Frequency and effects of extravasation of ionic and nonionic CT contrast media during rapid bolus injection

PURPOSE: To determine the frequency and clinical effects of extravasation related to rapid bolus infusion of ionic and nonionic contrast media. MATERIALS AND METHODS: Records of 5,106 computed tomographic studies in adult patients who underwent mechanical bolus injection of contrast medium through a plastic cannula in an upper extremity were retrospectively reviewed. RESULTS: Mean infusion rate was 2.8 mL/sec (range, 1-5 mL/sec). Extravasation occurred in 48 (0.9%) patients, including in four of 928 patients who received the median injection rate (2.5 mL/sec). Injection rate was not correlated with frequency or amount of extravasation. Average age and use of ionic versus nonionic contrast medium were identical in patients with and in those without extravasation. There was no sex difference. Thirty-one patients had extravasation of ionic contrast medium; nine of these had extravasation of at least 50 mL. Seventeen patients had extravasation of nonionic contrast medium; seven of these had extravasation of at least 50 mL. Hyaluronidase infiltration was often used as treatment for larger extravasations (in 10 patients each with extravasation of ionic or nonionic medium). No patient required surgical intervention, and none had severe or permanent long-term effects. CONCLUSION: The frequency of extravasation of contrast medium after mechanical bolus injection is higher than that reported for hand-injection or drip-infusion techniques, but there is no correlation between injection rate and extravasation frequency.     

Glucose induces glucose 6-phosphatase hydrolytic subunit gene transcription in an insulinoma cell line (INS-1)

OBJECTIVE: The goal of our study was to determine the effect of contrast material injection rate and patient demographic variables on vascular enhancement for abdominal CT angiography and compare test injection results with actual patterns of vascular enhancement. SUBJECTS AND METHODS: One hundred twenty-five patients underwent abdominal CT angiography. For each patient, CT attenuation values (Hounsfield units) of the aorta were determined before and after IV contrast administration, every 3 sec between 21 and 60 sec. A peak aortic enhancement value and the time needed to reach peak and aortic enhancement thresholds of 150 and 200 H were determined. All patients received 150 ml of nonionic contrast material at 3 ml/sec in 25 patients and 4 ml/sec in 100 patients. A test injection of 15 ml was used to compute a scan delay in 46 patients. Patient age, sex, weight, injection rate, and test injection results were compared with vascular enhancement patterns. RESULTS: For the 125 patients, the mean aortic enhancement at each time point was greater than 150 H. Patient weight was inversely correlated (r2 = -.62) with aortic enhancement. The test injection did not accurately predict actual aortic enhancement peak value or time. Test injection delay time was significantly correlated with time to reach aortic enhancement thresholds of 150 and 200 H. The 4 ml/sec rate resulted in a higher peak aortic enhancement (320+/-58 H versus 281+/-49 H) (mean +/- SD, p < .01) that was reached quicker than with the 3 ml/sec injection rate (45+/-5 sec versus 52+/-5 sec) (p < .01). Injecting at 4 ml/sec resulted in greater aortic enhancement values at 24-45 sec, whereas 3 ml/sec produced significantly better aortic enhancement at 54-60 sec. CONCLUSION: The test injection correlated better with time to reach specific aortic enhancement thresholds than with time to peak aortic enhancement. For a given amount of contrast material, faster injection rates resulted in greater vascular enhancement that occurred earlier.     

Topoisomerase I inhibitor with potential radiosensitizing effect

The principal aim of this study was to evaluate, on biochemical grounds, whether injection of a low-osmolar nonionic contrast medium (iohexol) can induce a prothrombotic state and/or a change in fibrinolysis. Fifteen patients were submitted to urographic examination and the assays listed below were performed: before the injection (T0), 1 h after (T1), and 24 h after (T24) the injection of the contrast medium. The following assays were performed: fibrinopeptide A (FPA), prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT) and D dimer (D-D). The assays were carried out on 6 of the patients to whom a saline infusion was administered. Only a mild statistically significant increase was found in FPA levels at 1 h after injection of the contrast medium (mean and CI 95%: T0 4.4, 3.7-5.5; T1 6.0, 4.9-9.1; p = 0.003). F1+2, TAT and D-D did not show any significant change after the injection. These findings show that after injection of iohexol, only a mild, though statistically significant, increase in FPA levels was observed as an expression of increased thrombin activity. In the absence of any significant increases in TAT, F 1+2 and D-D, we have no evidence of a prethrombotic state.     

Aspirin and fraxiparine in the prevention of laser induced thrombosis in the presence of iodinated contrast media

The purpose of this study was to investigate the thromboembolic properties of ionic and nonionic contrast media in rats pretreated with aspirin and/or fraxiparine using an experimental model of laser induced thrombosis in the mesenteric microvessels of 17 groups of five male Wistar rats each. Two ionic (ioxaglate and diatrizoate) and two nonionic contrast media (iopamidol and iohexol), alone or associated with antithrombotic drugs (aspirin and/or fraxiparine) were studied. To evaluate the effects of these substances in this model, the number of laser beams needed to induce platelet thrombus formation, the number of emboli detached from the thrombus and the duration of embolization were quantified. Platelet aggregation induced by ADP, induced hemorrhagic time (IHT) and haemoglobin loss level were also determined. Both contrast media injected at 3 ml/kg caused a significant increase in the number of emboli and the duration of embolization (p<0.05). Pretreatment with aspirin and/or fraxiparine in the presence of ionic contrast media showed antithrombotic activities equal to those obtained when they were tested alone (p<0.05), while in the presence of nonionic contrast media, these drugs only neutralised the prothrombotic effects. There were no differences with the NaCl treated group (p>0.05). The ionic contrast media, and to a lesser extent the nonionic contrast medium: iohexol, inhibited platelet aggregation, while iopamidol behaved as an activator. The antithrombotic drugs tested in this study prevent the prothrombotic activities of contrast media therefore suggesting their use before radiographic procedures.     

Effects of iodinated contrast media on pulmonary airway resistance in anesthetized guinea pigs

RATIONALE AND OBJECTIVES: Bronchospasm is occasionally observed following iodinated X-ray contrast medium administration. We performed an in vivo study in guinea pigs to investigate the effects of a number of iodinated contrast media on pulmonary airway resistance and the mechanisms underlying the potential bronchoconstrictor effect. METHODS: The contrast media studied were the pharmaceutical formulations of iomeprol (400 mg I/ml), iopamidol (370 mg I/ml), and iohexol (350 mg I/ml), which are nonionic, triiodinated contrast media; diatrizoate (370 mg I/ml), an ionic, triiodinated contrast medium; iotrolan (300 mg I/ml), a nonionic, hexaiodinated contrast medium; and iocarmate (280 mg I/ml) and ioxaglate (320 mg I/ml), which are both hexaiodinated and ionic contrast media. Each contrast medium was administered intravenously at 2 g I/kg. Changes in pulmonary airway resistance were evaluated by measuring intratracheal pressure at the moment of maximum insufflation, or maximal insufflation pressure (MIP), in anesthetized guinea pigs submitted to forced ventilation. RESULTS: All contrast media except ioxaglate caused mean increases of MIP of no more than 20%. By contrast, ioxaglate caused a marked bronchoconstrictor effect, increasing MIP by 242% +/- 46%. Of the drugs tested for antagonistic action on this increase in MIP, salbutamol inhibited almost completely the increase in MIP for the first 40 min posttreatment. Similarly, lysine acetylsalicylate and indomethacin consistently reduced MIP after contrast media administration to levels only 30% and 14% above those of baseline precontrast media, respectively. Promethazine had only a minor inhibitory effect, and the response to prednisolone varied. CONCLUSION: There was no apparent relationship between the size of the increase in airway resistance and the charge or molecular weight of the contrast agent molecule or the pharmaceutical formulation. The increase induced by ioxaglate must be attributed to inherent molecular toxicity mediated through a direct action on the production of bradykinin and/or the prostanoid products of the cyclooxygenase pathway, rather than through a direct action on the release of histamine.     

Sustained transmission of mumps in a highly vaccinated population: assessment of primary vaccine failure and waning vaccine-induced immunity

Electrolyte addition to nonionic contrast media has been suggested to further reduce the incidence of ventricular fibrillation during coronary arteriography. The present study was designed to investigate the effects of adding 30 mM NaCl, 0.9 mM KCl, 0.15 mM CaCl2 and 0.1 mM MgCl2 to iohexol on cardiac electrophysiology and hemodynamics (iohexol+electrolytes = IPE). Contrast media were injected into the left main coronary artery in 9 open-chest, anesthetized dogs before and after induction of acute ischemic heart failure. IPE increased left ventricular inotropy (LV dP/dtmax) with no initial decrease, even during heart failure. During heart failure IPE induced the same hemodynamic effects as iohexol without electrolyte addition. IPE slightly lengthened epicardial monophasic action potential duration before heart failure. We conclude that IPE appears to be well tolerated hemodynamically. The electrophysiologic differences between IPE and iohexol are small when the injection time is not longer than 5 s.     

Emergency and Resuscitation Emergency Mobile Service--Neuchatel experience

RATIONALE AND OBJECTIVES: We investigated the possible cardiac effects of oxygen addition to contrast media (CM) during coronary arteriography in dogs that did and did not have ischemic heart failure. METHODS: Acute ischemic heart failure was induced by injecting small plastic microspheres into the left coronary artery of 18 dogs. Hemodynamic and electrophysiologic measurements were performed during a single injection before and during heart failure and during a single injection and five rapidly repeated CM injections during heart failure. Iohexol supplemented with electrolytes (iohexol + electrolytes = IPE), oxygenated IPE (IPE+O), Ringer acetate, and oxygenated Ringer acetate were injected into the left coronary artery. RESULTS: Single injections of IPE and IPE+O induced small hemodynamic and electrophysiologic effects. However, repeated injections of IPE and IPE+O increased left ventricular inotropy (maximum value of the first derivative of the left ventricular pressure) by 36% and 39%, reduced heart rate by 7% (for both), and lengthened QTc time (corrected QT interval) by 39 and 38 msec, respectively. A comparison of IPE and IPE+O revealed no statistically significant differences. CONCLUSION: Although electrolyte addition to nonionic CM may reduce the risk of cardiac complications during coronary arteriography, oxygenation does not seem to significantly further reduce this risk.     

The 2-His-1-carboxylate facial triad--an emerging structural motif in mononuclear non-heme iron(II) enzymes

PURPOSE: To determine in-line pressures generated in small-bore central venous catheters during power injection of computed tomographic (CT) contrast media. MATERIALS AND METHODS: Five 3.0-7.0-F central venous catheters for pediatric patients were tested at full and half lengths in vitro. In-line pressures were measured during power injection of three contrast media. Rates of injection were increased in steps from 0.1 to 5.0 mL/sec or until a peak pressure of 100 psi (700 kPa) was achieved. The maximum tolerated flow rate was determined with reference to the manufacturer's suggested operating pressure limit for each catheter. RESULTS: At full length, the maximum tolerated flow rates were as follows: 2-3 mL/sec for the large lumen and 1-1.4 mL/sec for the small lumen of the 7.0-F double-lumen catheter; 0.2-0.4 and 0.8-1.2 mL/sec for the 3.0- and 4.0-F peripherally inserted central catheters, respectively; 0.7-1.2 mL/sec for the 6.6-F catheter; and only 0.2 mL/sec for the 4.2-F catheter, which ruptured during testing at higher flow rates. CONCLUSION: Flow rates were documented at which certain small-bore central venous catheters should tolerate power injection of CT contrast media with peak pressures remaining below the manufacturer's recommended operating pressure limits. These data may serve as a guide for clinical use.     

Delayed-type hypersensitivity to a nonionic, radiopaque contrast medium

BACKGROUND: True allergic reactions to iodinated radiocontrast media are rare, and only a few well-documented cases of delayed-type hypersensitivity reactions caused by contrast media have been described. METHODS: We report a 61-year-old patient in whom percutaneous transluminal coronary angioplasty (PTCA) was performed with iopamidol, a nonionic contrast medium. Seven days later, the patient developed generalized maculopapular exanthema. Repeated patch tests with several iodinated agents were performed. RESULTS: A first patch test with iopamidol was positive. Repetition of the patch tests showed positive results to iopamidol as well as to iohexol and ioversol, two other nonionic contrast media, but not to other iodinated substances. Three months later, PTCA was repeated, and iopamidol was used again. Despite premedication, pruritic macular exanthema developed 1 day later. Whether iopamidol or trometamol -- an additive substance in the contrast medium -- was causative could not be determined, since a third set of patch tests was negative. CONCLUSIONS: Delayed-type hypersensitivity reactions to iodinated contrast media are rare. We recommend that patients with delayed exanthematous reactions undergo patch or intradermal tests with different contrast media and their additives, and that readings be performed immediately and later at days 2 and 3.     

Molecular cloning and functional expression of a recombinant 72.5 kDa fragment of the 110 kDa regulatory subunit of smooth muscle protein phosphatase 1M

RATIONALE AND OBJECTIVES: We compared adverse reactions and image quality for hysterosalpingography (HSG) performed with ionic (diatrizoate meglumine combined with iodipamide meglumine [DM + IM]) and nonionic (iohexol) contrast media. METHODS: We performed a study of 95 patients who had HSG and were randomly selected to receive DM + IM or iohexol. Patients reported episodes of abdominal pain and other adverse reactions immediately and 24 hr after the procedure and categorized severity of symptoms on a subjective scale. Two radiologists evaluated image quality for diagnosis. RESULTS: Prevalence of abdominal pain and other reactions both immediately and 24 hr after HSG was lower in patients who received iohexol than in patients who received DM + IM. Moderate or severe abdominal pain was significantly lower in the iohexol group than in the DM + IM group (p < .05). Visualization of the uterine cavity and ampullary rugae was judged excellent with both contrast media (87% with iohexol and 92% with DM + IM). CONCLUSION: Iohexol and DM + IM are excellent contrast media for use during HSG; iohexol 300 may cause fewer episodes of more severe and prolonged abdominal pain.     

Influence of indapamide and chlorthalidone on reperfusion-induced ventricular fibrillation in isolated guinea pig hearts

The delayed rectifier potassium current (IK) is a major repolarizing current in guinea pig ventricular myocytes. Blockade of IK or other repolarizing currents is of increasing interest for development of antiarrhythmic drugs; however, these interventions may also be proarrhythmic. In the present study, we compared the potential antiarrhythmic properties of indapamide and chlorthalidone, two structurally related sulfonamide diuretics which differ in their ability to block the slow component of the delayed rectifier (IKs) in isolated, buffer-perfused guinea pig hearts. Hearts underwent 30-min global no-flow ischemia and 10-min reperfusion. Dose-response (10(-7)-10(-4) M) effects of indapamide or chlorthalidone on reperfusion-induced arrhythmias, coronary flow, and heart rate (HR) were evaluated in a randomized blinded fashion. There was no significant difference in the incidence of ventricular fibrillation (VF) for either compound as compared with untreated controls. However, VF duration was reduced to < 40 s in all hearts treated with indapamide 10(-4) M). Mean VF duration with indapamide 10(-4) M was 31 +/- 4 versus 70 +/- 40 s in controls (p < 0.05). Chlorthalidone did not protect against reperfusion-induced arrhythmias. HR was unchanged with either compound; coronary flow during the control perfusion period increased approximately 43% with indapamide 10(-4) M (p < 0.05 vs. all treatment groups). These results demonstrate that indapamide, but not chlorthalidone, confers significant protection against reperfusion-induced VF in this experimental preparation and suggest that selective block of IKs may be antiarrhythmic.     

Postrepolarization refractoriness versus conduction slowing caused by class I antiarrhythmic drugs: antiarrhythmic and proarrhythmic effects

BACKGROUND: Conduction block may be both antiarrhythmic and proarrhythmic. Drug-induced postrepolarization refractoriness (PRR) may prevent premature excitation and tachyarrhythmia induction. The effects of propafenone and procainamide on these parameters, and their antiarrhythmic or proarrhythmic consequences, were investigated. METHODS AND RESULTS: In 11 isolated Langendorff-perfused rabbit hearts, monophasic action potentials (MAPs) were recorded simultaneously from six to seven different right and left ventricular sites, along with a volume-conducted ECG. All recordings were used to discern ventricular tachycardia (VT) or ventricular fibrillation (VF) induced by repetitive extrastimulation (S2-S5) or 10-second burst stimulation at 25 to 200 Hz at baseline and after addition of procainamide (20 micromol/L) or propafenone (1 micromol/L) to the perfusate. MAPs were analyzed for action potential duration at 90% repolarization (APD90), conduction times (CT) between the pacing site and the other MAPs, and PRR (effective refractory period-APD90=PRR) and related to the induction of VT or VF. During steady-state pacing, procainamide and propafenone prolonged APD90 by 12% and 14%, respectively. Procainamide slowed mean CT by 40% during S2-S5 pacing, whereas propafenone slowed mean CT by up to 400% (P<0.001 versus baseline and procainamide). Wavelength was not changed significantly by procainamide but was shortened fourfold by propafenone at S5. Both drugs produced PRR, which was associated with a 70% decrease in VF inducibility with procainamide and elimination of VF with propafenone. Despite this protection from VF, monomorphic VT was induced with propafenone in 57% of burst stimulations. CONCLUSIONS: Drug-induced PRR protects against VF induction. Propafenone promotes slow monomorphic VT, probably by use-dependent conduction slowing and wavelength shortening.     

Analysis of the factors influencing the osmolality of eight monomeric nonionic iodinated contrast medium molecules

RATIONALE AND OBJECTIVES: Because the measured osmolality of a contrast medium solution differs considerably from the theoretical one, the author analyzed the relative influence of various parameters on the experimental osmolality and derived an equation permitting the prospective calculation of the real osmolality of monomeric nonionics. The author discusses the consequences of the results. MATERIALS: Eight monomer nonionic iodinated molecules (ioversol, iohexol, P-569, iobitridol, P-530, iopamidol, and iopromide) were analyzed. A parameter combining the hydrophilic and the hydrophobic aspects of these molecules was calculated, the relative weight of each composing term was calculated with the multiple nonlinear regression technique. RESULTS: The regression equation was determined based on seven compounds. A high proportion of explained variance was achieved. The prediction for ioxilan (with the lowest osmolality of the eight molecules) yielded a good result, confirming that structural influences determine the osmolality of a molecule. CONCLUSIONS: The study of the parameters influencing the osmolality of eight nonionic iodinated monomer contrast medium molecules led to the development of a regression equation. It is shown that both the hydrophilic and hydrophobic characteristics of a molecule are important in the determination of the osmolality. This equation can be useful prospectively.     

Urine profiles and kidney histology after ionic and nonionic radiologic and magnetic resonance contrast media in rats with cisplatin nephropathy

RATIONALE AND OBJECTIVES: The nephrotoxic drug cisplatin has been used successfully in treating some cancers. Patients with suspected carcinoma frequently undergo examinations with contrast media. We examined whether ionic and nonionic radiologic and magnetic resonance contrast media would have any effect on cisplatin nephropathy in rats. METHODS: Urine and serum profiles were monitored for 24 days after intravenous (i.v.) injections of saline, diatrizoate, iohexol, gadopentetate dimeglumine, and gadodiamide in high doses (4.59 mmol/kg body weight) in rats that received a weekly intraperitoneal (i.p.) injection of cisplatin (1 mg/kg) for 10 weeks. There were 10 rats in each group. Another 10 rats injected with both i.p. and i.v. saline served as control subjects. After euthanization, rats' kidneys were removed for examination by light microscopy and electron microscopy. RESULTS: Light and electron microscopy showed severe morphologic changes, including tubular dilatation, atrophy, and necrosis induced by cisplatin; however, the contrast media did not induce any additional morphologic changes. Gadopentetate dimeglumine, diatrizoate, and iohexol significantly increased (3-20 times) albuminuria compared with i.v. saline in cisplatin nephropathy, whereas gadodiamide did not. Albuminuria was highest after diatrizoate injection. All four contrast media caused an immediate and transient significant increase in the excretion of the brush border enzymes alkaline phosphatase and gamma-glutamyltransferase (125-500 times) and the cytoplasmatic enzymes alanine aminopeptidase and lactate dehydrogenase (16-100 times). Compared with saline, the ionic agents significantly increased the excretion of both glucose (two times) and sodium (three to five times), whereas the nonionic agents did not. CONCLUSION: High doses of radiologic and magnetic resonance contrast agents cause temporary dysfunction in rats with cisplatin nephropathy. Gadodiamide caused the least dysfunction and diatrizoate the most.     

Implantable cardioverter-defibrillator therapy for prevention of sudden cardiac death

Patients with known symptomatic VT or VF are at high risk for sudden cardiac death. Various therapeutic choices can be used to reduce the incidence of arrhythmic sudden cardiac death. These include beta-blockers, class I and III antiarrhythmic agents, VT focal ablations, and ICD therapy. The overall incidence of sudden cardiac death in ICD recipients is less than 2% per year, a rate of survival not achieved with any of the available antiarrhythmic agents. VT surgical therapy can produce comparable survival results, but the minimal operative mortality is higher than that with ICD therapy. In patients with noninducible VT/VF or inducible polymorphic VT, and in those refractory to or intolerant of antiarrhythmic agents and poor left ventricular function, ICD therapy may be the only realistic option.     

Enhanced effects of adriamycin by combination with a new ribonucleotide reductase inhibitor, trimidox, in murine leukemia

For invasive catheter procedures both ionic and nonionic contrast media (CM) with excellent tolerability are available. The governing practical factors for CM are X-ray opacity and biocompatibility. Tolerability of a contrast medium is governed among its physical properties by its viscosity, osmolality, and ionic concentration. In Germany the nonionic CM are currently preferred. Because of its low thrombotic complications, the ionic CM Ioxaglat is an important alternative in high risk interventions. In patients with known CM incompatibility, the prophylactic application of H1-receptor antagonists and corticosteroids allows catheterization safely without complications. In impaired renal function, hydration is the most effective prophylactic measure to be taken.     

Power injection of peripherally inserted central catheters

PURPOSE: To study the tolerance of peripherally inserted central catheters (PICCs) of varying sizes and materials to power injection of radiographic contrast agents. MATERIALS AND METHODS: Eight different models of silicone and five different models of polyurethane single-lumen PICCs were injected with increasing rates of iothalamate 60% with use of a power injector. Tolerated and bursting rates and pressures were recorded. RESULTS: There was a wide range of tolerated rates and pressures, depending on the inner and outer diameters of the catheters and on the catheter material. Silicone PICCs tolerated rates between 0.4 and 7.0 mL/sec and polyurethane PICCs tolerated rates between 0.6 and 10.2 mL/sec, depending on the specific catheter. The 5-F silicone PICCs and the 4-F and 5-F polyurethane PICCs tested all tolerated rates greater than 4 mL/sec. Silicone catheters tolerated pressures between 107 and 184 psi, and polyurethane catheters tolerated pressures between 160 and 314 psi. CONCLUSIONS: Larger single-lumen silicone and polyurethane PICCs may be suitable for power injection of contrast agents.     

Vasorelaxing activity of resveratrol and quercetin in isolated rat aorta

PURPOSE: To assess the severity of adverse reactions to contrast media in outpatient computed tomographic (CT) examinations in a conventional clinical setting. MATERIALS AND METHODS: In 4,936 patients, CT was performed with four protocols: ionic contrast medium with sodium meglumine as the cation (in one protocol, contrast material was warmed to 35 degrees C before injection; in another protocol, it was administered at ambient temperature); warmed, ionic contrast medium with nonsodium pure meglumine as the cation; and warmed, nonionic iopamidol. RESULTS: Adverse reactions to ionic contrast material statistically significantly decreased (P<.05) when it was warmed before administration. Reactions to ionic contrast media without a sodium cation were statistically significantly fewer (P<.001) than reactions to those with a sodium cation. In all protocols, pediatric patients had fewer reactions than adult patients. CONCLUSION: In outpatient CT examinations, nonionic, warmed contrast medium was the best option because no severe reactions resulted from its use. Prevalence of adverse reactions was comparable to that in controlled randomized studies.     

Treatment of sudden deafness apropos of 447 cases

Tibial nerve and S1 dermatome somatosensory evoked potentials (SSEPs) were recorded before and after iohexol lumbar myelography in order to evaluate possible neurotoxic effects of this contrast medium. No significant change in SSEP latencies nor amplitudes was noted after iohexol myelography, supporting the low neurotoxic profile of this contrast agent. Results were compared to those of a control group of patients before and after lumbar puncture (LP), without injection of contrast agent. In this group also no significant change in SSEP components was found, indicating that a preceding LP does not affect this electrophysiological examination.     

Antifibrillatory effects of BRL-32872 in anesthetized Yucatan minipigs with regional myocardial ischemia

The antifibrillatory potential of BRL-32872, a novel antiarrhythmic compound with K+ and Ca2+ channel blocking activities, was examined in a minipig model of ischemia-induced arrhythmia. The effects of intravenous (i.v.) BRL-32872 (0.3 and 1.0 mg/kg, n = 8), dofetilide (0.3 mg/kg, n = 8), and flecainide (2.0 mg/kg, n = 8), were investigated on the incidence of ventricular fibrillation (VF) during a 20-min occlusion of the left anterior descending coronary artery (LAD). Ischemia-induced VF occurred in 6 of 9 vehicle-treated pigs. BRL-32872 reduced the incidence of ischemic VF to 13% at 0.3 mg/kg (p < 0.05) and to 0% at 1.0 mg/kg (p < 0.01). Dofetilide also prevented the occurrence of VF (0%, p < 0.01) In contrast, flecainide did not reduce the incidence of VF (63%). Indeed, flecainide shortened the time to onset of VF from 17 +/- 1 min in the vehicle group to 10 +/- 1 min (p < 0.001). The antifibrillatory effects of BRL-32872 and dofetilide were associated with a prolongation of QT interval on ECG. Flecainide did not prolong repolarization, but slowed the ventricular conduction velocity, as shown by significant increases in PR and QRS intervals. During early reperfusion, 1 of 8 surviving pigs in each group treated with BRL-32872 and 4 of 8 in the dofetilide group developed VF. This study demonstrated an antifibrillatory effect of BRL-32872 associated with prolonged ventricular repolarization and showed enhanced efficacy over dofetilide on reperfusion arrhythmias which is most likely a consequence of its Ca2+ blocking activity.