Diabetic cardiomyopathy and diastolic heart failure -- difficulties with relaxation.

Diabetic patients carry a four- to five-fold increased risk of heart failure. Hyperglycaemia plays a central role in the pathogenesis of diabetic cardiomyopathy. Diabetic cardiomyopathy represents a distinct structural and functional disorder of the myocardium characterized by cardiac hypertrophy and an increased myocardial stiffness. At an early stage, diabetic cardiomyopathy is manifested by diastolic heart failure with preserved ejection fraction. In some patients, diastolic dysfunction may progress to heart failure with reduced ejection fraction and result in overt systolic heart failure. Diastolic dysfunction can accurately be diagnosed by echocardiography and BNP measurement in daily clinical practice. Early treatment is prognostically important. Optimal control of blood glucose levels and blood pressure is beneficial. So far metformin is the only antidiabetic agent not associated with harm in diabetic patients with heart failure. Incretin-based therapies potentially provide cardiovascular benefits. ACE inhibitors, angiotensin-1 receptor antagonists and beta-blockers should be preferred in heart failure therapy.

Three-dimensional echocardiography: in-vitro validation of a new, voxel-based method for rapid quantification of ventricular volume in normal and aneurysmal left ventricles.

BACKGROUND: Previous approaches to ventricular volume calculations by 3-dimensional echocardiography (3-DE) required multiple transverse tomographic sectioning and summation of the volumes of parallel disks. These methods were time consuming and beared the risk of missing the apical volume. METHODS: We investigated the accuracy of a new, rapid method of 3-DE volume measurements in normal (LV) and aneurysmal (aneurLV) left ventricles in fixed pig hearts. 3-D data sets of 12 LV and 8 experimentally created aneurLV were obtained using a TomTec 3-DE system. For 3-DE volume calculations, a rotational axis in the center of the left ventricle (apical-basal orientation) was defined and 3, 6 and 12 equi-angular rotational planes were created. In each plane the endocardial border was traced and the volume of the corresponding wedge was automatically calculated. The measurements were performed by 2 independent investigators blinded to the anatomic volume and were analyzed for inter- and intraobserver variability. RESULTS: The anatomic volumes ranged from 5 to 150 ml and 9 to 40 ml in LV and aneurLV, respectively. The correlation between 3-DE and anatomic volume was excellent for LV and aneurLV traced in 3, 6 and 12 planes (r = 0.94-0.99). Ventricular volume was well predicted by 3-DE reconstruction: SEE 5.5-7.1 ml (LV), 3.0-3.2 ml (aneurLV). The correlation for interobserver measurements was good in both, LV (r = 0.99) and aneurLV (r = 0.94-0.99) even in 3 planes. The intra- and interobserver variabilities were 1.6-3.0 ml (<7%) and 7.2-7.3 ml (<15%) in LV and 1.1-1.6 (<6%) and 2.1-3.3 ml (<14%) in aneurLV respectively. CONCLUSION: This new 3-DE method of ventricular volume measurements using a rotational approach provides rapid, accurate and reproducible volume measurements in LV and aneurLV.

Detection of viable myocardium by transvenous myocardial contrast echocardiography using harmonic power Doppler: canine model of acute coronary occlusion and reperfusion.

STUDY OBJECTIVE: To assess whether myocardial contrast echocardiography (MCE) using harmonic power Doppler (HPD) in conjunction with the transvenous contrast agent SHU 563A would be useful in detecting stunned but viable myocardium. DESIGN: Acute coronary occlusion (2 to 3 h) followed by 1 h of reperfusion was created in 10 dogs in an open-chest model. MEASUREMENTS AND RESULTS: Continuous harmonic B-mode for wall motion analysis and ECG triggered HPD for assessment of myocardial perfusion was employed during coronary occlusion and after reperfusion. Postmortem 2,3,5-triphenyltetrazolium chloride (TTC) staining was performed to verify infarction. Extent of wall motion abnormality (WMA), perfusion defect size, and anatomic infarct size (myocardial infarction [MI]) were analyzed in a 5-segment model. All 10 dogs showed WMA in 23 of 50 segments during coronary occlusion. In eight dogs, HPD detected perfusion defects in 18 of 50 segments. The concordance rate between WMA and perfusion defect was 86%. Mean linearized power (MLP) in segments with WMA was significantly lower compared to normal segments (60.7 +/- 38.9 vs 110.5 +/- 108.8, p < 0.05). After reperfusion, the extent of WMA was larger than the area of perfusion defect (percentage of left ventricular slice area): 30 +/- 13% vs 9 +/- 8%, p < 0.01. Eventual infarct size was 6 +/- 7%. WMAs were seen in 18 of 50 segments. TTC confirmed MI in 7 of 18 segments. MLP in segments with WMA but no MI was significantly higher compared to segments with WMA and MI (84.5 +/- 67.3 vs 13.2 +/- 9.6, p < 0.01). Thus, the extent of WMA after reperfusion was greater than the size of perfusion defect and eventual MI, indicating the presence of stunned but viable myocardium. CONCLUSION: MCE using HPD and the contrast agent SHU 563A can demonstrate the efficacy of reperfusion, identify necrotic regions, and aid in the recognition of stunned but viable myocardium. This approach could be useful clinically in patients with acute MI undergoing reperfusion therapy.

Assessment of myocardial perfusion by myocardial contrast echocardiography using harmonic power and the transvenous contrast agent SHU 563A in acute coronary occlusion and after reperfusion.

BACKGROUND: Harmonic power Doppler imaging is a novel technique for the assessment of myocardial perfusion by contrast echocardiography. In this study, we examined whether myocardial contrast echocardiography using harmonic power Doppler and the new transvenous contrast agent SHU 563A can identify myocardial perfusion defects during coronary occlusion and reperfusion. METHODS: To assess the potential of this technique, we occluded either the left anterior descending coronary artery or the circumflex coronary artery for 2 to 3 h followed by 1 h reperfusion in 10 dogs in an open chest model. After transvenous administration of SHU 563A, an air-filled, polymeric contrast agent, myocardial contrast echocardiography was performed in short and long axis views with triggered harmonic power Doppler imaging after coronary occlusion and reperfusion. Post-mortem triphenyl tetrazolium chloride staining was performed to verify infarction. Harmonic power Doppler and anatomic data were analyzed by independent observers. RESULTS: During coronary occlusion, harmonic power Doppler showed perfusion defects in all 10 dogs. The defect size in the short axis view at papillary muscle level ranged 4-51% (14+/-13%) and 3-43% (16+/-10%) in the long axis view (% total LV slice area). After reperfusion (1 h) and infusion of dipyridamole (0.56 mg/kg), power Doppler demonstrated perfusion defects in seven dogs: 0-20% (9+/-8%) (short axis view) and 0-48% (13+/-14%) (long axis view). Five dogs showed anatomic infarction. The anatomic infarct area was 0-18% (6+/-8%) (slices corresponding to the echocardiographic short axis images). Perfusion defect size by harmonic power Doppler correlated well with residual infarct size (r=0.82, P<0.01). CONCLUSIONS: Myocardial contrast echocardiography using harmonic power Doppler and the new contrast agent SHU 563A accurately displays perfusion defects during acute coronary occlusion and after reperfusion. The site and size of residual myocardial infarction is reliably identified on line, in color. This approach has excellent potential for clinical application.

[Myocardial contrast echocardiography with harmonic power Doppler and lung traversing SHU 563A ultrasound contrast medium for imaging myocardial perfusion disorders]. / Myokardiale Kontrastechokardiografie mit harmonischem Power Doppler Verfahren und dem lungengängigen Ultraschallkontrastmittel SHU 563A zur Darstellung von myokardialen Perfusionsstörungen. Tierexperimentelle Untersuchungen bei akuter Ischämie und nach Reperfusion.

The current approach for the assessment of myocardial perfusion using contrast echocardiography involves black-and-white gray scale imaging in b-mode. For better appreciation of perfusion abnormalities, off-line postprocessing techniques including color encoding are used. In this study, we examined whether we could exploit the contrast microbubble response to high ultrasound amplitude--the phenomenon of stimulated acoustic emission--that could be recorded with harmonic power Doppler (HPD) in color to identify myocardial perfusion defects. To assess the potential of HPD, we occluded branches of the left coronary artery for 2-3 h followed by 1 h reperfusion in 10 dogs. After transvenous administration of the new air-filled contrast agent SHU 563A, echocardiographic imaging was performed with ECG-triggered harmonic b-mode (HBM) and the harmonic power Doppler (HPD) approach in different short (SAX) and long axis (LAX) views. Post-mortem TTC staining was performed to verify infarction. HBM, HPD and TTC data were analyzed by independent observers. During coronary occlusion, HPD with SHU 563A showed perfusion defects in 10 dogs in all SAX and LAX views. HBM demonstrated perfusion defects in all dogs in SAX and in 8 dogs in LAX. The correlation of perfusion defect size between HPD and HBM images was good (SAX: r = 0.9, p < 0.001, LAX: r = 0.7, p < 0.01). One hour after reperfusion, both HPD and HBM showed perfusion defects with SHU 563A in 7 dogs. Five dogs showed TTC evidence of infarction. Perfusion defect size by HPD correlated well with residual infarct size (r = 0.8, p < 0.01), while defect size by HBM showed poor correlation (r = 0.3, p = ns). Myocardial contrast echocardiography with HPD and contrast agent SHU 563A identifies perfusion defects in acute coronary occlusion as reliably as HBM. After reperfusion HPD and SHU 563A accurately portray the site and size of residual myocardial infarction on line, in color. This approach has excellent potential for clinical application.

Quantitative 3-dimensional contrast echocardiographic determination of myocardial mass at risk and residual infarct mass after reperfusion: experimental canine studies with intravenous contrast agent NC100100.

Two-dimensional contrast echocardiography has been shown to enable the evaluation of myocardial perfusion abnormalities. However, its ability to quantify a regional myocardial mass is limited. The goal of this study was to examine the quantitative value of 3-dimensional echocardiography (3DE) in the estimation of myocardial mass at risk, salvaged mass, and residual infarct mass after intravenous injection of contrast. We created acute coronary occlusion, followed by reperfusion in 10 dogs. Three-dimensional echocardiographic data were acquired at the end of each stage, and the perfusion defect mass and dysfunctional mass were measured. The true mass at risk and infarct mass were determined by anatomic methods. The anatomic mass at risk (x) (27.1+/-14.6 g or 23.8%+/-9.7% of the left ventricle [%LV]) correlated well with the 3DE-determined perfusion defect mass (y) during coronary occlusion (y = 0.5x+8.9; r = 0.90; P<.001; mean difference -4.8+/-8.1 g; or y = 0.7x + 6.5; r = 0.83, P<.01; mean difference -0.1+/-5.4 %LV). Good correlation was also found between the anatomic infarct mass (x) (9.3+/-8.1 g or 9.1+/-8.8 %LV) and the 3DE perfusion defect mass after reperfusion (y) (y = 1.2x+1.2; r = 0.93; P<.001; mean difference 2.3+/-4.0 g; or y = 1. 3x, r = 0.98, P <.0001; mean difference 2.7+/-3.7 %LV). The salvaged mass was 13.6 +/-11.0 %LV from anatomic methods and 14.2+/-13.0 %LV by 3DE. To conclude, with the use of intravenous contrast, 3DE could quantify the actual mass at risk during acute ischemia, and in the setting of reperfusion, the residual infarct mass and salvaged mass.

Late (five to nine years) follow-up after balloon dilation of valvular pulmonary stenosis in adults.

The transvalvular gradient was investigated in 14 patients with pulmonary stenosis 5 to 9 years after balloon valvuloplasty. None of the patients had developed restenosis, and in those who had a peak gradient >100 mm Hg before valvuloplasty, the gradient decreased further due to resolution of subvalvular muscular hypertrophy within 3 months after intervention.

Right ventricular function before and after percutaneous balloon mitral valvuloplasty.

Aim of this study was to evaluate right ventricular performance in patients with mitral stenosis and its modification by balloon valvuloplasty. Right ventricular volumes of 24 patients with postrheumatic mitral stenosis were determined by thermodilution 1 or 2 days before and 1 or 2 days after valvuloplasty. Right ventricular ejection fraction at rest was 43 (36-47)% (median and interquartile range). Right ventricular end-diastolic volume was 100 (86-119) ml/m2. Supine bicycle exercise (50 Watt) reduced right ventricular ejection fraction to 30 (29-37)% (P < 0.0001) and increased right ventricular end-diastolic volume to 124 (112-141) ml/m2 (P < 0.0001). At rest, right ventricular ejection fraction correlated inversely with pulmonary vascular resistance (r = -0.64, P < 0.0001), while no significant correlation with mitral valve area was found. Valvuloplasty increased right ventricular ejection fraction at rest to 48 (44-50)% (P < 0.005), and during exercise to 42 (38-45)% (P < 0.0001). This improvement of right ventricular ejection fraction correlated inversely with the value of this parameter before valvuloplasty (r = -0.88, P < 0.0001) and with the gain in stroke volume (r = 0.57, P < 0.01). The right ventricular function curve, disturbed before commissurotomy, was reestablished by the procedure. In conclusion, at the here investigated stage of mitral stenosis right ventricular function is reversibly impaired. This is predominantly caused by the hemodynamic consequences of the valvular defect and not by an impairment of right ventricular myocardial function.

[Balloon dilatation of valvular pulmonary stenoses in adults]. / Ballondilatation valvulärer Pulmonalstenosen bei Erwachsenen.

Balloon valvuloplasty of pulmonary stenosis has become the treatment of choice in children and adults. This is a report about the long term results in adult patients. Forty-six patients (mean age 37 +/- 17 years) with pulmonary stenosis were treated between 1984 and 1994 by this method. Thirty-four of 46 patients were re-examined 3 months to 9 years (mean 3.4 years) later by right heart catheterization and echocardiography. These 34 patients were representative for the whole group concerning age, severity of the pulmonary stenosis, and acute results after the intervention. The pressure gradient was acutely reduced by balloon valvuloplasty from 86 +/- 35 to 38 +/- 17 mm Hg (p < 0.0001) (n = 46) and was 32 +/- 10 mm Hg (n.s.) (n = 34) at follow-up. Within 3 months after the intervention, 8 of 13 patients with a pressure gradient > or = 100 mm Hg, showed spontaneously further reduction of the gradient due to the resolution of the subvalvular muscular hypertrophy. During a bicycle exercise test with 9 patients, the gradient rose significantly from 29 +/- 10 to 53 +/- 23 mm Hg (p < 0.01) as determined by right heart catheterization. All of these patients had normal cardiac output at rest and during exercise. None had signs of right ventricular hypertrophy in the electro- or echocardiogram. It is concluded that balloon valvuloplasty of pulmonary stenosis is the first line treatment in adults.

[Balloon mitral valve commissurotomy in pregnancy]. / Ballon-Mitralkommissurotomie in der Schwangerschaft.

HISTORY AND CLINICAL FINDINGS: A 31-year-old woman with known postrheumatic mitral valve stenosis developed for the first time left heart failure in the 19th week of her fifth pregnancy. After intensive drug treatment she was in stage 3 (New York Heart Association classification). Apart from that the patient was in a good general condition and obstetrical status was according to the estimated duration of pregnancy. Auscultation revealed an apical diastolic murmur and mitral opening snap. INVESTIGATIONS: Echocardiography demonstrated a mitral valve opening area of 0.85 cm2 (pressure-half time method); the mean gradient was 19 mm Hg. TREATMENT AND COURSE: Because of the severity of the findings a percutaneous transvenous balloon valvotomy (according to Inoue) was performed in the 27th week of pregnancy, after careful lead shielding of abdomen and pelvis. Radiological screening time was 10 min. The invasively measured transvalvar pressure gradient was reduced from 28 to 4 mm Hg, echocardiographically determined mitral opening area increased to 1.5 cm2. Delivery was induced in the 36th week of pregnancy because of third-degree renal pelvis congestion. A healthy child, weighing 2850 g was delivered vaginally. CONCLUSION: High-grade symptomatic mitral stenosis can, if necessary, be treated with a low-risk to mother and child by percutaneous balloon valvotomy.

[Interventional closure of an open foramen ovale in a patient with recurrent cerebral ischemia]. / Interventioneller Verschluss eines offenen Foramen ovale bei einer Patientin mit rezidivierenden zerebralen Ischämien.

In a 24-year-old female patient suffering from recurrent ischemia, an aneurysm of the atrial septum and a patent foramen ovale with significant right-to-left shunt during the Valsalva maneuver were detected by means of contrast Doppler echocardiography. After other causes had been excluded, paradoxical embolism was suspected to be the cause of the cerebral symptoms. The defect was closed by a 17-mm Rashkind occluder without complications. Six months later no residual shunt was detected and no further neurological event had occurred. This case demonstrates the feasibility of non-operative closure of those defects. This new technique could represent an alternative to long-term anticoagulation or operative procedures in selected patients.

Dexamethasone-induced sodium influx in human lymphocytes.

We evaluated the direct effects of glucocorticoids on intracellular sodium content and cellular transport systems. Cytosolic free sodium concentration ([Na+]i) was measured in intact human lymphocytes using the sodium-sensitive fluorescent dye sodium-binding benzofuran-isophthalate. Administration of dexamethasone for 60 min increased lymphocytic [Na+]i from 17.6 +/- 2.0 mmol/L to 24.3 +/- 3.9 nmol/L (n = 12; P < 0.01). The dexamethasone-induced [Na+]i increase was abolished in the absence of extracellular sodium, by mifepristone and by actinomycin D. The dexamethasone-induced [Na+]i increase was also seen after inhibition of Na+,K(+)-ATPase by 1 mmol/L ouabain. The present results indicate that dexamethasone produces a trans-plasma membrane sodium influx probably by early occurring genomic effects.

[Closure of an atrial septum defect using an umbrella prosthesis]. / Verschluss eines Vorhofseptumdefektes mittels Schirmprothese.

About three and a half years after direct suture of a secundum atrial septal defect (ASD) the now 72-year-old patient developed heart failure with pulmonary congestion and pleural effusion which responded to medical treatment. The electrocardiogram showed atrial fibrillation with an irregular ventricular rate and right bundle branch block. Right heart catheterization established recurrence of the ASD with a left to right shunt of 60% (Qp/Qs = 2.5) and a pulmonary artery pressure of 45/12 mmHg. Because of the clinical state, the risk of re-operation and the suitable anatomy, non-operative percutaneous transvenous catheter closure of the defect with a double-umbrella device was indicated. Following this procedure the cardiomegaly regressed, while colour-Doppler echocardiography demonstrated a minimal residual left to right shunt. The pulmonary artery pressure had fallen to 32/13 mmHg. Three months later the patient was without symptoms and resumed her usual activity. The ECG now showed sinus rhythm, and there was no evidence of a shunt. Anticoagulation with acetyl salicylic acid (100 mg daily) was continued for 3 months.

Filling state of intracellular Ca2+ pools triggers trans plasma membrane Na+ and Ca2+ influx by a tyrosine kinase-dependent pathway.

The relations between the filling state of intracellular calcium stores that are regulated by the endoplasmic Ca(2+)-ATPase and trans plasma membrane sodium and calcium influx were investigated. The effects of specific inhibition of endoplasmic Ca(2+)-ATPase by thapsigargin, cyclopiazonic acid, and 2,5-di-(tert-butyl)-1,4-benzohydroquinone (BHQ) on cytosolic free sodium concentration ([Na+]i) and cytosolic free calcium concentration ([Ca2+]i) were evaluated in lymphocytes from healthy subjects using the fluorescent dyes sodium-binding benzofuran isophthalate and fura2. The specific inhibition of endoplasmic Ca(2+)-ATPase by thapsigargin, cyclopiazonic acid, or BHQ increased lymphocytic [Na+]i and [Ca2+]i. The thapsigargin-induced [Na+]i increase was abolished in the absence of external sodium, indicating that thapsigargin induced a trans plasma membrane sodium influx. In the absence of external calcium the thapsigargin-induced [Ca2+]i increase was significantly reduced, whereas the thapsigargin-induced [Na+]i increase remained the same. This finding indicates that the filling state of intracellular calcium pools rather than the elevation of [Ca2+]i per se regulates the plasma membrane permeability for sodium in lymphocytes. The inhibition of the tyrosine kinase by genistein inhibited the thapsigargin-induced increases of both [Na+]i and [Ca2+]i in lymphocytes. The present study shows that the filling state of intracellular thapsigargin-sensitive calcium pools regulates trans plasma membrane sodium and calcium influx via a tyrosine kinase-dependent pathway.

Effect of magnesium on cytosolic free sodium in human lymphocytes.

Cytosolic free sodium concentration ([Na+]i) was measured in intact human lymphocytes using the novel sodium-sensitive fluorescent dye sodium-binding benzofuran-isophthalate. In the presence of 1 mmol/l external Mg2+ the resting [Na+]i was significantly lower compared to the value in the absence of external Mg2+ (22.7 +/- 1.1 mmol/l vs. 37.6 +/- 1.4 mmol/l; p < 0.0001). The thapsigargin induced [Na+]i increase was significantly lower in the presence of 1 mmol/l external Mg2+ compared to the value in the absence of external Mg2+ (73.4 +/- 6.0 mmol/l vs. 120.7 +/- 5.8 mmol/l; p < 0.001). Since Mg2+ is known to be a cofactor of the membrane Na+,K(+)-ATPase these measurements in intact lymphocytes indicate that deprivation of external Mg2+ causes an increase of [Na+]i.

[Right ventricular function in patients with rheumatic mitral valve stenosis. Effect of balloon mitral valvuloplasty]. / Rechtsventrikuläre Funktion bei Patienten mit rheumatischer Mitralstenose. Effekt der Ballon-Mitralvalvuloplastie.

UNLABELLED: Postrheumatic mitral stenosis might cause impairment of right ventricular (RV) function due to both an increase in RV afterload and rheumatic myocardial disease. Therefore, we investigated in 19 patients with postrheumatic mitral stenosis and sinus rhythm right ventricular volumes and hemodynamics by a computerized thermodilution catheter during rest and supine bicycle exercise. In 14 patients the investigation was repeated within 2 days after balloon mitral valvuloplasty. Resting RV ejection fraction was decreased (43 (15-53)%, median (range)) and correlated significantly with RV end-systolic volume index (r = -0.90), stroke volume index (r = 0.77), RV end-diastolic volume index (r = -0.76), heart rate (r = -0.69), pulmonary artery resistance (r = -0.69), and mean pulmonary artery pressure (r = -0.68). RV end-diastolic volume index was 107 (81-200) ml/m2. Exercise induced a decrease of RV ejection fraction to 36 (13-48)% at 50 Watt (p < 0.001), while it increased RV end-diastolic volume index to 131 (78-231) ml/m2 (p < 0.001). Balloon mitral valvuloplasty improved RV ejection fraction at rest from 41 (15-47)% to 48 (39-55)% (p < 0.005) and from 30 (13-46)% to 43 (27-56)% during exercise (p < 0.005). The increase of RV ejection fraction after valvuloplasty was caused by an increase in stroke volume, but not by a reduction in RV end-diastolic volume. CONCLUSION: Depending on the increased RV afterload, RV function is markedly depressed in mitral stenosis. An immediate and almost complete improvement of RV function occurs with the reduction of RV afterload after balloon mitral valvuloplasty.(ABSTRACT TRUNCATED AT 250 WORDS)

[Resorbable antibiotic delivery systems in local treatment of chronic osteitis--polyglycolic acid/poly-L-lactide as drug carrier. Experimental studies in vitro]. / Resorbierbare Antibiotikumträger zur lokalen Behandlung der chronischen Osteitis--Polyglykolsäure/Poly-L-Laktid als Träger. Experimentelle Untersuchungen in vitro.

Resorbable polyglycolic acid (PGA)- and poly-L-lactic acid (PLLA) cylinders were investigated in vitro to explore their properties as an antibiotic deposit (Ciprobay, Bayer Leverkusen) with prolonged release. PGA cylinders sized 3.2 x 5 mm, 4.5 x 5 mm and 4.5 x 7 mm respectively were shaped in monofil and polyfil technique. The Ciprofloxacin concentration varied from 0.5 mg to 5.0 mg of each cylinder. The cylinders were eluated in phosphate buffer, pH-value of 7.4, at 37 degrees C. The daily antibiotic release was measured by high performance liquid chromatography. Best combinations we could find demonstrated an initial delivery of Ciprofloxacin in vitro of 67 mg/l. The average daily release was about 16 mg/l during the first 36 days. After complete hydrolysis of the PGA carriers the recovery of Ciprofloxacin reached up to 6.5% and 11.6% respectively. For 40 bioactive cylinders (size phi 3.5 mm x 5 mm, containing 4 mg Ciprofloxacin) were eluated with phosphate buffer (pH 7.4 at 37 degrees C) respectively fresh human blood plasma and tested under various conditions. A gentamicin-polymethylmetacrylate (PMMA) chain (Septopal, E. Merck, Darmstadt) was exposed to equal test conditions for comparison. The quantities of released Ciprofloxacin and Gentamicin were analysed by a microbiological method (bioassay). Initially released rates of Ciprofloxacin were measured very high (up to 180 mg/l) but decreased rapidly within the first 5 days (4.2-22.5 mg/l). The release of Gentamicin produces an initial sharp decrease in concentration during the first 3 days (from 227.5 mg/l to 77.5 mg/l); this is then followed by an almost constant release over a long period of time (about 20 mg/l).(ABSTRACT TRUNCATED AT 250 WORDS)

Ciprofloxacin-impregnated poly-L-lactic acid drug carrier. New aspects of a resorbable drug delivery system in local antimicrobial treatment of bone infections.

Resorbable poly-L-lactic acid (PLLA) cylinders (3.5 mm diameter, 5 mm in length) carrying 6% of weight ciprofloxacin (Ciprobay, Bayer AG, Leverkusen, FRG) were investigated in vitro to explore their properties as a slow-release antibiotic deposit. Forty bioactive cylinders stored in test tubes were covered with phosphate buffer (pH 7.4 at 37 degrees C) and 40 with fresh human blood plasma and tested under various conditions. For comparison a gentamicin-polymethylmethacrylate (PMMA) chain (Septopal, E. Merck, Darmstadt, FRG) was exposed to similar test conditions. The quantities of ciprofloxacin and gentamicin released were analysed by a microbiological method (bioassay). The concentrations of ciprofloxacin released were analysed by a microbiological method (bioassay). The concentrations of ciprofloxacin released from 40 cylinder were initially very high (up to 180 mg/l) but they decreased rapidly within the first 5 days (4.2-22.5 mg/l). Early release of gentamicin reached up to 227.5 mg/l but dropped to of 22 mg/l on the 14th day. Complete degradation of the PLLA-cylinders was not seen in the observed period of 92 days. The mean loss of mass was 8.4%. The recovery of incorporated ciprofloxacin was 6.5% on average.