play a role in the smaller intimal proliferation of the fish oil-fed animals.

"Offsetting" of the septal tricuspid leaflet in normal hearts and in hearts with Ebstein's anomaly. Anatomic and echographic correlation.

Apical displacement of the septal tricuspid valve leaflet is considered the most reliable criterion to diagnose Ebstein's anomaly. This feature is best assessed using 2-dimensional echocardiography. However, the anatomy in Ebstein's anomaly is highly variable; therefore, the problem arises as to how to distinguish between the abnormal displacement in borderline cases of Ebstein's disease and the lowered septal offsetting of the tricuspid valve in normal persons. To solve this problem the minimal and maximal differences in offsetting of the tricuspid and mitral valves have been studied, both anatomically and echocardiographically, in fetuses, infants, children and adults. In fetuses in the first trimester of pregnancy it was impossible to measure a difference in offsetting of the 2 atrioventricular valves. Thereafter, a gradual increase occurred with age. In normal hearts the most significant separation was usually recorded in anteriorly angulated 4-chamber views, whereas in hearts with Ebstein's anomaly maximal separation appeared to posteriorly angulated views. The anatomic and echographic measurements showed a constant relation. When the minimal distances in offsetting were measured, an overlap was found between cases with and those without Ebstein's anomaly. The maximal values, however, clearly discriminated between the 2 conditions. The critical difference in children was 15 mm, and in adults the discriminating value was 20 mm.

Alloreactive lymphoid infiltrates in human heart transplants. Loss of class II-directed cytotoxicity more than 3 months after transplantation.

From 535 endomyocardial biopsies (87 heart transplant recipients) 283 cell cultures could be generated. All cultures tested contained T lymphocytes and in most cases CD4 was the predominant phenotype at any time posttransplant. A significantly higher proportion of CD8-dominated cultures was found among cultures from biopsies without myocytolysis. In the first 3 months post transplant 57% of cultures showed cytotoxicity against both class I and class II mismatched donor major histocompatibility complex (MHC) antigens, changing to an incidence of 33% at greater than 90 days. This proved to be due to a significant decrease in the number of cultures with human leukocyte antigen class II-directed cytotoxicity. This study shows that early after transplantation a heart transplant is infiltrated with activated donor-specific cytotoxic T cells which recognize a broad spectrum of mismatched donor MHC antigens, and that in time this spectrum becomes more restricted.

Juxtaductal pulmonary artery coarctation. An underestimated cause of branch pulmonary artery stenosis in patients with pulmonary atresia or stenosis and a ventricular septal defect.

An angiographic and clinical study was performed to establish the prevalence of juxtaductal pulmonary artery coarctations in patients with pulmonary atresia or stenosis and a ventricular septal defect or a complex intracardiac defect. The present study is an adjunct to a previously reported portmortem study, in which the incidence of these pulmonary artery coarctations was found to be unexpectedly high. Pulmonary artery coarctations were identified angiographically in 10 of the 15 patients with pulmonary atresia. One additional patient had a bilateral ductus arteriosus and confluent pulmonary arteries, but did not have a pulmonary artery coarctation. Pulmonary artery coarctations were much less prevalent in the cases with pulmonary stenosis (5/50). However, these pulmonary artery coarctations appeared identical to those of the cases with pulmonary atresia. Fourteen pulmonary artery coarctations were located in the pulmonary artery at the side of the ductus arteriosus; this was left sided in 12 and right sided in two patients. In one patient the side of the ductus could not be established. The types and the locations of the pulmonary artery coarctations in the present study were identical to those in the previous postmortem study. Ductal tissue was found in many of the pulmonary artery coarctations of the postmortem study and is likely to be present in the clinical cases as well. The majority of the angiographically identified pulmonary artery coarctations were subsequently confirmed at operation or at autopsy. The clinical outcome and follow-up of the patients is discussed, and it is concluded that juxtaductal pulmonary artery coarctations should be specifically looked for before and during any type of surgical intervention in these patients.

Restenosis 3 months after successful percutaneous aortic valvoplasty. A clinicopathological report.

A 76-year-old man with severe, calcific aortic stenosis experienced recurrence of symptoms 3 months after a successful percutaneous aortic valvoplasty. Echo Doppler revealed a marked increase of peak aortic flow velocity as compared with the immediate post-valvoplasty value. The patient underwent an uncomplicated aortic valve replacement. Adjacent to fragmented calcification, histology demonstrated a scarring reaction which might well be a major factor in the restenosis process.

Competition of coronary arteries and ventriculo-coronary arterial communications in pulmonary atresia with intact ventricular septum.

Pulmonary atresia with intact ventricular septum can be complicated by the presence of large ventriculo-coronary arterial communications which disturb normal myocardial perfusion. In the selection of patients for surgery the presence of these communications provides an additional problem. On the basis of previous cineangiocardiographic study, we performed a histopathological study of 16 cases. Twelve presented with ventriculo-coronary arterial communications and four only showed myocardial sinusoids. A tripartite right ventricle was seen in the latter group but not exclusively. It is shown that subepicardial coronary arterial pathology is exclusively present in cases with ventriculo-coronary arterial communications although not solely at a connection site between a communication and an artery. The affected coronary artery is itself focally abnormal and hypoplastic and can be blocked or even absent. The interruption of such an artery can also occur after birth and not necessarily at a site of connection with a communication. This implies that infants with communications either already have a coronary circulation partly or completely dependent on ventriculo-coronary arterial communications at birth or can develop such a condition in time. This hazard to myocardial perfusion, often compromised by a large "steal" from the aorta to the right ventricle, limits the choice of surgical procedures.

Electrical impedance of layered atherosclerotic plaques on human aortas.

Electrical impedance measurements were performed on 13 atherosclerotic human aortic segments at 67 measuring spots in order to determine whether or not on the basis of these data a distinction can be made between atherosclerotic lesions and normal tissue. Stenosis localization and guidance of interventional techniques could be among the applications of an impedance measuring technique implemented on a catheter system. The experimental results, obtained with a two-electrode measuring technique, show that the apparent resistivity of an atherosclerotic spot does not necessarily deviate much from the resistivity of normal tissue. This is clarified by histology which shows that the majority of lesions has a surface layer of connective, fibrous tissue having almost similar conducting properties as the normal arterial wall. For gaining a deeper understanding of the way in which the measured data come about, a physical model of an atherosclerotic lesion is presented and confronted with the data. Both experimental data and theoretical considerations lead to the conclusion that only when the superficial fibrous layer is absent or very thin in relation to the size of the measuring electrode, the measured resistivity at a lesion is much higher than at normal spots. This occurs as a consequence of the high ohmic properties of the calcified or lipid deposits in the atherosclerotic lesion.

The effect of nifedipine on ischemia-induced changes in the biochemical properties of isolated sarcolemmal vesicles and the ultrastructure of myocardium.

To investigate whether slow Ca2+ channel blockers protect against development of changes in properties of the sarcolemma and in the tissue ultrastructure during myocardial ischemia, nifedipine was administered prior to occlusion (up to 3 hours) of the left anterior descending coronary artery in anesthetized pigs. Intravenous doses which reduced arterial blood pressure by 20-25%, had no effect on the time-dependent reduction of Ca2+-calmodulin and cyclic AMP-dependent 32P incorporation into sarcolemmal phospholamban-like protein. Nifedipine blocked the reduction in the activity of sarcolemmal 5'-nucleotidase. Nifedipine had no significant effect on the long-chain fatty acylcarnitine accumulation in sarcolemma. A marked delay in the appearance of ultrastructural indicators of irreversible tissue injury in subepicardial myocardium was observed, when nifedipine was infused. Particularly the reduced appearance of electron-dense bodies in mitochondria suggested a reducing effect of nifedipine on cellular net gain of Ca2+. Apparently, ischemia-induced loss of the ability of the proteinkinases to incorporate phosphate into sarcolemmal phospholamban-like protein is not a process secondary to Ca2+ overload of the myocardium. The involvement of accumulation of long-chain fatty acylcarnitine within the sarcolemma may also be excluded. The membrane defect as indicated by a change in phosphorylation-mediated control of Ca2+ transport may itself be associated with the development of ischemia (-reperfusion)-induced Ca2+ overload.

Fluorescence in situ hybridisation on formalin fixed fetal tissue in the diagnosis of chromosomal syndromes.

Two cases of stillborn children with multiple congenital anomalies are presented. No routine karyotyping was performed. After dysmorphologic evaluation a tentative diagnosis of trisomy 18 and triploidy, respectively, could be made. Fluorescence in situ hybridisation with several chromosome specific probes on formalin fixed paraffin embedded tissue confirmed the suspected diagnosis in both cases. In view of the important consequences for the parents (relatively low recurrence risk, availability of prenatal diagnosis in subsequent pregnancies) fluorescence in situ hybridisation for the common chromosomal aneuploidies should be performed in selected cases of stillborn fetuses with multiple congenital malformations.

Fluorocarbons and the microcirculation.

A short discussion of oxygen transport and delivery by fluorocarbon containing blood substitutes is presented. Those physical properties of the preparations that would tend to cause improvement in oxygenation in areas of damaged or impeded microcirculation are also discussed. A number of studies carried out at the Erasmus University, Rotterdam have demonstrated certain important characteristics of fluorocarbons with respect to tissue oxygenation. In the first instance, it has been demonstrated that extracorporal perfusion with Fluosol-DA 20% can maintain oxygenation and viability of isolated extremities for periods of up to 48 hours. Secondly it has been shown that the preparation can indeed penetrate compromised capillary beds, its low viscosity enabling it to travel along collateral perfusion pathways and to provide oxygenation of areas of ischaemic hypoxia. The low particle of the emulsion may, in combination with the low viscosity of the product, contribute to the re-establishment of perfusion in areas of circulatory arrest. The clinical implications of the above findings are numerous and wide spread. The importance of Fluosol in maintaining and improving micro-circulatory oxygenation should not be underestimated.

Treatment with cyclosporin and risks of graft rejection in male kidney and heart transplant recipients with non-O blood.

In a consecutive series of 146 kidney transplant recipients treated with cyclosporin A a strong correlation between matching for the HLA-A, HLA-B, and HLA-DR loci specificities and outcome of the grafts was observed in male recipients with non-O blood groups. Such a beneficial effect of matching was not found in female patients or male patients with blood group O. In these patients survival of the grafts at one year was good irrespective of the number of HLA-A, B, and DR mismatches. Also in 47 male heart transplant recipients immune responsiveness against mismatched HLA antigens was related to blood group. A significantly higher incidence of rejection episodes was observed in male patients with non-O blood groups (n = 32) than in those with blood group O (n = 15). Matching for HLA-DR reduced the number of acute rejection episodes in male patients with non-O blood. These findings may help explain the controversial reports about the importance of HLA matching in organ transplantation. Furthermore, as most candidates for heart transplantation are male and not of blood group O, the higher incidence of graft rejection in these patients underscores the need for an exchange strategy of donor hearts.