Pulmonary venous flow pattern--its relationship to cardiac dynamics. A pulsed Doppler echocardiographic study

We studied the physiology of pulmonary venous flow in 13 normal subjects and five patients with atrial rhythm disorders and atrioventricular conduction disturbances with pulsed Doppler and two-dimensional echocardiography. The left atrium, mitral valve, and pulmonary venous ostia were visualized through the apical four-chamber view. Mitral and pulmonary venous flows were obtained by placing the Doppler sample volume at the appropriate orifice. Pulmonary venous flow was biphasic: a rapid filling wave was observed during systole when the mitral valve was closed; a second wave was observed in diastole during the rapid ventricular filling phase of mitral flow, but was significantly delayed. In patients without atrial contraction (atrial fibrillation and sinoatrial standstill), the initial rapid filling was greatly diminished and only the second diastolic wave appeared to contribute to left atrial filling. In patients with high-grade atrioventricular block, each atrial contraction was followed by a surge in flow from the pulmonary veins. These results are consistent with data obtained from invasive measurements in both dogs and man, and confirm the validity of the use of pulsed Doppler echocardiography in the study of pulmonary venous flow. We suggest that pulmonary venous flow is influenced by dynamic changes in left atrial pressure created by contraction and relaxation of the atrium and ventricle. The initial peak in pulmonary venous flow occurs with atrial relaxation simultaneously with the reduction of left atrial pressure, and the second peak occurs with left ventricular relaxation and rapid transmitral filling of the ventricle.     

Role of left atrial booster pump function in a worsening course of congestive heart failure.

We evaluated changes in left ventricular (LV) preload and the Doppler-derived transmitral late to early diastolic peak velocity ratio (A/E ratio) during the exercise in 27 patients with ischemic heart disease. After the exercise, A/E ratio decreased in 16 patients with a remarkable elevation in LV preload, and increased in 11 with a mild elevation. Further, Doppler transmitral flow in conjunction with pulmonary venous flow and hemodynamic parameters were analyzed in 11 dogs during a worsening course of heart failure induced by dextran infusion. The relationship of A/E ratio to LV end-diastolic pressure showed a quadratic curve concave to the pressure axis. A/E ratio, an index expressing left atrial (LA) contribution to LV filling, returned to that seen before volume loading under the condition of cardiac dysfunction. Pulmonary venous reflux fraction determined as the ratio of peak velocity of pulmonary venous reflux during LA systole to the sum of systolic and diastolic peak velocities of pulmonary venous antegrade flow, did not increase here. In this situation, blood could not be ejected from the left atrium into the left ventricle and even into the pulmonary veins during LA contraction. Finally, LV filling was not compensated by the left atrium, and LA booster pump function itself was deteriorated.     

Transesophageal Doppler echocardiographic assessment of pulmonary venous flow pattern in subjects without cardiovascular disease

This study was designed to assess pulmonary venous flow dynamics using transesophageal Doppler echocardiography. Under general anesthesia, we studied 54 surgical patients with no history or physical evidence of cardiac disorders. In all patients pulmonary venous flow was easily identified by transesophageal color flow mapping. Pulmonary venous flow pattern, which was obtained clearly in 85% (4654) of patients by transesophageal pulsed Doppler echocardiography, was tri- or quadriphasic. The first wave, which was often biphasic in elderly patients, occurred during ventricular systole (S wave). The second wave occurred in diastole during the early ventricular filling phase of mitral flow (D wave). The third wave was reverse flow toward the pulmonary vein during atrial contraction (A wave). The following variables were measured: the peak flow velocities of each wave (PFVs, PFVd, PFVa), and the ratio of PFVs to PFVd (PFV(S/D)). The PFVd correlated with age (r=–0.56, P<0.001), indicating age-related decrease. The PFV(S/D) correlated with age (r=0.61, p<0.001), indicating age-related increase. These results would indicate that the contribution of pulmonary venous flow during diastole to total pulmonary venous flow decreases with age.Our data suggest that age-related diastolic dysfunction of the left ventricle would affect pulmonary venous flow dynamics and that left atrial storage volume during ventricular systole would increase with age.     

Echocardiographic Diagnosis and Transcatheter Occlusion of Pulmonary Arteriovenous Fistula in Cyanotic Newborn

Pulmonary arteriovenous malformation (PAVM) is a rare cause of cyanosis in newborn. A 12‐day‐old male newborn (2.8 kg) was referred to our hospital with the complaints of cyanosis and respiratory distress. On two‐dimensional echocardiography, the right pulmonary artery (PA) appeared larger than left PA and the left atrium, left ventricle were dilated. The right heart chambers were in normal limits. A color flow Doppler echocardiogram revealed a turbulent flow due to a PAVM originating from medium branch of right PA, and continuous wave Doppler showed continuous flow pattern. Agitated saline injection resulted in the delayed appearance of the contrast in the left‐side chambers three to four heart cycles after appearance in the right‐side chambers; the study was considered positive and indicative of an intrapulmonary shunt. Selective angiography of the right PA confirmed the diagnosis of a large solitary PAVM in the right middle lobe with a feeding artery. Amplatzer vascular plug I, which is designed to close abnormal vascular structures, was chosen to close the PAVM. The deployment of device performed safely and the oxygen saturation of baby increased to 95% immediately after deployment. Heart failure and respiratory distress also resolved after the procedure.     

Influence of left ventricular dysfunction on the role of atrial contraction: an echocardiographic-hemodynamic study in dogs

OBJECTIVES: The purpose of this study was to understand the significance of an effective atrial systole and the interactions between atrial and ventricular function. BACKGROUND: The significance of atrial function is controversial, particularly in the setting of left ventricular (LV) dysfunction. METHODS: Serial, rapid pacing in five dogs that had undergone radiofrequency ablation and implantation of right atrial and ventricular pacemakers produced reversible atrial and ventricular dysfunction (alone and in combination). Atrial function (echocardiograph-determined transmitral diastolic flow, left atrial appendage emptying, and pulmonary venous flow), cardiac output, and right heart pressures were measured at matched paced heart rates of 80 beats/min. RESULTS: Isolated rapid atrial pacing (LV ejection fraction approximately 60%) decreased atrial booster pump in the body and appendage of the left atrium, but increased the conduit function of the left atrium. Isolated LV dysfunction (LV ejection fraction approximately 34%) increased atrial booster pump function. The decreased atrial booster pump function in animals with combined atrial and ventricular dysfunction was incompletely compensated by the redistribution of the reservoir and conduit functions of the left atrium. As a result, cardiac output decreased and right heart pressures increased only after superimposed pacing. CONCLUSIONS: In the presence of a normal left ventricle (LV), atrial failure has little effect on cardiac output and right heart pressures because of compensatory conduit function, but when early LV dysfunction coexists, changes in reservoir and conduit functions are insufficient to compensate for an impairment of atrial contraction.     

Right atrial flow topography in healthy subjects studied with real-time two-dimensional Doppler flow imaging technique

The pattern of normal blood flow in the right atrial cavity was studied using the newly developed real-time two-dimensional Doppler flow imaging technique as a standard reference for the Doppler diagnosis of heart diseases with intracardiac shunts at the atrial level. The study was performed primarily with use of the apical four chamber and the parasternal right ventricular inflow tract views in 21 healthy subjects. The following patterns were observed: blood from the inferior vena cava flowed up along the posterior wall of the right atrium and joined with blood from the superior vena cava in the posterocranial part of the right atrial cavity; the flow then coursed along the roof of the right atrium toward the tricuspid valve in the atrial relaxation phase. This flow was always noted along the interatrial septum in the four chamber view. During and after mid-systole of the right ventricle, additional blood flow away from the tricuspid valve appeared, moving from the valve to the central part of the right atrial cavity, that is, at the lower right of the preceding inflow; this flow was interpreted as arising from eddy currents caused by the preceding inflow. In early diastole of the right ventricle, the flow signal area along the interatrial septum and the roof of the right atrium extended into the right ventricular cavity through the tricuspid valve. In the atrial contraction phase only the blood near the tricuspid valve in the right atrial cavity appeared to flow into the right ventricular cavity. Inflow from the coronary sinus was almost undetectable.(ABSTRACT TRUNCATED AT 250 WORDS)     

Atrial contraction is an important determinant of pulmonary venous flow

Pulmonary venous flow has two phases (systolic and diastolic) in normal subjects when studied by pulsed Doppler echocardiography. Only one phase of pulmonary venous flow (diastolic) was observed in six patients without synchronous atrial contraction (four patients with atrial fibrillation and two with complete atrioventricular [AV] block). This pattern reversed to normal (biphasic) when AV synchrony was reestablished by cardioversion to sinus rhythm in patients with atrial fibrillation and by AV sequential pacing in patients with complete AV block. Thus, both atrial and ventricular contraction and relaxation are important determinants of pulmonary venous flow.     

Persistence of the right venous sinus valve simulating a right atrial myxoma in a case of total anomalous pulmonary venous return. Echocardiographic, anatomo-clinical and surgical aspects

A case of persistence of the right venous sinus valve that on echocardiographic examination simulated right atrial myxoma is reported in a patient with total abnormal pulmonary venous return in the coronary sinus. Echocardiography showed a mobile, pedunculated mass present in systole in the right atrium that shifted to diastole in the right ventricle, highly suggestive of right atrial myxoma. The right ventricle also showed a volume overload and a space without echoes behind the left atrium. A membrane was encountered in the right atrium at surgery. This was removed and the venous return corrected.     

Secretion of atrial natriuretic peptide from the heart in man

Plasma concentrations of atrial natriuretic peptide were measured in eight patients undergoing elective cardiac catheterisation and angiography. All patients had normal resting pressures in the cardiac chambers and no clinical evidence of heart failure. Plasma atrial natriuretic peptide rose significantly from the superior vena cava into the right atrium and right ventricle. The increase into the right atrium was variable, with no increase in three subjects, but there was a consistent increase in all subjects from the superior vena cava to to the right ventricle. These findings in the right atrium are probably caused by inadequate mixing and streaming of blood from the coronary sinus containing high concentrations of atrial natriuretic peptide. There was no increase in the concentration of natriuretic peptide from the pulmonary artery to the left ventricle, but the concentrations in the left ventricle were significantly higher than in the superior vena cava. These findings demonstrate that the heart secretes atrial natriuretic peptides in the absence of cardiac failure. Studies based on sampling of the right atrium will not accurately measure cardiac secretion of atrial natriuretic peptide and will therefore be likely to obscure the mechanisms responsible for regulating its secretion. The right ventricle and pulmonary artery are the best sampling sites to measure atrial natriuretic peptide release from the right atrium.     

Secretion of atrial natriuretic peptide from the heart in man.

Plasma concentrations of atrial natriuretic peptide were measured in eight patients undergoing elective cardiac catheterisation and angiography. All patients had normal resting pressures in the cardiac chambers and no clinical evidence of heart failure. Plasma atrial natriuretic peptide rose significantly from the superior vena cava into the right atrium and right ventricle. The increase into the right atrium was variable, with no increase in three subjects, but there was a consistent increase in all subjects from the superior vena cava to to the right ventricle. These findings in the right atrium are probably caused by inadequate mixing and streaming of blood from the coronary sinus containing high concentrations of atrial natriuretic peptide. There was no increase in the concentration of natriuretic peptide from the pulmonary artery to the left ventricle, but the concentrations in the left ventricle were significantly higher than in the superior vena cava. These findings demonstrate that the heart secretes atrial natriuretic peptides in the absence of cardiac failure. Studies based on sampling of the right atrium will not accurately measure cardiac secretion of atrial natriuretic peptide and will therefore be likely to obscure the mechanisms responsible for regulating its secretion. The right ventricle and pulmonary artery are the best sampling sites to measure atrial natriuretic peptide release from the right atrium.     

Early diastolic clicks after the Fontan procedure for double inlet left ventricle: anatomical and physiological correlates

M mode echocardiograms and simultaneous phonocardiograms were recorded in four patients with early diastolic clicks on auscultation. All had double inlet left ventricle and had undergone the Fontan procedure with closure of the right atrioventricular valve orifice by an artificial patch. The phonocardiogram confirmed a high frequency sound occurring 60-90 ms after aortic valve closure and coinciding with the time of maximal excursion of the atrioventricular valve patch towards the ventricular mass. One patient had coexisting congenital complete heart block. The M mode echocardiogram showed "reversed" motion of the patch towards the right atrium during atrial contraction. Doppler flow studies showed that coincident with this motion there was forward flow in the pulmonary artery with augmentation when atrial contraction coincided with ventricular systole. The early diastolic click in these patients was explained by abrupt cessation of the motion of the atrioventricular valve patch towards the ventricular mass in early diastole. In one patient atrial contraction led to a reversal of this motion and was associated with forward flow in the pulmonary artery.     

Early diastolic clicks after the Fontan procedure for double inlet left ventricle: anatomical and physiological correlates.

M mode echocardiograms and simultaneous phonocardiograms were recorded in four patients with early diastolic clicks on auscultation. All had double inlet left ventricle and had undergone the Fontan procedure with closure of the right atrioventricular valve orifice by an artificial patch. The phonocardiogram confirmed a high frequency sound occurring 60-90 ms after aortic valve closure and coinciding with the time of maximal excursion of the atrioventricular valve patch towards the ventricular mass. One patient had coexisting congenital complete heart block. The M mode echocardiogram showed "reversed" motion of the patch towards the right atrium during atrial contraction. Doppler flow studies showed that coincident with this motion there was forward flow in the pulmonary artery with augmentation when atrial contraction coincided with ventricular systole. The early diastolic click in these patients was explained by abrupt cessation of the motion of the atrioventricular valve patch towards the ventricular mass in early diastole. In one patient atrial contraction led to a reversal of this motion and was associated with forward flow in the pulmonary artery.     

Doppler echocardiographic features of the atrial and ventricular filling modes and their significance in restrictive myocardial diseases

The filling modes into the right atrium and both ventricles were observed using pulsed Doppler echocardiography in six cases of restrictive myocardial diseases, and these were compared with those of 13 cases of constrictive pericarditis, six cases of lone atrial fibrillation and 16 healthy subjects. Special attention was paid to the mechanical properties of the cardiac walls which might be reflected in the filling modes. 1. In the restrictive cases, right atrial filling from the superior caval vein during ventricular systole was reduced in velocity and duration, but the atrial filling during ventricular diastole was not appreciably changed. This flow pattern was similar to that of lone atrial fibrillation, indicating reduced distensibility or impaired contraction and ejection fraction of the right atrium. In constrictive pericarditis, the right atrial filling time was shortened both in ventricular systole and diastole, reflecting stiffening of the pericardium. 2. In the restrictive cases, the first half of the left ventricular rapid filling wave was steep and the skirt of the descending limb was prolonged, while there was no such tendency in the right ventricle. In constrictive pericarditis, the rapid filling time was shortened in the right ventricle, and was not significantly changed in the left ventricle. 3. The differences in the atrial and ventricular filling patterns between restrictive myocardial disease and constrictive pericarditis may serve to distinguish these two disease entities.     

Transcutaneous doppler jugular venous flow velocity recording

Transcutaneous bidirectional Doppler jugular venous flow velocity patterns were classified and correlated in 82 patients with right heart hemodynamics. The normal forward flow pattern was biphasic with systolic flow (Sf) greater than the diastolic flow (Df). With rare exceptions, flow patterns of Sf = Df, Sf is less than Df and Df alone indicated abnormal right heart hemodynamics. Abnormal flow patterns (Sf = Df and Sf is less than Df) seen in post cardiac surgery states, and in some rare patients with severe mitral regurgitation despite normal right-sided pressures, were probably secondary to postoperative change in right atrial compliance in the former and to a Bernheim effect in the latter. The most common cause of retrograde systolic flow in the absence of atrioventricular dissociation was tricuspid regurgitation. Persistent retrograde end-diastolic flow with normal forward flow was associated with high right atrial "a" wave pressures, indicating significant decrease in right ventricular compliance with a vigorous atrial contraction. The study clearly established that the jugular venous flow velocity pattern truly reflected derangements in the right heart hemodynamics, irrespective of the underlying etiology. The applicability to bedside evaluation of the jugular venous pulse and the right heart hemodynamics is emphasized.     

Diastolic forward blood flow in the pulmonary artery detected by Doppler echocardiography

The etiology of diastolic motion of the pulmonary valve seen on the M-mode echocardiogram has been the subject of much debate. To further investigate diastolic events in the pulmonary artery, the patterns of diastolic pulmonary artery blood flow velocity were studied using pulsed Doppler echocardiography in patients with a normal heart. Two diastolic waveforms were found, one in early diastole related to passive filling of the right ventricle and one in late diastole related to atrial contraction. These waveforms were also related to the two recognized phases of diastolic pulmonary valve motion detected by M-mode echocardiography. The presence of biphasic diastolic blood flow in the pulmonary artery was confirmed by electromagnetic flow velocimetry in four additional patients with various cardiac diseases and normal right heart pressures. It is concluded that both atrial contraction and passive right ventricular filling produce blood flow in the pulmonary artery.     

Doppler echocardiographic evaluation of pulmonary artery flow after modified Fontan operation: importance of atrial contraction

Doppler echocardiography was used to evaluate blood flow in the pulmonary artery in 14 patients 2 to 42 months (mean (SD) 17 (12) months) after a modified Fontan operation incorporating a direct atriopulmonary anastomosis. Preoperatively six patients had tricuspid atresia, six had a double inlet left ventricle, and two had pulmonary atresia with an intact ventricular septum. The postoperative rhythm was sinus in 11 patients, junctional in one, ventricular pacing in one, and atrioventricular sequential pacing in one. In one patient the Doppler trace was unsatisfactory for analysis. In all patients forward flow in the pulmonary artery had biphasic peaks related to both atrial and ventricular contraction. The mean (SD) peak flow velocity that was synchronous with atrial contraction was 80 (30) cm/s and that synchronous with ventricular contraction was 74 (23) cm/s. The atrial contribution to total pulmonary artery flow, assessed by velocity-time integrals, varied between 22% and 73% (mean (SD) 45 (14)%). In patients with tricuspid atresia the mean (SD) peak flow velocity with atrial contraction was 90 (27) cm/s and that with ventricular contraction was mean (SD) 68 (24) cm/s. In patients with double inlet left ventricle the mean (SD) peak flow velocity was 67 (36) cm/s with atrial contraction and 80 (25) cm/s with ventricular contraction. The atrial contribution to total pulmonary blood flow in patients with tricuspid atresia was significantly higher (53 (11)%) than in those with double inlet left ventricle (37 (14)%). Pulmonary artery flow after modified Fontan operation was biphasic and was related to both atrial and ventricular contraction. The atrial contribution to pulmonary blood flow is greater in patients with tricuspid atresia than in those with a double inlet left ventricle. The mechanism of the second peak related to ventricular contraction is unknown.     

Doppler echocardiographic evaluation of pulmonary artery flow after modified Fontan operation: importance of atrial contraction.

Doppler echocardiography was used to evaluate blood flow in the pulmonary artery in 14 patients 2 to 42 months (mean (SD) 17 (12) months) after a modified Fontan operation incorporating a direct atriopulmonary anastomosis. Preoperatively six patients had tricuspid atresia, six had a double inlet left ventricle, and two had pulmonary atresia with an intact ventricular septum. The postoperative rhythm was sinus in 11 patients, junctional in one, ventricular pacing in one, and atrioventricular sequential pacing in one. In one patient the Doppler trace was unsatisfactory for analysis. In all patients forward flow in the pulmonary artery had biphasic peaks related to both atrial and ventricular contraction. The mean (SD) peak flow velocity that was synchronous with atrial contraction was 80 (30) cm/s and that synchronous with ventricular contraction was 74 (23) cm/s. The atrial contribution to total pulmonary artery flow, assessed by velocity-time integrals, varied between 22% and 73% (mean (SD) 45 (14)%). In patients with tricuspid atresia the mean (SD) peak flow velocity with atrial contraction was 90 (27) cm/s and that with ventricular contraction was mean (SD) 68 (24) cm/s. In patients with double inlet left ventricle the mean (SD) peak flow velocity was 67 (36) cm/s with atrial contraction and 80 (25) cm/s with ventricular contraction. The atrial contribution to total pulmonary blood flow in patients with tricuspid atresia was significantly higher (53 (11)%) than in those with double inlet left ventricle (37 (14)%). Pulmonary artery flow after modified Fontan operation was biphasic and was related to both atrial and ventricular contraction. The atrial contribution to pulmonary blood flow is greater in patients with tricuspid atresia than in those with a double inlet left ventricle. The mechanism of the second peak related to ventricular contraction is unknown.     

Evaluation of pulmonary venous flow by transesophageal echocardiography in subjects with a normal heart: comparison with transthoracic echocardiography

Nineteen normal subjects and five patients with atrial fibrillation underwent transesophageal and transthoracic echocardiographic studies to evaluate the normal pulmonary venous flow pattern, compare right and left pulmonary venous flow and assess the effect of sample volume location on pulmonary venous flow velocities. Best quality tracings were obtained by transesophageal echocardiography. Anterograde flow during systole and diastole was observed in all patients by both techniques. Reversed flow during atrial contraction was observed with transesophageal echocardiography in 18 of the 19 subjects in normal sinus rhythm, but in only 7 subjects with transthoracic echocardiography. Two forward peaks during ventricular systole were clearly identified in 14 subjects (73%) with transesophageal echocardiography, but in none with the transthoracic technique. The early systolic wave immediately followed the reversed flow during atrial contraction and was strongly related to the timing of atrial contraction (r = 0.78; p less than 0.001), but not to the timing of ventricular contraction, and appeared to be secondary to atrial relaxation. Conversely, the late systolic wave was temporally related to ventricular ejection (r = 0.66; p less than 0.001), peaking 100 ms before the end of the aortic valve closure and was unrelated to atrial contraction time. Quantitatively, significantly higher peak systolic flow velocities were obtained in the left upper pulmonary vein compared with the right upper pulmonary vein (60 +/- 17 vs. 52 +/- 15 cm/s; p less than 0.05) and by transesophageal echocardiography compared with transthoracic studies (60 +/- 17 vs. 50 +/- 14 cm/s; p less than 0.05). Increasing depth of interrogation beyond 1 cm from the vein orifice resulted in a significant decrease in the number of interpretable tracings.(ABSTRACT TRUNCATED AT 250 WORDS)     

改良房坦手术后右心房内球囊搏动辅助循环的实验研究

目的：为了提高改良房坦（Ｆｏｎｔａｎ）手术的早期生存率，我们研制了一种新型右心球囊辅助装置，通过机械辅助的方法帮助有房坦手术危险因素的患者。方法：该装置由标准的主动脉内球囊反搏机和一套并连的单球囊管和双球囊管组成，通过调节主动脉内球囊反搏机的充气时相，来驱动经外周静脉送入右心房和腔静脉内的球囊使之产生类似右心室收缩的效果，从而增加肺血流量。本实验比较了应用该装置在搏动频率１：１、１：２和停搏３种状态下对６条犬急性改良房坦模型的血液动力学的影响。各项指标由八导生理记录仪做同步记录，所有数据用配对ｔ检验做统计学分析。结果：研究发现，肺动脉血流量增加十分显著，当搏动频率为１：１和１：２时，分别比停搏时增加了８２％和６４％（Ｐ＜０．０５和Ｐ＜０．０１）。结论：可以认为新型辅助装置能有效地改善改良房坦手术后早期右心功能，这将为帮助有房坦手术危险因素的患者安全渡过围术期提供一种新的途径。     

An echocardiographic assessment of atrial mechanical behaviour

Relations between movement of the atrioventricular ring and changes in left atrial and ventricular dimensions were studied by echocardiography and compared with apexcardiography and Doppler mitral flow velocity traces in 20 healthy controls and in patients with left ventricular hypertrophy (n = 28) or dilatation (n = 16). During left ventricular systole the atrioventricular ring, a structure common to ventricle and atrium, moved towards the ventricular apex, thus increasing left atrial volume. This action matched pulmonary venous return because it was in phase with the transverse left atrial dimension measured from aortic root to posterior left atrial wall. During early diastole, the mitral ring moved rapidly towards the atrium as transmitral flow accelerated. This requires a force directed from ventricle to atrium, likely to be the result of elastic recoil arising from compression of the ventricular myocardium or stretching of the atrial myocardium during ventricular systole. Two additional mechanisms of ventricular filling with atrial systole were recognised: (a) an increase in ventricular volume as the atrioventricular ring moved upwards and (b) transverse left ventricular expansion by pressure driven transmitral flow. The former is undetectable by Doppler from the apex; it accounted for 10% of ventricular filling in the healthy controls, but for significantly less in those with ventricular dilatation. In left ventricular hypertrophy, left ventricular filling was maintained by both mechanisms compensating for the reduced increase in volume early in diastole. Interactions between the atrium and ventricle are functionally important during ventricular systole, early diastole, and in atrial systole. They are not included in the traditional separation of atrial function into reservoir, conduit, and pump functions.