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PubMed1991

Binding profiles of class I antiarrhythmic agents to cardiac muscarinic receptors: competitive and allosteric interactions with the receptors and their pharmacological significance.

The binding profiles of the class I antiarrhythmic agents disopyramide, pirmenol and pentisomide (CM7857) to cardiac muscarinic receptors were characterized by the binding assay using [3H]-N-methyl scopolamine ([3H]NMS) as a ligand and their anti-muscarinic actions were investigated functionally in left atrial preparations. All the agents displaced the specific binding of 200 pM [3H]NMS from guinea pig left atrial membranes. Computer-assisted analysis indicated that pirmenol interacted with a single class of binding sites, but the displacement curves of disopyramide and pentisomide were shallow and best fitted to a two-site model. When the concentration of [3H]NMS was increased to 1 nM, the displacement curve of pirmenol was best fitted to a two-site model. In higher concentrations, these agents inhibited the dissociation of [3H]NMS initiated by 1 microM atropine in a concentration-dependent manner, thus revealing allosteric interactions. Two enantiomers of pirmenol possessed qualitatively the same binding properties as the racemate. In guinea pig left atria, disopyramide, pirmenol and pentisomide shifted the concentration-response curves for the negative inotropic effect of carbachol in a parallel manner. The slopes of Schild plot were not significantly different from unity, indicating that they act as a competitive antagonist of cardiac muscarinic receptors. Excellent correlation between the high affinity pKi values and the pA2 values was established for the antiarrhythmic agents. These findings suggest that disopyramide, pirmenol and pentisomide all interact with cardiac muscarinic receptors in both a competitive fashion and an allosteric one. The dual mode of the interaction with cardiac muscarinic receptors seems to be independent of their chiralities.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

[Tissue Doppler echocardiography: a new stage in the study of myocardial function].

Tissue Doppler echocardiography is a new technique that allows selective visualization and measurement of myocardial velocities, affording a new perspective on cardiac function. It has been showing promising and exciting preliminary results on coronary artery disease, hemodynamics, cardiomyopathies, right ventricular and aortic diseases and arrhythmias, opening a new era in the analysis of regional myocardial function.

Aorta↗
PubMed1995

[Transesophageal echocardiography in patients with atrial fibrillation, candidates for cardioversion: usefulness and limitations].

BACKGROUND: Thromboembolic complications after electrical cardioversion (CV) of atrial fibrillation (AF) have been attributed to the dislodgment of preexistent left atrial thrombus during the resumption of atrial contraction. Transesophageal echocardiography (TEE) has been used to identify patients without thrombus, who potentially could undergo CV without anticoagulation. However, embolic events after CV in patients without evidence of thrombus on TEE have recently been reported. AIM OF THE STUDY: To evaluate if absence of thrombi or prethrombotic conditions such as spontaneous echo contrast or left atrial appendage disfunction can justify electrical CV without anticoagulant therapy. METHODS: Seventy-four patients with AF and candidates for CV underwent monoplane TEE. Patients were cardioverted without anticoagulation in case of: 1) absence of thrombus and/or spontaneous echocardiographic contrast and 2) good visualization of left atrial appendage, with a well defined peak blood flow velocity greater than 20 cm/sec. In all other cases, patients underwent anticoagulant therapy which started 3 weeks before CV and continued for 4 weeks afterwards. RESULTS: Forty-six patients, without thrombus or "prethrombotic" conditions, did not receive anticoagulation, while 28 followed traditional therapy with warfarin. Four patients with a thrombus in the left atrial appendage were identified: 1 died of cerebral embolism 3 days after the beginning of anticoagulation, in another one CV was definitely deferred because of the persistence of thrombus after 1 month of warfarin therapy. One patient, with left atrial appendage disfunction, died suddenly after 5 days of anticoagulation. Two patients reverted spontaneously in sinus rhythm. Two patients refused electrical CV. The remaining 67 patients underwent electrical CV which was successful in 56 of them. Cerebral embolism occurred 24 hours after CV in one patient who did not receive anticoagulation. Repeat TEE soon after embolism showed absence of thrombus or spontaneous echo contrast, but the presence of low flow velocity in the left atrial appendage. CONCLUSIONS: In patients in AF candidates for CV, exclusion of thrombi or prethrombotic conditions by TEE does not exclude the risk of thromboembolic events and the need for anticoagulant therapy. Left atrial appendage function can be stunned or impaired immediately after CV, favouring a thrombogenic milieu and subsequent embolic events. Therapeutic anticoagulation at the time of as well as after cardioversion is actually recommended.

Aged↗
PubMedDate not supplied

Circuit model-based analysis of the impedance rheopneumogram.

Impedance rheopneumography, like other applications of electrical bio-impedance, is receiving increasing attention as a simple, non-invasive tool for clinical diagnosis of the pulmonary circulation. However, one major drawback of this method lies in the difficulty in computing accurately the time domain parameters therefrom for diagnostic purposes. This paper presents a model-oriented analysis technique based on physiological consideration of both the arterial and venous pathways of the pulmonary circulatory system. The technique involves a combination of a two-segment model and a modified form of the 'Windkessel' model, the summed response of which is curve-fitted to measurement data via the non-linear method of Marquardt to obtain the system parameters. A simple illustrative application is also given to explain the changes in wave morphology for a subject under measurement in the supine and sit-up positions. The result suggests that this technique shows promise of providing useful physiological information and better insight of system behaviour than existing technique.

Algorithms↗
PubMed1996

Successful transplantation of cadaver hearts harvested one hour after hypoxic cardiac arrest.

BACKGROUND: A shortage of donor organs in clinical transplantation prompted us to study whether resuscitated "dead" hearts could be used for successful orthotopic heart transplantation. METHODS: Donor hearts were resuscitated with cardiopulmonary bypass after 3 minutes (the control group; n = 8) or 60 minutes (the experimental group; n = 6) of hypoxic cardiac arrest after induction of brain death. RESULTS: All the animals of each group were successfully weaned from cardiopulmonary bypass with 5 micrograms/kg/min of dopamine 1 hour after transplantation, and cardiac function with or without dopamine was better preserved in the experimental group than the control group (with maximum slope of pressure-volume relationship with dopamine: 198.0% +/- 36.8% versus 121.2% +/- 47.2%; maximum slope of pressure-volume relationship without dopamine: 130.6% +/- 41.5% versus 70.8% +/- 21.5% [mean +/- standard deviation] as percentage of values after brain death, respectively; p < 0.01 by unpaired t test). CONCLUSIONS: These results indicate that cadaver hearts 60 minutes after anoxic arrest can be successfully reanimated and orthotopically engrafted with various methods and drugs.

Animals↗
PubMed1977

Echocardiography after mitral valve replacement and criteria of paraprosthetic regurgitation.

19 patients with Björk-Shiley mitral tilting disc valve prostheses were studied by echocardiography before the valve replacement operation and postoperatively every three months up to one year. In 14 patients with normal prosthetic function the left atrial diameter decreased markedly after operation (p less than 0.001), but echocardiographic dimensional indices of left ventricular performance remained unchanged. Paradoxical or markedly hypokinetic motion of the interventricular septum was observed within 3 months of operation in 46% of the patients, but in only 28% in studies performed 9 - 12 months after the replacement. The ampliture of the disc was on average 11 +/- 2 mm. In 5 patients with paraprosthetic regurgitation the left atrial diameter increased with the development of regurgitation and decreased again after successful reoperation. In these patients the left ventricular end diastolic and stroke volumes were great (p less than o.01) than in patients with normal prostheses. The septal motion was in the normal direction in all these 5 patients and the septal amplitudes were greater (p less than 0.01) than in the patients with normal prostheses. The amplitudes of the disc were normal, but abnormal anterior movement of the disc at the beginning of the diastole was observed. These data demonstrate that echocardiography is useful in the diagnosis of paraprosthetic mitral valve regurgitation.

Adult↗
PubMed1995

[Atrial filling fraction predicts left ventricular systolic function after myocardial infarction: pre-discharge echocardiographic evaluation].

Aim of the study was to examine the relation between Doppler-derived indices of left ventricular diastolic and systolic function early after myocardial infarction. Fifty-three patients (31 males, 22 females) recovering from acute myocardial infarction underwent predischarge Doppler echocardiographic examination. Patients with age > 70 years, previous myocardial infarction, more than mild mitral and aortic regurgitation, mitral and aortic stenosis were excluded. Twenty-two healthy subjects (13 males; 9 females) free of coronary risk factors were selected as the control group. Both end-diastolic and end-systolic volumes and ejection fraction were measured by two-dimensional echocardiography. Pulsed Doppler was used to evaluate mitral inflow and left ventricular outflow velocity patterns. The following indices were measured: peak velocity of early (E) and late (A) flows, ratio of E/A peak velocities, ratio of early to late time velocity integrals, atrial filling fraction (time velocity integral A / time velocity integral of flow during total diastole) and deceleration time of E wave for mitral inflow; peak and time-velocity integral for left ventricular outflow. Stroke volume and cardiac output were obtained by pulsed Doppler using the left ventricular outflow method. The two groups were comparable for age, with blood pressure (p < 0.05) and heart rate (p < 0.01) reduced in myocardial infarction patients. Both end-diastolic and end-systolic volumes were significantly higher (both p < 0.0001) and ejection fraction (p < 0.0001) lower after myocardial infarction. Also stroke volume and cardiac output (both p < 0.0001) were reduced in myocardial infarction patients. No significant difference in Doppler indices of diastolic function was observed between the two groups, except for shortened deceleration time (p < 0.0001) in myocardial infarction patients. Multilinear regression analyses were performed separately into the two groups to identify determinants of left ventricular systolic function. After adjusting for age, heart rate, systolic blood pressure and both end-diastolic and end-systolic volumes, atrial filling fraction was an independent predictor of stroke volume, with a direct relation (beta coefficient = 0.53, p < 0.001), in myocardial infarction patients but not in health subjects. In conclusion, our study confirms the pseudonormalization of diastolic pattern after myocardial infarction. The direct relation between atrial filling fraction and stroke volume indicates the importance of atrial contribution to maintain an adequate systolic performance in patients with myocardial infarction.

Atrial Function, Right↗
PubMed1985

The effects of left atrial and left ventricular cannulation on left ventricular function.

A study in anesthetised dogs was undertaken to investigate the immediate effects of cannulation of the heart for left heart bypass on left ventricular function. Twenty-six mongrel dogs were studied. In the first group of 13 dogs (Group A), left atrial cannulation was performed through the atrial appendage and in the second group of 13 dogs (Group B), the left ventricular apex was also cannulated. Systemic blood pressure, heart rate, left atrial pressure, left ventricular end diastolic pressure and dP/dT showed no difference in left ventricular function between Groups A and B. Global ejection fraction (EF) measured by injection of technetium99m-labelled human serum albumen with gated left ventricular imaging, showed no significant difference between the two groups but analysis of the regional contribution to global EF in Group B dogs demonstrated a significant reduction in left ventricular function at the site of ventricular cannulation (P less than 0.05). These findings, together with other reported disadvantages of left ventricular cannulation, suggest that the left atrium is the preferred site for cannulation when left heart bypass is required. Many reports attest to the value of mechanical circulatory support in patients with ventricular dysfunction who cannot be weaned from cardiopulmonary bypass (2, 4, 10, 11, 15). Initial support is commonly provided by an intra-aortic balloon pump but, in more severe cases, use of a left ventricular assist device may be warranted. More recently, such devices have also been employed in the management of patients with cardiogenic shock refractory to medical therapy (10).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1998

Long-term effect of VVI pacing on atrial and ventricular function in patients with sick sinus syndrome.

We conducted a prospective, 6-month echocardiographic study on the effect of VVI pacing on left atrial and ventricular function and dimensions in patients with sick sinus syndrome. Thirty-nine patients (23 women and 16 men, aged 71 +/- 9.2 years; 30 in sinus rhythm and 9 in atrial fibrillation) who had a VVI pacemaker implanted because of sick sinus syndrome were recruited in the study. In 26 patients who presented with and remained in sinus rhythm, paced left ventricular ejection fraction and stroke volume were significantly decreased (71.4% +/- 11.8% to 67.0% +/- 13.6%, and 73.9 +/- 29.0 cm3 to 66.3 +/- 21.1 cm3, respectively, P < 0.001 for both), whereas the paced diastolic dimension of the left atrium was significantly increased (3.2 +/- 0.7 cm to 3.7 +/- 0.9 cm, P < 0.001) at 6 months as compared with preimplantation. In nine patients with atrial fibrillation at implantation paced left ventricular ejection fraction at follow-up was significantly decreased (67.7% +/- 10.1% to 64.2% +/- 10.6%, P =0.003), but paced stroke volume and left atrial diastolic dimension were not significantly changed (75.1 +/- 25.6 cm3 to 79.0 +/- 22.7 cm3, and 4.3 +/- 1.2 cm to 4.6 +/- 1.5 cm, P = NS for both) at follow-up. Cessation of pacing and restoration of sinus rhythm in 21 patients at follow-up did not result in any significant change of ejection fraction (67.5% +/- 10.2% ti 67.6% +/- 9.7%, P = NS) whereas stroke volume was increased (59.1 +/- 19.6 cm3 to 69.1 +/- 22.3 cm3, P < 0.0001) in comparison with paced values. However, compared with preimplantation values, ejection fraction was significantly decreased (70.4% +/- 10.0% to 67.6% +/- 9.7%, P = 0.001), whereas stroke volume was not significantly changed (68.4 +/- 22.3 cm3 to 69.1 +/- 22.3 cm3, P = NS) during sinus rhythm at follow-up. In 14 of those patients, discontinuation of pacing resulted in a significant increase of left atrial fractional shortening (8.1% +/- 1.7% to 20.1% +/- 4.3%, P < 0.001) and significant increase of left atrial diastolic dimension compared with paced and preimplantation levels (3.8 +/- 0.7 cm vs 3.6 +/- 0.7 cm and 3.0 +/- 0.5 cm, respectively, P < 0.001). Long-term VVI pacing in patients with sick sinus syndrome results in increase of the left ventricular end-systolic dimension and permanent reduction of the left ventricular ejection fraction. In the left atrium, VVI pacing causes an immediate reduction of the fractional shortening as well as long-term increase of the diastolic dimension.

Aged↗
PubMed1996

Extracardiac adjustment of mitral chordae replacement.

This study was designed to determine the feasibility of completing mitral chord repair externally when the heart was weaned from bypass. Ten anesthetized dogs (22.9 +/- 4.6 kg) were placed on cardiopulmonary bypass through a left thoracotomy. The left atrium was opened and one or two marginal chords of the anterior mitral leaflet were divided. A double-armed 2-O polypropylene suture was placed in the margin of the mitral leaflet, and both suture ends were brought outside of the ventricle through the anterior papillary muscle, but were not anchored. Production of mitral incompetence was verified when the animals were weaned from bypass. Mean left atrial pressure (LAPm), the v wave of the left atrial pressure (LAPv), systolic billowing of the anterior leaflet into the left atrium above the mitral closure line (two-dimensional echocardiography, long axis), and function curves (left atrial-aortic systolic pressure, LAPv-AoSP) were used to determine valve competence and functionality of the repair. All values are expressed as means +/- SE. Acute mitral incompetence in this model was associated with severe left atrial bulging, left atrial billowing of the anterior leaflet (7-12 mm, 9.6 +/- 1.6 mm), significantly increased left atrial pressure [LAPv, 30.5 +/- 5.8; LAPm, 23.6 +/- 4.3 mm Hg; both P < 0.01 vs control (10.5 +/- 2.5 and 7.5 +/- 2.7 mm Hg, respectively)], and decreased systemic pressure development (AoSP, 84 +/- 8.8 vs 108 +/- 12.3 mm Hg; P < 0.01). The slope of the atrial-systemic pressure curve was decreased significantly, shifted to the right and reduced by more than half (2.1069 vs 0.9190; P < 0.05). External adjustment of the pledgeted suture ends returned all values to within control limits (LAPv, 12.7 +/- 4.1; LAPm, 9.8 +/- 4.3; AoSP, 104 +/- 10.5; LAP-AoSP slope, 2.0909; all P = n.s.), atrial bulging was not evident, and atrial displacement of the valve leaflet could no longer be visualized. These data suggest that mitral chord repair is feasible through a thoracotomy and, more importantly, final adjustments to obtain optimal chord length can be completed externally, guided by changes in dynamic, physiologic parameters.

Animals↗