PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “atrial function”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 343 records · Page 19Linked to original sources
PubMed1994

Left atrial appendage function determined by transesophageal echocardiography in patients with rheumatic mitral valve disease.

Left atrial thrombi have been considered to be the major source of systemic arterial embolization in patients with rheumatic mitral valve disease. Almost half of the left atrial thrombi are found in the left atrial appendage (LAA). To investigate LAA size and LAA contractile function in patients with rheumatic mitral valve disease, transesophageal echocardiographic and Doppler studies were performed in 61 patients. Among them, 46 patients were in atrial fibrillation (group 1), while the other 15 were in sinus rhythm (group 2). Thirty-six patients with nonrheumatic atrial fibrillation were chosen as control to group 1. Another 22 patients with various cardiovascular diseases and sinus rhythm served as control to group 2. When compared to the patients with nonrheumatic atrial fibrillation (control group), group 1 patients tended to have a larger LAA maximal area (9.7 +/- 5.2 vs. 5.9 +/- 2.8 cm2; p < 0.001). LAA ejection fraction and LAA peak emptying velocity were also lower. A significantly higher incidence of LAA spontaneous echo contrast (SEC) and thrombus formation was also found in these patients. Group 2 patients were also found to have a larger LAA maximal area when compared to the control group (8.8 +/- 3.7 vs. 5.2 +/- 3.0 cm2; p < 0.001). LAA ejection fraction and LAA peak emptying velocity were lower in this group, too. A higher incidence of LAA SEC formation was found in these patients with rheumatic mitral valve disease (4/15 vs. 0/22; p = 0.021). There was no significant difference, however, in LAA thrombus formation between group 2 and its control group (1/15 vs. 1/22; p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Stratification of thromboembolic risk of atrial fibrillation by transthoracic echocardiography and transesophageal echocardiography: the relative role of left atrial appendage function, mitral valve disease, and spontaneous echocardiographic contrast.

The role of transesophageal echocardiography (TEE) in thromboembolic risk stratification in atrial fibrillation (AF) has not been established. Left atrial appendage contractile dysfunction in patients with AF predisposes to thrombus formation. The extent of blood stasis and propensity for thrombus can be assessed during TEE by measurement of the peak Doppler velocity of blood outflow from the appendage. Spontaneous echocardiographic contrast (SEC) is a swirling pattern of blood echogenicity that may be detected by TEE in the left atrium in patients with AF. The presence of SEC reflects left atrial blood stasis and a prothrombotic state. SEC is associated with an increased risk of systemic thromboembolic events. Parameters derived from TEE may provide additional prognostic data to clinical history and transthoracic echocardiography in thromboembolic risk stratification in AF.

Atrial Fibrillation↗
PubMed2004

Effects of dipper and non-dipper status of essential hypertension on left atrial mechanical functions.

AIM: This study was designed in order to investigate the effects of dipper and non-dipper status of hypertension on left atrial mechanical (reservoir, conduit and booster pump) functions with left atrial volume measurements by means of two-dimensional echocardiography in untreated systemic hypertensive patients. METHOD: A total of 27 untreated dipper hypertensive patients, group I (15 female, 12 male, mean age 57+/-12 years); 23 untreated non-dipper hypertensive patients, group II (12 female, 11 male, mean age: 53+/-18 years); and 25 voluntary healthy individuals, group III (13 female, 12 male, mean age 53+/-10 years) were included into the study. Twenty-four hour blood pressure (BP) measurement was performed by the cuff-oscillometric method to evaluate the nocturnal decrease of BP. The patients whose night time mean blood pressure measurements were found 10% or more lower compared to mean day time measurements were classified as dipper hypertensive patients and the ones with a decrease of less than 10% were classified as non-dipper hypertensive patients. Left atrial (LA) volumes were measured echocardiographically according to biplane area-length method in apical four-chamber and two-chamber views. LA maximal volume (V(max)) was recorded at the onset of mitral opening, LA minimal volume (V(min)) was recorded at the onset of mitral closure and LA presystolic volume (V(p)) was recorded at the beginning of the atrial systole (p wave on ECG). All volume measurements were corrected to body surface area, and following LA emptying functions parameters were calculated: LA passive emptying volume (LAPEV)=V(max)-V(p), LA passive emptying fraction (LAPEF)=LAPEV/V(max), Conduit volume (CV)=left ventricular output volume-(V(max)-V(min)), LA active emptying volume (LAAEV)=V(p)-V(min), LA active emptying fraction (LAAEF)=LAAEV/V(p), LA total emptying volume (LATEV)=V(max)-V(min), LA total emptying fraction (LATEF)=LATEV/V(max). RESULTS: LA volume indexes, V(max), V(min), and V(p), were significantly increased in the hypertensive subgroups (groups I and II) than in controls (p<0.001, p<0.001, p<0.001, respectively), but no significant difference was found in the V(p) values between group I and group II. V(max) and V(min) were larger in non-dipper hypertensive group than in dipper hypertensive group (p<0.05 and p<0.05, respectively). LAPEV and LAPEF were observed to be significantly reduced in both dipper and non-dipper hypertensives than in control (p<0.001 and p<0.05, respectively), and this difference was more obvious in non-dipper than dipper cases (p<0.001). Conduit volume was significantly lower in hypertensive groups than controls (p<0.05). LA active emptying volume (p<0.001) and LAA active emptying fraction (p<0.001) were significantly greater in hypertensive cases than in controls. Furthermore, LA active emptying volume in non-dipper hypertensive subjects was significantly greater than dipper hypertensive cases (p<0.05). Left atrial total emptying volume and left atrial total emptying fraction in both hypertensive groups were similar to control (p>0.05). CONCLUSIONS: Atrial reservoir and booster pump functions increase in hypertensive patients, but this result is more prominent in non-dipper hypertensives than in dipper hypertensive patients.

Adult↗
PubMed1987

Ventricular function after atrial cardioplegia.

Continuous retrograde coronary sinus cardioplegia (CSCP) has previously been carefully evaluated experimentally and shown to be efficacious during ischemia, even in the presence of coronary lesions and in the hypertrophied state. A new technique of retrograde cardioplegia delivery through the right atrium, using right ventricular distension and pressures of 60 mm Hg, has recently been described with excellent clinical results. This study was designed to specifically examine right ventricular function after atrial cardioplegia and acute passive right ventricular distension. CSCP (n = 10) was compared with cardioplegia delivered through the right atrium both continuously (n = 10) and intermittently (n = 8). When ventricular function was examined with the use of the load-independent relationship of stroke work vs end-diastolic length, there was a profound deterioration of right ventricular function in both atrial cardioplegia groups (44% and 37% of control values, respectively) after 1 hr of reperfusion. In contrast, biventricular function was fully preserved in the CSCP group 1 hr after reperfusion. Left ventricular function measured at the end of reperfusion was preserved in all three groups. Right ventricular ATP levels were slightly but significantly depressed in all groups and in the atrial cardioplegia groups, this metabolic change was also seen in the left ventricle. These metabolic and hemodynamic data may reflect the inability of atrial cardioplegia to cool the myocardium below 16 degrees C. Postoperative right ventricular dysfunction may be more common than has been previously thought when atrial cardioplegia is used, particularly in the absence of topical cooling.

Adenine Nucleotides↗
PubMed1999

Decreased left atrial appendage function is an important predictor of elevated left ventricular filling pressure in patients with congestive heart failure.

OBJECTIVE: The aim of this study was to investigate whether left atrial (LA) appendage function, as indicated by LA appendage blood flow velocities and its ejection fraction, could identify elevated left ventricular filling pressure in patients with chronic congestive heart failure. METHODS: Using transesophageal echocardiography, adequate pulsed Doppler LA appendage active emptying and filling velocities could be recorded in 25 consecutive patients (16 men and 9 women, aged 57+/-10 years) with chronic congestive heart failure (symptom duration > or =1 year). LA appendage ejection fraction calculated as (LA appendage maximal area)-(LA appendage minimal area)/(LA appendage maximal area) x 100 was also determined in these patients. Left ventricular end-diastolic pressure was recorded during cardiac catheterization performed within 24 h of echocardiographic study. RESULTS: Left ventricular end-diastolic pressure was 2 to 47 mm Hg. There were close negative correlations of LA appendage emptying velocity (r=-0.508; P<0.01), filling velocity (r=-0.429; P<0.05) and LA appendage ejection fraction (r=-0.523; P<0.005) with left ventricular end-diastolic pressure. LA appendage active emptying velocity <30 cm/s predicted left ventricular end-diastolic pressure >25 mm Hg with a sensitivity of 72.7%, a specificity of 92.9% and a positive and negative predictive value of 88.9 and 81.3%. CONCLUSIONS: The findings suggest that measurement of LA appendage blood flow velocities and contractile function by transesophageal echocardiography can be used to predict elevated left ventricular filling pressure in patients with congestive heart failure.

Atrial Function, Left↗
PubMed1996

Pulmonary edema following electrical cardioversion of atrial fibrillation.

A 61-year-old man with hypertrophic cardiomyopathy developed acute pulmonary edema 29 h following cardioversion of chronic atrial fibrillation to sinus rhythm. Doppler echocardiographic evaluation of atrial function showed return of right atrial contraction but absent left atrial systole. This has not been reported previously in a case of postcardioversion pulmonary edema.

Atrial Fibrillation↗
PubMed2005

Pulmonary venous flow reversal and its relationship to atrial mechanical function in normal subjects--Umeå General Population Heart Study.

AIMS: Although pulmonary venous flow reversal (Ar) is useful in the evaluation of left ventricular (LV) diastolic function, it is often difficult to study with transthoracic echocardiography (TTE). We determined the relationship between Ar and left atrial (LA) mechanical function and sought to define surrogate measurements for Ar. METHODS AND RESULTS: A total of 130 healthy subjects, mean age 54.3+/-18.3 years, 62 women, were studied and classified into three groups: [young (Y), 25-44 years; n=44], [middle-age (M), 45-64 years; n=43] and [elderly (E), > or =65 years; n=43]. Pulmonary venous flow and LV inflow studies were performed by TTE and LV basal free-wall motion was studied by Doppler tissue imaging (DTI). All images were acquired with a superimposed electrocardiogram. RR interval was similar in all groups while LA dimension and PR interval were increased in Group E vs. Y (P<0.001). LA contraction (A(m)) on DTI, transmitral A-wave (A) and Ar were simultaneous and started 84ms after onset of P wave and this interval increased with age (P=0.02). Similarly, the time intervals from the same landmark to peak A(m), A, and Ar were prolonged with age (all, P<0.001). Despite this prolongation, peak A(m) coincided with peak Ar in every age group (r=0.97, P<0.001) and Ar acceleration and deceleration times were consistently equal. CONCLUSION: The timing of A(m) obtained by DTI can be used to accurately estimate corresponding measurements of Ar recorded by TTE in subjects without cardiac disease.

Adult↗
PubMed2006

Significance of left atrial contractile function in asymptomatic subjects with hereditary hemochromatosis.

Patients with hereditary hemochromatosis (HH) have been reported to develop diastolic functional abnormalities detectable by echocardiography, but it is unknown whether these occur in asymptomatic subjects. Thus, this study tested whether echocardiographic left ventricular (LV) relaxation abnormalities are detectable in subjects with asymptomatic HH. Forty-three asymptomatic subjects with HH (C282Y homozygosity in the HFE gene) and 21 age- and gender-matched control subjects without known HFE mutations underwent echocardiography with comprehensive diastolic functional evaluations. Subjects with HH were in New York Heart Association functional class I and consisted of 22 newly diagnosed patients (group A) and 21 chronically phlebotomized subjects with stable iron levels (group B). Group A subjects showed significant iron overload compared with group B subjects and controls (group C) (ferritin 1,164 +/- 886 [p <0.05 vs groups B and C], 128 +/- 262, and 98 +/- 76 microg/L and transferrin saturation 79 +/- 19% [p <0.05 vs groups B and C], 42 +/- 21%, and 26 +/- 10% for groups A, B, and C, respectively). Echocardiographic evaluation revealed (1) no statistically significant abnormalities of Doppler LV relaxation in HH groups; (2) significant augmentation of atrial contractile function in subjects with HH compared with controls, which was not correlated with iron levels and treatment status; and (3) the preservation of overall LV systolic function in HH groups. In conclusion, the results of this study suggest that the augmentation of atrial contraction appears to be an early detectable echocardiographic cardiac manifestation of abnormal diastolic function in asymptomatic subjects with HH, which may reflect undetectable subclinical LV relaxation abnormalities.

Atrial Function, Left↗
PubMed1991

Allosteric modulation by ATP of the bovine adrenal natriuretic factor R1 receptor functions.

Atrial natriuretic factor (ANF-R1) receptor is a 130-kDa protein that contains a cytoplasmic guanylate cyclase domain. We report that ATP interacts in an allosteric manner with the ANF-R1 receptor, resulting in reduced ANF binding and enhanced ANF-stimulated guanylate cyclase activity. The modulatory properties of various nucleotides indicate a preference for the adenine family with a rank order of potency of ATP greater than App(NH)p greater than or equal to ADP greater than or equal to AMP while cyclic and guanine nucleotides except GTP are inactive. The negative modulation by ATP of ANF binding is specific for the ANF-R1 receptor subtype since the amount of ANF bound by the guanylate cyclase uncoupled ANF-R2 subtype is increased in the presence of ATP. Furthermore, the effects of ATP on ANF-R1 receptor binding function are still observed with the affinity-purified ANF-R1 receptor, suggesting an allosteric binding site for ATP on the ANF-R1 receptor. In intact membranes, limited proteolysis of the ANF-R1 receptor with trypsin dose-dependently prevents the ATP-induced decrease in ANF binding concomitantly with the formation of a membrane-associated ANF-binding fragment of 70 kDa. These results confirm the direct modulatory role of ATP on hormone binding activity of ANF-R1 receptor and suggest that the nucleotide regulatory binding site is located in the intracellular domain vicinal to the protease-sensitive region.

Adenosine Triphosphate↗
PubMed2002

[The relationship of the left atrial spontaneous echo contrast integrated backscatter with left atrial appendix function and tissue doppler characteristics].

OBJECTIVE: Integrated backscatter (IBS) is an objective method to measure spontaneous echo contrast (SEC) quantitatively. The purpose of this study was to investigate the relationship between the quantitative values of left atrial SEC measured by using IBS with its qualitative gradation as well as the left atrial appendix (LAA) functions and LAA tissue Doppler characteristics (TD). METHODS: Thirty-two patients (23 female, 9 male) with various diseases undergoing transesophageal echocardiography (TEE) were included. Mean age was 52 + 13 years. Left atrial SEC was graded as no SEC (n = 12), mild (n = 12) or severe SEC (n = 8) in patients underwent TEE. LAA peak emptying and LAA apical and basal TD velocities were measured. LAA ejection fraction was assessed by standard means. RESULTS: Between no SEC and mild SEC groups, left atrium IBS and LAA apical TD values were found statistically significant. But there were no differences between two groups regarding LAA emptying velocities, LAA ejection fraction values and LAA basal TD values. All of these parameters were found statistically different between severe and mild SEC groups. The left atrial IBS values were found to be correlated positively with the qualitative SEC grade. The left atrial IBS values correlated negatively with LAA emptying, apical TD velocities and LAA ejection fraction values. CONCLUSION: Integrated backscatter provides an objective quantitative measure of SEC that correlates well with LAA apical TD velocities and the other parameters of LAA.

Atrial Appendage↗
PubMed2004

Left atrial volumes, function and work before and after mitral valve repair in chronic mitral regurgitation.

BACKGROUND AND AIM OF THE STUDY: Despite the effect of mitral valve repair in left ventricular (LV) function having been extensively studied, investigations of left atrial (LA) performance indices are minimal. This prospective study was undertaken to analyze LA volumes, function and work in patients with chronic mitral valve regurgitation (MR) who underwent mitral valve repair; the analyses were conducted both before and six months after surgery. METHODS: Twenty patients (15 males, five females; mean age 51.4 +/- 12.5 years) with severe MR (grade IV) due to floppy mitral valve/mitral valve prolapse (FMV/MVP; anterior, posterior or both) underwent mitral valve repair. LA volumes, maximal at mitral valve opening (LAmax); minimal at valve closure (LAmin); and at onset of atrial systole (P-wave on ECG, LAP); and transmitral Doppler A-wave velocity were measured before and six months after surgery. LA stroke volume (LASV) = LAP - LAmin; LA ejection fraction (LAEF) = LASV/LAP; LA kinetic energy (LAKE) = 1/2 x LASV x 1.06 (specific gravity of blood) x A2 (dyne x cm x 10(3)); LA and LV dimensions and functions were assessed at the same time. RESULTS: NYHA functional class was improved postoperatively by at least one grade. LV systolic and diastolic dimensions were reduced significantly in all patients (p <0.001). LA volumes (LAmax, LAmin and LAP) were decreased significantly in all patients (p <0.001); LASV remained unchanged. LAEF and LAKE were increased significantly (both p <0.001). The A-wave was also increased (p <0.001). CONCLUSION: Increased LA work (LAKE) after mitral valve repair, despite a decrease in LA volumes, suggests that LA muscle dysfunction was present before surgery. LA involvement may precede LV involvement. The determination of LA performance and work will help to optimize the timing of surgery in patients with FMV/MVP and MVR.

Adult↗
PubMed1992

Effect of pharmacological manipulation of endogenous atriopeptin activity on renal function.

Atrial stretch causes the release of atriopeptin (AP, ANF) from preformed vesicular storage sites. The circulating hormone acts on unique receptor sites (containing guanylate cyclase) to release guanosine 3',5'-cyclic monophosphate (cGMP) that mediates the natriuresis and vasodilation and probably the suppression of renin, aldosterone, and vasopressin. The biological effects of atriopeptin are transient because of the rapid inactivation of the circulating hormone (by neutral endopeptidase or clearance receptors) or the second messenger (by cGMP-phosphodiesterase). Heart failure due to chronic cardiac volume overload [aortovenocaval (A-V) fistula] exhibits markedly elevated circulating AP blood levels and urinary cGMP levels, accompanied by induction of ventricular AP gene and protein expression and release. Pharmacological manipulation of endogenous AP, either by inhibiting cGMP phosphodiesterase (i.e., mediator prolongation) or neutral endopeptidase (i.e., prolongation of hormone half-life) in A-V fistula animals results in profound natriuresis and diuresis without hypotension. These pharmacological maneuvers bypass the suppressed renal response to exogenous AP seen in heart failure and provide a rational therapeutic strategy based on our understanding of the underlying physiological and pathological mechanisms.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1994

Haemodynamic actions of a novel sino-atrial node function modulator, ZENECA ZD7288, in the anaesthetized dog: a comparison with zatebradine, atenolol and nitrendipine.

1. ZENECA ZD7288 (4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino) pyrimidinium chloride, formerly ICI D7288) is a novel sino-atrial node function modulator which selectively slows sinus node rate. Its effects on haemodynamic function have been studied in pentobarbitone anaesthetized dogs, in comparison with zatebradine, atenolol and nitrendipine. 2. ZD7288 lowered heart rate in the dose-range 0.02 to 1.0 mg kg-1 i.v. from 152 to 77 beats min-1. Myocardial contractile function (measured as both dPLV/dtmax and right ventricular free wall developed force) decreased along with rate. Stroke volume increased as rate decreased. Cardiac output decreased at doses in excess of 0.2 mg kg-1, i.v. 3. These haemodynamic changes were reversed when heart rate reduction was reversed by atrial pacing and are, therefore, considered to be indirect consequences of heart rate changes induced by ZD7288. 4. The effects of zatebradine paralleled those of ZD7288 (heart rate reduced from 149 to 60.5 beats min-1 over the dose-range 0.02 to 1.0 mg kg-1, i.v.), except that dPLV/dtmax did not decrease with heart rate and increased during arial pacing. 5. Neither ZD7288 nor zatebradine had significant effects on atrio-ventricular conduction at intrinsic heart rates, but both significantly and dose-dependently prolonged the atrio-ventricular conduction interval during atrial pacing at 180 beats min-1. 6. The observed effects of atenolol were commensurate with removal of beta-sympathetic cardiac drive. Atrial pacing was found not to restore the pre-atenolol heamodynamic state completely. 7. Nitrendipine up to 0.2 mg kg- i.v. induced changes indicative of direct vasodilatation accompanied by reflex compensation, followed by cardiac depression at higher doses. Atrial pacing failed to compensate for the effects of vasodilatation, but caused atrio-ventricular conduction block at doses above 0.5mgkg-1, i.v.8.data show ZD7288 has marked heart rate slowing properties and that accompanying haemodynamic changes appear to be secondary to the rate changes, being reversed by atrial pacing even in the continued presence of the drug. Heart rate slowing without depression of contractile function should prove to be of benefit in the treatment of myocardial ischaemia, particularly in the presence of myocardial dysfunction.

Animals↗
PubMed2005

Effect of cardiac resynchronization therapy on left atrial appendage function and pulmonary venous flow pattern.

BACKGROUND: Previous studies have shown improvement in left ventricular function and development of the reverse remodeling in the left ventricle and left atrium after cardiac resynchronization therapy (CRT). The aim of this study was to investigate the effect of CRT on left atrial appendage (LAA) function and pulmonary venous flow pattern. METHODS: Eighteen patients with systolic heart failure and complete left bundle branch block underwent implantation of biventricular pacemaker devices. In order to follow changes in LAA, transthoracic and transesophageal echocardiographic examinations were performed 1 week before and repeated 1 and 6 months after pacemaker implantation. RESULTS: CRT resulted in significant clinical improvement and decrease in NYHA functional class in 17 patients (94%). Maximum and minimum areas of left atrial appendage (LAAAmax and LAAAmin) decreased, with a concomitant increase in LAA ejection fraction. [LAAAmax: from 4.6+/-2 to 4.2+/-1.8 cm2 at the first (P < 0.001) and to 4.0+/-1.8 cm2 at the sixth month (P < 0.001); LAAAmin: from 2.7+/-1.3 to 2.3+/-1.2 cm2 at the first (P < 0.001) and to 2.2+/-1.2 cm2 at the sixth month (P < 0.001) and LAA ejection fraction: from 41+/-12% to 46+/-10% at the first (P = 0.007) and to 47+/-8% at the sixth month (P = 0.003)]. LAA active emptying and filling flow and pulmonary venous systolic velocities also increased after CRT. The appendage active emptying velocity correlated significantly with left ventricular ejection fraction (r = 0.50, P = 0.002), LAA ejection fraction (r = 0.51, P = 0.002), left atrial maximal volume, LAVmax (r = -0.44, P = 0.007), left atrial minimal volume, LAVmin (r = -0.50, P = 0.002) and pulmonary vein systolic flow velocity (r = 0.33, P = 0.05). CONCLUSION: Treatment of heart failure by CRT results with marked improvements in LAA function and increases pulmonary venous systolic velocity.

Adult↗
PubMed1993

An alternative surgical technique in orthotopic cardiac transplantation.

Forty patients underwent orthotopic cardiac transplantation at Wythenshawe Hospital between May 1991 and November 1992. Twenty patients had transplantation using an alternative technique that preserves the shape of the left atrium and leaves the right atrium intact (group A). The remaining twenty had conventional transplantation using the technique described by Lower and Shumway (group B). The patients were randomized to either the new or the conventional technique on an alternate basis. There was no mortality in group A, but two patients in group B developed right ventricular failure and died. Two patients in each group developed nodal rhythm and all four recovered sinus rhythm. Echocardiography and Doppler velocimetry at the transvalvular level confirmed normal atrial function in group A with erratic atrial contraction wave in group B. There was also slightly lower incidence of mitral and tricuspid valve regurgitation in group A than in group B. The improved atrial function in group A may play a part in the prevention of right sided failure following cardiac transplantation.

Echocardiography↗
PubMed1994

The haemodynamic actions of ZENECA ZD7288, a novel sino-atrial node function modulator, in the exercising beagle: a comparison with zatebradine and propranolol.

1. ZENECA ZD7288 (4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino) pyrimidinium chloride, formerly ICI D7288) is a novel sino-atrial node function modulator which selectively slows heart rate. 2. The haemodynamic effects of ZD7288 (0.1, 0.3 and 1.0 mg kg-1, i.v.) have been evaluated and compared with those of placebo (physiological saline), zatebradine (ULFS 49, 0.1, 0.3 and 1.0 mg kg-1, i.v.) and propanolol (0.03, 0.1, and 0.3 mg kg-1, i.v.) in beagles chronically instrumented for measurement of heart rate, aortic pressure, aortic flow and dPLV/dtmax. The dogs were trained to run at 6.5 k h-1 on a level treadmill for 5 min at half hourly intervals over a period of 4 h. Drugs were dosed cumulatively after the second, fourth and sixth exercise periods. 3. Control experiments demonstrated a degree of accommodation to repeated exercise over a period of 4 h. Resting heart rate decreased by 21 beats min-1, but heart rate response to exercise was maintained, whereas dPLV/dtmax at rest remained steady while the response to exercise decreased significantly (by 25% after 2 h, P < 0.05). 4. ZD7288 and zatebradine both decreased heart rate during exercise in a dose-dependent manner, whilst heart rate at rest did not differ from resting heart rates in saline dosed control animals. In contrast, heart rate at rest and during exercise were lowered equally by the lowest doses of propranolol (approximately by 30 beats min-1), and additional doses caused only minor additional decreases. The exercise-induced tachycardia was maintained within 12% of pre-dose levels, presumably by withdrawal of vagal tone.5. Cardiac inotropism, as indicated by dPLv/dt max, was not affected by ZD7288 or zatebradine at rest,although the inotropic response to exercise decreased in proportion to the decreases in exercise-induced tachycardia. Propranolol caused a marked dose-dependent decrease in the exercise-induced inotropic response (by 85% at 0.3mg kg-1).6. Whilst the sino-atrial node modulators increased stroke volume at rest, and augmented increases in response to exercise, propranolol did not affect resting stroke volume and decreased the responses to exercise.7. Cardiac output at rest and cardiac output increases during exercise were well maintained in the presence of ZD7288 and zatebradine in contrast to propranolol which induced a significant depression of cardiac output, both at rest and during exercise. Propranolol also caused significant systemic vasoconstriction.8. In conclusion, ZD7288 has haemodynamic actions comparable to those of zatebradine despite their chemical dissimilarity. ZD7288 may be of benefit in the treatment of ischaemic heart disease by reducing heart rate without impairing cardiac function.

Animals↗