Selective coronary artery perfusion in vitro: a method to study cardiac effects of contrast media.

RATIONALE AND OBJECTIVES: The authors evaluated selective perfusion of the coronary arteries in the isolated rat heart as a model for studying contrast medium-induced cardiac effects and compared the effects of iodixanol, iotrolan, and ioxaglate with this model. MATERIALS AND METHODS: Isolated, spontaneously beating rat hearts were used. Control hearts were perfused in the Langendorff or the selective perfusion mode receiving Krebs Henseleit buffer. Contrast media were injected selectively into the left coronary artery. Left ventricular pressure and electrocardiographic parameters were monitored continuously throughout the experiments. RESULTS: The stability of the selective perfusion preparation was similar to that of the conventional Langendorff preparation. Ioxaglate (0.3 g iodine per kilogram body weight) significantly (P < .05) depressed left ventricular contractility and decreased (P < .05) left ventricular pressure. Iodixanol and iotrolan had minor cardiac effects. CONCLUSION: Selective coronary artery perfusion seems to be a suitable model for studying direct cardiac effects of contrast media. The nonionic dimers, iodixanol and iotrolan, induce only minor changes in cardiac function.

Acute cardiotoxicity of gadolinium-based contrast media: findings in the isolated rat heart.

RATIONALE AND OBJECTIVE: The study was designed to compare acute and direct cardiotoxicity of gadopentetate dimeglumine, gadoteridol injection, and gadodiamide injection. METHODS: Two consecutive injections of contrast material (0.3 to 1.5 mmol/kg body weight) were given to spontaneously beating, isolated rat hearts. Cardiac function was assessed by measuring left ventricular developed pressure (LVDP), perfusion pressure, and electrocardiographic (ECG) parameters. RESULTS: Gadopentetate dimeglumine decreased LVDP, and its first derivatives (+/- dP/dt max) substantially more than gadodiamide injection. Gadoteridol increased these variables. PR and RT intervals lengthened after 1.5 mmol/kg gadopentetate dimeglumine and gadoteridol injection. Bradycardia and ventricular tachyarrhythmias were seen after injection of 1.5 mmol/kg gadopentetate dimeglumine. Except for isolated ventricular premature beats, gadodiamide injection and gadoteridol injection did not provoke any serious arrhythmia. CONCLUSION: Gadopentatate dimeglumine induced negative inotropy and more pronounced ECG disturbances. Gadoteridol injection and gadodiamide injection induced only small changes in left ventricular inotropy and minor electrophysiologic effects.

Cardiac effects of iodixanol compared to those of other nonionic and ionic contrast media on the isolated rat heart.

This study was designed to compare the cardiac electrophysiology and mechanical effects of iodixanol to those of iotrolan, iopromide, ioxaglate and diatrizoate. Two consecutive injections of contrast media (CM) (0.3 g I/kg and 0.9 g I/kg b.w.) were given to spontaneously beating, Langendorff-perfused rat hearts. CM were given as a single, short-lasting bolus injection (i.e. over 2 and 5 s). Changes in aortic pressure, left ventricular pressures and ECG were continuously recorded during constant volume perfusion. The nonionic CM had less pronounced effects on aortic pressure than had the ionic media. The peak rate of isovolumetric contraction (LV dP/dt(max)) was slightly decreased by iodixanol and iotrolan, slightly more decreased by iopromide and markedly decreased by ioxaglate and diatrizoate. Similarly, the peak rate of pressure decline (LV dP/dt (min)) was only slightly decreased by iodixanol and iotrolan. Also, the 2 nonionic dimers had the smallest effects on the left ventricular end diastolic pressure (LVEDP) and heart rate. Ioxaglate lengthened the PQ-interval, but less so than diatrizoate. THe QT-interval was only slightly lengthened by iodixanol and iotrolan, as compared to the lenghthening caused by iopromide, ioxaglate and diatrizoate. Single ventricular extrasystoles were seen in all groups. Extrasystoles up to 3 coupled beats were registered after ioxaglate and diatrizoate. No episodes of ventricular fibrillation occurred with any CM. In conclusion, the nonionic dimers, and in particular iodixanol, induce only minor changes in cardiac function, whereas the ionic dimer ioxaglate and the ionic monomer diatrizoate induce pronounced effects.

Absorption and excretion of iodixanol after intragastric administration to rats.

Absorption and excretion of iodixanol 320 mg I/ml were investigated in rats after intragastric administration of 2.5 g I/kg b.w. Animals were observed for up to 96 hours after treatment, and blood, urine and feces taken at several time-points throughout the experiment. Concentrations of iodixanol in serum and urine were measured by means of reversed-phase high-performance liquid chromatography. Fecal concentrations of iodixanol, based on iodine measurements, were determined by X-ray fluorescence spectrometry. Serial radiographs were obtained and histopathological examination was performed on selected tissues. The results indicate that less than 1% of the intragastric dose of iodixanol is absorbed from the intestine into the blood stream. No adverse clinical signs were observed, and there were no treatment-related histomorphological findings.