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PubMed1991

Effects of aprindine on monophasic action potentials.

Using a catheter electrode developed by the authors for recording monophasic action potentials (MAPs), the atrial and ventricular MAPs of seven mongrel dogs were simultaneously recorded. The results were used to evaluate the effect of the new antiarrhythmic drug aprindine on MAPs. An electrophysiologic study was also carried out to evaluate the effect of aprindine on the conduction system. Aprindine caused a significant increase in both the AH interval (at a basic cycle length of 400 ms) and the HV interval (at basic cycle lengths of 400 and 500 ms). The effective refractory period increased in both the right atrium and the right ventricle. Although an increase in MAP duration at repolarizations to 90% MAP (MAPD90) was not observed in the right atrium, a significant increase was noted in MAPD90 in the right ventricle. There were no significant changes in the ratio between the effective refractory period and MAPD90 of the right ventricle before and after administration of aprindine. This result suggests that increases in MAPD90 contribute to an increase in the effective refractory period of the right ventricle.

Action Potentials↗
PubMed1986

Calcitonin gene-related peptide as potential neurotransmitter in guinea pig right atrium.

The potential neurotransmitter role of calcitonin gene-related peptide (CGRP) in cardioacceleratory nonadrenergic noncholinergic (NANC) nerves was examined in the guinea pig right atrium in vitro. In the presence of atropine, a muscarinic antagonist, and atenolol, a beta-adrenoceptor antagonist, transmural nerve stimulation (TNS) of the isolated right atrium caused a positive chronotropic response, which is slow in both onset and decay. This TNS-induced slow response was assumed to be mediated by NANC nerves in the right atrium since tetrodotoxin inhibited the response. Dense distribution of CGRP-like immunoreactive (CGRP-I) nerves was demonstrated in the sinus node. Exogenously applied CGRP exerted a positive chronotropic effect on the isolated right atrium in a dose-dependent manner. Both CGRP-I nerves and NANC response induced by TNS were not affected by surgical sympathectomy and reserpine pretreatment but were abolished by the pretreatment of animals with capsaicin. The results suggest that CGRP is the neurotransmitter of cardioacceleratory NANC nerves in the right atrium of the guinea pig.

Animals↗
PubMed1989

The effect of medetomidine, an alpha 2-adrenoceptor agonist, on plasma atrial natriuretic peptide levels, haemodynamics and renal excretory function in spontaneously hypertensive and Wistar-Kyoto rats.

1. The effects of the selective alpha 2-adrenoceptor agonist, medetomidine, were assessed on plasma levels of immunoreactive atrial natriuretic peptide (IR-ANP), haemodynamics and on urine water and solute excretion in conscious, chronically cannulated, 7 month-old spontaneously hypertensive (SHR) and age-matched Wistar-Kyoto (WKY) rats, in order to examine the role of alpha 2-adrenoceptors in the control of ANP secretion. 2. A 60 min i.v. infusion of medetomidine (0.2 or 0.6 microgram kg-1 min-1) decreased heart rate dose-dependently in both strains. Medetomidine infusion (0.6 microgram kg-1 min-1) resulted in an increase in mean arterial pressure in WKY, whereas both doses decreased blood pressure in SHR. There was a slight increase in the right atrial pressure in both strains (WKY: +1.18 +/- 0.26 mmHg; SHR: +1.64 +/- 0.64 mmHg, NS) in response to infusion of 0.6 microgram kg-1 min-1 of medetomidine. 3. No differences were found in resting plasma IR-ANP levels between WKY (114 +/- 8 pg ml-1, n = 19) and SHR (117 +/- 10 pg ml-1, n = 21). Infusion of equibradycardic doses of medetomidine increased dose-dependently plasma IR-ANP levels in WKY, but did not affect the plasma IR-ANP concentration in SHR rats. 4. Despite the different effect of medetomidine on ANP release in WKY and SHR rats, i.v. administration of medetomidine affected renal excretory functions similarly in both strains; urine flow and sodium excretion increased and urine osmolality decreased significantly, while there was no consistent change in urinary potassium excretion. Urine osmolality decreased to hypo-osmotic levels during the infusion of 0.6 yg kg-1 min1 of medetomidine, suggesting a possible interaction between alpha 2-adrenoceptor stimulation and the vasopressin system. 5. These results show that the alpha 2-adrenoceptor agonist medetomidine increased plasma levels of ANP in WKY rats, probably through an increase in mean arterial and right atrial pressures, whereas the SHR had attenuated ANP release to alpha 2-adrenoceptor stimulation. Our findings, that medetomidine caused marked natriuretic and diuretic effects in both strains and that these effects on the excretory functions of the kidneys were not related to changes in plasma levels of IR-ANP, demonstrate that changes in plasma ANP levels alone do not account for the diuretic and natriuretic effect of alpha 2-agonists.

Adrenergic alpha-Agonists↗
PubMed1998

[Pathophysiologic mechanisms of atrial rhythm disorders. II. Atrial flutter].

Atrial flutter is a common cardiac dysrhythmia which responds for half of the supraventricular tachycardias with exception of atrial fibrillation. Activation and entrainment mapping studies in man and in animals confirmed the reentry mechanism of atrial flutter and demonstrated that the reentry circuit is located in the right atrium. The most important anatomical structures which enable the occurrence of atrial flutter are crista terminalis, Eustachian valve/ridge and tricuspid annulus. In typical atrial flutter the impulse rotates "counterclockwise". According to the present knowledge the reentry circuit surrounds a central obstacle made by the orifices of the superior and inferior vena cava linked by a line of functional block in the region of crista terminalis. The anterior barrier is created by tricuspid annulus. The anterolateral wall of the right atrium is activated craniocaudally. Crista terminalis and tricuspid annulus form a funnel which leads the impulse into the isthmus with slow conduction located between the vena cava orifice and tricuspid annulus. Septal activation is ascending and the activation wave considerably widens and becomes irregular. The upper link of the circuit is located above and anteriorly to the superior vena cava. The left atrium is activated passively and does not play an important role in the reentrant circuit. Reverse flutter has the same substrate as typical flutter but rotates in an opposite "clockwise" manner.

Animals↗
PubMed1987

Noninvasive evaluation of right ventricular function.

Numerous technologic advances have greatly facilitated the noninvasive analysis of right ventricular function. Nevertheless, important clues continue to be available to the astute clinician by physical examination. The chest x-ray is of rather limited utility. The electrocardiogram can show evidence of right atrial enlargement or right ventricular hypertrophy. Unfortunately, both sensitivity and specificity are deficient. Echocardiography is a widely available and potentially very accurate source of information concerning right ventricular dysfunction. Careful temporal analysis of the M-mode echocardiogram can give information beyond chamber size and wall thickness. Two-dimensional echocardiography allows more accurate determination of chamber size and wall thickness and also permits analysis of segmental wall motion and chamber contour. Doppler echocardiography allows measurement of pressure differences and flow kinetics. Preliminary data indicate that one can accurately assess pulmonary artery pressure and possibly right ventricular diastolic function. Color-flow mapping allows for accurate determination of valvular regurgitation and enhances the accuracy of standard Doppler echocardiographic techniques. Radionuclide analysis of the right ventricle by blood-pool imaging allows accurate determination of ejection fraction and wall motion. In addition, it may be possible to estimate pulmonary artery pressure. Use of short-acting radionuclides allows for serial imaging of the right ventricle after pharmacologic intervention or exercise. Perfusion scanning can show evidence of exercise-induced ischemia, although applicability to the right ventricle is somewhat limited. Avid scanning allows localizing of myocardial injury to the right ventricle. CT scanning of the heart is of limited clinical utility, because cardiac motion occurs too rapidly for accurate imaging. The advent of the cine-CT may overcome this problem and allow evaluation of right ventricular volumes and wall motion. Digital subtraction imaging allows for accurate video densitometric calculation of ejection fractions, but offers no advantage over other currently available techniques. Magnetic resonance imaging may prove to be the methodology of choice for analysis of right ventricular function, because it can give accurate measurement of right ventricular wall motion, ejection fraction, and (similar to Doppler flow studies) some indication of flow within the right-sided chambers. It will soon be possible to generate information concerning the biochemical content of the right ventricular myocardium, perhaps providing early evidence of hypertrophy or myopathy.(ABSTRACT TRUNCATED AT 400 WORDS)

Cardiac Output↗
PubMed1999

Electrophysiological effects of homocysteine in isolated rat right ventricular papillary muscles and left atria.

There is clinical and epidemiological evidence that elevated plasma homocysteine (Hcy) levels are associated with increased myocardial infarction mortality; however, very little is known about Hcy's direct cardiac effects. Thus, we aimed to characterize the cellular electrophysiologic effects of Hcy, a sulfur-containing amino acid in isolated rat hearts. A conventional microelectrode technique was used in left atria and right ventricular papillary muscles. At concentrations higher than 10(6) M, Hcy significantly decreased the maximum rate of rise of the depolarization phase (Vmax) in both cardiac preparations in a dose-dependent manner. Hcy at 10(-4)-5 x 10(-4) M concentrations increased the action potential duration (APD) at late stages of repolarization (at 75% and 90% of APD) both in atria and in ventricles. There was a slight decrease in action potential amplitude in ventricular papillary muscles and atria at concentrations higher that 10(-5) M. The resting membrane potential and the early repolarization phase (APD25 and APD50) remained unchanged in every preparation studied at all concentrations of Hcy administered. The present data suggest that homocysteine may decrease the Na+ channel activity in in vitro cardiac preparations. reserved.

Action Potentials↗
PubMed1985

Functional and anatomical correlates in atrial septal defect. An echocardiographic analysis.

The results of cross sectional echocardiography, intracardiac contrast echocardiography, and balloon sizing techniques and conventional haemodynamic assessment were correlated in 40 consecutive patients evaluated for an isolated left to right shunt at atrial level. Echo free areas along the septum were identified in 23 of 25 patients with a secundum defect, but not in two with a fenestrated defect, and in the upper atrial septum in three of four patients with a sinus venosus defect. No false positive results occurred in 11 patients with a probe patent foramen ovale. Saline contrast injection into the left atrium showed significant left to right shunting in all patients with atrial septal defect; inferior vena caval injection produced right to left shunting in 15 of 29 patients and a negative contrast effect in eight of 29 patients with an atrial septal defect, although neither correlated quantitatively with defect diameter or magnitude of the left to right shunt. Echocardiographic assessment of defect size as small, moderate, or large showed a highly significant correlation with balloon measurement of defect diameter, although some overlap between the groups was evident. In contrast, the correlation between defect diameter and pulmonary to systemic blood flow ratio was poor, mainly because of highly variable shunting in patients with an anatomically large defect. Cross sectional echocardiography has high sensitivity and specificity in the diagnosis of the non-fenestrated atrial septal defect and provides quantitative information about defect diameter. Contrast studies do not add to the diagnostic value of imaging from the subcostal position. The poor correlation between defect size and the measured shunt suggests that the latter may not be the best criterion for surgical management and that size could be an important factor likely to influence both the long term prognosis and the decision for closure.

Adolescent↗
PubMed1979

Electrophysiologic effects of lidocaine in children.

The effects of intravenous lidocaine on the refractory periods of the atrium, AV node and right ventricular myocardium were studied using His bundle recordings and the extrastimulus technique with and without atrial and ventricular pacing. The drug was administered in an intravenous bolus dose of 1 mg/Kg followed by an infusion of 100 micrograms/Kg/min. The AH, HV intervals and resting sinus cycle length as well as functional and effective refractory periods of atrium, AV node and right ventricle were measured before and 5 min afrer bolus injection of lidocaine. Neither of the refractory periods nor AH and HV intervals changed significantly following administration of lidocaine. The result of this first study in children is in agreement with previous reports of the effects of lidocaine on the cardiac conduction system in adults.

Adolescent↗
PubMedDate not supplied

Successful surgical correction in two patients with tricuspid atresia using autologous pericardial valve-bearing tube graft.

A modification of the Fontan procedure has been used successfully to correct tricuspid atresia in two children who had severe hypoplasia of pulmonary artery. In the first patient (who had functioning Gleen anastomosis) the hypoplastic left pulmonary artery was widened by an angioplasty, and then a Dacron external conduit containing an autologous pericardial valve (an autologous pericardial valve-bearing tube graft) was positioned to lead from the right atrial appendage to the left pulmonary artery. A large secondum type atrial septal defect was closed by a Dacron patch. In the 2nd patient, a Dacron external conduit without any valve was placed between the right appendage and the hypoplastic right ventricle and then the pulmonary outflow tract was widened by using an autologous pericardial valve patch, which was an extension of the external conduit. The ventricular and atrial septal defects were closed with patches. Both patients made a satisfactory recovery and doing well 4 months after the operation. This type of modification of the Fontan procedure may provide a more effective functional correction for patients with tricuspid atresia who are accompanied with severe pulmonary hypoplasia.

Bioprosthesis↗
PubMed1995

Age-related effects in rabbit hearts of N6-R-phenylisopropyladenosine, an adenosine A1 receptor agonist.

Interventions known to increase cytoplasmic Ca2+ appear to amplify age-related impairment of cardiac function. In addition, increased release of interstitial adenosine, an endogenous nucleoside, has been suggested to mediate the diminished beta-adrenergic responsiveness in senescent heart. However, the direct effects of adenosine A1 receptor activation on senescent myocardium have not been investigated thoroughly. Therefore, the effects of N6-R-phenylisopropyladenosine (R-PIA), an A1 agonist, on atrial rate and contractility (+dF/dt) in adult (6-8 months) and senescent (5-7 years) New Zealand White rabbits were compared in spontaneously beating right atria and electrically stimulated isolated right papillary muscles. Although senescent right atria appeared to be more sensitive to the negative chronotropic-effects of R-PIA, the effective concentrations producing 50% of the maximum response (EC50 values) of R-PIA were not significantly different between adult (26 nM, 95% confidence limits: 12-52 nM) and senescent (13 nM; 95% confidence limits: 10-16 nM). However, senescent right ventricular papillary muscles were more sensitive to the negative inotropic effects of R-PIA. For example, at 90 contractions/min, 100 nM R-PIA decreased +dF/dt 25.3 +/- 7.4% and 61.9 +/- 4.8% in adult and senescent papillary muscles, respectively. To investigate whether R-PIA might alter sarcoplasmic reticulum (SR) function as a mechanism of decreased inotropy, we determined the inotropic effects of R-PIA on steady-state and 30-s postrest-potentiated contractions (PRP; an index of SR Ca2+ release) of left atria. R-PIA did not selectively decrease contractility of PRP compared to steady state in either adult or senescent left atria.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1983

Transient neonatal tricuspid regurgitation: possible relation with premature closure of the ductus arteriosus.

Normal fetal circulation requires patency of the ductus arteriosus. Prenatal ductal closure causes profound circulatory changes, such as massive tricuspid regurgitation. After delivery, the clinical picture of these severely distressed cyanotic newborns usually improves rapidly as the circulation is no longer dependent on ductal patency after onset of respiration. This case report deals with a newborn infant with severe tricuspid regurgitation and a large atrial right to left shunt who was treated with prostaglandin E1 infusion at 12 hours of age and in whom cardiac angiography revealed no evidence of either patent or functionally closed ductus arteriosus and no anatomic cardiac abnormalities at 30 hours of age. On the basis of physiologic and morphologic observations in this infant, the possible role of premature ductal narrowing or closure in the pathogenesis of transient neonatal tricuspid regurgitation is discussed. It is recommended that documentation of ductal presence or absence should become part of the diagnostic evaluation of newborns with transient tricuspid regurgitation.

Adult↗
PubMed2005

Intraatrial repair of transposition of the great arteries: use of MR imaging after exercise to evaluate regional systemic right ventricular function.

PURPOSE: To prospectively assess regional systemic right ventricular (RV) function at rest and in response to exercise by using magnetic resonance (MR) imaging in patients who have undergone surgical correction at the atrial level for transposition of the great arteries (TGA). MATERIALS AND METHODS: Informed consent was obtained, and the medical review board approved this study. In 25 adult patients (mean age, 25.8 years +/- 4.7 [standard deviation]; 13 men) who had undergone correction for TGA (23.4 years +/- 4.9 after surgery) and 11 healthy volunteers (mean age, 27.4 years +/- 2.7; six men), systemic ventricular function was assessed with MR imaging (turbo field echo-planar imaging) at rest and during supine bicycle exercise. Regional wall thickness and wall thickening of the systemic RV were assessed and compared with those of the left ventricle in healthy volunteers by two investigators working together. Regional wall parameters were calculated by using the three-dimensional centerline method. Independent-samples t test and paired-samples t test were used for statistical analysis. RESULTS: Ejection fraction of the systemic RV did not increase after exercise (56% +/- 8 at rest to 55% +/- 7 after exercise, P = .196). Mean RV wall thickening was impaired in patients with TGA at all levels both at rest and in response to exercise (P < .05). Moreover, the free wall and the anterior wall of the systemic RV had a smaller end-systolic thickness and a diminished thickening at rest and after exercise compared with findings in the normal left ventricle (P < .05). CONCLUSION: The systemic RV of patients after intraatrial correction for TGA reveals regional functional disturbances at rest and in response to exercise.

Adult↗
PubMed1998

Alternative approach to the repair of Ebstein's malformation: intracardiac repair with ventricular unloading.

BACKGROUND: Moderate to severe Ebstein's malformation remains a surgical challenge. Although the various approaches that have been used are appropriate and successful in many patients, there are many for which these approaches are suboptimal. To improve the prognosis for patients across the full spectrum of Ebstein's malformation, alternative surgical approaches are necessary. METHODS: From December 1995 to October 1997, 10 patients (median age, 9 years) with moderate or severe Ebstein's malformation and mild to severe tricuspid regurgitation had partial biventricular repair with reduction of right ventricular volume load. All patients were symptomatic in New York Heart Association functional class II (n = 9) or III (n = 1). In addition to bidirectional cavopulmonary anastomosis and closure of intracardiac defects in all patients, 6 underwent tricuspid valve repair using a variety of procedures, most often simple horizontal annuloplasty. RESULTS: There were no deaths. Early reoperation was required in 1 patient (atrial septostomy on the day after operation for right ventricular failure) and another required revision of the tricuspid valve repair 10 months postoperatively for recurrent regurgitation. At follow-up ranging from 2 to 24 months, all patients are in New York Heart Association class I and have trivial tricuspid regurgitation, including the 4 who had no tricuspid valvuloplasty performed. CONCLUSIONS: We have presented an alternative approach to the management of severe Ebstein's malformation that focuses on both the tricuspid valve and the right ventricle. Just as tricuspid valve repair and reduction of regurgitation will likely improve right ventricular performance, reducing the volume load on the ventricle may improve both ventricular (right and left) and tricuspid valve function. All patients have demonstrated improved exercise tolerance and right heart function at follow-up ranging to 24 months. Additional experience will be necessary to evaluate this strategy more completely.

Adult↗
PubMed1984

The cardiovascular effects of hypertonic sodium bicarbonate in conscious dogs: underlying mechanisms of action.

Mechanisms underlying the transient hypotensive effect (central or peripheral) of rapid bolus administration of hypertonic sodium bicarbonate (NaHCO3) were studied in conscious dogs. Thirteen animals equipped with an electromagnetic flow probe positioned around the ascending aorta were utilized. NaHCO3 (18.5 mequiv. of 1786 mosmol/L), hypertonic saline solution having the same sodium concentration as NaHCO3, and mannitol solution with the same osmolarity as NaHCO3, were injected in the right and in the left atrium. Intra-arterial NaHCO3 was tested to assess its direct peripheral vascular effects. Blood ionic as well as acid-base modifications following NaHCO3 were also studied. Our results indicate that right atrial injection of NaHCO3 elicited transient hypotension (-10 to -15 mmHg (1 mmHg = 133.322 Pa)) and myocardial depression as revealed by a significant decrease of stroke volume (-8%), stroke power (-18%), stroke work (-12%), maximum systolic flow (-13%), peak velocity (-13%), and maximum acceleration (-24%). When the solution is injected in the left atrium, myocardial depression is more pronounced suggesting that the coronary bed is the site of action. Hypertonic saline injections indicate that the sodium load plays a role in this decrement of myocardial function while hyperosmolarity per se, as exemplified with mannitol injections, elicits no negative effect. Transient ionic as well as acid-base disturbances are other mechanisms that have to be considered along with coronary vasoconstriction. Decrement in peripheral resistance appears only with right intra-atrial NaHCO3 suggesting that the pulmonary vascular bed is the origin of this reflex.

Acid-Base Equilibrium↗
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↗
PubMed2004

Echocardiographic assessment of the right ventricular stress-velocity relationship under normal and chronic overload conditions.

UNLABELLED: The effects of chronic volume or pressure overload on the velocity of right ventricular ejection have not been previously well defined. We hypothesized that, as formerly shown for the left ventricle, there would be a direct relationship between the velocity of ejection and an estimate of systolic wall stress. METHODS: Echocardiograms of asymptomatic patients, not on cardiac medications, with either an isolated secundum atrial septal defect > or = 5 mm in diameter or isolated pulmonic stenosis with a peak instantaneous pressure gradient > or = 20 mmHg, were reviewed. Forty-one patients with an atrial septal defect and 34 with pulmonary stenosis met criteria, and were compared to age-matched normal controls. Total subjects were 127 with ages ranging from 1 day to 54 years. Right ventricular monoplane ejection fraction, ejection time corrected for heart rate (ETc), mean normalized systolic ejection rate (MNSERc) and meridianal peak-systolic wall stress (WSps) were measured. RESULTS: Compared to controls, ejection fractions were not significantly different, but WSps averaged 81% and 110% higher, ETc 8% and 9% longer, and MNSERc 5% and 9% slower in the atrial septal defect and pulmonary stenosis groups, respectively. Among all subjects WSps had a significant linear correlation with ETc (r = 0.61, P < 0.01), MNSERc (r =-0.46, P < 0.01), and ejection fraction (r =-0.19, P < 0.05). CONCLUSIONS: Increases in WSps cause an incremental slowing of MNSERc in the right ventricle, with a relationship that is linear over a wide range of normal and abnormal loading conditions.

Adolescent↗