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Chronic hemodynamic overload of the atria is an important factor for gap junction remodeling in human and rat hearts.

OBJECTIVES: The expression and distribution of connexins is abnormal in a number of cardiac diseases, including atrial fibrillation, and is believed to favor conduction slowing and arrhythmia. Here, we studied the role of atrial structural remodeling in the disorganization of gap junctions and whether redistributed connexins can form new functional junction channels. METHODS: Expression of connexin-43 (Cx43) was characterized by immunoblotting and immunohistochemistry in human right atrial specimens and in rat atria after myocardial infarction (MI). Gap junctions were studied by electron and 3-D microscopy, and myocyte-myocyte coupling was determined by Lucifer yellow dye transfer. RESULTS: In both chronically hemodynamically overloaded human atria in sinus rhythm and in dilated atria from MI-rats, Cx43 were dephosphorylated and redistributed from the intercalated disc to the lateral cell membranes as observed during atrial fibrillation. In MI-rats, the gap junctions at the intercalated disc were smaller (20% decrease) and contained very little Cx43 (0 or 1 gold particle vs. 42 to 98 in sham-operated rats). In the lateral membranes of myocytes, numerous connexon aggregates comprising non-phosphorylated Cx43 were observed. These connexon aggregates were in no case assembled into gap junction plaque-like structures. However, N-cadherin was well organized in the intercalated disc. There was very little myocyte-myocyte coupling in MI-rat atria and no myocyte-fibroblast coupling. Regression of the atrial remodeling was associated with the normalization of Cx43 localization. CONCLUSION: Structural alteration of the atrial myocardium is an important factor in the disorganization of connexins and gap junction. Moreover, redistributed Cx43 do not form junction channels.

Animals↗

Ventricular development and function in complete transposition: angiocardiographic evaluation.

We studied 50 left ventricular cineangiograms and 41 right ventricular cineangiograms of 40 patients with usual atrial arrangement (situs solitus) together with concordant atrioventricular and discordant ventriculo-arterial connexions (complete transposition), catheterized between 1 day and 12 months of age. Our purpose was to evaluate ventricular development and function. The patients were subdivided on the basis of associated lesions into groups with intact ventricular septum; with ventricular septal defect; with ventricular septal defect together with pulmonary stenosis and with pulmonary stenosis in isolation. Each group was further separated according to age into those patients below and above 60 days. Ventricular volumes, ejection fraction and the ratio between systolic pressure and end-systolic volume were evaluated for both ventricles. The left ventricular mass, stress, and the ratio of stress to end-systolic volume were also calculated. A volume overload leads to increased left ventricular volume even at birth. With an intact ventricular septum, the left ventricle in patients with complete transposition is normal at birth and also during the first weeks of life. Myocardial mass, however, does not increase proportionately with increase in volume as the patient grows and it remains inadequate by the age of one year. The left ventricular mass is also inadequate in patients with associated anomalies when the left ventricular pressure is less than 60 mm Hg. Moreover, the left ventricle in presence of an intact ventricular septum presents a decrease in contractility during the first year of life despite the finding of a satisfactory arterial oxygen saturation. The right ventricle has a normal volume at birth which increases during the first year due to a greater diastolic filling following atrial septostomy. We noted a progressive decrease in ejection fraction, however, which is related to various factors including a reduction in contractility.

Angiocardiography↗

Functional significance of myocellular hypertrophy in dilated cardiomyopathy: histomorphometric analysis on 40 endomyocardial biopsies.

Dilated cardiomyopathy is characterized by an increase in myocardial mass. In order to study the functional significance of myocellular hypertrophy in dilated cardiomyopathy, 40 left ventricular endomyocardial biopsies were investigated, by comparing morphometrical data with functional indexes. The extent of myofibril volume fraction was directly associated with a better functional condition, as measured by ejection fraction (p < 0.01) and cardiac index (p < 0.05). Patients with oversize nuclei (nuclear area being > or = 70 microns 2) had a worse functional status (p < 0.05), as determined by ejection fraction and cardiac index. Finally, the extent of interstitial fibrosis was directly correlated to mean right atrial pressure (p < 0.01), right ventricular end-diastolic pressure (p < 0.02) and mean pulmonary artery pressure (p < 0.02). In conclusion, a worse functional status correlates with a reduced myofibril volume fraction and an oversize nuclear area, as in hypertrophic cells undergoing regressive changes.

Adult↗

Effect of direct current shocks on left atrial mechanical function in patients with structural heart disease.

OBJECTIVES: This study examined the effect of endocardial and transthoracic direct current (DC) shocks on left atrial and left atrial appendage function in humans with structural heart disease. BACKGROUND: DC cardioversion of atrial fibrillation (AF) to sinus rhythm is associated with transient left atrial and left atrial appendage dysfunction and the development of spontaneous echo contrast (SEC). This phenomenon has been termed atrial "stunning" and may be associated with thrombus formation and embolic stroke. To what extent the shock itself contributes to atrial stunning is unclear. METHODS: Thirteen patients in sinus rhythm undergoing implantation of a ventricular implantable cardioverter defibrillator (ICD) were prospectively evaluated. All patients had significant structural heart disease. To evaluate the effects of DC shocks on left atrial and left atrial appendage function, biphasic R wave synchronized endocardial shocks of 1, 10 and 20 J were delivered between the right ventricular electrode and the left pectoral generator of the ICD in sinus rhythm. R wave synchronized transthoracic shocks of 360 J were also delivered between anteriorly and posteriorly positioned chest electrodes. Transesophageal echocardiography was performed to evaluate left atrial appendage velocities, mitral inflow velocities and the presence of SEC before and immediately after each DC shock. RESULTS: There were no significant changes in left atrial or left atrial appendage function after endocardial or transthoracic DC shocks. Left atrial SEC did not develop after endocardial or transthoracic DC shocks. CONCLUSIONS: Endocardial and transthoracic DC shocks are not directly responsible for left atrial and left atrial appendage stunning and do not contribute to the stunning that is observed after the cardioversion of AF to sinus rhythm.

Aged↗

Hemodynamic and inotropic effects of milrinone after heart transplantation in the setting of recipient pulmonary hypertension.

BACKGROUND: Right ventricular failure remains an important cause of early morbidity and death after heart transplantation and is commonly related to preexistent recipient chronic pulmonary hypertension, which occurs as a result of long-standing congestive heart failure. In this study, the hemodynamic and inotropic effects of milrinone were assessed after bicaval heart transplantation in the setting of monocrotaline pyrrole-induced recipient chronic pulmonary hypertension. METHODS: Twenty dogs were used for 10 successfully completed transplantation experiments. Recipient animals underwent right atrial injection of 3 mg/kg monocrotaline pyrrole 4 months before transplantation. Hemodynamic and functional data were taken 1 hour after termination of cardiopulmonary bypass and after milrinone infusion. Myocardial function was assessed with load-insensitive means (preload-recruitable stroke work) and pulmonary vascular impedance was calculated with Fourier analysis. RESULTS: At the time of transplantation, before cardiopulmonary bypass, pulmonary hemodynamic indexes in recipient animals were significantly increased when compared with donors and were further significantly increased after cardiopulmonary bypass. Two animals died after transplantation as a result of acute right ventricular failure. In surviving animals milrinone infusion led to significant increases in right ventricular function, which occurred in association with significant improvements in pulmonary vascular impedance and transpulmonary efficiency. CONCLUSIONS: In the setting of monocrotaline pyrrole-induced recipient pulmonary hypertension, milrinone was associated with significant improvements in pulmonary vascular impedance, right ventricular function, and transpulmonary efficiency. These data suggest that milrinone is an effective means to improve right ventricular dysfunction and pulmonary vascular efficiency after bicaval heart transplantation in the setting of recipient chronic pulmonary hypertension.

Animals↗

[Reciprocating tachycardia and anterograde conduction by a nodoventricular pathway].

Two patients were investigated for paroxysmal regular tachycardia with left bundle branch block centrifugation. A right-sided nodo-ventricular accessory pathway was demonstrated in both cases at electrophysiological investigation with His bundle recording and atrial and ventricular programd pacing techniques. However, the function of this pathway was different in the two cases. In the first case, there were no signs of an accessory pathway on the surface ECG in sinus rhythm but it could be unmasked by simple right atrial pacing at the same rhythm (widening of the QRS and shortening of HV from 40 to 25 ms). The tachycardias could be only initiated by ventricular extrastimulus. They showed major pre-excitation with left sided delay and a 1/1 atrio-ventricular response. There was no His potential before the ventriculogramme which retained the same configuration throughout the attack. The investigations also suggested the presence of a dual nodal pathway with the accessory pathway connected to the slow pathway. In the second case, the presence of an accessory pathway could be suspected from the appearance of the QRS complex in sinus rhythms. Tachycardia was initiated by an atrial extrastimulus with initially a first complex showing slightly more marked pre-excitation and a distinct His potential before the QRS but with a shorter HV interval than in sinus rhythm. Then the reciprocating tachycardia had appearances of major pre-excitation, left-sided delay and a 1/1 atrio-ventricular response. However, in contrast to the first case, all ventricular complexes were preceded by a His potential and the degree of pre-excitation was variable with a HV interval ranging from 0 to 15 ms. These two cases merit attention because of: --their points in common: nodal duality and an accessory pathway which was not atrio-ventricular (decremental conduction) but nodo-right ventricular, conducting well in the anterograde direction but more or less masked in sinus rhythm; the presence of the accessory pathway was clearly visible during reciprocating tachycardia; --the differences: in the first case the nodo-ventricular pathway formed part of the circuit of the reciprocating tachycardia which was antidromic: descending limb, the slow nodal pathway and then the accessory nodo-ventricular pathway; ascending limb, the His bundle and then the rapid nodal pathway. In the second case, the reciprocating tachycardia was entirely intranodal, the accessory pathway not being involved in the circuit but connected to it in parallel with the normal Hisian pathway.

Adult↗

Effects of growth hormone in rats with postinfarction left ventricular dysfunction.

Growth hormone may affect cardiac function. In rats, chronic hypersecretion of growth hormone leads to increased maximum isometric contractile force of the left ventricular papillary muscle in vitro. In humans, administration of growth hormone can increase myocardial contractility. However, cardiac effects of growth hormone in heart failure or cardiac dysfunction have not been studied to date. The current study was to evaluate the cardiac effects of growth hormone in conscious rats with postinfarction left ventricular dysfunction and sham controls. Ligation of the left coronary artery or sham operation was performed, then 4 weeks after surgery, recombinant human growth hormone (2 mg/kg/day, SC) or vehicle was administered for 15 days. Catheters were implanted 13 days after treatment with growth hormone or vehicle. Hemodynamic parameters were measured in conscious rats 2 days after catheterization. In vehicle-treated rats, left ventricular systolic pressure, maximum dP/dt, and arterial pressure were significantly decreased and left ventricular end-diastolic pressure was significantly increased in the ligation group compared with sham controls. Growth hormone treatment increased left ventricular systolic pressure (p < 0.05) and dP/dt (p < 0.05) and reduced left ventricular end-diastolic pressure (p < 0.05), significantly in the ligated rats. In sham rats, growth hormone tended to decrease arterial pressure but did not alter ventricular contractility. Neither ligation nor growth hormone significantly altered heart rate and right atrial pressure. These results suggest that growth hormone treatment may improve cardiac function by increasing myocardial contractility in cardiac dysfunction or heart failure.

Analysis of Variance↗

Electrical changes produced by injury to the rat myocardium in vitro and the protective effects of certain antiarrhythmic drugs.

Glass microelectrodes were used to record intracellular electrical activity from rat isolated and superfused atrial myocardium during external electrical stimulation. After 2 h in normal oxygenated physiological salt solution the muscle was exposed for 30 min to a superfusate simulating the composition of extracellular fluid during myocardial ischaemia (SI). This fluid contained lactate (20 mM), a raised potassium concentration (7 mM), no glucose and a pH lowered to 6.4, and was gassed with N2 in place of O2 (hypoxia). During SI the diastolic threshold voltage for stimulation increased, the speed of action potential conduction between the right and left atria slowed, and both the effective and functional refractory periods of the right atrium shortened, as did the duration of the right atrial action potential. The only component of SI which separately caused electrical changes similar to those of the full simulation was hypoxia. Addition to the superfusate of verapamil (0.5 micrograms ml-1), sulphinpyrazone (1-20 micrograms ml-1) or indomethacin (10-20 micrograms ml-1) attenuated many of the SI-induced electrical changes, although indomethacin was much less effective than the other two drugs. Lowering the calcium concentration of the superfusate from 2 mM to 0.5 mM protected against the SI-induced electrical changes that were inhibitable with sulphinpyrazone and verapamil.

Animals↗

Prolonged cardiac recovery from exercise in asymptomatic adults late after atrial correction of transposition of the great arteries: evaluation with magnetic resonance flow mapping.

After atrial correction of transposition of the great arteries (TGA), dysfunction of the systemic right ventricle at rest and during exercise has been reported. Information on changes in systemic right ventricular function during recovery from exercise is lacking. This study evaluates cardiac recovery from supine exercise using magnetic resonance (MR) imaging in patients with asymptomatic TGA after atrial correction. Flow in the ascending aorta, representing stroke volume of the systemic ventricle, was assessed with MR flow mapping in 10 asymptomatic patients with atrially corrected TGA and in 12 controls at rest during exercise and an 8-minute recovery period. In response to exercise, the patients had a smaller increase in heart rate, stroke volume, and cardiac output than did controls. After exercise, no significant difference in halftime of heart rate recovery was observed (patients, 48 +/- 7 seconds; controls, 39 +/- 4 seconds [p >0.05]). In the patients, the time course of stroke volume recovery was significantly different (p <0.001). Stroke volume in the patients, as a percent difference from rest, remained significantly elevated, from 2.5 minutes (+16 +/- 5% vs +7 +/- 6%; p <0.05) to 8 minutes (+4 +/- 7% vs -3 +/- 5%; p <0.05) after exercise. Subsequently, cardiac output remained significantly elevated, from 4.5 minutes (+27 +/- 13% vs +15 +/- 11%; p <0.05) to 7 minutes (+22 +/- 11% vs +12 +/- 12%; p <0.05) after exercise. We conclude that heart rate recovery is within normal limits in patients with atrially corrected TGA. Furthermore, cardiac recovery from exercise, assessed with MR flow mapping, is prolonged in patients with asymptomatic TGA after atrial correction. Abnormal recovery may reflect dysfunction of the systemic right ventricle and an altered metabolic response to exercise.

Adolescent↗

Age-dependent changes in the beta-adrenoceptor-G-protein(s)-adenylyl cyclase system in human right atrium.

With increasing age, cardiac beta-adrenoceptor function decreases. To study possible mechanisms underlying this process, we assessed in right atrial appendages from 52 patients of different ages (group A, < 20 years, mean age 3.7 +/- 1.0 years, n = 20; group B, 20-50 years, mean age, 37.9 +/- 2.3 years, n = 9; group C, > 50 years, mean age 66.1 +/- 1.5 years, n = 23) without apparent heart failure who were undergoing open heart surgery beta-adrenoceptor number and subtype distribution (by (-)-[125I]-iodocyanopindolol [ICYP] binding), adenylyl cyclase activity, and Gs- and Gi-protein alpha-subunits (by quantitative Western blotting). beta-Adrenoceptor number in the three groups was not significantly different; in contrast, basal, 10 microM GTP-, 100 microM isoprenaline (ISO), 10 mM NaF-, 100 microM forskolin-, and 10 mM Mn(2+)-stimulated adenylyl cyclase activity was significantly higher in group A than in group B and was further decreased in group C. Similarly, 100 microM terbutaline-, 100 microM histamine-, and 100 microM 5-HT-stimulated adenylyl cyclase activity significantly decreased from group A to group C. Moreover, all these adenylyl cyclase parameters were significantly negatively correlated with the age of the patients. Although Gs alpha was not altered, Gi alpha in group C was significantly higher than in group A; moreover, there was a weak but significant positive correlation between Gi alpha and the age of the patients. We conclude that an impairment of the activity of the catalytic unit of adenylyl cyclase is involved in the decrease in cardiac beta-adrenoceptor function with age; an increase in Gi alpha might contribute further to the reduced beta-adrenoceptor function.

Adenylyl Cyclases↗

Nonphysiological left heart AV intervals as a result of DDD and AAI "physiological" pacing.

DDD and AAI pacemakers are considered physiological, since they preserve atrioventricular (AV) synchrony. Artificial pacing, however, is performed largely from right heart chambers, causing aberrant depolarization pathways. Pacing at the right atrial appendage (RAP) is known to delay left atrial contraction due to interatrial conduction time (IACT), and right ventricular (RV) apical pacing (RVP) delays left ventricular (LV) contraction due to interventricular conduction time (IVCT). These delays may render the left heart AV intervals (LAV) either too short or too long, thus affecting LV systolic function. The purpose of this study was to evaluate the actual LAV intervals during conventional, right heart AAI and DDD pacing. Resulting LAV intervals were compared to programmed AV values during all DDD pacing modalities. Ten patients with DDD and six patients with AAI pacemakers were studied. IACT was measured from the atrial spike to the onset of left P wave, as recorded by an esophageal lead. Systolic time intervals were measured using either a carotid pulse tracing or a densitogram (photoplethysmography). LV function was appraised by measuring rate-corrected LV ejection time (LVETc). IVCT was measured indirectly as the lengthening of LV preejection period (PEP) caused by RV pacing, as compared to normal depolarization pathway. Intrinsic IACT and IVCT were considered zero. Right heart AV intervals (RAV) were measured from surface ECG and LAVs were calculated according to the following equations: Sinus Rhythm: LAV = RAV; Atrial Pace + Ventricular Sense: LAV = RAV - IACT; Atrial Sense + Ventricular Pace: LAV = RAV + IVCT; Sequential AV Pace: LAV = RAV - IACT + IVCT.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Chronic aortic counterpulsation with latissimus dorsi in heart failure: clinical follow-up.

BACKGROUND: Dynamic aortomyoplasty is an alternative technique to heart transplantation. The goal of our study was to evaluate the benefits of aortic counterpulsation obtained by dynamic thoracic aortomyoplasty in patients with heart failure refractory to pharmacologic treatment and contraindications to heart transplant or cardiomyoplasty. METHODS: In this study we compared preoperative and postoperative data from five out of six carefully selected patients who were treated with dynamic thoracic aortomyoplasty. This surgical technique wraps the right latissimus dorsi muscle flap around the ascending aorta. This muscle flap was electrically stimulated during diastole, following a muscle-conditioning protocol, to obtain diastolic augmentation. At the 6-month follow-up period we evaluated, invasively and noninvasively, the hemodynamic and clinical effects of aortomyoplasty. RESULTS: We observed a significant decrease in the number of hospitalizations (P = 0.01), NYHA functional class (P = 0.01), cardiothoracic ratio (P = 0.02), right ventricular diameter (P = 0.03), left atrial diameter (P = 0.04), and pulmonary artery systolic pressure (P = 0.04); and a significant increase in the 6-minute walking test (P = 0.01), cardiac index (P = 0.04), noninvasive evaluation of diastolic augmentation (P = 0.01), left ventricular shortening fraction (P = 0.01), and radioisotopic left ventricular ejection fraction (P = 0.02). We also found a nonsignificant decrease in the left ventricular diameter (P = 0.08) and wedge pressure (P = 0.19); and a nonsignificant increase in peak oxygen consumption (P = 0.13). CONCLUSIONS: Dynamic thoracic aortomyoplasty in heart failure resulted in an important improvement of hemodynamic parameters, heart functional data, and clinical functional class, when comparing preoperative data with the 6-month follow-up data.

Adult↗

Transcatheter closure of atrial septal defects in children with a hypoplastic right ventricle.

The efficacy and safety of device closure of atrial defects in children with complex congenital heart disease and a hypoplastic right ventricle have not been detailed. The objective of this study was to determine the clinical impact and outcomes of a staged surgical catheter-based management strategy. A retrospective analysis of 17 children with a hypoplastic right ventricle who had undergone cardiac catheterization and attempted device occlusion of an atrial defect was undertaken. Clinical data, anatomical diagnoses, previous surgeries, and interventions were noted. The clinical course and echocardiographic findings were compared before and after defect closure (6 +/- 4 months of follow-up). Nine children had pulmonary atresia with an intact ventricular septum, six had Ebstein's anomaly of the tricuspid valve, and two had isolated right ventricular hypoplasia. The mean age at defect closure was 6.6 +/- 3.4 years. Under general anesthesia, closure of the atrial defect was undertaken after initial temporary test occlusion. The Qp:Qs ratio before closure was 1.1 +/- 0.4. Oxygen saturation improved in all children from 91% +/- 1% to 98% +/- 1% (P < 0.0005). Mean right atrial pressure increased from 9 +/- 3 to 11 +/- 4 mm Hg after closure, but the difference was not statistically significant (P = 0.2). Follow-up revealed an increased right ventricular length (P = 0.009) and Z-score (P = 0.02), although no significant increase in the diameter of the tricuspid valve annulus was observed in children with pulmonary atresia. Right ventricular systolic pressures or systolic function did not change significantly during follow-up (P = 0.5 and 0.29, respectively). Exercise tolerance improved in all children and clinical evidence of right ventricular decompensation was absent. Catheter closure of atrial defects in children with a hypoplastic right ventricle is well tolerated, safe, and effective as a treatment strategy in the staged management.

Cardiac Catheterization↗

[Surgical treatment of secundum atrial septal defects in adults over 30 years old].

OBJECTIVE: To summarize the experience of surgical treatment of secundum atrial septal defects in adults over 30 years old. METHODS: There were 469 patients with secundum atrial septal defects in our study (male 144, female 325; ages 30-68, mean 38.6 years old). There were 105 cases with pulmonary hypertension and 458 cases with arrhythmia in the group. Surgical closure of defects were performed in all patients. Surgical closure of 358 cases were done by patches including 305 autologous pericardial patches. The low dose (6 x 10(-6)) nitric oxide inhalation was used in 25 postoperative patients with pulmonary hypertension. Right sided maze procedures were done in 5 cases with atrial fibrillation. RESULTS: Surgical mortality was 0.6% (3 cases), the others were healed. In the group, there were 180 cases with arrhythmia, 27 cases with left ventricular function amyoplasia, 28 cases with low cardiac output syndrome, 12 cases in secondary operation for bleeding and 1 case with air-embolism. The level of mean pulmonary artery pressure of 25 postoperative patients with pulmonary hypertension inhaled nitric oxide was down 28.5%. After right sided maze procedures were done in 5 cases with atrial fibrillation, atrial fibrillation disappeared. 352 cases were followed up from 3 months to 20 years (mean 5.6 years). Twenty-nine cases were in class I-II of cardiac function, and the others were better than class I of cardiac function. CONCLUSIONS: Atrial septal defects in adult should be operated as early as possible. When patch is needed, an autologous pericardial patch is the first selection. Inhaled nitric oxide is an effective method to postoperative pulmonary hypertension. The maze operation should be performed for atrial septal defect with atrial fibrillation while the surgical closure of defect was done. During and after operation, much attention should be paid to preventing and curing arrhythmia and protecting and supporting left heart function.

Administration, Inhalation↗

Cardiac resynchronization: a novel therapy for heart failure.

Despite advances in medical therapy for patients with congestive heart failure, morbidity and mortality remain high. Conduction abnormalities, such as left bundle branch block, right bundle branch block, and nonspecific conduction delay, are observed commonly in patients with dilated cardiomyopathy. In patients with heart failure, the presence of intraventricular conduction delay is associated with more severe mitral regurgitation and worsened left ventricular systolic and diastolic function, and is an independent risk factor for increased mortality. Conventional dual-chamber (right atrial and right ventricular) pacing with a short atrioventricular delay was initially introduced as therapy for patients with advanced congestive heart failure to improve diastolic dysfunction and reduce mitral regurgitation. The acute beneficial hemodynamic effects observed in early, uncontrolled studies were not confirmed in subsequent randomized, controlled studies with longer follow-up. Cardiac resynchronization with novel biventricular (left and right ventricular) pacing systems has resulted in hemodynamic and functional benefits in patients with congestive heart failure and an underlying intraventricular conduction delay. Improvements in cardiac index, systolic blood pressure, and functional class have been reported with biventricular pacing, both acutely and at more than 1 year of follow-up. These encouraging preliminary results with biventricular pacing in patients with congestive heart failure will be validated in two prospective, randomized, controlled trials, Multicenter InSync Randomized Clinical Evaluation (MIRACLE) and Comparison of Medical Therapy, Pacing, and Defibrillation in Chronic Heart Failure (COMPANION). These studies are designed to evaluate the long-term efficacy of biventricular pacing in improving exercise capacity and in reducing morbidity and mortality in patients with advanced, symptomatic congestive heart failure. (c)2001 by CHF, Inc.

Journal Article↗

Factors affecting the postoperative exercise capacity of patients with mitral stenosis and aortic regurgitation.

Factors affecting the exercise capacity of patients with mitral stenosis (MS) and aortic regurgitation (AR) are incompletely understood. Accordingly, exercise capacity was assessed in 13 patients with MS and in 13 with AR by means of cardiopulmonary exercise testing before as well as 3, 6 and 12 months after valve replacement. Left- and right-ventricular function were evaluated echocardiographically. Both in MS and in AR exercise capacity expressed by maximal oxygen consumption (VO2max) increased significantly after valve replacement and was directly related to right ventricular (RV) function assessed by the ratio of RV acceleration time to RV ejection time (r = 0.87, p < 0.001 and r = 0.74, p < 0.001, respectively) and inversely related to left atrial diameter (r = -0.72, p < 0.001 and r = -0.76, p < 0.001, respectively). No relation between VO2max and resting left-ventricular function was found. Thus, the postoperative improvement in the exercise capacity both in mitral stenosis and in aortic regurgitation is associated with an improvement in right-ventricular function and a decrease in left-atrial size.

Aortic Valve Insufficiency↗

Hypoxia reduces atrial natriuretic peptide clearance receptor gene expression in ANP knockout mice.

We tested the hypotheses that hypoxic exposure is associated with exacerbated pulmonary hypertension and right ventricular (RV) enlargement, reduced atrial natriuretic peptide (ANP) clearance receptor (NPR-C) expression, and enhanced B-type natriuretic peptide (BNP) expression in the absence of ANP. Male wild-type [ANP(+/+)], heterozygous [ANP(+/-)], and homozygous [ANP(-/-)] mice were studied after a 5-wk hypoxic exposure (10% O(2)). Hypoxia increased RV ANP mRNA and plasma ANP levels only in ANP(+/+) and ANP(+/-) mice. Hypoxia-induced increases in RV pressure were significantly greater in ANP(-/-) than in ANP(+/+) or ANP(+/-) mice (104 +/- 17 vs. 45 +/- 10 and 63 +/- 7%, respectively) as were increases in RV mass (38 +/- 4 vs. 26 +/- 5 and 29 +/- 4%, respectively). NPR-C mRNA levels were greatly reduced in the kidney, lung, and brain by hypoxia in all three genotypes. RV BNP mRNA and lung and kidney cGMP levels were increased in hypoxic mice. These findings indicate that disrupted ANP expression worsens hypoxic pulmonary hypertension and RV enlargement but does not alter hypoxia-induced decreases in NPR-C and suggest that compensatory increases in BNP expression occur in the absence of ANP.

Animals↗

Randomized trials for selective site pacing: do we know where we are going?

Clinical evidence is accumulating that pacing from traditional right-sided sites (right ventricular apex and right atrial appendage) may be associated with long-term detriment to left ventricular function and promotion of atrial arrhythmias. Large numbers of small studies, some randomized, have addressed the effects of pacing from nontraditional or alternate sites, but the studies have varied in design such that comparison of results is often difficult. Many studies show data from acute studies only, although more recently longer-term data have started to become available; definition and description of pacing site also varies, adding further to the difficulties in comparing data. This article attempts to examine the randomized studies available to date, and to consider how future studies may contribute to our understanding of the effects of pacing from traditional and selected, specific sites on the right side of the heart.

Cardiac Pacing, Artificial↗