Peter Drescher

COMPARISON OF IODINATED CONTRAST MEDIA-INDUCED RENAL VASOCONSTRICTION IN HUMAN, RABBIT, DOG, AND PIG ARTERIES

RATIONALE AND OBJECTIVES Contrast media (CM)-induced renal vasoconstriction is an important factor in the pathogenesis of CM-induced nephrotoxicity. The effects of ionic, high-osmolar CM sodium/meglumine diatrizoate and nonionic, low-osmolar CM iohexol and iopamidol were studied in rabbit, dog, and pig renal arteries and compared with human tissue in an organ bath. METHODS Isometric contractions were induced by increasing concentrations of CM and high-osmolar glucose solution. RESULTS Contrast media and glucose elicited contractions in human renal arteries of 32% (diatrizoate), 20% (iohexol), 30% (iopamidol), and 22% (glucose). Rabbit and dog renal arteries demonstrated contractions of 30% and 46% (diatrizoate), 15% and 23% (iohexol), 15% and 26% (iopamidol), and 11% and 40% (glucose), respectively, of the control. There was a vasorelaxing effect of all CM tested on pig renal artery. CONCLUSIONS Responses in rabbit and dog renal arteries were similar to those in human renal arteries and could serve as models for investigating CM-induced renal vasoconstriction.

Longitudinal Quality of Life Assessment of Patients with Hepatocellular Carcinoma after Primary Transarterial Chemoembolization

PURPOSE To determine the effects of primary chemoembolization on the health-related quality of life (HRQOL) of patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS Single-center prospective data collection with longitudinal analysis of HRQOL scores obtained via the Short Form-36 (SF-36) assessment tool was performed before and during serial chemoembolization procedures in 73 patients with HCC. Baseline HRQOL scores were evaluated for significant (P < .05) change within the total patient population during 4, 8, and 12 months of treatment, and separately within a subset of 23 patients who underwent three or more chemoembolization procedures. RESULTS Patients had decreased pretreatment baseline scores within all eight scales of the SF-36 compared with healthy age-adjusted norms. Within the total population, mental health scores improved after 4 months of chemoembolization (rate of change, 5.6; P = .05; n = 48), but no significant change was present at 8 or 12 months. Subset patients experienced improvements of mental health scores after the first (score change, 13; P = .008; n = 21) and second procedures (score change, 12.2; P = .002; n = 23) and improvements of bodily pain scores (score change, 9.9; P = .047; n = 21) after the initial procedure. Vitality scores worsened (score change, -7.8; P = .044; n = 21) in the subset after the first chemoembolization. CONCLUSIONS Patients with HCC are likely to perceive improved mental health during the first 4 months of primary treatment with chemoembolization. In addition, if patients ultimately undergo more than two procedures, they are likely to perceive improved mental health during the first two sessions, with decreased bodily pain during the initial session. Patient-perceived vitality will likely worsen after the initial procedure.

Initial Experience with the Combination of Reteplase and Abciximab for Thrombolytic Therapy in Peripheral Arterial Occlusive Disease: A Pilot Study

PURPOSE To report the efficacy of catheter-directed thrombolysis with a combination of a thrombolytic agent (reteplase) and a glycoprotein (GP) IIb/IIIa platelet receptor antagonist (abciximab) in peripheral arterial occlusive disease. MATERIALS AND METHODS Fifteen patients with lower extremity arterial thromboses (age range, 40-96 y; mean, 73 y) were prospectively enrolled in a protocol approved by the Institutional Review Committee. Nine patients had native arterial occlusions, three (33%) of whom had subacute symptoms (>14 d) and one of whom had chronic symptoms (>3 mo). Four patients had acute arterial graft thromboses. Two patients with lower extremity bypass grafts presented with subacute limb ischemia. All patients received catheter-directed infusion of reteplase (0.5 U/h) in combination with intravenous administration of abciximab (0.25-mg/kg bolus followed by 0.125 microg/kg/min infusion) for 12 hours without systemic heparinization. The thrombolytic success was studied by Doppler ultrasonography (US) and angiography. RESULTS Complete thrombolysis and clinical success was achieved in 14 of the 15 patients (93%). One patient with unsuccessful thrombolysis underwent major amputation. The mean thrombolysis time per Doppler US procedure was 6.8 hours (range, 2-30 h). Angiographic patency was achieved at a mean of 17.5 hours (range, 4-36 h) corresponding to a mean dose of reteplase of 8.8 U. The mean increase in ankle-brachial index was 0.52 (range, 0-0.9). No major hemorrhagic complications occurred. The 30-day primary patency rate was 93%. CONCLUSION The combination of reteplase and abciximab in catheter-directed arterial thrombolysis is feasible and effective. This combination therapy pilot study suggests short thrombolysis times and minimal adverse effects in catheter-directed thrombolytic therapy for peripheral arterial occlusive disease.

Prevention of contrast medium-induced renal vasospasm by phosphodiesterase inhibition.

RATIONALE AND OBJECTIVES This study investigated the involvement of cyclic adenosine monophosphate (cAMP) in contrast medium-induced renal vasomotor effects and the efficacy of selective phosphodiesterase (PDE) inhibitors influencing cAMP in preventing contrast medium-induced renal vasospasm. METHODS Isometric contractions of rabbit renal artery rings were subjected to increasing concentrations of the ionic contrast medium sodium/meglumine diatrizoate (DIA) and the nonionic contrast media iopamidol (IOP) and iodixanol (IOD) and compared with a potassium chloride control. Subsequently increasing concentrations of the nonselective phosphodiesterase inhibitors theophylline and papaverine and the following selective phosphodiesterase inhibitors were applied: vinpocetine, trequinsin, zardaverine, rolipram, and dipyridamole (subtypes I-V) before restimulation of the arterial tissue with contrast medium. RESULTS Diatrizoate, iopamidol, and iodixanol induced contractions up to 30%, 15%, and 3.5% of the potassium chloride control, respectively. All phosphodiesterase inhibitors markedly inhibited the contrast medium-induced contractions in a dose-dependent manner. The selective phosphodiesterase inhibitors rolipram and trequinsin attenuated these contractions significantly more (92% and 94%) than did zardaverine, dipyridamole, and vinpocetine, with an inhibitory potency of 37%, 41%, and 62%, respectively. CONCLUSIONS Nonionic contrast media induced renal vasoconstriction less potently than ionic contrast media. Significant differences in the ability to prevent contrast medium-induced vasoconstriction were observed among the various phosphodiesterase subtypes studied. selective phosphodiesterase inhibition with inhibitor subtypes II and IV showed the most promising results in specifically preventing contrast medium-induced renal vasospasm.

Variable effects of iodinated contrast media on different rabbit arteries in vitro

Vasoconstriction caused by iodinated contrast media (CM) has been considered specific for the renal artery only. We examined the vascular effect of CM in rabbit carotid, aorta, renal, iliac, mesenteric and celiac arteries and found that other arteries also respond with a contraction to CM. Isolated arterial rings were exposed to diatrizoate (high osmolar CM), iohexol (low osmolar CM) or glucose solution, and the isometric contraction response was expressed as percentage of an initial KCl control contraction. Diatrizoate evoked contractions of 82% (carotid), 63% (aorta), 30% (renal), 24% (iliac), 28% (mesenteric) and 18% (celiac), respectively. Iohexol caused contractions of 31% (carotid), 24% (aorta), 15% (renal) and 14% (iliac), whereas the mesenteric and celiac arteries were relaxed by iohexol. A high osmolar glucose solution elicited contractions of 78%, 77%,11%, 27%, 3% and 5%, respectively, in the arteries. CM have contraction potency in arterial vasculature other than the renal artery.

Attenuation of contrast material-induced renal artery vasoconstriction by nitric oxide donors.

RATIONALE AND OBJECTIVES The authors studied the role of the endothelium and associated endothelial pathways in contrast material-induced renal vasoconstriction. MATERIALS AND METHODS Isometric contractions in human and rabbit renal artery rings with intact and denuded endothelium were stimulated with phenylephrine and increasing concentrations of the ionic contrast material diatrizoate, the nonionic contrast materials iopamidol and iomeprol, and the dimeric contrast material iodixanol in a tissue perfusion bath. Rings with intact endothelium were incubated with endothelium-stimulating compounds such as the NO synthetase inhibitor Ng nitro-L-arginine methyl ester (L-NAME) to study the endothelium-mediated vasomotor regulation and the NO-liberating substances molsidomine (SIN-1) and nitroprusside (NPR) to study the endothelial-mediated vasorelaxation before being stimulated with contrast material. RESULTS Contrast material-induced, dose-dependent, reversible renal artery contractions are dependent on the type of contrast material. No differences in the contractions were found between intact and denuded rings. L-NAME had no effect on contrast material-induced contractions. Contractions were inhibited by the NO donors SIN-1 and NPR. SIN-1 was the most potent inhibitor. CONCLUSION Contrast material-induced renal vasoconstriction is endothelium-independent. Selective pharmacologic stimulation of the endothelium by NO donors, however, may still be useful in the prophylaxis of contrast material-induced renal vasoconstriction and, thus, potentially nephrotoxicity.

Vascular response to gadolinium-containing contrast media in an ex vivo rabbit arterial model.

Rauch D, Bohnemann L, Kurtz C, et al. Vascular response to gadolinium-containing contrast media in an ex vivo rabbit arterial model. Invest Radiol 2001;36:589–596. rationale and objectives. To assess the influence of gadolinium-containing magnetic resonance contrast agents on contractility of the arterial vessel wall. methods.Bilateral segments of rabbit carotid arteries were mounted in flow chambers, surrounded by aerated (95% O2, 5% CO2) Krebs’ solution, and perfused at a constant rate by separated and aerated Krebs’ solution. Therefore, changes in pressure of the circulating Krebs’ solution indicated alterations of vessel wall contractility. Viability of the artery was tested by 124 mmol/L KCl, 3 × 10−5 mol/L phenylephrine, and 10−5 mol/L acetylcholine. After a washout phase, gadopentate (n = 10) or gadoteridol (n = 10) was added to the perfusate of one carotid artery in increments of 0.1, 0.3, and 0.6 mmol/L. Concentrations up to 0.9 mmol/L and 1.2 mmol/L were tested, respectively. The contralateral artery served as a control. To assess potential relaxing effects of the media, vessels were brought into a contracted status with 3 × 10−5 mol/L phenylephrine and then received gadolinium chelates. results.Potassium chloride and phenylephrine increased and acetylcholine decreased the pressure, indicating vasoconstriction and vasodilatation, respectively. After gadopentate and gadoteridol infusion, no statistically significant pressure changes could be detected, ruling out any vasoconstrictor or vasodilator effect. conclusions.Gadopentetate and gadoteridol in doses of up to 1.2 mmol/L did not alter vessel wall tone. The impact of contrast media on blood pressure, as has been shown in some clinical trials, probably is not due to direct changes in arterial wall tone.

Effect of contrast medium on corpus cavernosum smooth muscle.

RATIONALE AND OBJECTIVES Changes in contractility of corpus cavernosum (CC) smooth muscle caused by radio contrast medium may result in misinterpretations of cavernosography used diagnostically in erectile dysfunction. METHODS The authors investigated the direct effect of various contrast media on rabbit CC smooth muscle tissue strips in an in vitro model by adding contrast medium to the tissue in a perfusion bath and recording the resulting contractions. Glucose addition was used as control. RESULTS Application of high-osmolar, ionic contrast medium diatrizoate-induced CC smooth muscle contractions of 57% of the control potassium chloride (124 mM) induced contractions. The low-osmolar (862 mOsm/kg) nonionic monomer contrast medium, iohexol, and the iso-osmolar (300 mOsm/kg) nonionic-dimer contrast medium, iodixanol, elicited contractions of 34% and 36% of the potassium chloride control contractions, respectively. High- and Iso-osmolar glucose solutions caused contractions of 51%, 38%, and 24% of the control, respectively. Cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) regulate CC smooth muscle contractions. These are influenced by different drugs including phosphodiesterases (PDEs), forskolin, and 3-morpholinsydnonimine hydrochloride (SIN-1). The nonspecific PDE inhibitors papaverine (0.1 mM) and theophylline (1 mM) reduced the contrast medium-induced contractions to 66% and 69%, respectively. The specific PDE inhibitor milrinone (0.1 mM) reduced the contractions to 69%; 0.1 mM forskolin and SIN-1 reduced the contractions to 34% and 41%, respectively. CONCLUSIONS Contrast medium induces CC smooth muscle contractions, depending mainly on the osmolality of the solution. The contractions are reduced but not abolished by elevating the intracellular cAMP and cGMP concentrations. The clinical applications in cavernosography are discussed.

Sparfloxacin, Temafloxacin, Difloxacin, and Ciprofloxacin in the Treatment of Acute Prostatitis: An Experimental Model in Rats

The pharmacokinetics of sparfioxacin, temafloxacin, and difloxacin were investigated in rats under steady-state conditions. After an IV bolus injection of 10 mgJkg, continuous infusion of sparfloxacin (2 mg/kg/hour), temafloxacin (0.5 mgJkgJ hour), or difloxacin (2 mgJkgJhour) was given for 2 hours. Drug concentrations were determined by bioassay. All 3 drugs concentrated in the prostate. The prostatic tissue: serum concentration ratios were 3.9 ± 0.7 for sparfioxacin, 1.8 ± 0.6 for temafloxacin, and 1.8 ± 0.7 for difloxacin. The serum concentrations of all 3 drugs were well above their MIC for Escherichia coli (sparfioxacin 0.02 mgJL; temafloxacin 0.05 mgfL; difloxacin 0.25 mgfL). The urine concentrations were 3 to 80 times greater than the serum concentrations. Acute prostatitis was induced by intravesical inTable I. Number of cfu/g of tissue after 3 days of treatment with sparfloxacin, temafloxacin, difloxacin or ciprofloxacin in rats with experimental Escherichia coli prostatitis