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Aim: A new transpulmonary echo contrast agent (SH U 508) was injected intracoronally to six anaesthetised sheep to examine its possible direct cardiac effects., Method: SH U 508 was injected in randomised order in three different volumes (2, 4 and 8 ml; n = 12, 10, 9) with the same drug concentration of 200 mg/ml., Results: The 2 ml and 4 ml injections had no relevant effect on the arterial, pulmonary-arterial and ventricular pressures, on the left ventricular contraction velocity and on the myocardial blood flow (less than +/- 10% of the control value). The left ventricular relaxation velocity decreased by 20%. The disturbance of the left ventricular relaxation at a volume of 8 ml was pronounced (about 40% decrease). Slight left ventricular dysfunction further manifested itself in a decreased systolic pressure (-15%) and increased left ventricular enddiastolic pressure (20%)., Conclusion: In summary the overall effect of the intracoronary injections of SH U 508 exhibited only minor cardiac side effects. If the current results are extrapolated to peripheral-venous application, the clinically required central-venous 8 ml injection of a 400 mg/ml suspension is not expected to produce any coronary haemodynamic side effects, due to drug dilution in the pulmonary circulation and resulting low intra-coronary concentrations.

The haemodynamic side-effects of ionic (amidotrizoate) and non-ionic (iopamidol) contrast media after injection into the right atrium were compared in experimental and clinical studies. Pulmonary hypertension was induced in 10 dogs by embolization of the pulmonary vascular bed with agar-agar solution (mean pulmonary artery pressure = 44.2 mmHg). Iopamidol (1.5 ml kg-1) caused a moderate decrease in pulmonary and systemic vascular resistance, slight increases in right ventricular end-diastolic pressure and a marked rise in right ventricular contractility (dP/dtmax). Amidotrizoate (1.5 ml kg-1) caused considerable systemic vasodilation and initial increases in pulmonary vascular resistance and pressure followed by a substantial increase in right ventricular end-diastolic pressure and a decrease in contractility. Central and peripheral haemodynamics were measured in 20 patients with pulmonary hypertension (mean pulmonary artery pressure = 38.1 mmHg) due to valvular heart disease before and following injections with 40 ml of both types of contrast medium in randomized order. Heart rate, cardiac output and right atrial pressure rose significantly more after amidotrizoate and this contrast medium caused more extensive systemic vasodilation and a larger decrease in aortic pressure as compared to iopamidol. Pulmonary artery pressure went up moderately with both contrast media. It is concluded that non-ionic low-osmolality contrast media like iopamidol induce less pronounced haemodynamic alterations, in particular less increase in right ventricular filling pressure. This may be beneficial to patients with pulmonary hypertension undergoing angiocardiography or digital subtraction angiography.

Electrophysiological effects of intracoronarily administered contrast media have been documented in 12 thoracotomized dogs at the cellular level by use of a modified microelectrode technique. Injections (n = 63) of 4 different contrast media uniformly led to a temporary cellular hyperpolarisation of the resting potential and prolongation of the action potential. Additional experiments with intracoronary injections of several electrolyte solutions indicate that the observed effects can be explained by contrast-induced changes in the extracellular electrolyte concentrations, mainly by a local deficiency of potassium ions and an excess of sodium ions. The significance of the findings for mechanisms underlying ECG-changes and ventricular arrhythmia by radiographic contrast media will be discussed.

Our aim was to determine whether large central venous doses of ionic diatrizoate, nonionic iopromide, or nonionic iotrolane produce pulmonary edema or pulmonary congestion in dogs. Eighteen dogs (six per group) anesthetized with piritramide and N2O received three sequential doses (1.5 mL/kg body weight) of one contrast medium in less than 20 seconds. Before the first injection, and again 1, 5, 10, 20, and 30 minutes after each contrast injection, extravascular lung water, pulmonary blood volume, and cardiac output were determined by thermal-dye dilution. Neither extravascular lung water nor pulmonary blood volume increased after any contrast medium. Pulmonary blood volume and cardiac output decreased slightly but not significantly after all contrast media during the course of the study. We conclude that diatrizoate, iopromide, or iotrolane do not produce pulmonary edema or congestion in dogs.

In 16 patients with CAD, hemodynamic and electrophysiologic side effects were examined following selective coronary artery injections with Urografin 76%, a commonly used ionic contrast medium. A Millar transducer tipped catheter was placed in the left ventricle for continuous pressure recording also during injections. The unmodified contrast medium decreases peak left ventricular pressure (-22 +/- 8%) and dp/dt max (-27 +/- 13%) markedly at injection. With added calcium (22.5 mEq/l) this cardiodepressive reaction becomes diminished to -15 +/- 7% and -13 +/- 8% respectively with high significance (p < 0.001). This positive effect is even more marked using higher volumes of contrast material for injection. In contrast to animal experiments, calcium did not completely compensate the negative inotropic reaction even in higher concentration (33.75 mEq/l). The marked sinus slowing (-29 +/- 14%)--observed in patients and not influenced by the calcium addition--has an additional effect in the sense of a "negative frequency-inotropism" and is responsible for the residual cardiodepressive reaction. An influence on electrophysiologic side reactions can also be observed with added calcium but only in injections with higher volumes of contrast medium. QT-elongation, T-wave changes are reduced significantly. We did not see any unfavorable reactions caused by added calcium. The cardiodepressive side effects on the contractile force by commonly used ionic contrast media can be reduced by adding calcium in the above-mentioned concentration. This may be helpful when studying high risk patients and using high injection volumes.

The acute cardiovascular side effects of iopamidol (osmolality: 0.8 osmol/kg), metrizamide (0.6 osmol/kg), and amidotrizoate (2.1 osmol/kg) during coronary arteriography (n = 30) and left ventriculography (n = 9) have been compared in anesthetized closed-chest dogs (n = 5). The influences of these contrast media on hemodynamics, coronary circulation, ECG and physicochemical properties of coronary sinus blood were evaluated. Following intracoronary injection, iopamidol and metrizamide cause positive inotropism while amidotrizoate initially induces cardiodepression. All contrast solutions lead to marked increase of myocardial blood flow. Electrocardiographic changes are greater after amidotrizoate (P less than 0.05). A fall of cationic content in coronary sinus blood is seen after each contrast medium. Amidotrizoate leads to more decrease of potassium (P less than 0.01) and both ionized and total calcium (P less than 0.001). Increase of osmolality and hydrogen ionic content is greater after amidotrizoate than after iopamidol and metrizamide (P less than 0.01). Following left ventricular injection, marked peripheral vasodilation, as seen after amidotrizoate, does not occur after low osmolality compounds. There are no significant differences between iopamidol and metrizamide in spite of the slightly higher osmolality of the former. Thus, both contrast materials should be equivalent with respect to their acute cardiovascular side effects under clinical conditions. Advantages of low osmolality radiological contrast media are discussed.

Intravenous administration of contrast material is a prerequisite for the imaging of the cardiovascular system with computed tomography and digital subtraction techniques. Fatal side effects after intravenous contrast injection, particularly in patients with pulmonary hypertension, have been reported repeatedly. The object of this study was to compare hemodynamic side effects of a conventional, ionic contrast medium (amidotrizoate; 2.1 osmol/kg) and a modern, non-ionic compound (iopamidol; 0.8 osmol/kg) after intravenous bolus injection (1.5 ml/kg). Experiments were carried out in 10 open-chest dogs with pulmonary normotension and hypertension induced by embolisation. Under control conditions (PPA = 19.9 mm Hg) both contrast media produced marked pulmonary and peripheral vasodilation. Major effects were seen after amidotrizoate (RPULM 60.3%, RPERI 32.1% vs 72.5% and 70.4% of controls). In pulmonary hypertension (PPA = 44.2 mmHg), iopamidol had similar hemodynamic effects compared to control conditions. In contrast, amidotrizoate initially led to a significant increase in pulmonary pressure and resistance (PPA = 118.6%; RPULM = 141.7%) followed by a delayed depression of right ventricular function (dP/dt = 65.3%; PRVED = 180.9%). Resuscitation was required in 3 dogs with pulmonary hypertension after amidotrizoate injection. Because of these unfavorable hemodynamic side effects of the conventional high osmolality contrast medium in animal experiments, it can be expected that modern compounds with low osmolality pruduce smaller side effects during diognostic interventions in patients with pulmonary hypertension.

The advantages of a new low osmolality contrast medium (sodium meglumine ioxaglate) in clinical coronary angiography are demonstrated at two groups of patients in comparison to sodium meglumine diatrizoate. One group included patients undergoing diagnostic angiography in chronic state of CHD, the other during diagnosis and therapy (intracoronary lysis) in state of acute myocardial infarction. Injection of the low osmolality contrast material was followed in both groups by significant reduction of pressure drop and cardiac slowing. In both groups there was also a reduction of changes in ECG compared to side effects of the conventional contrast material.

To investigate the basis of cardiodepressive side effects in coronary arteriography, the isolated effects of different contrast media on electrolyte levels in blood (and blood fractions) were quantified in vitro. Due to their sodium content and calcium chelation, ionic media cause an imbalance in the extracellar Na+/Ca++-ratio that determines myocardial contractility. Ca++-chelation exceeded that due to stabilizing additives indicating a binding by the contrast agents themselves. The amount of calcium bound varied with different media and was greatest with Renografin. It is suggested that the degree of Na+/Ca++-imbalance in blood explains the extent of acute cardiodepression.

The cardiotoxicity of commonly used contrast media such as sodium methylglucamine diatrizoate is related to nonphysiologic concentrations of ions and high osmolality. Following injection there is an excessive decrease in ambient calcium which disturbs the extracellular Na+/Ca2+ ratio and results in myocardial depression. In animal studies (anesthetized, intact mongrel dogs) this cardiodepressive effect could be fully compensated by adding 22.5 mEq/1 of ionic calcium to the contrast medium. In 16 patients studied for coronary artery disease (CAD) 72 injections of sodium methylglucamine diatrizoate, mainly in the left coronary artery, were thoroughly investigated. There was marked depression of left ventricular pressure (-22%) and (dP/dt)max (-27%), and marked heart rate slowing (-29%). Added calcium in the concentration cited reduced significantly (p < 0.001) the myocardial depression to -15% and -13%, respectively, but did not completely compensate it. The heart rate slowing was not altered significantly. It was concluded that the addition of calcium may be helpful when studying high-risk patients and using high injection volumes.