Comparative next-generation mapping of the Phytophthora infestans resistance gene Rpi-dlc2 in a European accession of Solanum dulcamara.

Phytophthora infestans, the causal agent of late blight, remains the main threat to potato production worldwide. Screening of 19 accessions of Solanum dulcamara with P. infestans isolate Ipo82001 in detached leaf assays revealed strong resistance in an individual belonging to accession A54750069-1. This plant was crossed with a susceptible genotype, and an F(1) population consisting of 63 individuals was obtained. This population segregated for resistance in 1:1 ratio, both in detached leaf assays and in an open-field experiment. Presence of the formerly mapped Rpi-dlc1 gene as the cause of the observed segregating resistance could be excluded. Subsequently, AFLP analyses using 128 primer combinations enabled identification of five markers linked to a novel resistance gene named Rpi-dlc2. AFLP markers did not show sequence similarity to the tomato and potato genomes, hampering comparative genetic positioning of the gene. For this reason we used next-generation mapping (NGM), an approach that exploits direct sequencing of DNA (in our case: cDNA) pools from bulked segregants to calculate the genetic distance between SNPs and the locus of interest. Plotting of these genetic distances on the tomato and potato genetic map and subsequent PCR-based marker analysis positioned the gene on chromosome 10, in a region overlapping with the Rpi-ber/ber1 and -ber2 loci from S. berthaultii. Pyramiding of Rpi-dlc2 and Rpi-dlc1 significantly increased resistance to P. infestans, compared with individuals containing only one of the genes, showing the usefulness of this strategy to enhance resistance against Phytophthora.

A high-quality genome sequence of Rosa chinensis to elucidate ornamental traits.

Rose is the world's most important ornamental plant, with economic, cultural and symbolic value. Roses are cultivated worldwide and sold as garden roses, cut flowers and potted plants. Roses are outbred and can have various ploidy levels. Our objectives were to develop a high-quality reference genome sequence for the genus Rosa by sequencing a doubled haploid, combining long and short reads, and anchoring to a high-density genetic map, and to study the genome structure and genetic basis of major ornamental traits. We produced a doubled haploid rose line ('HapOB') from Rosa chinensis 'Old Blush' and generated a rose genome assembly anchored to seven pseudo-chromosomes (512 Mb with N50 of 3.4 Mb and 564 contigs). The length of 512 Mb represents 90.1-96.1% of the estimated haploid genome size of rose. Of the assembly, 95% is contained in only 196 contigs. The anchoring was validated using high-density diploid and tetraploid genetic maps. We delineated hallmark chromosomal features, including the pericentromeric regions, through annotation of transposable element families and positioned centromeric repeats using fluorescent in situ hybridization. The rose genome displays extensive synteny with the Fragaria vesca genome, and we delineated only two major rearrangements. Genetic diversity was analysed using resequencing data of seven diploid and one tetraploid Rosa species selected from various sections of the genus. Combining genetic and genomic approaches, we identified potential genetic regulators of key ornamental traits, including prickle density and the number of flower petals. A rose APETALA2/TOE homologue is proposed to be the major regulator of petal number in rose. This reference sequence is an important resource for studying polyploidization, meiosis and developmental processes, as we demonstrated for flower and prickle development. It will also accelerate breeding through the development of molecular markers linked to traits, the identification of the genes underlying them and the exploitation of synteny across Rosaceae.

The genesis of the third and fourth heart sounds. A pressure-flow study in dogs.

To examine the mechanism of mitral flow deceleration in diastole and its potential influence on the genesis of third (S3) and fourth (S4) heart sounds, we simultaneously recorded left atrial and left ventricular pressures (micromanometers), mitral flow velocity (electromagnetic catheter-tip flow velocity meter), and internal and external phonocardiograms in 25 open-chest dogs. Diastolic time intervals, transmitral pressure gradients (planimetry), maximum mitral flow velocity, and acceleration and deceleration of flow were measured under different loading conditions. It was found that deceleration of mitral flow in early and late diastole is always caused by a negative transmitral pressure gradient. After volume loading, diastolic pressures, positive (forward) and negative (backward) transmitral pressure gradients, and acceleration and deceleration of flow increased, and an S3 or S4 appeared (20:25 dogs). These sounds occurred during the phase of flow deceleration and could be recorded from the chest wall, inside the left ventricle, and directly from the epicardial surface of the freely exposed left ventricular wall. After balloon occlusion of the inferior vena cava (17:25 dogs), the opposite changes were observed and gallop sounds disappeared. The results indicate that the left ventricular pressure rise in response to filling reverses the transmitral pressure gradient and decelerates flow. Deceleration of inflow by the left ventricular wall in early and late diastole may represent a key mechanism in the genesis of S3 and S4.

Coronary reperfusion by thrombolysis and early beta-adrenergic blockade in acute experimental myocardial infarction.

The effects of beta-adrenergic blockade, thrombolysis and their combination on infarct size and left ventricular function were investigated in a canine model of thrombotic occlusion of the left anterior descending coronary artery. Metoprolol was administered intravenously (0.5 mg/kg) over 10 min, starting 15 min after occlusion. Recombinant human tissue-type plasminogen activator (rt-PA) was given intravenously 1 h after occlusion for clot lysis. Anatomic infarct size was measured as a percent of perfusion area and ventricular mass. Left ventricular function was assessed by ejection fraction and the centerline method. Groups 1, 3, 5 and 7 were evaluated after 24 h and received, respectively, metoprolol plus rt-PA, rt-PA, metoprolol and no treatment; groups 2, 4, 6 and 8 were studied after 1 week and treated, respectively, as groups 1, 3, 5 and 7. Metoprolol did not influence infarct size and global or regional ventricular function after 24 h and 1 week. Thrombolysis reduced infarct size from 69.5 +/- 3.4% (24 h) and 76.6 +/- 1.8% (1 week) in the control group to, respectively, 44.1 +/- 11.6% and 39.5 +/- 10.5% (p greater than 0.05), did not influence left ventricular function after 24 h and was accompanied after 1 week by a definite recovery of global and regional left ventricular function when compared with findings in control dogs. Metoprolol plus rt-PA further reduced infarct size (percent perfusion area) to 20.4 +/- 3.7% and 19.9 +/- 8.1% after 24 h and 1 week, respectively (p = NS versus rt-PA).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiographic assessment of the infarct-related residual coronary stenosis after spontaneous or therapeutic thrombolysis.

The severity of the infarct-related residual coronary stenosis after spontaneous or therapeutic thrombolysis was quantitatively assessed in 91 patients with an acute myocardial infarction who were allocated to treatment in the acute stage with either a thrombolytic agent (100 mg of recombinant tissue-type plasminogen activator given over 3 h, 49 patients) or a placebo (42 patients). Heparin and aspirin were given to both groups until angiography was performed. Digital subtracted images of the infarct-related coronary vessel were obtained 10 to 14 days after hospital admission and were subsequently analyzed with the use of a computer-assisted coronary stenosis measurement system. Neither treatment group differed significantly in age, gender or location of the culprit coronary lesion. Median values (90% range) in the thrombolysis and control groups were, respectively, 1.95 (0.9 to 5.3) mm versus 1.7 (0.9 to 3.4) mm for stenosis length; 1.4 (0.8 to 2.7) mm versus 1.4 (0.9 to 1.8) mm for minimal luminal diameter; 57% (36% to 75%) versus 58% (44% to 71%) for diameter obstruction; 82% (59% to 95%) versus 82% (68% to 92%) for geometric area obstruction; and 78% (58% to 91%) versus 79% (66% to 90%) for densitometric area obstruction. The difference between the two groups was not statistically significant for any of these measurements. Thus, in this study no significant differences in anatomy or severity of residual coronary stenosis could be demonstrated at 10 to 14 days after an acute myocardial infarction in patients with a recanalized infarct-related vessel, whether or not thrombolytic therapy was given on admission. These results indicate that with effective antithrombotic treatment, gradual endogenous fibrinolysis or more rapid lysis induced by the infusion of a thrombolytic agent results in a similar infarct-related coronary lesion at the time of hospital discharge.

Coronary thrombolysis with recombinant tissue-type plasminogen activator: patency rate and regional wall motion after 3 months.

In a double-blind, placebo-controlled, randomized trial the long-term (+/- 3 months) effects of intravenous administration of recombinant tissue-type plasminogen activator (rt-PA) versus placebo were compared in relation to left ventricular function, coronary patency rate and antigenicity in 28 patients with a first myocardial infarction. Patency rate of the infarct-related coronary artery at the end of the rt-PA/placebo infusion and after 3 months of medical treatment (including oral anticoagulant agents) was 86 and 71%, respectively, in the rt-PA group, and 21 and 58%, respectively, in the placebo group. Regional wall motion of the infarct-related area was quantitated with digital subtraction angiography. Intrapatient comparisons revealed significant improvement in regional wall motion after 3 months in both the rt-PA and placebo groups. The improvement in the rt-PA group was not significantly greater than that in the placebo group. Thirteen patients (10 with rt-PA and 3 with placebo) with persistent patency (both early and late) of the infarct-related coronary artery showed a significant improvement of both global and regional left ventricular function, while 8 patients (2 with rt-PA and 6 with placebo) with persistent occlusion showed no changes. Antibodies against rt-PA were not detected in serum 2 weeks after the infusion, which is indicative of the lack of antigenicity of rt-PA and allows for its repeated administration.

Sensing and pacing with floating electrodes in the right atrium and right atrial appendage.

Unipolar and bipolar floating atrial electrograms from 58 pacemaker patients were recorded and compared. Twenty-four floating unipolar electrodes and 29 floating bipolar electrodes were used at mid-right atrial level and five orthogonal atrial J leads within the right atrial appendage. Each signal was analyzed in the time domain: peak to peak deflection of P wave and QRS complex, duration of P wave and QRS complex and slew rate; and in the frequency domain: maximum of the energy spectrum and frequency at which a decrease of 3 dB from the maximal amplitude occurred. Atrial P (1.31 +/- 0.94 mV, mean +/- SD) and QRS (1.0 +/- 0.56 mV) waves from unipolar floating electrodes were comparable, whereas they were significantly different from bipolar floating electrodes (1.15 +/- 0.77 mV and 0.25 +/- 0.39 mV). Amplitudes of P waves from orthogonal J leads were largest (3.1 +/- 2.6 mV) and QRS complexes (0.21 +/- 0.13 mV) smallest. The P waves had the highest frequency content (17.1 +/- 19.4 Hz). It is concluded that atrial electrograms from orthogonal electrodes (bipolar or orthogonal J) offer superior sensing characteristics because of the large amplitude P wave and discriminating power between P and QRS waves (P/QRS voltage 15:1). An orthogonal J lead can thus be used for P synchronous pacing at the atrial level, whereas an orthogonal ventricular lead can be used for rate-response pacing systems.

Early intravenous administration of metoprolol enhances myocardial salvage by thrombolysis with recombinant tissue-type plasminogen activator after thrombotic coronary artery occlusion in the dog by improvement of the collateral blood flow to the area at risk.

OBJECTIVES: We studied the effects of beta 1-adrenergic blockade preceding thrombolysis on hemodynamic variables, myocardial blood flow and infarct size in a canine model of thrombotic occlusion of the left anterior descending coronary artery. BACKGROUND: Previous work suggested a reduction in infarct size and improvement in left ventricular function by intravenous beta-blockade preceding thrombolysis. METHODS: Experiments were conducted in 34 anesthetized dogs; 17 received 0.975 mg/kg body weight of metoprolol intravenously starting 15 min after occlusion, and thrombolysis was initiated 60 min after occlusion. Seventeen dogs received saline solution followed by thrombolysis. Coronary blood flow was measured by radioactive microspheres, infarct size by a dye method, hemodynamic variables by catheter-tipped pressure transducers and cardiac output by the thermodilution method. RESULTS: Infarct size in metoprolol- and placebo-treated dogs was 23.62 +/- 18.04% and 41.50 +/- 16.03% of area at risk, respectively (p < 0.01). Before occlusion, myocardial blood flow and hemodynamic variables were similar. Sixty minutes after occlusion, cardiac output (1.94 +/- 0.41 vs. 2.32 +/- 0.68 liters/min, p < 0.01) was lower in the metoprolol-treated dogs. Collateral flow to the area at risk (17.27 +/- 7.44 vs. 10.25 +/- 5.33) and to its epicardial (21.68 +/- 8.04 vs. 11.5 +/- 6.10), midmyocardial (14.30 +/- 8.63 vs. 7.35 +/- 4.94) and endocardial (13.18 +/- 8.21 vs. 6.26 +/- 5.34 cm3/min per 100 g) layers was higher (p < or = 0.05) in the metoprolol-treated dogs. The ratio of epicardial flow area at risk/circumflex territory was inversely correlated to infarct size (r = -0.69, p < 0.01). After 5 min of occlusion, collateral flow was comparable in the five dogs of each group; over the next 55 min it remained constant in the metoprolol group but decreased in the placebo dogs. CONCLUSIONS: Intravenous metoprolol, administered before thrombolysis, enhances infarct size limitation, partly by improvement of collateral flow to area at risk.

Effect of superoxide dismutase on infarct size and postischemic recovery of myocardial contractility and metabolism in dogs.

The effects of superoxide dismutase treatment on infarct size, postischemic recovery of contractile function and tissue content of high energy phosphates were examined in a canine model of myocardial ischemia and reperfusion. Ischemia was induced by thrombotic occlusion of a coronary artery and reperfusion was achieved by intravenous thrombolysis. Average duration of ischemia was 90 min. Fifty closed chest anesthetized dogs were randomized to receive either superoxide dismutase (34,000 IU/min intravenously) or placebo, starting approximately 30 min before and continuing for 30 min into the reperfusion phase. Left ventricular ejection fraction and regional segmental shortening of the postischemic area were calculated from contrast angiograms after 4 h, 48 h and 1 week of reperfusion. Tissue content of high energy phosphates was determined from transmural biopsy after 4 h and 1 week. Infarct size was measured by planimetry of dye-stained heart slices. In the superoxide dismutase and placebo-treated groups, respectively, the mortality rate was 25% and 16%, collateral flow 20 +/- 10 and 23 +/- 18 ml/min per 100 g, area at risk 25 +/- 6% and 26 +/- 7% of the left ventricle and infarct size 28 +/- 19% and 36 +/- 27% of the area at risk. Multiple regression analysis failed to show any beneficial effect of superoxide dismutase treatment on infarct size. Left ventricular ejection fraction, regional segmental shortening of the postischemic area and tissue content of high energy phosphates recovered to a similar extent and at a similar rate in both treated and placebo groups up to 1 week after reperfusion. Thus, in this model of coronary occlusion and reperfusion superoxide dismutase treatment is of no benefit.

Collateral bronchopulmonary circulation after spontaneous recanalisation of pulmonary thromboemboli in the dog.

STUDY OBJECTIVE: The aim was to study the fate of enlarged bronchial arteries after resolution of experimental pulmonary embolism. DESIGN: Embolisation of the pulmonary arteries of both lungs was performed with intravenous gelfoam. Pulmonary pressure and pulmonary arteriolar resistance were measured 1 h, 40 d and 80 d after embolisation. Pulmonary angiography and aortography were performed at the same time to evaluate the pulmonary emboli and the collateral bronchopulmonary circulation. Aortography and gross pathological and histological examination of the lungs was performed after 80 d. EXPERIMENTAL MATERIAL: 15 adult mongrel dogs of either sex were studied, weight 22-25 kg. Nine dogs were embolised and there were six controls. MEASUREMENTS AND MAIN RESULTS: All animals survived until 80 d. There was a rise (p less than 0.001) in mean pulmonary artery pressure and arteriolar resistance 1 h after embolisation. Pulmonary artery pressures and resistances were still raised 40 d after embolisation but had returned to normal after 80 d. Pulmonary arteriography at 1 h confirmed massive thromboembolism. After 40 d antegrade pulmonary blood flow was almost completely restored, and the thromboemboli had largely disappeared. Pulmonary angiograms were completely normal after 80 d. Aortography after 40 d showed a well developed collateral bronchopulmonary circulation, most pronounced in the lower lobes, which persisted unchanged until 80 d. Aortography and gross pathological and histological examination at necropsy confirmed the presence of hypertrophic well developed bronchial arteries to both lower lobes and to a lesser extent to the middle and upper lobes, with only a few organised and recanalised thrombi in segmental arteries of both lower lobes. CONCLUSIONS: Our data show a temporal dissociation between the resolution of pulmonary thromboemboli in the present model and the eventual regression of developed bronchopulmonary collateral vessels. The mechanism of this dissociation could not be elucidated.

Evaluation of transmitral pressure gradients at different heart rates: divergent action of isoprenaline and atropine.

STUDY OBJECTIVE: The aim was to record diastolic transmitral pressure gradients at high sensitivity to quantitate the effect on transmitral pressure gradients of changing the heart rate. DESIGN: Diastolic left atrial and left ventricular pressures were recorded at high sensitivity (40 mm Hg = 10 mm recorded deflection) in control conditions (heart rate 70 beats.min-1) and after intravenous administration of atropine or isoprenaline (heart rate 110 beats.min-1). A special ventricular extrasystole protocol enabled the zero level of the transmitral pressure gradients to be unequivocally determined at high heart rates. The effect of atropine and isoprenaline on the pressure gradients, absolute diastolic pressures, and diastolic time intervals was investigated. EXPERIMENTAL MATERIAL: 16 mongrel dogs, 16-25 kg, were used. MEASUREMENTS AND RESULTS: Below a heart rate of 110 beats.min-1, four distinct periods were identified, during which a pressure gradient existed. During early and late diastole, a positive pressure gradient was consistently followed by a negative pressure gradient. Mean negative pressure gradient during early diastole correlated with the pressure difference of rapid filling wave (r = 0.72, p less than 0.01) and with mean positive pressure gradient during early diastole (r = 0.66, p less than 0.01). At a heart rate of 110 beats.min-1, isoprenaline augmented, while atropine reduced, the mean positive pressure gradient during early diastole without affecting the time interval over which the gradient occurred. This divergent action of the two drugs was related to their different effects on the decay of left ventricular pressure, which fell faster and deeper with isoprenaline but not with atropine. Both drugs shortened the time interval of the negative pressure gradient in early diastole without significantly affecting the mean negative pressure gradient during this period. In late diastole, atropine augmented the mean positive pressure gradient more than isoprenaline, reflecting the higher afterload after administration of atropine. Neither drug affected the time interval of the positive pressure gradient. As a result of a shortening of the P-R interval, isoprenaline shortened the time interval of the negative pressure gradient and reduced its mean value. Such an effect was not observed with the dose of atropine used. CONCLUSIONS: We conclude that a pressure gradient reversal in early diastole is always observed below a heart rate of 110 beats.min-1 and that isoprenaline and atropine affect the pattern of transmitral pressure gradients in a different way.

Axial pressure gradient in the canine superior vena cava.

In the superior vena cava of anaesthetised open chest dogs the axial pressure gradient was measured simultaneously with the blood flow velocity under different preload conditions. Both pressure gradient and velocity curves showed distinct systolic and diastolic waves. Peak pressure gradient ranged between 26 and 93 Pa X cm-1 (0.2-0.7 mm Hg X cm-1) and velocity varied between 0.095 and 0.19 m X s-1. Peak systolic pressure gradient, but not peak diastolic pressure gradient, was significantly linearly correlated to peak systolic velocity and peak diastolic velocity respectively. The shape of the two curves corresponded fairly well, but variations in pressure gradient preceded the variations in velocity. Both the correspondence in shape and the phase lag between pressure gradient and velocity waves were evaluated by the normalised cross correlation technique. During volume expansion the shape correspondence improved and the phase lag decreased. It is concluded that the transient vena caval blood velocity variations are directly related to the pulsatile axial pressure gradient.

Apparent pulse wave velocity in the canine superior vena cava.

In order to evaluate clinically recorded jugular vein pulses it is necessary to understand the transmission process of the right atrial pressure pulse through the caval veins up to the jugular veins. The transmission speed at distinct points of the venous pressure curve was studied in the superior vena cava of 20 anaesthetised dogs. Under control conditions the propagation velocities varied from 1.2 +/- 0.49 to 2.5 +/- 1.36 m . s-1. During increased preload of the heart propagation velocities rose significantly from 2.2 to 4.2 m . s-1 per kPa as a function of mean venous pressure and from 2.3 to 5.8 m . s-1 per kPa as a function of phasic pressures. Right atrial pacing (between 60 and 120 beats . min-1) did not influence the propagation velocity of the studied distinct points. It was found that the summits of the pressure pulse propagate at only a slightly higher speed than the nadirs.

Bronchial arteries in experimental pulmonary infarction: angiographic and morphometric study.

OBJECTIVES: The aim was to investigate (1) whether collateral bronchopulmonary circulation developing due to chronic pulmonary embolism could prevent the evolution of pulmonary infarction after induction of pulmonary venous outflow impairment; and (2) how collateral bronchopulmonary circulation developed after acute embolisation of the lung with impaired pulmonary venous outflow. METHODS: Fifty two mongrel dogs were studied. Thirty six dogs were experimental animals and 16 were in a control group. Unilateral impairment of pulmonary venous outflow was induced by constriction of the left pulmonary veins in two groups of experimental dogs: (1) three months after and (2) one hour before bilateral embolisation of the pulmonary artery. All animals were killed 12 days after constriction. The size of the bronchial arteries was evaluated from angiograms. The diameter and the wall thickness of the arteries were measured during histology. RESULTS: In all experimental dogs, haemorrhagic infarctions developed distally to emboli in the left lung regardless of whether the bronchial arteries were dilated before induction of pulmonary venous constriction or whether collateral circulation started to develop after pulmonary venous constriction. Constriction of the pulmonary veins was an essential factor for pulmonary infarction to develop as no infarction developed in the embolised regions of the right lungs with intact pulmonary venous outflow. Pulmonary venous constriction alone did not cause dilatation or hypertrophy of the bronchial arteries. After pulmonary artery embolisation, the same enlargement and hypertrophy of the bronchial arteries occurred both in the left lung with previously impaired venous outflow and in the right lung with intact pulmonary veins. CONCLUSIONS: Expanded bronchopulmonary circulation did not prevent the development of infarction in the embolised region of the lung with impaired pulmonary venous outflow. Development of collateral bronchopulmonary circulation was not influenced by previously impaired pulmonary venous outflow.

Long term spontaneous evolution of left ventricular function after experimental acute coronary occlusion.

In a canine model of acute occlusion of the left anterior descending artery (LAD), left ventriculography was performed before and immediately after occlusion and also one and three weeks later. Regional left ventricular function was evaluated by the centreline method. Global and regional left ventricular function were significantly depressed immediately after occlusion and showed no significant recovery after one and three weeks, except for a decrease in the paradoxical motion of the LAD territory, which was probably due to stiffening of the infarct area.

Biocompatibility of polymer-coated oversized metallic stents implanted in normal porcine coronary arteries.

Polymer coatings have been suggested to decrease the thrombogenicity of metallic intravascular stents. The purpose of the present study was to investigate the intimal response to two different polymers when used as coatings for stents implanted in normal porcine coronary arteries. Non-articulated stainless steel-slotted tube stents were coated with either a biodegradable poly(organo)phosphazene with amino-acid ester side groups or a biostable polyurethane prepared from an amphiphilic polyether, dephenylmethane-4,4'-diisocyanate and butane diol as chain extender. In order to induce vascular wall injury, the stents were deployed using an oversized balloon. At 6 weeks follow-up, the angiographic luminal diameter measured in four polyurethane-coated stents and in six bare metallic stents was similar and 20% less than immediately post-stenting. However, in four polyphosphazene-coated stents the difference was 65% (P = 0.01 when compared to bare metal). At post-mortem morphometry the degree of luminal area stenosis was also similar in polyurethane-coated and in bare metallic stents (32 +/- 7.6% vs. 39 +/- 14%, NS) but reached 81 +/- 19% in polyphosphazene-coated stents (P < 0.03 when compared to bare metal). Thus, poly(organo)phosphazene induced a more pronounced histiolymphocytic and fibromuscular reaction than amphiphilic polyurethane, which appeared to be promising as biocompatible stent coating and, consequently, as a potential carrier for vasoactive drugs.

Safety and efficacy of low dose simvastatin in cardiac transplant recipients treated with cyclosporine.

Hyperlipidemia is common in heart transplant patients. Lipid-lowering therapy poses special problems, yet may be important because accelerated graft atherosclerosis is the major factor limiting long-term survival. Simvastatin 5 mg/day was started > 6 months after surgery in 26 consecutive cardiac transplant recipients with a total serum cholesterol level of > 250 mg/dl. The dose of simvastatin was increased in 5-mg increments until total serum cholesterol fell below 220 mg/dl or until side effects developed or up to a maximal dose of 20 mg/day. The final average daily dose was 10 mg. Changes in serum lipid levels after 6 months of therapy were compared with data from a matched and concurrent control group of heart transplant patients not taking simvastatin. Immunosuppression for both groups consisted of CsA, AZA, and corticosteroids. In the simvastatin-treated group, the serum level of total cholesterol decreased by 27% from 315 +/- 53 to 230 +/- 38 mg/dl (P < 0.0001), low density lipoprotein cholesterol decreased by 40% from 205 +/- 30 to 123 +/- 32 mg/dl (P < 0.0001), and triglycerides decreased by 21% from 177 +/- 89 to 140 +/- 49 mg/dl (P < 0.01). There was no significant change in high density lipoprotein cholesterol level. Body weight and CsA blood levels remained stable. Steroid intake decreased during the study period to a similar extent in both the treated and the control groups. In the control group, no significant changes in serum lipid levels were observed. Two patients experienced a mild form of myotoxicity. In one other patient simvastatin treatment was stopped after an acute pancreatitis of uncertain etiology developed. Low dose simvastatin effectively lowers total serum cholesterol, low density lipoprotein cholesterol, and triglycerides in heart transplant patients. With due precautions, the safety profile of the drug in this patient population seems reasonable.

Three-dimensional correction for spillover and recovery of myocardial PET images.

UNLABELLED: PET permits the quantification of myocardial blood flow, but is hampered by the limited spatial resolution of PET images. METHODS: We evaluated two methods for the correction of resolution effects in PET perfusion 13NH3-ammonia images. In one model, the spillover and recovery coefficients are estimated in the kinetic modeling analysis. The new, second model uses an explicit delineation of the left ventricular wall and a convolution model for the system point spread function to compute the regional values of the spillover and recovery coefficients. RESULTS: The new method is validated with phantom measurements. The two methods are evaluated on animal experiments using 13NH3-ammonia. Both two- and three- compartment models were used to compute absolute flow values. Excellent linear correlations with microsphere data were obtained. The slope of the regression line was lower for corrections based on kinetic modeling as compared to convolution-based correction. In animal experiments, recovery coefficients of 59% for the myocardial wall and 86% for the blood pool were obtained. Spillover from the blood pool into the myocardial was was 14%. CONCLUSION: The new correction method strongly suppresses spillover and recovery effects due to limited resolution.

Angina pectoris and coronary artery disease in severe aortic regurgitation.

A consecutive series of 198 patients (148 men and 50 women, mean age 51 years, range 18 to 76) with pure, isolated, severe aortic regurgitation was retrospectively studied to determine the prevalence of angiographically significant coronary artery disease (CAD) and its relation to angina pectoris and coronary risk factors. Significant CAD (coronary diameter stenoses greater than 50%) was found in 28 patients (14%). Typical angina was present in 18% and atypical chest pain in 16%. Angina alone had a sensitivity of 57% to detect significant CAD. The predictive accuracy of a positive history of angina was 46% and that of a negative test 93%. By using multivariate logistic regression, a risk score could be calculated that increased the sensitivity to 74% at equal specificity. Almost 40% of the total population had a risk score of less than -2.9 (only 1 patient in this group had CAD). It is concluded that coronary arteriography can safely be omitted in many patients with severe aortic regurgitation if they have no symptoms of myocardial ischemia or risk factors known to increase its incidence.

Frequency of angina pectoris and coronary artery disease in severe isolated valvular aortic stenosis.

A consecutive series of 192 patients (121 men and 71 women, mean age 59 years, range 28 to 82) with isolated, severe valvular aortic stenosis was with isolated, severe valvular aortic stenosis was analyzed retrospectively to determine the relation of angina pectoris and coronary risk factors to angiographically significant coronary artery disease (CAD). Significant CAD (diameter reduction greater than or equal to 50%) was found in 47 patients (24%). Angina was present in 83% of them, but it was also found in 61% of the non-CAD patients. This symptom had as a result a low positive predictive value (31%). Of the patients without angina (n = 65) 12% had significant CAD. The negative predictive value of angina alone was thus 88%. By using multivariate logistic regression, a risk score could be calculated based on angina, age and sex, which increased the negative predictive value to 95%. It was concluded that coronary arteriography can only be omitted in severe aortic valvular stenosis, when patients have no angina and when they are less than 40 years of age for men and less than 50 years for women. For all other cases, coronary arteriography should be recommended.