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PubMed1999

Effects of hirsutine and dihydrocorynantheine on the action potentials of sino-atrial node, atrium and ventricle.

The effects of hirsutine, an indole alkaloid from Uncaria rhynchophylla MIQ. JACKSON with antihypertensive, negative chronotropic and antiarrhythmic activity, and its C3 structural epimer, dihydrocorynantheine, on membrane potentials of rabbit sino-atrial node and guinea-pig right ventricle and left atrium were studied with microelectrode techniques. In sino-atrial node preparations, hirsutine and dihydrocorynantheine (0.1 microM to 10 microM) concentration-dependently increased cycle length, decreased slope of the pacemaker depolarization (phase 4 depolarization), decreased maximum rate of rise and prolonged action potential duration. In atrial and ventricular preparations, both compounds (0.1 microM to 30 microM) concentration-dependently decreased maximum rate of rise and prolonged action potential duration. These results indicate that hirsutine and dihydrocorynantheine have direct effects on the action potential of cardiac muscle through inhibition of multiple ion channels, which may explain their negative chronotropic and antiarrhythmic activity.

Action Potentials↗
PubMed2001

Long-term endothelin receptor blockade improves cardiovascular function in diabetes.

To evaluate the potential contribution of endothelin-1 (ET-1) toward the cardiovascular complications of diabetes, the present study examined the effects of chronic ET receptor blockade with bosentan on heart function and vascular reactivity in streptozotocin (STZ)-induced diabetic rats. Wistar rats were divided into four groups: control, control bosentan-treated, diabetic, and diabetic bosentan-treated. After chronic bosentan treatment, cardiac function and vascular reactivity were assessed. Exvivo working heart function was determined in terms of rate of contraction (+dP/dt), rate of relaxation (-dP/dt), and left ventricular developed pressure (LVDP). Contractile responses to ET-1 were determined in isolated superior mesenteric arteries. In addition, ET-1-like immunoreactivity was determined in ventricular and vascular tissues by immunohistochemistry. Cardiac function was depressed in the untreated-diabetic group. Bosentan treatment improved working heart function; hearts from the diabetic bosentan-treated group exhibited improved LVDP and -dP/dt. The contractile responses of mesenteric arteries to ET-1 were exaggerated in the untreated-diabetic group. Long-term bosentan treatment normalized these responses. Immunohistochemical analyses revealed increased ET-1-like immunoreactivity in ventricular and vascular tissues from untreated diabetic rats. These data show the beneficial effects of ET(A/B) receptor blockade on cardiovascular function in STZ-diabetic rats. An altered ET-1 system may contribute toward the pathogenesis of cardiovascular dysfunction in diabetes.

Animals↗
PubMed1998

What range of programmable AV delays is necessary in antibradycardia DDD stimulation?

DDD pacemakers differ considerably in device specific extents of AV delay (AVD) programmability. To demonstrate the requirements of a mean DDD pacemaker patient population optimal AVDs in 200 DDD pacemaker patients (age 8 to 91 years) were estimated by left atrial electrography. The results should help to define an AVD programmability standard. Left atrial electrograms were recorded via a bipolar filtered esophageal lead. The method aims on adjusting the left atrial electrogram to 70 ms prior to the ventricular spike, both during VDD and DDD operation of the pacemaker. In atrial sensed stimulation the optimal AVD varied from 40 to 205 ms (100.5 +/- 24.5 ms) and in atrial paced stimulation from 85 to 245 ms (169.1 +/- 24.5 ms). The difference of the mean values is statistically significant (p < 0.001). The difference between both values in the individual patient, the individual AVD correction time, varied from 0 to 170 ms (68.7 +/- 26.6 ms). Thus, from our findings requirements on AV delay programmability standard can be derived: AVDs (1) should have a range from 40 to 250 ms, (2) should be independently programmable during atrial sensed and atrial paced operation, and (3) should provide as nominal settings 100 ms for atrial sensed and 170 ms for atrial paced stimulation.

Aged↗
PubMed1995

Inhaled nitric oxide and hemodynamic evaluation of patients with pulmonary hypertension before transplantation.

OBJECTIVES: We investigated the effect of inhaled nitric oxide and infused acetylcholine in patients with pulmonary hypertension undergoing cardiac catheterization before cardiopulmonary transplantation. BACKGROUND: The fate of patients under consideration for transplantation of the heart or lungs, or both, is influenced by the evaluation of their pulmonary vascular reactivity. METHODS: We evaluated 11 patients who were classified into two groups on the basis of mean left atrial pressure > 15 mm Hg (group I, n = 6) or < or = 15 mm Hg (group II, n = 5). All patients inhaled nitric oxide at 80 ppm. This was preceded by an infusion of 10(-6) mol/liter of acetylcholine in seven consecutive patients (n = 3 in group I, n = 4 in group II). RESULTS: In group I, inhaled nitric oxide decreased pulmonary artery pressure from (mean +/- SE) 71 +/- 13 to 59 +/- 10 mm Hg (p < 0.05), pulmonary vascular resistance from 14.9 +/- 3.8 to 7.6 +/- 1.7 Um2 (p < 0.05) and intrapulmonary shunt fraction from 17.8 +/- 3.6% to 12.7 +/- 2.1% (p < 0.05). Left atrial pressure tended to increase from 27 +/- 4 to 32 +/- 5 mm Hg (p = 0.07). In group II pulmonary vascular resistance decreased in response to nitric oxide from 36.4 +/- 9.0 to 31.1 +/- 7.9 Um2 (p < 0.05). Cardiac index, systemic pressure and resistance did not change in either group. Seven patients who received acetylcholine had no significant alteration in pulmonary hemodynamic variables. CONCLUSIONS: These preliminary observations suggest that nitric oxide is a potent pulmonary vasodilator with minimal systemic effects. It may be useful in discriminating patients needing combined heart and lung transplantation from those requiring exchange of the heart alone.

Acetylcholine↗
PubMed2001

Noninvasive right and left heart catheterization: taking the echo lab beyond an image-only laboratory.

The assessment of cardiovascular hemodynamics is an extremely important component of managing patients with cardiac diseases. For years, this has been accomplished primarily through the use of right and left heart catheters placed within the cardiac chambers. Since this is an invasive technique, it should only be used when necessary; patient discomfort, infections, and overall risks for physicians would be reduced if noninvasive methods were utilized when available. Echocardiography (echo) provides the greatest ability to determine cardiovascular hemodynamics noninvasively, but requires the utmost precision and care to avoid misinterpretation. When used correctly, echocardiographic modalities provide an even greater assessment of the cardiac patient than invasive techniques. A safer and more comprehensive interpretation is available, and thus, echo should be considered the modality of choice-the new gold standard.

Atrial Function↗
PubMed1993

[Mid-term clinical and prognostic evaluation of idiopathic atrial fibrillation].

Forty-six patients with idiopathic or lone atrial fibrillation (AF) underwent clinical evaluation in the cardiology outpatient department. The follow-up period was 4.6 +/- 2.5 years. The prevalence of idiopathic AF was 19% (89% paroxysmal and 11% permanent) in a population of 244 patients with atrial fibrillation. The global prevalence was 1.15% out of 4,000 patients examined over the same period. A history of paroxysmal atrial fibrillation over a 6 +/- 4 year period was obtained in 61% of the patients with idiopathic AF before the study. At inclusion, 24% of patients were asymptomatic. During follow-up, 12 patients (26%) developed cardiovascular disease and/or hypertension. The size of the left atrium was measured by echocardiography in 45 patients and reevaluated in 30 of them during follow-up without any statistically significant difference being observed between the two values. There were no thromboembolic complications or deaths during follow-up. These results show that idiopathic AF is not uncommon in cardiology clinics. The evolution of the paroxysmal forms is variable--but the medium-term prognosis is excellent. In some cases, idiopathic AF may be a manifestation of asymptomatic coronary artery disease but the relationship between the two pathologies has not been definitely established.

Adult↗
PubMed1995

Relationship between interatrial conduction times and left atrial dimension in patients undergoing atrioventricular stimulation.

Interatrial conduction time (IACT) and left atrial dimension (LAD) were determined in 75 patients (41 males, 34 females, mean age 78.2 +/- 7.9 years) undergoing atrioventricular (AV) stimulation. The LAD was measured by M mode echocardiography as the distance between the posterior aortic wall and the posterior left atrial wall. The IACT was determined during a transvenous dual chamber pacemaker implant done under local anesthesia (lidocaine). The spontaneous interatrial conduction time (SIACT) was measured from the intrinsic deflection (ID) of the right atrium recorded in a unipolar mode (unipolar J-shaped lead positioned in the right appendage) to the ID of the left atrium (bipolar esophageal lead, left atrial positive deflection equal to the negative one) during sinus rhythm. The right atrium then was paced at a rate slightly greater than the spontaneous one. The paced interatrial conduction time (PIACT) was measured from the stimulus artifact to the left atrial ID. The PIACT was also measured during incremental right atrial pacing (10 beats/min step increase to 180 beats/min) and, from these measurements, the maximum increase of PIACT (MIPIACT) was deduced. The LAD was measured at 39.5 +/- 8.7 mm, SIACT at 70.3 +/- 24.8 msec, PIACT at 118.8 +/- 27.9 msec, and MIPIACT at 16.5 +/- 16.4 msec. We found highly significant relationships between SIACT and LAD (P = 0.0006, r = 0.39), PIACT and LAD (P = 0.0001, r = 0.45), and MIPIACT and LAD (P = 0.0006, r = 0.38). We also noted that the LAD was greater in patients in whom MIPIACT was > 10 msec than in patients in whom the MIPIACT was negligible (P < 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1999

Role of genomic mechanisms on cAMP-dependent positive inotropism in isolated left atrium of rat.

It is well known that beta-adrenoceptor stimulation induces positive inotropism by cAMP-dependent phosphorylation of cardiac calcium channels. Furthermore, hypertrophy of different tissues including the heart have been related to the stimulation of these adrenoceptors via mechanisms coupled to activation of transcription and protein synthesis. Early effects of isoproterenol mediated via this pathway has also been associated to the stimulation of beta-adrenoceptors. However, the effects on the inotropism through genomic mechanisms have not yet been described. Isoproterenol (3 nM to 3 microM) induced a concentration-dependent positive inotropism, in isolated left atrium of male Wistar rats electrically stimulated (0.5 Hz, 5 ms, 30-50% above the threshold voltage), which was antagonized by atenolol (1 microM) and inhibited by a protein kinase A inhibitor, (R)p-cAMPS (10 microM). The inhibitor of transcription, actinomycin D (4 microM), and the protein synthesis inhibitor, cycloheximide (35.5 microM), significantly decreased the positive inotropism induced by isoproterenol. Forskolin (0.1 to 3 microM), an activator of adenylyl cyclase, induced a concentration-dependent positive inotropism which was also inhibited by (R)p-cAMPS, actinomycin D and cycloheximide. In the left atrium of rat, isoproterenol induced a positive inotropism which seems, at least in part, dependent upon intact transcription and protein synthesis, as suggested by the fact that the response was inhibited by the incubation with actinomycin D and cycloheximide. In addition, this genomic effect seems to be mediated by a cAMP-dependent mechanism. As it was inhibited by a protein kinase A inhibitor ((R)p-cAMPS) and similarly to isoproterenol, the positive inotropism induced by forskolin, which increases cytosolic cAMP, was also inhibited by actinomycin D and cycloheximide.

Adrenergic beta-Agonists↗
PubMed1993

[Surgical management of left cor triatriatum in adults].

Cor triatriatum sinistrum is a rare congenital cardiac anomaly in which a membrane divides the left atrium. Severity of the disease depends on the size of the opening on the membrane. The anomaly presents with severe pulmonary hypertension and prognosis is unfavourable without surgery. From 1976 through 1992, 5 adult patients were treated surgically in our institution. Cor triatriatum can be corrected surgically with a low mortality and excellent late results if an early preoperative diagnosis has been made. Clinical findings and cardiac catheterization do not provide sufficient data for the correct diagnosis. From a review of our experience it is concluded that echocardiography is superior to angiography for diagnosing cor triatriatum.

Adult↗
PubMed1994

Edema development and recovery in neurogenic pulmonary edema.

We determined the time course of changes in extravascular lung water (EVLW) that occur after massive sympathetic activation produced by intracisternal veratrine administration in chloralose-anesthetized dogs. Three groups of dogs were studied. In the first group (n = 9), acute increases in EVLW (occurring within minutes) were determined both by measuring extravascular thermal volume and by gravimetric analysis. In the second (n = 6) and third (n = 7) groups, changes in EVLW were followed for 2-3 h after veratrine administration. Extravascular thermal volume was measured in the second group. In the third group, right atrial injections of a vascular indicator (125I-labeled serum albumin) and an extravascular indicator (3HOH) were made while blood was sampled from the pulmonary artery (PA) and left atrium, and EVLW was determined by deconvolution of the left atrial and PA concentration-time curves. Indicator-dilution and gravimetric EVLW increased acutely only in dogs in which PA pressure exceeded 60 Torr, with two- to four-fold increases in EVLW being observed in dogs that developed the highest PA pressures (maximum 94 Torr). Thus, severe edema can develop rapidly after massive sympathetic nervous system activation but requires extreme degrees of pulmonary hypertension. In several dogs after the acute increase in EVLW associated with the pulmonary hypertension, the indicator-dilution EVLW decreased with time. These decreases appear to effect clearance of edema fluid rather than alterations in perfusion.

Animals↗
PubMed1993

Myocardial blood flow and VO2 in lambs with an aortopulmonary shunt during strenuous exercise.

To determine how much myocardial O2 consumption (VO2) would increase during an additional load on the heart in shunt as compared with control lambs, we studied 12 7-wk-old lambs with an aortopulmonary left-to-right shunt (59 +/- 3% of left ventricular output, mean +/- SE) and 11 control lambs during exercise at 80% of their predetermined peak VO2 (VO2peak), at 12 +/- 1 days after surgery. During exercise, systolic aortic pressure increased by 25% in the two groups. Left atrial pressure and left ventricular stroke volume did not change significantly and remained considerably higher in shunt than in control lambs. Heart rate, however, increased less in shunt than in control lambs (163 +/- 8 to 235 +/- 8 vs. 107 +/- 7 to 230 +/- 8 beats/min). The same was true for left ventricular myocardial blood flow (245 +/- 19 to 391 +/- 27 vs. 128 +/- 10 to 320 +/- 45 ml.min-1 x 100 g-1) and myocardial VO2 (847 +/- 101 to 1,692 +/- 136 vs. 528 +/- 58 to 1,579 +/- 178 mumol O2 x min-1 x 100 g-1). We conclude that, despite the volume load, myocardial VO2 of shunt lambs does not increase to a greater extent than in control lambs during a considerable additional load on the heart.

Anastomosis, Surgical↗
PubMedDate not supplied

In vivo and in vitro studies on the mechanism and clinical significance of spontaneous echocardiographic contrast in patients with atrial dysrhythmias.

The pathogenesis of spontaneous echocardiographic contrast (SEC) is complex and multifactorial. Although originally described in low-flow state situations such as in the left atrium of patients with mitral stenosis or in the false lumen of patients with aortic dissection, its detection is highly dependent on technical factors such as the frequency of the transducer used. Multiple blood components have been implicated in SEC formation and erythrocyte aggregation currently appears to be the most likely mechanism. SEC is related to atrial fibrillation and is commonly found in patients with thrombus or prior history of thromboembolism. In addition, it may represent a prognostic marker for patients with atrial fibrillation because patients with SEC have a higher incidence of subsequent thromboembolic events. Therapeutic options include anticoagulation and, perhaps, antiplatelet therapy. Further prospective studies are necessary to better define SEC pathogenesis and treatment.

Arrhythmias, Cardiac↗
PubMed1993

[Hypoplastic left heart syndrome. Present experiences and future possibilities].

The authors report experiences from Norwood's staged palliation for hypoplastic left heart syndrome performed in Philadelphia on Norwegian children. Although there is no universal agreement that these children should be operated at all, the Norwegian health authorities have decided that all expenses for transport, examination and treatment shall be covered by the National Health Insurance Scheme. Since 1987 a total of 21 children have been transported to USA for operation. Eight of these children have completed all the planned stages of the operative treatment. Two are waiting for stage 3. 11 children have died. The authors discuss how to proceed with regard to treatment of this complicated patient group in future.

Atrial Function, Left↗
PubMedDate not supplied

[Duration-outcome relations in nonpharmacological treatment of chronic cardiac failure developed after acute myocardial infarction].

Left-ventricular (LV) systolic-diastolic function and cardiac rhythm variability, the rate of pathological LV remodeling and outcomes of the disease for 18 months were studied in 394 males at the age 35-68 years suffering from chronic cardiac failure (CCF) of NYHA functional class I-II consequent to myocardial infarction occurring 9.6-4.2 months before. It was found that long-term (12-24 weeks) taking sauna, underwater dousch-massage, general effervescent baths and exercise in combination with drug therapy in patients with asymptomatic CCF inhibit the rate of LV remodeling, decrease LV hypertrophy, improve diastolic function of the heart. This results in lowering a cumulative risk of unfavourable outcomes of the disease by 42% (p = 0.006). The best of effect of the combined therapy is not achieved in angina of effort, massive myocardial hypoperfusion zones, no viable myocardium in the zones of the lesion, marked LV hypertrophy.

Acute Disease↗
PubMed1996

Plasma endothelin-1 level in athletes after exercise in a hot environment: exercise-induced dehydration contributes to increases in plasma endothelin-1.

We investigated whether dehydration due to exercise contributes to the increase in plasma endothelin-1 (ET-1) concentration. We measured the plasma concentration of ET-1 before and after exercise in a hot environment (about 30 degrees C). Five male intercollegiate Kendo (Japanese fencing) players entered the present study. Each athlete participated in 15 min of Kendo fighting, followed by 5 min of rest and another 15 min of Kendo fighting (i.e., total exercise 30 min), with or without oral intake of 700 ml of water. Body weight and left atrial diameter, a parameter that reflects changes in circulating plasma volume, were significantly decreased after exercise under both conditions. However, the decreases in both values were significantly greater after exercise without water intake than after exercise with water intake, indicating that dehydration and decreased circulating plasma volume were more marked after exercise without water intake. The extent of the increase in plasma ET-1 concentration appeared to be closely related to the extent of exercise-induced dehydration; the greater the dehydration, the greater the increase in plasma ET-1 concentration. These findings suggest that exercise-induced dehydration may contribute to increases in plasma ET-1 concentrations.

Adult↗
PubMed1995

Left atrial size--a risk factor for left atrial thrombi in mitral stenosis.

In a follow-up study, 77 patients with predominant mitral stenosis were examined to investigate the role of left atrial (LA) enlargement in LA thrombi. Fifteen (19.4%) patients had LA thrombi. Of these, 2 (13.3%) were in sinus rhythm and 13 (86.7%) in atrial fibrillation. Fourteen (93.3%) of the patients with LA thrombi had an LA size > or = 4.8 cm. Only one (6.7%) patient had an LA size of 4.4 cm and was in atrial fibrillation. The median LA size in patients with LA thrombi was 5.2 cm compared with 4.75 cm in patients without LA thrombi (p < 0.01). The relative risk for LA thrombi in patients with an LA size > or = 4.8 cm compared with patients with an LA size < 4.8 cm was 10.0 (95% confidence interval 1.4 to 71.4). It was thus confirmed that LA enlargement > or = 4.8 cm is an independent risk factor for LA thrombi in patients with mitral stenosis.

Adult↗
PubMed1995

Left atrial performance indices in chronic mitral valve disease.

Multidimensional left atrial (LA) performance indices have not been extensively studied in chronic mitral valve disease. LA maximal volume, stroke volume (LA volume at atrial systole minus LA minimal volume), LA ejection fraction (stroke volume/volume at atrial systole) and A-wave velocity, were measured in 14 patients with mitral stenosis (mean mitral valve area 1.5 cm2); 14 patients with chronic mitral regurgitation all in sinus rhythm; and were compared to 20 age and sex matched normal control subjects using biplane transthoracic echo and pulsed Doppler. Although LA volumes--maximal and at onset of atrial systole--were greater in mitral regurgitation and mitral stenosis (p < 0.01) compared to normal subjects, LA ejection fraction was not statistically different among the three groups. LA stroke volume was greater in mitral regurgitation and mitral stenosis compared to normal subjects, p < 0.01. LA kinetic energy (LAKE) = 1/2 mv2 (m = LA stroke volume x 1.06, blood's specific gravity, v = A wave velocity) was increased in mitral stenosis and mitral regurgitation compared to normal subjects (p < 0.001). An inverse correlation (r = 0.66, p < 0.01) was present between LAKE and mitral valve area in mitral stenosis. It is concluded that LA function, a complex interplay of multiple factors, requires multidimensional methods of analysis beyond standard measurements of size and volume, which provide additional insight into normal LA function, and better definition of LA function changes involved in the natural history of chronic mitral valve disease.

Adult↗
PubMed1993

Administration of nebivolol after coronary artery bypass in patients with altered left ventricular function.

This prospective, double-blind study used invasive monitoring and echo-Doppler techniques to compare the hemodynamic effects of nebivolol, a new beta 1-selective beta-blocking agent with those of atenolol in patients recovering from coronary artery bypass grafting surgery. Five milligrams nebivolol and 50 mg atenolol equally decreased heart rate (HR) and blood pressure (BP) but, nebivolol, in contrast to atenolol, caused no decrease in stroke index (SI), cardiac index (CI), and right ventricular ejection fraction (RVEF). These differences appeared to be related in part to different peripheral effects of the two agents because nebivolol administration was associated with a reduction in systemic vascular resistance (SVR). After < or = 10 days of treatment, acceleration of aortic flow velocity increased and isovolumic relaxation time decreased with nebivolol but not with atenolol treatment. Both drugs were equally well tolerated. Therefore, nebivolol shares most of its effects with classical beta 1-blockers but is devoid of the potentially harmful effects on cardiac output (CO) and peripheral resistance.

Adrenergic beta-1 Receptor Antagonists↗