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PubMed1991

Doppler assessment of right ventricular filling dynamics during volume loading in ischemic heart disease.

To assess the effects of volume loading on right ventricular (RV) filling dynamics, the RV inflow pattern was recorded using pulsed Doppler echocardiography (PDE) during dextran infusion in 7 normal subjects (Group I) and 24 patients with ischemic heart disease. The patients with ischemic heart disease were divided into three groups according to the left ventricular (LV) and RV ejection fractions (EF). Group II consisted of 11 patients whose LVEF and RVEF exceeded 50%. Group III consisted of 7 patients whose LVEF was lower than 50% and RVEF was higher than 50%. Group IV was comprised of 6 patients whose LVEF and RVEF were lower than 50%. Peak flow velocity of the RV rapid filling wave in early diastole [R(T)] and that of the atrial contraction wave [A(T)] were measured, and the ratio of A(T) to R(T) [A(T)/R(T)] in each cardiac cycle was calculated. In some of the subjects, simultaneous right-sided cardiac catheterization was performed with a Swan-Ganz thermodilution catheter. The LV and RV function during volume loading were calculated according to the following formulae: delta Stroke volume index (SVI)/delta pulmonary artery wedge pressure (PAWP) and delta SVI/delta right atrial pressure (RAP), respectively. After dextran infusion, R(T) increased significantly in Groups I, II, and III, but not in Group IV. The A(T) and A(T)/R(T) ratio remained unchanged in all groups. The percent change of the R(T) correlated well with delta SVI/delta RAP (r = 0.56, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Paracrine coronary endothelial control of left ventricular function in humans.

BACKGROUND: Similar to endothelial modulation of vascular tone, myocardial contraction may be modulated by cardioactive agents released from the coronary endothelium. To investigate such modulation in humans, we performed invasive assessment of left ventricular (LV) function before, during, and after bicoronary infusion of substance P, which releases nitric oxide from the endothelium. METHODS AND RESULTS: Eight healthy subjects were investigated during diagnostic coronary angiography and eight transplant recipients during annual catheterization. Tip-micromanometer LV pressure was recorded before, during, and after bicoronary (n = 16) and right atrial (n = 14) infusion of substance P (20 pmol/min). LV angiograms (n = 11) were obtained before and at the end of the substance P infusion. At the end of the intracoronary substance P infusion, we observed (1) a fall in LV peak systolic pressure from 147 +/- 16 to 139 +/- 15 mm Hg (P < .01) in healthy subjects and from 147 +/- 25 to 141 +/- 22 mmHg (P < .05) in transplant recipients; (2) a downward and rightward shift of the average LV end-systolic pressure-volume point consistent with depressed systolic performance; and (3) a rise in LV end-diastolic volume at comparable end-diastolic pressure, consistent with increased end-diastolic distensibility. Five minutes after the substance P infusion, LV peak systolic pressure was higher than at baseline in healthy subjects (154 +/- 18 mm Hg; P < .05). Right atrial infusion of substance P did not reproduce these changes. CONCLUSIONS: Bicoronary infusion of substance P modulates LV function in humans, probably through paracrine myocardial action of cardioactive agents released from the coronary endothelium.

Cardiac Catheterization↗
PubMed1979

[Coronary collaterals and function of the left ventricle. Practical applications of a collateral score].

The most important collateral pathways in the coronary artery system goes through the apex, the ventricular septum, left and right atrial branches and the ventricular wall of the left ventricle. In a collective of 52 patients who underwent aortocoronary-bypass surgery we controlled the collateral circulation and left ventricle function. Patients with multiple-vessel-disease had in 71% good collateral circulation and the collateral score was more than twice as high as in patients with one-vessel-disease. In addition we compared the LVEDP in these 52 operated patients and in 52, whose condition did not permit coronary surgery. The enddiastolic pressure is lower in patients with good collaterals and was also better in patients who underwent surgery.

Blood Pressure↗
PubMed1998

Long-term follow-up in patients with the permanent form of junctional reciprocating tachycardia treated with radiofrequency ablation.

This study sought to determine the long-term follow-up, safety, and efficacy of radiofrequency catheter ablation of patients with the permanent form of junctional reciprocating tachycardia (PJRT). We assessed the reversibility of tachycardia induced LV dysfunction and we detailed the location and electrophysiological characteristics of these retrograde atrioventricular decremental pathways. PJRT is an infrequent form of reciprocating tachycardia, commonly incessant, and usually drug refractory. The ECG hallmarks include an RP interval > PR with inverted P waves in leads II, III, a VF, and V3-V6. During tachycardia, retrograde VA conduction occurs over an accessory pathway with slow and decremental conduction properties, located predominantly in the posteroseptal zone. It is known that long-lasting and incessant tachycardia may result in tachycardia induced severe ventricular dysfunction. We included 36 patients (13 men, 23 women, mean +/- SD, aged 44 +/- 22 years) with the diagnosis of PJRT. Seven patients had tachycardia induced left ventricular dysfunction. Radiofrequency energy was delivered at the site of earliest retrograde atrial activation during ventricular pacing or during reciprocating tachycardia. All patients were followed at the outpatient clinic and serial echocardiograms were performed in those who presented with depressed LV function. Radiofrequency ablation was performed in 36 decremental accessory pathways. Earliest retrograde atrial activation was right posteroseptal in 32 patients (88%), right mid-septal in 2 (6%), right posterolateral in 1 (3%), and left anterolateral in 1 (3%). Thirty-five accessory pathways were successfully ablated with a mean of 5 +/- 3 applications. A mid-septal accessory pathway could not be ablated. After a mean follow-up of 21 +/- 16 months (range 1-64) 34 patients are asymptomatic. There were recurrences in 8 patients after the initial successful ablation (mean of 1.2 months), 5 were ablated in a second ablation procedure, 2 patients required a third procedure, and 1 patient required four ablation sessions. All patients with LV dysfunction experienced a remarkable improvement after ablation. Mean preablation LV ejection fraction in patients with tachycardiomyopathy was 28% +/- 6% and rose to 51% +/- 16% after ablation (P < 0.02). Our study supports the concept that radiofrequency catheter ablation is a safe and effective treatment for patients with PJRT. Radiofrequency ablation should be the treatment of choice in these patients because this arrhythmia is usually drug refractory. The majority of accessory pathways are located in the posteroseptal zone. Cessation of the arrhythmia after successful ablation results in recovery of LV dysfunction.

Adolescent↗
PubMed1986

Right-sided cardiac transplantation: importance of functional valves.

An original surgical procedure had been developed entailing the implantation of a right-sided heterotrophic cardiac graft in 14 dogs. The benchwork preparation included creation of both atrial and ventricular septal defects which allowed transplantation with the avoidance of extracorporeal circulation and the utilization of all transplanted myocardium and parts. The structure and function of this graft were sequentially evaluated using rapid cine-computed tomograms which permitted assessment of forward graft flow, ventricular wall contraction, and diastolic thickness for both the native and grafted hearts. These parameters were followed during the early (E) (less than 3 days), intermediate (I) (4-21 days), and late (L) (greater than 21 days) postoperative periods. Forward flow (E: 3.0, I: 1.5, L: 2.6) through the transplant was maintained by the competence of the implanted valves despite a progressive decrease in the contraction (E: 3.0, I: 1.3, L: 1.0) and associated decrease in the wall thickness (E: 3.0, I: 2.6, L: 2.4). These findings were consistent with severe cardiac graft rejection without immunosuppression. In summary, long-term structural and functional forward flow of this configurated right-sided transplantation had been maintained by the competent valves on both sides of the graft despite severe rejection without immunosuppression as documented by rapid cine-computed tomograms.

Animals↗
PubMed1991

Preserved atrial natriuretic peptide secretory function after cardiac transplantation.

The purpose of this investigation was to determine whether atrial natriuretic peptide (ANP) secretory function is preserved after cardiac transplantation. Thirteen hemodynamically stable outpatients performed supine exercise on a bicycle an average of 7 months after orthotopic cardiac transplantation. Right atrial pressure increased 2.2-fold (6 +/- 1 to 13 +/- 2 mm Hg) and pulmonary artery wedge pressure 2.1-fold (11 +/- 1 to 23 +/- 7 mm Hg) with exercise in the transplant recipients. Resting venous ANP level (114 +/- 19 pg/ml) and peak exercise venous level (373 +/- 61 pg/ml) was elevated in transplant recipients (p less than 0.001) compared with control subjects (21 +/- 1 and 92 +/- 14 pg/ml, respectively. This represents a 3.3-fold (114 +/- 19 to 373 +/- 61 pg/ml) increase in the ANP level from resting to exercise in transplant recipients and a 4.4-fold (21 +/- 1 to 92 +/- 14 pg/ml) increase in control subjects. A correlation between venous ANP levels and hemodynamics (right atrial pressure) was observed r = 0.49 p = 0.01. It is concluded that ANP levels at rest are elevated after cardiac transplant, the levels correlate with the intracardiac hemodynamics, and exercise-induced augmentation of plasma levels occurs.

Adult↗
PubMed2002

[Therapeutic management of primary pulmonary hypertension].

SEVERITY AND TREATMENT: The management of primitive pulmonary hypertension starts by the evaluation of its severity, based on the New York Heart Association's (NYHA) functional classification and right cardiac catheterization data. Hemodynamic criteria of poor prognosis are: an increase in right atrial pressure > 10 mm Hg, a decrease in cardiac output (cardiac index < 2.2 l/min/m2), an increase in pulmonary vascular resistance > to 20 mm Hg/l/min/m2, and saturation of the oxygen content in venous blood < 63%. These prognostic data will condition treatment. CALCIUM CHANNEL BLOCKERS: Are the only vasodilators that have demonstrated efficacy in primitive pulmonary hypertension (PPH). However, only 20% of patients respond to calcium blockers. To determine a positive response to these agents, a carbon monoxide inhalation test is required during right cardiac catheterization. Prescription of calcium channel blockers to non-responders is often responsible for adverse events, from enhanced dyspnoea to sudden death. Continuous intravenous infusion of epoprostenol has considerably improved the prognosis of PPH and related pulmonary hypertension (PH). Despite the constraints, such treatment should be proposed to NYHA functional class III and IV patients not responding to carbon monoxide tests, until new, equally efficient products have been launched on the market. If epoprostenol fails or provokes severe side effects, pulmonary or cardio-pulmonary transplantation should be envisaged.

Administration, Oral↗
PubMed1981

Right atrial stretch decreases supraoptic neurosecretory activity and plasma vasopressin.

It is generally held that left atrial stretch (LAS) but not right atrial stretch (RAS) reflexly inhibits vasopressin release and results in a diuresis. To reexamine the influence of RAS on the release of vasopressin and on the behavior of antidromically identified supraoptic neurosecretory neurons, RAS and LAS were applied in pentobarbital-anesthetized cats. Weighted 20 or 30 g sutures were placed in the left atrium pulmonary vein junction and at the base of the right atrial appendage. Antidromically identified supraoptic nucleus neurons were inhibited by both RAS and LAS applied independently and together, although fewer neurons were responsive to RAS alone. Simultaneous stretch of both atria resulted in greater inhibition of these neurons than did stretch of either atrium alone. Stretch of the right atrium alone also resulted in a significant decrease in plasma arginine vasopressin measured by radioimmunoassay. Differences between these results and other reports may stem from differences in the method of RAS or the specific right atrial receptors affected.

Animals↗
PubMed1996

Total atrioventricular cardiac transplantation preserves atrial systole and ventricular diastolic filling.

BACKGROUND: Total orthotopic heart transplantation was recently introduced into clinical practice as an alternative technique for orthotopic cardiac transplantation. Total cardiac transplantation uses separate bicaval and left and right pulmonary anastomoses, whereas the standard technique of cardiac transplantation uses atrioplasty. Because the anatomic differences between total and standard orthotopic heart transplantation occur at the atrial level, this study compares atrial systolic function and biventricular filling (dV/dt) between the standard and total transplantation techniques. METHODS AND RESULTS: Forty-eight mongrel canines (23 to 31 kg) were used for 12 total and 12 standard orthotopic cardiac transplantations. Right and left ventricular (RV/LV) function and AV synchrony were analyzed with micromanometry, sonomicrometry, ultrasonic flow meters, and intraoperative echocardiography. Results are expressed as mean +/- SEM (ANOVA, paired and unpaired t tests, and chi 2 test). There were no significant differences in baseline function (pretransplantation), bypass times, and cardiac ischemic times between the two groups. Posttransplantation sinus rhythm was preserved in all total (P < 0025) and in only one standard transplantation recipient (all required atrial diastole pacing). Significant decreases in RV/LV dV/dt from 113 +/- 13 and 123 +/- 14 mL/s to 69 +/- 6 and 85 +/- 10 mL/s after transplantation were measured in the standard group. No significant changes occurred in the total group after transplantation with respect to RV/LV diastolic filling. After transplantation, left atrial contractility and relaxation (-dP/dt) decreased significantly in the standard group by 43% and 70%, respectively, whereas in the total transplantation group, there were no observed changes in left atrial contractility and-dP/dt. A significant increase in the septum to RV free wall dimension in the standard group suggests altered geometry. CONCLUSIONS: Total AV transplantation is a feasible alternative to standard cardiac transplantation and conserves both normal sinus rhythm and synchronized beating of the atria and ventricles. Ischemic and bypass times are comparable in patients undergoing either method. These data suggest that RV/LV diastolic function and geometry and atrial systole are better preserved in the total AV transplantation technique.

Animals↗
PubMed1983

[Evaluation of left ventricular function in patients with atrial septal defect by exercise echocardiography].

In order to evaluate left ventricular function in atrial septal defect (ASD), 12 cases with ASD, 18 postoperative cases of ASD and 27 normal controls were examined by means of exercise echocardiography using supine bicycle ergometer (50 watts and 3 min). M-mode echocardiograms and left ventricular (LV) short-axis views by two-dimensional echocardiography were subjected to the observation. M-mode echocardiographic studies: ASD group showed an increased stroke dimension (SD) during exercise mainly due to a marked increase of left ventricular end-diastolic dimension ( LVDd ) and a slight decrease of left ventricular end-systolic dimension ( LVDs ). Postoperative ASD group showed an increased SD during exercise mainly due to a marked decrease of LVDs and a slight decrease of LVDd . On the other hand, in normal control group exercise increased SD only by a significant decrease of LVDs . Right ventricular dimension was decreased during exercise in ASD group, but did not change significantly in postoperative ASD and normal control groups. During exercise in ASD group, peak velocity of circumferential fiber shortening (VCF) was increased most markedly, and negative peak VCF was decreased most strikingly. Eight of 12 patients with ASD who showed abnormal interventricular septal motion demonstrated remarkable improvement of the motion during exercise. Two-dimensional echocardiographic studies: Left ventricular short-axis views demonstrated that the shape of the left ventricular cavity changed from flattened to more circular configuration during exercise at end- and early-diastole in ASD group. The shape of the left ventricular cavity at late-systole did not change significantly during exercise in this group. In postoperative ASD group, the left ventricular short-axis view demonstrated circular configuration of the left ventricle at end-diastole both in rest and during exercise. The shape of the left ventricular cavity did not change by exercise. It was concluded that in ASD group cardiac output is increased during exercise by decreasing a left to right shunt at the atrial level and increasing left ventricular filling rate. Therefore, the left ventricular function was found to be good in ASD.

Adolescent↗
PubMed1993

[Successful repair of partial atrioventricular septal defect in a 70-year-old female patient].

A 70-year-old female with partial atrioventricular septal defect underwent a total correction of the anomaly. The patient was in NYHA functional class II. Preoperative cardiac catheterization demonstrated a primum-type atrial septal defect through which 33% of left to right shunt occurred and a cleft of mitral valve causing moderate regurgitation. The operative procedure as our routine for this anomaly consisted of suture of mitral septal commissure and closure of atrial septal defect with autologous pericardial patch. Postoperative examination showed satisfactory competence of mitral valve and improved functional capacity. A successful correction for the case aged more than 66 with this anomaly has not been reported so far in Japanese literature. We conclude that surgical treatment should be basically considered for this anomaly in spite of senility.

Aged↗
PubMed1983

Segmental right ventricular function after acute myocardial infarction: two-dimensional echocardiographic study in 63 patients.

Right ventricular (RV) segmental contraction was studied in 63 patients with acute myocardial infarction (MI), using 2-dimensional (2-D) echocardiography. Group A included 32 patients with ischemic RV dysfunction: 19 had a disproportionate increase in right atrial pressure at the time of the examination (Group AI) and in 13 patients, right atrial pressure was normal when the echocardiogram was obtained (Group AII). Group B included 31 patients without ischemic RV dysfunction. Alkinesia or dyskinesia of the RV wall was found in 30 patients: 19 from Group AI, 8 from Group AII, and 3 from Group B. Asynergy could be identified in all segments of the RV wall including the outflow tract, RV apex, and anterior wall, but was more frequently found in the posterior wall (29 patients), best seen in the transversal subcostal short-axis view. A significant difference was found either in the frequency of wall motion abnormalities or in the number of segments with asynergy among the 3 groups (p less than 0.001). However, asynergy of the RV wall may be present in some patients with normal right heart hemodynamic function, suggesting that asynergy may be more sensitive than hemodynamic function in the diagnosis of acute RV infarction. Paradoxical septal motion was found in 8 patients, all in Group AI, and all had a right atrial pressure equal to or greater than pulmonary capillary pressure.

Adult↗
PubMed1994

Atrial natriuretic peptide and its relation to cardiac dimensions and function in patients with systemic sclerosis.

OBJECTIVES: Were to determine whether plasma atrial natriuretic peptide (ANP) is increased in patients with systemic sclerosis (SScl) and to evaluate its relation to cardiac dimensions and function. METHODS: Using radio-immunoassay, plasma ANP was determined in 30 patients with SScl and 48 age and sex matched controls. The plasma ANP level was related to cardiac structure and function as determined by two-dimensional echocardiography (2-D echo). RESULTS: Plasma ANP was markedly elevated among patients as compared to controls (239,4 +/- 59 vs 178.2 +/- 36 pmpl/l, p < 0.0005). The left atrial long-axis and area were increased, and ANP was directly related to both measurements (r = 0.27, p < 0.05 and r = 0.40, p < 0.005, respectively). Plasma ANP was also related to the increased right atrial long-axis (r = 0.27, p < 0.05). The ANP level was not related to LV systolic function as estimated by ejection fraction, fractional area change and end-systolic wall stress, neither did these measures differ between patients and controls. However, there was an inverse correlation between ANP level and stroke volume (r = -0.35, p < 0.05), which was lower among the patients (p < 0.005). ANP displayed also an inverse relation to LV long axis diameter (r = -0.37, p < 0.005) and area (r = -0.42, p < 0.005) as well as to LV end-diastolic volume (r = -0.42, p < 0.005). Various measurements indicated LV hypertrophy among the SScl patients in spite of a small LV cavity. ANP was directly related to measures of LV hypertrophy, as interventricular septum thickness (r = 0.44, p < 0.005), LV posterior wall thickness (r = 0.34, p < 0.05), the wall thickness to cavity dimension ratio (r = 0.36, p < 0.05), and LV myocardial area (r = 0.36, p < 0.05). There was no relationship between ANP concentration and heart rate, blood pressure or total peripheral resistance. CONCLUSION: These results suggest that the ANP production is not reduced in SScl. Rather, circulating ANP is elevated in relation to the degree of LV hypertrophy. This implies that ANP may be useful for the identification of cardiac involvement in patients with SScl.

Adult↗
PubMed2002

Left atrial function: bridge to central and hormonal determinants of exercise capacity in patients with chronic heart failure.

UNLABELLED: The stroke volume response to exercise is a critical determinant in meeting peripheral metabolic demands in patients with chronic hear failure. The Left atrium, by its position, is important in coupling right and left ventricles, to left preload reserve and to modulate sympathetic activity. We performed this study to investigate the relationship between exercise capacity and diastolic and systolic left atrium function in patients with chronic heart failure. METHODS: We considered 128 consecutive patients with severe chronic heart failure (EF < 35%) due to ischemic or idiopathic dilated cardiomyopathy. Cardiac output, right atrial pressure, pulmonary artery pressures and mean pulmonary wedge pressure (A, X, V, Y wedge pressures) were determined during right cardiac catheterization. By Echocardiography evaluation, we measured atrial pressures and volume during early and late left atrial systolic filling and we calculated left atrial chamber stiffness by this equation P = A*eKV1. (P = left atrial pressure; A = elastic constant (mmHg*ml); e = the base of the natural logarithm; V1 = left atrial volume (ml); K = left atrial chamber stiffness constant (ml-1) = ln (V/X)/(maximal--minimal left atrial volumes)). All patients performed cardiopulmonary exercise test with modified Noughton protocol. Plasma norepinephrine and Atrial natriuretic factor levels were determined. RESULTS: Maximal and minimal left atrial volumes were inversely related to oxygen consumption (r = -.44, p < .001; r = -.61, p < .001). At rest, no differences were found in plasma norepinephrine concentrations (309 +/- 152 pg/ml vs 309 +/- 394 pg/ml; p = ns) and systemic vascular resistance (1706 +/- 435 vs 1771 +/- 524 dynes/cm sec-5; p = ns) in patients with large or normal left atrial volumes. During exercise the chronotropic response increased less in patients with large atrial volumes (56 +/- 13 vs 45 +/- 14; p = .001). The left atrial chamber stiffness constant was inversely related to peak oxygen consumption and exercise time. Patients with different chamber stiffness showed statistical difference in peak VO2 (16 +/- 4 vs 11 +/- 3 ml/kg/min; p = .0001). Left atrial ejection fraction was directly related to peak oxygen consumption (r = 0.55), but the most strongly correlation was with atrial filling fraction (r = .67). CONCLUSIONS: This study demonstrates a strong relationship between left atrial function and exercise capacity in patients with chronic heart failure.

Chronic Disease↗
PubMedDate not supplied

Right ventricular filling abnormalities in acute inferior wall myocardial infarction--a pulsed Doppler study.

Pulsed Doppler derived velocity profile of right ventricular filling was used to assess right ventricular diastolic function in 29 patients with acute inferior wall myocardial infarction. The peak velocities of the early filling wave 'E' and the atrial wave 'A' were measured. Diastolic dysfunction, defined as E/A ratio less than 1.0, was seen in 15 patients. Of these 15 patients, 9 had electrocardiographic evidence of right ventricular infarction and only 6 had clinical evidence of right ventricular failure. None of the 14 patients without right ventricular diastolic dysfunction (E/A ratio more than 1.0) had electrocardiographic evidence of right ventricular infarction or clinical evidence of right ventricular failure. Pulsed Doppler appears to be a sensitive technique in identifying hemodynamic derangements induced by right ventricular infarction.

Echocardiography, Doppler↗
PubMed1987

Liver function abnormalities in chronic heart failure. Influence of systemic hemodynamics.

To characterize the incidence and severity of liver function abnormalities in patients with congestive heart failure, we analyzed systemic hemodynamics and biochemical profiles in 133 patients with stable chronic congestive heart failure, secondary to a dilated cardiomyopathy. The patients were divided into three groups, based on the severity of the reduction in cardiac index (CI). The mean values of all liver function tests in groups 1 (n = 43; CI greater than or equal to 2.0 L/min/m2) and 2 (n = 48; CI greater than 1.5 and less than 2.0 L/min/m2) were essentially normal, except for minimally elevated alkaline phosphatase levels and slightly decreased albumin levels in both groups, and slight increases in levels of gamma-glutamyl transpeptidase and total bilirubin in group 2. In contrast, group 3 patients (n = 42; CI less than or equal to 1.5 L/min/m2) had the most severe heart failure, as assessed by the lowest CI and highest cardiac filling pressures, and significantly higher levels of aspartate aminotransferase (65 +/- 82 U/L), alanine aminotransferase (77 +/- 102 U/L), lactate dehydrogenase (282 +/- 91 U/L), and total bilirubin (29 +/- 14 mumol/L [1.7 +/- 0.8 mg/dL]). The percentage of patients in group 3 with these abnormalities ranged between 27% and 80%. Although linear regression analysis showed that the elevations in right atrial and pulmonary wedge pressures, and the decreases in CI, were significantly correlated with liver function abnormalities, the correlation coefficients were small. Thus, liver function abnormalities remain common in patients with congestive heart failure but are generally small in magnitude and not associated with clinically apparent hepatic disease. It is likely that reduced forward flow and passive backward congestion are both contributing factors in the pathogenesis of these biochemical abnormalities, although nonhemodynamic factors may also be important.

Adult↗
PubMed2000

Tolerance to ischemia and hypoxia is reduced in aged human myocardium.

BACKGROUND: Recovery of cardiac function after cardiac surgery and other interventional cardiac procedures in elderly patients is inferior to that in younger patients, suggesting that the aged myocardium is more sensitive to ischemia and other stresses. Although convincing data from animal studies of senescence now exist, there is a dearth of controlled in vitro studies that examine the specific response of aged human myocardium to the stress of hypoxia or ischemia. OBJECTIVE: We sought to determine the effect of age on the capacity of human atrial trabeculae to recover contractile function after in vitro hypoxic or ischemic stress. METHODS: Atrial pectinate trabeculae were dissected from the tip of 58 right atrial appendages harvested during an operation in patients aged between 34 and 89 years and electrically stimulated at 1 Hz in oxygenated Ringer's solution at 37 degrees C. Tissues experienced 30 minutes of either hypoxia (N(2) and perfusate) or simulated ischemia (humidified N(2) without perfusate) and were returned to normoxia for recovery of function for 30 minutes. Developed force and other contractile variables were determined during each period. RESULTS: Under normoxic conditions, no significant age difference was observed for any contractile function variable. However, after hypoxia, the old (70-89 years) and intermediate age groups (60-69 years) showed reduced recovery of developed force (48.5% +/- 22.2% [n = 11] and 44.9% +/- 19% [n = 12], respectively) compared with that found (66.4% +/- 19.7% [n = 15]) in the younger (34-59 years) group (mean +/- SD, P =.02). Similarly, after simulated ischemia, the groups of 70- to 89-year-old and 60- to 69-year-old subjects showed reduced recovery of developed force (35.7% +/- 17% [n = 5] and 51.1% +/- 11.8% [n = 9], respectively) compared with that found (68.2% +/- 10.4% [n = 6]) in the group of 34- to 59-year-old subjects (P =.01). Multivariable analysis, comparing 20 factors of surgical patient characteristics and recovery of developed force, found that only age (P =.01) and hypertension (P =.01) were predictors of reduced recovery of developed force after either hypoxia or simulated ischemia. CONCLUSIONS: In aged human atrial myocardium, the capacity to recover contractile function after in vitro hypoxia or simulated ischemia is reduced compared with the younger myocardium of mature adults. These findings suggest that enhanced myocardial protective strategies may be indicated for elderly patients undergoing cardiac surgery.

Adult↗
PubMed2003

Beneficial effects of phosphodiesterase 5 inhibition in pulmonary hypertension are influenced by natriuretic Peptide activity.

BACKGROUND: Phosphodiesterase type 5 (PDE5) inhibitors (eg, sildenafil) are a novel, orally active approach to the treatment of pulmonary arterial hypertension. The role of natriuretic peptides in the response to sildenafil was examined in mice lacking NPR-A, a guanylyl cyclase-linked natriuretic peptide receptor, in which pulmonary hypertension was induced by hypoxia. METHODS AND RESULTS: Mice homozygous for NPR-A (NPR-A+/+) and null mutants (NPR-A-/-) were studied. Sildenafil inhibited the pressor response to acute hypoxia in the isolated perfused lungs of both genotypes. This effect was greater in the presence of atrial natriuretic peptide in the perfusate in NPR-A+/+ mice but not NPR-A-/- animals. In vivo, NPR-A mutants had higher basal right ventricular (RV) systolic pressures (RVSPs) than did NPR-A+/+ mice, and this was not affected by 3 weeks of treatment with sildenafil (25 mg x kg(-1) x d(-1)). Both genotypes exhibited a rise in RVSP and RV weight with chronic hypoxia (10% O2 for 21 days); RVSP and RV weight were reduced by continuous sildenafil administration in NPR-A+/+ mice, but only RVSP showed evidence of a response to the drug in NPR-A-/- mice. The effect of sildenafil on hypoxia-induced pulmonary vascular muscularization and cyclic GMP levels was also blunted in NPR-A-/- mice. CONCLUSIONS: The natriuretic peptide pathway influences the response to PDE5 inhibition in hypoxia-induced pulmonary hypertension, particularly its effects on RV hypertrophy and vascular remodeling.

3',5'-Cyclic-GMP Phosphodiesterases↗