Cardiovascular effects of protamine sulfate.

Rapid administration of protamine sulfate after arteriography or cardiopulmonary bypass has occasionally been associated with marked hypotension. Since it is unclear whether this is due entirely to vasodilatation or to myocardial depression in addition to vasodilatation, the authors assessed the direct myocardial and systemic circulatory effects of this drug in seven anesthetized dogs. Direct effects of protamine sulfate on global and regional myocardial function and peripheral arterial resistance were determined in the presence and absence of segmental myocardial ischemia. Effects on the myocardium were determined by intracoronary administration of protamine; effects on the systemic circulation were determined after intravenous administration. Intracoronary administration of protamine caused no significant change in left ventricular contractility in either the normal or ischemic state. Intravenous administration produced hypotension due to peripheral vasodilation.

Effects of intracoronary administration of contrast materials on left ventricular function in the presence of severe coronary artery stenosis.

The effects of intracoronary administration of contrast materials on regional and global left ventricular (LV) function were assessed in anesthetized dogs with segmental myocardial ischemia produced by critical stenosis of the circumflex coronary artery. Effects caused by sodium meglumine diatrizoate (R76), sodium meglumine calcium metrizoate (ISO), and metrizamide were evaluated. In the nonischemic state R76 produced an early (0-10 seconds) decrease in LV contractility followed by a late (10-20 seconds) positive inotropic effect. In the presence of regional ischemia there was prolongation of the negative inotropic effect. ISO produced only positive inotropic effects without significant differences between responses in the nonischemic and ischemic states. Metrizamide produced almost no alterations in LV function.

Effects of ionic and nonionic contrast agents on left ventricular and extracellular fluid dynamics during angiocardiography in an infant model.

Concern for side effects of contrast materials limits the volume that can be used for angiocardiography in infants; many of these effects are related to hyperosmolality. The effects of intracardiac injections of ionic (meglumine sodium diatrizoate) and nonionic (metrizamide) contrast agents on the left ventricle and body fluids were compared in an infant model. Immediately after injection, meglumine sodium diatrizoate (MSD) caused increases in left ventricular peak systolic pressure (LVPSP) (+26 +/- 5%) (control (C) = 92 mmHg), LV dp/dt (+21 +/- 6%) (C = 2610 mmHg/sec), left ventricular end-diastolic dimension (LVEDD) (+31 +/- 5%) (C = 10.5 mm), and left ventricular end-systolic dimension (LVESD) (+28 +/- 6%) (C = 7mm). Subsequently, LVPSP and dp/dt decreased to -16 +/- 6% and -23 4 +/- 6% of control, while LVEDD and LVESD rose. Dimension changes resolved by 15 minutes. Metrizamide caused immediate increases in LVPSP (+27 +/- 4%) (C = 86 mmHg) and LV dp/dt(+25 +/- 4%) (C = 2640 mmHg/sec). These parameters never declined significantly below control levels and were at control level at 15 seconds. Initial increases in LVEDD (+17 +/- 3%) (C = 10 mm) and LVESD (+6 less than 4%) (C = 6.5 mm) with metrizamide were significantly less than with MSD (P less than 0.008). MSD caused greater and more persistent elevations of serum osmolalities than metrizamide. Differences between the two agents were accentuated during systemic hypoxemia. Thus, ionic contrast agents appear to have a greater propensity for inducing toxic cardiovascular effects in infants than nonionic agents.

Direct myocardial effects of intracoronary administration of new contrast materials with lost osmolality.

The effects of LV dynamics of the intracoronary administration of three new contrast materials with reduced osmolality were compared with those of a monomeric ionic material, sodium iothalamate, and the nonionic material, metrizamide. In eight anesthetized dogs, the monacid dimer, P286, caused increases in LV dimensions and decreases in LV systolic pressure and parameters of the contractile state. The changes were less than those caused by sodium iothalamte. The alterations in LV function tended to be greater, but not significantly so, during systemic hypoxemia compared to the normal state. The nonionic materials, P297 and iopamidol, like metrizamide, caused no deleterious effects on LV dynamics in either the normal or hypoxemic state. Nonionic materials actually caused a slight increase in parameters of the LV contractile state.

Identification and evaluation of the contribution of the chemoreflex in the hemodynamic response to intracarotid administration of contrast materials in the conscious dog: comparison with the response to nicotine.

Intracarotid administration of ionic contrast material and nicotine in conscious, unsedated dogs caused similar biphasic reflex responses consisting of initial decreases followed by increases in heart rate and pressures. Both phases were characterized by increases in respiratory amplitude. The initial hypotension was not observed when heart rate was maintained constant. The initial bradycardia was absent after denervation of the carotid body and cholinergic blockade. The tachycardia was attenuated after ligation of the internal carotid artery and beta adrenergic blockade. Hwever, the hypertension persisted after denervation of the carotid body and ligation of the internal carotid artery but was attenuated after alpha adrenergic blockade. Nonionic contrast material caused almost no reflex hemodynamic effects. Like noxious substances such as nicotine, ionic contrast materials cause complex hemodynamic effects as a consequence of actions on the cardiovascular centers of the brain, carotid body chemoreceptors, and chemosensitive tissue in the external carotid circulation.