Igor Huk

l-Arginine Treatment Alters the Kinetics of Nitric Oxide and Superoxide Release and Reduces Ischemia/Reperfusion Injury in Skeletal Muscle

BACKGROUND Constitutive nitric oxide synthase (cNOS) may produce species involved in ischemia/reperfusion (I/R) injury: NO in the presence of sufficient L-arginine and superoxide at the diminished local L-arginine concentration accompanying I/R. METHODS AND RESULTS During hindlimb I/R (2.5 hours/2 hours), in vivo NO was continuously monitored (porphyrinic sensor), and L-arginine (chromatography), superoxide (chemiluminescence), and I/R injury were measured intermittently. Normal rabbits were compared with those infused with L-arginine 4 mg x kg(-1) x min(-1) for 1 hour. In both groups, approximately 6 minutes into ischemia, a rapid increase of NO from its basal level of 50+/-17 to 115+/-7 nmol/L, P<.005 (microvessels), was observed. In animals not treated with L-arginine, NO dropped below basal to undetectable levels (<1 nmol/L) during reperfusion. In animals treated with L-arginine, the decrease of NO was slower, such that substantial amounts accumulated during reperfusion (25 nmol/L). Decreased NO during I/R was accompanied by increased superoxide, which during reperfusion reached 50 nmol/L without or 23 nmol/L with L-arginine treatment. Calcium-dependent cNOS was a major source of superoxide release (inhibited 70% by L-NMMA and 25% by L-NAME) during I/R. CONCLUSIONS L-Arginine treatment decreased superoxide generation by cNOS while increasing NO accumulation, leading to protection from constriction (microvessel area, 17.77+/-0.95 versus 11.66+/-2.21 microm2 untreated, P<.0005) and reduction of edema after reperfusion (interfiber area, 16.56+/-2.13% versus 27.68+/-7.70% untreated, P<.005).

Chlamydia pneumoniae in Carotid Artery Atherosclerosis A Comparison of Its Presence in Atherosclerotic Plaque, Healthy Vessels, and Circulating Leukocytes From the Same Individuals

Background and Purpose— There is growing clinical and experimental evidence that infections with Chlamydia pneumoniae might contribute to the development and progression of atherosclerosis. However, studies detecting the pathogen in atherosclerotic lesions examined either only atherosclerotic vessels or control vessels without atherosclerosis obtained from a different group of individuals. We analyzed atherosclerotic plaques of the carotid artery, samples of apparently healthy greater saphenous veins, and circulating leukocytes from the same individual patients for the presence of C pneumoniae. Methods— From each of 46 patients undergoing carotid endarterectomy for symptomatic carotid artery stenosis, these samples were analyzed by nested polymerase chain reaction for C pneumoniae–specific DNA. Furthermore, we determined IgA and IgG titers specific for the pathogen and plasma levels of C-reactive protein in these patients. Results— C pneumoniae DNA was detected in 86.9% of the leukocytes and in 82.6% of the atherosclerotic plaques but in only 6.5% of the saphenous veins. In 85% of patients who also had leukocytes positive for C pneumoniae, the atherosclerotic plaques were positive and the saphenous veins were negative. The presence of C pneumoniae–specific DNA in leukocytes significantly coincided with the presence of the respective DNA in the plaques of the carotid arteries (P =0.0002). No association between the presence of C pneumoniae and specific IgA or IgG levels was seen. C-reactive protein levels were significantly higher in patients with chlamydia-positive atherosclerotic plaques and with positive leukocytes than in patients with negative plaques of the carotid arteries or negative leukocytes, respectively (P <0.01, P <0.05). Conclusions— Our observation of >80% incidence of C pneumoniae in atherosclerotic plaques of the carotid artery does not prove causality between an infection with the pathogen and the development of atherosclerosis. It must be emphasized, however, that >90% of apparently healthy saphenous veins were negative for C pneumoniae. Given the structural and functional differences between veins and arteries, careful interpretation of our results regarding a possible causative role of C pneumoniae seems warranted.

Patency Rate of Implantable Devices During Long-Term Intraaterial Chemotherapy

Intrarterial implantable drug delivery systems have been considered as an alternative method for treating patients with unresectable liver malignancies. However, catheter problems with external implanted devices have resulted in limited application of chemotherapy. The introduction of subcutaneous devices offers an opportunity for long-term locoregional chemotherapy. Twelve external intraarterial catheters were implanted into 12 patients and 52 subcutaneously placed devices into 51 patients, all with various hepatic malignancies. Retrospec tive analyses comparing those two intraarterial systems were conducted taking into account the function and complication rate (hepatic artery thrombosis, infection, leaking, hemorrhage, and dislocation). The follow-up time for the external system was two to eight months (median five weeks), the thrombosis rate 33.3%, and the infection rate 25%. One instance of severe bleeding from the hepatic artery occurred during chemotherapy. One catheter dislocated. For the subcutaneously implanted intraarterial devices the follow-up time was five to forty-one months (median sixteen months), the thrombotic complication rate 17.3%, and the infection rate 7.6% (all patients with simultaneous bowel sur gery). Catheter dislocation one year later required reimplantation; in 1 patient therapy had to be discontinued because of a catheter leak. The overall function rate was 71.3% with a median follow-up time of eight months. Anticoagulation therapy for subcutaneously implanted devices starting from the beginning of intraarterial chemotherapy is recommended to achieve long-term patency. No implantation should be performed simultaneously with bowel surgery. The sub cutaneously placed intraarterial devices had a higher function rate and were available for a longer period as compared with external implanted catheters.

Influence of a short-term acute ischemia and reperfusion on skeletal muscle metabolism and morphology in rabbits

The duration of the ischemia and reperfusion of the limbs determines the extent of tissue damage. The purpose of this study was to validate anin vivo model of ischemia-reperfusion injury with a short-term ischemic period of 1 hour which is comparable to several clinical situations. Thirteen New Zealand rabbits were randomly assigned to either (1) the sham operation (control), or (2) ischemiareperfusion group response to 1 hour of ischemia followed by 2 hours of reperfusion. Ischemia was created by clamping bilateral common femoral arteries and tourniquet occlusion of collateral circulation. Alterations of plasma potassium, malondialdehyde (MDA), muscle tissue intercellular thromboxane B2 (TxB2) concentrations, and morphometric determinations of skeletal muscle were parameters used to quantify reperfusion injury. Interstitial edema (median fraction of muscle interfiber area was 16.57% vs 13.39% in control,p=0.02), muscle cell shrinkage (median muscle fiber area was 3.70×103 μm2 vs 4.55×103 in control,p= 0.04), increased plasma potassium (median 4.7 mmol/L vs 3.6,p=0.02) in 2 hours and increased interstitial TxB2 in 1 hour were manifestation of reperfusion injury. We conclude that expansion of the extracellular space not accompanied by changes of plasma MDA may indicate that lipidperoxidation in reperfused muscle was negligible and interstitial edema was related to thromboxane A2 synthesis.

Measurement of Nitric Oxide in Single Cells and Tissue Using a Porphyrinic Microsensor

This unit describes the preparation and applications of porphyrinic sensors for quantitative measurement of nitric oxide (NO) in single cells and in tissues. The determination of NO is based on the electrochemical oxidation of NO on a carbon fiber electrode covered with a thin layer of a conducting polymeric metalloporphyrin catalyst, overlaid with another thin film of Nafion, a cation exchange material. The electric current generated during NO oxidation on the surface of the polymeric porphyrin is linearly proportional to the concentration of NO, so this current is used as an analytical signal which can be measured in either the amperometric or the voltammetric mode. Both methods provide a quantitative signal. This unit describes the electrochemical setup for measurement of NO in single cells and tissue. Support protocols describe porphyrin synthesis, sensor preparation, and sensor calibration.

Operative therapie der choledocholithiasis bei einem negativ selektionierten krankengut

ZusammenfassungEs wird über 612 Choledochuseingriffe (davon 222 Rezidive) während eines Zeitraumes von 7 Jahren an einem negativ selektionierten Krankengut berichtet. In 43,3% der Fälle wurde die Choledochotomie mit T-Drain abgeschlossen, in 29,6% transduodenal sphinkterotomiert und in 27,1% eine biliodigestive Anastomose angelegt. Die transduodenale Sphinkterotomie zeigt durch Beschränkung auf ihre absolute Indikation eine rückläufige Operationsfrequenz. Bei 3,4% blieben Residualkonkremente zurück. Die Letalität im gesamten Krankengut betrug 4%, eine signifikante Erhōhung fand sich ab einem Alter von 65 Jahren. Verbesserungen der Ergebnisse scheinen durch eine konsequente intraoperative Diagnostik mōglich.Summary612 operations of the common bile duct (222 reoperations) during 7 years are reported. In 43,3% the choledochotomy was finished with a T-tube, in 29,6% transduodenal sphincterotomy and in 27,1% biliodigestive anastomoses were performed. Transduodenal sphincterotomy shows due to restriction in indication a decreasing frequency. In 3,4% retained stones were found by postoperative cholangiography. Lethality was 4%, a significant rising was found in patients older than 65 years. More consequence in intraoperative diagnosis should improve results.

Inflammatory Abdominal Aortic Aneurysms

Inflammatory aneurysms of the abdominal aorta (inflammatory AAAs) are a distinct clinicopathological entity, different from typical atherosclerotic abdominal aneurysms (atherosclerotic AAAs).1 Marked lamellar and perianeurysmal fibrosis, a thick aneurysm wall, and adhesions to the surrounding organs are characteristic pathological features of inflammatory AAAs.2,3

209. Zur Kritik der Indikation der Dünndarm-Bypass-Operation bei extremer Fettsucht

SummaryFrom 1972–1978 a 40:20 cm end to end jejunoileal bypass was applied to 34 patients on strictest indication. 5 patients suffered from postoperative complications which could easily be controlled. 15 patients suffered from late complications like serious electrolyte imbalance, diarrhea, abnormal liver function or vitamin and iron deficiency. Restoration of intestinal continuity had to be done on two patients. Because of these complications, the gastric bypass is more often used, which is less inclined to provoke these complications.ZusammenfassungVon 1972–1978 wurden bei strengster Indikation in 34 Fällen ein 40:20 cm End-zu-End jejunoilealer Bypass angelegt. Bei 5 Patienten traten postoperativ leicht beherrschbare Komplikationen auf. Bei 15 Patienten wurden Spätfolgen festgestellt. Es handelte sich um rezidivierende schwere Elektrolytentgleisungen, Diarrhoen, pathologische Leberfunktionsproben, Vitamin- und Eisenmangelerscheinungen. Bei 2 Patienten mußte der Bypass aufgelassen werden. Wegen der sich häufenden Spätfolgen wird seit Oktober 1978 nur noch der komplikationslosere Magen-Bypass durchgeführt.