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.

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.

Ischemic and reperfusive release of the endogenous purines and its influence on the myocardial viability during beta-adrenergic blockade.

The aim of this study was to estimate ischemic and reperfusive release of myocardial adenosine degradation products (MADP) during beta-adrenergic blockade and its relation to infarct size (IS) and viable myocardium size (VM). In a group of 24 shepherd-mongrel dogs, randomly assigned to a metoprolol (M-) and placebo-group (P-group), occlusion of the left anterior descending coronary artery (LAD) followed by reperfusion with recombinant tissue plasminogen activator was performed. Regional myocardial blood flow (MBF) was measured by the radiolabelled microsphere technique. Blood samples from aorta and great cardiac vein were collected to evaluate the concentrations of MADP. The triphenyltetrazolium chloride perfusion and fixation technique was used for infarct size measurement. MBF in the area at risk decreased in both groups during ischemia, but it was significantly higher (p = 0.013) in M-group. Recanalization of LAD was associated with an increase in flow in postischemic vascular bed. MBF was significantly higher (p = 0.024) in P-group during late reperfusion. In M-group IS was smaller (p = 0.007) and VM was bigger (p = 0.007). The correlation between arterial adenosine concentration during early reperfusion and IS (p = 0.044, r = -0.588) or VM (p = 0.036, r = 0.607) in M-group was noted. Values of net MADP balances significantly increased during early reperfusion. The correlation between reperfusive net MADP balance and IS (p = 0.00005, r = 0.906) or VM (p = 0.016, r = -0.675) in M-group was observed. The amount of MADP released during reperfusion correlates with the IS and is inversely proportional to the area of VM. The endogenously released adenosine may have additional cardioprotective effect during beta-adrenergic blockade.

Influence of an early adrenergic blockade on thrombotic infarct size and myocardial metabolism.

To evaluate the extent to which the protective effect of metoprolol was accompanied by changes in myocardial oxygen consumption and metabolism, thrombotic occlusion of coronary artery followed by infusion of metoprolol or placebo was performed in twenty four German Shepherds. To restore a coronary blood flow rt-PA was administered. Plasma levels of oxygen, glucose, lactic acid, non esterified fatty acids, triacylglyceride and adenosine breakdown products were measured before and at the end of the occlusion and in the early and late reperfusion periods. Regional myocardial blood flow was measured by means of radioactive tracer microspheres. Infarct size was estimated after perfusion and staining of excised hearts with Evans blue. Plasma levels of metoprolol were determinated before the end of occlusion and during reperfusion and therapeutic concentrations were confirmed. The infarct size was smaller in dogs receiving metoprolol (21.6 +/- 20.7 vs 43.0 +/- 17.3% p. < 0.02). Coronary collateral blood flow was greater in metoprolol than in placebo dogs (18.68 +/- 7.58 vs 11.05 +/- 6.10 ml/min/100g, p. < 0.01). As a consequence of myocardial ischemia a shift toward carbohydrate utilization, the myocardial lactate release and the accompanying symptoms of diminished myocardial lipid uptake were observed. A washout of adenosine degradation products during early reperfusion was also noticed. In beta 1 blocked animals the reduction of myocardial oxygen consumption and preserved myocardial uptake of lactate and non esterified fatty acids were documented.

Assessment of the optimal atrioventricular delay in dual chamber-paced patients by a portable scintillation probe (VEST).

BACKGROUND: The optimal atrioventricular delay in dual-chamber pacing differs from patient to patient. The availability of a portable scintillation probe (VEST) enables noninvasive monitoring of left ventricular function. METHODS AND RESULTS: Hemodynamic variations were measured in 10 patients with programmable DDD pacemakers. The ejection fraction, stroke volume, and diastolic and systolic volume were evaluated, programming six different atrioventricular delays ranging from 75 to 200 msec, to determine the most favorable atrioventricular delay. Comparing left ventricular ejection fraction (LVEF), stroke volume, and end-diastolic and end-systolic volume at each DVI mode with a preceding DVI setting of 75 msec, all parameters at 200 msec were statistically different from those at 100 msec. An increase of LVEF and stroke volume and a decrease of end-systolic volume was found. In only five patients a switch of VVI mode to the optimal DVI mode results in an increase of LVEF of more than 5%. CONCLUSIONS: Our study stresses the importance of optimizing atrioventricular delay. The VEST system permits these measurements, increasing the accuracy of the determination of optimal atrioventricular delay, and appears to be valuable in the management of patients with cardiac dual-chamber pacemakers.

Local Angiopeptin Delivery Using Coated Stents Reduces Neointimal Proliferation in Overstretched Porcine Coronary Arteries.

BACKGROUND: Systemic administration of angiopeptin has been shown to inhibit myointimal thickening after arterial injury in several animal species. METHODS AND RESULTS: To explore to what extent high and long-lasting local concentrations of angiopeptin influence the healing process after vascular injury, tantalum balloon-expandable stents were first coated with a polymer loaded with angiopeptin 250 µg. Implantation of these stents in porcine coronary arteries resulted in tissue concentrations of 10.7 pg/ml wet weight in the stented arterial segment 24 hours after stent implantation, gradually declining to 2.0 pg/ml wet weight at day 8. Finally, 20 pigs were randomly treated with either an angiopeptin-loaded or a blank-coated stent. At baseline, the angiographic parameters were similar between both groups but, after 6 weeks, the minimal luminal diameter of the stented arterial segment was larger in the angiopeptin-treated pigs when compared to controls (2.20 +/- 0.57 mm vs 1.57 +/- 0.68 mm, p < 0.01) This angiographic finding was confirmed by post-mortem morphometry where the respective lumen area values were 1.00 +/- 0.54 mm2 and 0.43 +/- 0.28 mm2 (p < 0.01). CONCLUSION: Polymer coated stents can be loaded with angiopeptin, which after implantation in porcine right coronary arteries result in high local tissue concentrations gradually declining over more than 8 days. These high local concentrations inhibit myointimal proliferation induced by poly(organo)phosphazene coated overstretched stents.

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.

Can dobutamine echocardiography distinguish necrotic from ischemic myocardium, early after myocardial infarction?

UNLABELLED: The aim of this study was to evaluate the usefulness of dobutamine echocardiography (DE) in distinguishing necrotic from ischemic myocardium in infarct zones. We performed DE in 39 patients, 3 to 5 days after admission for a first, acute myocardial infarction, treated with thrombolysis. DE was considered positive if wall motion in the infarct zone worsened progressively during increasing dose of dobutamine or if wall motion in the infarct zone initially improved at low dose of dobutamine and deteriorated at higher dose. The results of DE were correlated to the evolution of wall motion in the infarct zone after 3 months and to the need for supplementary balloon dilatation. In 15 of the 39 patients, there was evidence of residual ischemia in the infarct zone. Twenty of the 39 patients had a positive dobutamine echocardiogram. Eleven of these 20 patients had evidence of residual ischemia in the infarct zone. They showed generalized changes of wall motion in the total infarct territory during DE. The other 9 patients demonstrated only localized changes of wall motion in isolated segments of the infarct zone during DE. None of these patients had evidence of residual ischemia. IN CONCLUSION: DE seems worthwhile in the detection of residual ischemia in the region of infarction. To reduce the number of false positive DE early after myocardial infarction, only extensive changes of wall motion in the total infarct territory should be accepted as indicative of residual ischemia in the infarct zone.

Right atrial tumor arising on an atrial septal aneurysm. Assessment by MR imaging.

An elderly women presenting with transient ischemic events underwent transesophageal echocardiography, which detected an aneurysm of the interatrial septum. A tumor protruding from the right atrial aspect of the aneurysm also was found incidentally. Not only was magnetic resonance (MRI) imaging helpful in better characterizing the aneurysm, but also the use of gadolinium diethylaminetriamine pentaacetic acid permitted differentiation between the tumor and adherent thrombus. To the best of our knowledge, this represents the first report of a tumor arising from an atrial septal aneurysm.

Biocompatibility of biodegradable and nonbiodegradable polymer-coated stents implanted in porcine peripheral arteries.

PURPOSE: To investigate the neointimal response to poly(organo)phosphazene- and amphiphilic polyurethane-coated, oversized, stainless steel stents implanted in porcine peripheral arteries. METHODS: Nonarticulated, stainless steel, slotted-tube stents were coated with 1) a biodegradable poly-(organo)phosphazene with aminoacid ester side groups and 2) a biostable polyurethane prepared from an amphiphilic polyether, diphenyl methane-4,4'-diisocyanate and butane diol as chain extender. The stents were deployed in porcine peripheral arteries using an oversized balloon. RESULTS: The neonintimal response to amphiphilic polyurethane-coated stents was similar to the uncoated metallic stents. Poly(organo)phosphazene-coated stents, however, induced a severe histiolymphocytic and fibromuscular reaction resembling a foreign body reaction. CONCLUSIONS: Amphiphilic polyurethane is very promising as a biocompatible stent coating. Poly-(organo)phosphazene, however, appears unsuitable for this purpose.

In vivo comparison between two tip pressure transducer systems.

Experimental findings are presented of an in vivo comparison between a Sentron catheter and another tip transducer manometer: a Millar microtip catheter. Both catheters have been used simultaneously in the left ventricle of dogs. Pressure variations were elicited by drug infusion. Pressure values and derivatives obtained from both systems were compared. A cross correlation between episodes of the two pressures was computed. Results from this study showed good correlation between left ventricular systolic pressure measured with both manometers (R = 0.992, p < 0.0001), end-diastolic pressure (R = 0.809, p < 0.0001) and between first derivatives: positive derivative (R = 0.993, p < 0.0001) and negative (R = 0.634, p < 0.0001). The mean cross correlation between both pressure signals was 0.61 +/- 0.04. In the frequency domain no statistical difference was found between the location of the maxima of the peaks. It is concluded that a Sentron manometer can be a valid alternative, at a reasonable price, to a cheaper, though less accurate fluid filled catheter and a more expensive 'golden standard' microtip catheter.

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.

Determinants of transmitral inflow pattern 10-14 days after acute myocardial infarction.

AIM: The administration of thrombolytic therapy after an acute myocardial infarction can reduce the size of the infarct and improve left ventricular function. We used pulsed Doppler to assess left ventricular diastolic function after an acute myocardial infarction in patients treated with recombinant tissue plasminogen activator (rTPA). PATIENTS AND METHODS: We studied 104 patients after an acute myocardial infarction, 48 treated with a placebo and 56 with rTPA. They were compared with 36 age-matched controls. The Doppler parameters measured included the early peak in diastolic flow velocity, the peak during atrial contraction, the atrial: early ratio, mean deceleration, deceleration time, and half-filling fraction. Doppler parameters for large and small infarct sizes were compared. RESULTS: The Doppler parameters did not differ between treatment groups. Compared with the normal controls, significant differences were observed in both treatment groups for the early peak (placebo P < 0.05; rTPA P < 0.001), the atrial: early ratio (placebo P < 0.05; rTPA P < 0.01), and the half-filling fraction (P < 0.001 for both). In patients with large infarcts, the atrial peak was depressed (P = 0.008). Multivariate analysis showed that end-diastolic pressure, age, end-systolic volume, and regional wall motion parameters were major predictors of Doppler parameters.

Intraarterial biocompatibility of polyethylene terephthalate self-expandable stents implanted in porcine peripheral arteries.

RATIONALE AND OBJECTIVES: We tested deployment feasibility and intraarterial biocompatibility of polyethylene terephthalate (PET) self-expandable vascular stents in a porcine peripheral artery model. METHODS: To assess the thrombogenicity and neointimal response to oversized PET self-expandable stents, we implanted 10 stents in porcine common iliac arteries, followed by a 6-mm balloon inflation to 6 atm. RESULTS: All pigs survived until the study termination 6 weeks after stent implantation. Control angiography revealed stent closure in three pigs. Minimal stent luminal diameter (MSLD) was measured using a semiautomated edge detection algorithm. The difference in MSLD after stent implantation and at control after 6 weeks was not significant (4.9 +/- 0.5 mm-->4.7 +/- 1.0 mm). Histopathologic examination showed signs of thrombotic occlusion and revascularization in occluded stents. In patient stents only a mild fibromuscular neointimal response was seen. CONCLUSION: PET self-expandable stents implanted in porcine iliac arteries are possibly thrombogenic but do not lead to a significant neointimal response.

Determinants of left ventricular function two weeks and one year after an acute myocardial infarction.

This study examines possible covariates of left ventricular function two weeks and sixteen months after an acute infarction. It was performed in a group of 312 patients randomized double blindly to recombinant tissue plasminogen activator (rt-PA) (n = 156) or placebo treatment and followed thereafter for at least one year. Two weeks after the infarction, enzymatic infarct size, infarct-related vessel, and number of diseased coronary arteries were significant determinants of the infarct-related regional wall motion (centerline method) (R2 = 0.25 to 0.60, P = 0.0001). Enzymatic infarct size, regional wall motion of both infarct-related and remote areas, reinfarction, and treatment allocation were significant independent correlates of ejection fraction (R2 = 0.76), end-diastolic volume (R2 = 0.20), and end-systolic volume (R2 = 0.69, P < 0.0001). Infarct-related coronary artery and predischarge end-systolic volume were significant independent covariates of ejection fraction at rest (R2 = 0.47) after sixteen months. Age, enzymatic infarct size, and predischarge end-diastolic volume were independent determinants of the maximal (R2 = 0.49, P < 0.0001) and peak exercise ejection fraction (R2 = 0.49, P < 0.0001).

Dobutamine stress echocardiography after heart transplantation.

Dobutamine stress echocardiography was performed in 28 heart transplant recipients to study its value in the detection and staging of transplant vasculopathy. Fourteen patients had angiographic evidence of coronary artery disease (group 1), and 14 had angiographically normal coronary arteries (group 2). The dobutamine stress protocol called for a dose increase of dobutamine every 3 minutes until the age-predicted maximal heart rate was achieved. In groups 1 and 2, the mean maximal dose of dobutamine was, respectively, 24 +/- 9 micrograms/kg min and 29 +/- 8 micrograms/kg min, and the mean rate-pressure product was, respectively, 12386 +/- 1777 mm Hg/min and 10753 +/- 1085 mm Hg/min at rest, increasing to 20987 +/- 4020 mm Hg/min and 19795 +/- 2728 mm Hg/min at maximal dose. No patient in group 1 or 2 had deterioration of global or regional wall motion under dobutamine stress. In group 1, seven patients had wall motion abnormalities at rest, normalizing in five of them under dobutamine stress. In group 2, four patients had wall motion abnormalities at rest, normalizing in all patients under dobutamine stress. Consequently, this protocol of dobutamine stress echocardiography is unsuitable for the early detection of transplant vasculopathy despite its proven value in the general population. Conversely, these data suggest that the functional sequelae of transplant vasculopathy are not necessarily prominent, despite the known angiographic underestimation of the extent of the disease.

Platypnoea syndrome caused by atrial septal aneurysm.

A patient with platypnoea after right pneumonectomy and radiotherapy is described. On transoesophageal contrast echocardiography and cardiac catheterization, an atrial septal aneurysm with interatrial right-to-left shunting was detected. Symptoms disappeared after surgical correction. To the best of our knowledge, this is the first report of a patient with a septal aneurysm and severe platypnoea.

Automatic detection of ventricular tachycardia and fibrillation using ECG processing and intramyocardial pressure measurement.

Ventricular electrograms and intramyocardial pressure signals were recorded in 11 dogs during sinus rhythm, during paced ventricular tachycardia, and at the onset of and during ventricular fibrillation. The autocorrelation function and the probability density function of short episodes of the electrograms were analyzed off-line on a digital computer. Peak-to-peak values of the intramyocardial pressure were calculated during sinus rhythm and during ventricular tachycardia and fibrillation. An algorithm was developed to recognize tachycardia and fibrillation using the autocorrelation function, the probability density function, and the intramyocardial pressure as input signals. Results show that in case of sinus rhythm all detection methods are reliable (recognition rate of 100%). In case of ventricular tachycardia with hemodynamic impairment the autocorrelation function is slightly better (66.6%) than the probability density function (44.4%). The onset of ventricular fibrillation is sensed in 81.8% of all episodes with the autocorrelation function and in 63.6% with the probability density function. During ventricular fibrillation this improves, respectively, to 92.3 and 69.2%. In all previous cases the intramyocardial pressure signal was 100% reliable. It is concluded that in this arrhythmia model, the sensitivity of an automatic ventricular tachycardia/fibrillation detection system was increased by combining ECG processing with analysis of an hemodynamic parameter.

Intravenous metoprolol preceding thrombolysis in acute thrombotic myocardial infarction in the dog; effects on infarct size, myocardial blood flow, and left ventricular function.

Intravenous (i.v.) metoprolol preceding thrombolysis in an anesthetized dog model of thrombotic occlusion of the anterior descending coronary artery helps limit infarct size (IS). We wished to determine whether these effects are caused at least in part by enhancement of collateral blood flow to the area at risk (AAR). Thrombotic occlusion was provoked by a copper-coil technique. We measured intracardiac pressures and their derivatives by catheter-tip micromanometers, cardiac output (CO) by thermodilution method, regional myocardial blood flow (RMBF) by radioactive microspheres technique, global and regional left ventricular (LV) function by ventriculography, and IS with triphenyltetrazolium at the end of the experiment. Measurements were performed before and after 60-min occlusion and after 30- and 90-min reperfusion. Received fifteen minutes after occlusion, 12 dogs metoprolol 0.3 mg/kg i.v. followed by 0.3 mg/kg/h; 12 received saline. Thrombolysis was performed in all dogs after 60-min occlusion with recombinant tissue-type plasminogen activator (rt-PA) 10 micrograms/kg/min for 30 min. Hemodynamic findings were similar in both groups. During occlusion, collateral flow to total AAR (18.6 +/- 7.5 vs. 11.0 +/- 6.1 ml/min/100 g), to its subepicardial (22.1 +/- 8.1 vs. 12.2 +/- 7.2 ml/min/100 g), midmyocardial (16.0 +/- 8.9 vs. 8.0 +/- 5.5 ml/min/100 g), and endocardial (14.1 +/- 8.1 vs. 7.3 +/- 6.0 ml/min/100 g) layers was higher (p < or = 0.03) in metoprolol than in placebo-treated dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

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.