•
Diagnostic Radiology
Effects of Metrizamide, a New Nonionic Contrast Medium, on Cardiac Function During Coronary Angiography in the Dogt,2 Sengt Tragardh, M.D., Peter R. Lynch, Ph.D., and Thomas Vinciguerra
Metrizamide is a new non-ionic radiopaque agent with lowosmolarity and lowintravenous toxicity. Hyperosmolarity is one of the factors involved in the decrease of myocardial contractility, alterations of aortic pressure, and disturbances in the cardiac rhythm which contrast media induce during coronary angiography. Metrizamide has been compared to other commonly used contrast media and was shown to produce fewer changes on the cardiac functions recorded. INDEX TERMS: Contrast Media, comparative studies. Coronary Angiography • Heart, effects of drugs on • Metrizamide Radiology 115:59-62, April 1975
• ETRIZAMIDE is a new nonionic contrast medium with very low intravenous toxicity (14). Contrast media used for coronary angiography have several effects, such as a reduction of contractile force of the myocardium, changes in ventricular and aortic pressures, alteration of heart rate, and production of cardiac arrhythmias (8, 17). Additional effects on the peripheral vasculature and the central nervous system may further influence various cardiac functions (11). The induced arrhythmias during coronary angiography have obvious clinical importance, but the decreased contractility is also of increasing significance since angiography is often performed on patients with a 'weakened myocardium. Decreased contractility can give rise to an acute cardiac insufficiency. Pulmonary edema sometimes follows coronary arteriography (1). The effects of contrast media have been related not only to the anion per se and to the induced transitory ischemia, but also to various other properties of these media, such as viscosity, hyperosmolarity, and improper cationic compositional balance (4,6,9, 10, 18). As a nonionic radiopaque medium metrizamide has a low osmolarity. It has been shown to cause less increase in blood flow during femoral arterial injections in dogs and to have less effect on the contractility of the isolated rabbit heart than other commonly used contrast. media (2, 3). The purpose of the present investigation is to examine the effect of metrizamide and other contrast agents on the contractility of the intact heart and on the left ventricular and aortic pressures during left coronary arterial injections in mongrel dogs.
M
MATERIALS AND METHODS
Eight mongrel dogs weighing 16 to 20 kg were used in this investigation. They were anesthetized with 32 mg/kg of intravenously injected sodium pentobarbital. A tracheostomy was performed and the left carotid artery and right jugUlar vein were surgically isolated. A metal catheter with the tip covered with a short segment of polyethylene tubing (PE 60) was introduced into the carotid artery retrograde, ending in the main stem of the left coronary artery (19). From the jugular vein another catheter (Odman-Lodin, KIFA 10/00 1.2/2.2 mm) was introduced with a sharp metal obturator into the right atrium. With the aid of the metal stylus, the atrial wall was punctured, and the catheter was introduced through the left atrium into the left ventricle for pressure recordings. The aortic pressure was measured by a polyethylene catheter (PE 240) placed in the femoral artery so that the tip of the catheter was in the descending aorta. Little filtration was used for the recordings of the aortic pressure. A Harvard respirator was connected to the tracheal cannulae, and the chest was opened through a midsternal incision. The pericardium was opened, and a Walton-Brodie strain gauge was sewn onto the left ventricle for the measurement of contractile force. Through the coronary catheter the following contrast media solutions were injected into the left coronary artery: sodium/meglumine diatrizoate (Renografin-76), sodium/meglumine iothalamate (Vascoray), sodium/calcium/meglumine metrizoate (Isopaque 370) and metrizamide. All solutions were administered with an iodine
=
1 From the Departments of Radiology and Physiology, and the Specialized Center of Research (Thrombosis), Temple University School of Medicine, Philadelphia, Pa. 19140. Accepted for publication in October 1974. Supported inpartby USPHS, NIH, NHLI Grants HA 08886-10 and HL 14217-04. 2 We wish to thank Nyegaard & Co. for its kindness in supplying the necessary drugs to carry outthis investigation. Metrizamide (Amipaque), is manufactured byNyegaard & Co., AlS, Oslo 4, Norway. Additional articles on its use will befound onpages 91 and 237 of this issue. ah
59
B. TRAGARDH, P. R. LYNCH,
60
AND T. VINCIGUERRA
April 1975
INJ.
o
LVP
3 6
10 13
15 SEC
10 13
15 SEC
JJVlJ\JVl
AP~~-J'~
1 INJ.
o
CF
3 6
JJIJIJ¥\ll i
LVP
'.JIJwVl[lJ
AP ~'--J"'--)~.J"-...
2--Figs. 1 and 2. Effects of 3 ml of metrizamide (Fig. 1) and 3 ml of diatrizoate (Fig. 2) on the electrocardiogram (ECG), the contractile force (CF), the left ventricular pressure (LVP), and the aortic pressure (AP) in the same dog 1 to 3, 6 to 10, and 13 to 15 seconds after the completion of the injection.
concentration of 370 mg/ml. A Viamonte/Hobbs injector delivered either 3 or 6 ml of the substances at a speed of 0.8 ml/sec. First, the 3-ml injections were given in random order; thereafter, the 6-ml injections were administered in the same order as the previous 3ml injections. The pressure readings, the tracings from the contractility strain gauge, and ECG (lead II) were recorded on a six-channel photographic recorder." The nadir of the decrease of the contractile force and the pressures during the injections were calculated in per cent of the preinjection level of these factors (Figs. 1 and 2). Control recordings were examined before each injection, making sure that the animal was in the same physiological state before any new procedure was followed. RESULTS
In one dog ventricular fibrillation developed during the injection of 6 ml of the sodium/meglumine iothalamate; it had already been given the 6-ml injections of metrizamide and sodium/meglumine diatrizoate and the 3-ml injections of all four compounds. The other animals tolerated the procedure well. The strain gauge measuring contractile force showed 3
Electronics for Medicine, Inc., Type 2000.
constant control values and varied less than ± 10% of the mean value during the examination of each animal. The recorded control pressure values also remained stable and varied less than ± 15 % of the mean value. One dog had a mean systolic/diastolic aortic pressure of 90/40 mm Hg during the experiment. All the other animals had a mean systolic/diastolic aortic pressure within the range of 110-140170-90 mm Hg. All substances caused a decrease of the myocardial contractile force starting 6 to 10 heart beats after the beginning of the automatic injection, reaching a maximum after 10 to 20 heart beats, and returning to control levels after 20 to 40 seconds (Figs. 1 and 2). TABLE I demonstrates how diatrizoate and iothalamate caused a significantly (paired f-tests; p
Diagnostic Radiology
Effects of Metrizamide, a New Nonionic Contrast Medium, on Cardiac Function During Coronary Angiography in the Dogt,2 Sengt Tragardh, M.D., Peter R. Lynch, Ph.D., and Thomas Vinciguerra
Metrizamide is a new non-ionic radiopaque agent with lowosmolarity and lowintravenous toxicity. Hyperosmolarity is one of the factors involved in the decrease of myocardial contractility, alterations of aortic pressure, and disturbances in the cardiac rhythm which contrast media induce during coronary angiography. Metrizamide has been compared to other commonly used contrast media and was shown to produce fewer changes on the cardiac functions recorded. INDEX TERMS: Contrast Media, comparative studies. Coronary Angiography • Heart, effects of drugs on • Metrizamide Radiology 115:59-62, April 1975
• ETRIZAMIDE is a new nonionic contrast medium with very low intravenous toxicity (14). Contrast media used for coronary angiography have several effects, such as a reduction of contractile force of the myocardium, changes in ventricular and aortic pressures, alteration of heart rate, and production of cardiac arrhythmias (8, 17). Additional effects on the peripheral vasculature and the central nervous system may further influence various cardiac functions (11). The induced arrhythmias during coronary angiography have obvious clinical importance, but the decreased contractility is also of increasing significance since angiography is often performed on patients with a 'weakened myocardium. Decreased contractility can give rise to an acute cardiac insufficiency. Pulmonary edema sometimes follows coronary arteriography (1). The effects of contrast media have been related not only to the anion per se and to the induced transitory ischemia, but also to various other properties of these media, such as viscosity, hyperosmolarity, and improper cationic compositional balance (4,6,9, 10, 18). As a nonionic radiopaque medium metrizamide has a low osmolarity. It has been shown to cause less increase in blood flow during femoral arterial injections in dogs and to have less effect on the contractility of the isolated rabbit heart than other commonly used contrast. media (2, 3). The purpose of the present investigation is to examine the effect of metrizamide and other contrast agents on the contractility of the intact heart and on the left ventricular and aortic pressures during left coronary arterial injections in mongrel dogs.
M
MATERIALS AND METHODS
Eight mongrel dogs weighing 16 to 20 kg were used in this investigation. They were anesthetized with 32 mg/kg of intravenously injected sodium pentobarbital. A tracheostomy was performed and the left carotid artery and right jugUlar vein were surgically isolated. A metal catheter with the tip covered with a short segment of polyethylene tubing (PE 60) was introduced into the carotid artery retrograde, ending in the main stem of the left coronary artery (19). From the jugular vein another catheter (Odman-Lodin, KIFA 10/00 1.2/2.2 mm) was introduced with a sharp metal obturator into the right atrium. With the aid of the metal stylus, the atrial wall was punctured, and the catheter was introduced through the left atrium into the left ventricle for pressure recordings. The aortic pressure was measured by a polyethylene catheter (PE 240) placed in the femoral artery so that the tip of the catheter was in the descending aorta. Little filtration was used for the recordings of the aortic pressure. A Harvard respirator was connected to the tracheal cannulae, and the chest was opened through a midsternal incision. The pericardium was opened, and a Walton-Brodie strain gauge was sewn onto the left ventricle for the measurement of contractile force. Through the coronary catheter the following contrast media solutions were injected into the left coronary artery: sodium/meglumine diatrizoate (Renografin-76), sodium/meglumine iothalamate (Vascoray), sodium/calcium/meglumine metrizoate (Isopaque 370) and metrizamide. All solutions were administered with an iodine
=
1 From the Departments of Radiology and Physiology, and the Specialized Center of Research (Thrombosis), Temple University School of Medicine, Philadelphia, Pa. 19140. Accepted for publication in October 1974. Supported inpartby USPHS, NIH, NHLI Grants HA 08886-10 and HL 14217-04. 2 We wish to thank Nyegaard & Co. for its kindness in supplying the necessary drugs to carry outthis investigation. Metrizamide (Amipaque), is manufactured byNyegaard & Co., AlS, Oslo 4, Norway. Additional articles on its use will befound onpages 91 and 237 of this issue. ah
59
B. TRAGARDH, P. R. LYNCH,
60
AND T. VINCIGUERRA
April 1975
INJ.
o
LVP
3 6
10 13
15 SEC
10 13
15 SEC
JJVlJ\JVl
AP~~-J'~
1 INJ.
o
CF
3 6
JJIJIJ¥\ll i
LVP
'.JIJwVl[lJ
AP ~'--J"'--)~.J"-...
2--Figs. 1 and 2. Effects of 3 ml of metrizamide (Fig. 1) and 3 ml of diatrizoate (Fig. 2) on the electrocardiogram (ECG), the contractile force (CF), the left ventricular pressure (LVP), and the aortic pressure (AP) in the same dog 1 to 3, 6 to 10, and 13 to 15 seconds after the completion of the injection.
concentration of 370 mg/ml. A Viamonte/Hobbs injector delivered either 3 or 6 ml of the substances at a speed of 0.8 ml/sec. First, the 3-ml injections were given in random order; thereafter, the 6-ml injections were administered in the same order as the previous 3ml injections. The pressure readings, the tracings from the contractility strain gauge, and ECG (lead II) were recorded on a six-channel photographic recorder." The nadir of the decrease of the contractile force and the pressures during the injections were calculated in per cent of the preinjection level of these factors (Figs. 1 and 2). Control recordings were examined before each injection, making sure that the animal was in the same physiological state before any new procedure was followed. RESULTS
In one dog ventricular fibrillation developed during the injection of 6 ml of the sodium/meglumine iothalamate; it had already been given the 6-ml injections of metrizamide and sodium/meglumine diatrizoate and the 3-ml injections of all four compounds. The other animals tolerated the procedure well. The strain gauge measuring contractile force showed 3
Electronics for Medicine, Inc., Type 2000.
constant control values and varied less than ± 10% of the mean value during the examination of each animal. The recorded control pressure values also remained stable and varied less than ± 15 % of the mean value. One dog had a mean systolic/diastolic aortic pressure of 90/40 mm Hg during the experiment. All the other animals had a mean systolic/diastolic aortic pressure within the range of 110-140170-90 mm Hg. All substances caused a decrease of the myocardial contractile force starting 6 to 10 heart beats after the beginning of the automatic injection, reaching a maximum after 10 to 20 heart beats, and returning to control levels after 20 to 40 seconds (Figs. 1 and 2). TABLE I demonstrates how diatrizoate and iothalamate caused a significantly (paired f-tests; p
