Can phosphorus limitation contribute to the maintenance of sex? A test of a key assumption.

Why sex is so common remains unclear; what is certain is that the predominance of sex despite its profound costs means that it must confer major advantages. Here, we use elemental and nucleic acid assays to evaluate a key element of a novel, integrative hypothesis considering whether sex might be favoured because of differences in body composition between sexuals and asexuals. We found that asexual Potamopyrgus antipodarum, a New Zealand snail, have markedly higher bodily phosphorus and nucleic acid content per unit mass than sexual counterparts. These differences coincide with and are almost certainly linked to the higher ploidy of the asexuals. Our results are the first documented body composition differences between sexual and asexual organisms, and the first detected phenotypic difference between sexual and asexual P. antipodarum, an important natural model system for the study of the maintenance of sex. These findings also verify a central component of our hypothesis that competition between diploid sexuals and polyploid asexuals could be influenced by phosphorus availability.

Diagnostic and prognostic value of serial dobutamine stress echocardiography for noninvasive assessment of cardiac allograft vasculopathy: a comparison with coronary angiography and intravascular ultrasound.

BACKGROUND: Routine methods for surveillance of cardiac allograft vasculopathy (CAV) are coronary angiography and intravascular ultrasound (IVUS). This study analyzed the diagnostic and prognostic value of dobutamine stress echocardiography (DSE) for noninvasive assessment of CAV. METHODS AND RESULTS: In 109 heart transplant recipients, 333 DSEs were compared with 285 coronary angiograms and 199 IVUS analyses. Studies were repeated after 1, 2, 3, 4, and >/=5 years in 88, 74, 37, 18, and 7 patients, respectively. Resting 2D echocardiography detected CAV defined by IVUS and angiography with a sensitivity of 57% (specificity 88%). DSE increased the sensitivity to 72% (P=0.002). M-mode analysis increased the sensitivity of 2D rest and stress analysis (P=0.001, 0.004). Cardiac events occurred after 1.9% of normal stress tests by 2D analysis (combined 2D and M-mode: 0%), compared with 6.3% (3.8%) of normal resting studies. Worsening of serial DSE indicated an increased risk of events compared with no deterioration (relative risk 7.26, P=0.0014). Serial deterioration detected by stress only was associated with a higher risk of events than changes evident from resting studies (relative risk 3.06, P=0.0374). CONCLUSIONS: DSE identifies patients at risk for events and facilitates monitoring of CAV. A normal DSE predicts an uneventful clinical course and justifies postponement of invasive studies. The prognostic value of DSE is comparable to that of IVUS and angiography.

Verapamil impairs secretion of stimulated atrial natriuretic factor in humans.

The adaptation of the secretory rate of atrial natriuretic factor to repeated adequate stimuli and the influence of the calcium antagonist verapamil on the release of atrial natriuretic factor were investigated in 16 patients. In eight patients (Group 1) right atrial pressure was abruptly increased by rapid right ventricular pacing for 4 min (stimulation I). After a 15 min interval, the identical stimulation was repeated (stimulation II). Eight patients (Group 2) underwent the same protocol but received 5 mg of verapamil intravenously after stimulation I. Pacing increased right atrial pressure in both groups identically by 70%. In Group 1, release of atrial natriuretic factor caused by the second stimulation (median 290 pg/ml over basal) was significantly (2.5-fold) larger than atrial natriuretic factor release induced by the first stimulation (median 116 pg/ml over basal). In the verapamil-treated patients (Group 2), the effect of right atrial pressure increase on release of atrial natriuretic factor was abolished after stimulation II. In both groups, changes in plasma concentrations of cyclic guanosine monophosphate corresponded to changes in atrial natriuretic factor concentrations. Thus, the myoendocrine cells are apparently capable of a fast upward regulation of their response to repeated secretory stimuli. Verapamil appears to block the stimulatory effect of a sudden increase in right atrial pressure upon release of atrial natriuretic factor.

Serial changes during acute cardiac allograft rejection: quantitative ultrasound tissue analysis versus myocardial histologic findings.

OBJECTIVES: The aim of this study was to assess 1) whether quantitative ultrasound tissue analysis by serial measurements of myocardial echo amplitudes can detect and monitor the onset and degree of acute cardiac rejection, as well as its resolution of acute rejection during treatment, and 2) whether changes in myocardial echo amplitudes are modified by repeat additional rejection episodes. BACKGROUND: Previous experimental studies, all involving heterotopic heart transplantation, have consistently shown reproducible alterations in myocardial echo amplitude during acute rejection episodes untreated by immunosuppressive agents. METHODS: Two-dimensional echocardiographic long-axis views were obtained daily under strict standardization in 12 dogs after heterotopic cervical heart transplantation (mean survival time 16.1 days) and digitized into a 256 x 256 x 8 matrix. Myocardial echo amplitudes were analyzed by gray level histogram statistics in regions of interest (45 x 12 pixels) within the proximal septum and posterior wall and correlated with the results of daily transmural myocardial biopsies. Maintenance immunosuppressive therapy consisted of cyclosporine, azathioprine and steroids. Additive steroids were given during acute cardiac rejection. RESULTS: All dogs experienced at least one moderate or severe episode of acute cardiac rejection. Successful resolution and repeat acute rejection were observed in three dogs. On 65 days, the left ventricular biopsy specimens showed no evidence of acute rejection. Mild acute rejection was present on 36, moderate on 29 and severe rejection on 40 days. End-diastolic mean (+/- SD) gray level increased progressively from 100.7 +/- 20.4 for no acute cardiac rejection to 113.8 +/- 23.1 for mild rejection (p = NS vs. no rejection) to 126.0 +/- 16.1 for moderate rejection (p < 0.01) and to 136.3 +/- 12.6 for severe rejection (p < 0.01). In each individual dog, a correlation between daily measurements of mean gray levels and histologic cardiac rejection grades was found (rmean = 0.80 +/- 0.14 [range 0.57 to 0.97], n = 12). In three dogs with transient complete histologic resolution of acute cardiac rejection, mean gray level did not return to values before rejection (108.0 +/- 15.4 vs. 87.2 +/- 8.4). The subsequent second episode of rejection was characterized by higher gray level values than those associated with the first rejection episode (141.3 +/- 14.4 vs. 124.3 +/- 20.9). CONCLUSIONS: Acute cardiac rejection is associated with a progressive increase in mean gray level. Changes in myocardial echo amplitudes in individuals may thus prove a useful tool for the noninvasive detection and monitoring of acute rejection. Increased mean gray level values after resolution of rejection may indicate persistent structural tissue abnormalities after rejection and demonstrate the need to define new baseline values after histologic resolution of an acute rejection episode.

Aldosterone influences free intracellular calcium in human mononuclear leukocytes in vitro.

Mineralocorticoid receptors have been detected in human mononuclear leukocytes (HML) and a physiological effector mechanism was demonstrated subsequently by which aldosterone is able to prevent the loss of intracellular sodium, potassium and cell water during incubation in an aldosterone-free medium. In the present paper, free intracellular calcium, [Ca2+]i, was measured in HML from normal subjects by Quin-2 and Fura-2 fluorescence after incubation for 1 h at 37 degrees C in RPMI-1640 medium. In fresh HML, [Ca2+]i was 54 +/- 15 nM (Fura-2, mean +/- SD, n = 26). After incubation without aldosterone, [Ca2+]i in HML was 118 +/- 27 nM (Quin-2, n = 11) and 50 +/- 13 nM (Fura-2). After incubation with 1.4 (Fura-2) or 2.8 nM (Quin-2) aldosterone, [Ca2+]i was 139 +/- 38 nM (Quin-2, P less than 0.05 compared with value after incubation without aldosterone) and 57 +/- 11 nM (Fura-2, P less than 0.00001). The Kd-value for dose-response curve was 0.4 nM. The effect of aldosterone was antagonized by N-ethyl-isopropylamiloride, but not by canrenoate, canrenone, cycloheximide and actinomycin D. It was absent in a sodium-free buffer. Corticosterone and hydrocortisone were active as agonists. These results show that aldosterone exerts an effect on the [Ca2+]i in HML in vitro which could be involved in hemodynamic responses to mineralocorticoids if also present in cardiovascular tissues.

The inositol-1,4,5-trisphosphate system is involved in rapid effects of aldosterone in human mononuclear leukocytes.

There is increasing evidence for rapid steroid action on electrolyte transport in human mononuclear leukocytes (HML). In HML, aldosterone stimulates the Na+/H+ antiporter within a few minutes. Because a variety of hormones and growth factors activate the Na+/H+ antiporter via protein kinase C and inositol phospholipids, a possible involvement of inositol-1,4,5-trisphosphate (IP3) in the rapid effects of aldosterone in HML was investigated. The stimulation of IP3 generation was started by the addition of aldosterone, concanavalin A, or other steroids. A significant increase in IP3 levels by aldosterone (1 nmol/L, P < 0.05) was found after 1 min, similar to that found after concanavalin A (25 micrograms/mL). Aldosterone caused a concentration-dependent elevation of IP3 levels, with an apparent EC50 of approximately 0.1 nmol/L. Fludrocortisone stimulated IP3 generation at similar concentrations, whereas a weaker IP3 stimulation by glucocorticoids (hydrocortisone, dexamethasone) occurred at micromolar concentrations only. Canrenone, a potent inhibitor of classical aldosterone action, was not effective up to a concentration of 100 nmol/L. These findings show kinetic and pharmacological similarities with both the functional data on Na+/H+ antiport stimulation by aldosterone and the studies of 125I-aldosterone binding to plasma membranes of HML. Thus, these data are the first to indicate an involvement of the phosphoinositide pathway in the rapid membrane effects of aldosterone.

Rapid effects of aldosterone on sodium transport in vascular smooth muscle cells.

Increasing evidence has accumulated for rapid nongenomic steroid actions in various cell systems and, more recently, for rapid aldosterone effects on the Na(+)-H+ antiport in human mononuclear leukocytes. The aim of the present study was to demonstrate a rapid, nongenomic aldosterone action in rat vascular smooth muscle cells as a key effector cell in cardiovascular regulation. Basal 22Na+ influx in quiescent vascular smooth muscle cells was 22.1 +/- 1.9 nmol/mg protein per minute (mean +/- SEM, n = 9). Aldosterone (1 nmol/L) stimulated influx to 28.6 +/- 1.5 nmol/mg protein per minute after 4 minutes (n = 9, P < .05), with a half-maximal effect between 0.1 and 0.5 nmol/L; the effects were inhibited by ethylisopropylamiloride, the specific inhibitor of the Na(+)-H+ exchanger, demonstrating the involvement of this transport system in rapid effects of aldosterone. Hydrocortisone (1 mumol/L) was ineffective, and fludrocortisone and deoxycorticosterone increased influx with half-maximal effects at approximately 0.5 nmol/L. Canrenone, a classic antagonist of aldosterone action, did not inhibit stimulation by aldosterone at a 1000-fold excess concentration. Aldosterone significantly stimulated intracellular inositol 1,4,5-trisphosphate levels (P < .05) after 30 seconds; the inhibitors of phospholipase C, neomycin and U-73122, inhibited aldosterone-stimulated Na+ influx and increase of intracellular inositol 1,4,5-trisphosphate. The rapid stimulation of sodium transport in vascular smooth muscle cells and the pharmacological characteristics of this effect are clearly incompatible with the classic, genomic pathway of steroid action and represent further evidence for nongenomic effects of aldosterone.

Rapid cardiovascular action of aldosterone in man.

Rapid nongenomic in vitro effects of aldosterone have been demonstrated recently in cultured vascular smooth muscle and endothelial cells. But there is, as yet, little evidence for corresponding in vivo effects. The present study thus investigates the rapid nongenomic effects of aldosterone on human cardiovascular function. In a double-blind placebo-controlled randomized parallel trial on 17 patients with suspected coronary heart disease, the effect of 1 mg aldosterone iv on cardiovascular function was assessed during cardiac catheterization. Hemodynamic parameters (such as heart rate, left ventricular and atrial pressures, arterial pressures, vascular resistances, and cardiac output) were measured before and 3 and 10 min after administration of aldosterone or placebo. Significant changes were found for systemic vascular resistance, cardiac output, and cardiac index, compared with the placebo group (Wilcoxon test, P < 0.02-0.05). The effect of aldosterone dissipated within 10 min. The results are in line with the in vitro data cited above and consistent with earlier findings on acute cardiovascular effects of aldosterone, which have now been confirmed and extended by contemporary techniques. The hypotheses of rapid nongenomic in vivo effects of aldosterone are further substantiated by this study.

Induction and circumvention of nitrate tolerance applying different dosage intervals.

There is increasing evidence that constant nitrate plasma levels, as induced by at least three-times-daily ingestions of isosorbide dinitrate in sustained-release form, lead to an attenuation or even complete loss of the anti-ischemic effects (nitrate tolerance). Therefore, the dependence of tolerance development on dosage intervals according to once-daily and twice-daily ingestions was assessed. Tablets of isosorbide dinitrate (80 mg) in sustained-release form were administered once-daily at 8 A.M. (dosage interval 24 hours) or twice-daily at 8 A.M. and 8 P.M. (dosage interval 12 hours), as well as at 8 A.M. and 2 P.M., respectively (maximal dosage interval 18 hours). A total of 34 patients with angiographically proven coronary artery disease, a history of stable, exercise-dependent angina pectoris, and a reproducible, exercise-induced ST-segment depression of at least 0.15 mV (1.5 mm), who initially showed a response to 80 mg of isosorbide dinitrate, were enrolled. The anti-ischemic effects of isosorbide dinitrate on exercise-induced ischemia were objectively determined by the measurement of exercise-induced ST-segment depression before as well as two, six, and 12 hours after the ingestion at the first and the 15th day of the studies. Since the dosage interval of 12 hours resulted in constant plasma levels, the initially beneficial anti-ischemic effects of isosorbide dinitrate were considerably attenuated after two weeks of treatment. In contrast, the once-daily regimen with its intermittent peaks and valleys of nitrate plasma levels showed identical anti-ischemic effects at the 15th day as compared with the first day. Ingestions at 8 A.M. and 2 P.M. also circumvented the development of nitrate tolerance, however, combined with an even more pronounced anti-ischemic effect after 12 hours as compared with the once-daily regimen. Thus, the circumvention of nitrate tolerance requires a daily "nitrate-poor" interval. The best compromise between a maximal possible anti-ischemic effect and the circumvention of tolerance development was found for the "eccentric" dosage regimen in which the tablets were ingested in the morning and early afternoon.

The Na(+)-H+ exchanger is stimulated and cell volume increased in lymphocytes from patients with essential hypertension.

A stimulation of the Na(+)-H+ exchanger has been shown in platelets of hypertensive man and lymphocytes of spontaneously hypertensive rats. In the present paper, human mononuclear leukocytes (HML) were investigated in 12 patients with essential hypertension with regard to the activity of the Na(+)-H+ exchanger and HML volume. The swelling of HML in isotonic sodium propionate was determined using a Coulter Channelyzer. Compared with matched normotensives, the cell volume of HML in a physiological buffer was significantly increased in essential hypertension (P less than 0.05). The amiloride-inhibitable rate of cell swelling in isotonic sodium propionate was also increased in HML from hypertensives. Amiloride (400 mumol/l) abolished the difference in cell volume within 1 min. These data show a functional swelling of HML in essential hypertension, probably due to an activation of the Na(+)-H+ exchanger. If also representative of smooth muscle cells, these findings could explain hypertensive vessel wall hypertrophy, in part, as functional cell swelling.

Prevention of osteoporosis after cardiac transplantation: a prospective, longitudinal, randomized, double-blind trial with calcitriol.

BACKGROUND: Accelerated bone loss is a well-recognized complication after cardiac transplantation (HTx) due to immunosuppressive therapy. The purpose of this prospective, longitudinal, randomized, placebo-controlled, double-blind study was to investigate the effect of calcitriol (1,25-dihydroxyvitamin D3) in the prevention of bone loss and fracture rate after HTx. METHODS: Basic therapy included 1000 mg of calcium daily and sex hormone replacement in hypogonadal patients. A total of 132 patients (111 male, 21 female; mean age: 51+/-10 years; 35+/-25 months after HTx) were randomized to 0.25 microg of calcitriol or placebo. Bone mineral density (BMD, g/cm2; T score, %) of the lumbar spine and x-rays for the assessment of vertebral fractures were performed at baseline and after 12, 24, and 36 months. Biochemical indexes of mineral metabolism were measured every 3 months. RESULTS: Overall BMD was significantly decreased after HTx (T score 87+/-13%). BMD increased continuously within the study period in the calcitriol group (1 year: 2.2+/-4.8%; 2 years: 3.9+/-5.4%; 3 years: 5.7+/-4.4%) as well as in the placebo group (1 year: 1.8+/-4.9%; 2 years: 3.7+/-6.5%; 3 years: 6.1+/-7.8%) without statistical difference between the groups. Fracture incidence was low during the study interval (1 year: 2.0%; 2 years: 3.4%; 3 years: 0%). Hypogonadism (20%) was associated with a lower BMD (78+/-12% vs. 88+/-12%; P<0.01) and a higher increase (35%) after hormone replacement in comparison to normogonadal patients. Increased intact parathyroid hormone and bone resorption markers decreased significantly during therapy. CONCLUSIONS: Calcium supplementation and sex hormone replacement in hypogonadism proved a sufficient long-term prevention therapy to improve decreased BMD and to prevent fractures after HTx. Besides immunosuppression, both concomitant hypogonadism and secondary hyperparathyroidism play a major role in the long-term bone loss and should therefore be monitored and treated adequately. Low-dose calcitriol demonstrated no significant extra benefit regarding BMD and fracture rate in the long-term period after HTx.

Predictors of reduced coronary flow reserve in heart transplant recipients without angiographically significant coronary artery disease.

BACKGROUND: Determination of coronary flow reserve (CFR) is increasingly used to assess the functional significance of cardiac allograft vasculopathy. Although the relation between CFR and angiographically defined vasculopathy has been studied extensively, little is known about other factors determining CFR in heart transplant recipients without significant lesions by coronary angiography. METHODS: Sixty consecutive patients were studied 0.5 to 148 months after heart transplantation with intracoronary Doppler and intravascular ultrasound. An endothelium-independent CFR< or =2.5 was defined as abnormal. Stepwise logistic regression analysis was used to identify factors (demographic data of donor and recipient, lipid profile, epicardial vessel morphology by intravascular ultrasound, left ventricular hypertrophy, acute rejection episodes, and hemodynamics) potentially associated with a reduced CFR. RESULTS: Only the presence of left ventricular hypertrophy (48% vs. 14%, P=0.007 and P=0.023, bivariate and multivariate analysis, respectively) and higher donor ages (41+/-12 vs. 29+/-11 years, P=0.002 and P=0.013, bivariate and multivariate analysis, respectively) showed an independent association with an abnormal flow reserve. CFR in patients with left ventricular hypertrophy was reduced due to higher baseline flow velocities (27+/-11 vs. 20+/-6 cm/sec, P=0.004). Furthermore, resting flow velocity increased as a function of donor age (r=0.264, P=0.047), while hyperemic flow velocity was not different. Other patient characteristics and hemodynamics did not affect CFR. CONCLUSION: The presence of left ventricular hypertrophy and higher donor ages independently contribute to a reduced CFR in patients after heart transplantation. This reduction in CFR is due to elevated baseline flow velocities rather than to a change in hyperemic flow velocities. These findings should be taken into account for the interpretation of reduced CFR values obtained by intracoronary Doppler in heart transplant recipients without angiographically overt coronary lesions.

Intraindividual variability of cardiac allograft vasculopathy as assessed by intravascular ultrasound.

To investigate the intraindividual extent of cardiac allograft vasculopathy (CAV), 43 heart transplant recipients were studied 0.5 to 108 months after transplantation with intravascular ultrasound (IVUS). In these patients, 216 segments in 71 coronary arteries were analyzed quantitatively: 26 of 43 patients (60%) underwent study of > or = 2 arteries, and 80 of 216 segments (37%) were located distally (5.0 +/- 2.4 segments/patient were analyzed). Intimal index and mean IVUS grade were less pronounced in segments of the left circumflex artery (9 +/- 14 and 2.1 +/- 1.6) than in segments of the left anterior descending artery (21 +/- 19 and 3.3 +/- 2.1), right coronary artery (22 +/- 19 and 3.5 +/- 2.1), and left main coronary artery (16 +/- 4 and 3.3 +/- 1.9) (p < 0.01 and p < 0.001, respectively). In 21 of 43 patients, both the left anterior descending and left circumflex arteries were studied: Higher values in the intimal index were seen in the left anterior descending artery (20 +/- 14 vs 9 +/- 13, p < 0.005). When distal and proximal segments of the same vessel were compared, CAV was found in 44 of 56 arteries and the proximal segments were more affected in 64%. The difference between minimal and maximal IVUS grade in patients with only 1 artery studied (n = 17) was 1.7 +/- 1.8 compared with 3.1 +/- 1.7 in patients with > or = 2 arteries analyzed (n = 26). This in vivo study with IVUS shows a large variability of CAV involvement between different coronary arteries and segments in 1 patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of the calcium antagonist diltiazem on atrioventricular conduction in chronic atrial fibrillation.

The effect of oral diltiazem treatment on the mean ventricular rate was studied in 10 patients with stable atrial fibrillation (AF). The profile of mean ventricular rate was analyzed by means of 24-hour electrocardiographic recordings. Both single-dose (120 mg) and maintenance therapy (80 mg 3 times daily) reduced the mean ventricular rate significantly. After the single dose, the effect set in after 120 +/- 40 minutes (mean +/- standard deviation) and persisted for 347 +/- 84 minutes. Histograms of RR intervals were plotted and their changes after diltiazem therapy were also analyzed. The shortest and longest atrioventricular (AV) conduction times were defined as 5% and 95% values of the cumulative frequency curve, respectively. There were 2 distinct types of the RR-interval histographic changes: In 50% of the patients, the longest and shortest RR intervals prolonged proportionately; in the other 50%, the longest intervals increased disproportionately. Results indicate that oral diltiazem treatment can significantly decrease the mean ventricular rate in patients with AF by influencing the concealed conduction in the AV node. The changes of the RR-interval histograms suggest that in 50% of the patients, the increase of the concealed conduction was probably caused primarily by the increase of AF rate, and in 50% both increased AF rate and prolonged refractory period in the AV node contributed to the increase of concealed conduction.

Intraoperative myocardial contrast echocardiography for assessment of regional bypass perfusion.

The intraoperative determination of the success of surgical myocardial revascularization remains problematic because of major limitations in all currently used methods. To assess the regional blood flow of the bypass graft-dependent myocardial segments, 2 ml of sonicated iopromid (a nonionic x-ray contrast medium) was injected into the bypass graft in the beating heart. Simultaneously electromagnetic flow measurements were performed. Eleven graft injections in 8 men (mean age +/- standard deviation 60 +/- 4 years) were performed without any adverse effects. Excellent 2-dimensional cross-sectional views of the left ventricle were obtained in all cases. Ten of 11 injections resulted in adequate myocardial opacification. Computer-assisted evaluation by videodensitometry resulted in time-intensity curves with contrast decay half-times (T1/2) from 2.2 to 6.9 seconds (mean 4.3 +/- 1.4). The corresponding electromagnetic flow ranged from 55 to 100 ml/min (mean 80.0 +/- 16.2). there was no correlation between contrast 2-dimensional echocardiography-derived T1/2 and electromagnetic flow (r = 0.32; p = 0.38). Thus, myocardial contrast echocardiography is a feasible and safe method for intraoperative evaluation of the success of bypass graft surgery. It offers online visualization of perfusion of revascularized myocardium and may allow immediate intraoperative revision of unsuccessful bypass graft placement.

Serial intravascular ultrasound and quantitative coronary angiography after self-expandable wallstent coronary artery implantation.

Serial intracoronary ultrasound studies revealed significant postprocedural stent expansion accompanied by significant stent shortening during long-term follow-up. The disadvantageous lumen loss by neointimal formation could be balanced by late stent expansion.

Low-dose aspirin versus anticoagulants for prevention of coronary graft occlusion.

The prevention of graft occlusion by aspirin (100 mg/day) or heparin followed by phenprocoumon was investigated in a randomized trial in 235 patients after aortocoronary bypass operation. Aspirin treatment started 24 hours before, and heparin 6 hours and phenprocoumon 2 days after surgery. The results of the vein graft angiography and the clinical outcome 3 months postoperatively did not differ: 22% of 218 vein graft distal anastomoses in the aspirin group and 20% of 272 in the anticoagulant group were occluded. At least 1 occluded distal anastomosis was present in 38% of 74 patients in the aspirin-treated group and in 39% of 86 in the anticoagulant group. Worst-case analysis of all randomized patients showed graft occlusions, cardiovascular complications or lost to follow-up in 42% of 122 aspirin-treated patients compared with 41% of 113 patients treated with anticoagulants. For grafts with endarterectomy the occlusion rate was lower in the aspirin (12% of 49) than in the anticoagulant (22% of 41) group (p less than or equal to 0.05). Increased perioperative blood loss in the aspirin group (1,211 +/- 814 ml in the first 48 hours vs 874 +/- 818 ml in the anticoagulant group [p less than or equal to 0.001]) without a higher reoperation rate indicates effective platelet inhibition with low-dose aspirin. Because occlusion rates were equal but high in these patients with advanced stage of coronary artery disease, a combination of low-dose aspirin and anticoagulation should be investigated to reduce graft occlusion rates further.

Dobutamine stress echocardiography for noninvasive diagnosis of cardiac allograft vasculopathy: a comparison with angiography and intravascular ultrasound.

This study was performed to assess the value of dobutamine stress echocardiography for noninvasive diagnosis of cardiac allograft vasculopathy (CAV) compared with coronary angiography and intravascular ultrasound (IVUS) in 50 consecutive orthotopic heart transplant recipients. In 46 of 50 patients, a technically adequate echocardiogram could be obtained. Using a 16-segment model, a total of 675 segments were analyzed. At rest, wall motion abnormalities were found in 61 of 675 (9.0%) left ventricular segments in 15 of 46 patients. At maximal dobutamine stress, 103 of 675 segments (15.3%) had wall motion abnormalities (25 of 46 patients). Based on IVUS and angiographic findings, patients were allocated to 2 groups. Group I (n=18) had absent or only mild intimal hyperplasia (mean IVUS grade < or = 3.0 on a 6-grade scale). Group II (n=28) had moderate to severe intimal hyperplasia (mean grade > 3.0 with or without angiographic evidence of CAV. The prevalence of wall motion abnormalities was significantly higher in group II than in group I, both at rest (50 of 415 vs 11 of 270 coronary segments in 13 of 28 vs 2 of 18 patients) and during maximal stress (88 of 415 vs 15 of 270 coronary segments in 22 of 28 vs 3 of 18 patients). Quantitative M-mode echocardiography demonstrated decreased wall thickening in group II versus group I patients at maximal dobutamine dosage in the septum (48 +/- 18% vs 61 +/- 17%; p < 0.01) as well as in the left ventricular posterior wall (77 +/- 21% vs 96 +/- 21%; p <0.005). Regional myocardial dysfunction as assessed by dobutamine stress echocardiography was associated with IVUS evidence of moderate to severe intimal hyperplasia. Dobutamine stress echocardiography appears to be a feasible noninvasive method for detection of CAV in heart transplant recipients, which may reduce the need for routine coronary angiography.

Cyclosporine versus tacrolimus (FK 506) for prevention of cardiac allograft vasculopathy.

This study prospectively compared the impact of cyclosporine A and tacrolimus on the development of cardiac allograft vasculopathy. By using serial intravascular ultrasound examinations, a trend toward a more pronounced progression was noted in the tacrolimus group in the first year after heart transplantation.

Antiarrhythmic therapy with flecainide in combination and comparison with propranolol.

In a prospective study of 10 patients with chronic ventricular arrhythmias, flecainide 50mg tid and propranolol 20mg tid were administered, alone and in combination, in a crossover design. Before and after each treatment phase, routine ECG and 24-hour ECG were recorded, morning plasma concentrations of the drugs were measured, and side effects recorded. Treatment with flecainide alone resulted in a 38% mean reduction (p less than 0.05) of ventricular premature complexes, a 75% (p less than 0.01) mean reduction of couplets, and elimination of ventricular tachycardia. At the dosage administered, propranolol alone had no antiarrhythmic effect. The combination of flecainide and propranolol showed no additional therapeutic benefit although there was a small, but not significant, increase in ventricular premature complexes and couplets. Use of flecainide resulted in a 12% widening of the QRS complex, with no significant change in PQ time, QTc and heart rate. Combined therapy with propranolol and flecainide resulted in a 12% decrease of average heart rate. The same effect was achieved when propranolol was given alone. The average plasma concentration of flecainide increased by 25% during combined therapy with propranolol. There were few side effects related to flecainide at the dosage administered and no additional side effects were recorded during the combined treatment.